Raghavan et al.
JOCArticle
funnel fitted with a rubber septum, and an argon inlet, is charged
with carbon tetrabromide (8 g, 24 mmol) and then dry dichloro-
methane (30 mL) is added. The solution is cooled in an ice bath
and a solution of triphenylphosphine (12.6 g, 48 mmol) in dry
dichloromethane (30 mL) is then added dropwise via the addi-
tional funnel over 20 min. The reaction mixture is stirred at 0 °C
for 10 min, and then the solution of the aldehyde (2.16 g,
12 mmol) in dichloromethane (20 mL) is added over 5 min via
cannula. The solution is stirred at 0 °C for 1 h, and then water is
added. The water layer is separated, then extracted 3 times with
CH2Cl2 (30 mL). The combined organic layers were washed with
brine, dried over Na2SO4, filtered, and concentrated. The
residue was diluted with diethyl ether (50 mL), cooled to 0 °C,
and filtered. This was repeated 4 times. The ether layers were
concentrated and the residue was purified by small flash column
chromatography. The product was directly used in the next step.
Yield 95% (11.4 mmol). To a solution of the above dibromo
compound in tetrahydrofuran (95 mL) cooled at -78 °C was
added n-butyllithium (10.1 mL, 2.5 M, 25 mmol). The reaction
mixture was stirred at the same temperature for 30 min, then a
solution of acetaldehyde (14 mmol) in tetrahydrofuran (15 mL)
was added dropwise with cannula. After 30 min the reaction was
quenched by adding aq saturated ammonium chloride. The aq
layer was separated and reextracted with ether. The combined
organic layers were washed successively with water and brine,
dried over Na2SO4, and evaporated. The crude product was
purified by column chromatography with 15% EtOAc/hexanes
(v/v) to afford the sulfide 41 as an inseperable mixture (9.69
mmol) in 80% yield. Orange liquid; Rf 0.25 (20% EtOAc/
hexanes, v/v); IR (neat) 3418, 2975, 2926, 1634, 1582, 1442,
1326, 1074, 1023, 740 cm-1; 1H NMR (300 MHz, CDCl3) δ 7.27
(d, J = 7.4 Hz, 2H), 7.18 (t, J = 7.5 Hz, 2H), 7.10 (t, J = 7.0 Hz,
1H), 4.45-4.31 (m, 1H), 3.01 (dd, J = 13.0, 6.6 Hz, 1H), 2.79
(dd, J = 13.0, 7.3 Hz, 1H), 2.68-2.39 (m, 1H), 1.30 (d, J = 6.6
Hz, 3H), 1.16 (d, J = 6.8 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ
135.9, 129.5, 128.7, 126.1, 86.5, 83.6, 58.0, 40.4, 26.1, 24.3, 19.9;
MS (ESI) 221 [M þ H]þ; HRMS (ESI) m/z [M þ H]þ calcd for
C13H17OS 221.0994, found 221.1000.
anhydrous Na2SO4, and evaporated. The crude product was
purified by column chromatography with (50% EtOAc/
hexanes, v/v) to afford an equimolar inseparable mixture of
diastereomeric sulfoxides 44 (5.60 mmol) in 92% yield. Viscous
liquid; Rf 0.25 (60% EtOAc/hexanes, v/v); IR (neat) 3394, 2965,
1
2925, 1723, 1447, 1294, 1086, 1020, 750, 694 cm-1; H NMR
(300 MHz, CDCl3) δ 7.64-7.56 (m, 4H), 7.55-7.43 (m, 6H),
5.68 (dd, J = 10.5, 9.4 Hz, 1H), 5.37 (dd, J = 10.5, 9.4 Hz, 1H),
5.27 (t, J = 10.7 Hz, 1H), 5.12 (t, J = 10.7 Hz, 1H), 4.72-4.58
(m, 2H), 3.48-3.22 (m, 2H), 2.91 (dd, J = 12.4, 4.1 Hz, 1H), 2.85
(dd, J = 13.2, 6.9 Hz, 1H), 2.62 (dd, J = 13.2, 6.2 Hz, 1H), 2.46
(dd, J = 12.4, 11.7 Hz, 1H), 1.26 (d, J = 6.2 Hz, 3H), 1.23 (d,
J = 6.2 Hz, 3H), 1.18 (d, J = 6.8 Hz, 3H), 1.09 (d, J = 6.8 Hz,
3H); 13C NMR (75 MHz, CDCl3) δ 143.6, 143.3, 135.5, 134.3,
133.3, 133.0, 131.5, 131.2, 129.4, 129.3, 124.0, 123.9, 64.1,
63.8, 63.1, 62.4, 28.3, 27.8, 23.2, 22.6, 21.2, 20.8; MS (ESI) 239
[M þ H]þ; HRMS (ESI) m/z [M þ Na]þ calcd for C13H18O2NaS
261.0929, found 261.0925.
Compound 48: To a solution of cyclopropylcarbinol (0.25
mmol) in 1,2-dichloroethane (2 mL, 0.13 M) and water (0.33
mmol) was added mercuric trifluoroacetate (0.5 mmol) and
HgO (0.13 mmol). The reaction was stirred in the dark at rt
for 16 h under nitrogen atmosphere. The reaction was quenched
by the addition of aq KBr and extracted with dichloromethane.
The organic layer was washed with water and brine, dried over
Na2SO4, and evaporated to furnish the crude organomercuric
bromide, which was purified by column chromatography to
afford the compound 48 (133 mg, 0.22 mmol) as a single
diastereomer in 89% yield. Amorphous solid; mp 155-156
°C; Rf 0.25 (40% EtOAc/hexanes, v/v); [R]25D þ37 (c 1, CHCl3);
IR (neat) 3446, 2929, 2855, 1636, 1512, 1249, 1089, 1035, 835
cm-1; 1H NMR (300 MHz, CDCl3) δ 7.59 (d, J = 8.3 Hz, 2H),
7.36 (d, J = 8.3 Hz, 2H), 4.70-4.58 (m, 1H), 4.07-3.94 (m, 1H),
3.32 (dd, J = 12.8, 9.8 Hz, 1H), 2.81 (dd, J = 12.8, 1.8 Hz, 1H),
2.44 (s, 3H), 2.15-2.06 (m, 1H), 1.66-1.44 (m, 2H), 1.43-1.17
(m, 10H), 0.88 (t, J = 6.8 Hz, 3H); 13C NMR (75 MHz, CDCl3)
δ 142.5, 138.6, 130.3, 124.5, 74.2, 71.7, 60.9, 46.2, 34.8, 31.7,
29.5, 29.1, 25.9, 22.5, 21.4, 14.0; MS (ESI) 606 [M]þ; HRMS
(ESI) m/z [M þ Na]þ calcd for C18H29O3NaSHgBr 629.1045,
found 629.1049.
Compounds 42 and 43: The crude compound obtained by
reduction of 41, following the procedure mentioned earlier for
the synthesis of 10 and 11 from 9, was purified by column
chromatography (12% EtOAc/hexanes, v/v) to afford the allylic
alcohols roughly as a 1:1 mixture of diasteriomers in 85%
combined yield. Compound 42: pale yellow liquid; Rf 0.22
(20% EtOAc/hexanes, v/v); IR (neat) 3376, 2965, 2924, 1582,
Compound 49: To the solution of the organomercuric bromide
48 (130 mg, 0.22 mmol) in THF (2.2 mL) cooled at -78 °C was
added lithium borohydride (0.14 mL, 2 M in THF, 0.28 mmol)
dropwise when mercury began to precipitate almost immedi-
ately. The reaction mixture was stirred at -78 °C for 1 h. The
reaction mixture was quenched with aq saturated NH4Cl solu-
tion and extracted with ethyl acetate. The combined extracts
were washed with brine, dried over Na2SO4, and concentrated to
furnish the crude product. The crude compound was purified by
column chromatography (40% EtOAc/hexanes, v/v) to afford
the diol 49 (68 mg, 0.21 mmol) as a single diastereomer in 85%
1
1478, 1442, 1371, 1059, 1027, 740 cm-1; H NMR (300 MHz,
CDCl3) δ 7.36-7.22 (m, 4H), 7.22-7.11 (m, 1H), 5.44 (dd, J =
10.9, 8.8 Hz, 1H), 5.25 (dd, J = 9.8, 8.8 Hz, 1H), 4.54-4.42 (m,
1H), 2.95-2.72 (m, 3H), 1.24 (d, J = 6.2 Hz, 3H), 1.13 (d, J =
6.4 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 136.5, 134.4, 133.8,
128.8, 128.7, 125.7, 63.9, 40.6, 32.0, 23.6, 20.7; MS (ESI) 261
[M þ O þ H]þ. Compound 43: pale yellow liquid; Rf 0.20 (20%
EtOAc/hexanes, v/v); IR (neat) 3376, 2965, 2924, 1582, 1478,
1442, 1371, 1059, 1027, 740 cm-1; 1H NMR (300 MHz, CDCl3)
δ 7.38-7.22 (m, 4H), 7.22-7.13 (m, 1H), 5.46 (dd, J = 10.5, 9.0
Hz, 1H), 5.16 (dd, J = 10.5, 9.6 Hz, 1H), 4.50-4.37 (m, 1H),
2.95 (dd, J = 12.0, 3.7 Hz, 1H), 2.87-2.75 (m, 1H), 2.71 (dd, J =
12.0, 8.3 Hz, 1H), 1.19 (d, J = 6.0 Hz, 3H), 1.08 (d, J = 6.0 Hz,
3H); 13C NMR (75 MHz, CDCl3) δ 136.2, 134.5, 134.4, 129.1,
128.9, 126.1, 63.3, 40.6, 32.4, 22.9, 21.0; MS (ESI) 261 [M þ O þ
H]þ; HRMS (ESI) m/z [M þ H]þ calcd for C13H19O2S 239.1110,
found 239.1105.
yield. Viscous liquid; Rf 0.25 (45% EtOAc/hexanes, v/v); [R]25
D
þ39 (c 1, CHCl3); IR (neat) 3446, 2929, 2855, 1636, 1512, 1249,
1089, 1035, 835 cm-1; 1H NMR (200 MHz, CDCl3) δ 7.52 (d,
J = 8.3 Hz, 2H), 7.32 (d, J = 8.3 Hz, 2H), 4.44 (dt, J = 9.8, 2.6
Hz, 1H), 3.91-3.77 (m, 1H), 3.04 (dd, J = 12.9, 9.1 Hz, 1H),
2.70 (dd, J = 12.9, 2.3 Hz, 1H), 2.43 (s, 3H), 1.92-1.73 (m, 2H),
1.62-1.13 (m, 9H), 0.91 (d, J = 7.6 Hz, 3H), 0.89 (t, J = 8.3 Hz,
3H); 13C NMR (75 MHz, CDCl3) δ 142.1, 140.2, 130.2, 123.9,
75.5, 73.2, 60.7, 41.6, 34.9, 31.8, 29.3, 26.0, 22.6, 21.4, 14.1, 5.4;
MS (ESI) 327 [M þ H]þ; HRMS (ESI) m/z [M þ H]þ calcd for
C18H31O3S 327.2006, found 327.1993.
Compound 44: To a solution of the sulfide 42 (1.48 g, 6 mmol)
in dichloromethane (30 mL) cooled at -40 °C was added m-
CPBA (6 mmol) and the progress of the reaction was followed
by TLC. After 1 h the reaction mixture was diluted with
dichloromethane, washed successively with aq saturated NaH-
SO3, aq saturated NaHCO3, water, and brine, dried over
General Procedure for Oxymercuration-Demercuration of
Cyclopropylcarbinols. To a solution of cyclopropylcarbinol
(0.25 mmol) in 1,2-dichloroethane (2 mL, 0.13 M) and water
(0.33 mmol) was added mercuric trifluoroacetate (0.5 mmol)
and HgO (0.13 mmol). The reaction was stirred in the dark at rt
for 16 h under nitrogen atmosphere. The reaction was quenched
564 J. Org. Chem. Vol. 76, No. 2, 2011