Z.-Y. Xue, Y. Jiang, W.-C. Yuan, X.-M. Zhang
SHORT COMMUNICATION
selective hydrosilylation to provide the dihydrobenzoxazi- tion mechanism and the utility of this reaction in the con-
none with acceptable yield and ee value (Table 2, Entry 12). struction of complex unnatural amino acid derivatives.
Finally, an aliphatic and cyclic α-imino ester 2m was re-
duced to give the desired product with good yield but very
low ee.
Experimental Section
General Procedure for the Asymmetric Hydrosilylation of α-Imino
Esters: A solution of trichlorosilane (102 µL, 1.00 mmol, 2.0 equiv.)
in CH2Cl2 (0.5 mL) was added dropwise to a solution of the cata-
lyst (0.05 mmol), the corresponding α-imino ester (0.50 mmol), and
pentanoic acid additive (0.0025 mmol, 2.6 µL, no additive for 2a)
in dry CH2Cl2 (1.5 mL) at –40 °C. The reaction mixture was stirred
at –40 °C until the α-imino ester disappeared (by TLC). Then, the
reaction was quenched with a saturated aqueous solution of
NaHCO3. The mixture was extracted with EtOAc, and the com-
bined extract was washed with brine and dried with anhydrous
MgSO4. Concentration in vacuo followed by flash chromatography
on silica gel (petroleum ether/ethyl acetate) afforded the α-amino
ester. The ee value was determined by using established HPLC
techniques with chiral stationary phases.
Table 2. Enantioselective hydrosilylation of α-imino esters 2 cata-
lyzed by 1i.
Supporting Information (see footnote on the first page of this arti-
cle): Experimental procedures and spectral and analytical data for
the catalysts, α-imino esters, and α-amino esters; HPLC chromato-
grams for the α-amino esters.
Acknowledgments
We are grateful for financial support from the National Sciences
Foundation of China (20772122).
[1] G. C. Barrett, Chemistry and Biochemistry of the Amino Acids,
Chapman and Hall, London, 1985.
[2] For selected reviews, see: a) M. A. Gallop, R. W. Barrett, W. J.
Dower, S. P. A. Fodor, E. M. Gordon, J. Med. Chem. 1994, 37,
1233–1251; b) M. D. Taylor, G. L. Amidon (Eds.), Peptide
Based Drug Design: Controlling Transport and Metabolism,
ACS, Washington, D.C., 1995; c) T. Darbre, J.-L. Reymond,
Acc. Chem. Res. 2006, 39, 925–934; d) L. S. Hegedus, Acc.
Chem. Res. 1995, 28, 299–305; e) L. Wang, P. G. Shultz, Angew.
Chem. Int. Ed. 2004, 43, 34–66.
[3] For selected reviews, see: a) R. M. Williams, Synthesis of Op-
tically Active α-Amino Acids, Pergamon, Oxford, 1989; b) D. J.
Ager, S. A. Laneman in Asymmetric Catalysis on Industrial
Scale (Eds: H. U. Blaser, E. Schmidt), Wiley-VCH, Weinheim,
2004, p. 258; c) G. Cardillo, L. Gentilucci, A. Tolomelli, Ald-
richimica Acta 2003, 36, 39; d) M. J. O’Donnell, Acc. Chem.
Res. 2004, 37, 506–517; e) K. Maruoka, T. Ooi, Chem. Rev.
2003, 103, 3013–3028; f) C. Nájera, J. M. Sansano, Chem. Rev.
2007, 107, 4584–4671.
[a] Unless specified otherwise, reactions were carried out with cata-
lyst 1i (10 mol-%), pentanoic acid (0.5 mol-%), and HSiCl3
(2.0 equiv.) on a 0.5-mmol scale in CH2Cl2 (2.0 mL) at –40 °C.
[b] Isolated yield based on the α-imino ester. [c] The ee values were
determined by using chiral HPLC. [d] The reaction was carried out
without pentanoic acid. [e] Determined by comparison of the op-
tical rotation value of 3a with the literature data.[5c] [f] Determined
by comparison of the optical rotation value of 3l with the literature
data.[5b]
[4] For selected reviews, see: a) W. Tang, X. Zhang, Chem. Rev.
2003, 103, 3029–3069; b) I. D. Gridnev, T. Imamoto, Acc.
Chem. Res. 2004, 37, 633–644; c) H. U. Blaser, E. Schmidt
(Eds.), Asymmetric Catalysis on Industrial Scale, Wiley-VCH,
Weinheim, 2004, pp. 21, 39, 269; d) C. M. Jakel, R. Paciello,
Chem. Rev. 2006, 106, 2912–2942.
[5] a) R. I. Storer, D. E. Carrera, Y. Ni, D. W. C. MacMillan, J.
Am. Chem. Soc. 2006, 128, 84–86; b) M. Rueping, A. P. Anton-
chick, T. Theissmann, Angew. Chem. Int. Ed. 2006, 45, 6751–
6755; c) G. Li, Y. Liang, J. C. Antilla, J. Am. Chem. Soc. 2007,
129, 5830–5831; d) Q. Kang, Z. A. Zhao, S. L. You, Adv. Synth.
Catal. 2007, 349, 1657–1660; e) Q. Kang, Z. A. Zhao, S. L.
You, Org. Lett. 2008, 10, 2031–2034.
Conclusions
In summary, novel, chiral Lewis bases derived from
trans-4-hydroxy--proline were developed and found to be
highly enantioselective in catalyzing the hydrosilylation of
α-imino esters. Thus, we have established the first general,
highly enantioselective Lewis base organocatalyzed hydro-
silylation of α-imino esters. Through this approach, a broad
range of chiral α-amino esters were synthesized in good
yields and with high levels of enantioselectivity. The abso-
lute configurations of two of the products were determined
as R by comparison of their rotation value with the litera-
ture data. Further work is in progress to elucidate the reac-
[6] For reviews on Lewis base activation of Lewis acids, see: a) S.
Rendler, M. Oestreich, Synthesis 2005, 11, 1727–1747; b) Y.
Orito, M. Nakajima, Synthesis 2006, 9, 1391–1401; c) S. E.
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