Jenny Wettergren et al.
FULL PAPERS
d=1.45 (d, J=6.4 Hz, 3H), 1.8 (s br, 1H), 4.82 (q, J=
5.6 Hz, 1H), 5.94 (s, 2H), 6.76 (dd, J=8.0 Hz, J=1.6 Hz,
1H), 6.81 (dd, J=8.1 Hz, J=1.6 Hz, J=0.4 Hz, 1H), 6.89
(dd, J=1.6 Hz, J=0.4 Hz, 1H); 13C NMR (75 MHz,
CDCl3): d=25.3, 70.5, 101.2, 106.3, 108.3, 118.9, 140.2, 147.1,
148.0; GLC (CP Chirasil DEX CB):1108C hold for 2 min,
rate 18CminÀ1 to 1318C, hold for 0 min, rate 808CminÀ1 to
readily available, inexpensive N-protected amino acid
hydroxy-amide ligands make this protocol very attrac-
tive.
Experimental Section
2008C and hold 5 min:
tRACTHEURNG(R-isomer)=18.49 min, tRACHTREUNG(S-
isomer)=19.03 min; [a]2D0: À40 (c 2.1, CHCl3) {lit.[15] [a]D:
General Procedure for the Transfer Hydrogenation of
Electron-Rich Ketones Presented in Table 1
+46.5 (c 1.01, CHCl3), 97% ee R-isomer}.
(R)-1-(2,3,4-Trimethoxyphenyl)ethanol[19]
(Table 1,
1
entry 5): Yield: 39%; 95% ee; H NMR (400 MHz, CDCl3):
d=1.49 (d, J=6.8 Hz, 3H), 2.41 (s br, 1H), 3.85 (s, 3H),
3.86 (s, 3H), 3.96 (s, 3H), 5.05 (m, 1H), 6.66 (d, J=8.8 Hz,
1H) 7.03 (d, J=8.8 Hz , 1H); 13C NMR (100 MHz, CDCl3):
d=23.7, 55.9, 60.6, 61.1, 65.8, 107.1, 120.3, 131.2, 141.9,
151.0, 153.0; GLC (CP Chirasil DEX CB): 1108C hold
0 min, rate 208CminÀ1 to 1308C, hold 30 min, rate
18CminÀ1 to 1358C, rate 208CminÀ1 to 2008C and hold for
5 min; [a]2D0: +20.8 (c 3.6, CHCl3); absolute configuration
determined as presented below.
Ligand 2a (13.5 mg, 0.055 mmol) and [RuCl2ACHTRE(UGN p-cymene)]2
(15.2 mg, 0.025 mmol, catalyst loading: 1 mol%) were dried
under vacuum in a dry Schlenck tube for 15 min. 2-Propanol
(22.5 mL) and 2.5 mL of 0.1M solution of i-PrONa (5
mol%) were added under a nitrogen atmosphere. The solu-
tion was stirred for 5 min and the ketone (5 mmol) was
added. The reaction mixture was stirred at room tempera-
ture for time stated in Table 1. The reaction was quenched
by addition of aqueous NH4Cl, extracted withEtOAc and
the organic phase was subsequently passed through a pad of
silica and evaporated under vacuum. The products were pu-
rified using SiO2 column chromatography. The ee of the
products were analyzed by GLC (CP Chirasil DEX CB) or
HPLC (AD or AS chiral columns).
(S)-1-(3,4,5-Trimethoxyphenyl)ethanol[19]
(Table 1,
1
entry 6): Yield: 84%; 99% ee; H NMR (300 MHz, CDCl3):
d=1.49 (d, J=6.4 Hz, 3H), 1.81 (s, br, 1H), 3.84 (s, 3H),
3.88 (s, 6H), 4.84 (m, 1H), 6.61 (s, 2H); 13C NMR
(100 MHz, CDCl3): d=25.2, 56.0, 60.7, 70.5, 102.2, 137.0,
141.7, 153.2; GLC (CP Chirasil DEX CB): 1108C, hold
2 min, rate 208CminÀ1 to 1598C, hold 0 min, rate
0.38CminÀ1 to 1648C, 208CminÀ1 to 2008C, hold 10 min:
(S)-1-(2,5-Dimethoxyphenyl)ethanol[16] (Table 1, entry 1):
1
Yield: 69%; 96% ee; H NMR (400 MHz, CDCl3): d=1.49
(d, J=6.8 Hz, 3H), 2.63 (s br, 1H), 3.78 (s, 3H), 3.82 (s,
3H), 5.06 (m, 1H), 6.75 (dd, J=8.8 Hz, J=3.2 Hz, 1H), 6.80
(d, J=8.8 Hz, 1H), 6.94 (d, J=3.2 Hz, 1H); 13C NMR
(75 MHz, CDCl3): d=23.2, 55.9, 56.0, 66.8, 111.6, 112.5,
112.7, 134.9, 150.9, 154.0; GLC (CP Chirasil DEX CB):
1108C hold for 0 min, rate 208CminÀ1 to 1308C and hold
for 30 min, rate 18CminÀ1 to 1358C, rate 208CminÀ1 to
(R-isomer)=12.38 min, tR (S-isomer)=12.15 min; [a]2D0:
tRACHTREUNG
À27.8 (c 2.8, CHCl3); absolute configuration determined as
presented below.
(R)-4-Chromanol [(R)-3,4-dihydro-2H-1-benzopyran-4-
ol][20] (Table 1, entry 7): Yield: 59%;>99% ee; 1H NMR
(400 MHz, CDCl3): d=1.82 (m, 1H), 2.01–2.18 (m, 2H),
4.26–4.29 (m, 2H), 4.79 (m, 1H), 6.84 (d, J=8.2 Hz, 1H),
6.92 (m, 1H), 7.21 (m, 1H), 7.31 (d, J=7.69 Hz, 1H);
13C NMR (100 MHz, CDCl3): d=30.8, 61.9, 63.3, 117.1,
120.6, 124.3, 129.6, 129.7, 154.6; GLC (CP Chirasil DEX
CB): 1108C, hold 0 min, rate 208CminÀ1 to 1258C, hold
0 min, rate 0.58CminÀ1 to 1358C, hold 0 min, rate
2008C and hold for 5 min: tRACTHERNGU(R-isomer)=22.7 min, tRHCATRE(UGN S-
isomer)=24.9 min; [a]2D0: À29.6 (c 5, CHCl3) {lit.[16] [a]D:
À25.8 (c 0.9, CHCl3),>95% ee}.
(S)-1-(3,5-Dimethoxyphenyl)ethanol[17] (Table 1, entry 2):
1
Yield: 90%; 97% ee; H NMR (300 MHz, CDCl3): d=1.50
(d, J=7.2 Hz, 3H), 1.80 (s br, 1H), 3.81 (s, 6H), 4.83 (q, J=
8.1 Hz, 1H), 6.38 (t, J=1.0 Hz, 1H) 6.53 (d, J=1.0 Hz, 1H);
13C NMR (75 MHz, CDCl3): d=25.3, 55.6 (2C), 70.7, 99.6,
103.5 (2C), 148.7, 161.2; GLC (CP Chirasil DEX CB):
1108C hold for 0 min, rate 208CminÀ1 to 1308C and hold
for 30 min, rate 18CminÀ1 to 1358C, rate 208CminÀ1 to
208CminÀ1 to 2008C, hold 5 min: t
RA
(S-isomer)=16.91 min; [a]2D0: +65 (c 1.0, CHCl3) {lit.[20]
RACHTRE(UNG R-isomer)=16.57 min,
t CHTREUNG
[a]D: À67.45(c 0.5, EtOH), 98% ee, S-isomer}.
(S)-1,2,3,4-Tetrahydro-7-methoxy-1-naphthalenol[21]
2008C and hold for 5 min: tRACTHERNGU(R-isomer)=29.2 min, tRHCATRE(UGN S-
1
(Table 1, entry 8): Yield: 42%; 98% ee; H NMR (400 MHz,
isomer)=30.2 min; [a]20: À32.7 (c 2.0, CHCl3); the absolute
configuration determinDed as presented below.
CDCl3): d=1.57–2.03 (m, br, 5H), 2.63–2.78 (m, br, 2H),
3.80 (s, 3H), 4.75 (m, 1H), 6.78 (m, 1H), 6.99–7.03 (m, 2H);
13C NMR (100 MHz, CDCl3): d=19.2, 28.4, 32.4, 55.3, 68.5,
112.6, 114.4, 129.1, 129.9, 139.8, 158.0; HPLC (AD) 2% 2-
(S)-1-(3,4-Dimethoxyphenyl)ethanol[15] (Table 1, entry 3):
1
Yield: 58%; 98% ee; H NMR (300 MHz, CDCl3): d=1.49
(d, J=6.3 Hz, 3H), 1.93 (s br, 1H), 3.86 (s, 3H), 3.88 (s,
3H), 4.83 (q, J=6.3 Hz, 1H), 6.82 (d, J=8.1 Hz, 1H), 6.89
(dd, J=8.1 Hz, J=0.9 Hz, 1H), 6.93 (d, J=1.5 Hz, 1H);
13C NMR (75 MHz, CDCl3): d=25.3, 56.0, 56.2, 70.4, 108.9,
111.2, 117.7, 138.8, 148.6, 149.3; GLC (CP Chirasil DEX
CB): 1108C hold for 2 min, rate 18CminÀ1 to 1318C, hold
for 0 min, rate 808CminÀ1 to 2008C and hold for 5 min: tR-
propanol in hexane, 0.5 mLminÀ1, t
CHTRE(UNG S-isomer)=59 min, tR-
RA
(R-isomer)=67 min; [a]20: +43.5 (c 1.05, CHCl3); {lit.[21]
[a]D: +45.8 (c 3.63, CHCl3), 100% ee}.
(S)-N-[4-(1-Hydroxyethyl)phenyl]acetamide[22] (Table 1,
entry 9): Yield: 31%; 95% ee; 1H NMR (400 MHz,
CD3OD): d=1.44 (d, J=6.6 Hz, 3H), 2.13 (s, 3H), 4.81 (q,
J=6.6 Hz, 1H), 7.32 (d, J=8.4, 2H), 7.52 (d, J=8.6 Hz,
2H); 13C NMR (100 MHz, CD3OD): d=23.9, 25.6, 70.6,
121.3, 127.1, 139.0, 143.5, 171.7; HPLC (AD) 2% 2-propanol
A
t
G
[a]2D0:
À38.3 (c 2.85, CHCl3) {lit.[18] [a]D: +40.5 (c 1.1, CHCl3),
97% ee R-isomer}.
in hexane, 0.5 mLminÀ1
, tRACHTREU(NG S-isomer)=47.2 min, tRACHTREUNG(R-
entry 4): Yield: 65%; 95% ee; H NMR (400 MHz, CDCl3):
isomer)=50.1 min; [a]2D0: À40.6 (c 0.75, CHCl3).
1280
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2006, 348, 1277 – 1282