Enantioselective Borohydride Reduction
4485 4509
135.6, 139.4, 204.5; IR (KBr): nÄ 3446, 3052, 2980, 1664, 1188, 823, 748,
477 cmÀ1; m.p. 120.7 121.68C; HRMS: m/z: calcd for C24H20O2: 340.1463;
found: 340.1456 [M ]. HPLC: Daicel Chiralpak AD (25% propan-2-ol in
2-acetonaphthone 20b (85.1 mg, 0.5 mmol), and catalyst 22 (18.6 mg,
0.05 mmol) was added the solution of the premodified borohydride
(3.2 mL, 0.4 mmol) under a dry nitrogen atmosphere at À208C. After
stirring for 12 h at À208C, the reaction was quenched by a precooled
aqueous THF solution at À208C and pH 7 buffer solution; then the crude
products were extracted with AcOEt. The combined organic layers were
washed with brine and dried over anhydrous sodium sulfate. After filtration
and evaporation, the residue was purified by silica gel column chromatog-
raphy (hexane/AcOEt) to give undecan-2-ol 21a (4.0 mg, 5%) and 1-(2-
naphthyl)-1-ethanol 21b (38.3 mg, 45%).
hexane, flow 1.0 mLminÀ1), 20.2 min (minor), 22.4 min (major); [a]2D4
96.28 (c 1.083in CHCl ).
3
anti-1,3-Di(p-bromophenyl)-3-hydroxy-2-methyl-1-propanone
(19d):
1H NMR (CDCl3): d 1.05 (d, 3H, J 7.5 Hz), 2.92 (d, 1H, J 4.4 Hz),
3.70 (quin, 1H, J 7.5 Hz), 4.95 (dd, 1H, J 4.4, 7.5 Hz), 7.29 (d, 2H, J
8.7 Hz), 7.50 (d, 2H, J 8.7 Hz), 7.62 (d, 2H, J 8.7 Hz), 7.83(d, 2H, J
8.7 Hz); 13C NMR (CDCl3): d 15.6, 47.9, 76.1, 121.8, 128.3, 128.6, 129.8,
131.5, 131.9, 135.1, 140.9, 203.3; IR (KBr): nÄ 3494, 2978, 1661, 1581, 1396,
1244, 1069, 1009, 964, 822, 742 cmÀ1; m.p. 114.2 114.98C; HRMS: m/z:
Preparation of 1,2-dialkyl-3-aryl-1,3-diketones: The 1-alkyl-3-aryl-1,3-di-
ketones (RC(O)CH2C(O)Ar) were prepared by conventional Claisen
condensation of the corresponding RCOMe and ArCO2Et, and then their
sodium enolates were treated with the corresponding R'X to obtain the 1,2-
dialkyl-3-aryl-1,3-propanediones (RC(O)CH(R')C(O)Ar).
calcd for C16H14Br2O2: 395.9362; found: 395.9390 [M ]. HPLC: Daicel
Chiralpak AD-H (10% propan-2-ol in hexane, flow 1.0 mLminÀ1),
22.5 min (minor), 24.9 min (major); [a]2D4 97.88 (c 1.038 in CHCl3).
2,4-Dimethyl-1-phenyl-1,3-pentanedione (23a):[74] 1H NMR (CDCl3): d
1.03(d, 3H, J 6.9 Hz), 1.10 (d, 3H, J 6.9 Hz), 1.45 (d, 3H, J 7.0 Hz),
2.77 (sept, 1H, J 6.9 Hz), 4.64 (q, 1H, J 7.0 Hz), 7.46 7.53(m, 2H),
7.56 7.64 (m, 1H), 7.93 8.00 (m, 2H); 13C NMR (CDCl3): d 13.8, 18.6,
19.2, 39.5, 54.4, 128.5, 128.8, 133.5, 135.9, 197.5, 210.8; HRMS: m/z: calcd
anti-1,3-Di(p-methoxyphenyl)-3-hydroxy-2-methyl-1-propanone
(19e):
1H NMR (CDCl3): d 1.06 (d, 3H, J 7.5 Hz), 2.98 (d, 1H, J 4.4 Hz),
3.75 (quin, 1H, J 7.5 Hz), 3.81 (s, 3H), 3.88 (s, 3H), 4.94 (dd, 1H, J 4.4,
7.5 Hz), 6.89 (d, 2H, J 8.9 Hz), 6.94 (d, 2H, J 8.9 Hz), 7.34 (d, 2H, J
8.9 Hz), 7.97 (d, 2H, J 8.9 Hz); 13C NMR (CDCl3): d 16.0, 47.6, 55.3,
55.5, 76.4, 113.71, 113.73, 127.7, 129.6, 130.7, 134.4, 159.0, 163.5, 203.2; IR
(KBr): nÄ 3366, 2977, 2934, 1664, 1599, 1516, 1252, 1174, 1032, 973, 825,
576 cmÀ1; elemental analysis calcd (%) for C18H20O4: C 71.98, H 6.71;
found: C 71.86, H 6.72; m.p. 80.8 81.78C. HPLC: Daicel Chiralcel OD-H
(10% propan-2-ol in hexane, flow 1.0 mLminÀ1), 21.3min (major),
26.4 min (minor); [a]D24 124.88 (c 1.079 in CHCl3).
for C13H16O2: 204.1150; found: 204.1131 [M ].
2-Ethyl-4-methyl-1-phenyl-1,3-pentanedione (23b):[75] 1H NMR (CDCl3):
d 0.95 (t, 3H, J 7.3Hz), 0.99 (d, 3H, J 6.8 Hz), 1.06 (d, 3H, J
6.8 Hz), 2.02 (double quint, 2H, J 7.3, 14.6 Hz), 2.75 (sept, 1H, J
6.8 Hz), 4.49 (t, 1H, J 7.3Hz), 7.46 7.53 (m, 2H), 7.57 7.63 (m, 1H),
7.94 8.01 (m, 2H); IR (neat): nÄ 2971, 1721 (nC O), 1674 (nC O), 1448, 1273,
1209, 694 cmÀ1; HRMS: m/z: calcd for C14H18O2: 218.1307; found: 218.1281
anti-1,3-Diphenyl-2-ethyl-3-hydrodxy-1-propanone (19 f):[72, 73] 1H NMR
(CDCl3): d 0.82 (t, 3H, J 7.3Hz), 1.48 1.61 (m, 1H), 1.66 1.80 (m,
1H), 3.07 (d, 1H, J 6.4 Hz), 3.78 (q, 1H, J 6.4 Hz), 5.03(t, 1H, J
6.4 Hz), 7.22 7.49 (m, 7H), 7.51 7.58 (m, 1H), 7.88 7.95 (m, 2H);
13C NMR (CDCl3) d 11.8, 23.8, 54.3, 75.7, 126.3, 127.7, 128.2, 128.4,
128.5, 133.1, 138.1, 142.6, 205.4; IR (KBr): nÄ 3411, 3061, 2958, 2877, 1671,
1447, 1269, 1207, 1001, 768, 703cm À1; m.p. 63.0 63.88C; elemental analysis
calcd (%) for C17H18O2: C 80.28, H 7.13; found: C 80.24, H 7.28. HPLC:
Daicel Chiralpak AD (1.5% propan-2-ol in hexane, flow 1.0 mLminÀ1),
59.1 min (major), 67.5 min (minor); [a]2D4 90.78 (c 1.046 in CHCl3).
[M ].
1
2-Allyl-4-methyl-1-phenyl-1,3-pentanedione (23c): H NMR (CDCl3): d
1.01 (d, 3H, J 6.8 Hz), 1.06 (d, 3H, J 6.8 Hz), 2.64 2.81 (m, 3H), 4.68 (t,
1H, J 7.1 Hz), 5.02 (d, 1H, J 10.3Hz), 5.08 (d, 1H, J 17.1 Hz), 5.69
5.82 (m, 1H), 7.46 7.54 (m, 2H), 7.58 7.64 (m, 1H), 7.95 8.01 (m, 2H);
13C NMR (CDCl3): d 18.4, 19.0, 33.1, 39.8, 60.4, 117.2, 128.5, 128.8, 133.6,
134.7, 136.4, 195.8, 208.9; IR (neat): nÄ 2974, 1722 (nC O), 1675 (nC O), 1448,
1000, 919, 693cm À1; HRMS: m/z: calcd for C15H18O2: 230.1307; found:
230.1300 [M ].
2,4,4-Trimethyl-1-phenyl-1,3-pentanedione (23d): 1H NMR (CDCl3): d
1.14 (s, 9H), 1.42 (d, 3H, J 7.1 Hz), 4.93(q, 1H, J 7.1 Hz), 7.47 7.54 (m,
2H), 7.57 7.64 (m, 1H), 7.94 (m, 2H); 13C NMR (CDCl3): d 15.4, 26.8,
44.7, 49.3, 128.4, 128.8, 133.4, 135.4, 197.2, 211.1; IR (KBr): nÄ 2970, 1716
(nC O), 1663( nC O), 1451, 1345, 1217, 972, 694cmÀ1; m.p. 93.5 94.28C;
anti-2-Allyl-1,3-diphenyl-3-hydrodxy-1-propanone (19g): 1H NMR
(CDCl3): d 2.24 2.35 (m, 1H), 2.37 2.50 (m, 1H), 3.17 (d, 1H, J
5.4 Hz), 3.90 (q, 1H, J 6.8 Hz), 4.88 5.06 (m, 3H), 5.55 5.69 (m, 1H),
7.23 7.47 (m, 7H), 7.51 7.58 (m, 1H), 7.85 7.91 (m, 2H); 13C NMR
(CDCl3): d 34.8, 52.6, 75.5, 117.5, 126.3, 127.8, 128.2, 128.4, 128.5, 133.1,
134.2, 137.7, 142.2, 204.5; IR (KBr): nÄ 3374, 3073, 1671, 1448, 1241, 1209,
1012, 916, 767, 704, 607 cmÀ1; m.p. 79.3 80.2 8C; elemental analysis calcd
(%) for C18H18O2: C 81.17, H 6.81; found: C 81.07, H 6.78. HPLC: Daicel
Chiralcel OD-H (3% propan-2-ol in hexane, flow 1.0 mLminÀ1), 17.7 min
HRMS: m/z: calcd for C14H18O2: 218.1307; found: 218.1321 [M ].
2-Methyl-1-phenyl-1,3-dodecanedione (23e):[76] 1H NMR (CDCl3): d 0.87
(t, 3H, J 7.1 Hz), 1.12 1.33 (m, 12H), 1.45 (d, 3H, J 7.1 Hz), 1.47 1.57
(m, 2H), 2.38 (dt, 1H, J 7.3, 17.6 Hz), 2.51 (dt, 1H, J 7.3, 17.6 Hz), 4.49
(q, 1H, J 7.1 Hz), 7.46 7.52 (m, 2H), 7.57 7.62 (m, 1H), 7.95 8.00 (m,
2H).
(minor), 19.1 min (major); [a]2D4 74.78 (c 1.053in CHCl ).
3
anti-2-Benzyl-1,3-diphenyl-3-hydrodxy-1-propanone (19h):[73] 1H NMR
(CDCl3): d 2.91 (dd, 1H, J 7.0, 13.3 Hz), 3.05 (dd, 1H, J 7.0,
13.3 Hz), 3.45 (d, 1H, J 7.0 Hz), 4.09 (q, 1H, J 7.0 Hz), 4.97 (t, 1H,
J 7.0 Hz), 7.07 7.37 (m, 12H), 7.42 7.48 (m, 1H), 7.63 7.68 (m, 2H);
13C NMR (CDCl3): d 36.7, 54.7, 75.4, 126.0, 126.3, 127.6, 128.0, 128.2, 128.3,
128.4, 128.9, 133.0, 137.8, 138.4, 142.5, 205.3; IR (KBr): nÄ 3434, 3062, 3035,
1674, 1456, 1206, 1047, 1010, 751, 703cm À1; m.p. 115.6 116.58C; HRMS:
2,5-Dimethyl-1-phenyl-1,3-hexanedione (23 f): 1H NMR (CDCl3): d 0.80
(d, 3H, J 6.8 Hz), 0.86 (d, 3H, J 6.8 Hz), 1.44 (d, 3H, J 7.0 Hz), 2.13
(nonet, 1H, J 6.8 Hz), 2.27 (dd, 1H, J 6.8, 17.1 Hz), 2.39 (dd, 1H, J
6.8, 17.1 Hz), 4.47 (q, 1H, J 7.0 Hz), 7.45 7.53(m, 2H), 7.56 7.63(m,
1H), 7.93 8.00 (m, 2H); 13C NMR (CDCl3): d 13.6, 22.4, 24.0, 49.4, 56.8,
128.6, 128.8, 133.5, 136.0, 197.1, 206.5; IR (neat): nÄ 2958, 1717 (nC O), 1677
(nC O), 1449, 1226, 969, 689 cmÀ1; HRMS: m/z: calcd for C14H18O2:
m/z: calcd for C22H20O2: 316.1463; found: 316.1481 [M ]. HPLC: Daicel
Chiralcel OD-H (5% propan-2-ol in hexane, flow 1.0 mLminÀ1), 15.4 min
218.1307; found: 218.1307 [M ].
(major), 17.3min (minor); [ a]2D4 À8.78 (c 1.024 in CHCl3).
2-Methyl-1,4-diphenyl-1,3-butanedione (23g): 1H NMR (CDCl3): d 1.44
(d, 3H, J 7.1 Hz), 3.71 (d, 1H, J 15.9 Hz), 3.82 (d, 1H, J 15.9 Hz), 4.57
(q, 1H, J 7.1 Hz), 7.09 7.16 (m, 2H), 7.18 7.31 (m, 3H), 7.39 7.46 (m,
2H), 7.53 7.60 (m, 1H), 7.77 7.85 (m, 2H); 13C NMR (CDCl3): d 13.8,
48.2, 54.6, 127.1, 128.4, 128.6, 128.7, 129.6, 133.4, 133.5, 135.7, 197.4, 204.4; IR
anti-1,3-Diphenyl-3-hydrodxy-2-isopropyl-1-propanone (19i): 1H NMR
(CDCl3): d 0.87 (d, 3H, J 6.8 Hz), 1.15 (d, 3H, J 6.8 Hz), 2.24 2.35
(m, 1H), 3.59 (dd, 1H, J 4.4, 8.3Hz), 4.04 (d, 1H, J 8.1 Hz), 5.17 (dd,
1H, J 4.4, 8.1 Hz), 7.08 7.14 (m, 1H), 7.18 7.35 (m, 6H), 7.42 7.48 (m,
1H), 7.60 7.66 (m, 2H); 13C NMR (CDCl3): d 21.1, 21.3, 29.6, 58.7, 73.5,
125.5, 127.1, 127.9, 128.2, 128.3, 133.0, 138.6, 143.0, 207.1; IR (KBr): nÄ
3435, 2952, 1666, 1447, 1271, 1207, 1010, 768, 700, 570 cmÀ1; m.p. 84.0
(neat): nÄ 1718 (nC O), 1675 (nC O), 1449, 1330, 1215, 970, 702 cmÀ1
;
HRMS: m/z: calcd for C17H16O2: 252.1150; found: 252.1113[ M ].
Chemo-, diastereo-, and enantioselective reduction of 2,4-dimethyl-1-
phenyl-1,3-pentanedione (Scheme 7): Under a dry nitrogen atmosphere in
a precooled vessel at À208C were placed the (R,R)-catalyst 3b (7.2 mg,
85.28C; HRMS: m/z: calcd for C18H20O2: 268.1463; found: 268.1502 [M ].
HPLC: Daicel Chiralpak AD-H (15% propan-2-ol in hexane, flow
1.0 mLminÀ1), 8.3min (minor), 11.2 min (major); [ a]2D4 40.18 (c
0.261 in CHCl3).
0.0125 mmol),
2,4-dimethyl-1-phenyl-1,3-pentanedione
(51.0 mg,
0.25 mmol), and CHCl3 (12.0 mL). The five portions of the 0.1 equiv of
the premodified borohydride (0.2 mL, 0.025 mmol) were successively
added at 1 h intervals to the reaction mixture, and stirred for 24 h at
À208C. The reaction was quenched by a precooled aqueous THF solution
Chemoselective reduction of 2-undecanone and 2-acetonaphthone in the
presence of b-ketoiminato cobalt complex catalyst (Scheme 6): To the
CHCl3 solution (20 mL) of 2-undecanone 20a (85.2 mg, 0.5 mmol),
Chem. Eur. J. 2003, 9, 4485 4509
¹ 2003Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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