Synthesis 2004(9): 1509-1521  
DOI: 10.1055/s-2004-822392
PAPER
© Georg Thieme Verlag Stuttgart · New York

Catalytic Direct Asymmetric Michael Reactions: Addition of Unmodified Ketone and Aldehyde Donors to Alkylidene Malonates and Nitro Olefins

Juan M. Betancort, Kandasamy Sakthivel, Rajeswari Thayumanavan, Fujie Tanaka, Carlos F. Barbas III*
The Skaggs Institute for Chemical Biology and the Departments of Chemistry and Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
Fax: +1(858)7842583; e-Mail: carlos@scripps.edu;
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Publikationsverlauf

Received 20 April 2004
Publikationsdatum:
26. Mai 2004 (online)

Abstract

The Michael additions of a number of ketones and aldehydes to alkylidene malonates and nitro olefins were studied. The reactions employ small organic molecules as catalyst under mild reaction conditions and do not require preactivation of the carbonyl donors. These reactions afforded a variety of highly functionalized products in good yields with moderate to good enantioselectivity.

35

When (S)-1-(2-pyrrolidinylmethyl)pyrrolidine and 2,4-pentanedione are mixed in equimolar amounts in DMSO, enamine formation is detected through UV spectroscopy. Furthermore, while pyrrolidine itself promotes the Michael reaction, the N-methyl derivative, which lacks the secondary amine is ineffective as catalyst. Alexakis et al. have also reported detection of enamine intermediates by GC-MS. See ref. 26c.