Enzymatic resolution of aromatic chlorohydrins is known
to work very well with Pseudomonas cepacia lipase.1,9 For
these chlorohydrins, Candida antarctica lipase B also gives
good results albeit slower.1b Our choice of enzyme was
therefore the former lipase, and the selectivity of this enzyme
with the acyl donor isopropenyl acetate in toluene was
determined for a few substrates (Table 1). The kinetic
The racemization was investigated for a few substrates. The
results are shown in Table 2. As can be seen from Table 2,
Table 2. Racemization of Enantiopure (R)-ꢀ-Chloroalcoholsa
Table 1. Kinetic Resolution of Chlorohydrinsa
a 0.015 mmol RuCl(CO)2(η5C5Ph5) and 0.3 mmol Na2CO3 were mixed
in 0.3 mL of toluene, and 0.03 mmol t-BuOK (dissolved in 30 µL of dry
THF) was added. After 6 min, 0.3 mmol substrate (dissolved in 0.3 mL of
dry toluene and dried over molecular sieves) was added. b Determined by
chiral GC. c Enantiomeric excess of (R)-alcohol. d Determined by chiral
HPLC.
1-aryl-2-chloroethanols are racemized fast at room temperature
whereas chloroalcohol 2e is racemized slow under these
conditions. For a good dynamic kinetic resolution, the racem-
ization should be at least 10 times faster than the conversion of
the slow-reacting enantiomer in the kinetic resolution. For the
aromatic alcohols (arylalcohols), the racemization is fast so this
requirement will be fulfilled with the enzyme amounts used in
Table 1.
a With 0.5 mmol Na2CO3, 25 mg of PS-C “Amano” II, 1 mL of dry
toluene, 0.5 mmol ꢀ-chloroalcohol, and 1.0 mmol isopropenyl acetate.
b Calculated value. c The enantiomeric excess of (S)-acetate and (R)-alcohol
was determined by chiral GC, and from these figures, the E value was
calculated. d Determined by HPLC. e With 2.5 mg of PS-C “Amano” II at
80 °C.
(9) Bevianakatti, H. S.; Banerji, A. A. J. Org. Chem. 1991, 56, 5372–
5375.
(10) (a) Hiratake, J.; Inagaki, M.; Nishioka, T.; Oda, J. J. Org. Chem.
1988, 53, 6130. (b) McCubbin, J. A.; Maddess, M. L.; Lautens, M. Synlett
2008, 289–293.
(11) Pa`mies, O.; Ba¨ckvall, J. E. Chem. ReV. 2003, 103, 3247–3262.
(12) Ahn, Y.; Ko, S.-B.; Kim, M.-J.; Park, J. Coord. Chem. ReV. 2008,
252, 647–658.
(13) (a) Mart´ın-Matute, B.; Ba¨ckvall, J. E. Curr. Opin. Chem. Biol. 2007,
11, 226–232. (b) Mart´ın-Matute, B.; Ba¨ckvall, J. E. Dynamic Kinetic
Resolutions. In Asymmetric Organic Synthesis with Enzymes Gotor, V.,
Alfonso, I., Garc´ıa-Urdiales, E., Eds.; Wiley-VCH: New York, 2008; pp
89-113.
resolution reactions were run at room temperature (except
entry 6). As can be seen from Table 1, aromatic chlorohy-
drins give excellent enantioselectivity with E values >300,
whereas aliphatic chlorohydrins give very poor results (entry
7). The presence of different substituents on the aromatic
ring does not seem to influence the enantioselectivity of the
enzyme. For substrate 2e, we also carried out the kinetic
resolution at an elevated temperature (80 °C) since the
racemization of this substrate is slow at room temperature
(vide infra). At 80 °C, the E value for 2e dropped to 81.
For the aliphatic substrate 2f, the enzyme showed poor
selectivity (entry 7, Table 1). PS-C “Amano” I and PS-D
“Amano” II were also tested in a kinetic resolution of this
substrate but showed low selectivity as well.
(14) (a) Bornscheuer, U. T.; Kazlauskas, R. J. Hydrolases in Organic
Synthesis, 2nd ed.; Wiley-VCH: Weinheim, Germany, 2005. (b) Faber, K.
Biotransformations in Organic Chemistry, 5th ed.; Springer: Berlin,
2004.
(15) (a) Mart´ın-Matute, B.; Edit, M.; Boga´r, K.; Ba¨ckvall, J. E. Angew.
Chem., Int. Ed. 2004, 43, 6535–6539. (b) Mart´ın-Matute, B.; Edit, M.;
Boga´r, K.; Kaynak, F. B.; Ba¨ckvall, J. E. J. Am. Chem. Soc. 2005, 127,
8817–8825.
(16) For some recent applications, see: (a) Norinder, J.; Boga´r, K.;
Kanupp, L.; Ba¨ckvall, J. E. Org. Lett. 2007, 9, 5095–5098. (b) Boga´r, K.;
Hoyos Vidal, P.; Alca´ntar Leo´n, A. R.; Ba¨ckvall, J. E. Org. Lett. 2007, 9,
3401–3404. (c) Leijondahl, K.; Bore´n, L.; Braun, R.; Ba¨ckvall, J. E. Org.
Lett. 2008, 10, 2027–2030.
(17) Boga´r, K.; Mart´ın-Matute, B.; Ba¨ckvall, J. E. Beilstein J. Org.
Chem. 2007, 3, 50.
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