7918 J. Am. Chem. Soc., Vol. 122, No. 33, 2000
EVans et al.
and chlorodiphenylphosphine (37 µL, 0.21 mmol). The resulting slurry
was loaded onto a plug of silica and purified by flash chromatography
(1 × 3 cm, 95% hexane, 5% ethyl acetate) to yield 11a as an oil (77
Hz), 1.21 (d, 3H, J ) 6.3 Hz), 1.20 (s, 9H), 1.13 (d, 3H, J ) 6.8 Hz),
0.94 (d, 3H, J ) 6.7 Hz); 13C NMR (125 MHz, CDCl3) δ 68.4, 57.9,
42.6, 32.1, 30.0, 21.5, 20.8, 20.0; TLC Rf 0.50 (90% hexane, 10% ethyl
acetate); exact mass calcd for C10H22S1O1-NH4 requires m/z 208.1735,
found m/z 208.1742 (CI-NH3).
23
mg, 94% yield). [R]d +22.3° (c 0.26, CH2Cl2); IR (CH2Cl2) 2965,
1
1480, 1436, 1024, 934, 882 cm-1; H NMR (500 MHz, C6D6) δ 7.64
(q, 4H, J ) 7.4 Hz), 7.38 (d, 2H, J ) 7.5 Hz), 7.12 (t, 2H, J ) 7.4
Hz), 7.09-6.96 (m, 6H), 6.90 (t, 1H, J ) 7.4 Hz), 4.42 (qdd, 1H, J )
7.8, 6.3, 3.5 Hz), 2.93 (dd, 1H, J ) 6.4, 3.5 Hz), 2.09 (oct, 1H, J )
6.7 Hz), 1.40 (d, 3H, J ) 6.3 Hz), 1.01 (d, 3H, J ) 6.7 Hz), 0.95 (d,
3H, J ) 6.7 Hz); 13C NMR (125 MHz, C6D6) δ 143.9 (d, J ) 18 Hz),
143.0 (d, J ) 17 Hz), 138.7, 131.3, 131.0, 130.6, 130.4, 129.5, 129.3,
129.2, 129.0, 128.5, 128.4, 126.0, 78.3 (d, J ) 21 Hz), 63.7 (d, J ) 6
Hz), 30.8, 21.7, 20.7, 20.4 (d, J ) 5 Hz); 31P NMR (202 MHz, C6D6)
δ 108.8 (s); TLC Rf 0.6 (95% hexane, 5% ethyl acetate); exact mass
calcd for C24H27O1P1S1-H requires m/z 395.1599, found m/z 395.1590
(CI-NH3).
(b) (2R,3R)-3-tert-Butylthio-4-methyl-2-pentanol (5k). The fol-
lowing reagents were combined in the amounts indicated according to
the general procedure for the reduction of â-hydroxysulfoxides: 19k
(703 mg, 3.6 mmol) and BH3-THF (12 mL, 1.0 M in THF, 12.0 mmol).
The product was purified by flash chromatography (4 × 6 cm, 90%
hexane, 10% ethyl acetate) to yield 5k as an oil (635 mg, 92% yield):
[R]d23 -49.2° (c 0.45, CH2Cl2); IR (film) 3474, 2963, 2872, 1456, 1436,
1421, 1384, 1365, 1324, 1267, 1211, 1160, 1127, 1076, 1042, 967,
931, 830, 816, 739 cm-1; 1H NMR (500 MHz, C6D6) δ 3.60 (m, 1H),
2.89 (br d, 1H, J ) 2.2 Hz), 2.40 (dd, 1H, J ) 7.5, 2.6 Hz), 1.81
(dquint, 1H, J ) 6.8, 3.0 Hz), 1.21 (d, 3H, J ) 6.1 Hz), 1.14 (s, 9H),
0.99 (d, 3H, J ) 6.7 Hz), 0.81 (d, 3H, J ) 6.7 Hz); 13C NMR (125
MHz, C6D6) δ 67.6, 59.9, 42.5, 32.2, 30.0, 22.2, 21.1, 17.8; TLC Rf
0.50 (90% hexane, 10% ethyl acetate); exact mass calcd for C10H22S1O1-
NH4 requires m/z 208.1735, found m/z 208.1733 (CI-NH3).
General Procedure for Addition of tert-Butyl Isobutylsulfoxide
to Aldehydes: (a) (RS,2S,3R)-3-tert-Butylsulfinyl-4-methyl-2-pen-
tanol (18k). To a cooled (-78 ° C) solution of diisopropylamine (1.16
mL, 8.3 mmol) in THF (0.27 M) was added n-BuLi (1.59 M in hexanes,
5.2 mL, 8.3 mmol). The reaction was warmed to 0 °C and stirred for
30 min. The reaction was cooled to -78 °C, and a solution of 17 (1.25
g, 7.7 mmol) in THF (0.63 M) at -78 °C was added via cannula to the
reaction and stirred for 1 h. Acetaldehyde (522 µL, 8.3 mmol) was
added to the reaction mixture dropwise via syringe at -78 °C, and the
reaction was stirred for 30 min. The reaction was quenched with
saturated NH4Cl(aq), diluted with Et2O, and washed twice with saturated
NH4Cl(aq) and once with brine. The combined aqueous solutions were
extracted with CH2Cl2, and the combined organic solutions were dried
over MgSO4, filtered, and concentrated in vacuo. The crude reaction
mixture shows a 1:1 mixture of diastereomers at C2. Separation of
diastereomers by MPLC (Michel-Miller column size D, 80% hexane,
20% acetone) followed by recrystallization from cyclohexane yielded
(c) [(2S,3R)-3-tert-Butylthio-4-methylpent-2-oxy]diphenylphos-
phine (10k). The following reagents were combined in the amounts
indicated according to the general procedure for phosphinite incorpora-
tion: 4k (607 mg, 3.2 mmol), n-BuLi (1.41 M in hexanes, 2.3 mL, 3.2
mmol), and chlorodiphenylphosphine (574 µL, 3.2 mmol). The resulting
slurry was loaded onto a plug of silica and purified by flash
chromatography (3 × 3 cm, 95% hexane, 5% ethyl acetate) to yield
23
10k as an oil (1.0 g, 83% yield). [R]d +25.3° (c 0.56, CH2Cl2); IR
(CH2Cl2) 3073, 3045, 2964, 2871, 1959, 1890, 1733, 1480, 1461, 1435,
1374, 1318, 1246, 1160, 1129, 1096, 1071, 1046, 971, 930, 800, 825,
787 cm-1; 1H NMR (500 MHz, C6D6) δ 7.68 (q, 4H, J ) 7.5 Hz), 7.14
(m, 4H), 7.05 (m, 2H), 4.30 (dq, 1H, J ) 14.9, 6.3 Hz), 2.60 (dd, 1H,
J ) 6.8, 3.3 Hz), 2.32 (dquint, 1H, J ) 6.8, 3.3 Hz), 1.50 (d, 3H, J )
6.3 Hz), 1.18 (s, 9H), 1.00 (d, 6H, J ) 6.8 Hz); 13C NMR (125 MHz,
C6D6) δ 144.1 (d, J ) 19 Hz), 143.2 (d, J ) 18 Hz), 131.6, 131.5,
130.8, 129.5, 129.2, 128.5, 128.4, 128.3, 127.9, 80.5 (d, J ) 20 Hz),
55.9, 46.6, 42.6, 32.2, 29.0, 22.0, 21.5 (d, J ) 5 Hz), 18.4; 31P NMR
(202 MHz, C6D6) δ 109.9 (s); TLC Rf 0.6 (95% hexane, 5% ethyl
acetate); exact mass calcd for C22H31O1P1S1-H requires m/z 375.1912,
found m/z 375.1900 (CI-NH3).
23
18k as a white solid (750 mg, 47% yield): mp 88.4-88.7 °C; [R]d
+131° (c 1.02, CH2Cl2); IR (film) 3420, 2960, 2872, 2361, 1844, 1792,
1653, 1636, 1559, 1540, 1507, 1465, 1436, 1386, 1365, 1267, 1209,
1178, 1126, 1056, 1030, 984, 913, 856, 736 cm-1; 1H NMR (500 MHz,
CDCl3) δ 4.66 (br q, 1H, J ) 6.6 Hz), 2.49 (m, 2H), 1.38 (d, 3H, J )
6.6 Hz), 1.32 (d, 3H, J ) 6.5 Hz), 1.29 (s, 9H), 1.03 (d, 3H, J ) 6.8
Hz); 13C NMR (125 MHz, CDCl3) δ 67.1, 62.7, 54.6, 25.9, 23.4, 23.3,
20.5, 20.1; TLC Rf 0.18 (80% hexane, 20% acetone); exact mass calcd
for C10H23S1O2 requires m/z 207.1419, found m/z 207.1428 (CI-NH3).
(b) (RS,2R,3R)-3-tert-Butylsulfinyl-4-methyl-2-pentanol (19k). From
the reaction described above, separation of diastereomers by MPLC
followed by recrystallization from cyclohexane yielded 19k as a white
(d) [(2R,3R)-3-tert-Butylthio-4-methylpent-2-oxy]diphenyl-phos-
phine (11k). The following reagents were combined in the amounts
indicated according to the general procedure for phosphinite incorpora-
tion: 5k (614 mg, 3.2 mmol), n-BuLi (1.41 M in hexanes, 2.3 mL, 3.2
mmol), and chlorodiphenylphosphine (574 µL, 3.2 mmol). The resulting
slurry was loaded onto a plug of silica and purified by flash
chromatography (3 × 3 cm, 95% hexane, 5% ethyl acetate) to yield
23
solid (645 mg, 40% yield): mp 72.8-73.1 °C; [R]d -74.0° (c 1.00,
CH2Cl2); IR (film) 3442, 2980, 2361, 2090, 1652, 1559, 1541, 1521,
1506, 1465, 1456, 1436, 1395, 1368, 1333, 1298, 1257, 1206, 1168,
1104, 1074, 1002, 958, 915 cm-1; 1H NMR (500 MHz, CDCl3) δ 4.31
(dq, 1H, J ) 9.2, 6.3 Hz), 2.70 (dd, 1H, J ) 10.5, 2.1 Hz), 1.88 (dquint,
1H, J ) 7.0, 2.1 Hz), 1.33 (d, 3H, J ) 6.3 Hz), 1.31 (s, 9H), 1.00 (d,
3H, J ) 7.2 Hz), 0.91 (d, 3H, J ) 7.2 Hz); 13C NMR (125 MHz, CDCl3)
δ 66.1, 65.2, 55.3, 28.9, 23.7, 22.0, 19.5, 18.6; TLC Rf 0.20 (80%
hexane, 20% acetone); exact mass calcd for C15H24S1O2 requires m/z
207.1419, found m/z 207.1408 (CI-NH3).
23
11k as an oil (1.1 g, 91% yield). [R]d -12.6° (c 0.63, CH2Cl2); IR
(CH2Cl2) 3073, 3047, 2962, 2901, 2869, 1960, 1591, 1480, 1461, 1436,
1380, 1366, 1329, 1221, 1161, 1130, 1097, 1058, 1034, 970, 953, 932,
870, 828 cm-1; 1H NMR (500 MHz, C6D6) δ 7.68 (t, 2H, J ) 7.7 Hz),
7.63 (t, 2H, J ) 7.2 Hz), 7.10 (m, 4H), 7.02 (m, 2H), 4.50 (m, 1H),
2.67 (t, 1H, J ) 3.8 Hz), 2.23 (dsext, 1H, J ) 6.8, 4.3 Hz), 1.46 (d,
3H, J ) 6.5 Hz), 1.21 (s, 9H), 1.06 (d, 3H, J ) 6.7 Hz), 0.99 (d, 3H,
J ) 6.7 Hz); 13C NMR (125 MHz, C6D6) δ 143.8 (d, J ) 20 Hz),
143.6 (d, J ) 18 Hz), 131.5, 131.3, 130.3, 130.2, 129.6, 129.1, 128.5,
128.3, 128.1, 127.9, 81.7 (d, J ) 21 Hz), 54.1 (J ) 5 Hz), 42.6, 31.8,
28.1, 22.8, 20.9, 18.7 (d, J ) 5 Hz); 31P NMR (202 MHz, C6D6) δ
109.0 (s); TLC Rf 0.6 (95% hexane, 5% ethyl acetate); exact mass calcd
for C22H31O1P1S1-H requires m/z 375.1912, found m/z 375.1916 (CI-
NH3).
General Procedure for the Reduction of â-Hydroxysulfoxides:
(a) (2S,3R)-3-tert-Butylthio-4-methyl-2-pentanol (4k). To a solution
of â-hydroxysulfoxide 18k (703 mg, 3.6 mmol) in THF (0.1 M) was
added BH3-THF (12 mL, 1.0 M in THF, 12.0 mmol) and the reaction
was stirred at room temperature for 12 h. The reaction mixture was
then cooled to 0 °C and saturated NH4Cl(aq) was slowly added. The
reaction mixture was diluted with Et2O, washed with saturated NH4-
Cl(aq), saturated NaHCO3(aq), and brine. The combined aqueous solutions
were extracted with CH2Cl2. The combined organic solutions were dried
over MgSO4, filtered, concentrated in vacuo, and purified by flash
chromatography (4 × 6 cm, 90% hexane, 10% ethyl acetate) to yield
4k as an oil (650 mg, 95% yield): [R]d23 +0.99° (c 0.49, CH2Cl2); IR
(film) 3446, 2962, 2903, 2872, 1460, 1365, 1328, 1261, 1211, 1162,
(e) [(2S,3R)-3-tert-Butylthio-4-methylpent-2-oxy]bis(r-naphthyl)-
phosphine (49 g). The following reagents were combined in the
amounts indicated according to the general procedure for phosphinite
incorporation: 4k (221 mg, 1.16 mmol), n-BuLi (1.41 M in hexanes,
820 µL, 1.16 mmol), and chlorobis(R-naphthyl)phosphine (373 mg,
1.16 mmol). The resulting slurry was loaded onto a plug of silica and
purified by flash chromatography (2 × 3 cm, 5% ethyl acetate, 95%
1
23
1110, 1074, 1049, 1029, 970, 930, 861, 818, 821, 747, 731 cm-1; H
hexane) to yield 49g as a solid (0.5 g, 91% yield). [R]d -11.4° (c
NMR (500 MHz, C6D6) δ 3.98 (dq, 1H, J ) 6.3, 1.5 Hz), 2.44 (dd,
1H, J ) 6.4, 4.8 Hz), 2.37 (d, 1H, J ) 7.8 Hz), 1.88 (sext, 1H, J ) 6.7
0.38, CH2Cl2); IR (CH2Cl2) 3077. 3041, 2997, 2963, 2932, 2895, 2874,
1726, 1589, 1504, 1461, 1382, 1365, 1331, 1161, 1044, 1022, 971,