Frimpong et al.
JOCArticle
III. Formation of Enediyne Compounds from Hydroxy Sul-
fides. III.a. General Procedure: Acid Catalyzed Conditions. III.
a.1. Formation of 6-Butylhex-3-ene-1,5-diyne-3-phenyl Sulfide. A
solution of the hydroxy sulfide mixture (25:75 syn/anti) (100 mg,
0.39 mmol) in a 9:1 THF/H2O mixture (10 mL) was treated with
a catalytic amount of p-toluenesulfonic acid . The solution was
stirred at room temperature for 8-12 h and diluted with 10%
sodium bicarbonate solution (aqueous, 10 mL). After 5 min of
stirring, 20 mL of dichloromethane was added to the solution
with stirring for 10 min. The separated aqueous layer was
extracted with 3ꢀ10 mL of dichloromethane. The organic layers
were combined, washed with 3 ꢀ 10 mL of water, dried over
MgSO4, and concentrated. Purification was accomplished by
radial chromatography on silica gel (elution with 25:1 hexanes-
ethyl acetate) to give a mixture of diastereomers as a colorless oil
in a 73:27 cis/trans ratio: yield=82 mg (0.34 mmol)=87%; 1H
NMR (300 MHz, CDCl3) δ 0.90-1.51 (m, 7H), 2.07 (m, 2H),
2.63 (s, 0.27H), 2.71 (s, 0.73H), 5.90 (s, 0.73H), 6.21 (s, 0.27H)
7.10-7.25 (m, 5H); 13C NMR (75 MHz, CDCl3) δ (13.9, 14.1),
17.1, 22.9, 31.6, 77.2, (79.5, 80.3), (83.1, 83.7), (90.5, 91.7),
(113.3, 113.9), 125.1, 128.4(2), 129.3(2), 134.0, (145.9, 146.2);
MS m/z (Mþ) calcd 240.0973, obsd 240.0973. Anal. Calcd for
C16H16S: C, 79.95; H, 6.71. Found: C, 80.09; H, 6.60.
7.07-7.30 (m, 10H): 13C NMR (75 MHz, CDCl3) δ (81.5, 81.7),
83.0, 89.3, (92.6, 93.0), (114.0, 119.2), 122.0, 125.7, 128.1 (2),
(128.3, 128.5), 128.8 (2), 129.5 (2), 133.6 (2), (134.0, 134.5),
(144.6, 145.1).
III.a.3. Formation of 6-Trimethylsilylhex-3-ene-1,5-diyne-3-
phenyl Sulfide. III.a.3.a. Anti-Isomer Only. A solution of the
hydroxy sulfide (200 mg 0.73 mmol) in a 9:1 THF/H2O mixture
(20 mL) was treated with a catalytic amount of p-toluenesulfonic
acid. The solution was stirred at room temperature for 10-15 h
and diluted with 10% sodium bicarbonate solution (aqueous,
20 mL). After 5 min of stirring, 30 mL of dichloromethane was
added to the solution with stirring for 10 min. The separated
aqueous layer was extracted with 3ꢀ10 mL of dichloromethane.
The organic layers were combined, washed with 3ꢀ10 mL of
water, dried over MgSO4, and concentrated. Purification was
accomplished by radial chromatography on silica gel (elution
with 15:1 hexanes-ethyl acetate) to give the product as a
colorless oil in a 97:3 E/Z ratio (the minor isomer was detected
by GC-MS; the minor isomer was not seen by NMR):
yield = 123 mg (0.0.48 mmol) = 65%; 1H NMR (300 MHz,
CDCl3) δ 0.0.11 (s, 9H), 2.87 (s, 1H), 6.20 (s, 1H), 7.10-7.29
(m, 5H); 13C NMR (75 MHz, CDCl3) δ 0.09 (3), 78.7, 81.2,
95.3, 100.9, 112.5, 124.8, 127.2(2), 128.7(2), 131.8, 142.1. Anal.
Calcd for C15H16SSi: C, 70.25; H, 6.29. Found: C, 69.99;
H, 6.43.
III.a.3.b. Mixture of Isomers. A solution of the hydroxy sulfide
mixture (40:60 syn/anti) (200 mg 0.73 mmol) in a 9:1 THF/H2O
mixture (20 mL) was treated with a catalytic amount of p-
toluenesulfonic acid. The solution was stirred at room tempera-
ture for 10-15 h and diluted with 10% sodium bicarbonate
solution (aqueous, 20 mL). After 5 min of stirring, 30 mL of
dichloromethane was added to the solution with stirring for 10
min. The separated aqueous layer was extracted with 3ꢀ10 mL of
dichloromethane. The organic layers were combined, washed
with 3ꢀ10 mL of water, dried over MgSO4, and concentrated.
Purification was accomplished by radial chromatography on
silica gel (elution with 15:1 hexanes-ethyl acetate) to give a
mixture of diastereomers as a colorless oil in a 50:50 E/Z ratio:
yield=120 mg (0.48 mmol)=65%; 1H NMR (300 MHz, CDCl3) δ
0.09 (s, 4.5H) 0.10 (s, 4.5H) 2.81 (s, 0.5H), 2.87 (s, 0.5H), 5.77 (s,
0.5H), 6.20 (s, 0.5H), 7.10-7.29 (m, 5H); 13C NMR (75 MHz,
CDCl3) δ 0.09 (3), (78.7, 79.1), (81.2, 81.8), (95.3, 95.9), 100.9,
(112.5, 116.1), 124.8, 127.2(2), 128.7(2), (131.8, 132.9), (142.1,
143.5).
III.a.4. Formation of 6-(tert-Butyldimethylpropoxysilyl)hex-
3-ene-1,5-diyne-3-phenyl Sulfide. A solution of the hydroxy
sulfide mixture (15:85 syn/anti) (250 mg 0.67 mmol) in a 9:1
THF/H2O mixture (10 mL) was treated with a catalytic amount
of p-toluenesulfonic acid. The solution was stirred at room
temperature for 8-12 h and diluted with 10% sodium bicarbo-
nate solution (aqueous, 10 mL). After 5 min of stirring, 20 mL of
dichloromethane was added to the solution with stirring for 10
min. The separated aqueous layer was extracted with 3ꢀ10 mL
of dichloromethane. The organic layers were combined, washed
with 3ꢀ10 mL of water, dried over MgSO4, and concentrated.
Purification was accomplished by radial chromatography on
silica gel (elution with 10:1 hexanes-ethyl acetate) to give a
mixture of diastereomers as a colorless oil in an 82:18 cis/trans
ratio: yield=192 mg (0.54 mmol)=80%; 1H NMR (300 MHz,
CDCl3) δ 0.15 (s, 6H), 0.93 (s, 9H), 1.27 (m, 2H), 2.11(m, 2H),
2.71 (s, 0.82H), 2.80 (s, 0.18H), 3.75 (m, 2H), 5.93 (s, 0.82H),
6.16 (s, 0.18H), 7.07-7.26 (m, 5H); 13C NMR (75 MHz, CDCl3)
δ 0.13(2), (13.9, 14.1), (15.0, 15.1), 21.3(3), 33.9, (64.9, 65.3),
(77.3, 78.1), (79.7, 80.1), (83.2, 84.1), (93.1, 93.7), (114.1, 115.0),
125.4, 127.7(2), 129.1, 129.3, (133.7, 134.0), (144.9, 145.4); MS
m/z (Mþ) calcd 356.1630, obsd 355.9891. Anal. Calcd for
C21H28OSSi: C, 70.73; H, 7.91. Found: C, 70.81; H, 8.01.
III.a.2. Formation of 6-Phenylhex-3-ene-1,5-diyne-3-phenyl
Sulfide. III.a.2.a. Anti-Isomer Only. A solution of the hydroxy
sulfide (200 mg 0.72 mmol) in a 9:1 THF/H2O mixture (20 mL)
was treated with a catalytic amount of p-toluenesulfonic acid.
The solution was stirred at room temperature for 10-15 h and
diluted with 10% sodium bicarbonate solution (aqueous,
20 mL). After 5 min of stirring, 30 mL of dichloromethane
was added to the solution with stirring for 10 min. The separated
aqueous layer was extracted with 3ꢀ10 mL of dichloromethane.
The organic layers were combined, washed with 3ꢀ10 mL of
water, dried over MgSO4, and concentrated. Purification was
accomplished by radial chromatography on silica gel (elution
with 25:1 hexanes-ethyl acetate) to give the product as a
colorless oil in a 97:3 E/Z ratio (the minor isomer was detected
by GC-MS; the minor isomer was not seen by NMR): ield=156
mg (0.60 mmol)=83%; 1H NMR (300 MHz, CDCl3) δ 0.2.95 (s,
1H), 6.01 (s, 1H), 7.07-7.30 (m, 10H): 13C NMR (75 MHz,
CDCl3) δ 81.7, 82.9, 89.3, 92.6, 114.0, 122.0, 125.7, 128.1 (2),
128.3, 128.8 (2), 129.5 (2), 133.6 (2), 134.0, 144.6. Anal. Calcd for
C18H12S: C, 83.04; H, 4.65. Found: C, 82.91; H, 4.80.
III.a.2.b. Mixture of Isomers. A solution of the hydroxy
sulfide mixture (20:80 syn/anti) (200 mg, 0.72 mmol) in a 9:1
THF/H2O mixture (20 mL) was treated with a catalytic amount
of p-toluenesulfonic acid. The solution was stirred at room
temperature for 10-15 h and diluted with 10% sodium bicar-
bonate solution (aqueous, 20 mL). After 5 min of stirring, 30 mL
of dichloromethane was added to the solution with stirring for
10 min. The separated aqueous layer was extracted with 3ꢀ10 mL
of dichloromethane. The organic layers were combined, washed
with 3ꢀ10 mL of water, dried over MgSO4, and concentrated.
Purification was accomplished by radial chromatography on silica
gel (elution with 25:1 hexanes-ethyl acetate) to give a mixture of
diastereomers as a colorless oil in a 77:23 E/Z ratio: yield=160 mg
(0.61 mmol) = 85%; 1H NMR (300 MHz, CDCl3) δ 0.2.95
(s, 0.77H), 3.01 (s, 0.23H), 6.04 (s, 0.77H), 6.35 (s, 0.27H),
J. Org. Chem. Vol. 74, No. 16, 2009 5869