Development of the Lewis Acid Catalyzed Allenoate-Claisen Rearrangement. Investigations of Enantioselective Catalysis of the Allenoate-Claisen Rearrangement. Studies Towards the Total Synthesis of Erythrolide E

Citation

Lambert, Tristan Hayes (2004) Development of the Lewis Acid Catalyzed Allenoate-Claisen Rearrangement. Investigations of Enantioselective Catalysis of the Allenoate-Claisen Rearrangement. Studies Towards the Total Synthesis of Erythrolide E. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/QVJB-E506. https://resolver.caltech.edu/CaltechETD:etd-12112003-091509

Abstract

The development of a new Lewis acid catalyzed sigmatropic reaction is described. This process, termed the allenoate-Claisen rearrangement, involves the metal-catalyzed condensation of an allenic ester with a tertiary allylic amine. The zwitterionic intermediate resulting from this condensation undergoes facile [3,3] bond reorganization to provide β-amino-α,β,ε,ζ-unsaturated-γ,δ-disubstituted ester products. The allenoate-Claisen reaction has been demonstrated to allow for the production of a diverse range of Claisen adducts in high yield and with very high diastereoselectivities. Perhaps most notably, this process is amenable to the rapid generation of quaternary carbon stereogenicity with nearly complete stereocontrol.

Investigations of an enantioselective catalytic variant of the allenoate-Claisen rearrangement have been initiated. Enantioselectivities of up to 49% have been achieved with the use of a titanium bis(binaphthyl) catalyst and a bidentate chelating allenic partner. The effects of solvent and method of catalyst preparation on enantioselectivity are described.

Progress towards the total synthesis of the briarane diterpene, erythrolide E, has been made. Using acyl-Claisen methodology developed in the MacMillan laboratories, both key fragments of the erythrolide framework have been prepared in racemic fashion. In addition, a highly enantioselective route to the core fragment has been developed using an enantioselective organocatalytic Diels-Alder reaction and Ireland-Claisen methodology.

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