Supporting Information File Dias et al. 1______________________________________________________________________________________________

Addition of kinetic boron enolates generated from β−alkoxy methyl ketones to aldehydes. Density functional theory

calculations on the transition structures.

Luiz C. Dias,* Sávio M. Pinheiro, Vanda M. de Oliveira, Marco A. B. Ferreira, Cláudio F. Tormena, Andrea M. Aguilar, J. Zukerman-Schpector and Edward R.T. Tiekink

Chemistry Institute, University of Campinas, UNICAMP P.O. Box 6154, 13084-971, Campinas, SP, Brazil (ldias@iqm.unicamp.br)

__________________________________________________________________________________

General Informations: All reactions were carried out under an atmosphere of argon or nitrogen in

flame-dried glassware with magnetic stirring. Dichloromethane, acetonitrile, triethylamine, 2,6-

lutidine, diisopropylamine, dimethylformamide, titanium tetrachloride and N-methylpyrrolidone were

distilled from CaH2. Dimethyl sulfoxide was distilled under reduced pressure from calcium hydride

and stored over molecular sieves. THF and toluene were distilled from sodium/benzophenone ketyl.

Oxalyl chloride was distilled immediately prior to use. MeOH was distilled from Mg(OMe)2.

Purification of reaction products was carried out by flash chromatography using silica-gel (230-400

mesh). Analytical thin layer chromatography was performed on silica gel 60 and GF (5-40-μm

thickness) plates. Visualization was accomplished with UV light and anisaldehyde, ceric ammonium

nitrate stain or phosphomolybdic acid followed by heating or I2 staining. 1H and proton-decoupled 13C NMR spectra were taken in C6D6 or CDCl3 at 250, 300 or 500 MHz (1H) and 62.5, 75 or 125

MHz (13C). The chemical shifts (δ) are reported in ppm using solvent as an internal standard (C6D6 at

7.16 ppm and CDCl3 at 7.26 ppm) or with addition of TMS. Data are reported as: s = singlet, d =

doublet, t = triplet, q = quartet, quint = quintuplet, sext = sextet, dd = doublet of doublets, dt = doublet

of triplets, ddd = doublet of doublet of doublets, m = multiplet, qd = quartet of doublets, dhept =

doublet of heptet, brd = broad doublet, brs = broad singlet, dq = doublet of quartet; coupling

constant(s) in Hz; integration.

Representative Procedure for Aldol Reactions of Methyl Ketones (5) and (8) To a solution of the corresponding methyl ketone (0.21 mmol) in Et2O (4 mL), under argon

atmosphere at –78 ºC, was added dropwise dicyclohexylboron chloride (3 equiv.0.63 mmol). After

this, Et3N (3.5 equiv., 0.74 mmol) was added dropwise and the resulting mixture was stirred for 1

hour. The solution of aldehyde (4 equiv., 0.84 mmol) in Et2O (0.5 mL) was added dropwise into the

enolate solution at –78 ºC and the resulting mixture was stirred for 2 hours in the same conditions.

The reaction was quenched by addition of 3.0 mL of pH 7.0 aqueous phosphate buffer solution at 0

Supporting Information File Dias et al. 2______________________________________________________________________________________________ ºC. After that, MeOH (2 mL) and H2O2 30% (2.4 mL) were added dropwise at 0 ºC. The resulting

mixture was stirred for 1 hour at 0 ºC. The solution was diluted with H2O (3 mL), and the mixture was

extracted with Et2O (4 times), washed with saturated aqueous solution of NaHCO3, brine, and dried

over MgSO4. The solvent was removed under reduced pressure, and the resulting oil was purified by

flash column chromatography to give the aldol adducts.

PROOF OF THE RELATIVE STEREOCHEMISTRY FOR ALDOL ADDUCT (6)

The relative stereochemistries for the major products 6 (Scheme 1) and 9b ( R = iPr) (Scheme 2)

were confirmed by comparison of the spectroscopic properties of the corresponding diols after

removal of the TBS and PMB protecting groups, respectively, by comparison with data described in

the literature (Luke, G. P.; Morris, J. J. Org. Chem. 1995, 60, 3013).

O

Me

TBSO

Me

Me MeOH

Me

O

Me

TBSO

Me

Me MeOH

Me

+ds 30:70

6

7

1,5-anti

1,5-syn

HF (48%)-CH3CN (1:19)

O

Me

OH

Me

Me MeOH

Me

O

Me

OH

Me

Me MeOH

Me

+ds 30:70

1,5-anti

1,5-syn

major productmajor product

99%

Representative Procedure for Aldol Reactions of Methyl Ketones (11) and (17)

To a solution of the corresponding methyl ketone (0.18 mmol) in Et2O (5 mL) at –30 ºC, was added

dicyclohexylboron chloride (3 equiv., 0.12 mmol) under fast magnetic stirring. Next, Et3N (3.5 equiv.,

0.63 mmol) was added dropwise, leading to the precipitation of a white solid of Et3N.HCl. Right

away, the crude aldehyde (4 equiv.) was added in the enolate solution at –78 ºC. The resulting mixture

was stirred for 5 minutes at –78 ºC. Next, the temperature was adjusted to –40 ºC and pH 7.0 aqueous

phosphate buffer solution (3 mL) was added. After that, MeOH (2 mL) and H2O2 30% (2.4 mL) were

added dropwise at 0 ºC. The resulting mixture was stirred for 1 hour at 0 ºC. The solution was diluted

with H2O (3 mL), and the mixture was extracted with Et2O (4 times), washed with saturated aqueous

solution of NaHCO3, brine, and dried over MgSO4. The solvent was removed under reduced pressure,

and the resulting oil was purified by flash chromatography (silica gel 200–400 mesh, 15–40% EtOAc

in hexanes), giving the aldol adducts.

Supporting Information File Dias et al. 3______________________________________________________________________________________________

N

OMe

Me

OH

MeO

O

Bn (S)-4-benzyl-3-((2S,3R)-3-hydroxy-2,4-dimethylpentanoyl)oxazolidin-2-one:

1.3 mL of Di–n–butylborontrifluoromethanesulfonate (5.4 mmol) was added to a solution of (S)–4–

benzyl–3–propionyloxazolidin–2–one (1.0 g, 4.28 mmol) in 9.6 mL of CH2Cl2 at –12 ºC. After 5

minutes, 0.8 mL of Et3N (5.56 mmol) was added dropwise. After 10 minutes, the resulting yellow

solution was cooled to –78 ºC and 0.43 mL of isobutyraldehyde (4.71 mmol) was added slowly. After

1 hour, the solution was warmed to 0 ºC and stirred at that temperature for 1 hour. The reaction was

quenched by addition of a solution of 21.5 mL of pH 7.0 aqueous phosphate buffer solution and

MeOH in 3:1 ratio (bath temperature = 0 ºC). Next, 16 mL of a solution of MeOH and 30% H2O2

aqueous solution in 3:1 ratio was added carefully and the resulting yellow solution was stirred at 0 ºC

for 1 hour. The volatiles were removed at aspirator pressure and the residue was extracted with Et2O

(3 times). The combined organic extracts were washed with saturated aqueous NaHCO3, brine, and

dried over anhydrous MgSO4. The crude material was purified by silica gel flash column

chromatography (40% EtOAc/hexanes) to give the syn–aldol adduct (85 %) as colorless oil.

Yield: 85%, ds > 95:5; [α]D20 +34 (c 0.98, CHCl3); 1H NMR (300 MHz, CDCl3) δ 7.34−7.19 (m, 5H),

4.74−4.66 (m, 1H), 4.26−4.16 (m, 2H), 3.96 (qd, J 6.9, 2.6 Hz, 1H), 3.54 (dd, J 8.4, 2.7 Hz, 1H), 3.26

(dd, J 13.8, 3.3 Hz, 1H), 2.79 (dd, J 13.5, 9.6 Hz, 1H), 2.47 (brd, 1H), 1.79−1.67 (m, 1H), 1.24 (d, J

7.5 Hz, 3H), 1.04 (d, J 6.6 Hz, 3H), 0.91 (d, J 7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 177.8,

152.9, 135.0, 129.4, 129.0, 127.4, 76.6, 66.1, 55.1, 39.6, 37.7, 30.8, 19.2, 18.9, 9.9; IR (Film): ν 3518,

3065, 3028, 2965, 2865, 1775, 1685, 1604, 1444, 1385, 1209, 1109, 979, 761, 703, 644 cm−1.

N

OMe

Me

OH

Me

OMe

Me (2S,3R)-3-hydroxy-N-methoxy-N,2,4-trimethylpentanamide: At 0 ºC, to a

suspension of N,O–dimethylhydroxylamine hydrochloride (610.4 mg, 6.26mmol) in THF (3.3 mL)

was added AlMe3 (2.0 M in toluene, 3.2 mL, 6.41 mmol). The resultant solution was stirred for 30

minutes at room temperature, and then cooled to –15 ºC. A solution of aldol adduct (642 mg) in THF

(3.3 mL) was added dropwise. After an additional 2.5 hours at 0 ºC, the reaction mixture was poured

slowly into a solution of aqueous HCl (0.5 N, 32.6 mL) and CH2Cl2 (16.1 mL) and stirred vigorously

at 0 ºC for 1 hour. The aqueous phase was extracted with CH2Cl2 (2 times), and the combined organic

layers were washed with water (2 times), brine, and dried over MgSO4, filtered and concentrated.

Concentration of the residual liquid and flash column chromatography (40% EtOAc/hexanes)

afforded Weinreb amide (87 %) as a colorless oil and (S)–4–benzyl–3–propionyloxazolidin–2–one

Supporting Information File Dias et al. 4______________________________________________________________________________________________ (56%) as white needles crystals. Yield: 87%; [α ]D

20 +17.0 (c 0,81, CHCl3); 1H NMR (300 MHz,

CDCl3) δ 3.71 (s, 3H), 3.43 (dd, J 8.9, 2.6 Hz, 1H), 3.31 (brs, 1H), 3.20 (s, 3H), 3.11−3.09 (m, 1H),

1.81−1.65 (m, 1H), 1.15 (d, J 6.9 Hz, 3H), 1.04 (d, J 6.6 Hz, 3H), 0.88 (d, J 7.2 Hz, 3H); 13C NMR

(75 MHz, CDCl3) δ 178.3, 76.8, 61.4, 35.7, 31.8, 30.2, 18.9, 18.8, 9.9; IR (Film): ν 3448, 2957, 2877,

1790, 1635, 1460, 1379, 1179, 1105, 996, 876 cm−1.

N

OMe

Me

TBSO

Me

OMe

Me (2S,3R)-3-(tert-butyldimethylsilyloxy)-N-methoxy-N,2,4-

trimethylpentanamide: 2,6–Lutidine (0.2 mL, 1.72 mmol) and TBSOTf (0.35 mL, 1.52 mmol) were

added to a stirred solution of the Weinreb amide in 1.3 mL of CH2Cl2 at room temperature. After 30

minutes, the reaction mixture was quenched by the addition of 2 mL of H2O. The organic layer was

separated and the aqueous phase was extracted with Et2O. The combined organic phases were washed

with H2O, brine, and dried over MgSO4. The crude product was purified by flash column

chromatography (10% EtOAc/hexanes) to give the TBS ether (95%) as colorless oil.

Yield: 95%; [α]D20 +9 (c 1.36, CHCl3); 1H NMR (300 MHz, C6D6) δ 4.11 (dd, J 8.0, 3.2 Hz, 1H),

3.16−3.10 (m, 1H), 3.05 (s, 3H), 2.87 (s, 3H), 1.94−1.84 (m, 1H), 1.35 (d, J 6.9 Hz, 3H), 1.04 (s, 9H),

1.02 (d, J 8.7 Hz, 3H), 1.01 (d, J 6.9 Hz, 3H), 0.15 (s, 3H), 0.10 (s, 3H); 13C NMR (75 MHz, C6D6) δ

177.0, 78.4, 60.9, 39.4, 33.6, 32.3, 26.6, 20.2, 18.9, 17.4, 15.8, −3.4, −3.5; IR (Film): ν 2960, 2932,

2858, 1665, 1461, 1383, 1212, 1051 cm−1.

Me

OMe

Me

TBSO

Me (5) (3S,4R)-4-(tert-butyldimethylsilyloxy)-3,5-dimethylhexan-2-one (5): To a

solution of previous TBS–ether (100 mg, 0,287 mmol) in THF (5.3 mL) was added dropwise MeLi

(1.3 M in Et2O, 0.88 mL, 1.15 mmol) at –78 ºC under argon atmosphere. The reaction mixture was

stirred for 45 minutes and next, was poured slowly into a solution of aqueous saturated NH4Cl and

Et2O and stirred vigorously at 0 ºC. The layers were separated and aqueous phase was extracted with

Et2O (3 times). The combined organic layers were washed with brine and dried over MgSO4. The

organic layer was concentrated under reduced pressure and purified by silica gel flash column

chromatography (10% EtOAc/hexanes) giving the methyl ketone 5 (96%) as colorless oil.

Yield: 96%; TLC: Rf 0.65 (EtOAc/Hex 5 %); [α]D20 +15.0 (c 1.0, CHCl3); 1H NMR (300 MHz, C6D6)

δ 3.79 (t, J 5.1, 1H), 2.68 (qt, J 6.9 Hz, 1H), 2.18 (s, 3H), 1.68 (dhept, J 2.4, 6.6 Hz, 1H), 1.09 (d, J

6.9 Hz, 3H), 0.91 (s, 9H), 0.90 (d, J 6.9 Hz, 3H), 0.87 (d, J 6.9 Hz, 3H), 0.07 (s, 3H), 0.03 (s, 3H);

Supporting Information File Dias et al. 5______________________________________________________________________________________________ 13C NMR (75 MHz, C6D6) δ 211.5, 77.4, 50.9, 33.0, 29.7, 29.6, 26.1, 19.8, 18.5, 17.9, 12.9, −3.8,

−4.0; IR (Film): ν 3021, 2960, 2929, 2858, 1709, 1473, 1360, 1254, 1051cm−1.

O

Me

PMBO

MeN

Me

Me

OMe

N-methoxy-3-(4-methoxybenzyloxy)-N,2,4-trimethylpentanamide: 1.13 g

of p–methoxybenzyl 2,2,2–trichloroacetimidate (4.0 mmol) and 31.8 mg of CSA (0.14 mmol) were

added to a stirred solution of aldol adduct (500 mg, 2.65 mmol) in 6.2 mL of CH2Cl2. The reaction

mixture was stirred for 13 hours at room temperature. Next, it was diluted with Et2O (18 mL) and

washed with saturated aqueous solution of NaHCO3 (2 times), H2O (2 times), brine, and dried over

MgSO4. The crude material was concentrated over reduced pressure and purified by silica gel flash

column chromatography (20 % EtOAc/hexanes), giving the product (72%) as colorless oil.

Yield: 72%; TLC: Rf 0.33 (EtOAc/Hex 30%); [α]D20 +10.3 (c 1.28, CHCl3); 1H NMR (300 MHz,

C6D6) δ 7.29 (d, J 8.4 Hz, 2H), 6.86 (d, J 8.4 Hz, 2H), 4.55 (d, J 10.8 Hz, 1H), 4.50 (d, J 10.8, 1H),

3.79 (s, 3H), 3.68 (s, 3H), 3.53 (dd, J 3.9, 7.8 Hz, 1H), 3.19 (s, 3H), 3.15 (brs, 1H), 1.76 (m, 1H), 1.25

(d, J 7.2 Hz, 3 H), 1.00 (d, J 6.6 Hz, 3H), 0.94 (d, J 6.9 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 159.1,

131.0, 129.4, 113.7, 85.2, 75.0, 61.4, 55.2, 38.7, 32.3, 31.6, 20.4, 17.0, 14.2; IR (Film): ν 3018, 2959,

2930, 1655, 1514, 1215 cm−1.

O

Me

PMBO

Me

MeMe

(8) (3S,4R)-4-(4-methoxybenzyloxy)-3,5-dimethylhexan-2-one (8): To a solution of

previous PMB–ether (1.11 g, 3.68 mmol) in THF (68.8 mL) was added dropwise MeLi (1.3 M in

ethylic ether, 11.6 mL, 15.06 mmol) at –78 ºC under argon atmosphere. The reaction mixture was

stirred for 45 minutes and was poured slowly into a solution of aqueous saturated NH4Cl and Et2O

and stirred vigorously at 0 ºC. The layers were separated and aqueous phase was extracted with Et2O

(3 times). The combined organic layers were washed with brine and dried over MgSO4. The organic

layer was concentrated under reduced pressure and purified by silica gel flash column

chromatography (20% EtOAc/hexanes) giving the methyl ketone 8 (97%) as colorless oil.

Yield: 97%; TLC: Rf 0.75 (EtOAc/Hex 30%); [α]D20 +13.0 (c 1.06, CHCl3); 1H NMR (300 MHz,

CDCl3) δ 7.24 (d, J 9.2 Hz, 2H), 6.86 (d, J 9.0 Hz, 2H), 4.44 (s, 2H), 3.79 (s, 3H), 3.50 (t, J 5.7 Hz,

1H), 2.19 (s, 3H), 1.77 (sext, J 6.6 Hz, 1H), 1.17 (d, J 6.9 Hz, 3H), 0.98 (d, J 6.6 Hz, 3H), 0.95 (d, J

6.9 Hz, 3H); 13C NMR (75 MHz, C6D6) δ 209.6, 159.6, 131.4, 129.4, 114.0, 84.8, 74.3, 54.8, 49.9,

32.0, 28.9, 20.2, 18.4, 12.1; IR (Film): ν 3020, 2966, 2882, 1709, 1614, 1544, 1217 cm−1.

Supporting Information File Dias et al. 6______________________________________________________________________________________________

O

Me

TBSO

Me

Me MeOH

Me

O

Me

TBSO

Me

Me MeOH

Me+

6

1,5-syn

7

1,5-anti

(3R,4S,7R)-3-(tert-butyldimethylsilyloxy)-7-

hydroxy-2,4,8-trimethylnonan-5-one (6) and (3R,4S,7S)-3-(tert-butyldimethylsilyloxy)-7-

hydroxy-2,4,8-trimethylnonan-5-one (7): Yield: 69% (ds 70:30); TLC: Rf 0.75 (EtOAc/Hex 30 %); 1H NMR (300 MHz, C6D6) δ 3.84 (m, 2H), 3.02 (brs, 1H), 2.42 (m, 4H), 1.64 (m, 2H), 0.99 (s, 9H),

1.17−0.92 (m, 12H); 13C NMR (75 MHz, C6D6) δ 214.1, 77.5, 77.2, 72.2, 72.2, 51.1, 50.7, 46.3, 46.1,

33.4, 33.3, 33.1, 26.3, 19.9, 19.8, 18.7, 18.6, 17.9, 18.7, 18.6, 17.9, 17.7, 17.7, 13.2, −3.7, −4.0; IR

(Film): ν 3504, 3019, 2961, 2935, 2858, 1699, 1471, 1254, 1215 cm−1.

1,5-syn1,5-anti

9b 10b

O

Me

OHPMBOMe

Me

O

Me

OHPMBOMe

Me

Me Me

MeMe (3R,4S,7S)-7-hydroxy-3-(4-

methoxybenzyloxy)-2,4,8-trimethylnonan-5-one (9b) and (3R,4S,7R)-7-hydroxy-3-(4-

methoxybenzyloxy)-2,4,8-trimethylnonan-5-one (10b): Yield: 95% (ds 62:38); TLC: Rf 0.62

(EtOAc/Hex 30 %); [α]D20 +20.0 (c 0.36, CHCl3); 1H NMR (250 MHz, C6D6) δ 7.35 (d, J 8.5 Hz,

2H), 6.77 (m, 2H), 4.52 (d, J 10.8 Hz, 1H), 4.43 (d, J 10.8 Hz, 1H), 3.86 (m, 1H), 3.55 (t, J 5.7 Hz,

1H), 3.39 (s, 3H), 2.57 (m, 1H), 1.81 (sext, J 6.5 Hz, 1H), 1.64 (m, 1H), 1.38 (m, 1H), 1.20 (d, J 7.1

Hz, 3H), 1.05 (d, J 6.7 Hz, 3H), 0.91 (d, J 6.8 Hz, 3H); 13C NMR (125 MHz, C6D6) δ 209.7, 159.6,

131.4, 129.5, 114.0, 84.7, 74.3, 54.7, 49.8, 31.9, 30.4, 28.8, 26.0, 23.8, 20.1, 18.3, 12.0; IR (Film): ν

3406, 3020, 2966, 2936, 1707, 1614, 1514, 1469, 1358, 1254, 1177, 1036 cm−1.

1,5-syn1,5-anti

9c 10c

O

Me

OHPMBOMe

Me

O

Me

OHPMBOMe

Me

Me Me

(3R,4S,7R)-7-hydroxy-3-(4-

methoxybenzyloxy)-2,4-dimethylnonan-5-one (9c) and (3R,4S,7S)-7-hydroxy-3-(4-

methoxybenzyloxy)-2,4-dimethylnonan-5-one (10c): Yield: 90% (ds 67:33); 1H NMR (250 MHz,

C6D6) δ 7.34 (d, J 8.5 Hz, 2H), 6.90 (d, J 8.6 Hz, 2H), 4.48 (m, 2H), 4.00 (brs, 1H), 3.57 (t, J 5.6 Hz,

1H), 3.40 (s, 3H), 3.15 (s, 1H), 2.65 (m, 1H), 2.30−2.55 (m, 2H), 2.47 (m, 3H), 1.82 (sext, J 6.6 Hz,

1H), 1.65−1.30 (m, 3H), 1.19 (d, J 7.0 Hz, 3H), 1.00 (m, 6H), 0.93 (d, J 7.0 Hz, 6H); 13C NMR (75

MHz, C6D6) δ 214.3, 159.7, 131.4, 129.6, 129.4, 114.0, 84.7, 74.4, 69.0, 54.7, 49.9, 48.3, 32.0, 29.8,

Supporting Information File Dias et al. 7______________________________________________________________________________________________ 20.0, 18.3; 11.9, 10.1; IR (Film): ν 3515, 3054, 2964, 2942, 2875, 1701, 1614, 1514, 1463, 1249,

1035 cm−1.

1,5-syn1,5-anti

9d 10d

O

Me

OHPMBOMe

Me

O

Me

OHPMBOMe

Me (1S,4S,5R)-1-hydroxy-5-(4-

methoxybenzyloxy)-4,6-dimethyl-1-phenylheptan-3-one (9d) and (1R,4S,5R)-1-hydroxy-5-(4-

methoxybenzyloxy)-4,6-dimethyl-1-phenylheptan-3-one (10d): Yield: 88% (ds 56:44); TLC: Rf

0.54 (EtOAc/Hex 30 %); 1H NMR (250 MHz, C6D6) δ 7.45−7.15 (m, 7H), 6.83 (d, J 9.0 Hz, 2H),

5.24 (brs, 1H), 4.44 (m, 2H), 3.51 (m, 1H), 3.41 (s + m, 4H), 2.80-2.40 (m, 3H), 1.78 (m, 1H), 1.15

(m, 3H), 1.02 (m, 3H), 0.88 (m, 3H); 13C NMR (62,5 MHz, C6D6) δ 213.5, 213.2, 159.7, 131.3, 131.2,

129.5, 129.4; 126.04, 125.98, 114.02, 84.7, 84.6, 74.3, 74.2, 70.2, 70.1, 54.7, 50.9, 50.0, 49.9, 32.0,

31.9, 20.04, 19.3, 18.4, 18.3, 11.5, 11.4; IR (Film): ν 3497, 3018, 2965, 2936, 2882, 1701, 1602,

1514, 1456, 1385, 1248, 1217, 1176, 1033 cm−1.

1,5-syn1,5-anti

9e 10e

O

Me

OHPMBOMe

Me

O

Me

OHPMBOMe

MeOMe OMe (1S,4S,5R)-1-hydroxy-5-(4-

methoxybenzyloxy)-1-(4-methoxyphenyl)-4,6-dimethylheptan-3-one (9e) and (1R,4S,5R)-1-

hydroxy-5-(4-methoxybenzyloxy)-1-(4-methoxyphenyl)-4,6-dimethylheptan-3-one (10e): Yield:

94% (ds 50:50); TLC: Rf 0.40 (EtOAc/Hex 30 %); 1H NMR (250 MHz, C6D6) δ 7.28 (m, 4H), 6.78

(m, 4H), 5.15 (brs, 1H), 4.35 (m, 2H), 3.43 (m, 1H), 3.31 (s + m, 4H), 2.75 (m, 2H), 2.53 (m, 2H),

1.93 (m, 3H), 1.70 (m, 3H), 1.07 (m, 3H), 0.79 (m, 3H); 13C NMR (125 MHz, C6D6) δ 213.5, 213.3,

159.7, 159.5, 136.22, 136.18, 131.3, 131.2, 129.5, 129.4, 127.3, 127.2, 114.0, 114.0, 84.7, 84.6, 74.3,

74.2, 69.9, 69.8, 54.8, 54.7, 50.0, 49.9, 32.0, 31.1, 20.1, 20.0, 18.4, 18.3, 11.5, 11.4; IR (Film): ν

3489, 3011, 2962, 2840, 1701, 1606, 1514, 1457, 1302, 1250, 1218, 1171, 1036 cm−1.

Supporting Information File Dias et al. 8______________________________________________________________________________________________

1,5-syn1,5-anti

9f 10f

O

Me

OHPMBOMe

Me

O

Me

OHPMBOMe

MeNO2 NO2 (1S,4S,5R)-1-hydroxy-5-(4-

methoxybenzyloxy)-4,6-dimethyl-1-(4-nitrophenyl)heptan-3-one (9f) and (1R,4S,5R)-1-hydroxy-

5-(4-methoxybenzyloxy)-4,6-dimethyl-1-(4-nitrophenyl)heptan-3-one (10f): Yield: 82% (ds

67:33); TLC: Rf 0.29 (EtOAc/Hex 30 %); 1H NMR (250 MHz, C6D6) δ 7.90 (d, J 8.5 Hz, 2H), 7.40

(d, J 8.5 Hz, 2H), 6.95 (d, J 9.0 Hz, 2H), 6.76 (d, J 9.0 Hz, 2H), 4.90 (m, 1H), 4.31 (m, 2H), 3.38 (m,

1H), 3.31 (s + m, 4H), 2.45 (m, 2H), 2.30 (m, 1H), 1.69 (sept, J 6.6 Hz, 1H), 1.04 (d, J 7.0 Hz, 3H),

0.92 (d, J 6.7 Hz, 3H), 0.80 (d + d, J 6.9 Hz, 3H); IR (Film): ν 3446, 3020, 2960, 2930, 2870, 1701,

1610, 1522, 1348, 1215, 1075, 1036.

PMBO OH

Me

O

N O

O

Bn (R)-4-benzyl-3-((2R,3S)-3-hydroxy-5-(4-methoxybenzyloxy)-2-

methylpentanoyl)oxazolidin-2-one: Di–n–butylborontrifluoromethanesulfonate (5.0 mL, 20.0

mmol) was added to a solution of (R)–4–benzyl–3–propionyloxazolidin–2–one (3.109 g, 13.3 mmol)

in 24.9 mL of CH2Cl2 at –12 ºC. Next, diisopropylamine (4.0 mL, 22.7 mmol) was added dropwise.

The resulting yellow solution was then cooled to –78 ºC and a refrigerated solution of aldehyde (1M,

3.401 g, 17.3 mmol) in CH2Cl2 was added slowly at –78 ºC. After 30 minutes, the solution was

warmed to –10 ºC and stirred at that temperature for 2 hours. The reaction was quenched by addition

of 29.8 mL of pH 7.0 aqueous phosphate buffer solution and 84.6 mL of MeOH (bath temperature =

–10 ºC). A solution of 79.6 mL of MeOH and 39.8 mL of 30% H2O2 aqueous solution was added

carefully and the resulting yellow solution was stirred at 0 ºC for 1 hour. The volatiles were removed

at aspirator pressure and the residue was extracted with Et2O (3 times). The combined organic extracts

were washed with saturated aqueous NaHCO3 and brine. The organic solution was dried over

anhydrous MgSO4 and purified by silica gel flash column chromatography (30% EtOAc/hexanes) to

give the syn–aldol adduct (59%) as colorless oil.

Yield: 59% (ds > 95:05); Rf 0.22 (Hex/EtOAc 30%), [α]D20 +42 (c 1.13, CH2Cl2); 1H NMR (500

MHz, CDCl3) δ 7.34–7.22 (m, 6H), 6.88 (d, J 8.5 Hz, 2H), 4.68 (m, 1H), 4.45 (s, 2H), 4.17 (m, 3H),

3.82 (m, 2H), 3.80 (s, 3H), 3.69 (m, 1H), 3.63 (m, 1H), 3.42 (brs, 1H), 3.25 (dd, J 13.3, 3.0 Hz, 1H),

2.79 (dd, J 13.3, 9.5 Hz, 1H), 1.87 (m, 1H), 1.74 (m, 1H), 1.29 (d, J 7.0 Hz, 3H); 13C NMR (125

MHz, CDCl3) δ 176.5 (C0), 159.1 (C0), 153.0 (C0), 135.0 (C0), 130.0 (C0), 129.4 (C1), 129.3 (C1),

128.8 (C1), 127.3 (C1), 113.7 (C1), 72.7 (C2), 70.3 (C1), 67.9 (C2), 66.0 (C2), 55.1 (C3), 55.1 (C1), 42.5

Supporting Information File Dias et al. 9______________________________________________________________________________________________ (C1), 37.6 (C2), 33.6 (C2), 11.1 (C3); IR νmax (film) 3478, 3055, 2935, 2869, 1780, 1695, 1612, 1514,

1385, 1265, 1094, 739 cm–1.

PMBO OH

Me

O

NMe

OMe

(2R,3S)-3-hydroxy-N-methoxy-5-(4-methoxybenzyloxy)-N,2-

dimethylpentanamide: At 0 ºC, a suspension or N,O–dimethylhydroxylamine hydrochloride (1.844

g, 18.9 mmol) in THF (13.8 mL) was cautiously treated with AlMe3 (2.0 M in toluene, 9.2 mL, 18.4

mmol). The resultant solution was stirred for 30 minutes at 0 ºC and 90 minutes at room temperature,

and then cooled to 20 ºC. A solution of aldol adduct (2.02 g, 4.73 mmol) in THF (10.3 mL) was added

dropwise. After additional 90 minutes at room temperature, the solution was poured slowly into a

solution of aqueous HCl (1.0 M, 27.4 mL) and CH2Cl2 (27.2 mL) and stirred vigorously at 0 ºC for 90

minutes. The aqueous phase was extracted with CH2Cl2 (3 times), and the combined organic layers

were washed with water (2 times), brine, and dried over MgSO4, filtered and concentrated. The crude

material was dissolved in a minimal amount of Et2O. An equal volume of hexanes was added, and the

resultant solution was refrigerated (4 ºC) overnight. Filtration of the crystals afforded chiral auxiliary.

Concentration of the residual liquid and flash column chromatography (40% EtOAc/hexanes and 50%

EtOAc/hexanes) afforded Weinreb amide (70%) as colorless oil.

Yield: 70%; Rf 0.25 (Hex/EtOAc 50%); [α]D20 +25 (c 1.03, CH2Cl2); 1H NMR (250 MHz, CDCl3) δ

7.24 (d, J 8.9 Hz, 2H), 6.86 (d, J 8.9 Hz, 2H), 4.44 (s, 2H), 4.03 (m, 1H), 3.92 (brs, 1H), 3.66 (s, 3H),

3.62 (m, 2H), 3.17 (s, 3H), 2.89 (m, 1H), 1.75 (m, 2H), 1.19 (d, J 7.1 Hz, 3H); 13C NMR (75 MHz,

CDCl3) δ 177.7 (C0), 159.1 (C0), 130.2 (C0), 129.3 (C1), 113.7 (C1), 72.8 (C2), 70.4 (C1), 68.0 (C2),

61.5 (C3), 55.2 (C3), 39.5 (C1), 33.9 (C2), 11.2 (C3); IR νmax (film) 3456, 2965, 2937, 2876, 1755,

1645, 1514, 1462, 1387, 1302, 1248, 1175, 1088, 1034, 991, 822 cm–1; HRMS (TOF-MS ES+): calcd

for C16H26NO5: m/z 312.1811; found: m/z 312.1823 [MH+].

O O

Me

O

NMe

OMe

PMP

(R)-N-methoxy-2-((2S,4S)-2-(4-methoxyphenyl)-1,3-dioxan-4-yl)-N-

methylpropanamide: To a solution of Weinreb amide (2.12g, 6.81 mmol) in 139.2 mL of CH2Cl2

was added powdered activated 4Å molecular sieves (2.12 g) and stirred for 15 minutes under argon

atmosphere. After that, the temperature was reduced to –10 ºC and DDQ was added (1.701 g, 7.49

mmol). After stirring for 3 hours at 0 ºC, the reaction mixture was diluted with Et2O (119 mL),

filtered through Celite column (h = 5 cm) and eluted with CH2Cl2. The filtered was washed with a

satured aqueous solution of NaHCO3 (3 times), brine (3 times) and dried over MgSO4. The organic

Supporting Information File Dias et al. 10______________________________________________________________________________________________ layer was concentrated under reduced pressure and the residue was purified by flash column

chromatography (50% EtOAc/hexanes) to give the product (72%) as colorless oil.

Yield: 72%; [α]D20 +27 (c 1.03, CH2Cl2); 1H NMR (250 MHz, CDCl3) δ 7.42 (d, J 8.8 Hz, 2H), 6.88

(d, J 8.8 Hz, 2H), 5.50 (s, 1H), 4.22 (dd, J 11.5, 5.0 Hz, 1H), 3.95 (m, 2H), 3.80 (s, 3H), 3.69 (s, 3H),

3.19 (s, 3H), 1.78 (m, 1H), 1.61 (m, 2H), 1.29 (d, J 6.8 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 175.2

(C0), 159.8 (C0), 131.3 (C0), 127.2 (C1), 113.5 (C1), 101.0 (C1), 78.6 (C1), 66.7 (C2), 61.6 (C3), 55.3

(C3), 41.0 (C1), 29.5 (C2), 14.3 (C3); IR νmax (film) 3055, 2970, 2860, 1763, 1655, 1518, 1464,

1389,1248, 1171, 1105, 1036, 887, 831, 739 cm–1; HRMS (TOF-MS ES+): calcd for C16H24NO5: m/z

310.1654; found: m/z 310.1667 [MH+].

11

O O

Me

O

Me

PMP

(R)-3-((2S,4S)-2-(4-methoxyphenyl)-1,3-dioxan-4-yl)butan-2-one (11): Under

argon atmosphere, to a solution of acetal (1.5113 g, 4.885 mmol) in dry THF (89.3 mL) was added

MeLi (1.3 M in ethylic ether, 15.3 mL, 24.43 mmol) dropwise at –78 ºC. The reaction mixture was

stirred for 45 minutes and was poured slowly into a solution of aqueous saturated NH4Cl and Et2O

and stirred vigorously at 0 ºC for 90 minutes. The organic layers were separated and the aqueous

phase was extracted with Et2O (3 times). The combined organic layers were washed with brine and

dried over MgSO4. The organic layer was concentrated under reduced pressure and purified by silica

gel flash column chromatography (15% EtOAc/hexanes) giving the methyl ketone 11 (88%) as white

solid.

Yield: 88%; Rf 0.48 (Hex/EtOAc 30%); mp: 30–32 ºC; [α]D20 +11 (c 1.17, CH2Cl2); 1H NMR (250

MHz, CDCl3) δ 7.39 (d, J 8.8 Hz, 2H), 6.89 (d, J 8.8 Hz, 2H), 5.47 (s, 1H), 4.23 (ddd, J 11.2, 5.0, 1.2

Hz, 1H), 4.03 (ddd, J 11.2, 6.8, 2.4 Hz, 1H), 3.93 (td, J 11.8, 2.5 Hz, 1H), 3.79 (s, 3H), 2.79 (q, J 7.0

Hz, 1H), 2.22 (s, 3H), 1.78 (dddd, J 12.2, 12.2, 12.2, 6.0 Hz, 1H), 1.50 (dd, J 13.0, 1.5 Hz; 1H), 1.21

(d, J 7.0 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 210.7 (C0), 159.8 (C0), 131.1 (C0), 127.2 (C1), 113.5

(C1), 101.1 (C1), 77.8 (C1), 66.7 (C2), 55.2 (C3), 51.6 (C1), 30.2 (C3), 28.5 (C2), 12.4 (C3); IR νmax

(film) 2970, 2858, 1711, 1616, 1518, 1364, 1250, 1103, 1036, 831, 735 cm–1; HRMS (TOF-MS ES+):

calcd for C15H21O4: m/z 265.1477; found: m/z 265.1436 [MH+].

Supporting Information File Dias et al. 11______________________________________________________________________________________________

12b

O O

Me

O

PMP

OHMe

Me (2R,5R)-5-hydroxy-2-((2S,4S)-2-(4-methoxyphenyl)-1,3-dioxan-4-yl)-6-

methylheptan-3-one (12b): Yield: 83% (ds 86:14); Rf 0.30 (Hex/EtOAc 30%); mp: 71–73 ºC; [α]D20

+15 (c 1.07, CH2Cl2); 1H NMR (250 MHz, C6D6) δ 7.57 (d, J 8.8 Hz, 2H), 6.82 (d, J 8.8 Hz, 2H), 5.31

(s, 1H), 3.92 (ddd, J 5.6, 5.0, 1.3 Hz, 1H), 3.79 (dd, J 6.6, 2.5 Hz, 1H), 3.75 (dd, J 6.6, 2.5 Hz, 1H),

3.46 (td, J 12.1, 2.5 Hz, 1H), 3.26 (s, 3H), 2.89 (brs, 1H), 2.54–2.27 (m, 3H), 1.55 (m, 1H), 1.04 (d, J

7.0 Hz, 3H), 0.91 (d, J 6.8 Hz, 3H), 0.85 (d, J 6.8 Hz, 3H); 13C NMR (75 MHz, C6D6) δ 213.4 (C0),

160.4 (C0), 132.0 (C0), 127.9 (C1), 113.7 (C1), 101.7 (C1), 78.1 (C1), 72.3 (C1), 66.6 (C2), 54.7 (C3),

51.6 (C1), 47.2 (C2), 33.5 (C1), 28.5 (C2), 18.7 (C3), 17.7 (C3), 12.3 (C3); IR νmax (film) 3531, 3053,

2964, 2869, 1703, 1616, 1518, 1462, 1371, 1265, 1168, 1105, 1034, 831, 739 cm–1; HRMS (TOF-MS

ES+): calcd for C19H29O5: m/z 337.2015; found: m/z 337.1917 [MH+].

12c

O O

Me

O

PMP

OHMe

(2R,5S)-5-hydroxy-2-((2S,4S)-2-(4-methoxyphenyl)-1,3-dioxan-4-

yl)heptan-3-one (12c): Yield: 84% (ds 80:20); Rf 0.23 (Hex/EtOAc 30%); mp: 70–72 ºC; [α]D20 +4

(c 1.13, CH2Cl2); 1H NMR (250 MHz, C6D6) δ 7.54 (d, J 8.8 Hz, 2H), 6.81 (d, J 8.8 Hz, 2H), 5.32 (s,

1H), 3.53 (m, 2H), 3.79 (ddd, J 11.3, 6.2, 2.3 Hz, 1H), 3.49 (td, J 11.8, 2.5 Hz, 1H), 3.28 (s, 3H),

2.52–2.23 (m, 3H), 1.62 (m, 1H), 1.48–1.23 (m, 3H), 1.05 (d, J 7.0 Hz, 3H), 0.89 (t, J 7.0 Hz, 3H); 13C NMR (62.5 MHz, C6D6) δ 213.1 (C0), 160.4 (C0), 132.0 (C0), 127.8 (C1), 113.7 (C1), 101.6 (C1),

78.0 (C1), 69.1 (C1), 66.6 (C2), 54.7 (C3), 51.5 (C1), 49.7 (C1), 29.9 (C2), 28.7 (C2), 12.3 (C3), 10.0

(C3); IR νmax (film) 2968, 1701, 1616, 1518, 1464, 1421, 1265, 1109, 1034, 739 cm–1; HRMS (TOF-

MS ES+): calcd for C18H27O5: m/z 323.1859; found: m/z 323.1867 [MH+].

12d

O O

Me

O

PMP

OH

(1R,4R)-1-hydroxy-4-((2S,4S)-2-(4-methoxyphenyl)-1,3-dioxan-4-yl)-1-

phenylpentan-3-one (12d): Yield: 95% (ds 86:14); Rf 0.31 (Hex/EtOAc 30%); mp: 89–92 ºC; [α]D20

+16 (c 1.43, CH2Cl2); 1H NMR (250 MHz, C6D6) δ 7.55 (d, J 8.6 Hz, 2H), 7.28 (d, J 8.5 Hz, 2H),

7.20–7.08 (m, 3H), 6.81 (d, J 8.6 Hz, 2H), 5.29 (s, 1H), 5.12 (m, 1H), 3.91 (ddd, J 11.3, 5.0, 1.1 Hz,

Supporting Information File Dias et al. 12______________________________________________________________________________________________ 1H), 3.74 (ddd, J 11.3, 6.4, 2.3 Hz, 1H), 3.45 (td, J 11.8, 2.5 Hz, 1H), 3.26 (s, 3H), 3.13 (s, 1H), 2.75

(dd, J 17.5, 9.2 Hz, 1H), 2.53 (dd, J 17.5, 3.2 Hz, 1H), 2.41 (t, J 6.8 Hz, 1H), 1.56 (m, 1H), 0.98 (d, J

7.0 Hz, 4H); 13C NMR (62.5 MHz, C6D6) δ 212.1 (C0), 160.4, (C0)144.2 (C0), 131.9 (C0),128.5 (C1),

128.0 (C1), 127.5 (C1), 126.1 (C1), 113.8 (C1), 101.6 (C1), 77.9 (C1), 70.2 (C1), 66.6 (C2), 54.8 (C3),

52.1 (C2), 51.5 (C1), 28.5 (C2), 11.9 (C3); IR νmax (film) 3497, 3055, 2974, 2860, 1705, 1614, 1518,

1454, 1373, 1265, 1171, 1107, 1034, 831, 739 cm–1; HRMS (TOF-MS ES+): calcd for C22H27O5: m/z

371.1859; found: m/z 371.2025].

12e

O O

Me

O

PMP

OH

OMe (1R,4R)-1-hydroxy-1-(4-methoxyphenyl)-4-((2S,4S)-2-(4-

methoxyphenyl)-1,3-dioxan-4-yl)pentan-3-one (12e): Yield: 82% (ds 87:13); Rf 0.16 (Hex/EtOAc

30%); mp: 108–110 ºC; [α]D20 +17 (c 1.07, CH2Cl2); 1H NMR (250 MHz, C6D6) δ 7.54 (d, J 8.8 Hz,

2H), 7.23 (d, J 8.5 Hz, 2H), 6.80 (d, J 8.5 Hz, 2H), 6.79 (d, J 8.8 Hz, 2H), 5.30 (s, 1H), 5.13 (dd, J

9.5, 3.5 Hz, 1H), 3.92 (dd, J 11.1, 3.8 Hz, 1H), 3.76 (ddd, J 11.2, 6.5, 2.3 Hz, 1H), 3.46 (td, J 11.7, 2.3

Hz, 1H), 3.32 (s, 3H), 3.26 (s, 3H), 2.82 (dd, J 17.3, 9.1 Hz, 1H), 2.58 (dd, J 17.2, 3.5 Hz, 1H), 2.46

(t, J 6.9 Hz, 1H), 1.57 (m, 1H), 1.29 (m, 1H), 1.01 (d, J 7.0 Hz, 3H); 13C NMR (125 MHz, C6D6) δ

212.2 (C0), 160.4 (C0), 159.5 (C0), 136.2 (C0), 132.0 (C0), 127.9 (C1), 127.3 (C1), 114.0 (C1), 113.7

(C1), 101.6 (C1), 77.9 (C1), 69.9 (C1), 66.6 (C2), 54.8 (C3), 52.2 (C2), 51.6 (C1), 28.5 (C2), 12.0 (C3);

IR νmax (film) 3491, 2932, 2854, 1705, 1614, 1516, 1373, 1250, 1173, 1034, 831, 739 cm–1; HRMS

(TOF-MS ES+): calcd for C23H29O6: m/z 401.1964; found: m/z 401.1987].

12f

O O

Me

O

PMP

OH

NO2 (1R,4R)-1-hydroxy-4-((2S,4S)-2-(4-methoxyphenyl)-1,3-dioxan-4-

yl)-1-(4-nitrophenyl)pentan-3-one (12f): Yield: 52% (ds 80:20); Rf 0.17 (Hex/EtOAc 30%); [α]D20

+7 (c 1.18, CH2Cl2); 1H NMR (250 MHz, C6D6) δ 7.86 (d, J 8.8 Hz, 2H), 7.49 (d, J 8.8 Hz, 2H), 6.96

(d, J 9.0 Hz, 2H), 6.79 (d, J 9.0 Hz, 2H), 5.25 (s, 1H), 4.92 (m, 1H), 3.91 (dd, J 11.3, 6.2 Hz, 1H),

3.70 (ddd, J 11.4, 5.6, 2.3 Hz, 1H), 3.44 (td, J 11.8, 2.3 Hz, 1H), 3.30 (s, 3H), 2.66 (dd, J 10.4, 4.5 Hz,

1H), 2.59–2.34 (m, 2H), 1.58 (m, 2H), 1.25 (m, 1H), 0.96 (d, J 7.0 Hz, 3H); 13C NMR (62.5 MHz,

C6D6) δ 211.7 (C0), 160.5 (C0), 150.7 (C0), 147.5 (C0), 131.6 (C0), 127.8 (C1), 126.4 (C1), 123.5 (C1),

113.8 (C1), 101.7 (C1), 78.1 (C1), 69.2 (C1), 66.6 (C2), 54.8 (C3), 51.5 (C2), 51.0 (C1), 27.8 (C2), 11.5

Supporting Information File Dias et al. 13______________________________________________________________________________________________ (C3); IR νmax (film) 3483, 3053,2935, 2856, 1707, 1614, 1520, 1348, 1250, 1169, 1105, 1034, 831,

737 cm–1; HRMS (TOF-MS ES+): calcd for C22H26NO7: m/z 416.1709; found: m/z 416.1717 [MH+].

12g

O O

Me

O

PMP

OH

Me (2R,5R)-5-hydroxy-2-((2S,4S)-2-(4-methoxyphenyl)-1,3-dioxan-4-yl)-6-

methylhept-6-en-3-one (12g): Yield: 67% (ds 85:15); Rf 0.34 (Hex/EtOAc 30%); mp: 43–46 ºC;

[α]D20 +6 (c 1.02, CH2Cl2); 1H NMR (250 MHz, CDCl3) δ 7.56 (d, J 8.7 Hz, 2H), 6.82 (d, J 8.7 Hz,

2H), 5.30 (s, 1H), 5.06 (s, 1H), 4.79 (s, 1H), 4.49 (d, J 8.8 Hz, 1H), 3.91 (ddd, J 11.4, 3.8, 1.1 Hz,

1H), 3.77 (ddd, J 11.2, 6.6, 2.4 Hz, 1H), 3.45 (td, J 12.0, 2.6 Hz, 1H), 3.25 (s, 3H), 2.78 (brs, 1H),

2.60 (dd, J 17.2, 9.3 Hz, 1H), 2.53–2.36 (m, 2H), 1.68-1.51 (m, 1H), 1.61 (s, 3H), 1.02 (d, J 7.0 Hz,

4H); 13C NMR (62.5 MHz, C6D6) δ 212.4 (C0), 160.4 (C0), 146.6 (C0), 131.9 (C0), 127.9 (C1), 113.7

(C1), 110.9 (C2), 101.7 (C1), 78.0 (C1), 71.4 (C1), 66.7 (C2), 54.7 (C3), 51.5 (C1), 48.6 (C2), 28.5 (C2),

18.4 (C3), 12.2 (C3); IR νmax (film) 3502, 3055, 2984, 2860, 1703, 1616, 1518, 1373, 1265, 1107,

1034, 905, 748 cm–1; HRMS (TOF-MS ES+): calcd for C19H27O5: m/z 335.1859; found: m/z

335.1953 [MH+].

OH

Me Me

O

N O

O

Bn

PMBO

(R)-4-benzyl-3-((2R,3S,4R)-3-hydroxy-5-(4-methoxybenzyloxy)-2,4-

dimethylpentanoyl)oxazolidin-2-one: Di–n–butylborontrifluoromethanesulfonate (3.1 mL, 12.11

mmol) was added to a solution of (R)–4–benzyl–3–propionyloxazolidin–2–one (1.88 g, 8.07 mmol) in

15.1 mL of CH2Cl2 at –12 ºC. Next, diisopropylamine (2.4 mL, 13.72 mmol) was added dropwise.

The resulting yellow solution was then cooled to –78 ºC and a refrigerated solution of aldehyde (1M,

2.0187 g, 10.5 mmol) in CH2Cl2 was added slowly at –78 ºC. After 30 minutes, the solution was

warmed to –10 ºC and stirred at that temperature for 2 hours. The reaction was quenched by addition

of 18.1 mL of pH 7.0 aqueous phosphate buffer solution and 51 mL of MeOH (bath temperature =

–10 ºC). A solution of 48.2 mL of MeOH and 24.1 mL of 30% H2O2 aqueous solution was added

carefully and the resulting yellow solution was stirred at 0 ºC for 1 hour. The volatiles were removed

at aspirator pressure and the residue was extracted with Et2O (3 times). The combined organic extracts

were washed with saturated aqueous NaHCO3 and brine. The organic solution was dried over

anhydrous MgSO4 and purified by silica gel flash column chromatography (25% EtOAc/hexanes) to

give the syn–aldol adduct (80%) as colorless oil.

Supporting Information File Dias et al. 14______________________________________________________________________________________________ Yield: 80% (ds > 95:05); Rf 0.30 (Hex/EtOAc 25%); [α]D

20 –32 (c 1.2, CHCl3); 1H NMR (300 MHz,

CDCl3) δ 7.32–7.20 (m, 7H), 6.86 (d, J 8.4 Hz, 2H), 4.75 (m, 1H), 4.42 (s, 2H), 4.17 (m, 2H), 3.99

(m, 2H), 3.70 (s, 3H), 3.45 (dd, J 4.8, 1.8 Hz, 2H), 3.23 (dd, J 13.2, 3.3 Hz, 1H), 3.14 (brs, 1H), 2.77

(dd, J 13.7, 9.6 Hz, 1H), 1.88 (m, 1H), 1.32 (d, J 6.6 Hz, 3H), 1.02 (d, J 6.9 Hz, 3H); 13C NMR (75

MHz, CDCl3) δ 177.0 (C0), 159.1 (C0), 152.8 (C0), 135.0 (C0), 130.2 (C0), 129.4 (C1), 129.2 (C1),

128.9 (C1), 127.4 (C1), 113.7 (C1), 73.9 (C1), 73.8 (C2), 72.9 (C2), 66.0 (C2), 55.2 (C3), 55.1 (C1), 40.5

(C1), 37.7 (C2), 36.1 (C1), 12.8 (C3), 12.4 (C3); IR νmax (film): 3481, 2965, 2935, 2858, 1780, 1701,

1514, 1387, 1246, 1111, 1034, 829, 737 cm–1.

PMBO OH

Me Me

O

NMe

OMe

(2R,3S,4R)-3-hydroxy-N-methoxy-5-(4-methoxybenzyloxy)-N,2,4-

trimethylpentanamide: At 0 ºC, a suspension of N,O–dimethylhydroxylamine hydrochloride (0.44g,

4.52 mmol) in THF (3.3 mL) was cautiously treated with AlMe3 (2.0 M in toluene, 2.2 mL, 4.41

mmol). The resultant solution was stirred for 30 minutes at 0 ºC and 90 minutes at room temperature,

and then cooled to 20 ºC. A solution of aldol adduct (0.5 g, 1,13 mmol) in THF (2.5 mL) was added

dropwise. After an additional 90 minutes at room temperature, the solution was poured slowly into a

solution of aqueous HCl (1.0 M, 3.3 mL) and CH2Cl2 (6.5 mL) and stirred vigorously at 0 ºC for 90

minutes. The aqueous phase was extracted with CH2Cl2 (3 times), and the combined organic layers

were washed with water (2 times), brine, and dried over MgSO4, filtered and concentrated. The crude

material was dissolved in a minimal amount of Et2O. An equal volume of hexanes was added, and the

resultant solution was refrigerated (4 ºC) overnight. Filtration of the crystals afforded chiral auxiliary.

Concentration of the residual liquid and flash column chromatography (40% EtOAc/hexanes)

afforded Weinreb amide (70%) as colorless oil.

Yield: 70%; Rf 0.24 (Hex/EtOAc 30%); [α]D20 –1 (c 1.72, CHCl3); 1H NMR (300 MHz, CDCl3) δ

7.22 (d, J 8.4 Hz, 2H), 6.86 (d, J 8.4 Hz, 2H), 4.42 (d, J 4.5 Hz, 2H), 3.83 (d, J 2.7 Hz, 1H), 3.80 (s,

3H), 3.63 (s, 3H), 3.51 (dd, J 9.3, 4.2 Hz, 1H), 3.41 (dd, J 9.3, 5.7 Hz, 1H), 3.16 (brs, 4H), 3.03 (m,

H), 1.91–1.81 (m, 1H), 1.21 (d, J 7.2 Hz, 3H), 1.03 (d, J 6.9 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ

177.6 (C0), 159.1 (C0), 130.2 (C0), 129.0 (C1), 113.7 (C1), 74.9 (C2), 74.5 (C2), 73.0 (C2), 61.5 (C3),

55.2 (C3), 37.5 (C1), 35.7 (C1), 12.6 (C3), 12.3 (C3); IR νmax (film) 3466, 3053, 2978, 2939, 2878,

1634, 1514, 1462, 1248, 1175, 1088, 1036, 995, 824, 739 cm–1; HRMS (TOF-MS ES+): calcd for

C17H28NO5: m/z 326.1967; found: m/z 326.1905 [MH+].

Supporting Information File Dias et al. 15______________________________________________________________________________________________

O O

Me Me

O

NMe

OMe

PMP

(R)-N-methoxy-2-((2S,4S,5R)-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-4-

yl)-N-methylpropanamide: To a solution of Weinreb amide (0.28 g, 0.86 mmol) in 17.6 mL of

CH2Cl2 was added powdered activated 4Å molecular sieves (0.28 g) and stirred for 15 minutes under

argon atmosphere. After that, the temperature was reduced to –10 ºC and DDQ was added (0.21g,

0.95 mmol). After stirring for 3 hours at 0 ºC, the reaction mixture was diluted with Et2O (15 mL),

filtered through Celite column (h = 5 cm) and eluted with CH2Cl2. The filtered was washed with a

saturated aqueous solution of NaHCO3 (3 times), brine (3 times) and dried over MgSO4. The organic

layer was concentrated under reduced pressure and the residue was purified by flash column

chromatography (30% EtOAc/hexanes) to give the product (70%) as colorless oil.

Yield: 70%; Rf 0.32 (Hex/EtOAc 30%); [α]D20 –34.0 (c 0.85, CHCl3); 1H NMR (300 MHz, CDCl3) δ

7.43 (d, J 8.7 Hz, 2H), 6.89 (d, J 8.7 Hz, 2H), 5.50 (s, 1H), 4.09 (m, 2H), 3.91 (d, J 9.3 Hz, 1H), 3.80

(s, 3H), 3.72 (s, 3H), 3.19 (brs, 4H), 1.77 (m, 1H), 1.29 (d, J 6.9 Hz, 3H), 1.17 (d, J 6.9 Hz, 3H); 13C

NMR (75 MHz, CDCl3) δ 175.5 (C0), 159.8 (C0), 131.4 (C0), 127.2 (C1), 113.5 (C1), 101.8 (C1), 81.5

(C1), 73.6 (C2), 61.5 (C3), 55.3 (C3), 37.7 (C1), 29.9 (C1), 15.4 (C3), 11.6 (C3); IR νmax (film) 3055,

2988, 1665, 1421, 1265, 1115, 897, 741 cm–1; HRMS (ESI TOF-MS): calcd for C17H26NO5: m/z

324.1811; found: m/z 324.1645 [MH+].

O O

Me Me

O

Me

PMP

17 (R)-3-((2S,4S,5R)-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-4-yl)butan-2-one

(17): Under argon atmosphere, to a solution of acetal (0.185 g, 0.572 mmol) in dry THF (10.5 mL)

was added MeLi (1.3 M in ethylic ether, 2.2 mL, 2.86 mmol) dropwise at –78 ºC. The reaction

mixture was stirred for 45 minutes and next, was poured slowly into a solution of aqueous saturated

NH4Cl and Et2O and stirred vigorously at 0 ºC for 90 minutes. The organic layers were separated and

the aqueous phase was extracted with Et2O (3 times). The combined organic layers were washed with

brine and dried over MgSO4. The organic layer was concentrated under reduced pressure and the

residue purified by silica gel flash column chromatography (10% EtOAc/hexanes) giving the methyl

ketone 17 (94%) as white solid.

Yield: 94%; Rf 0.40 (Hex/EtOAc 15%); [α]D20 +14.0 (c 1.02, CHCl3); 1H NMR (300 MHz, CDCl3) δ

7.41 (d, J 8.7 Hz, 2H), 6.89 (d, J 8.7 Hz, 2H), 5.48 (s, 1H), 4.08 (dd, J 11.1, 2.7 Hz, 1H), 4.02 (dd, J

9.9, 2.4 Hz, 1H), 3.96 (dd, J 11.1, 1.4 Hz, 1H), 3.80 (s, 3H), 2.93 (m, 1H), 2.21 (s, 3H), 1.76 (m, 1H),

Supporting Information File Dias et al. 16______________________________________________________________________________________________ 1.25 (d, J 6.9 Hz, 3H), 1.14 (d, J 6.9 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 210.7 (C0), 159.9 (C0),

131.4 (C0), 127.3 (C1), 113.6 (C1), 101.9 (C1), 80.5 (C1), 73.5 (C2), 55.3 (C3), 49.0 (C1), 30.0 (C1),

29.5 (C3), 14.6 (C3), 11.8 (C3); IR νmax (film) 3057, 2926, 2859, 1701, 1615, 1516, 1461, 1263, 1169,

1114, 1036, 748 cm–1; HRMS (ESI TOF-MS): calcd for C16H23O4: m/z 279.1596; found: m/z

279.1563 [MH+].

O O

Me Me

O

PMP

OH

Me

Me

18b (2R,5R)-5-hydroxy-2-((2S,4S,5R)-2-(4-methoxyphenyl)-5-methyl-1,3-

dioxan-4-yl)-6-methylheptan-3-one (18b): Yield: 97% (ds 86:14); Rf 0.33 (Hex/EtOAc 20%); mp:

82–85 ºC; [α]D20 +22 (c 1.0, Me2CO); 1H NMR (300 MHz, CDCl3) δ 7.41 (d, J 8.7 Hz, 2H), 6.89 (d, J

8.7 Hz, 2H), 5.48 (s, 1H), 4.08 (dd, J 11.4, 2.4 Hz, 1H), 4.04 (dd, J 9.2, 2.7 Hz, 1H), 3.95 (dd, J 11.4,

1.2 Hz, 1H), 3.81 (m, 1H), 3.80 (s, 3H), 2.88 (dd, J 9.9, 6.9 Hz, 1H), 2.75 (dd, J 18.9, 2.1 Hz, 1H),

2.51 (dd, J 17.4, 9.9 Hz, 1H), 1.69 (m, 2H), 1.24 (d, J 6.9 Hz, 3H), 1.15 (d, J 6.9 Hz, 3H), 0.94 (d, J

6.6 Hz, 3H), 0.92 (d, J 6.6 Hz, 3H); 1H NMR (300 MHz, C6D6) δ 7.57 (d, J 8.6 Hz, 2H), 6.84 (d, J 8.6

Hz, 2H), 5.38 (s, 1H), 3.98 (dd, J 10.1, 2.3 Hz, 1H), 3.75 (m, 1H), 3.72 (d, J 1.8 Hz, 2H), 3.28 (s, 3H),

2.82 (d, J 3.3 Hz, 1H), 2.66 (dd, J 6.9, 9.9 Hz, 1H), 2.27 (m, 2H), 1.50 (m, 2H), 1.11 (d, J 6.3 Hz,

3H), 1.10 (d, J 6.9 Hz, 3H), 0.91 (d, J 6.6 Hz, 3H), 0.85 (d, J 6.9 Hz, 3H); 13C NMR (75 MHz, C6D6)

δ 213.7 (C0), 160.4 (C0), 132.3 (C0), 127.8 (C1), 113.7 (C1), 102.3 (C1), 80.7 (C1), 73.4 (C2), 72.4 (C1),

54.7 (C3), 49.2 (C1), 46.2 (C2), 33.4 (C1), 30.4 (C1), 18.7 (C3), 17.5 (C3), 14.5 (C3), 12.0 (C3); IR νmax

(film) 3541, 3055, 2966, 2934, 2873, 1701, 1618, 1518, 1464, 1382, 1265, 1172, 1110, 1032 cm–1;

HRMS (TOF-MS ES+): calcd for C20H31O5: m/z 351.2172; found: m/z 351.2016 [MH+].

O O

Me Me

O

PMP

OH

18c

Me

(2R,5S)-5-hydroxy-2-((2S,4S,5R)-2-(4-methoxyphenyl)-5-methyl-1,3-

dioxan-4-yl)heptan-3-one (18c): Yield: 51% (ds 88:12); Rf 0.19 (Hex/EtOAc 20%); mp: 90–93 ºC;

[α]D20 +14 (c 0.54, CH2Cl2); 1H NMR (250 MHz, C6D6) δ 7.56 (d, J 8.8 Hz, 2H), 6.84 (d, J 8.8 Hz,

2H), 5.37 (s, 1H), 3.96 (dd, J 10.0, 2.2 Hz, 1H), 3.85 (m, 1H), 3.73 (d, J 1.8 Hz, 2H), 3.28 (s, 3H),

2.63 (dd, J 10.0, 7.0 Hz, 1H), 2.20 (m, 2H), 1.53–1.17 (m, 4H), 1.10 (t, J 6.9 Hz, 3H), 0.92 (d, J 6.6

Hz, 3H), 0.90 (t, J 7,8 Hz, 3H); 13C NMR (62.5 MHz, C6D6) δ 213.4 (C0), 160.4 (C0), 132.2 (C0),

127.8 (C1), 113.7 (C1), 102.3 (C1), 80.6 (C1), 73.4 (C2), 69.1 (C1), 54.7 (C3), 49.0 (C1), 48.7 (C2), 30.3

(C1), 29.8 (C2), 14.6 (C3), 12.0 (C3), 10.0 (C3); IR νmax (film) 3446, 3060, 2966, 2931, 2852, 1701,

Supporting Information File Dias et al. 17______________________________________________________________________________________________ 1612, 1518, 1464, 1265, 1115, 1034 cm–1; HRMS (ESI TOF-MS): calcd for C19H29O5: m/z 337.2015;

found: m/z 337.1917 [MH+].

18d

O O

Me Me

O

PMP

OH

(1R,4R)-1-hydroxy-4-((2S,4S,5R)-2-(4-methoxyphenyl)-5-methyl-1,3-

dioxan-4-yl)-1-phenylpentan-3-one (18d): Yield: 69% (ds 72:28); Rf 0.26 (Hex/EtOAc 20%); mp:

106–110 ºC; [α]D20 +19 (c 1.01, CH2Cl2); 1H NMR (300 MHz, C6D6) δ 7.55 (d, J 8.7 Hz, 2H), 7.28

(m, 2H), 7.19 (m, 2H), 7.09 (m, 1H), 6.83 (d, J 8.7 Hz, 2H), 5.36 (s, 1H), 5.08 (dd, J 8.7, 3.6 Hz, 1H),

3.94 (dd, J 10.1, 2.3 Hz, 1H), 3.71 (m, 2H), 3.27 (s, 3H), 2.98 (brs, 1H), 2.66 (m, 2H), 2.62 (ddd, J

14.3, 8.7, 3.6 Hz, 1H), 1.44 (m, 1H), 1.07 (d, J 6.6 Hz, 3H), 1.04 (d, J 6.9 Hz, 3H); 13C NMR (75

MHz, C6D6) δ 212.2 (C0), 160.4 (C0), 144.0 (C0), 132.2 (C0), 128.6 (C1), 127.80 (C1), 127.78 (C1),

126.0 (C1), 113.7 (C1), 102.2 (C1), 80.5 (C1), 73.4 (C2), 70.2 (C1), 54.7 (C3), 51.1 (C2), 49.2 (C1), 30.4

(C1), 14.3 (C3), 12.0 (C3); IR νmax (film) 3502, 3055, 2977, 2937, 2863, 1703, 1624, 1518, 1456,

1265, 1169, 1032 cm–1; HRMS (ESI TOF-MS): calcd for C23H29O5: m/z 385.2015; found: m/z

385.2003 [MH+].

18e

O O

Me Me

O

PMP

OH

OMe (1R,4R)-1-hydroxy-1-(4-methoxyphenyl)-4-((2S,4S,5R)-2-(4-

methoxyphenyl)-5-methyl-1,3-dioxan-4-yl)pentan-3-one (18e): Yield: 70% (ds 86:14); Rf 0.30

(Hex/EtOAc 30%); mp: 123–126 ºC; [α]D20 +17 (c 1.03, CH2Cl2); 1H NMR (300 MHz, CDCl3) δ 7.30

(d, J 9.0 Hz, 2H), 7.18 (d, J 9.0 Hz, 2H), 6.78 (d, J 8.7 Hz, 4H), 5.37 (s, 1H), 5.00 (dd, J 7.5, 5.1 Hz,

1H), 3.95 (dd, J 11.1, 2.7 Hz, 1H), 3.93 (dd, J 9.9, 2.7 Hz, 1H), 3.84 (dd, J 11.1, 1.2 Hz, 1H), 3.70 (s,

3H), 3.69 (s, 3H), 3.09 (brs, 1H), 2.77 (m, 3H), 1.56 (m, 1H), 1.10 (d, J 6.9 Hz, 3H), 1.02 (d, J 6.9 Hz,

3H); 13C NMR (75 MHz, CDCl3) δ 213.1 (C0), 159.8 (C0), 159.1 (C0), 134.9 (C0), 131.2 (C0), 127.2

(C1), 126.9 (C1), 113.9 (C1), 113.5 (C1), 101.9 (C1), 80.3 (C1), 73.4 (C2), 69.6 (C1), 55.2 (C3), 50.7

(C2), 48.9 (C1), 30.0 (C1), 14.4 (C3), 11.7 (C3); IR νmax (film) 3472, 3055, 2985, 1701, 1613, 1516,

1427, 1265, 1171, 1115, 1034 cm–1; HRMS (ESI TOF-MS): calcd for C24H30O6K: m/z 453.1679;

found: m/z 453.1748.

Supporting Information File Dias et al. 18______________________________________________________________________________________________

18f

O O

Me Me

O

PMP

OH

NO2 (1R,4R)-1-hydroxy-4-((2S,4S,5R)-2-(4-methoxyphenyl)-5-methyl-

1,3-dioxan-4-yl)-1-(4-nitrophenyl)pentan-3-one (18f): Yield: 55% (ds > 95:5); Rf 0.43 (Hex/EtOAc

40%), mp: 153–156 ºC; [α]D20 +42 (c 1.0, Me2CO); 1H NMR (250 MHz, CDCl3) δ 8.20 (d, J 8.8 Hz,

2H), 7.53 (d, J 8.8 Hz, 2H), 7.39 (d, J 8.8 Hz, 2H), 6.89 (d, J 8.8 Hz, 2H), 5.47 (s, 1H), 5.26 (dd, J 3.3

Hz, 1H), 4.07 (dd, J 8.9, 1.9 Hz, 1H), 3.97 (d, J 11.2 Hz, 1H), 3.80 (m, 3H), 3.60 (brs, 1H), 2.92 (m,

3H), 1.68 (m, 1H), 1.24 (d, J 7.1 Hz, 3H), 1.12 (d, J 6.9 Hz, 3H); 13C NMR (62.5 MHz, CDCl3) δ

212.6 (C0), 159.9 (C0), 149.9 (C0), 147.3 (C0), 131.1 (C0), 127.2 (C1), 126.4 (C1), 123.8 (C1), 113.6

(C1), 101.9 (C1), 80.2 (C1), 73.4 (C2), 69.1 (C1), 55.3 (C3), 50.3 (C2), 48.9 (C1), 30.0 (C1)14.5 (C3),

11.8 (C3); IR νmax (film) 3055, 2977, 2937, 2864, 1703, 1616, 1519, 1348, 1265, 1170, 1115, 1034

cm–1; HRMS (ESI TOF-MS): calcd for C23H28NO7: m/z 430.1866; found: m/z 430.1694.

18g

O O

Me Me

O

PMP

OH

Me (2R,5R)-5-hydroxy-2-((2S,4S,5R)-2-(4-methoxyphenyl)-5-methyl-1,3-

dioxan-4-yl)-6-methylhept-6-en-3-one (18g): Yield: 89% (ds 78:22); Rf 0.28 (Hex/EtOAc 20%);

mp: 73–75 ºC; [α]D20 +22 (c 1.03, Me2CO); 1H NMR (250 MHz, C6D6) δ 7.56 (d, J 8.7 Hz, 2H), 6.83

(d, J 8.7 Hz, 2H), 5.37 (s, 1H), 5.05 (s, 1H), 4.80 (s, 1H), 4.47 (dd, J 7.8, 4.0 Hz, 1H), 3.97 (dd, J 9.9,

2,2 Hz, 1H), 3.75 (m, 1H), 3.73 (d, J 1.8 Hz, 2H), 3.27 (s, 3H), 2.66 (dq, J 10.0, 7.0 Hz, 1H), 2.39 (m,

2H), 1.61 (s, 3H), 1.52 (m, 1H), 1.10 (d, J 7.0 Hz, 3H), 1.09 (d, J 7.0 Hz, 3H); 13C NMR (125 MHz,

C6D6) δ 212.4 (C0), 160.4 (C0), 146.5 (C0), 132.2 (C0), 127.9 (C1), 113.7 (C1), 110.9 (C2), 102.3 (C1),

80.5 (C1), 73.4 (C2), 71.5 (C1), 54.7 (C3), 49.2 (CX), 47.5 (C2), 30.3 (C1), 18.3 (C3), 14.5 (C3), 12.0

(C3); IR νmax (film) 3514, 3055, 2985, 2941, 2858, 1701, 1612, 1518, 1421, 1265, 1165, 1034 cm–1;

HRMS (ESI TOF-MS): calcd for C20H29O5: m/z 349.2015; found: m/z 349.2015 [MH+].

18h

O O

Me Me

O

PMP

OH

Me

(2R,5S)-5-hydroxy-2-((2S,4S,5R)-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-

4-yl)hexan-3-one (18h): Yield: 65% (ds 89:11); Rf 0.34 (Hex/EtOAc 40%); mp: 96–100 ºC; [α]D20

+28 (c 1.02, CH2Cl2); 1H NMR (500 MHz, C6D6) δ 7.56 (d, J 9.0 Hz, 2H), 6.83 (d, J 9.0 Hz, 2H),

5.36 (s, 1H), 4.10 (m, 1H), 3.95 (dd, J 10.0, 2.0 Hz, 1H), 3.71 (s, 2H), 3.27 (s, 3H), 2.61 (dq, J 10.0,

Supporting Information File Dias et al. 19______________________________________________________________________________________________ 7.0 Hz, 1H), 2.16 (m, 2H), 1.46 (m, 1H), 1.08 (d, J 6.5 Hz, 3H), 1.08 (d, J 7.0 Hz, 3H), 1.03 (d, J 6.5

Hz, 3H); 13C NMR (125 MHz, C6D6) δ 213.1 (C0), 160.4 (C0), 132.2 (C0), 127.8 (C1), 113.7 (C1),

102.2 (C1), 80.6 (C1), 73.4 (C2), 64.0 (C1), 54.7 (C3), 50.5 (C2), 48.9 (C1), 30.3 (C1), 22.7 (C3), 14.5

(C3), 12.0 (C3); IR νmax (film) 3502, 3055, 2972, 2930, 2863, 1703, 1518, 1462, 1265, 1115, 1043

cm–1; HRMS (ESI TOF-MS): calcd for C18H27O5: m/z 323.1859; found: m/z 323.1880.

18i

O O

Me Me

O

PMP

OH

(2R,5S)-5-hydroxy-2-((2S,4S,5R)-2-(4-methoxyphenyl)-5-methyl-

1,3-dioxan-4-yl)-7-phenylheptan-3-one (18i): Yield: 94% (ds 90:10); Rf 0.21 (Hex/EtOAc 20%);

mp: 112–115 ºC; [α]D20 +9 (c 1.01, Me2CO); 1H NMR (300 MHz, C6D6) δ 7.56 (d, J 8.7 Hz, 2H), 7.11

(m, 5H), 6.83 (d, J 8.7 Hz, 2H), 5.36 (s, 1H), 3.94 (dd, J 9.9, 2.1 Hz, 2H), 3.70 (d, J 1.8 Hz, 2H), 3.27

(s, 3H), 2.80 (m, 1H), 2.62 (m, 2H), 2.18 (d, J 5.9 Hz, 2H), 1.70 (m, 1H), 1.48 (m, 2H), 1.07 (d, J 7.1

Hz, 3H), 1.06 (d, J 7.0 Hz, 3H); 13C NMR (75 MHz, C6D6) δ 213.4 (C0), 160.4 (C0), 142.4 (C0), 132.2

(C0), 128.8 (C1), 128.7 (C1), 127.8 (C1), 126.1 (C1), 113.7 (C1), 102.3 (C1), 80.5 (C1), 73.4 (C2), 67.0

(C1), 54.7 (C3), 49.06 (C2), 49.00 (C1), 38.7 (C2), 32.1 (C2), 30.3 (C1), 14.6 (C3), 12.0 (C3); IR νmax

(film) 3055, 2985, 2930, 2858, 1701, 1617, 1518, 1265, 1165, 1115, 1032 cm–1; HRMS (ESI TOF-

MS): calcd for C25H33O5: m/z 413.2379; found: m/z 413.2328.

18j

O O

Me Me

O

PMP

OH

(2R,5R)-5-hydroxy-2-((2S,4S,5R)-2-(4-methoxyphenyl)-5-methyl-1,3-

dioxan-4-yl)hept-6-en-3-one (18j): Yield: 72% (ds 86:14); Rf 0.38 (Hex/EtOAc 20%); mp: 82–85

ºC; [α]D20 +11 (c 1.0, Me2CO); 1H NMR (250 MHz, C6D6) δ 7.55 (d, J 8.7 Hz, 2H), 6.83 (d, J 8.7 Hz,

2H), 5.73 (m, 1H), 5.36 (s, 1H), 5.29 (dt, J 17.2, 1.6 Hz, 1H), 5.00 (dt, J 10.2, 1.6 Hz, 1H), 4.50 (m,

1H), 3.95 (dd, J 9.9, 2.1 Hz, 1H), 3.72 (d, J 1.9 Hz, 1H), 3.28 (s, 3H), 2.61 (dd, J 11.0, 7.0 Hz, 1H),

2.30 (m, 2H), 1.48 (m, 1H), 1.07 (d, J 7.2 Hz, 6H); 13C NMR (62.5 MHz, C6D6) δ 212.1 (C0), 160.3

(C0), 139.9 (C1), 132.2 (C0), 127.8 (C1), 114.3 (C2), 113.7 (C1), 102.2 (C1), 80.5 (C1), 73.4 (C2), 68.6

(C1), 54.7 (C3), 49.1 (C1), 48.7 (C2), 30.3 (C1), 14.4 (C3), 12.0 (C3); IR νmax (film) 3518, 3055, 2984,

2940, 2858, 1703, 1623, 1518, 1382, 1265, 1176, 1115, 1032 cm–1; HRMS (ESI TOF-MS): calcd for

C19H27O5: m/z 335.1859; found: m/z 335.1925.

Supporting Information File Dias et al. 20______________________________________________________________________________________________

18k

O O

Me Me

O

PMP

OH

F (1R,4R)-1-(4-fluorophenyl)-1-hydroxy-4-((2S,4S,5R)-2-(4-

methoxyphenyl)-5-methyl-1,3-dioxan-4-yl)pentan-3-one (18k): Yield: 59% (ds 86:14); Rf 0.44

(Hex/EtOAc 30%); mp: 101–104 ºC; [α]D20 +20 (c 0.73, Me2CO); 1H NMR (250 MHz, C6D6) δ 7.55

(d, J 8.7 Hz, 2H), 7.06 (dd, J 8.5, 5.5 Hz, 2H), 6.86 (d, J 8.7 Hz, 2H), 6.83 (d, J 8.7 Hz, 2H), 5.35 (s,

1H), 4.96 (dd, J 10.4, 3.5 Hz, 1H), 3.94 (dd, J 9.8, 2.3 Hz, 1H), 3.72 (d, J 1.8 Hz, 2H), 3.28 (s, 3H),

3.03 (brs,1H), 2.62 (d, J 9.9, 7.0 Hz, 1H), 2.46 (m, 2H), 1.45 (m, 1H), 1.07 (d, J 6.9 Hz, 3H), 1.05 (d,

J 6.5 Hz, 3H); 13C NMR (62.5 MHz, C6D6) δ 212.1 (C0), 160.4 (C0), 138.6 (C0), 132.1 (C0), 127.8

(C1), 126.8 (C1), 115.5 (C1), 115.2 (C1), 113.7 (C1), 102.3 (C1), 80.4 (C1), 73.4 (C2), 69.5 (C1), 54.7

(C3), 51.1 (C2), 49.1 (C1), 30.3 (C1), 14.3 (C3), 12.0 (C3); IR νmax (film) 3483, 3051, 2934, 2852,

1707, 1616, 1512, 1375, 1265, 1169, 1032, 833, 739 cm–1; HRMS (ESI TOF-MS): calcd for

C23H27O5NaF: m/z 425.1740; found: m/z 425.1747 [MH+].

20

O O

Me

PMP

OHMe

Me

OH

Me (2S,3S,5R)-2-((2S,4S,5R)-2-(4-methoxyphenyl)-5-methyl-1,3-dioxan-4-yl)-

6-methylheptane-3,5-diol (20): 20 mg of aldol adduct 18b (0.0571 mmol) was dissolved in a

solution of THF:MeOH 4:1 (0.3 mL). Next, di–n–butylmethoxyborane (9 μL, 0.068 mmol) was added

at –78 ºC under argon atmosphere. The resulting solution was stirred for 15 minutes, before addition

of lithium borohydride solution (2.0 M in THF, 68 μL, 0.068 mmol). After stirring for 5 minutes at –

78 ºC, the mixture was allowed to warm to –40º C and then the reaction was quenched by addition of

pH 7.0 aqueous phosphate buffer solution (0.8 mL). After that, MeOH (1.5 mL) and H2O2 25% (0.6

mL) were added dropwise at 0 ºC. The resulting mixture was stirred for 1 hour at 0 ºC. The solution

was diluted with H2O (2.3 mL), and the mixture was extracted with ethyl acetate (4 times), washed

with saturated aqueous solution of NaHCO3, brine, dried with MgSO4, concentrated under vacuum.

The crude product was purified by flash chromatography (30% EtOAc/hexanes) to give the desired

product 20 (83 %).

Yield: 83% (ds > 95:05); Rf 0.28 (Hex/EtOAc 30%); [α]D20 +17 (c 3.38, CH2Cl2); 1H NMR (250

MHz, C6D6) δ 7.62 (d, J 8.7 Hz, 2H), 6.84 (d, J 8.7 Hz, 2H), 5.41 (s, 1H), 3.74 (m, 3H), 3.56 (dd, J

8.7, 1.8 Hz, 1H), 3.44 (ddd, J 10.2, 4.6, 1.5 Hz, 1H), 3.27 (m, 3H), 1.93 (m, 1H), 1.53 (m, 2H), 1.32–

1.24 (m, 3H), 1.13 (d, J 6.8 Hz, 3H), 0.92 (d, J 6.7 Hz, 3H), 0.89 (d, J 6.8 Hz, 3H); 13C NMR (62.5

Supporting Information File Dias et al. 21______________________________________________________________________________________________ MHz, C6D6) δ 160.4 (C0), 132.3 (C0), 127.8 (C1), 113.8 (C1), 102.2 (C1), 81.6 (C1), 78.1 (C1), 73.8

(C2), 73.5 (C1), 54.7 (C3), 41.6 (C1), 35.0 (C2), 34.6 (C1), 31.7 (C1), 18.7 (C3), 17.3 (C3), 12.1 (C3),

11.0 (C3); IR νmax (film) 3424, 3053, 2964, 1615, 1588, 1518, 1464, 1302, 1265, 1169, 1112, 1033

960, 739 cm–1. HRMS (ESI TOF-MS): calcd for C20H33O5: 353.2328; found: 353.2325.

21

O O

Me

OMe

Me

O

Me Me Me Me

Me (4S,5R)-4-((S)-1-((4S,6R)-6-isopropyl-2,2-dimethyl-1,3-dioxan-4-

yl)ethyl)-2,2,5-trimethyl-1,3-dioxane (21): The diol 20 (16.5 mg, 0.0468 mmol) was dissolved in

2,2–dimethoxypropane (1.2 mL), followed by addition of CSA in catalytic amounts at room

temperature. The reaction mixture was stirred for 1 hour before it was diluted with Et2O (2 mL) and a

solution of saturated aqueous NaHCO3. The organic layer was separated, and the aqueous layer was

further extracted with Et2O (3 times). The combined organic layer was dried over MgSO4, filtered and

concentrated. The crude product was purified by silica gel flash column chromatography (6%

EtOAc/hexanes) to afford the desired acetonide 21 (85 %).

Yield: 85%; Rf 0.40 (Hex/EtOAc 2%); [α]D20 +2 (c 0.92, CH2Cl2); 1H NMR (250 MHz, C6D6) δ 3.87

(dd, J 11.2, 2.6 Hz, 1H), 3.80 (dd, J 7.7, 2.3 Hz, 1H), 3.66 (ddd, J 10.8, 6.2, 3.2 Hz, 1H), 3.47 (dd, J

11.3, 1.7 Hz, 1H), 3.36 (ddd, J 10.7, 6.3, 3.1 Hz, 1H), 1.91 (m, 1H), 1.64 (m, 1H), 1.52 (s, 3H), 1.51

(s, 3H), 1.33 (d, J 8.1 Hz, 6H), 1.26–1.20 (m, 2H), 1.25 (s, 3H), 1.08 (d, J 6.8 Hz, 3H), 1.02 (d, J 6.7

Hz, 3H), 0.88 (d, J 6.8 Hz, 3H); 13C NMR (62.5 MHz, C6D6) δ 98.6 (C0), 98.0 (C0), 73.9 (C1), 73.0

(C1), 69.9 (C1), 67.0 (C2), 40.1 (C1), 33.3 (C1), 32.4 (C1), 30.3 (C3), 30.1 (C2), 29.9 (C3), 19.5 (C3),

18.9 (C3), 18.1 (C3), 18.0 (C3), 11.7 (C3), 10.9 (C3); IR νmax (film) 3053, 2991, 2875, 1463, 1380,

1265, 1243, 1090, 1008, 869, 739, 705 cm–1; HRMS (ESI TOF-MS): calcd for C18H35O4: m/z

315.2572; found: m/z 315.2596.

22

O O

Me

PMP

OMe

Me

OTBS TBS

Me (5R,7S)-5-isopropyl-7-((R)-1-((2S,4S,5R)-2-(4-methoxyphenyl)-5-methyl-

1,3-dioxan-4-yl)ethyl)-2,2,3,3,9,9,10,10-octamethyl-4,8-dioxa-3,9-disilaundecane (22): 2,6–

Lutidine (0.15 mL, 1.24 mmol) and TBSOTf (1.95 mL, 8.49 mmol) were added to a stirred solution of

the diol 20 (66.4 mg, 0.1884 mmol) in 1.8 mL of CH2Cl2 at 0 ºC. After 1 hour, the reaction mixture

was quenched by the addition of a saturated solution of NaHCO3. The organic layer was extracted

with CH2Cl2 (4 times), and the combined organic phases were dried over MgSO4, filtered and

Supporting Information File Dias et al. 22______________________________________________________________________________________________ concentrated under reduced pressure. The crude product was purified by flash column

chromatography (2.4% EtOAc/hexanes) to give the bis–TBS ether 22 (87%).

Yield: 87%; Rf 0.42 (Hex/EtOAc 5%); [α]D20 –14 (c 1.05, CH2Cl2); 1H NMR (500 MHz, C6D6) δ 7.62

(d, J 8.4 Hz, 2H), 6.84 (d, J 8.4 Hz, 2H), 5.37 (s, 1H), 3.99 (ddd, J 10.5, 3.3, 1.5 Hz, 1H), 3.92 (m,

1H), 3.82 (d, J 11.0 Hz, 1H), 3.71 (dd, J 11.0, 1.0 Hz; 1H), 3.47 (dd, J 9.5, 2.0 Hz, 1H), 3.29 (s, 3H),

2.10 (m, 1H), 1.87 (ddd, J 13.9, 11.0, 2.0 Hz, 1H), 1.80 (quint.d, J 6.5, 1.5 Hz, 1H), 1.58 (ddd, J 13.8,

10.8, 1.5 Hz, 2H), 1.38 (m, 1H), 1.28 (d, J 7.0 Hz, 3H), 1.27 (d, J 7.0 Hz, 3H), 1.12 (d, J 7.0 Hz, 3H),

1.07 (s, 9H), 1.03 (d, J 0.5 Hz, 3H), 1.01 (s, 9H), 0.97 (s, 3H), 0.25 (s, 3H), 0.20 (s, 3H), 0.10 (s, 3H),

0.08 (s, 3H); 13C NMR (62.5 MHz, C6D6) δ 160.3 (C0), 132.5 (C0), 127.8 (C1), 113.7 (C1), 102.2 (C1),

82.1 (C1), 73.3 (C2), 73.2 (C1), 68.3 (C1), 54.7 (C3), 41.2 (C1), 37.0 (C2), 31.0 (C1), 30.4 (C1), 26.2

(C3), 26.1 (C3), 21.1 (C3), 18.4 (C0), 18.2 (C0), 14.5 (C3), 11.9 (C3), 10.0 (C3), –3.7 (C3), –3.8 (C3), –

4.5 (C3), –4.6 (C3); IR νmax (film) 2957, 2858, 1618, 1518, 1377, 1250, 1169, 1041, 854, 835 cm–1;

HRMS (ESI TOF-MS): calcd for C32H61Si2O5: m/z 581.4058; found: m/z 581.4131.

23

OH O

Me

PMBO

Me

Me

OTBS TBS

Me (2R,3S,4R,5S,7R)-5,7-bis(tert-butyldimethylsilyloxy)-3-(4-

methoxybenzyloxy)-2,4,8-trimethylnonan-1-ol (23): A solution of DIBAL–H (1.5 M in toluene,

0.47 mL, 0.709 mmol) was added to a stirred solution of the PMP–acetal 22 (82.4 mg, 0.1418 mmol)

in 1.4 mL of CH2Cl2 at –30 ºC under argon atmosphere. The reaction mixture was stirred for 5

minutes, and the solution was poured slowly into a mixture of CH2Cl2/solution of aqueous Na/K

tartrate, and stirred vigorously at 0 ºC for 1 hour. The organic phase was separated and the aqueous

phase was extracted with CH2Cl2 (3 times). The combined organic phases were dried over MgSO4,

filtered and concentrated in vacuo. The crude product was purified by flash column chromatography

(10% EtOAc/hexanes) to give the alcohol 23 (85%) as colorless oil.

Yield: 85%; Rf 0.32 (Hex/EtOAc 5%); [α]D20 –21 (c 1.29, CH2Cl2); 1H NMR (250 MHz, CDCl3) δ

7.28 (d, J 8.7 Hz, 2H), 6.87 (d, J 8.7 Hz, 2H), 4.54 (d, J 10.8 Hz, 1H), 4.51 (d, J 10.8 Hz, 1H), 3.80

(m, 3H), 3.74–3.51 (m, 4H), 3.45 (dd, J 7.2, 2.3 Hz, 1H), 1.94 (m, 3H), 1.72 (m, 1H), 1.53 (m,1H),

1.10 (d, J 6.9 Hz, 3H), 0.94–0.89 (m,6H), 0.91 (s, 9H), 0.90 (s, 9H), 0.82 (d, J 6.8 Hz, 3H), 0.07 (s,

3H), 0.06 (s, 3H), 0.05 (s, 3H), 0.04 (s, 3H); 13C NMR (62.5 MHz, CDCl3) δ 159.1 (C0), 130.8 (C0),

129.3 (C1), 113.8 (C1), 80.9 (C1), 73.9 (C2), 72.8 (C1), 70.7 (C1), 66.0 (C2), 55.2 (C3), 41.1 (C1), 38.1

(C1), 36.0 (C2), 30.6 (C1), 26.0 (C3), 25.9 (C3), 19.8 (C3), 18.1 (C0), 18.0 (C0), 14.9 (C3), 10.74 (C3),

10.70 (C3), –4.0 (C3), –4.1 (C3), –4.6 (C3), –4.7 (C3); IR νmax (film) 3448, 1957, 1612, 1514, 1389,

Supporting Information File Dias et al. 23______________________________________________________________________________________________ 1250, 1041, 851, 835 cm–1; HRMS (ESI TOF-MS): calcd for C32H63Si2O5: m/z 583.4214; found: m/z

583.4224.

24

OBn O

Me

PMBO

Me

Me

OTBS TBS

Me (5S,7R)-5-((2R,3S,4R)-5-(benzyloxy)-3-(4-methoxybenzyloxy)-4-

methylpentan-2-yl)-7-isopropyl-2,2,3,3,9,9,10,10-octamethyl-4,8-dioxa-3,9-disilaundecane (24):

To a solution of alcohol 23 (64.0 mg, 0.1098 mmol) in 0.5 mL of DMF and under argon atmosphere

was added 60% NaH (17.6 mg, 0.44 mmol) and stirred for 1 hour at room temperature. Next, BnBr

(78.3 μL, 0.6587 mmol) and n–Bu4NI (catalytic amounts) were added. The reaction mixture was

stirred for 18 hours and concentrated under reduced pressure. The crude product was purified by flash

column chromatography (1% EtOAc/hexanes and 2% EtOAc/hexanes) to afford the benzyl ether 24

(53%) as colorless oil.

Yield: 53%; Rf 0.48 (Hex/EtOAc 5%); [α]D20 –35 (c 2.41, CH2Cl2); 1H NMR (250 MHz, CDCl3) δ

7.32–7.26 (m, 5H), 7.22 (d, J 8.7 Hz, 2H), 6.85 (d, J 8.7 Hz, 2H), 4.53 (d, J 10.7 Hz, 1H), 4.47 (s,

2H), 4.38 (d, J 10.7 Hz, 1H), 3.80 (s, 3H), 3.74 (m,1H), 3.65 (dd, J 8.5, 4.5 Hz, 1H), 3.48–3.42 (m,

2H), 3.31 (dd, J 8.8, 5.9 Hz, 1H), 1.93 (m, 1H), 1.69 (s, 1H), 1.52 (m, 1H), 1.04 (d, J 6.8 Hz, 3H),

0.94–0.89 (m, 6H), 0.92 (s, 9H), 0.90 (s, 9H), 0.07 (s, 3H), 0.04–0.03 (m, 12H); 13C NMR (62.5 MHz,

CDCl3) δ 159.0 (C0), 138.6 (C0), 131.4 (C0), 129.2 (C1), 128.3 (C1), 127.5 (C1), 113.7 (C1), 80.1 (C1),

74.6 (C2), 72.9 (C2), 72.8 (C2), 69.8 (C1), 55.3 (C3), 41.9 (Cx), 36.4 (C1), 36.0 (C1), 30.4 (C0), 26.0

(C1), 25.9 (C3), 25.8 (C3), 20.3 (C3), 18.1 (C0), 18.0 (C0), 17.7 (C3), 14.5 (C3), 10.6 (C3), 10.5 (C3), –

3.9 (C3), –4.1 (C3), –4.2 (C3), –4.3 (C3); IR νmax (film) 2957, 2856, 1514, 1362, 1250, 1051, 1007,

835, 773 cm–1; HRMS (ESI TOF-MS): calcd for C39H69Si2O5: m/z 673.4684; found: m/z 673.4765.

25

OBn O

Me

PMBOH

Me

Me

OH

Me (3R,5S,6S,7S,8R)-9-(benzyloxy)-7-(4-methoxybenzyloxy)-2,6,8-

trimethylnonane-3,5-diol (25): The benzyl ether 24 (136.8 mg, 0.2032 mmol) was dissolved in 4.6

mL of THF. A solution of TBAF (1.0 M in THF, 4.1 mL, 4.1 mmol) was added at 0 ºC and the

reaction mixture was stirred at room temperature for 6 days. The reaction mixture was diluted with

CH2Cl2 and quenched by a saturated solution of NH4Cl. After that, the organic layer was separated

and dried over MgSO4, filtered and concentrated under vacuo. The crude product was purified by

flash column chromatography (20% EtOAc/hexanes) to give the diol 25 (89%) as colorless oil.

Supporting Information File Dias et al. 24______________________________________________________________________________________________ Yield: 89%; Rf 0.27 (Hex/EtOAc 20%); [α]D

20 +5,5 (c 3.28, CH2Cl2); 1H NMR (250 MHz, CDCl3) δ

7.32–7.26 (m, 5H), 7.22 (d, J 8.7 Hz, 2H), 6.85 (d, J 8.7 Hz, 2H), 4.56 (d, J 10.9 Hz, 1H), 4.43 (s,

2H), 4.43 (d, J 10,1 Hz, 1H), 3.88–3.80 (m, 1H), 3.79 (s, 3H), 3.75 (t, J 4.5 Hz, 1H), 3.63 (ddd, J

10.0, 5.0, 1.5 Hz, 1H), 3.33 (dd, J 8.0, 7.1 Hz, 2H), 3.24 (brs, 2H), 2.07 (m, 1H), 1.89 (m, 1H), 1.65

(m, 2H), 1.38 (m, 1H), 1.06 (d, J 6.9 Hz, 3H), 0.92 (d, J 6.8 Hz, 6H), 0.90 (d, J 7.0 Hz, 3H); 13C NMR

(62.5 MHz, CDCl3) δ 159.2 (C0), 138.4 (C0), 130.4 (C0), 129.4 (C1), 128.3 (C1), 127.5 (C1), 113.7

(C1), 81.0 (C1), 77.5 (C1), 76.1 (C1), 73.4 (C2), 73.1 (C2), 72.9 (C2), 55.2 (C3), 41.0 (C1), 37.1 (C2),

35.4 (C1), 34.0 (C1), 18.3 (C3), 17.4 (C3), 13.0 (C3), 12.2 (C3); IR νmax (film) 3408, 2961, 2872, 1612,

1415, 1454, 1366, 1248, 1065, 824, 698 cm–1; HRMS (ESI TOF-MS): calcd for C27H40O5Na: m/z

467.2948; found: m/z 467.2773.

26

OBn O

Me

OHMe

Me

O

PMP

Me (R)-1-((2S,4S,5S,6S)-6-((R)-1-(benzyloxy)propan-2-yl)-2-(4-

methoxyphenyl)-5-methyl-1,3-dioxan-4-yl)-3-methylbutan-2-ol (26): To a solution of diol 25 (40.1

mg, 0.0902 mmol) in 2.0 mL of CH2Cl2, under argon atmosphere was added powdered activated 4Å

molecular sieves (40.1 g) and the reaction mixture was stirred for 15 minutes. After that, the

temperature was reduced to –10 ºC and DDQ was added (30.7 mg, 0.1353 mmol). After stirring for 1

hour at room temperature, the reaction mixture was diluted with Et2O (5 mL), filtered through Celite

column (h = 5 cm) and eluted with CH2Cl2. The filtered was concentrated under reduced pressure and

the residue was purified by flash column chromatography (15% EtOAc/hexanes) to afford the acetal

26 (44%) as colorless oil.

Yield: 44%; Rf 0.37 (Hex/EtOAc 20%); [α]D20 +26 (c 1.76, CH2Cl2); 1H NMR (500 MHz, C6D6) δ

7.77 (d, J 8.5 Hz, 2H), 7.26–7.20 (m, 1H), 7.14–7.10 (m, 1H), 6.79 (d, J 8.5 Hz, 2H), 5.95 (s, 1H),

4.26 (d, J 12.0 Hz, 1H), 4.20 (d, J 12.0 Hz, 1H), 4.00 (dd, J 10.0, 3.0 Hz, 1H), 3.99 (ddd, J 12.0, 9.5,

2.0 Hz, 1H), 3.51 (ddd, J 9.8, 5.0, 2.5 Hz, 1H), 3.25 (m, 3H), 3.19 (dd, J 9.0, 4.5 Hz, 1H), 3.14 (dd, J

9.0, 4.0 Hz, 1H), 2.86 (brs, 1H), 2.31 (dt, J 14.5, 10.0 Hz, 1H), 1.97 (m, 1H), 1.67 (quint.d, J 6.8, 1.5

Hz; 1H), 1.40 (qdd, J 7.0, 2.0, 1.0 Hz, 1H), 1.31 (ddd, J 14.4, 4.0, 2.5 Hz, 2H), 1.26 (d, J 6.5 Hz, 6H),

1.02 (d, J 6.5 Hz, 3H), 0.97 (d, J 6.5 Hz, 3H); 13C NMR (62.5 MHz, C6D6) δ 160.4 (C0), 139.1 (C0),

132.2 (C0), 128.8 (C1), 127.9 (C1), 127.8 (C1), 127.6 (C1), 113.9 (C1), 96.0 (C1), 81.4 (C1), 77.5 (C1),

76.7 (C1), 73.3 (C2), 71.7 (C2), 54.7 (C3), 35.5 (C1), 34.2 (C1), 34.1 (C2), 33.8 (C1), 19.0 (C3), 17.6

(C3), 14.9 (C3), 13.8 (C3); IR νmax (film) 3504, 2962, 2870, 1616, 1518, 1366, 1250, 1171, 1113, 825,

739 cm–1. HRMS (ESI TOF-MS): calcd for C27H38O5Na: 465.2617; found: 465.2632.

Supporting Information File Dias et al. 25______________________________________________________________________________________________

ppm-0123456789

Andrea AA121A21 cdcl3 out04aaH2Pulse Sequence: s2pul Solvent: CDCl3 Ambient temperatureFile: out04aaH2INOVA-500 "nmrsun"

Relax. delay 0.200 sec Pulse 39.2 degrees Acq. time 2.667 sec Width 6000.0 Hz 16 repetitionsOBSERVE H1, 300.0673570 MHzDATA PROCESSING Line broadening 0.3 HzFT size 32768Total time 0 min, 46 sec

7.311

7.3297.3

35

7.301

7.295

7.290 7.2

73 7.258 7.217 7.2

127.1

90

4.205

4.229

4.194

3.531

3.559

2.796

1.255

1.230

1.046

1.024

0.917

0.893

0.000

5.681.00

2.201.07

1.081.17

1.281.25

1.073.54

3.603.62

1H NMR - (CDCl3, 300 MHz)

ppm20406080100120140160180

177.84

7

152.85

0

135.02

0129

.389

128.95

2127

.399

76.628

77.000

77.194

77.421

76.563

66.111

55.109

37.748

39.609 30.

759

19.223

18.851

9.936

-0.047

Andrea AA121A21 cdcl3 out04aaCPulse Sequence: s2pul Solvent: CDCl3 Ambient temperatureFile: out04aaCINOVA-500 "nmrsun"

Relax. delay 2.000 sec Pulse 44.6 degrees Acq. time 0.800 sec Width 20000.0 Hz 2000 repetitionsOBSERVE C13, 75.4519980 MHzDECOUPLE H1, 300.0688576 MHz Power 41 dB continuously on WALTZ-16 modulatedDATA PROCESSING Line broadening 1.0 HzFT size 32768Total time 1 hr, 33 min, 37 sec

N

OMe

Me

OH

MeO

O

Bn

N

OMe

Me

OH

MeO

O

Bn

13C NMR - (CDCl3, 75 MHz)

Supporting Information File Dias et al. 26______________________________________________________________________________________________

N

OMe

Me

OH

MeO

O

Bn

IR (Film)

ppm01234567

Andrea "AA-122A8" cdcl3/bb5old out07aaH1Pulse Sequence: s2pul Solvent: CDCl3 Ambient temperatureFile: out07aaH1INOVA-500 "nmrsun"

Relax. delay 0.200 sec Pulse 39.2 degrees Acq. time 2.667 sec Width 6000.0 Hz 16 repetitionsOBSERVE H1, 300.0673526 MHzDATA PROCESSING Line broadening 0.3 HzFT size 32768Total time 0 min, 46 sec

3.708

3.411

3.4203.4

41

3.200

1.164

1.141

1.046

1.024

0.889

0.865

0.000

3.021.09

1.023.10

1.021.00

3.203.24

3.25

N

OMe

Me

OH

Me

OMe

Me

1H NMR - (CDCl3, 300 MHz)

Supporting Information File Dias et al. 27______________________________________________________________________________________________

ppm20406080100120140160180

Andrea "AA122A8" cdcl3/bb5old out05aaCPulse Sequence: s2pul Solvent: CDCl3 Ambient temperatureFile: out05aaCINOVA-500 "nmrsun"

Relax. delay 2.000 sec Pulse 44.6 degrees Acq. time 0.800 sec Width 20000.0 Hz 321 repetitionsOBSERVE C13, 75.4520029 MHzDECOUPLE H1, 300.0688576 MHz Power 41 dB continuously on WALTZ-16 modulatedDATA PROCESSING Line broadening 1.0 HzFT size 32768Total time 3 hr, 54 min, 4 sec

178.33

2

76.773

77.00077.

421

76.563

61.354

35.710

30.241

31.794

18.802

18.932 9.8

87

Andrea "AA122A8" cdcl3/bb5old out05aaCPulse Sequence: s2pul Solvent: CDCl3 Ambient temperatureFile: out05aaCINOVA-500 "nmrsun"

Relax. delay 2.000 sec Pulse 44.6 degrees Acq. time 0.800 sec Width 20000.0 Hz 321 repetitionsOBSERVE C13, 75.4520029 MHzDECOUPLE H1, 300.0688576 MHz Power 41 dB continuously on WALTZ-16 modulatedDATA PROCESSING Line broadening 1.0 HzFT size 32768Total time 3 hr, 54 min, 4 sec N

OMe

Me

OH

Me

OMe

Me

9.887

76.773

18.802

18.932

30.241

61.354

ppm20406080100120140160180

178.33

2

77.00077.

421

76.563

35.710

31.794

13C NMR - (CDCl3, 75 MHz)

N

OMe

Me

OH

Me

OMe

Me

IR (Film)

Supporting Information File Dias et al. 28______________________________________________________________________________________________

ppm-012345678

andrea c6d6 aa124a6 out11aaH2Pulse Sequence: s2pul Solvent: Benzene Ambient temperatureFile: out11aaH2INOVA-500 "nmrsun"

Relax. delay 0.200 sec Pulse 39.2 degrees Acq. time 2.667 sec Width 6000.0 Hz 16 repetitionsOBSERVE H1, 300.0673707 MHzDATA PROCESSING Line broadening 0.3 HzFT size 32768Total time 0 min, 46 sec

3.048

2.865

1.038

1.023

1.009

0.148

0.096

1.001.10

2.982.98

1.083.20

17.413.38

3.05

N

OMe

Me

TBSO

Me

OMe

Me

1H NMR - (C6D6, 300 MHz)

208 200 192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 0 -8Chemical Shift (ppm)

Chloroform-d

N

OMe

Me

TBSO

Me

OMe

Me

13C NMR - (CDCl3, 75 MHz)

Supporting Information File Dias et al. 29______________________________________________________________________________________________

4000 3500 3000 2500 2000 1500 100025

30

35

40

45

50

1212

1383

2933

3008

1051

1461

1655

2858

2960

Tran

smitâ

ncia

cm-1

R-10

N

OMe

Me

TBSO

Me

OMe

Me

IR (Film)

Vanda R11 cdcl3 jun08vmoH1Pulse Sequence: s2pul Solvent: CDCl3 Ambient temperatureFile: jun08vmoH1INOVA-500 "nmrsun"

Relax. delay 0.200 sec Pulse 39.2 degrees Acq. time 2.667 sec Width 6000.0 Hz 16 repetitionsOBSERVE H1, 300.0673565 MHzDATA PROCESSING Line broadening 0.3 HzFT size 32768Total time 0 min, 46 sec

ppm0.00.51.01.52.02.53.03.50.03

0.020.09

0.030.10

0.530.20

O

Me

TBSO

Me

MeMe

5

1H NMR (5) - (CDCl3, 300 MHz)

Supporting Information File Dias et al. 30______________________________________________________________________________________________

Vanda "R-13A" cdcl3/bb5old jun23vmoCPulse Sequence: s2pul Solvent: CDCl3 Ambient temperatureFile: jun23vmoCINOVA-500 "nmrsun"

Relax. delay 2.000 sec Pulse 41.0 degrees Acq. time 0.800 sec Width 20000.0 Hz 3328 repetitionsOBSERVE C13, 75.4519992 MHzDECOUPLE H1, 300.0688576 MHz Power 41 dB continuously on WALTZ-16 modulatedDATA PROCESSING Line broadening 1.0 HzFT size 32768Total time 3 hr, 54 min, 4 sec

ppm020406080100120140160180200

211.4

68

77.24

377

.421

77.00

076

.579

50.85

4

26.13

229

.578

29.74

032

.959 19.78

918

.446

17.86

412

.945

-3.78

4-4.

027

O

Me

TBSO

Me

MeMe

5

13C NMR (5) - (CDCl3, 75 MHz)

1.01.52.02.53.03.5 ppm

0.917

0.943

0.988

0.995

1.014

1.021

1.084

1.112

1.137

1.590

1.617

1.643

1.670

1.696

1.722

1.770

1.775

2.588

2.595

2.604

2.623

2.628

2.640

2.702

2.714

2.724

2.730

2.742

3.521

3.533

3.555

3.567

3.585

3.597

3.620

3.632

3.801

3.816

3.823

9.27

3

3.08

43.

301

2.17

2

1.95

4

3.25

1

1.00

7

1.00

0

Current Data ParametersNAME abr20smpH1EXPNO 1PROCNO 1

F2 - Acquisition ParametersDate_ 20090420Time 15.58INSTRUM spectPROBHD 5 mm QNP 1H/13PULPROG zg30TD 32768SOLVENT CDCl3NS 16DS 0SWH 5175.983 HzFIDRES 0.157958 HzAQ 3.1654389 secRG 4DW 96.600 usecDE 6.00 usecTE 300.0 KD1 1.00000000 secTD0 1

======== CHANNEL f1 ========NUC1 1HP1 13.00 usecPL1 -6.00 dBSFO1 250.1315447 MHz

F2 - Processing parametersSI 32768SF 250.1300006 MHzWDW EMSSB 0LB 0.30 HzGB 0PC 1.00

Sávio Est.TBS CDCl3 250MHz abr20smpH1

O

Me

OH

Me

Me MeOH

Me

O

Me

OH

Me

Me MeOH

Me

+ds 30:70

1,5-anti

1,5-syn

major product

1H NMR - (CDCl3, 250 MHz)

Supporting Information File Dias et al. 31______________________________________________________________________________________________

2.62.72.82.93.03.13.23.33.43.53.63.73.83.9 ppm

2.588

2.595

2.604

2.623

2.628

2.640

2.702

2.714

2.724

2.730

2.742

3.521

3.533

3.555

3.567

3.585

3.597

3.620

3.632

3.801

3.816

3.823

3.834

3.839

3.848

3.856

3.872

1.95

4

3.25

1

1.00

7

1.00

0Current Data ParametersNAME abr20smpH1EXPNO 1PROCNO 1

F2 - Acquisition ParametersDate_ 20090420Time 15.58INSTRUM spectPROBHD 5 mm QNP 1H/13PULPROG zg30TD 32768SOLVENT CDCl3NS 16DS 0SWH 5175.983 HzFIDRES 0.157958 HzAQ 3.1654389 secRG 4DW 96.600 usecDE 6.00 usecTE 300.0 KD1 1.00000000 secTD0 1

======== CHANNEL f1 ========NUC1 1HP1 13.00 usecPL1 -6.00 dBSFO1 250.1315447 MHz

F2 - Processing parametersSI 32768SF 250.1300006 MHzWDW EMSSB 0LB 0.30 HzGB 0PC 1.00

Sávio Est.TBS CDCl3 250MHz abr20smpH1

O

Me

OH

Me

Me MeOH

Me

O

Me

OH

Me

Me MeOH

Me

+ds 30:70

1,5-anti

1,5-syn

major product

1H NMR - (CDCl3, 250 MHz)

20406080100120140160180200 ppm

18.349

18.389

18.966

19.023

19.153

30.681

30.744

33.063

33.158

44.637

44.860

48.696

49.138

72.249

72.631

76.012

76.410

76.494

77.002

77.511

216.535

217.079

Current Data ParametersNAME abr20smpC1EXPNO 1PROCNO 1

F2 - Acquisition ParametersDate_ 20090420Time 16.19INSTRUM spectPROBHD 5 mm QNP 1H/13PULPROG zgpg30TD 32768SOLVENT CDCl3NS 263DS 0SWH 15060.241 HzFIDRES 0.459602 HzAQ 1.0879476 secRG 32768DW 33.200 usecDE 6.00 usecTE 300.0 KD1 2.00000000 secd11 0.03000000 secDELTA 1.89999998 secTD0 1

======== CHANNEL f1 ========NUC1 13CP1 10.00 usecPL1 0.00 dBSFO1 62.9015280 MHz

======== CHANNEL f2 ========CPDPRG2 waltz16NUC2 1HPCPD2 100.00 usecPL2 -6.00 dBPL12 18.00 dBPL13 18.00 dBSFO2 250.1310005 MHz

F2 - Processing parametersSI 32768SF 62.8952401 MHzWDW EMSSB 0LB 1.00 HzGB 0PC 1.40

Sávio Est.TBS CDCl3 250MHz abr20smpC1

O

Me

OH

Me

Me MeOH

Me

O

Me

OH

Me

Me MeOH

Me

+ds 30:70

1,5-anti

1,5-syn

major product

13C NMR - (CDCl3, 62.9 MHz)

Supporting Information File Dias et al. 32______________________________________________________________________________________________

101520253035404550556065707580 ppm

8.663

8.950

18.352

18.392

19.027

19.157

30.684

30.746

33.065

33.161

44.639

44.863

48.697

49.140

72.250

72.633

76.015

76.413

Current Data ParametersNAME abr20smpC1EXPNO 2PROCNO 1

F2 - Acquisition ParametersDate_ 20090420Time 16.26INSTRUM spectPROBHD 5 mm QNP 1H/13PULPROG dept135TD 32768SOLVENT CDCl3NS 102DS 0SWH 15060.241 HzFIDRES 0.459602 HzAQ 1.0879476 secRG 16384DW 33.200 usecDE 6.00 usecTE 300.0 KCNST2 145.0000000D1 2.00000000 secd2 0.00344828 secd12 0.00002000 secDELTA 0.00001273 secTD0 1

======== CHANNEL f1 ========NUC1 13CP1 10.00 usecp2 20.00 usecPL1 0.00 dBSFO1 62.9015280 MHz

======== CHANNEL f2 ========CPDPRG2 waltz16NUC2 1HP3 13.00 usecp4 26.00 usecPCPD2 100.00 usecPL2 -6.00 dBPL12 18.00 dBSFO2 250.1310005 MHz

F2 - Processing parametersSI 32768SF 62.8952396 MHzWDW EMSSB 0LB 1.00 HzGB 0PC 1.40

Sávio Est.TBS CDCl3 250MHz abr20smpDEPT135

O

Me

OH

Me

Me MeOH

Me

O

Me

OH

Me

Me MeOH

Me

+ds 30:70

1,5-anti

1,5-syn

major product

13C NMR (DEPT) - (CDCl3, 62.9 MHz)

Vanda R20F1 cdcl3 set05vmoH4Pulse Sequence: s2pul Solvent: CDCl3 Ambient temperatureFile: set05vmoH4INOVA-500 "nmrsun"

Relax. delay 0.200 sec Pulse 39.2 degrees Acq. time 2.667 sec Width 6000.0 Hz 16 repetitionsOBSERVE H1, 300.0673565 MHzDATA PROCESSING Line broadening 0.3 HzFT size 32768Total time 0 min, 46 sec

ppm12345670.08

0.080.07

0.120.11

0.040.14

0.030.11

0.110.10

O

Me

PMBO

MeN

Me

Me

OMe

1H NMR - (CDCl3, 300 MHz)

Supporting Information File Dias et al. 33______________________________________________________________________________________________

Vanda "R-20F1" cdcl3/bb5old set05vmoC4Pulse Sequence: s2pul Solvent: CDCl3 Ambient temperatureFile: set05vmoC4INOVA-500 "nmrsun"

Relax. delay 2.000 sec Pulse 41.0 degrees Acq. time 0.800 sec Width 20000.0 Hz 321 repetitionsOBSERVE C13, 75.4519992 MHzDECOUPLE H1, 300.0688576 MHz Power 41 dB continuously on WALTZ-16 modulatedDATA PROCESSING Line broadening 1.0 HzFT size 32768Total time 3 hr, 54 min, 4 sec

O

Me

PMBO

MeN

Me

Me

OMe

129.4

22

113.6

79

77.42

1

ppm20406080100120140160

159.0

79 130.9

91

85.21

9

77.00

076

.563

75.01

0

20.43

6

55.22

2

31.61

6

14.15

916

.958

61.35

4

32.28

0

38.65

5

13C NMR - (CDCl3, 75MHz)

4000 3500 3000 2500 2000 1500 100010

15

20

25

30

35

40

45

50

3452

992

117613

8512

54

1731

2930

2959

1036

1215

1464

1514

1655

3018

Tran

smitâ

ncia

cm-1

Amida PMB

O

Me

PMBO

MeN

Me

Me

OMe

IR (Film)

Supporting Information File Dias et al. 34______________________________________________________________________________________________

Vanda R-36F1 CDCl3/bb5 dez01vmoH3Pulse Sequence: s2pul Solvent: CDCl3 Ambient temperatureFile: dez01vmoH3INOVA-500 "nmrsun"

Relax. delay 0.200 sec Pulse 42.0 degrees Acq. time 2.667 sec Width 6000.0 Hz 16 repetitionsOBSERVE H1, 300.0616428 MHzDATA PROCESSING Line broadening 0.3 HzFT size 32768Total time 0 min, 46 sec

ppm-012345670.08

0.080.08

0.120.04

0.040.12

0.050.13

0.26

O

Me

PMBO

Me

MeMe

(8)

1H NMR (8) - (CDCl3, 300 MHz)

Vanda MC2 c6d6 mar22vmoC1Pulse Sequence: s2pul Solvent: Benzene Ambient temperatureFile: mar22vmoC1INOVA-500 "nmrsun"

Relax. delay 2.000 sec Pulse 39.5 degrees Acq. time 0.800 sec Width 20000.0 Hz 432 repetitionsOBSERVE C13, 75.4505394 MHzDECOUPLE H1, 300.0631690 MHz Power 39 dB continuously on WALTZ-16 modulatedDATA PROCESSING Line broadening 2.0 HzFT size 32768Total time 3 hr, 54 min, 4 sec

ppm20406080100120140160180200220

209.5

63

159.6

15

127.6

7612

8.000

128.3

0712

9.424

131.3

98

113.9

88

84.78

4

74.33

1

54.78

6 49.90

0

32.03

728

.866

20.16

118

.414

12.08

8

O

Me

PMBO

Me

MeMe

(8)

13C NMR (8) - (C6D6, 75 MHz)

Supporting Information File Dias et al. 35______________________________________________________________________________________________

4000 3500 3000 2500 2000 1500 100020

25

30

35

40

45

50

1171

1248

1361

1469

2882

2966

1036

1217

1514

1614

1709

3020

3408

Trna

smitâ

ncia

cm-1

MC2

IR (Film) – (8)

Vanda R13B1 c6d6 jun26vmoHPulse Sequence: s2pul Solvent: CDCl3 Ambient temperatureFile: jun26vmoHINOVA-500 "nmrsun"

Relax. delay 0.200 sec Pulse 39.2 degrees Acq. time 2.667 sec Width 6000.0 Hz 128 repetitionsOBSERVE H1, 300.0673408 MHzDATA PROCESSING Line broadening 0.3 HzFT size 32768Total time 6 min, 8 sec

2.731.04

4.543.66

1.5447.41

10.20

ppm0.51.01.52.02.53.03.54.04.5

1H NMR (6 + 7) - (C6D6, 500 MHz)

O

Me

TBSO

Me

Me MeOH

Me

O

Me

TBSO

Me

Me MeOH

Me+

6 7

1,5-syn 1,5-anti

O

Me

PMBO

Me

MeMe

(8)

Supporting Information File Dias et al. 36______________________________________________________________________________________________

vanda r13b cdcl3 jun22vmoC2Pulse Sequence: s2pul Solvent: CDCl3 Ambient temperatureFile: jun22vmoC2INOVA-500 "nmrsun"

Relax. delay 2.000 sec Pulse 41.0 degrees Acq. time 0.800 sec Width 20000.0 Hz 1192 repetitionsOBSERVE C13, 75.4519980 MHzDECOUPLE H1, 300.0688576 MHz Power 41 dB continuously on WALTZ-16 modulatedDATA PROCESSING Line broadening 1.0 HzFT size 32768Total time 3 hr, 54 min, 4 sec

ppm020406080100120140160180200220240

O

Me

TBSO

Me

Me MeOH

Me

O

Me

TBSO

Me

Me MeOH

Me+

6 7

1,5-syn 1,5-anti

13C NMR (6 + 7) - (C6D6, 75 MHz)

4000 3500 3000 2500 2000 1500 1000

0

10

20

30

40

50

60

1254

1391

2858

2935

3019

1051

1215

1471

1699

2961

3504

Tran

smitâ

ncia

cm-1

O

Me

TBSO

Me

Me MeOH

Me

O

Me

TBSO

Me

Me MeOH

Me+

6 7

1,5-syn 1,5-anti

IR (Film) - (6 + 7)

Supporting Information File Dias et al. 37______________________________________________________________________________________________

1.52.02.53.03.54.04.55.05.56.06.57.07.5 ppm

1,5-syn1,5-anti

9b 10b

O

Me

OHPMBOMe

Me

O

Me

OHPMBOMe

Me Me

Me

Me

Me

1 5 anti

1H NMR (9b + 10b) - (C6D6, 250 MHz)

ppm (f1)050100150200

0

500

1000

1500

2000

209.

741

159.

641

131.

388

129.

452

128.

291

113.

970

84.7

47

74.3

06

54.7

1149

.811

31.9

4530

.404

28.7

9526

.012

23.7

8420

.058

18.3

15

11.9

76

1,5-syn1,5-anti

9b 10b

O

Me

OHPMBOMe

Me

O

Me

OHPMBOMe

Me Me

Me

Me

Me

13C NMR (9b + 10b) - (C6D6, 125 MHz)

Supporting Information File Dias et al. 38______________________________________________________________________________________________

4000 3500 3000 2500 2000 1500 1000

15

20

25

30

35

1177

1254

1469

2936

2966

1036

1215

1358

1514

1614

1707

3020

3406

Trna

smitâ

ncia

cm-1

R85A

1,5-syn1,5-anti

9b 10b

O

Me

OHPMBOMe

Me

O

Me

OHPMBOMe

Me Me

Me

Me

Me

IR (Film) - (9b + 10b)

1.01.52.02.53.03.54.04.55.0

vanda R-92A/250 vmo H 1,5-syn1,5-anti

O OHPMBOPMBO O OH

5.56.06.57.07.5 ppm

1.01.21.41.61.82.02.22.42.6 ppm

1H NMR (9c + 10c) - (C6D6, 250 MHz)

9c 10cMe

Me

Me Me

Me MeMe

Me

Supporting Information File Dias et al. 39______________________________________________________________________________________________

210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

10.10

11.84

18.29

20.03

29.80

31.98

48.27

49.86

54.73

68.98

74.39

84.72

114.01

129.41

129.55

131.35

159.69

214.27

1,5-syn1,5-anti

9c 10c

O

Me

OHPMBOMe

Me

O

Me

OHPMBOMe

Me

MeMe

13C NMR (9c + 10c) - (C6D6, 75 MHz)

4000 3500 3000 2500 2000 1500 1000

0

10

20

30

40

50

38,6

882

3,54

1035

,6

1174

,512

49,7

1384

,714

63,8

1514

1614

,317

01

2964

,3

3515

3054

2875

2942

Tran

smitâ

ncia

cm-1

R92A

1,5-syn1,5-anti

9c 10c

O

Me

OHPMBOMe

Me

O

Me

OHPMBOMe

Me

MeMe

IR (Film) - (9c + 10c)

Supporting Information File Dias et al. 40______________________________________________________________________________________________

1.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0 ppm

Vanda R91-puro/250 vmoH1

2.52.62.72.82.9 ppm

1H NMR (9d + 10d) - (C6D6, 250 MHz)

210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 ppm

11.40

11.51

18.30

18.38

19.93

20.04

31.89

31.94

49.86

50.04

50.86

54.73

70.09

70.20

74.17

74.34

84.57

84.65

114.02

125.98

126.04

129.40

129.53

131.20

131.32

159.69

213.24

213.45

Vanda R91 Puro c6d6/qnp250 set12vmoC1

127128129130131 ppm

1,5-syn1,5-anti

9d 10d

O

Me

OHPMBOMe

Me

O

Me

OHPMBOMe

Me

1,5-syn1,5-anti

9d 10d

O

Me

OHPMBOMe

Me

O

Me

OHPMBOMe

Me

13C NMR (9d + 10d) - (C6D6, 62.5 MHz)

Supporting Information File Dias et al. 41______________________________________________________________________________________________

4000 3500 3000 2500 2000 1500 1000

0

10

20

30

40

50

60

962

1033

1176

1248

1385

1612

2882

2936

2965

1217

1456

1514

1701

3018

3497

Tran

smitâ

ncia

cm-1

R91

1,5-syn1,5-anti

9d 10d

O

Me

OHPMBOMe

Me

O

Me

OHPMBOMe

Me

IR (Film) - (9d + 10d)

1.01.52.02.53.03.54.04.55.05.56.06.57.07.5 ppm

2.62.83.03.23.4 ppm

1,5-syn1,5-anti

9e 10e

O

Me

OHPMBOMe

Me

O

Me

OHPMBOMe

MeOMe OMe

1H NMR (9e + 10e) - (C6D6, 250 MHz)

Supporting Information File Dias et al. 42______________________________________________________________________________________________

ppm (f1)050100150200

0

500

1000

1500

2000213.

519

213.

305

159.

664

159.

529

136.

217

136.

183

131.

328

131.

226

129.

538

129.

414

128.

292

127.

298

127.

223

114.

026

114.

010

84.6

6384

.603

74.3

3474

.172

69.9

3269

.841

54.7

7754

.725

50.9

5150

.038

49.8

9231

.958

31.9

1020

.068

19.9

7418

.405

18.3

3811

.517

11.4

30

1,5-syn1,5-anti

9e 10e

O

Me

OHPMBOMe

Me

O

Me

OHPMBOMe

MeOMe OMe

13C NMR (9e + 10e) - (C6D6, 125.0 MHz)

4000 3500 3000 2500 2000 1500 10000

10

20

30

40

50

60

1171

1218

1457

1606

2936

2840

1036

1250

1302

1514

1701

3011

2962

3489

Tran

smitâ

ncia

cm-1

R83

1,5-syn1,5-anti

9e 10e

O

Me

OHPMBOMe

Me

O

Me

OHPMBOMe

MeOMe OMe

IR (Film) - (9e + 10e)

Supporting Information File Dias et al. 43______________________________________________________________________________________________

1.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0 ppm

vanda "R-84" C6D6/250MHz

1.82.02.22.42.6 ppm

1,5-syn1,5-anti

9f 10f

O

Me

OHPMBOMe

Me

O

Me

OHPMBOMe

MeNO2 NO2

1H NMR (9f + 10f) - (C6D6, 250 MHz)

4000 3500 3000 2500 2000 1500 10000

10

20

30

40

50

60

107514

631701

2870

2930

2960

1036

1215

134815

2216

10

3020

3446

Tran

smitâ

ncia

cm-1

1,5-syn1,5-anti

9f 10f

O

Me

OHPMBOMe

Me

O

Me

OHPMBOMe

MeNO2 NO2

IR (Film) (9f + 10f)

Supporting Information File Dias et al. 44______________________________________________________________________________________________

PMBO O

MeOCH3

1H NMR (CDCl3, 300 MHz)

2030405060708090100110120130140150160170180 ppm

13.911

40.07

9

51.611

55.150

71.364

71.56

272.655

76.49

377

.001

77.51

0

113.

684

129.321

130

.141

159.09

5

175.254

Current Data ParametersNAME ago28ccpC1EXPNO 1PROCNO 1

F2 - Acquisition ParametersDate_ 20080828Time 15.34INSTRUM spectPROBHD 5 mm QNP 1H/13PULPROG zgpg30TD 32768SOLVENT CDCl3NS 216DS 0SWH 15060.241 HzFIDRES 0.459602 HzAQ 1.0879476 secRG 574.7DW 33.200 usecDE 6.00 usecTE 300.0 KD1 2.00000000 secd11 0.03000000 secDELTA 1.89999998 secTD0 1

======== CHANNEL f1 ========NUC1 13CP1 10.00 usecPL1 0.00 dBSFO1 62.9015280 MHz

======== CHANNEL f2 ========CPDPRG2 waltz16NUC2 1HPCPD2 100.00 usecPL2 -6.00 dBPL12 18.00 dBPL13 18.00 dBSFO2 250.1310005 MHz

F2 - Processing parametersSI 32768SF 62.8952438 MHzWDW EMSSB 0LB 1.00 HzGB 0PC 1.40

Sávio "éster PMB" ago28ccpC1 CDCl3

PMBO O

MeOCH3

13C NMR (CDCl3, 75 MHz)

Supporting Information File Dias et al. 45______________________________________________________________________________________________

2030405060708090100110120130 ppm

13.902

40.069

51.602

55.140

71.551

72.645

113.646

129.102

Current Data ParametersNAME ago28ccpD1EXPNO 1PROCNO 1

F2 - Acquisition ParametersDate_ 20080828Time 15.40INSTRUM spectPROBHD 5 mm QNP 1H/13PULPROG dept135TD 32768SOLVENT CDCl3NS 64DS 0SWH 15060.241 HzFIDRES 0.459602 HzAQ 1.0879476 secRG 16384DW 33.200 usecDE 6.00 usecTE 300.0 KCNST2 145.0000000D1 2.00000000 secd2 0.00344828 secd12 0.00002000 secDELTA 0.00001273 secTD0 1

======== CHANNEL f1 ========NUC1 13CP1 10.00 usecp2 20.00 usecPL1 0.00 dBSFO1 62.9015280 MHz

======== CHANNEL f2 ========CPDPRG2 waltz16NUC2 1HP3 13.00 usecp4 26.00 usecPCPD2 100.00 usecPL2 -6.00 dBPL12 18.00 dBSFO2 250.1310005 MHz

F2 - Processing parametersSI 32768SF 62.8952444 MHzWDW EMSSB 0LB 1.00 HzGB 0PC 1.40

Sávio "éster PMB" ago28ccpD1 CDCl3

PMBO O

MeOCH3

13C NMR – DEPT 135º (CDCl3, 75 MHz)

4 0 0 0 3 5 0 0 3 0 0 0 2 5 0 0 2 0 0 0 1 5 0 0 1 0 0 0

0

1 0

2 0

3 0

4 0

581

822

1036

1250

1302

1514

1612

1740

2860

2953

1462

Tran

smitâ

ncia

c m -1

É s te r

PMBO O

MeOCH3

IR νmax (film)

Supporting Information File Dias et al. 46______________________________________________________________________________________________

ppm12345672.07

2.092.00

3.132.00

1.191.06

1.151.11

3.26

PMBO OH

Me

1H NMR (CDCl3, 300 MHz)

Savio F37-48 P9 cdcl3 mai05smpCPulse Sequence: s2pul Solvent: CDCl3 Ambient temperatureFile: mai05smpCINOVA-500 "nmrsun"

Relax. delay 2.000 sec Pulse 41.0 degrees Acq. time 0.800 sec Width 20000.0 Hz 432 repetitionsOBSERVE C13, 75.4520041 MHzDECOUPLE H1, 300.0688576 MHz Power 41 dB continuously on WALTZ-16 modulatedDATA PROCESSING Line broadening 1.0 HzFT size 32768Total time 46 min, 48 sec

ppm20406080100120140160

159.0

63

129.0

9813

0.004

128.4

67

113.7

28

73.00

475

.107

76.56

377

.000

77.42

1

67.85

9

55.25

5

35.59

7 13.56

0

PMBO OH

Me

13C NMR (CDCl3, 75 MHz)

Supporting Information File Dias et al. 47______________________________________________________________________________________________

PMBO OH

Me

13C NMR – DEPT 135 and 90º (CDCl3, 75 MHz)

4000 3500 3000 2500 2000 1500 1000-10

-5

0

5

10

15

20

737

820

1036

1250

1464

1514

1610

1711

2876

2959

3418

Tran

smitâ

ncia

cm -1

F 3 7 -4 8 P 9

PMBO OH

Me

IR νmax (film)

Supporting Information File Dias et al. 48______________________________________________________________________________________________

ppm-012345678910

Andrea AA75A52-f cdcl3 mai04aaH1Pulse Sequence: s2pul Solvent: CDCl3 Ambient temperatureFile: mai04aaH1INOVA-500 "nmrsun"

Relax. delay 0.200 sec Pulse 39.2 degrees Acq. time 2.667 sec Width 6000.0 Hz 32 repetitionsOBSERVE H1, 300.0673574 MHzDATA PROCESSING Line broadening 0.3 HzFT size 32768Total time 1 min, 32 sec

9.705

9.701

6.889

7.219

7.2497.2

56

6.882

6.867 6.8

60

4.452

3.804

3.648

3.625

3.607

1.130

1.107

-0.00

0

0.752.33

2.172.00

3.292.26

0.953.07

PMBO O

MeH

1H NMR (CDCl3, 300 MHz)

Savio Aldeido P10A cdcl3 mai16smpC1Pulse Sequence: s2pul Solvent: CDCl3 Ambient temperatureFile: mai16smpC1INOVA-500 "nmrsun"

Relax. delay 2.000 sec Pulse 41.0 degrees Acq. time 0.800 sec Width 20000.0 Hz 1616 repetitionsOBSERVE C13, 75.4520029 MHzDECOUPLE H1, 300.0688576 MHz Power 41 dB continuously on WALTZ-16 modulatedDATA PROCESSING Line broadening 1.0 HzFT size 32768Total time 3 hr, 54 min, 4 sec

ppm20406080100120140160180200

203.6

53

159.1

11

129.1

1412

9.875

128.2

08

113.7

44

77.00

077

.421

76.57

972

.939

69.80

0

55.28

7

46.82

5

10.82

6

13C NMR (CDCl3, 75 MHz)

PMBO O

MeH

Supporting Information File Dias et al. 49______________________________________________________________________________________________

ppm020406080100120140160180200220240

Andrea AA75A52-f cdcl3 mai04aaD1Pulse Sequence: dept Solvent: cdcl3 Ambient temperatureFile: mai04aaD1INOVA-500 "nmrsun"

Relax. delay 2.000 sec Pulse 90.0 degrees Acq. time 0.800 sec Width 20000.0 Hz 512 repetitionsOBSERVE C13, 75.4520042 MHzDECOUPLE H1, 300.0688576 MHz Power 41 dB on during acquisition off during delay WALTZ-16 modulatedDATA PROCESSING Line broadening 1.0 HzFT size 32768Total time 48 min, 33 sec

PMBO O

MeH

13C NMR – DEPT 135 and 90º CDCl3, 75 MHz)

PMBO OH

Me Me

O

N O

O

Bn

1H NMR (CDCl3, 300 MHz)

Supporting Information File Dias et al. 50______________________________________________________________________________________________

PMBO OH

Me Me

O

N O

O

Bn

13C NMR (CDCl3, 75 MHz)

PMBO OH

Me Me

O

N O

O

Bn

13C NMR – DEPT 135 and 90º (CDCl3, 75 MHz)

Supporting Information File Dias et al. 51______________________________________________________________________________________________

4 0 0 0 3 5 0 0 3 0 0 0 2 5 0 0 2 0 0 0 1 5 0 0 1 0 0 00

1 0

2 0

3 0

4 0

5 0

6 0

7 0

737

839

1034

1111

1246

138715

14

1701

1780

2935

3481

2858

2965

3025

3049

Tran

smitâ

ncia

c m -1

F 6 2 -8 1 P 5 6

PMBO OH

Me Me

O

N O

O

Bn

IR νmax (film)

PMBO OH

Me Me

O

NOMe

Me

1H NMR (CDCl3, 300 MHz)

Supporting Information File Dias et al. 52______________________________________________________________________________________________

PMBO OH

Me Me

O

NOMe

Me

13C NMR (CDCl3, 75 MHz)

PMBO OH

Me Me

O

NOMe

Me

13C NMR – DEPT 135 and 90º (CDCl3, 75 MHz)

Supporting Information File Dias et al. 53______________________________________________________________________________________________

PMBO OH

Me Me

O

NOMe

Me

HRMS (TOF-MS ES+)

4000 3500 3000 2500 2000 1500 10000

10

20

30

40

50

739

824

995

1036

108811

7512

48

1462

1514

1634

1886

2058

2322

2878

293929

7830

53

3466

Tran

smitâ

ncia

cm -1

F29-63P 58A

PMBO OH

Me Me

O

NOMe

Me

IRνmax (film)

Supporting Information File Dias et al. 54______________________________________________________________________________________________

O O

Me Me

O

NMe

OMe

PMP

1H NMR (CDCl3, 300 MHz)

O O

Me Me

O

NMe

OMe

PMP

13C NMR (CDCl3, 75 MHz)

Supporting Information File Dias et al. 55______________________________________________________________________________________________

O O

Me Me

O

NMe

OMe

PMP

13C NMR – DEPT 135 and 90º (CDCl3, 75 MHz)

4000 3500 3000 2500 2000 1500 10000

10

20

30

40

50

741

897

999

1115

1265

142116

55

230726

87

2988

3055

Tran

smitâ

ncia

cm -1

F 1 4 -2 6 P 1 9 A

O O

Me Me

O

NMe

OMe

PMP

IR. νmax (film)

Supporting Information File Dias et al. 56______________________________________________________________________________________________

O O

Me Me

O

NMe

OMe

PMP

HRMS (TOF-MS ES+)

O O

Me Me

O

Me

PMP

17

1H NMR – (17) − (CDCl3, 300 MHz)

Supporting Information File Dias et al. 57______________________________________________________________________________________________

O O

Me Me

O

Me

PMP

17

13C NMR – (17) − (CDCl3, 75 MHz)

O O

Me Me

O

Me

PMP

17

13C NMR – DEPT 135 and 90º – (17) − (CDCl3, 75 MHz)

Supporting Information File Dias et al. 58______________________________________________________________________________________________

4 0 00 3 5 00 30 00 2 5 00 2 0 00 15 00 10 003 2

3 4

3 6

3 8

4 0

4 2

748

1169

1114

1461

1516

1615

3398 28

59

3057

1036

1263

1701

2926

Tran

smitâ

ncia

cm -1

F 1 2 -2 3 P 1 9 A

O O

Me Me

O

Me

PMP

17

IR νmax (film) – (17)

O O

Me Me

O

Me

PMP

17

HRMS (TOF-MS ES+) – (17) –