Racemization of Secondary Alcohols
FULL PAPER
(3.2 mg, 0.005 mmol) in toluene (2 mL), a solution of tBuOK (0.5m in
THF; 20 mL, 0.01 mmol) was added under an argon atmosphere. After
6 min, (S)-1-phenylethanol (120 mL, 1 mmol) was added. Samples of the
reaction mixture were collected under a rigorous argon atmosphere and
analyzed by chiral GC. After 30 min, chiral GC analysis showed complete
racemization of 1-phenylethanol.
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Preparation of 1-[4-[(1R)-1-hydroxyethyl]phenyl]-(2-[D3])-ethanone
[(S)-18]:[33] 1-[4-(1-Hydroxyethyl)phenyl]-ethanone[34] (1.43 g, 8.7 mmol),
NaOH (0.035 g, 0.87 mmol) and D2O (6 mL, 300 mmol) were stirred at
room temperature under an argon atmosphere during 19 h. The reaction
mixture was extracted with dry Et2O (56 mL), dried over Na2SO4, fil-
tered and evaporated. The crude product was treated with Candida ant-
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arctica lipase
B (CALB) (0.244 g) and isopropenyl acetate (2.7 mL,
24.3 mmol) in toluene (10 mL) under an argon atmosphere. After 2 h,
the enzyme was filtered off, and the solvent evaporated. After purifica-
tion by column chromatography (silica gel, pentane/EtOAc 4:1) (S)-18
(0.676 g, 46%) was obtained as a colorless liquid in >99% ee. 1H NMR
(CDCl3, 400 MHz): d=7.94 (d, J=8.5 Hz, 2H), 7.47 (d, J=8.5 Hz, 2H),
4.97 (q, J=6.7 Hz, 1H), 2.59 (m, 0.60H), 1.93 (brs, 1H), 1.51 ppm (d, J=
6.7 Hz, 3H). The integral at d=2.59 indicate a deuteration degree of
80%.
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liquid nitrogen bath before adding another equivalent of 1-phenyl-
ethanol.
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Determination of the deuterium isotope effect in racemization of (S)-1-
arylethanols: Deuterium isotope effect for racemization of (S)-1-phenyle-
thanol. Ruthenium catalyst 3a (0.13 mol%) was dissolved in toluene
(0.5 mL) under an argon atmosphere. A solution of tBuOK (0.25m in
THF, 0.26 mol%) was added. After 6 min, a solution of a 1:1 mixture
(2 mmol) of deuterated and nondeuterated alcohol ([D]-(S)-5 and (S)-5)
in toluene (0.5 mL) was added. The reaction was quenched with dilute
HCl at <12% conversion to the R alcohol. The reaction mixture was an-
alyzed by GC-MS using a chiral column connected to the mass spectrom-
eter and from the deuterium content in the R alcohol a kinetic isotope
effect kH/kD of 1.27ꢂ0.06 was obtained.
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Acknowledgements
We thank Mettler Toledo Autochem, Inc. for providing us with a Reac-
tIR TM 4000 from Mettler Toledo Autochem, Inc. for the in situ IR stud-
ies. We are grateful for financial support from the Swedish Research
Council, the Swedish Foundation for Strategic Research, and the Minis-
terio de Educación y Ciencia of Spain (B.M.M). We also thank Ms. Kris-
tina Romare and Associate Professor Ulrika Nilsson for their kind help
with the low-temperature NMR and GC-MS experiments, respectively.
[16] A ReactIRTM 4000 from Mettler Toledo Autochem, Inc. was em-
ployed.
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