Supporting Information - Wiley- · PDF fileSupporting Information for Angew. Chem. Int. Ed....

Supporting Information

for

Angew. Chem. Int. Ed. Z53400

© Wiley-VCH 2004

69451 Weinheim, Germany

A Mild Method for the Preparation of γ-Hydroxy-α,β-Acetylenic Esters

Shatrughan P. Shahi and Kazunori Koide*

General techniques. All reactions were carried out under a nitrogen atmosphere with dry, freshly

distilled solvents under anhydrous conditions, unless otherwise noted. Tetrahydrofuran (THF) was

distilled from sodium-benzophenone, and methylene chloride (CH2Cl2) was distilled from calcium hydride.

Acetonitrile was dried over 3Å molecular sieves. Yields refer to chromatographically and

spectroscopically (1H NMR) homogenous materials, unless otherwise stated.

All reactions were monitored by thin-layer chromatography (TLC) carried out on 0.25-mm E. Merck

silica gel plates (60F-254) using UV-light (254 nm), 2.4% phosphomolybdic acid/1.4% phosphoric

acid/5% sulfuric acid in water, anisaldehyde in ethanol, or 0.2% ninhydrin in ethanol and heat as

developing agents. TSI silica gel (230-400 mesh) was used for flash column chromatography.

NMR spectra were recorded on AM300 or AM500 (Bruker) instruments and calibrated using a solvent

peak or tetramethylsilane as an internal reference. The following abbreviations are used to indicate the

multiplicities: s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet; br, broad. High-resolution mass

spectra were obtained by using EBE geometry.

Abbreviations. Ac, acetyl; Cp, cyclopentadienyl; EI, electron impact; Et, ethyl; EtOAc, ethyl acetate;

EtOH, ethanol; Fmoc, 9-fluorenylmethoxycarbonyl; HRMS, high resolution mass spectrum; Me, methyl;

MeOH, methanol; Ph, phenyl; Tf, trifluoromethanesulfonyl; THF, tetrahydrofuran.

General protocol. Silver acetylide Ag-C≡C-CO2Me (305 mg, 1.60 mmol) and Cp2ZrCl2 (351 mg,

1.20 mmol) were added to a solution of an aldehyde (1.00 mmol) in anhydrous CH2Cl2 (3.4 mL) under a

nitrogen atmosphere at 23 °C. Silver trifluoromethanesulfonate (52 mg, 0.2 mmol) was added to the

reaction mixture at 23 °C and stirred at the same temperature for several hours (indicated in Table 2). The

reaction mixture was quenched by addition of sat. NaHCO3 (1.0 mL) and stirred for 5 min. The resulting

reaction mixture was filtered through a pad of celite and concentrated in vacuo. The resulting residue was

purified by column chromatography to afford the corresponding alcohol. The isolated yields are given in

Table 2.

The spectroscopic data of this compound were consistent with the literature: Cornelius, L.

A. M.; Bone, R. G. A.; Hastings, R. H.; Deardorff, M. A.; Scharlach, R. A.; Hauptmann, B.

E.; Stankovic, C. S.; Pinnick, H. W. J. Org. Chem. 1993; 58, 3188-3190.

Yellow oil; Rf 0.37 (30% EtOAc in hexanes); IR (film) 3419 (broad, O-H), 2956,

2237 (C≡C), 1716 (C=O), 1611, 1512, 1436, 1265, 750 cm-1; 1H NMR (300 MHz,

293K, 1% D2O in CDCl3) δ 7.43 (br d, 2H, J = 8.7 Hz), 6.90 (br d, 2H, J = 8.7

Hz), 5.50 (s, 1H), 3.81 (s, 3H), 3.78 (s, 3H); 13C NMR (75 MHz, 293K, CDCl3) δ 159.6, 153.8, 130.7,

128.0, 113.9, 87.1, 76.9, 63.3, 55.1, 52.7; HRMS (EI+) calcd for C12H12O4 (M+) 220.0736, found

220.0728.

Pale yellow oil; Rf 0.35 (15% EtOAc in hexanes); IR (film) 3417 (broad, O-H), 2929,

2854, 2235 (C≡C), 1719 (C=O), 1450, 1436, 1252, 751 cm-1; 1H NMR (300 MHz,

293K, 1% D2O in CDCl3) δ 4.27 (d, 1H, J = 6.2 Hz), 3.79 (s, 3H), 1.88-1.59 (m, 6H), 1.33-1.12 (m, 5H); 13C NMR (75 MHz, 293K, CDCl3) δ 153.9, 87.7, 76.9, 66.7, 52.8, 43.5, 28.3, 28.0, 26.1, 25.6, 25.1;

HRMS (EI+) calcd for C10H13O2 (M+-OMe) 165.0916, found 165.0913.


2956, 2237 (C≡C), 1717 (C=O), 1494, 1455, 1435, 1265 cm-1; 1H NMR (300 MHz, 293K,

1% D2O in CDCl3) δ 7.56-7.50 (m, 2H), 7.43-7.34 (m, 3H), 5.56 (s, 1H), 3.79 (s, 3H); 13C

NMR (75 MHz, 293K, CDCl3) δ 153.6, 138.2, 128.5, 128.4, 126.3, 86.7, 76.4, 63.7, 52.6; HRMS (EI+)

calcd for C11H10O3 (M+) 190.0630, found 190.0631.


2954, 2927, 2237 (C≡C), 1716 (C=O), 1435, 1265, 745, 701 cm-1; 1H NMR (300 MHz,

293K, CDCl3) δ 7.39-7.23 (m, 5H), 4.70 (apparent t, 1H, J = 6.3 Hz), 3.79 (s, 3H), 3.10

(dd, 1H, J = 13.7, 6.0 Hz), 3.04 (dd, 1H, J = 13.7, 6.7 Hz), 2.14 (br s, 1H); 13C NMR (75 MHz, 293K,

CDCl3) δ 153.7, 135.5, 129.6, 128.4, 127.0, 87.6, 76.7, 62.7, 52.7, 42.9; HRMS (EI+) calcd for C12H12O3

(M+) 204.0786, found 204.0793.

OH

CO2Me

OH

CO2MeMeO

OH

CO2Me

OH

PhCO2Me

OH

CO2Me

Ph


2927, 2237 (C≡C), 1717 (C=O), 1435, 1265, 740 cm-1; 1H NMR (300 MHz, 293K,

1% D2O in CDCl3) δ 7.48-7.32 (m, 5H), 6.81 (d, 1H, J = 15.9 Hz), 6.28 (dd, 1H, J =

15.9, 6.0 Hz), 5.18 (d, 1H, J = 6.0 Hz), 3.81 (s, 3H); 13C NMR (75 MHz, 293K, CDCl3) δ 153.8, 135.5,

133.1, 128.6, 128.3, 126.8, 125.6, 86.1, 77.1, 62.4, 52.9; HRMS (EI+) calcd for C13H12O3 (M+) 216.0786,

found 216.0787.

Pale yellow oil; Rf 0.36 (30% EtOAc in hexanes); IR (film) 3435 (broad, O-H),

3092, 2957, 2925, 2241 (C≡C), 1717 (C=O), 1532, 1437, 1352, 1260, 751, 740,

706 cm-1; 1H NMR (300 MHz, 293K, 1% D2O in CDCl3) δ 8.41 (br s, 1H), 8.25

(br d, 1H, J = 7.8 Hz), 7.88 (br d, 1H, J = 7.8 Hz), 7.61 (apparent t, 1H, J = 7.8 Hz), 5.70 (s, 1H), 3.82 (s,

3H); 13C NMR (75 MHz, 293K, CDCl3) δ 153.6, 148.3, 140.4, 132.6, 129.9, 123.7, 121.6, 85.1, 78.0, 63.0,

53.2; HRMS (EI+) calcd for C11H9NO5 (M+) 235.0481, found 235.0481.

Yellow oil; Rf 0.35 (30% EtOAc in hexanes); IR (film) 3429 (broad, O-H), 3112,

2957, 2927, 2240 (C≡C), 1717 (C=O), 1523, 1351, 1265, 747 cm-1; 1H NMR (300

MHz, 293K, 1% D2O in CDCl3) δ 8.28 (m, 2H), 7.73 (m, 2H), 5.71 (s, 1H), 3.82

(s, 3H); 13C NMR (75 MHz, 293K, CDCl3) δ 153.4, 148.0, 145.0, 127.4, 124.0, 85.0, 78.2, 63.1, 53.1;

HRMS (EI+) calcd for C11H9NO5 (M+) 235.0481, found 235.0478.

Colorless oil; Rf 0.37 (20% EtOAc in hexanes); IR (film) 3419 (broad, O-H

stretch), 2956, 2932, 2861, 2237 (C≡C), 1720 (C=O), 1436, 1264, 750 cm-1; 1H

NMR (300 MHz, 293K, CDCl3) δ 4.51 (apparent t, 1H, J = 6.6 Hz), 3.80 (s, 3H), 1.89 (br s, 1H), 1.82-1.25

(m, 8H), 0.91 (t, 3H, J = 6.8 Hz); 13C NMR (75 MHz, 293K, CDCl3) δ 153.9, 88.5, 76.0, 62.0, 52.8, 36.7,

31.4, 24.5, 22.4, 14.1; HRMS (EI+) calcd for C10H16O3 (M+) 184.1099, found 184.1092.

White solid; m.p. 121-122 °C; Rf 0.35 (40% EtOAc in hexanes); IR (film) 3403

(broad, O-H, N-H), 3065, 2952, 2240 (C≡C), 1715 (C=O), 1530, 1499, 1264, 741

cm-1; 1H NMR (300 MHz, 293K, CDCl3) δ 7.77 (d, 2H, J = 7.5 Hz), 7.59 (d, 2H, J = 7.5 Hz), 7.41

(apparent t, 2H, J = 7.5 Hz), 7.33 (apparent t, 2H, J = 7.5 Hz), 5.52 (apparent t, 1H, J = 5.8 Hz), 4.60-4.56

(br m, 1H), 4.44 (d, 2H, J = 6.7 Hz), 4.28-4.23 (br m, 1H), 3.87 (d, 1H, J = 5.8 Hz), 3.75 (s, 3H), 3.59-3.53

(m, 1H), 3.44-3.35 (m, 1H); 13C NMR (75 MHz, 293K, CDCl3) δ 157.1, 153.6, 144.2, 143.7, 141.2, 127.6,

124.9, 119.9, 85.6, 76.7, 67.0, 61.6, 52.9, 46.9, 46.0; HRMS (EI+) calcd for C21H19NO5 (M+) 365.1264,

found 365.1273.

OH

CO2MePh

OH

CO2Me

O2N

OH

CO2MeO2N

OH

CO2Me

OH

CO2Me

FmocHN


2889, 2233 (C≡C), 1715 (C=O), 1435, 1265, 1104, 1031 cm-1; 1H NMR (300 MHz,

293K, CDCl3) δ 3.95 (s, 4H), 3.78 (s, 3H), 2.10-1.71 (m, 8H); 13C NMR (75 MHz, 293K, CDCl3) δ 153.9,

107.9, 89.4, 75.2, 66.8, 64.3, 52.8,36.2, 30.8; HRMS (EI+) calcd for C11H13O4 (M+-OMe) 209.0814, found

209.0804.

Colorless oil; Rf 0.36 (40% EtOAc in hexanes); IR (film) 3435 (broad, O-H), 2955,

2240 (C≡C), 1719 (C=O), 1437, 1256, 1035 cm-1; 1H NMR (300 MHz, 293K,

CDCl3) δ 4.92 (br s, 1H), 4.90 (br s, 1H), 4.60 (d, 1H, J = 9.8 Hz), 3.80 (s, 3H), 3.05

(dd, 1H, J = 4.6, 0.9 Hz), 2.78 (d, 1H, J = 14.7 Hz), 2.74 (br d, 1H, J = 4.6 Hz), 2.39 (d, 1H, J = 9.8 Hz),

2.34 (br d, 1H, J =14.7 Hz), 1.79 (s, 3H); 13C NMR (75 MHz, 293K, CDCl3) δ 153.4, 139.9, 114.9, 84.4,

77.3, 62.5, 59.4, 52.8, 49.3, 39.4, 23.1; HRMS (EI+) calcd for C10H11O3 (M+-OMe) 179.0708, found

179.0709.

OH

CO2Me

O

O

OH

CO2MeO

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