Design of a New Cascade Reaction for the Construction of Complex Acyclic Architecture: The Tandem Acyl-Claisen Rearrangement
Tandem or domino reactions have long been established as powerful chemical tools for the rapid formation of complex cyclic and polycyclic architecture. Surprisingly, however, relatively few tandem strategies have been directed toward the production of acyclic structural motifs despite significant advances in the area of acyclic stereocontrol. In our recent study, we reported the development of the acyl-Claisen rearrangement, a catalytic [3,3]-bond reorganization that allows the stereoselective synthesis of α,β-disubstituted-γ,δ-unsaturated carbonyls. In this communication, we outline the development of the tandem acyl-Claisen reaction, a highly stereoselective three-component coupling that enables the rapid construction of complex acyclic systems in the context of 2,3,6-trisubstituted-1,7-dioxoheptane architecture (eq 1). This versatile cascade sequence is conducted by using simple allyl diamines and acid chlorides, chemicals that are widely available in a diverse range of structural formats. As such, we expect this tandem reaction to be of broad utility to a number of chemical fields that employ molecule construction including natural product and parallel medicinal agent synthesis.
Additional Information© 2001 American Chemical Society. Received 27 December 2000. Published online 16 February 2001. Published in print 1 March 2001. V.M.D. is grateful for an NSF predoctoral fellowship. Financial support was provided by the NIH (R01 GM61214-01).
Supplemental Material - ja005925t_s1.pdf