4-Aryloxybutenolides as "chiral aldehyde" equivalents: an efficient enantioselective synthesis of (+)-brefeldin a.
4-(2'-Naphthoxy)-2-butenolide, readily available with high enantiopurity by a dynamic kinetic asymmetric transformation (DYKAT) of racemic 4-acyloxybutenolides (available in two steps from furfural), serves as an excellent chiral building block where the naphthoxy group strongly directs the stereochemistry of cycloadditions to the double bond. Notably, the cycloadditions of trimethylenemethanepalladium intermediates which do not exhibit good diastereoselectivity in additions to acceptors that possess many common and important chiral auxiliaries undergo cycloadditions with excellent regio- and stereocontrol. The utility of this process set the stage for an efficient new synthesis of (+)-brefeldin A, a compound of growing pharmacological significance. This synthesis also highlights the Pd-catalyzed DYKAT of crotyl carbonate to create the remote stereocenter. A new two-step method to convert aldehydes to delta-hydroxy-E-alpha,beta-enoates is also outlined.
Trost
Barry M
BM
Department of Chemistry, Stanford University, California 94305-5080, USA. bmtrost@stanford.edu
Crawley
Matthew L
ML
D000447:Aldehydes / Q000737:chemistry*; D020126:Brefeldin A / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D000447:Aldehydes; D020126:Brefeldin A