C O MMU N I C A T I O N S
Table 1. Proline-Catalyzed Direct Asymmetric R-Amination of
Aldehydes
2-oxazolidinones and other natural and nonnatural R-amino and
R-hydrazino acid derivatives. (4) The operationally simple reac-
13
tions are rapid, and require a relatively low amount of an
inexpensive and nontoxic catalyst that is available in both enan-
tiomeric forms.
Scope and application of this novel transformation are currently
under active investigation in our laboratories and will be reported
in due course.
product
R
yield, %
ee, %
Acknowledgment. Support by the NIH (GM-63914) is most
gratefully acknowledged. We thank Linh Hoang for technical
assistance, M. G. Finn and his group for sharing chemicals, Warren
Lewis for help with NMR experiments, and Harry Martin for critical
manuscript reading.
1
2
3
4
5
i-Pr
n-Pr
n-Bu
Me
99
93
94
97
95
96
>95
97
>95
>95
Bn
Supporting Information Available: Experimental procedures and
spectral data for all compounds (PDF). This material is available free
of charge via the Internet at http://pubs.acs.org.
over Raney Nickel10 and worked up with phosgene to furnish
oxazolidinone (R)-6, a commercially available Evans auxiliary (eq
11
3).
References
(
1) Reviews: (a) Genet, J.-P.; Greck, C.; Lavergne, D. In Modern Amination
Methods; Ricci, A., Ed.; Wiley-VCH: Weinheim, Germany, 2000; Chapter
3
. (b) Krohn, K. In Organic Synthesis Highlights; VCH: Weinheim,
Germany, 1991; pp 45-53.(c) Greck, C.; Genet, J. P. Synlett 1997, 741-
48. (d) Boche, G. In StereoselectiVe Synthesis; Helmchen, G., Hoffmann,
R. W., Mulzer, J., Schaumann, E., Eds.; Thieme: Stuttgart, Germany,
996; Vol. 9, pp 5133-5157.
2) (a) Gennari, C.; Colombo, L.; Bertolini, G. J. Am. Chem. Soc. 1986, 108,
7
1
(
6
394-6395. (b) Evans, D. A.; Britton, T. C.; Dorow, R. L.; Dellaria, J.
F., Jr. J. Am. Chem. Soc. 1986, 108, 6395-6397. (c) Trimble, L. A.;
Vederas, J. C. J. Am. Chem. Soc. 1986, 108, 6397-6399. (d) Oppolzer,
W.; Moretti, R. HelV. Chim. Acta 1986, 69, 1923-1926.
We expect this novel route to be useful for the synthesis of
several other 4-substituted 2-oxazolidones, including various Evans
auxiliaries in both enantiomeric forms. By measuring the optical
rotation and ee of compound 6, we could furthermore establish the
(
3) (a) Evans, D. A.; Johnson, D. S. Org. Lett. 1999, 1, 595-598. (b)
Yamishita, Y.; Ishitani, H.; Kobayashi, S. J. Can. Chem. 2000, 78, 666-
672.
(
4) Evans, D. A.; Nelson, S. G. J. Am. Chem. Soc. 1997, 119, 6452-6453.
(expected) absolute configuration and the ee of alcohol 5.
(
5) Juhl, K.; Jørgensen, K. A. J. Am. Chem. Soc. 2002, 124, 2420-2421.
The observed sterochemistry can be explained with a proline-
enamine-involving transition state (A). The proposed model is based
(6) List, B. Synlett 2001, 1675-1686 and references therein.
(
7) Preformed enamines readily react with azodicarboxylates, see for ex-
ample: Forchiassin, M.; Risaliti, A.; Russo, C. Tetrahedron 1981, 37,
2921-2928.
on Houk’s calculated transition state of the Hajos-Parrish-Eder-
Sauer-Wiechert reaction (B)12 and is also consistent with our
(8) For other recent examples of using aldehyde-nucleophiles in enamine
catalysis, see: (a) Hagiwara, H.; Okabe, T.; Hakoda, K.; Hoshi, T.; Ono,
H.; Kamat, V. P.; Suzuki, T.; Ando, M. Tetrahedron Lett. 2001, 42, 2705-
2707. (b) Bøgevig, A.; Kumaragurubaran, N.; Jørgensen, K. A. Chem.
Commun. 2002, 620-621. (c) Cordova, A.; Watanabe, S.; Tanaka, F.;
Notz, W.; Barbas, C. F., III J. Am. Chem. Soc. 2002, 124, 1866-1867.
previously proposed transition states for intermolecular aldol and
Mannich reactions.6
(
9) The aldehyde intermediate can be isolated in excellent yield as a crystalline
solid. However, this product is configurationally labile and partially
racemizes upon isolation (ee 86%).
(
10) Udodong, U. E.; Fraser-Reid, B. J. Org. Chem. 1989, 54, 2103-2112.
(
11) (a) Ager, D. J.; Prakash, I.; Schaad, D. R. Aldrichim. Acta 1997, 30, 3-12.
(
b) Ager, D. J.; Prakash, I.; Schaad, D. R. Chem. ReV. 1996, 96, 835-
8
75.
(
(
12) Bahmanyar, S.; Houk, K. N. J. Am. Chem. Soc. 2001, 123, 9922-9923.
13) R-Hydrazino acids have recently received considerable attention because
of their biological activity and structural and metabolic effects they exert
after incorporation into peptidomimetics. See for example: (a) Lam, L.
K. P.; Arnold, L. D.; Kalantar, T. H.; Kelland, J. G.; Lane-Bell, P. M.;
Palcic, M. M.; Pickard, M. A.; Vederas, J. C. J. Biol. Chem. 1988, 263,
11814-11819. (b) Morley, J. S.; Payne, J. W.; Hennessey, T. D. Gen.
Microbiol. 1983, 129, 3701-3708. (c) Chen, S.; Chrusciel, R. A.;
Nakanishi, H.; Raktabutr, A.; Johnson, M. E.; Sato, A.; Weiner, D.; Hoxie,
J.; Saragovi, H. U.; Greene, M. I.; Kahn, M. Proc. Natl. Acad. Sci. U.S.A.
In summary we have developed the first direct catalytic asym-
metric R-amination of aldehydes. Among the unique features of
this novel transformation, the folowing are emphasized: (1) The
described reaction is the first direct R-amination of aldehydes. (2)
The reaction furnishes crystalline products in excellent enantio-
selectivities and yields. (3) The products are useful precursors for
1992, 89, 5872-5876.
JA0261325
J. AM. CHEM. SOC.
9
VOL. 124, NO. 20, 2002 5657