(S)-Selective Kinetic Resolution
FULL PAPER
Table 4. (Continued)
Acknowledgements
Entry
Substrate
KOtBu
[mol%]
t
Product
Yield
[%][b]
ee
[%][c]
We are grateful for financial support
from the Swedish Research Council,
the Swedish Foundation for Strategic
Research, and the Ministerio de Edu-
cación y Ciencia of Spain.
[h]
11[g]
6k
8
18
67
95
[a] Unless otherwise stated, all reactions were performed on a 1.0 mmol scale with 1.5 equiv of 10, 18 mg of
the enzyme surfactant mixture (enzyme/4/5=4:1:1), 1 mmol Na2CO3, 6 mol% of 3, 6–8 mol% of KOtBu, in
2 mL of THF at room temperature. Isolated yields in parentheses. [b] Determined by GC using a CP-Chirasil-
Dex CB column using racemic compounds as references. [c] Enantiomeric excess. [d] The enzyme surfactant
mixture was added in 2 portions (18 mg in each portion). The second portion was added after 16 h. [e] Re-
action run at 388C. The enzyme surfactant mixture was added in 2 portions (12 mg in each portion). The
second portion was added after 4.5 h. [f] 28 mg of supported enzyme were employed. After 24 h, a further
9 mg was added. [g] Reaction run at 388C and 30 mg of enzyme were employed.
chromatography (silica gel; pentane/diethyl ether 98:1)afforded ( S)-1-
phenylethyl pentanoate (12a)as a colorless oil (198 mg, 96%, 95% ee).
[1] a)J. Halpern, B. M. Trost, Proc. Natl. Acad. Sci. USA 2004, 101,
5347; b) Catalytic Asymmetric Synthesis, 2nd ed. (Ed.: I. Ojima),
Wiley-VCH, New York, 2000.
[2] M. Breuer, K. Ditrich, T. Habicher, B. Hauer, M. Kebeler, R.
Stürmer, T. Zelinski, Angew. Chem. 2004, 116, 806–843; Angew.
Chem. Int. Ed. 2004, 43, 788–824.
[3] a)R. S. Ward, Tetrahedron: Asymmetry 1995, 6, 1475–1490; b)U. T.
Strauss, U. Felfer, K. Faber, Tetrahedron: Asymmetry 1999, 10, 107–
117; c)H. Stecher, K. Faber, Synthesis 1997, 1, 1–16.
[4] a)O. Pàmies, J.-E. Bäckvall, Trends Biotechnol. 2004, 22, 130–135;
b)O. Pàmies, J.-E. Bäckvall, Chem. Rev. 2003, 103, 3247–3261; c)O.
Pàmies, J.-E. Bäckvall, Curr. Opin. Biotechnol. 2003, 14, 407–413;
d)M.-J. Kim, Y. Anh, J. Park, Curr. Opin. Biotechnol. 2002, 13, 578–
587, and erratum: M.-J. Kim, Y. Anh, J. Park, Curr. Opin. Biotech-
nol. 2003, 14, 131; e)F. F. Huerta, A. B. E. Minidis, J.-E. Bäckvall,
Chem. Soc. Rev. 2001, 30, 321–331.
[5] a)B. Martín-Matute, M. Edin, K. Bogµr, J.-E. Bäckvall, Angew.
Chem. 2004, 116, 6697–6701; Angew. Chem. Int. Ed. 2004, 43, 6535–
6539; b)B. Martín-Matute, M. Edin, K. Bogµr, F. B. Kaynak, J.-E.
Bäckvall, J. Am. Chem. Soc. 2005, 127, 8817–8825.
[6] a)J. H. Choi, Y.-H. Kim, S. H. Nam, S. T. Shin, M.-J. Kim, J. Park,
Angew. Chem. 2002, 114, 2479–2482; Angew. Chem. Int. Ed. 2002,
41, 2373–2376; b)J. H. Choi, Y. K. Choi, Y. H. Kim, E. S. Park, E. J.
Kim, M. J. Kim, J. Park, J. Org. Chem. 2004, 69, 1972–1977.
[7] For a DKR employing acid zeolites for racemization of benzylic al-
cohols, see: S. Wuyts, K. De Temmerman, D. E. De Vos, P. A.
Jacobs, Chem. Eur. J. 2005, 11, 386–397.
1H NMR (400 MHz, CDCl3, 258C): d=7.25–7.36 (m, 5H; 5CH), 5.91
3
3
(q, J(H,H)=6.4 Hz, 1H; CH), 2.33 (t, J(H,H)=7.6 Hz, 2H; CH2), 1.61–
1.66 (m, 2H; CH2), 1.54 (d, 3J(H,H)=6.4 Hz, 3H; CH3), 1.30–1.40 (m,
2H; CH2), 0.91 ppm (t, J(H,H)=7.6 Hz, 3H; CH3); 13C NMR (100 MHz,
3
CDCl3, 258C): d=173.05, 141.85, 128.43, 127.74, 126.01, 71.97, 34.32,
27.00, 22.23, 22.19, 13.66 ppm.
(S)-1-(4-Chlorophenyl)ethyl pentanoate (12e): 1H NMR (400 MHz,
CDCl3, 258C): d=7.31 (d, 3J(H,H)=8.8 Hz, 2H; 2CH), 7.27 (d,
3J(H,H)=8.8 Hz, 2H; 2CH), 5.84 (q, 3J(H,H)=6.4 Hz, 1H; CH), 2.32
(t, 3J(H,H)=7.6 Hz, 2H; CH2), 1.63–1.56 (m, 2H; CH2), 1.51 (d,
3J(H,H)=6.4 Hz, 3H; CH3), 1.36–1.28 (m, 2H; CH2), 0.90 ppm (t,
3J(H,H)=7.6 Hz, 3H; CH3); 13C NMR (100 MHz, CDCl3, 258C): d=
172.95, 140.38, 133.51, 128.62, 127.45, 71.26, 34.24, 26.97, 22.18, 22.16,
13.65 ppm.
(S)-1-(4-Trifluoromethylphenyl)ethyl
pentanoate
(12 f):
1H NMR
3
(300 MHz, CDCl3, 258C): d=7.60 (d, J(H,H)=8.2 Hz, 2H; 2CH), 7.45
(d, 3J(H,H)=8.2 Hz, 2H; 2CH), 5.91 (q, 3J(H,H)=6.9 Hz, 1H; CH),
2.34 (brd, 3J(H,H)=7.4 Hz, 2H; CH2), 1.67–1.52 (m, 2H; CH2), 1.53 (d,
3J(H,H)=6.6 Hz, 3H; CH3), 1.3 (sext, 3J(H,H)=7.2 Hz, 2H; CH2),
0.90 ppm (t, 3J(H,H)=7.4 Hz, 3H; CH3); 13C NMR (75 MHz, CDCl3,
258C): d=172.89, 145.92, 129.94 (q, 2J(13C,19F)=32.4 Hz), 126.22, 125.45
(q, 3J(13C,19F)=3.7 Hz), 124.04 (q, 1J(13C,19F)=272.3 Hz), 71.29, 34.17,
26.95, 22.25, 22.18, 13.61 ppm.
(S)-1-(3,5-Trifluoromethylphenyl)ethyl pentanoate (12g): 1H NMR
(300 MHz, CDCl3, 258C): d=7.78 (s, 3H; 3CH), 5.95 (q, 3J(H,H)=
6.6 Hz, 1H; CH), 2.37 (t, 3J(H,H)=6.3 Hz, 2H; CH2), 1.62 (quint,
3J(H,H)=7.1 Hz, 2H; CH2), 1.56 (d, 3J(H,H)=6.6 Hz, 3H; CH3), 1.32
(sext, 3J(H,H)=6.8 Hz, 2H; CH2), 0.90 ppm (t, 3J(H,H)=7.1 Hz, 3H;
CH3); 13C NMR (75 MHz, CDCl3, 258C): d=172.79, 146.54, 131.90 (q,
2J(13C,19F)=33.2 Hz), 126.18 (q, 3J(13C,19F)=2.6 Hz), 123.22 (q,
1J(13C,19F)=272.5 Hz), 121.73 (q, 3J(13C,19F)=3.7 Hz), 70.66, 34.9, 26.96,
22.29, 22.17, 13.57 ppm.
[8] For a related DKR of amines, see: M. T. Reetz, K. Schimossek,
Chimia 1996, 50, 668–669.
[9] a)G. K. M. Verzijl, J. G. de Vries, Q. B. Broxterman, Tetrahedron:
Asymmetry 2005, 16, 1603–1610; b)B. A. C. van As, J. van Buijte-
nen, A. Heise, Q. B. Broxterman, G. K. M. Verzijl, A. R. A. Pal-
mans, E. W. Meijer, J. Am. Chem. Soc. 2005, 127, 9964–9965.
[10] T. H. Riermeier, P. Gross, A. Monsees, M. Hoff, H. Trauthwein, Tet-
rahedron Lett. 2005, 46, 3403–3406.
[11] a)R. D. Schmid, R. Verger, Angew. Chem. 1998, 110, 1694–1720;
Angew. Chem. Int. Ed. 1998, 37, 1608–1633; b)K. Faber, Biotrans-
formations in Organic Chemistry, 4th ed., Springer, Berlin, 2000.
[12] R. J. Kazlauskas, A. N. E. Weissfloch, A. T. Rappaport, L. A.
Cuccia, J. Org. Chem. 1991, 56, 2656–2665.
[13] The terms (R)- and (S)-selective are used for typical sec-alcohols in
which the large group (cf. Figure 1)has the higher priority in the se-
quential rule for determining the configuration (according to the
Cahn–Ingold–Prelog system).
[14] a)R. J. Kazlauskas, A. N. E. Weissfloch, J. Mol. Catal. B 1997, 3,
65–72; b)P. A. Fitzpatrick, A. M. Klibanov, J. Am. Chem. Soc. 1991,
113, 3166–3171; c)R. J. Kazlauskas, A. N. E. Weissfloch, J. Org.
Chem. 1991, 56, 2656–2665.
(S)-1-Methyl-3-phenylpropyl pentanoate (12i): 1H NMR (300 MHz,
CDCl3, 258C): d=7.31–7.26 (m, 2H; 2CH), 7.21–7.19 (m, 3H; 3CH),
4.97 (sext, 3J(H,H)=6.3 Hz, 1H; CH), 2.74–2.57 (m, 2H; CH2), 2.29 (t,
3J(H,H)=7.7 Hz, 2H; CH2), 2.05–1.75 (m, 2H; CH2), 1.69–1.58 (m, 2H;
CH2), 1.37 (sext, 3J(H,H)=7.5 Hz, 2H; CH2), 1.25 (d, 3J(H,H)=6.1 Hz,
3
3H; CH3), 0.94 ppm (t, J(H,H)=7.4 Hz, 3H; CH3); 13C NMR (100 MHz,
CDCl3, 258C): d=173.42, 141.55, 128.35, 128.26, 125.85, 70.13, 37.63,
34.35, 31.79, 27.11, 22.23, 20.01, 13.68 ppm.
Valerate esters 12b–d, 12h, 12j, and 12k were transformed to the corre-
sponding alcohols and compared to commercially available pure samples
by using NMR spectroscopy.
Chem. Eur. J. 2006, 12, 225 – 232
ꢁ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
231