Supporting Information - Wiley-VCH · 1-(Pent-2-yne-1-sulfonyl)-pent-2-yne (2a): (a)...

Supporting Information

© Copyright Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, 2006

S 1

Syntheses of Substituted 1, 3-Diene Synthons by a Ru-Catalyzed Diyne Hydrative Cyclization

Barry M. Trost* and Xiaojun Huang

Department of Chemistry, Stanford University, Stanford, CA 94305

S 2

General Experimental Conditions: All reactions were carried out in a flame-dried flask

under dry nitrogen or argon. Dry acetone was distilled over drierite. Dry tetrahydrofuran

(THF) was distilled over sodium benzophenone ketyl or purified on an alumina column

purification system. All other solvents were purified on an alumina column purification

system. All solvents were HPLC grade or analytical pure. Flash chromatography

employed ICN silica gel (Kieselgel 60, 230 ± 400 mesh), analytical TLC was performed

with 0.2 mm silica-coated glass plates (E. Merck, DC-Platten Kieselgel 60 F254).

Infrared (IR) data were recorded on sodium chloride plates on a Perkin Elmer Paragon

500 FT-IR spectrometer. Proton and broadband decoupled 13C nuclear magnetic

resonance (NMR) data were acquired at room temperature on Varian GEM 300, Inova

Unity 400, or Inova Unity 500 spectrometer as indicated. Chemical shifts are reported in

ppm relative to CDCl3, or C6D6. Elemental analyses were performed by M-H-W

Laboratories (USA). HRMS (EI) m/z spectra were recorded by the Mass Spectrometer

Facility of the School of Pharmacy, University of California, San Francisco (USA).

EtS

Et

O

O2a

1-(Pent-2-yne-1-sulfonyl)-pent-2-yne (2a): (a) 1-Pent-2-ynylsulfanylpent-2-yne (6a): 1-

Bromopent-2-yne 5a (1 mL, 9.78 mmol) was added to a solution of Na2S (385 mg, 4.93

mmol) in methanol (10 mL) and the resulting mixture was stirred at room temperature for

5 h. The reaction mixture was quenched with H2O and the solvent was evaporated in

vacuo. The aqueous phase was extracted with Et2O and the extract was washed with H2O

and brine, dried (Na2SO4), filtered through a pad of silica gel and evaporated in vacuo to

give the crude sulfide 6a (750 mg, 92%) which was used directly into the next step. Rf =

0.72 (EtOAc/pet. ether 1:4); IR (thin film): ν = 2975, 2916, 2878, 2232, 1454, 1412,

1319, 1228, 1062, 742 cm−1; 1H NMR (300 MHz, CDCl3): δ = 3.36 (t, J = 2.4 Hz, 4H),

2.18 (qt, J = 7.5, 2.4 Hz, 4H), 1.10 (t, J = 7.5 Hz, 6H); 13C NMR (75.4 MHz, CDCl3): δ =

84.9, 74.4, 19.5, 13.9, 12.5.

(b) 1-(Pent-2-yne-1-sulfonyl)-pent-2-yne (2a): mCPBA (3.43 g, 13.5 mmol) was added in

one portion to a stirred solution of the crude propargylic sulfide 6a (750 mg, 4.51 mmol)

S 3

in CH2Cl2 (80 mL). Stirring was continued for 2 h. The mixture was diluted with

CH2Cl2 and washed successively with saturated aqueous Na2S2O3 (2×), saturated aqueous

NaHCO3 (2×) and H2O, dried (Na2SO4) and evaporated in vacuo. Flash chromatography

of the residue over silica gel, using 1:4 EtOAc/pet. ether, gave sulfone 2a (760 mg, 85%).

Rf = 0.4 (EtOAc/pet. ether 1:4); m.p. 46 oC; IR (thin film): ν = 2979, 2915, 2242, 1458,

1396, 1332, 1244, 1177, 1126, 1063, 869, 781 cm−1; 1H NMR (400 MHz, CDCl3): δ =

3.96 (t, J = 2.4 Hz, 4H), 2.23 (tq, J = 2.4, 7.2 Hz, 4H), 1.14 (t, J = 7.2 Hz, 6H); 13C NMR

(100.6 MHz, CDCl3): δ = 90.2, 66.3, 43.5, 13.3, 12.5; elemental analysis calcd (%) for

C10H14O2S: C 60.57, H 7.12; found: C 60.71, H 6.98.

SO

O

2b 1-(But-2-yne-1-sulfonyl)-but-2-yne (2b): (a) 1-But-2-ynylsulfanylbut-2-yne (6b): The

procedure for the preparation of 6a was followed, using 5b (0.9 mL, 10.3 mmol), Na2S

(406 mg, 5.20 mmol) and MeOH (10 mL), and a reaction time of 6 h. The crude sulfide

6b (720 mg, 100%) was used immediately for next step. Rf = 0.64 (EtOAc/pet. ether

1:4); IR (thin film): ν = 2918, 2855, 2230, 1437, 1413, 1230, 1030, 902, 677 cm−1; 1H

NMR (500 MHz, CDCl3): δ = 3.33 (q, J = 2.5 Hz, 4H), 1.80 (t, J = 2.5 Hz, 6H); 13C

NMR (125.7 MHz, CDCl3): δ = 79.9, 74.2, 19.5, 3.6.

(b) 1-(But-2-yne-1-sulfonyl)-but-2-yne (2b): The procedure for the preparation of 2a was

followed, using 6b (720 mg, 5.2 mmol), mCPBA (3.96 g, 15.6 mmol) and CH2Cl2 (80

mL), and a reaction time of 2 h. Flash chromatography of the crude product over silica

gel, using CH2Cl2, gave sulfone 2b (710 mg, 80%). Rf = 0.65 (EtOAc/pet. ether 1:1);

m.p. 93 oC; IR (thin film): ν = 2956, 2913, 2244, 1402, 1324, 1282, 1254, 1184, 1124,

876 cm−1; 1H NMR (500 MHz, CDCl3): δ = 3.94 (q, J = 2.5 Hz, 4H), 1.87 (t, J = 2.5 Hz,

6H); 13C NMR (125.7 MHz, CDCl3): δ = 84.6, 66.0, 43.5, 3.8; elemental analysis calcd

(%) for C8H10O2S: C 56.44, H 5.92; found: C 56.62, H 6.00.

SPh

O

O2c

S 4

[3-(But-2-yne-1-sulfonyl)-prop-1-ynyl]-benzene (2c): (3-But-2-ynylsulfanylprop-1-

ynyl)-benzene (6c): Thioacetic acid S-but-2-ynyl ester 7 (0.655 g, 5.11 mmol) was added

to a solution of KOH (287 mg, 5.11 mmol) and Na2S2O3 (10 mg, 0.063 mmol) in

methanol (10 mL) under nitrogen at 0 oC. After stirred at 0 oC for 30 min, (3-

Bromoprop-1-ynyl)-benzene 5c (997 mg, 5.11 mmol) was added dropwise to the reaction

mixture. Ice bath was removed and the mixture was stirred for 2 h. The reaction mixture

was quenched with H2O and the solvent was evaporated in vacuo. The aqueous phase

was extracted with Et2O and the extract was washed with H2O and brine, dried (Na2SO4),

filtered through a pad of silica gel and evaporated in vacuo to give the crude sulfide 6c

(920 mg) which was used directly into the next step. Rf = 0.72 (EtOAc/pet. ether 1:10).

[3-(But-2-yne-1-sulfonyl)-prop-1-ynyl]-benzene (2c): The procedure for the preparation

of 2a was followed, using 6c (920 mg, 4.59 mmol), mCPBA (3.0 g, 11.8 mmol) and

CH2Cl2 (50 mL), and a reaction time of 3 h. Flash chromatography of the crude product

over silica gel, using 2:7 EtOAc/pet. ether, gave sulfone 2c (570 mg, 53% over two

steps). Rf = 0.30 (EtOAc/pet. ether 1:4); m.p. 57 oC; IR (thin film): ν = 2958, 2912,

2243, 1491, 1444, 1395, 1331, 1260, 1229, 1174, 1126, 869, 759, 692 cm−1; 1H NMR

(500 MHz, CDCl3): δ = 7.42-7.50 (m, 2H), 7.28-7.38 (m, 3H), 4.24 (s, 2H), 4.20 (q, J =

2.5 Hz, 2H), 1.89 (t, J = 2.5 Hz, 3H); 13C NMR (125.7 MHz, CDCl3): δ = 132.0, 129.2,

128.4, 121.4, 87.7, 84.9, 76.0, 66.0, 44.0, 43.9, 3.9; elemental analysis calcd (%) for

C13H12O2S: C 67.21, H 5.21; found: C 66.97, H 5.05.

SO

O

2dOH

6-(But-2-yne-1-sulfonyl)-hex-4-yn-2-ol (2d): (a) 2-hexyne-1,5-diol: BuLi (2.5 M in

THF, 17 mL, 42.5 mmol) was added to a stirred and cooled (-78 oC) solution of 4-

pentyne-2-ol (2.0 mL, 21.2 mmol) in Et2O (40 mL) and THF (20 mL). After 30 min,

formaldehyde (636 mg, 22.3 mmol) was added all at once. The bath was removed and

stirring was continued for 6 h. The mixture was then poured into ice-water and extracted

with EtOAc (8×100 mL), dried and evaporated. Flash chromatography of the residue

over silica gel, using 2:1 EtOAc/pet. ether, gave 2-hexyne-1,5-diol (1.5 g, 62%). Rf =


S 5


3.87-3.99 (m, 1H), 3.61 (s, 2H), 2.22-2.45 (m, 2H), 1.21 (d, J = 6.3 Hz, 3H); 13C NMR

(75.4 MHz, CDCl3): δ = 82.6, 80.7, 66.3, 50.7, 29.0, 22.2.

(b) 6-bromohex-4-yn-2-ol (5d): CBr4 (1.51 g, 4.55 mmol) and Ph3P (1.19 g, 4.54 mmol)

were added successively to a stirred and cooled (0 oC) solution of 2-hexyn-1,5-diol (519

mg, 4.55 mmol) in CH2Cl2 (10 mL). The mixture was stirred for 10 h and the solvent

was evaporated. Flash chromatography of the crude mixture over silica gel, using 1:2

EtOAc/pet. ether, gave 6-bromohex-4-yn-2-ol 5d (725 mg, 90%). Rf = 0.58 (EtOAc/pet.

ether 1:1); IR (thin film): ν = 3374, 2972, 2909, 2233, 1420, 1211, 1115, 1085, 939, 609

cm−1; 1H NMR (300 MHz, CDCl3): δ = 3.80-4.00 (m, 3H), 2.20-2.50 (m, 3H), 1.21 (d, J

= 6.3 Hz, 3H); 13C NMR (75.4 MHz, CDCl3): δ = 84.2, 77.6, 66.2, 29.3, 22.3, 15.1.

(c) 6-But-2-ynylsulfanyl-hex-4-yn-2-ol (6d): The procedure for the preparation of 6c was

followed, using thioacetic acid S-but-2-ynyl ester 7 (0.506 g, 3.95 mmol), 5d (700 mg,

3.95 mmol), Na2S2O3 (8 mg, 0.05 mmol), KOH (222 mg, 3.96 mmol) and MeOH (5 mL),

and a reaction time of 4 h. Product 6d (800 mg) was used as crude.

(d) 6-(But-2-yne-1-sulfonyl)-hex-4-yn-2-ol (2d): The procedure for the preparation of 2a

was followed, using 6d (800 mg, ca. 3.95 mmol), mCPBA (2.9 g, 11.8 mmol) and


over silica gel, using 1:1 EtOAc/pet. ether, gave sulfone 2d (700 mg, 83% over two

steps). Rf = 0.47 (EtOAc/pet. ether 1:1); IR (thin film): ν = 3520, 2968, 2913, 2242,

1631, 1398, 1325, 1247, 1124, 940, 872 cm−1; 1H NMR (400 MHz, CDCl3): δ = 3.93-

4.02 (m, 5H), 2.32-2.48 (m, 2H), 2.12 (s, 1H), 1.87 (t, J = 2.4 Hz, 3H), 1.25 (d, J = 6.0

Hz, 3H); 13C NMR (100.6 MHz, CDCl3): δ = 85.8, 84.8, 69.5, 66.2, 66.0, 43.7, 43.5,

29.2, 22.4, 3.8; HRMS (EI): m/z: calcd for C10H15O3S: 215.0742 [M + H]+; found:

215.0744.

SO

O2e

OTBDPS

tert-Butyl-[5-(but-2-yne-1-sulfonyl)-1-methylpent-3-ynyloxy]-diphenylsilane (2e):

TBDPSCl (1.9 mL, 7.3 mmol) and imidazole (502 mg, 7.37 mmol) was added

successively to a stirred solution of 2d (518 mg, 2.417 mmol) in CH2Cl2 (50 mL), and the

S 6

mixture was stirred for 18 h. After quenched by saturated aqueous NH4Cl, the mixture

was extracted with Et2O, washed with brine, dried (Na2SO4) and evaporated. Flash

chromatography of the residue over silica gel, using 1:5 EtOAc/pet. ether, gave 2e (1.08

g, 99%) as colorless oil. Rf = 0.48 (EtOAc/pet. ether 1:4); IR (thin film): ν = 2960, 2243,

1589, 1428, 1334, 1126, 996, 870, 704 cm−1; 1H NMR (400 MHz, CDCl3): δ = 7.63-7.68

(m, 4H), 7.33-7.45 (m, 6H), 3.97 (sextet, J = 6.0 Hz, 1H), 3.89-3.93 (m, 4H), 2.32-2.37

(m, 2H), 1.86 (t, J = 2.4 Hz, 3H), 1.19 (d, J = 6.0 Hz, 3H), 1.04 (s, 9H); 13C NMR (100.6

MHz, CDCl3): δ = 135.77, 135.76, 133.92, 133.91, 129.7, 127.61, 127.59, 86.1, 84.6,

68.8, 67.8, 66.1, 43.5, 43.4, 29.3, 26.9, 22.9, 19.1, 3.8; elemental analysis calcd (%) for

C26H32O3SSi: C 68.98, H 7.13; found: C 69.12, H 6.91.

STMS

O

O

2f [3-(But-2-yne-1-sulfonyl)-prop-1-ynyl]-trimethylsilane (2f): (a) (3-Bromoprop-1-

ynyl)-trimethylsilane (5f): Propargylic bromide (80% in PhMe, 1.78 mL, 16 mmol) was

added to a stirred and cooled (-78 oC) solution of LDA (16 mmol) in Et2O (32 mL).

After 1 h, TMSCl (2.05 mL, 16 mmol) was added, and stirring was continued overnight

(-78 oC → room temperature). The mixture was quenched with saturated aqueous

NH4Cl, extracted with Et2O. The organic layer was washed with brine, dried (Na2SO4)

and evaporated. Flash chromatography of the residue over silica gel, using 1:50 Et2O/pet.

ether, gave 5f (1.45 g, 47%) as colorless oil. Rf = 0.77 (EtOAc/pet. ether 1:10); IR (thin

film): ν = 2961, 2900, 2181, 1422, 1252, 1206, 1042, 845, 761, 619 cm−1; 1H NMR (300

MHz, CDCl3): δ = 3.89 (s, 2H), 0.16 (s, 9H); 13C NMR (75.4 MHz, CDCl3): δ = 99.9,

92.3, 14.7, -0.4.

(b) 3-But-2-ynylsulfanylprop-1-ynyl)-trimethylsilane (6f): The procedure for the

preparation of 6c was followed, using thioacetic acid S-but-2-ynyl ester 7 (0.641 g, 5.00

mmol), 5f (956 mg, 5.0 mmol), Na2S2O3 (10 mg, 0.06 mmol), KOH (281 mg, 5.00 mmol)

and MeOH (10 mL), and a reaction time of 3 h. Product 6f (1 g) was used as crude.

(c) [3-(But-2-yne-1-sulfonyl)-prop-1-ynyl]-trimethylsilane (2f): The procedure for the

preparation of 2a was followed, using 6f (1 g, ca. 5.0 mmol), mCPBA (3.6 g, 14.6 mmol)

and CH2Cl2 (50 mL), and a reaction time of 15 h. Flash chromatography of the crude

S 7

product over silica gel, using 1:5 EtOAc/pet. ether, gave sulfone 2f (1.05 g, 92% over two


1395, 1335, 1252, 1128, 848, 762 cm−1; 1H NMR (400 MHz, CDCl3): δ = 4.00 (s, 2H),

3.94 (s, 2H), 1.86 (s, 3H), 0.16 (s, 9H); 13C NMR (100.6 MHz, CDCl3): δ = 94.1, 91.8,

84.7, 65.8, 44.2, 43.5, 3.8, -0.6; elemental analysis calcd (%) for C10H16O2SSi: C 52.59,

H 7.06; found: C 52.70, H 7.22.

SSiMe2Ph

O

O

2g [3-(But-2-yne-1-sulfonyl)-prop-1-ynyl]-dimethylphenylsilane (2g): (a) (3-Bromoprop-

1-ynyl)-dimethylphenylsilane (5g): The procedure for the preparation of 5f was followed,

using propargylic bromide (80% in PhMe, 0.89 mL, 10 mmol), LDA (10 mmol), Et2O

(20 mL) and PhMe2SiCl (1.7 mL, 10 mmol). Flash chromatography of the crude product

over silica gel, using 1:40 EtOAc/pet. ether, gave 5g (2.15 g, 85%) as colorless oil. Rf =

0.63 (EtOAc/pet. ether 1:10); 1H NMR (300 MHz, CDCl3): δ = 7.55-7.70 (m, 2H), 7.35-

7.45 (m, 3H), 3.95 (s, 2H), 0.46 (s, 6H); 13C NMR (75.4 MHz, CDCl3): δ = 136.2, 133.6,

129.6, 127.9, 101.6, 90,3, 14.5, -1.2.

(b) (3-But-2-ynylsulfanylprop-1-ynyl)-dimethylphenylsilane (6g): The procedure for the


mmol), 5g (1.27 g, 5.0 mmol), Na2S2O3 (10 mg, 0.06 mmol), KOH (281 mg, 5.00 mmol)

and MeOH (10 mL), and a reaction time of 3 h. Product 6f (1.35 g) was used as crude.

(c) [3-(But-2-yne-1-sulfonyl)-prop-1-ynyl]-dimethylphenylsilane (2g): The procedure for

the preparation of 2a was followed, using 6g (1.35 g, ca. 5.0 mmol), mCPBA (3.6 g, 14.6

mmol) and CH2Cl2 (50 mL), and a reaction time of 15 h. Flash chromatography of the

crude product over silica gel, using 1:5 EtOAc/pet. ether, gave sulfone 2g (1.4 g, 96%

over two steps). Rf = 0.37 (EtOAc/pet. ether 1:4): 0.37; IR (thin film): ν = 2960, 2911,

2244, 2185, 1429, 1335, 1251, 1127, 1043, 819, 734 cm−1; 1H NMR (500 MHz, CDCl3):

δ = 7.58-7.63 (m, 2H), 7.34-7.42 (m, 3H), 4.08 (s, 2H), 3.96 (q, J = 2.5 Hz, 2H), 1.88 (t, J

= 2.5 Hz, 3H), 0.44 (s, 6H); 13C NMR (125.7 MHz, CDCl3): δ = 135.7, 133.6, 129.7,

S 8

128.0, 93.5, 92.4, 84.8, 65.8, 44.3, 43.7, 3.8, -1.4; elemental analysis calcd (%) for

C15H18O2SSi: C 62.03, H 6.25; found: C 62.23, H 6.40.

SO

O

2h [3-(But-2-yne-1-sulfonyl)-prop-1-ynyl]-cyclopropane (2h): (a) (3-Bromoprop-1-ynyl)-

cyclopropane (5h): The procedure for the preparation of 5d was followed, using 3-

cyclopropylprop-2-yn-1-ol (768 mg, 7.99 mmol), CBr4 (2.65 g, 7.99 mmol), Ph3P (2.096

g, 7.99 mmol), and CH2Cl2 (16 mL), and a reaction time of 3 h. Bromide 5h (1.515 g,

mixed with CHBr3) was used as crude. 1H NMR (400 MHz, CDCl3): δ = 3.87-3.90 (m,

2H), 1.18-1.35 (m, 1H), 0.65-0.82 (m, 4H); 13C NMR (100.6 MHz, CDCl3): δ = 91.3,

70.5, 16.0, 8.4, -0.3.

(b) (3-But-2-ynylsulfanylprop-1-ynyl)-cyclopropane (6h): The procedure for the


mmol), 5h (1.515 g, mixed with CHBr3, ca. 3.95 mmol), Na2S2O3 (10 mg, 0.06 mmol),

KOH (270 mg, 4.81 mmol) and MeOH (7 mL), and a reaction time of 2 h. Sulfide 6h

(905 mg) was used as crude in the next step.

(c) [3-(But-2-yne-1-sulfonyl)-prop-1-ynyl]-cyclopropane (2h): The procedure for the

preparation of 2a was followed, using 6h (0.905 g), mCPBA (4.07 g, 16.5 mmol) and


over silica gel, using 1:3 EtOAc/pet. ether, gave sulfone 2h (532 mg, 34% over three


1329, 1246, 1176, 1126, 868 cm−1; 1H NMR (400 MHz, CDCl3): δ = 3.88-3.95 (m, 4H),

1.84 (t, J = 2.6 Hz, 3H), 1.18-1.30 (m, 1H), 0.62-0.80 (m, 4H); 13C NMR (100.6 MHz,

CDCl3): δ = 91.9, 84.5, 66.0, 61.9, 43.6, 43.3, 8.2, 3.7, -0.5; elemental analysis calcd (%)

for C10H12O2S: C 61.20, H 6.16; found: C 61.38, H 6.16.

SO

O

2i' OH 7-(But-2-yne-1-sulfonyl)-hept-5-yn-2-ol (2i’): (a) Hept-2-yne-1,6-diol: 5% Aqueous

NaHCO3 (90 mL), TEMPO (64 mg, 0.41 mmol), KBr (488 mg, 4.10 mmol) and bleach

S 9

(73 ml, ca. 60 mmol NaClO2) were added successively to a stirred and cooled (0 oC)

solution of 4-pentyne-1-ol (3.8 mL, 40 mmol) in CH2Cl2 (160 mL). Ice bath was

removed and stirring was continued for 1 h. The resulting two layers were separated, and

the CH2Cl2 layer was dried and concentrated to ca. 100 mL.

MeMgBr (3.0 M in Et2O, 13.5 mL, 40.5 mmol) was added to a stirred and cooled (-78 oC) aldehyde solution from above. Stirring was continued for 2h at -78 oC. The mixture

was quenched by saturated aqueous NH4Cl and separated. The organic phase was dried

(Na2SO4), and solvent was distilled (55 oC oil bath, 1 atm) to gave the crude 5-hexyne-2-

ol (3.45 g).

BuLi (2.5 M in THF, 29 mL, 72.5 mmol) was added to a stirred and cooled (-78 oC)

solution of 5-hexyne-2-ol (crude, 3.45 g, ca. 35 mmol) in THF (70 mL). After 30 min,

formaldehyde (1.10 g, 36.7 mmol) was added all at once. The bath was removed and

stirring was continued overnight. The mixture was quenched with saturated aqueous

NH4Cl (4 mL), dried (Na2SO4), filtered through a pad of silica gel (using EtOAc), and

evaporated. Flash chromatography of the residue over silica gel, using 2:1 EtOAc/pet.

ether, gave 2-heptyne-1,6-diol (2.1g, 41%, three steps). Rf = 0.26 (EtOAc/pet. ether 1:1); 13C NMR (125.7 MHz, CDCl3): δ = 85.7, 79.0, 67.0, 51.2, 37.3, 23.3, 15.3.

(b) 7-Bromo-hept-5-yn-2-ol (5i): The procedure for the preparation of 5d was followed,

using 2-Heptyne-1,6-diol (2.1 g, 16.4 mmol), CBr4 (5.44 g, 16.4 mmol), Ph3P (4.30 g,

16.4 mmol) and CH2Cl2 (36 mL), and a reaction time of 10 h. Flash chromatography of

the crude mixture over silica gel, using 1:2 EtOAc/pet. ether, gave 7-bromo-hept-5-yn-2-

ol 5i (2.62 g, 84%). Rf = 0.58 (EtOAc/pet. ether 1:1); IR (thin film): ν = 3360, 2967,

2232, 1428, 1215, 1128, 1078, 609 cm−1; 1H NMR (500 MHz, CDCl3): δ = 3.83-3.91 (m,

3H), 2.29-2.35 (m, 2H), 1.95 (s, 1H), 1.54-1.64 (m, 2H). 1.17 (d, J = 6.0 Hz, 3H); 13C

NMR (125.7 MHz, CDCl3): δ = 87.5, 75.7, 66.7, 37.2, 23.3, 15.50, 15.46.

(c) 7-But-2-ynylsulfanyl-hept-5-yn-2-ol (6i): The procedure for the preparation of 6c was

followed, using thioacetic acid S-but-2-ynyl ester 7 (1.75 g, 13.6 mmol), 5i (2.60 g, 13.6

mmol), Na2S2O3 (27 mg, 0.17 mmol), KOH (764 mg, 13.6 mmol) and MeOH (18 mL),

and a reaction time of 5 h. Flash chromatography of the residue over silica gel, using 1:3

EtOAc/pet. ether, gave sulfide 6i (2.6 g, 97%). Rf = 0.28 (EtOAc/pet. ether 1:4); IR (thin

film): ν = 3374, 2918, 2229, 1413, 1230, 1127, 1078, 907, 733 cm−1; 1H NMR (500

S 10

MHz, CDCl3): δ = 3.88 (s, 1H), 3.22-3.42 (m, 4H), 2.28 (s, 2H), 1.48-2.00 (m, 6H), 1.05-

1.30 (m, 3H); 13C NMR (125.7 MHz, CDCl3): δ = 82.9, 79.0, 75.7, 74.1, 67.0, 37.6, 23.3,

19.50, 19.46, 15.4, 3.6.

(d) 7-(But-2-yne-1-sulfonyl)-hept-5-yn-2-ol (2i’): The procedure for the preparation of 2a

was followed, using 6i (2.60 g, 13.2 mmol), mCPBA (9.8 g, 40 mmol) and CH2Cl2 (130

mL), and a reaction time of 5 h. Flash chromatography of the crude product over silica

gel, using 1:1 EtOAc/pet. ether, gave sulfone 2i’ (2.56 g, 85%). Rf = 0.53 (EtOAc/pet.

ether 1:1); IR (thin film): ν = 3531, 2964, 2919, 2241, 1631, 1397, 1325, 1246, 1124, 871

cm−1; 1H NMR (500 MHz, CDCl3): δ = 3.96 (t, J = 2.5 Hz, 2H), 3.94 (q, J = 2.5 Hz, 2H),

3.85-3.93 (m, 1H), 2.28-2.42 (m, 2H), 1.87 (t, J = 2.5 Hz, 3H), 1.77 (s, 1H), 1.57-1.69

(m, 2H), 1.08 (d, J = 6.5 Hz, 3H); 13C NMR (125.7 MHz, CDCl3): δ = 88.6, 84.7, 67.3,

66.7, 66.0, 43.51, 43.48, 37.0, 23.5, 15.4, 3.8; elemental analysis calcd (%) for

C11H16O3S: C 57.87, H 7.06; found: C 57.96, H 6.95.

SO

O

2i Cl 1-(But-2-yne-1-sulfonyl)-6-chlorohept-2-yne (2i): CCl4 (0.34 mL, 3.5 mmol) and Ph3P

(0.918 g, 3.5 mmol) were added successively to a stirred and cooled (0 oC) solution of

alcohol 2i’ (526 mg, 2.3 mmol) in CH3CN (23 mL). The mixture was stirred for 10 h and

the solvent was evaporated. Flash chromatography of the residue over silica gel, using

1:4 EtOAc/pet. ether, gave 2i (495 mg, 87%). Rf = 0.33 (EtOAc/pet. ether 1:4); IR (thin

film): ν = 2959, 2917, 2242, 1445, 1330, 1246, 1177, 1125, 870 cm−1; 1H NMR (400

MHz, CDCl3): δ = 4.07-4.17 (m, 1H), 3.95 (t, J = 2.0 Hz, 2H), 3.93 (q, J = 2.4 Hz, 2H),

2.39-2.46 (m, 2H), 1.77-1.96 (m, 2H), 1.86 (t, J = 2.4 Hz, 3H), 1.50 (d, J = 6.8 Hz, 3H); 13C NMR (100.6 MHz, CDCl3): δ = 87.3, 84.6, 67.8, 65.9, 57.0, 43.5, 43.4, 38.2, 25.1,

16.4, 3.8; elemental analysis calcd (%) for C11H15ClO2S: C 53.54, H 6.13; found: C

53.70, H 5.91.

SO

O

2j Br

S 11

6-Bromo-1-(but-2-yne-1-sulfonyl)-hept-2-yne (2j): The procedure for the preparation

of 5d was followed, using alcohol 2i’ (424 mg, 1.86 mmol), CBr4 (924 mg, 2.79 mmol),

Ph3P (731 mg, 2.79 mmol) and CH3CN (19 mL), and a reaction time of 3 h. Flash

chromatography of the crude mixture over silica gel, using 1:4 EtOAc/pet. ether, gave

bromide 2j (440 mg, 81%). Rf = 0.35 (EtOAc/pet. ether 1:4); IR (thin film): ν = 2958,

2918, 2242, 1443, 1330, 1245, 1176, 1125, 870 cm−1; 1H NMR (500 MHz, CDCl3): δ =

4.22 (sextet, J = 7.0 Hz, 1H), 3.97 (t, J = 2.5 Hz, 2H), 3.95 (q, J = 2.5 Hz, 2H), 2.46 (tt, J

= 7.0, 2.5 Hz, 2H), 1.96 (q, J = 7.0 Hz, 2H), 1.88 (t, J = 2.5 Hz, 3H), 1.72 (d, J = 7.0 Hz,

3H); 13C NMR (125.7 MHz, CDCl3): δ = 87.2, 84.7, 68.1, 66.0, 49.7, 43.6, 43.4, 39.0,

26.3, 17.7, 3.8; elemental analysis calcd (%) for C11H15BrO2S: C 45.37, H 5.19; found: C

45.57, H 5.09.

SO

O

2k OTBDPS tert-Butyl-[6-(but-2-yne-1-sulfonyl)-1-methylhex-4-ynyloxy]-diphenylsilane (2k):

TBDPSCl (0.9 mL, 3.46 mmol) and imidazole (242 mg, 3.55 mmol) was added

successively to a stirred solution of 2i’ (267 mg, 1.17 mmol) in CH2Cl2 (24 mL), and the

mixture was stirred for 12 h. After quenched by saturated aqueous NH4Cl, the mixture

was extracted with Et2O, washed with brine, dried (Na2SO4) and evaporated. Flash

chromatography of the residue over silica gel, using 1:5 EtOAc/pet. ether, gave 2k (531

mg, 97%) as colorless oil. Rf = 0.44 (EtOAc/pet. ether 1:4); IR (thin film): ν = 2961,

2858, 2243, 1589, 1428, 1334, 1126, 1025, 704 cm−1; 1H NMR (500 MHz, CDCl3): δ =

7.63-7.69 (m, 4H), 7.33-7.44 (m, 6H), 3.91 (sextet, J = 6.0 Hz, 1H), 3.90 (t, J = 2.5 Hz,

2H), 3.88 (q, J = 2.5 Hz, 2H), 2.30 (tt, J = 7.5, 2.5 Hz, 2H), 1.87 (t, J = 2.5 Hz, 3H), 1.57-

1.76 (m, 2H), 1.03 (d, J = 6.0 Hz, 3H), 1.03 (s, 9H); 13C NMR (125.7 MHz, CDCl3): δ =

135.83, 135.81, 134.5, 134.0, 129.6, 129.5, 127.6, 127.4, 88.9, 84.5, 68.3, 66.8, 66.0,

43.5, 43.3, 37.7, 27.0, 23.1, 19.2, 15.0, 3.8.

SO

O

2l O

S 12

7-(But-2-yne-1-sulfonyl)-hept-5-yn-2-one (2l): Dess-Martin reagent (2.33 g, 5.5 mmol)

was added to a stirred solution of 2i’ (628 mg, 2.75 mmol) in CH2Cl2 (27.5 mL). After

90 min, the mixture was diluted with Et2O, washed with a 1:1 mixture of saturated

aqueous NaHCO3 and 10% aqueous Na2S2O3, and brine, dried (Na2SO4) and evaporated.

Flash chromatography of the residue over silica gel, using 1:1 EtOAc/pet. ether, gave 2l

(614 mg, 99%) as a white solid. Rf = 0.55 (EtOAc/pet. ether 1:1); m.p. 65 oC; IR (thin

film): ν = 2958, 2914, 2242, 1713, 1400, 1369, 1326, 1246, 1168, 1124, 872, 735 cm−1; 1H NMR (500 MHz, CDCl3): δ = 3.85-3.95 (m, 4H), 2.63 (t, J = 7.0 Hz, 2H), 2.42 (tt, J =

7.0, 2.5 Hz, 2H), 2.10 (s, 3H), 1.82 (t, J = 2.5 Hz, 3H); 13C NMR (125.7 MHz, CDCl3): δ

= 206.1, 87.4, 84.4, 67.3, 65.9, 43.35, 43.26, 41.5, 29.7, 13.1, 3.7; elemental analysis

calcd (%) for C11H14O3S: C 58.38, H 6.24; found: C 58.28, H 5.93.

SO

O

2m' OH 8-(But-2-yne-1-sulfonyl)-oct-6-yn-2-ol (2m’): (a) 2-Octyne-1,7-diol: The procedure for

the preparation of hept-2-yne-1,6-diol was followed, using 5-hexyn-1-ol (5.6 mL, 50

mmol), CH2Cl2 (200 mL), 5% Aqueous NaHCO3 (110 mL), TEMPO (80 mg, 0.51

mmol), KBr (610 mg, 5.1 mmol), bleach (90 mL, ca. 75 mmol NaClO2); MeMgBr (17

mL, 3.0 M in Et2O, 51 mmol); BuLi (29 mL, 2.5 M in THF, 72.5 mmol), THF (70 mL),

formaldehyde (1.10 g, 36.7 mmol). Flash chromatography of the residue over silica gel,

using 3:2 EtOAc/pet. ether, gave 2-octyne-1,7-diol (2.15 g, 30% over three steps). Rf =


1375, 1133, 1013 cm−1; 1H NMR (400 MHz, CDCl3): δ = 4.12-4.22 (m, 2H), 3.71-3.83

(m, 1H), 3.25 (s, 1H), 2.50-2.60 (m, 1H), 2.13-2.24 (m, 2H), 1.41-1.65 (m, 4H), 1.40 (d, J

= 6.0 Hz, 3H); 13C NMR (100.6 MHz, CDCl3): δ = 85.7, 78.9, 67.5, 50.8, 38.0, 24.6,

23.3, 18.6.

(b) 8-Bromooct-6-yn-2-ol (5m): The procedure for the preparation of 5d was followed,

using 2-octyne-1,7-diol (1.76 g, 12.4 mmol), CBr4 (4.11 g, 12.4 mmol), Ph3P (3.25 g,

12.4 mmol), and CH2Cl2 (28 mL), and a reaction time of 12 h. Flash chromatography of

the residue over silica gel, using 1:2 EtOAc/pet. ether, gave bromide 5m (1.8 g, 71%). Rf

S 13

= 0.54 (EtOAc/pet. ether 1:1); IR (thin film): ν = 3364, 2965, 2232, 1634, 1456, 1374,


3.75 (sextet, J = 6.0 Hz, 1H), 2.22 (tt, J = 6.4, 2.4 Hz, 2H), 1.84 (s, 1H), 1.42-1.65 (m,

4H), 1.40 (d, J = 6.0 Hz, 3H); 13C NMR (100.6 MHz, CDCl3): δ = 87.8, 75.5, 67.4, 38.1,

24.5, 23.5, 18.8, 15.6; elemental analysis calcd (%) for C8H13BrO: C 46.85, H 6.39;

found: C 46.66, H 6.17.

(c) 8-But-2-ynylsulfanyl-oct-6-yn-2-ol (6m): The procedure for the preparation of 6c was

followed, using thioacetic acid S-but-2-ynyl ester 7 (1.13 g, 8.82 mmol), 5m (1.8 g, 8.78

mmol), Na2S2O3 (18 mg, 0.11 mmol), KOH (495 mg, 8.82 mmol) and MeOH (12 mL),

and a reaction time of 5 h. Product 6m (2.7 g) was used as crude in the next step. Rf =

0.19 (EtOAc/pet. ether 1:4).

(d) 8-(But-2-yne-1-sulfonyl)-oct-6-yn-2-ol (2m’): The procedure for the preparation of 2a

was followed, using 6m (2.70 g, ca. 8.78 mmol), mCPBA (6.5 g, 26.4 mmol) and CH2Cl2

(85 mL), and a reaction time of 5 h. Flash chromatography of the crude product over

silica gel, using 1:1 EtOAc/pet. ether, gave sulfone 2m’ (1.62 g, 76% over two steps). Rf

= 0.49 (EtOAc/pet. ether 1:1); IR (thin film): ν = 3535, 3404, 2962, 2914, 2241, 1631,

1327, 1125, 871 cm−1; 1H NMR (500 MHz, CDCl3): δ = 3.97 (t, J = 2.5 Hz, 2H), 3.95 (q,

J = 2.5 Hz, 2H), 3.81 (sextet, J = 6.0 Hz, 1H), 2.27 (tt, J = 7.0, 2.5 Hz, 2H), 1.88 (t, J =

2.5 Hz, 3H), 1.50-1.71 (m, 4H), 1.49 (br s, 1H), 1.18 (d, J = 6.0 Hz, 3H); 13C NMR

(125.7 MHz, CDCl3): δ = 88.8, 84.6, 67.3, 67.2, 66.0, 43.5, 43.4, 38.1, 24.3, 23.5, 18.7,

3.8; elemental analysis calcd (%) for C12H18O3S: C 59.47, H 7.49; found: C 59.60, H

7.52.

SO

O

2m O 8-(But-2-yne-1-sulfonyl)-oct-6-yn-2-one (2m): Dess-Martin reagent (1.99 g, 4.69

mmol) was added to a stirred solution of 2m’ (568 mg, 2.34 mmol) in CH2Cl2 (23 mL).

After 3 h, the mixture was diluted with Et2O, washed with a 1:1 mixture of saturated

aqueous NaHCO3 and 10% aqueous Na2S2O3, and brine, dried (Na2SO4) and evaporated.

Flash chromatography of the residue over silica gel, using 1:1 EtOAc/pet. ether, gave 2m

S 14

(555 mg, 99%). Rf = 0.54 (EtOAc/pet. ether 1:1). IR (thin film): ν = 2957, 2913, 2241,

1712, 1372, 1328, 1177, 1125, 871 cm−1; 1H NMR (500 MHz, CDCl3): δ = 3.95 (t, J =2.5

Hz, 2H), 3.92 (q, J = 2.5 Hz, 2H), 2.54 (t, J = 7.0 Hz, 2H), 2.26 (tt, J = 7.0, 2.5 Hz, 2H),

2.11 (s, 3H), 1.85 (t, J = 2.5 Hz, 3H), 1.75 (quintet, J = 7.0 Hz, 2H); 13C NMR (125.7

MHz, CDCl3): δ = 208.0, 88.0, 84.7, 67.8, 66.0, 43.5, 43.4, 41.8, 30.0, 21.9, 18.1, 3.8;

elemental analysis calcd (%) for C12H16O3S: C 59.97, H 6.71; found: C 59.74, H 6.86.

2n O

EtO2C

EtO2C

2-But-2-ynyl-2-(6-oxo-hept-2-ynyl)-malonic acid diethyl ester (2n): (a) 2-But-2-ynyl-

2-(6-hydroxyhept-2-ynyl)-malonic acid diethyl ester (2n’): 2-(2-butynyl)malonic acid

diethyl ester (608 mg, 2.86 mmol) in THF (2.8 mL) was added to a stirred and cooled (0 oC) solution of NaH (114 mg, 2.85 mmol) in THF (2.8 mL). After 30 min, bromide 5i

(365 mg, 1.91 mmol) in THF (2 mL) was added, and stirring was continued at 0 oC for 2

h. The mixture was quenched with saturated aqueous NH4Cl, extracted with Et2O, dried

(Na2SO4) and evaporated. Flash chromatography of the residue over silica gel, using 1:2

EtOAc/pet. ether, gave 2n’ (591 mg, 96%). Rf = 0.59 (EtOAc/pet. ether 1:1); IR (thin

film): ν = 3428, 2979, 2925, 2237, 1739, 1430, 1295, 1210, 1072, 1053, 861 cm−1; 1H

NMR (500 MHz, CDCl3): δ = 4.15 (q, J = 7.0 Hz, 4H), 3.83 (sextet, J = 6.5 Hz, 1H), 2.84

(t, J = 2.5 Hz, 2H), 2.82 (t, J = 2.5 Hz, 2H), 2.11-2.26 (m, 2H), 1.92 (s, 1H), 1.69 (t, J =

2.5 Hz, 3H), 1.52 (q, J = 6.5 Hz, 2H), 1.19 (t, J = 7.0 Hz, 6H), 1.13 (d, J = 6.5 Hz, 3H); 13C NMR (125.7 MHz, CDCl3): δ = 169.2, 82.9, 78.8, 74.8, 73.1, 66.8, 61.6, 56.9, 37.6,

23.2, 22.78, 22.76, 15.2, 13.9, 3.4.

(b) 2-But-2-ynyl-2-(6-oxo-hept-2-ynyl)-malonic acid diethyl ester (2n): Dess-Martin

reagent (1.08 g, 2.55 mmol) was added to a stirred solution of 2n’ (411.5 mg, 1.276

mmol) in CH2Cl2 (13 mL). After 90 min, the mixture was diluted with Et2O, washed

with a 1:1 mixture of saturated aqueous NaHCO3 and 10% aqueous Na2S2O3, and brine,

dried (Na2SO4) and evaporated. Flash chromatography of the residue over silica gel,

using 1:3 EtOAc/pet. ether, gave 2n (408 mg, 100%). Rf = 0.59 (EtOAc/pet. ether 1:1);

IR (thin film): ν = 2983, 2924, 2237, 1736, 1430, 1367, 1291, 1209, 1053, 861 cm−1; 1H

S 15

NMR (400 MHz, CDCl3): δ = 4.15 (q, J = 7.2 Hz, 4H), 2.84 (t, J = 2.4 Hz, 2H), 2.81 (q, J

= 2.4 Hz, 2H), 2.55 (t, J = 7.2 Hz, 2H), 2.32 (tt, J = 7.2, 2.4 Hz, 2H), 2.11 (s, 3H), 1.69 (t,

J = 2.4 Hz, 3H), 1.20 (t, J = 7.2 Hz, 6H); 13C NMR (100.6 MHz, CDCl3): δ = 206.7,

169.1, 81.9, 78.8, 74.9, 73.1, 61.6, 56.8, 42.6, 29.8, 22.73, 22.67, 14.0, 13.2, 3.4;

elemental analysis calcd (%) for C18H24O5: C 67.48, H 7.55; found: C 67.60, H 7.36.

TsN

O2o N-But-2-ynyl-4-methyl-N-(6-oxohept-2-ynyl)-benzenesulfonamide (2o): N-But-2-

ynyl-N-(6-hydroxyhept-2-ynyl)-4-methylbenzene-sulfonamide (2o’): Ph3P (525 mg, 2

mmol) and DIAD (0.4 mL, 2 mmol) was added successively to a stirred and cooled (0 oC)

solution of N-but-2-ynyl-4-methylbenzenesulfonamide (446 mg, 2 mmol) and 2-heptyne-

1,6-diol (256 mg, 2 mmol) in THF (20 mL). The cooling bath was removed and stirring

was continued overnight. The solvent was evaporated in vacuo. Flash chromatography

of the residue over silica gel, using 1:2 EtOAc/pet. ether, gave 2o’ (400 mg, 60%) as

colorless oil. Rf = 0.40 (EtOAc/pet. ether 1:1); 1H NMR (400 MHz, CDCl3): δ = 7.67 (d,

J = 8.4 Hz, 2H), 7.26 (d, J = 8.4 Hz, 2H), 4.06 (t, J = 2.0 Hz, 2H), 4.02 (q, J = 2.0 Hz,

2H), 3.76 (sextet, J = 6.4 Hz, 1H), 2.38 (s, 3H), 2.10 (tt, J = 6.4, 2.0 Hz, 2H), 1.66 (s,

1H), 1.61 (t, J = 2.0 Hz, 3H), 1.44 (q, J = 6.4 Hz, 2H), 1.13 (d, J = 6.4 Hz, 3H); 13C NMR

(100.6 MHz, CDCl3): δ = 143.5, 135.4, 129.2, 127.9, 85.6, 81.6, 72.8, 71.5, 66.8, 37.3,

36.58, 36.57, 23.3, 21.5, 15.1, 3.4.

(b) N-But-2-ynyl-4-methyl-N-(6-oxohept-2-ynyl)-benzenesulfon-amide (2o): Dess-Martin

reagent (656 mg, 1.55 mmol) was added to a stirred solution of 2o’ (258 mg, 0.774

mmol) in CH2Cl2 (8 mL). After 1h, the mixture was diluted with Et2O, washed with a 1:1

mixture of saturated aqueous NaHCO3 and 10% aqueous Na2S2O3, and brine, dried

(Na2SO4) and evaporated. Flash chromatography of the residue over silica gel, using 2:5

EtOAc/pet. ether, gave 2o (230 mg, 90%). Rf = 0.55 (EtOAc/pet. ether 1:1); IR (thin

film): ν = 2921, 2236, 1718, 1598, 1433, 1350, 1163, 1094, 904, 748, 659 cm−1; 1H NMR

(400 MHz, CDCl3): δ = 7.64 (d, J = 8.0 Hz, 2H), 7.24 (d, J = 8.0 Hz, 2H), 4.01 (t, J = 2.0

Hz, 2H), 4.00 (q, J = 2.4 Hz, 2H), 2.45 (t, J = 7.2 Hz, 2H), 2.36 (s, 3H), 2.21 (tt, J = 7.2,

2.0 Hz, 2H), 2.07 (s, 3H), 1.58 (t, J = 2.4 Hz, 3H); 13C NMR (100.6 MHz, CDCl3): δ =

S 16

206.2, 143.4, 135.3, 129.2, 127.9, 84.5, 81.6, 72.8, 71.3, 41.9, 36.5, 36.4, 29.7, 21.4, 12.9,

3.3; elemental analysis calcd (%) for C18H21NO3S: C 65.23, H 6.39; found: C 65.03, H

6.21.

S 17

Compound 2d (13C NMR)

S 18

Compound 2d (1H NMR)

S 19

Compound 2k (13C NMR)

S 20

Compound 2k (1H NMR)

S 21

Compound 3h (13C NMR)

S 22

Compound 3h (1H NMR)

S 23

Compound 3j (13C NMR)

S 24

Compound 3j (1H NMR)

S 25

Compound 3j’ (13C NMR)

S 26

Compound 3j’ (1H NMR)

S 27

Compound 3k’ (13C NMR)

S 28

Compound 3k’ (1H NMR)

S 29

Compound 3n’ (13C NMR)

S 30

Compound 3n’ (1H NMR)

S 31

Compound 4c (13C NMR)

S 32

Compound 4c (1H NMR)

S 33

Compound 4k (13C NMR)

S 34

Compound 4k (1H NMR)

S 35

Compound 7 (13C NMR)

S 36

Compound 7 (1H NMR)

S 37


S 38

Compound 13 (1H NMR)

S 39


S 40


S 41


S 42


S 43


S 44


Supporting Information - Wiley-VCH · 1-(Pent-2-yne-1-sulfonyl)-pent-2-yne (2a): (a)...

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