SCHEME 3. Possible Mechanism for the Asymmetric
Borane Reduction of Prochiral Oxime Ethers Promoted by a
Chiral Spiroborate Ester
evaporated to give a colorless oil, which upon distillation under
reduced pressure and purification via chromatography on silicon
gel column furnished (S)-1-aralkylamine.
(S)-1-Phenylethylamine (A): colorless liquid, 76% yield 98%
ee, [R]20D -28.3 (c 0.92, MeOH) for the reduction of acetophenone
O-methyloxime; 74% yield, 89% ee, [R]20D -25.7 (c 0.98, MeOH)
[lit.12 [R]20 -29 (MeOH)] for the reduction of acetophenone
D
O-benzyloxime. IR (neat, cm-1): ν 3363, 3286, 3061, 3026, 2963,
2924, 2865, 1604, 1492, 1451, 1367, 764, 701. 1H NMR (300 MHz,
CDCl3): δ 1.42 (d, J ) 6.6 Hz, 3H), 1.62 (s, 2H), 4.13 (q, J ) 6.6
Hz, 1H), 7.23-7.35 (m, 5H). 13C NMR (75 MHz, CDCl3): δ 26.6,
52.0, 125.8, 126.9, 128.5, 147.6. Anal. Calcd for C8H11N: C, 79.29;
H, 9.15; N, 11.56. Found: C, 79.03; H, 9.25; N, 11.42.
(S)-1-phenylpropy1amine (B): colorless liquid, 78% yield, 92%
ee, [R]27D -7.82 (c 0.92, EtOH) for the reduction of propionophe-
none O-methyloxime; 80% yield, 81% ee, [R]27 -6.87 (c 0.96,
D
EtOH) for the reduction of propionophenone O-benzyloxime; 76%
yield, 80% ee, [R]27 -6.38 (c 0.89, EtOH) [lit.13 [R]27 +8.1 (c
D
D
7.9, EtOH)] for the reduction of propionophenone O-n-butyloxime.
IR (neat, cm-1): ν 3363, 3296, 3061, 3027, 2962, 2930, 2874, 1603,
1492, 1453, 1373, 762, 701. 1H NMR (300 MHz, CDCl3): δ 0.92
(t, J ) 7.2 Hz, 3H), 1.63 (s, 2H), 1.75 (m, J ) 7.2 Hz, 2H), 3.84
(t, J ) 7.2 Hz, 1H), 7.27-7.34 (m, 5H). 13C NMR (75 MHz,
CDCl3): δ 12.1, 33.2, 58.5, 126.5, 126.9, 128.4, 146.2. Anal. Calcd
for C9H13N: C, 79.95; H, 9.69; N, 10.36. Found: C, 79.76; H,
9.48; N, 10.52.
size of the alkyl group in the aralkyl ketone in terms of
enantioselectivity and yield (entries 9-11).
(S)-1-(4-Nitrophenyl)ethylamine (C): yellow liquid, 86% yield,
It should be pointed out that all oxime ethers used in the
experiment are E isomers. The E and Z isomers can be
efficiently separated by chromatography on silicon gel column,
though a mixture of both the isomers was obtained in the
preparative course. Only the major E isomer was collected and
examined because the Z isomer was minor.
The mechanism for asymmetric reduction of prochiral oxime
ethers promoted by the chiral spiroborate ester is suggested
(Scheme 3). The structure of the intermediate (R,S)-2 has
previously been proved.10a In the mixed system consisting of
(R,S)-1, borane, and the ketoxime ether in THF, the oxime ether
replaces THF in (R,S)-2 to form the complex (R,S)-3 which
undergoes hydrogen transfer and rearrangement and (S)-ami-
noborane 5 is liberated as the spiroborate is reformed. Com-
pound 5 will yield the corresponding amine at aqueous workup.
Thus, a catalytic cycle is accomplished.
96% ee, [R]24 -16.0 (c 0.76, CHCl3) for the reduction of 1-(4-
D
nitrophenyl)ethanone O-methyloxime; 84% yield, 90% ee, [R]24
D
-14.8 (c 0.82, CHCl3) for the reduction of 1-(4-nitrophenyl)-
ethanone O-benzyloxime; 78% yield, 75% ee, [R]24D -12.5 (c 0.68,
CHCl3) [lit.14 [R]24 +16.9 (CHCl3)] for the reduction of 1-(4-
D
nitrophenyl)ethanone O-n-butyloxime. IR (neat, cm-1): ν 3376,
3311, 3108, 3076, 2968, 2927, 2869, 1603, 1517, 1345, 1108, 855,
1
755, 700. H NMR (300 MHz, CDCl3): δ 1.40 (d, J ) 6.6 Hz
3H), 1.57 (s, 2H), 4.26 (q, J ) 6.6 Hz, 1H), 7.53 (d, J ) 8.4 Hz,
2H), 8.19 (d, J ) 8.4 Hz, 2H). 13C NMR (75 MHz, CDCl3): δ
26.0, 51.1, 124.0, 126.9, 147.1, 155.3. Anal. Calcd for
C8H10N2O2: C, 57.82; H, 6.07; N, 16.86. Found: C, 57.64; H, 6.15;
N, 16.72.
(S)-1-(4-Methoxyphenyl)ethylamine (D): colorless liquid, 83%
yield, 90% ee, [R]24D -23.0 (c 0.88, CHCl3) [lit.15 [R]24D +24.6 (c
1.0, CHCl3)] for the reduction of 1-(4-methoxyphenyl)ethanone
O-methyloxime. IR (neat, cm-1): ν 3364, 3291, 3060, 3029, 998,
2960, 2926, 2836, 1611, 1585, 1512, 1463, 1370, 1247, 1177, 1034,
921, 832, 808, 733, 700. 1H NMR (300 MHz, CDCl3): δ 1.35 (d,
J ) 6.6 Hz, 3H), 1.52 (s, 2H), 3.78 (s, 3H), 4.07 (q, J ) 6.6 Hz,
1H), 6.85 (d, J ) 8.4 Hz, 2H), 7.25 (d, J ) 8.4 Hz, 2H). 13C NMR
(75 MHz, CDCl3): δ 26.1, 51.0, 55.6, 114.0, 127.0, 140.1, 158.5.
Anal. Calcd for C9H13NO: C, 71.49; H, 8.67; N, 9.26. Found: C,
71.28; H, 8.72; N, 9.42.
In summary, a class of new and effective chiral promoter for
borane reduction of prochiral aralkylketoxime ethers has been
discovered. They are readily prepared as stable solids and can
be stored on shelf.
Experimental Section
(S)-1-(4-Methoxyphenyl)propylamine (E): colorless liquid,
87% yield, 89% ee, [R]24D -14.2 (c 0.92, EtOH) [lit16 [R]24D +13
(c 0.8, EtOH)] for the reduction of 1-(4-methoxyphenyl)propan-
1-one O-methyloxime. IR (neat, cm-1): ν 3364, 3297, 3060, 3029,
2998, 2960, 2931, 2874, 2836, 1611, 1585, 1512, 1463, 1302, 1247,
General Procedure for the Borane Reduction of the Aralkyl-
ketoxime Ethers Promoted by Chiral Spiroborate Ester. An
oven-dried, two-necked, round-bottom flask charged with a septum,
argon inlet, and magnetic stirring bar was cooled to room
temperature under a continuous flow of dry Ar gas, and a THF
solution (50 mL) of (R,S)-1 (5 mmol) dried with 4 Å molecular
sieves and BH3‚THF (1 M, 7.5 mmol) were added in sequence.
After being stirred for 30 min, the contents were cooled to 0-5
°C, followed by addition of an aralkylketoxime (5 mmol) via syringe
within 15 min. The resulting mixture was stirred at the same
temperature for 48 h and then decomposed with 2 M HCl to give
a homogeneous solution. The solution was evaporated under
reduced pressure to remove THF, and a white solid was isolated,
filtered, washed with water, and then recrystallized in toluene
(recovery of enantiopure BINOL). The water phase was basified
with ammonium hydroxide and extracted with diethyl ether (3 ×
15 mL). The ether layer was dried over anhydrous Na2SO4 and
1
1177, 1036, 832, 736, 693. H NMR (300 MHz, CDCl3): δ 0.84
(t, J ) 7.2 Hz, 3H), 1.53 (s, 2H), 1.62 (m, J ) 7.2 Hz, 2H), 3.74
(t, J ) 7.2 Hz, 1H), 3.78 (s, 3H), 6.85 (d, J ) 8.4 Hz, 2H), 7.21
(d, J ) 8.4 Hz, 2H). 13C NMR (75 MHz, CDCl3): δ 11.2, 32.7,
55.5, 57.4, 113.9, 127.6, 138.8, 158.7. Anal. Calcd for C10H15NO:
C, 72.69; H, 9.15; N, 8.48. Found: C, 72.42; H, 9.21; N, 8.36.
(12) Leithe, W. Chem. Ber. 1931, 64, 2827.
(13) Warren, M. E.; Smith, H. E. J. Am. Chem. Soc. 1965, 87, 1757.
(14) Perry, C. W.; Brossi, A.; Deitcher, K. H.; Tautz, W.; Teitel, S.
Synthesis 1977, 492.
(15) Wu, M. J.; Pridgen, L. N. J. Org. Chem. 1991, 56, 1340.
(16) Bataille, B.; Paterne, M.; Brown, E. Tetrahedron: Asymmetry 1999,
10, 1579.
4000 J. Org. Chem., Vol. 71, No. 10, 2006