Z. Gercek et al. / Tetrahedron: Asymmetry 16 (2005) 1743–1746
1745
enantioselectivity in acetonitrile and toluene towards 1,
in regard to the ee of the remaining substrate (R)-1
(93%, 99%). Lipase from C. antarctica displayed high
enantioselectivity in toluene towards 1, in regard to
the ee of the remaining substrate (S)-1 (96%) and in
THF towards 1, in respect to the ee of the product
(R)-2 (96%).
the tables. Optical rotations were measured with a Kruss
¨
P3002RS automatic polarimeter.
4.2. General procedure for the lipase-catalyzed asym-
metric transesterification of ( )-1
Racemic alcohol 1 (293 mg, 2 mmol) and vinyl acetate
(344 mg, 4 mmol) were dissolved in the appropriate
organic solvent (8 mL) while lipases (200–300 mg) were
added [reactions without organic solvents: a mixture of
racemic alcohol 1 (292 mg, 2 mmol), vinyl acetate
(344 mg, 4 mmol) and lipase (200–300 mg) were stirred
at 37 °C].The reaction mixture was stirred at 37 °C.
The reaction was monitored by TLC and HPLC and
when the maximum conversion was reached, the reac-
tion was terminated by way of filtration. Substrate 1
and product 2 were separated by flash chromatography
over silica (n-hexane/ethyl acetate, 4:1).
C. antarctica lipase was the enzyme of choice used in the
transesterification of rac-1 using vinyl acetate without
solvent on a preparative scale synthesis of (R)-2. An E
value of more than 200 was observed with the reaction
terminated after 90 h to afford (R)-2 with more than
99% ee, in 38% yield with alcohol (S)-1 recovered in
86% ee and 34% yield. Compound (S)-1 (96% ee, 41%
yield) was obtained in preparative scale by using
C. antarctica lipase in toluene. For the preparative scale
synthesis of (R)-1 lipase from P. cepacia was used and
transesterification of rac-1 in acetonitrile furnished (S)-
2 in 36% yield and 42 % ee and the remaining (R)-1
was isolated in 43% yield and 99% ee. Compound (S)-
2 (96% ee, 40% yield) was obtained on a preparative
scale by using P. cepacia lipase under solvent free
condition.
4.2.1. (R)-2-Chloro-1-(2-furyl)ethanol (R)-1.3 Colour-
25
D
less oil (126 mg, 43%, 99% ee), ½aꢁ ¼ ꢀ21.7 (c 0.42,
20
CHCl3), {lit.3 ½aꢁ ¼ þ23 (c 0.52, CHCl3) for (S)-1}.
D
HPLC: Chiralcel OD column, UV detection at
254 nm,
eluent:
hexane/2-propanol = 95:5,
flow
0.50 mL minꢀ1 20 °C (retention time: 18 min). 1H
NMR (400 MHz, CDCl3): d 2.60 (br s, 1H, OH), 3.71–
3.81 (m, 2H), 4.87–4.93 (m, 1H), 6.27 (d, J = 3.1 Hz,
1H), 6.32 (dd, J = 1.6, 3.1 Hz, 1H), 7.25 (s, 1H). 13C
NMR (CDCl3): d 47.3, 68.0, 107.5, 112.8, 142.3, 152.9.
By applying the related literature procedure,9 hydrolysis
of (S)-2 (K2CO3/MeOH) furnished (S)-1 in 83%
yield while the acetylation of (R)-1 (Et3N, Ac2O)
furnished (R)-2 in 86% yield (Scheme 1). These processes
could be carried out without any loss of enantiomeric
excess.
4.2.2. (S)-2-Chloro-1-(2-furyl)ethanol (S)-1. Colourless
25
D
oil (120 mg, 41%, 96% ee), ½aꢁ ¼ þ18.3 (c 0.35, CHCl3)
HPLC: Chiralcel OD column, UV detection at 254 nm,
eluent: hexane/2-propanol = 95:5, flow 0.50 mL minꢀ1
20 °C (retention time: 22 min).
3. Conclusion
In summary, we have reported herein the first efficient
synthesis of both enantiomers of 2-chloro-1-(2-furyl)-
ethanol 1 and 2-chloro-1-(2-furyl)ethyl acetate 2, via
enzymatic kinetic resolution. Chlorination of 1-(2-
furyl)ethanone furnished 2-chloro-1-(2-furyl)ethanone
3 in high yield. Reduction of 3 with BH3SMe2 furnished
rac-1 in high yield. Enzyme catalyzed transesterification
of rac-2-chloro-1-(2-furyl)ethanol rac-1 using vinyl ace-
tate afforded both enantiomers of 2-chloro-1-(2-furyl)-
ethanol 1 and 2-chloro-1-(2-furyl)ethyl acetate 2 in high
enantiomeric excess.
4.2.3. (S)-2-Chloro-1-(2-furyl)ethyl acetate (S)-2. Col-
25
D
ourless oil (150 mg, 40%, 96% ee), ½aꢁ ¼ þ14.5 (c 0.2,
CHCl3). HPLC: Chiralcel OD column, UV detection
at 254 nm, eluent: hexane/2-propanol = 95:5, flow
0.50 mL minꢀ1 20 °C (retention time: 12.5 min). 1H
NMR (CDCl3): d 2.01 (s, 3H), 3.73–3.81 (m, 2H), 5.93
(dd, J = 5.9 Hz, 1H), 6.25–6.28 (m, 1H), 6.32 (d,
J = 3.2 Hz, 1H), 7.33 (s, 1H). 13C NMR (CDCl3): d
20.7, 43.0, 96.1, 109.8, 110.4, 142.8, 149.5, 169.1. Anal.
Calcd for C8H9ClO3 (188.6): C, 50.94; H, 4.81. Found:
C, 50.75; H, 4.72.
4. Experimental
4.2.4. (R)-2-Chloro-1-(2-furyl)ethyl acetate (R)-2. Col-
25
D
ourless oil (142 mg, 38%, 99% ee), ½aꢁ ¼ ꢀ16.6 (c 0.2,
4.1. Materials and methods
CHCl3). HPLC: Chiralcel OD column, UV detection
at 254 nm, eluent: hexane/2-propanol = 95:5, flow
0.50 mL minꢀ1 20 °C (retention time: 14 min).
NMR spectra were recorded on a Bruker DPX 400.
Chemical shifts d are reported in ppm relative to CHCl3
(1H: d = 7.27), CDCl3 (13C: d = 77.0) and CCl4 (13C:
d = 96.4) as internal standards. Column chromato-
graphy was conducted on silica gel 60 (40–63 lm).
TLC was carried out on aluminum sheets pre-coated
with silica gel 60F254 (Merck), and the spots were visua-
lized with UV light (k = 254 nm). Enantiomeric excesses
were determined by HPLC and LC–MS analysis using a
Thermo Finnigan Surveyor equipped with an appropri-
ate chiral phase column, as described in the footnotes of
Acknowledgements
Financial support from the Scientific and Technical
Research Council of Turkey (TUBITAK), the Turkish
¨
Academy of Sciences (TUBA), the Turkish State Plan-
ning Organization (for LC–MS and HPLC), the Middle
East Technical University (DOSAP) and Zonguldak
Karaelmas University is gratefully acknowledged.