Geminal dicarboxylates as carbonyl surrogates for asymmetric synthesis. Part II. Scope and applications.
An enantioselective synthesis of allylic esters has been achieved by a novel asymmetric alkylation of allylic gem-dicarboxylates. The catalyst derived from palladium(0) and R,R-1,2-di(2'-diphenylphosphinobenzamido)cyclohexene efficiently induced the alkylation process with a variety of nucleophiles to provide allylic esters as products in good yield. High regio- and enantioselectivities were observed in the alkylation with most nucleophiles derived from malonate, whereas a modest level of ee's was obtained in the reactions with less reactive nucleophiles such as bis(phenylsulfonyl)ethane. In the latter case, a slow addition procedure proved effective, leading to significantly improved ee's. The utility of the alkylation products was demonstrated by several synthetically useful transformations including allylic isomerizations, allylic alkylations, and Claisen rearrangements. Using these reactions, the chirality of the initial allylic carbon-oxygen bond could be transferred to new carbon-oxygen, carbon-carbon, or carbon-nitrogen bonds in a predictable fashion with high stereochemical fidelity. The conversion of gem-diesters to chiral esters by the substitution reaction is the equivalent of an asymmetric carbonyl addition by stabilized nucleophiles. In conjunction with the subsequent reactions that occur with high stereospecificity, allylic gem-dicarboxylates serve as synthons for a double allylic transformation.
Trost
B M
BM
Department of Chemistry, Stanford University, Stanford, CA 94305, USA.
Lee
C B
CB
D000478:Alkylation; D000498:Allyl Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D002384:Catalysis; D003998:Dicarboxylic Acids / Q000737:chemistry*; D004952:Esters / Q000138:chemical synthesis / Q000737:chemistry*; D008314:Malonates / Q000737:chemistry; D008956:Models, Chemical; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry; D013237:Stereoisomerism
D000498:Allyl Compounds; D003998:Dicarboxylic Acids; D004952:Esters; D008314:Malonates; D010165:Palladium