The First General Enantioselective Catalytic Diels−Alder Reaction with Simple α,β-Unsaturated Ketones
The first general approach to enantioselective catalysis of the Diels−Alder reaction with simple ketone dienophiles has been accomplished. The use of iminium catalysis has enabled enantioselective access to a fundamental Diels−Alder reaction variant that has previously been unavailable using chiral Lewis acid catalysis. A new chiral amine catalyst has been developed that allows a variety of monodentate cyclic and acyclic ketones to successfully participate in enantioselective [4 + 2] cycloadditions. A wide spectrum of cyclic and acyclic diene substrates can also be accommodated in this new organocatalytic transformation. A computational model is provided that is in accord with the sense of enantioinduction observed for all reactions conducted during the course of this study.
Additional Information© 2002 American Chemical Society. Received 29 November 2001. Published online 23 February 2002. Published in print 1 March 2002. Financial support was provided by kind gifts from AstraZeneca, Boehringer-Ingelheim, Dupont, GlaxoSmithKline, Johnson and Johnson, Lilly, Materia, Merck Research Laboratories, Pfizer, Pharmacia, and Roche Biosciences. We also thank Great Lakes for their generous donation of (S)-phenylalanine. D.W.C.M is grateful for support from Research Corporation under the Cottrell Scholarship program. A.B.N. is grateful for a NSF predoctoral fellowship. Note Added in Proof. Shortly prior to publication it came to the authors attention that an enantioselective boron-catalyzed ketone Diels−Alder reaction has been accomplished. This work will be submitted for communication in the near future. Joel M. Hawkins, Pfizer Global Research, personal communication.
Supplemental Material - ja017641u_s1.pdf