Submitted on February 20, 2006
Accepted on March 20, 2007
Enantioselective Organocatalysis Using SOMO Activation
Teresa D. Beeson 1,
Anthony Mastracchio 1,
Jun-Bae Hong 1,
Kate Ashton 1,
David W. C. MacMillan 1*
1 Merck Center for Catalysis, Department of Chemistry, Princeton University, Princeton, NJ 08544, USA; Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
* To whom correspondence should be addressed.
David W. C. MacMillan , E-mail: dmacmill{at}princeton.edu
The asymmetric
-addition of relatively non-polar hydrocarbon substrates, such as allyl and aryl groups, to aldehydes and ketones remains a largely unsolved problem in organic synthesis, despite the wide potential utility of direct routes to such products. We reasoned that well-established chiral amine catalysis, which activates aldehydes toward electrophile addition by enamine formation, could be expanded to this important reaction class by applying a single-electron oxidant to create a transient radical species from the enamine. Here we demonstrate the concept of singly occupied molecular orbital (SOMO) activation with a highly selective
-allylation of aldehydes, and also present preliminary results for enantioselective heteroarylations and cyclization/halogenation cascades.