β-Chlorovinylsilanes as Masked Alkynes in Oligoyne ...5-(Trimethylsilyl)penta-2,4-diyn-1-ol Me 3Si...

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β-Chlorovinylsilanes as Masked Alkynes in Oligoyne

Assembly: Synthesis of the First Aryl-End-Capped

Dodecayne

Simon M. E. Simpkinsa Michael D. Wellera and Liam R. Cox*

Supporting Information I

General Experimental

1 Instrumentation

Elemental analyses were recorded on a Carlo Erba EA1110 simultaneous CHNS

analyser. UV-Vis spectra were recorded on a UV-3101PC Shimadzu spectrometer in

CH2Cl2. Infrared spectra were recorded either neat as thin films between NaCl discs

or as a Nujol mull between NaCl discs, on a Perkin Elmer 1600 FTIR spectrometer.

The intensity of each band is described as s (strong), m (medium) or w (weak), and

with the prefix v (very) and suffix br (broad) where appropriate. 1H-NMR and 19F-

NMR spectra were recorded in CDCl3 at 500 MHz, 400 MHz, or 300 MHz, using

Bruker DRX 500, Bruker AMX 400, Bruker AV 400, Bruker AV 300 and Bruker AC

300 spectrometers. 13C-NMR spectra were recorded in CDCl3 at 125 MHz, 100 MHz,

or 75 MHz, respectively, using Bruker DRX 500, Bruker AMX 400, Bruker AV 400,

Bruker AV 300 and Bruker AC 300 spectrometers. Chemical shifts are reported as δ

values (ppm) referenced to the following solvent signals: CHCl3, δH 7.26; CDCl3, δC

# Supplementary Material (ESI) for Chemical Communications# This journal is (c) The Royal Society of Chemistry 2007

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77.0. The term "stack" is used to describe a region where resonances arising from

non-equivalent nuclei are coincident, and multiplet, m, to describe a region where

resonances arising from a single nucleus (or equivalent nuclei) are coincident but

coupling constants cannot be readily assigned. Mass spectra were recorded on a

Micromass LCT spectrometer utilizing electrospray ionisation (and a methanol

mobile phase), and a Micromass Zabspec spectrometer using m-nitrobenzylalcohol

(3-NOBA) as the matrix, and a Bruker biflex IV MALDI-TOF spectrometer and are

reported as (m/z (%)). HRMS were recorded on a Micromass LCT spectrometer

using a lock mass incorporated into the mobile phase. Melting points were

determined using open capillaries on a Gallenkamp MPD350 melting point apparatus

and are uncorrected. Crystal structure determinations were recorded on a Rigaku R-

axis IIc diffractometer.

2 Chemicals and Reagents

All reagents were obtained from commercial sources and used without further

purification unless stated otherwise. CH2Cl2 and MeCN were freshly distilled under

N2 from CaH2. THF and Et2O were freshly distilled under N2 from sodium

benzophenone ketyl. MeOH was distilled under a N2 atmosphere from Mg / I2 and

stored over activated 4 Å molecular sieves. All solutions are aqueous and saturated

unless stated otherwise. iPr2NH, Et3N and TMEDA were all distilled under a N2

atmosphere from KOH and stored under N2 at rt over activated 4 Å molecular sieves

(activated by heating under a vacuum for 15 min with a Bunsen flame immediately

before use).


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3 Reactions

All reactions were conducted in oven-dried (140 °C) or flame-dried glassware under a

N2 atmosphere, and at ambient temperature (20 to 25 °C) unless otherwise stated,

with magnetic stirring. Volumes of 1 mL or less were measured and dispensed with

Hamilton gastight syringes. Evaporation and concentration under reduced pressure

was performed at 50 - 500 mbar. Residual solvent was removed under high vacuum

(1 mbar).

Reactions were monitored by TLC using pre-coated glass-backed ICN silica-rapid

plates (60A F254) and visualised by UV detection (at 254 nm) and with ammonium

molybdate(IV) - cerium(IV) sulfate staining dip or potassium manganate(VII) staining

dip. Column chromatography was performed on Merck silica gel (particle size 40-63

µm mesh) or Fluka 60 (40-60 µm mesh) silica gel.

Experimental Data

5-(Trimethylsilyl)penta-2,4-diyn-1-ol

Me3Si

OH

MeLi•LiBr complex (39.2 mL of a 1.3 M solution in Et2O, 51 mmol) was added over

2 min to a solution of 1,4-bis(trimethylsilyl)buta-1,3-diyne (9.91 g, 51 mmol) in Et2O

(100 mL) at rt. The reaction mixture was stirred for 5 h before cooling to 0 ºC

whereupon paraformaldehyde (2.3 g, 76.4 mmol) was added. The reaction mixture


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was allowed to warm to rt. After 16 h, the reaction mixture was diluted with Et2O (50

mL) and quenched with NH4Cl solution (100 mL). The phases were separated and

the aqueous phase was extracted with Et2O (4 × 25 mL). The combined organic

extracts were washed with H2O (3 × 50 mL), brine (3 × 50 mL) and dried (MgSO4).

The solvent was removed under reduced pressure to afford the crude product as a

yellow-brown oil. Purification by flash column chromatography (33% Et2O in

hexane) yielded 5-(trimethylsilyl)penta-2,4-diyn-1-ol as a yellow oil (5.97 g, 77%); Rf

= 0.19 (17% Et2O in hexane); Anal Calcd for C8H12OSi: C, 63.10; H, 7.94. Found:

C, 62.91; H, 7.89; νmax(film)/cm-1 3048br, 2961m, 2900w, 2224w, 2108s (C≡C),

1412w, 1251s, 1180w, 1018s, 844s, 760m, 666m; δH(300 MHz, CDCl3 with D2O

quench) 0.17 (9H, s, Si(CH3)3), 4.28 (2H, s, CH2OD); δC(75 MHz, CDCl3) -0.6 (CH3,

Si(CH3)3), 50.9 (CH2, CH2OH), 70.3 (quat. C), 75.8 (quat. C), 87.1 (quat. C), 87.5

(quat. C); m/z (EI+) 152 (M+, 13%), 137 [100, (M-CH3)+], 120 (7), 109 [23, (M-

C2H3O)+], 83 (20), 75 (60).

5-(tert-Butyldiphenylsilyloxy)-1-(trimethylsilyl)penta-1,3-diyne

Me3Si

OSitBuPh2

Imidazole (6.26 g, 91.9 mmol) was added to a solution of 5-(trimethylsilyl)penta-2,4-

diyn-1-ol (5.74 g, 37.7 mmol) in CH2Cl2 (70 mL) at 0 ºC. The solution was stirred for

15 min to dissolve the imidazole, before adding tBuPh2SiCl (13.51 mL, 44.1 mmol) at

0 ºC. The reaction mixture was allowed to warm to rt. After 16 h, the reaction

mixture was diluted with Et2O (200 mL) and the organics were washed with H2O (2 ×

100 mL), brine (2 × 100 mL) and dried (MgSO4). Removal of the solvent under


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reduced pressure afforded a cloudy yellow oil. Purification by flash column

chromatography (10% Et2O in hexane) gave 5-(tert-butyldiphenylsilyloxy)-1-

(trimethylsilyl)penta-1,3-diyne as a yellow oil (14.52 g, 99%); Rf = 0.6 (hexane:Et2O;

2:1); Anal Calcd for C24H30OSi2: C, 73.79; H, 7.74. Found: C, 73.97; H, 7.65;

νmax(film)/cm-1 3071s, 2959s, 2858s, 2224w, 2110s (C≡C), 1959w, 1887w, 1822w,

1722w, 1658w, 1590m, 1472s, 1428s, 1372s, 1251s, 1187m, 1113s, 1079s, 939w,

845s, 701s; δH(300 MHz, CDCl3) 0.20 (9H, s, Si(CH3)3), 1.05 (9H, s, C(CH3)3), 4.35

(2H, s, CH2O), 7.38-7.45 (6H, stack, ArH), 7.67-7.76 (4H, stack, ArH); δC(75 MHz,

CDCl3) -0.4 (CH3, Si(CH3)3), 19.2 (quat. C, C(CH3)3), 26.6 (CH3, C(CH3)3), 53.0

(CH2, CH2O), 69.9 (quat. C, C≡C), 76.1 (quat. C, C≡C), 86.9 (quat. C, C≡C), 87.6

(quat. C, C≡C), 127.8 (CH, Ph), 129.9 (CH, Ph), 132.7 (quat. C, ipso Ph), 135.6 (CH,

Ph); m/z (TOF ES+) 413 [(M+Na)+, 100%], 445 [12, (M+Na+MeOH)+]; HRMS (TOF

ES+) Found (M+Na)+ 413.1742. C24H30NaOSi2 requires (M+Na), 413.1733.

(E)-5-(tert-Butyldiphenylsilyloxy)-1-(trimethylsilyl)-3,4-bis(trimethylstannyl)-

pent-3-en-1-yne

SnMe3

SnMe3

Me3Si

OSitBuPh2

Li shot (3.24 g, 467 mmol) was added in one portion to a solution of Me3SnCl (18.61

g, 93.4 mmol) in THF (140 mL) at 0 °C under an Ar atmosphere. After 2 h, the

solution had turned dark green and all the excess Li was black. Stirring was stopped

and the reaction mixture left to settle for 10 min. Three filter cannulas were used

concurrently to transfer the supernatant to a dry 500 mL Schlenk flask. The resulting


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solution of Me3SnLi was faintly turbid and grey-green in appearance. The reaction

mixture was cooled to –50 °C before adding CuBr·SMe2 (19.2 g, 93.4 mmol) in one

portion, whereupon the reaction mixture turned dark red. After stirring at –50 °C for

30 min, a solution of 5-(tert-butyldiphenylsilyloxy)-1-(trimethylsilyl)penta-1,3-diyne

(14.03 g, 35.9 mmol) in THF (30 mL) was added via cannula. The reaction mixture

was stirred at –50 °C for a further 30 min before allowing to warm to rt. After 18 h,

the reaction mixture was diluted with Et2O (100 mL) and stirred for 10 min before

passing through a Celite plug, washing with Et2O (100 mL). NH4Cl solution (150

mL) was added and the biphasic solution was stirred vigorously for 45 min until the

aqueous phase turned blue. The two phases were separated and the aqueous layer was

extracted with Et2O (2 × 100 mL). The combined organics were washed with brine

(200 mL) and dried (MgSO4). The solvent was removed under reduced pressure to

yield an orange-red oil. The product was purified by flash column chromatography

(5% Et2O in hexane) to give a yellow solid (24.73 g, 96%); Rf = 0.77 (hexane:Et2O;

10:1); νmax(film)/cm-1 3071s, 3051s, 2960s, 2858s, 2356w, 2106 (C≡C), 1958w,

1889w, 1824w, 1697w, 1590s (C=C), 1428s, 1249s, 1112m, 1039m, 842s; δH(300

MHz, CDCl3) -0.09 (9H, s (& d satellite, 2JH-Sn, 53.3), Sn(CH3)3), 0.18 (9H, s,

Si(CH3)3), 0.32 (9H, s (& d satellite, 2JH-Sn, 54.4), Sn(CH3)3), 1.05 (9H, s, C(CH3)3),

4.28 (2H, s (& 2 × d satellites, 3JH-Sn, 4JH-Sn, 43.4, 10.7), CH2O), 7.34-7.42 (6H, stack,

ArH), 7.64 (4H, d, J 7.7, ArH); δC(125 MHz, CDCl3) -7.6 (CH3, (& 2 × d satellites,

1JC-119

Sn 338.8, 1JC-117

Sn 324.1), Sn(CH3)3), -6.5 (CH3, (& 2 × d satellites, 1JC-119

Sn

339.4, 1JC-117

Sn 324.4), Sn(CH3)3), 0.1 (CH3, Si(CH3)3), 19.2 (quat. C, C(CH3)3), 27.0

(CH3, C(CH3)3), 73.2 (CH2, (& 3 × d satellites, 2JC-119

Sn 61.5, 2JC-117

Sn 58.9, 3JC-Sn

38.8) CH2O), 100.9 (quat. C), 108.6 (quat. C), 127.7 (CH, Ph), 129.7 (CH, Ph), 133.3

(quat. C), 135.8 (CH, Ph), 136.1 (quat. C), 173.4 (quat. C); m/z (TOF ES+) 740.9


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[(M+Na)+, 100%]; HRMS (TOF ES+) Found (M+Na)+ 743.1154.

C30H48ONaSi2120Sn2 requires (M+Na), 743.1185.

(E)-3-(tert-Butyldiphenylsilyl)-1-(trimethylsilyl)-4-(trimethylstannyl)-pent-3-en-

1-yn-5-ol

SnMe3

SitBuPh2

Me3Si

OH

BuLi (3 mL of a 2.34 M solution in hexanes, 7.0 mmol) was added to a solution of

(E)-5-(tert-butyldiphenylsilyloxy)-1-(trimethylsilyl)-3,4-bis(trimethylstannyl)-pent-3-

en-1-yne (5.0 g, 7.0 mmol) in THF (36 mL) at –78 °C, resulting in the formation of a

dark red solution. The reaction was monitored carefully by TLC and after 2 h, was

quenched at –78 °C by the addition of NH4Cl solution (40 mL). The product was

extracted with EtOAc (3 × 25 mL), and the combined extracts were washed with brine

(3 × 25 mL), and dried (MgSO4). Concentration under reduced pressure and

purification of the residue by column chromatography (hexane:Et2O; 15:1) afforded

(E)-3-(tert-butyldiphenylsilyl)-1-(trimethylsilyl)-4-(trimethylstannyl)pent-3-en-1-yn-

5-ol as a pale yellow crystalline solid (3.3 g, 84%); m.p. 90-94 °C; Rf = 0.18

(hexane:Et2O; 10:1); νmax(film)/cm-1 3582w (OH), 3073w, 3015w, 2960m, 2858m,

2117m (C≡C), 1428m, 1249s, 1216w, 1104s, 998m, 842s, 759vs, 703s; δH(300 MHz,

CDCl3) 0.21 (9H, s, Si(CH3)3), 0.30 (9H, s (& d satellite, 2JH-Sn, 55.1), Sn(CH3)3),

0.49 (1H, t, J 6.6, OH), 1.11 (9H, s, C(CH3)3), 3.77 (2H, d, J 6.6 (& dd satellite, 3JH-

Sn, 55.5, 2JH-H 6.6), CH2OH), 7.39-7.41 (6H, stack, ArH), 7.75-7.78 (4H, stack, Ar-H);

δC(100 MHz, CDCl3) -7.9 (CH3, (& 2 × d satellites, 1JC-119

Sn 345.1, 1JC-

117Sn

329.9),


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Sn(CH3)3), -0.7 (CH3, Si(CH3)3), 18.6 (quat. C, C(CH3)3), 27.0 (CH3, C(CH3)3), 67.0

(CH2, (& d satellite, 2JC-Sn 33.0), CH2O), 99.3 (quat. C), 110.7 (quat. C, (& 2 × d

satellites, 2JC-119

Sn 66.4, 2JC-

117Sn

63.5) =CSi), 128.2 (CH, Ph), 129.7 (CH, Ph), 133.3

(quat. C), 135.6 (quat. C), 136.0 (CH, Ph), 182.9 (quat. C, (& 2 × d satellites, 1JC-119

Sn

411.8, 1JC-117

Sn 393.7) =CSn); m/z (TOF ES+) 579.0 [(M+Na)+, 100%]; HRMS (TOF

ES+) Found (M+Na)+ 579.1520. C27H40ONaSi2120Sn requires (M+Na), 579.1537.

Crystals suitable for X-ray analysis were also obtained and confirmed the

regiochemistry of the retro-Brook rearrangement.


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(E)-3-(tert-Butyldiphenylsilyl)-4-chloro-1-(trimethylsilyl)-pent-3-en-1-yn-5-ol

Cl

SitBuPh2

Me3Si

OH

CuCl2 (198 mg, 1.47 mmol) was added in one portion to a solution of (E)-3-(tert-

butyldiphenylsilyl)-1-(trimethylsilyl)-4-(trimethylstannyl)pent-3-en-1-yn-5-ol (372

mg, 0.67 mmol) in THF (7.5 mL) at 0 °C. The reaction was allowed to slowly warm

to rt. After 7 h, the reaction mixture was diluted with hexane (25 mL) and the

precipitated Cu salts were removed by filtration through a short silica plug. Washing

the silica plug with a mixture of hexane:Et2O (10:1; 3 × 20 mL) and concentrating the

combined filtrates under reduced pressure afforded the crude vinyl chloride, which

was further purified by column chromatography to provide (E)-3-(tert-

butyldiphenylsilyl)-4-chloro-1-(trimethylsilyl)pent-3-en-1-yn-5-ol as white crystals

(286 mg, quant.); Anal Calcd for C24H31ClOSi2: C, 67.49; H, 7.32. Found: C, 67.35;

H, 7.05; m.p. 79-81°C; Rf = 0.41 (hexanes:Et2O; 2:1); UV-Vis (CH2Cl2): 262

(10560), 271sh, (9190); νmax(nujol)/cm-1 3364br (OH), 2128s (C≡C), 1533s (C=C),

1462s, 1250s, 1106s, 1064s, 844m; δH(300 MHz, CDCl3) 0.25 (9H, s, Si(CH3)3), 0.96

(1H, t, J 6.3, OH), 1.14 (9H, s, C(CH3)3), 3.73 (2H, d, J 6.3, CH2OH), 7.42-7.44 (6H,

stack, ArH), 7.75-7.78 (4H, stack, ArH); δC(75 MHz, CDCl3) -0.3 (CH3, Si(CH3)3),

19.2 (quat. C, C(CH3)3), 27.2 (CH3, C(CH3)3), 65.7 (CH2, CH2O), 104.5 (quat. C),

107.1 (quat. C), 119.9 (quat. C), 128.1 (CH, Ph), 129.9 (CH, Ph), 133.5 (quat. C),

135.6 (CH, Ph), 153.7 (quat. C); m/z (TOF ES+) 449.0 [(M+Na)+, 100%]; HRMS

(TOF ES+) Found (M+Na)+ 449.1498. C24H31ONaSi2Cl requires (M+Na), 449.1500.


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Crystals suitable for X-ray analysis were also obtained and confirmed the

stereoselectivity of the chlorodestannylation.

(E)-3-(tert-Butyldiphenylsilyl)-4-chloro-1-(trimethylsilyl)-pent-3-en-1-yn-5-al

Cl

SitBuPh2

Me3Si

O

Method 1.

A suspension of activated MnO2 (6.96 g, 80 mmol) and (E)-3-(tert-

butyldiphenylsilyl)-4-chloro-1-(trimethylsilyl)pent-3-en-1-yn-5-ol (1.72 g, 4.0 mmol)

in CH2Cl2 (30 mL) was stirred at rt. After 18 h, the reaction mixture was diluted with

CH2Cl2 (30 mL) and filtered through a silica and MgSO4 layered plug. The plug was

washed with CH2Cl2 (4 × 25 mL). Concentration of the combined filtrates under

reduced pressure and purification of the residue by column chromatography

(hexane:Et2O; 10:1) provided (E)-3-(tert-butyldiphenylsilyl)-4-chloro-1-

(trimethylsilyl)pent-3-en-1-yn-5-al as a viscous, yellow oil (1.66 g, 96%); Rf = 0.26


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(hexane:Et2O; 10:1); νmax(film)/cm-1 3358w, 3073m, 2962s, 2861s, 2122s (C≡C),

1689s (C=O), 1589w (C=C), 1501s (C=C), 1429s, 1250s, 1152s, 1106s, 847m, 701s;

δH(300 MHz, CDCl3) 0.30 (9H, s, Si(CH3)3), 1.22 (9H, s, C(CH3)3), 7.26-7.46 (6H,

stack, ArH), 7.74 (4H, dd, J 7.2, 1.6, ArH), 9.22 (1H, s, CHO); δC(75 MHz, CDCl3) -

0.6 (CH3, Si(CH3)3), 19.5 (quat. C, C(CH3)3), 27.4 (CH3, C(CH3)3), 104.7 (quat. C),

124.1 (quat. C), 128.3 (CH, Ph), 130.2 (CH, Ph), 133.1 (quat. C), 135.6 (CH, Ph),

139.8 (quat. C), 148.2 (quat. C), 184.2 (CH, CHO); m/z (TOF ES+) 447 [(M+Na)+,

100%]; HRMS (TOF ES+) Found (M+Na)+ 447.1341. C24H29ONaSi2Cl requires

(M+Na), 447.1343.

Method 2.

Dess-Martin Periodinane (1.45 g, 3.41 mmol) was added in one portion to a solution

of (E)-3-(tert-butyldiphenylsilyl)-4-chloro-1-(trimethylsilyl)pent-3-en-1-yn-5-ol (832

mg, 1.95 mmol) in CH2Cl2 (25 mL) at rt. After 30 min, the reaction was quenched by

the addition of NaS2O3 solution-NaHCO3 solution (1:1, 50 mL). The resulting

biphasic mixture was stirred at rt for 30 min and then the two phases were separated.

The organic layer was washed with NaHCO3 solution (20 mL), H2O (20 mL) and then

dried (MgSO4). Concentration under reduced pressure afforded (E)-3-(tert-

butyldiphenylsilyl)-4-chloro-1-(trimethylsilyl)pent-3-en-1-yn-5-al as a viscous,

yellow oil (821 mg, quant.). Data were consistent with those reported above (see

Method 1).


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(E)-3-(tert-Butyldiphenylsilyl)-4-chloro-6,6-dibromo-1-(trimethylsilyl)-hexa-3,5-

dien-1-yne

Cl

SitBuPh2

Me3Si

Br

Br

A solution of PPh3 (12.27 g, 46.8 mmol) in CH2Cl2 (40 mL) was added to a cooled (0

°C) solution of CBr4 (7.8 g, 23.4 mmol) in CH2Cl2 (30 mL) via a dropping funnel

over 5 min, resulting in the formation of a golden yellow solution. After 1 h at 0 °C, a

solution of (E)-3-(tert-butyldiphenylsilyl)-4-chloro-1-(trimethylsilyl)pent-3-en-1-yn-

5-al (4.97 g, 11.7 mmol) in CH2Cl2 (30 mL) was added dropwise over 5 min. The

dropping funnel was rinsed with additional CH2Cl2 (10 mL). After 1 h, hexane was

added to the solution with vigorous stirring to precipitate the Ph3P=O side-product.

The suspension was filtered through a silica plug and the plug was washed with

additional hexane (6 × 25 mL). The combined filtrates were concentrated under

reduced pressure. Recrystallisation from hexane gave (E)-3-(tert-butyldiphenylsilyl)-

4-chloro-6,6-dibromo-1-(trimethylsilyl)hex-3,5-dien-1-yne as a colourless, crystalline

solid (6.07 g, 84%); Anal Calcd for C25H29Br2ClSi2: C, 51.69; H, 5.03. Found: C,

51.61; H, 5.21; m.p. 116-117 °C (from hexane); Rf = 0.42 (hexane); νmax (film)/cm-1

3074s, 3054s, 2960s, 2861s, 2128s (C≡C), 1954w, 1885w, 1818w, 1589s (C=C),

1511w, 1460s, 1428s, 1378m, 1250s, 1107s, 843s; δH(300 MHz, CDCl3) 0.26 (9H, s,

Si(CH3)3), 1.19 (9H, s, C(CH3)3), 6.46 (1H, s, -CH=), 7.43-7.44 (6H, stack, ArH),

7.73-7.76 (4H, stack, ArH); δC(75 MHz, CDCl3) -0.3 (CH3, Si(CH3)3), 19.3 (quat. C,

C(CH3)3), 27.8 (CH3, C(CH3)3), 98.4 (quat. C), 104.7 (quat. C), 110.2 (quat. C), 123.2

(quat. C), 128.0 (CH), 129.8 (CH), 132.4 (CH), 135.3 (CH), 135.9 (CH), 144.0 (quat.


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C); m/z (TOF ES+) 688.9 [(M+109Ag)+, 76%], 686.9 [64, (M+107Ag)+], 459 (45), 415.0

[100, (M-TBDPSCl+109Ag)+], 413.0 [80, (M-TBDPSCl+107Ag)+], 383 (52), 381 (40);

HRMS (TOF ES+) Found (M+107Ag)+ 686.8881. C25H29Si2ClBr2107Ag requires

(M+107Ag), 686.8894. Found (M+109Ag)+ 688.8881. C25H29Si2ClBr2109Ag requires

(M+109Ag), 688.8890. Crystals suitable for X-ray analysis were also obtained and

confirmed the structure of this intermediate.

(E)-3-(tert-Butyldiphenylsilyl)-4-chloro-1-(trimethylsilyl)-hex-3-en-1,5-diyne (3)

Cl

SitBuPh2

Me3Si

H

3

BuLi (0.80 mL of a 2.7 M solution in hexanes, 2.15 mmol) was added over 5 min to a

pre-chilled (0 °C) solution of iPr2NH (0.32 mL, 2.26 mmol) in THF (5 mL). After 30

min, the resulting LDA solution was cooled to –78 °C and transferred via cannula to a

cooled (-78 °C) solution of (E)-3-(tert-butyldiphenylsilyl)-4-chloro-6,6-dibromo-1-

(trimethylsilyl)hex-3,5-dien-1-yne (212 mg, 0.365 mmol) in THF (5 mL). After 25


14

min, the resulting purple solution was quenched at –78 °C with NH4Cl solution (15

mL) and allowed to warm to rt. The product was extracted with hexane (3 × 10 mL),

and the combined extracts were washed with brine (3 × 10 mL), dried (MgSO4), and

concentrated under reduced pressure to afford masked triyne 3 as an opaque orange

oil, which was used directly in the subsequent dimerisation step without further

purification (150 mg, 98%); selected data: Rf = 0.22 (hexane); νmax(film)/cm-1 3292s

(C≡CH), 3073w, 2958s, 2925s, 2857s, 2127m (C≡C), 2091m (C≡C), 1590w, 1504m,

1464m, 1428s, 1250s, 1192w, 1107s, 1078s, 937w, 845s, 760m, 740m, 700s; δH(300

MHz, CDCl3) 0.23 (9H, s, Si(CH3)3), 1.17 (9H, s, C(CH3)3), 2.84 (1H, s, C≡CH),

7.35-7.41 (6H, stack, ArH), 7.70-7.74 (4H, stack, ArH); δC(75 MHz, CDCl3) -0.4

(CH3, Si(CH3)3), 19.6 (quat. C, C(CH3)3), 27.8 (CH3, C(CH3)3), 80.7 (quat. C), 88.9

(CH, C≡CH), 104.5 (quat. C), 114.1 (quat. C), 127.5 (CH), 128.1 (quat. C), 129.4

(CH), 129.7 (quat. C), 132.9 (quat. C), 136.2(CH); satisfactory MS data could not be

obtained on this compound.

(3E,9E)-3,10-Bis(tert-butyldiphenylsilyl)-4,9-dichloro-1-12-bis(trimethylsilyl)-

dodeca-3,9-dien-1,5,7,11-tetrayne (4)

4

Cl

SitBuPh2

Me3Si Cl

Ph2tBuSi

SiMe3

Cu(OTf)2 (18 mg, 0.05 mmol) was added in one portion to a solution of TMEDA (26

µL, 0.175 mmol) in CH2Cl2 (5 mL) at rt. The catalyst solution was stirred for 45 min


15

at rt and then transferred to a solution of masked triyne 3 (210 mg, 0.50 mmol) in

CH2Cl2 (2 mL). O2 was bubbled through the resulting brown solution and the

temperature of the reaction mixture was maintained at rt. After 8 h, the solution was

quenched with EDTA solution (pH 8.0, 5 mL) and the product extracted with CH2Cl2

(3 × 5 mL). The combined extracts were washed with brine (5 mL), dried (Na2SO4),

and the solvent removed under reduced pressure. The addition of MeCN to the

residue resulted in precipitation of masked hexayne 4, which was isolated as pale

yellow needles (139 mg, 66%); Anal Calcd for C50H56Cl2Si4: C, 71.47; H, 6.72.

Found: C, 71.20; H, 6.79; m.p. 170 °C (decomp); Rf = 0.59 (hexane:Et2O:toluene;

17:1:2); UV-Vis (CH2Cl2): 311sh (26910), 327 (34742), 345 (38091), 372 (37290),

402 (38792); νmax(nujol)/cm-1 2114s (C≡C), 1498w, 1461s, 1377m, 1250m, 1124w,

1108w, 1084w, 843m, 698w; δH(300 MHz, CDCl3) 0.22 (18H, s, 2 × Si(CH3)3), 1.13

(18H, s, 2 × C(CH3)3), 7.25-7.33 (12H, stack, ArH), 7.56-7.58 (8H, stack, ArH);

δC(75 MHz, CDCl3) -0.4 (CH3, Si(CH3)3)), 19.7 (quat. C, C(CH3)3), 27.9 (CH3,

C(CH3)3), 83.7 (quat. C), 84.0 (quat. C), 105.0 (quat. C), 117.1 (quat. C), 127.7 (CH,

Ph), 128.6 (quat. C), 129.7 (CH, Ph), 130.8 (quat. C), 132.3 (quat. C), 136.0 (CH, Ph);

m/z (TOF ES+) 861.4 [(M+Na)+, 100%]; HRMS (TOF ES+) Found (M+Na)+

861.2751. C50H56NaSi4Cl2 requires (M+Na), 861.2734.


16

(3E, 9E)-3,10-bis(tert-butyldiphenylsilyl)-4,9-dichloro-12-[3,5-

bis(trifluoromethyl)phenyl]-1-trimethylsilyl-dodeca-3,9-dien-1,5,7,11-tetrayne (6)

Cl

SitBuPh2

Me3Si Cl

Ph2tBuSi

CF3

CF3

Cl

SitBuPh2

Me3Si Cl

Ph2tBuSi

H

Cl

SitBuPh2

Me3Si Cl

Ph2tBuSi

SiMe3

4

5

6

AgNO3 (5 mg, 25 µmol) and H2O (225 µL, 12.5 mmol) were added to a pre-chilled (0

°C), degassed (3 × freeze/thaw cycles) solution of masked hexayne 5 (102 mg, 125

µmol) in THF (3 mL). The reaction mixture was stirred in the absence of light for 4 h

when TLC indicated that the predominant product was the desired mono-deprotected

substrate 5. The stirring was then stopped and the Ag salts were left to precipitate

over 30 min. In a separate flame-dried Schlenk flask charged with degassed (3 ×

freeze/thaw cycles) THF (2 mL) was added Pd(OAc)2 (4 mg, 10 mol%), and PPh3 (7

mg, 20 mol%). The resulting pale yellow solution was stirred for 5 min and then

Et3N (35 µL, 250 µmol), and 3,5-bis(trifluoromethyl)iodobenzene (44 µL, 250 µmol)

were added, followed immediately by the supernatant THF solution from the TMS-


17

monodeprotection reaction which was transferred via cannula. The Ag salts were

rinsed with additional degassed THF (1 mL) and the washings also transferred to the

Schlenk flask. CuI (4 mg, 10 mol%) was then added, and the final mixture was

degassed once more (2 × vac/N2) and then stirred in the absence of light at rt. After 1

h, TLC analysis showed that the starting material had been consumed. The reaction

mixture was diluted with hexane (5 mL) and the resulting precipitated salts were

removed by filtering the mixture through a short silica plug. The plug was washed

with a hexane:Et2O (7:3) (5 × 10 mL) and the combined filtrates were concentrated

under reduced pressure to afford a red oil. Purification of the residue by column

chromatography (hexane:toluene; 9:1) gave the monoaryl end-capped masked

hexayne 6 as a yellow oil (39 mg, 43%); Rf = 0.28 (hexane:toluene, 9:1); UV-Vis

(CH2Cl2): 315 (22700), 330 (25650), 350 (30900), 380sh (34100), 385 (34350), 416

(28900); νmax(film)/cm-1 3074m, 3051m, 2964s, 2897m, 2861s, 2176w, 2116m

(C≡C), 1957w, 1886w, 1817w, 1613w, 1589w, 1488m, 1462m, 1428s, 1385s, 1364m,

1305m, 1279s, 1265s, 1252s, 1183s, 1141s, 1107s, 1078m, 999w, 898s, 848s, 819m,

740s, 699s, 650m; δH(300 MHz, CDCl3) 0.24 (9H, s, Si(CH3)3), 1.15 (9H, s,

C(CH3)3), 1.20 (9H, s, C(CH3)3), 7.28-7.39 (12H, stack, ArH), 7.57-7.61 (8H, stack,

ArH), 7.75 (2H, br s, 2 × CCHC(CF3)), 7.82 (1H, br s, C(CF3)CHC(CF3)); δF(300

MHz, CDCl3) -63.1; δC(100 MHz, CDCl3) -0.4 (CH3, Si(CH3)3), 19.7 (quat. C,

C(CH3)3), 19.9 (quat. C, C(CH3)3), 27.9 (CH3, C(CH3)3), 28.2 (CH3, C(CH3)3), 83.6

(quat. C), 83.7 (quat. C), 84.3 (quat. C), 84.7 (quat. C), 93.8 (quat. C), 104.9 (quat. C),

105.1 (quat. C), 117.7 (quat. C), 122.1 (septet, 3JC-F 3.8, CH, C(CF3)CHC(CF3)),

122.8 (q, 1JC-F 271, quat. C, C(CF3)), 125.4 (quat. C), 127.7 (CH, Ph), 127.9 (CH, Ph),

128.4 (quat. C), 129.2 (quat. C), 129.5 (quat. C), 129.8 (CH, Ph), 130.1 (CH, Ph),

131.2-131.0 (CH, showing unresolved 3JC-F coupling, CCHC(CF3)), 131.5 (quat. C),


18

132.0 (quat. C, ipso Ph), 132.1 (q, 2JC-F 33.5, quat. C, C(CF3)), 132.3 (quat. C, ipso

Ph), 135.99 (CH, Ph), 136.0 (CH, Ph); m/z (TOF ES+) 1087 [(M+Ag)+, 100%];

HRMS (TOF ES+) Found (M+Ag)+ 1087.1559. C55H50F6Cl2Si3109Ag requires

(M+Ag), 1087.1549.

(3E, 9E, 15E, 21E)-1,24-Bis(3,5-bis(trifluoromethyl)phenyl)-4,9,16,21-

tetrachloro-3,10,15,22-tetrakis(tert-butyldiphenylsilyl)-tetracosta-3,9,15,21-

tetraen-1,5,7,11,13,17,19,23-octayne (8)

Cl

SitBuPh2

H Cl

Ph2tBuSi

CF3

CF3

Cl

SitBuPh2

Me3Si Cl

Ph2tBuSi

CF3

CF3

Cl

SitBuPh2

Cl

Ph2tBuSi

CF3

CF3

Cl

Ph2tBuSi

Cl

SitBuPh2

F3C

F3C

6

7

8

K2CO3 (15 mg, 0.11 mmol) was added in one portion to a cooled (0 °C) solution of

masked hexayne 6 (48 mg, 0.05 mmol) in THF (2 mL) and MeOH (1 mL). The

reaction mixture was stirred for 15 min in the absence of light and then quenched at 0

°C with NH4Cl solution (10 mL). The product was extracted with Et2O (3 × 10 mL).


19

The combined organic extracts were washed with brine (10 mL), dried (Na2SO4), and

concentrated under reduced pressure to afford free alkyne 7 as a brown oil, which was

used immediately in the subsequent dimerisation without further purification; selected

data: Rf = 0.27 (hexane:toluene, 9:1); νmax(film)/cm-1 3302w (C≡CH), 3072w, 2931

m, 2859m, 2127w (C≡C), 1612w, 1461w, 1428m, 1384s, 1278s, 1182s, 1140s, 1107s,

897m, 848w, 818w, 739m, 698s, 683m; m/z (TOF ES+) 929 [(M+Na)+, 100%].

Cu(OTf)2 (13 mg, 75 mol%) was added in one portion to a solution of TMEDA (19

µL, 0.13 mmol) in CH2Cl2 (1 mL) at rt. The catalyst solution was stirred open to the

air for 45 min at rt, and then transferred to a suspension of the free acetylene 7 (44

mg, 0.05 mmol) and 4 Å molecular sieves (4 microspatula tips) in CH2Cl2 (1 mL).

The resulting suspension was placed in the dark, under an air atmosphere for 20 h,

after which time, the suspension was loaded on to a short silica-plug and the product

was eluted with hexane:EtOAc; 95:5 (4 × 15 mL). The orange filtrates were

concentrated under reduced pressure. The masked dodecayne was isolated from the

residue by precipitation from a CH2Cl2:MeOH mixture to afford masked dodecayne 8

as an orange powder (33 mg, 75%): m.p. 178-182 °C (decomp.), Rf = 0.28

(hexane:EtOAc, 19:1); UV-Vis (CH2Cl2): 328sh (35280), 342 (36820), 370 (39770),

400 (40350), 443 (39610), 466sh (31300); νmax(nujol)/cm-1 1614w, 1461s, 1429m,

1378m, 1280m, 1261m, 1184m, 1138m, 1100m, 1021m, 896w, 803m, 736w, 719w,

698m; δH(300 MHz, CDCl3) 1.11-1.28 (36H, stack, 4 × C(CH3)3), 7.31-7.42 (24H,

stack, ArH), 7.57-7.81 (22H, stack, ArH); δF(300 MHz, CDCl3) -63.6; δC(100 MHz,

CDCl3) 19.7 (quat. C, C(CH3)3), 19.9 (quat. C, C(CH3)3), 27.9 (CH3, C(CH3)3), 28.2

(CH3, C(CH3)3), 84.3 (quat. C), 84.5 (quat. C), 85.0 (quat. C), 85.7 (quat. C), 90.0

(quat. C), 93.8 (quat. C), 94.1 (quat. C), 105.5 (quat. C), 122.2 (septet, 3JC-F 4.6, CH,

C(CF3)CHC(CF3)), 122.8 (q, 1JC-F 271, quat. C, C(CF3)), 125.4 (quat. C), 127.9 (CH,


20

Ph), 128.0 (quat. C), 129.0 (quat. C), 130.0 (CH, Ph), 130.05 (CH, Ph), 130.1 (quat.

C), 130.2 (quat. C), 130.4 (quat. C), 131.1-131.0 (m, showing unresolved 3JC-F

coupling, CH, CCHC(CF3)), 131.8 (quat. C, ipso Ph), 132.0 (quat. C, ipso Ph), 132.1

(q, 2JC-F 34.7, quat. C, C(CF3)), 135.97 (CH, Ph), 135.99 (CH, Ph); m/z (TOF ES+)

1836 [(M+Na)+, 100%], 1852 [15, (M+K)+].

1,24-Bis(3,5-bis(trifluoromethyl)phenyl) tetracostadodeca-1, 3, 5, 7, 9, 11, 13, 15,

17, 19, 21, 23-yne (9)

F3C

F3C

CF3

CF39

Masked dodecayne 8 (5.5 mg, 3.3 µmol) was weighed into a 2 mL volumetric flask

and a stock solution was made with UV-grade CH2Cl2. A 5 µL aliquot of the stock

solution was then diluted to a volume of 3 mL with CH2Cl2, and the UV spectrum of

the solution was recorded. TBAF (6 µL of a 0.005 M solution in CH2Cl2, 4 equiv)

was then added, the cuvette was stoppered and inverted quickly several times to

ensure total mixing and the UV spectrum was recorded. After 10 min, no further

changes was observed in the spectrum and the reaction was assumed to be complete.

Recording the UV spectrum again at later intervals (20 min, 30 min, 40 min, 1 h)

showed extensive product decomposition. Attempts to isolate dodecayne 9 after

reaction scale-up were unsuccessful due to product instability: UV-Vis (CH2Cl2): 258

(40240), 269 (44930), 279 (45540), 290 (42940), 303 (41590), 319 (49760), 334


21

(79410), 354 (157040), 377 (268300), 405 (294550), 432 (40880), 474 (5630), 484sh

(4400), 514 (2630), 562 (795).

The inset in Figure 2 of the paper shows an expansion of Region II of the UV-vis

spectrum illustrating the long wavelength, low absorptions for 9, which are

characteristic of oligoynes. In order to obtain a better resolved spectrum in this

region, the UV-vis experiment was carried out at increased concentration (x 12).

In a second experiment, masked dodecayne 8 (2.9 mg, 1.6 µmol) was weighed into a

1 mL volumetric flask and a stock solution was made with UV-grade CH2Cl2. A 25

µL aliquot of the stock solution was then transferred to a clean sample vial for

reaction. TBAF (32 µL of a 0.005 M solution in CH2Cl2, 4 equiv) was added to this

aliquot and the vial was stoppered and then inverted several times quickly to ensure

total mixing. 1 µL of the reaction mixture was layered on to a plate for analysis by

MALDI-TOF mass spectrometry. To this was added 1 µL of matrix (solution of 10

mg mL-1 6-aza-2-thiothymine (ATT) in MeOH) and the plate was left to dry in air for

~1 min. MALDI-TOF spectra were recorded by irradiation of the sample at 337 nm.

A second sample was run in the absence of ATT matrix and gave better results; m/z

(MALDI-TOF, ATT matrix) 769 [(M+Na+MeOH)+, 11%], 737 [5, (M+Na)+]; m/z

(MALDI-TOF, no matrix) 521 [100%], 715 [20, (M+H)+]. The peak at 521 in the

matrix-free experiment was assigned to an adduct formed by reaction between the

silyl fluoride (TBDPSF) by-product and TBAF reagent. To verify this, a control

experiment was performed: TBDPSCl (20 µL of a 0.002 M solution in CH2Cl2) was

transferred to a clean sample vial for reaction. TBAF (30 µL of a 0.005 M solution in


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CH2Cl2, 3.8 equiv) was added and the vial was stoppered and then inverted several

times quickly to ensure total mixing. 1 µL of the reaction mixture was layered on to a

plate for analysis in the absence of matrix by MALDI-TOF mass spectrometry. The

plate was left to dry in air for ~1 min and MALDI-TOF spectra was recorded by

irradiation at 337 nm; m/z (MALDI-TOF, no matrix) 244 [(NBu4)+, 100%], 521 (9).

All attempts to characterise dodecayne 9 by ES, FT-ICR, and EI proved unsuccessful.

In-situ-monitoring of the unmasking step (8 to 9) by NMR was considered but not

performed for the following reasons:

i) Millimolar concentrations of sample are typically used in NMR experiments. We

knew already from our UV-vis experiments that dodecayne 9 decomposes on a

minute timescale at nanomolar concentrations (i.e. a million times less concentrated

than standard concentrations used to record NMR spectra). The rate of decomposition

of the product is significantly faster when the unmasking reaction is carried out at

higher concentrations.

ii) Not only would product decomposition be a major hindrance to carrying out the

in-situ NMR experiment, we also questioned whether we would be able to obtain any

useful information from such an experiment. 13C-NMR spectroscopy is the only

useful NMR spectroscopic technique for characterising both the masked oliogynes (8)

and unmasked products (9); however, the very poor sensitivity of this technique

precludes its application in this instance. Our only option therefore would be to look

at 1H- and 19F-NMR. Looking at the starting material 8, product 9 and the eight


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intermediates, which can be generated in the unmasking reaction (depending on the

order in which the β-chlorovinylsilanes undergo elimination), the 19F resonances in all

these compounds are found only in the aryl end-caps, and the 1H resonances in the

aryl end-caps and silyl groups which are undergoing elimination. Since the nuclear

environments of these do not change significantly on going from starting material to

product, even if we were able to differentiate the resonances of the product,

intermediates and starting material, we reasoned that trying to deconvolute the data in

the knowledge that the end product (and probably advanced intermediates) will be

decomposing at the same time to provide other products, which would also exhibit

similar spectra, would be impossible.

iii) The presence of resonances from the four equivalents of Bu4NF, used to effect

unmasking, would further hamper our monitoring of the reaction by NMR.


β-Chlorovinylsilanes as Masked Alkynes in Oligoyne ...5-(Trimethylsilyl)penta-2,4-diyn-1-ol Me 3Si...

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Transcript of β-Chlorovinylsilanes as Masked Alkynes in Oligoyne ...5-(Trimethylsilyl)penta-2,4-diyn-1-ol Me 3Si...