Enantioselective Reductions of Ketones
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colorless solid was purified by column chromatography to
give 6b; yield: 0.68 g (74%); mp 163–165 8C; Rf =0.35 (n-
hexane/ethyl acetate, 3:2); [a]2D0: +176 (c 1, chloroform);
1H NMR (500 MHz, DMSO-d6): d=2.44 (s, 3H, CH3), 4.96
(s, 1H, 2-H), 5.64(1H, s, OH), 6.64(d, J=8.5 Hz, 2H, aro-
matic H), 6.98–7.36 (m, 10H, aromatic H), 7.45 (d, J=
8.2 Hz, 2H, aromatic H), 7.58 (d, J=8.5 Hz, 2H, aromatic
H), 7.69 (d, J=7.25 Hz, 2H, aromatic H); 13C NMR
(125 MHz, DMSO-d6): d=21.6 (CH3), 60.9 (C-2), 80.3 (C-
1), 112.8–130,4 (aromatic C), 145.9 (aromatic C), 147.3–
147.6 (aromatic C); MS (FAB, NBA): m/z (%)=482 (7)
[M+ +Na], 460 (29) [M+1]+, 443 (30), 329 (13), 307 (39),
289 (27), 276 (100); anal. calcd. for C27H25NO4S: C 70.57, H
5.48, N 3.05; found: C 70.40, H 5.61, N 3.09.
08C for 3 h. Then, nonafluorobutanesulfonyl fluoride
(1.56 g, 0.94mL, 5.17 mmol) was added in a countercurrent
of nitrogen. The mixture was stirred at room temperature
overnight, poured into a saturated solution of sodium car-
bonate and extracted with three 50 mL portions of diethyl
ether. The combined organic layers were dried with magne-
sium sulfate and the solvent was removed in a rotary evapo-
rator. The residue was purified by column chromatography
to give colorless solid 6d; yield: 1.74g (74%); mp 113–
1158C, Rf =0.47 (n-hexane/ethyl acetate, 2:1); [a]2D0: +131 (c
1
1, chloroform); H NMR (500 MHz, DMSO-d6): d=1.97 (s,
2H, NH2), 5.07 (s, 1H, OH), 5.74(s, 1H, 2-H), 6.96–7.05 (m,
3H, aromatic H), 7.14–7.39 (m, 9H, aromatic H), 7.71 (d,
J=7.9 Hz, 2H, aromatic H); 13C NMR (125 MHz, DMSO-
d6): d=61.6 (C-2), 79.9 (C-1), 123.9, 127.0, 130.7 (CF2), 123
(CF3), 120.5 (aromatic C), 126.2–130.7 (aromatic C), 140.9,
143.7, 146,2, 149.3 (aromatic ipso C); 19F NMR (470 MHz,
CDCl3): d=À81.1 (CF3), À109.3, À121.3, À126.3 (CF2); MS
(FAB, NBA): m/z (%)=588 (18) [M+1]+, 404 (27), 183
(17), 154(100), 77 (58); anal. calcd. for C 24H18F9NO4: C
49.07, H 3.09, N 2.38; found: C 49.12, H 3.17; N 2.34.
(R)-2-Amino-2-[4-(trifluoromethanesulfonyloxy)phen-
yl]-1,1-diphenylethanol (6c)
A 50-mL two-necked flask was equipped with a magnetic
stirrer, connected to the combined nitrogen/vacuum line,
charged with an 80% suspension of sodium hydride in min-
eral oil (0.29 g, 9.5 mmol), and closed with a septum. The air
in the flask was replaced by nitrogen, and anhydrous DMF
(20 mL) was injected by syringe. The mixture was cooled in
an ice bath and a solution of 5 (1.53 g, 5.0 mmol) in anhy-
drous DMF (25 mL) was slowly added under stirring so that
the temperature did not exceed 58C. Stirring was continued
in an ice bath for 3 h. In a counter current of nitrogen, N-
phenylbis(trifluoromethanesulfonamide) (2.32 g, 6.5 mmol)
was added in one portion. The ice bath was removed, and
the mixture was stirred at room temperature overnight. The
mixture was poured into a saturated solution of sodium car-
bonate (8 mL) and extracted three times with ethyl ether
(50 mL portions). The combined organic layers were dried
with magnesium sulfate and the solvent was removed under
reduced pressure. The residue was purified by column chro-
matography to give colorless, solid 6c; yield: 1.09 g (50%);
mp 125–1278C; Rf =0.39 (n-hexane/ethyl acetate, 2:1); [a]2D0:
+188 (c 1, chloroform); 1H NMR (500 MHz, DMSO-d6):
d=1.97 (s, 2H, NH2), 5.07 (s, 1H, OH), 5.75 (s, 1H, 2-H),
6.97–7.06 (m, 3H, aromatic H), 7.15–7.38 (m, 9H, aromatic
H), 7.71 (d, J=7.9 Hz, 2H, aromatic H); 13C NMR
(125 MHz, CDCl3): d=61.2 (C-2), 79.5 (C-1), 120 (CF3),
120.1 (aromatic C), 125.8–130.3 (aromatic C), 140.6, 143.2,
145.8, 148.6 (aromatic ipso C); 19F NMR (470 MHz, CDCl3):
d=À73 (CF3); MS (FAB, NBA): m/z (%)=438 (68) [M+
1]+, 420 (90), 343 (10), 307 (38), 289 (26), 254 (100); anal.
calcd. for C21H18F3NO4S: C 57.67, H 4.51, N 3.20; found: C
57.59, H 4.15, N 3.26.
(R)-2-Amino-2-(biphenyl-4-yl)-1,1-diphenylethanol
(6e)
Under nitrogen, a mixture containing 6d (0.88 g, 1.5 mmol),
tributylphenylstannane (0.49 mL, 0.55 g, 1.5 mmol), lithium
chloride (0.19 g, 4.5 mmol), tetrakistriphenylphosphane
(0.045 g, 0.039 mmol), 10 mL of freshly distilled 1,4-dioxane,
and a few crystals of 2,6-di-tert-butyl-4-methylphenol was
heated under stirring at 98–1008C for 23 h. After cooling to
room temperature, a 10% solution of ammonium hydroxide
(20 mL) was added. The mixture was diluted with diethyl
ether and filtered through celite. The filtrate was washed
with water and with brine, dried with magnesium sulfate
and concentrated under vacuum. The residue was purified
by column chromatography to give colorless solid 6e; mp
193–1958C; Rf =0.4( n-hexane/ethyl acetate, 1:1); [a]2D0:
+242 (c 1, chloroform); 1H NMR (500 MHz, DMSO-d6):
d=1.89 (s, 2H, NH2), 5.08 (s, 1H, OH), 5.68 (s, 1H, 2-H),
6.92–7.08 (m, 3H, aromatic H), 7.21–7.43 (m, 12H, aromatic
H), 7.58 (d, J=7.25 Hz, 2H, aromatic H), 7.75 (d, J=
7.25 Hz, 2H, aromatic H); 13C NMR (125 MHz, DMSO-d6):
d=61.9 (C-2), 80.0 (C-1), 126.5–129.5 (aromatic C), 139.6–
141.2 (aromatic ipso C), 144.2 (aromatic ipso C); MS (FAB,
NBA): m/z (%)=366 (10) [M+1]+; anal. calcd. for
C26H23NO: C 85.44, H 6.34, N 3.83; found: C 85.50, H 6.58,
N 3.83.
General Procedure for the Enantioselective
Reduction of Ketones 7, 9, 11 or 13 with Borane-
Dimethyl Sulfide in the Presence of Amino Alcohol
6d
(R)-2-Amino-2-[4-(nonafluorobutanesulfonyloxy)phen-
yl]-1,1-diphenylethanol (6d)
A 50-mL two-necked flask was equipped with a magnetic
stirrer, connected to the combined nitrogen/vacuum line,
charged with an 80% suspension of sodium hydride in min-
eral oil (0.23 g, 7.6 mmol), and closed with a septum. The air
in the flask was replaced by nitrogen, and anhydrous DMF
(40 mL) was added by syringe. The mixture was cooled in
an ice-bath, and a solution of 5 (1.22 g, 4.0 mmol) in anhy-
drous DMF (40 mL) was injected at such a rate that the
temperature was kept below 58C. Stirring was continued at
A 25-mL two-necked flask was charged with amino alcohol
6d (0.059 g, 0.10 mmol), equipped with a magnetic stirrer
and a connection to the combined nitrogen/vacuum line and
closed with a septum. The air in the flask was replaced by
nitrogen. The amino alcohol 6 was dissolved in THF (6 mL)
under stirring and a 2M solution of the borane-dimethyl sul-
fide complex in THF (0.66 mL, 1.32 mmol) was added by sy-
ringe. After stirring at room temperature for 24h, the fresh-
Adv. Synth. Catal. 2007, 349, 337 – 342
ꢁ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
341