The Development of Organocatalytic Reactions Pertaining to Indoles

Citation

Austin, Joel Francis (2006) The Development of Organocatalytic Reactions Pertaining to Indoles. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/CDXN-8R73. https://resolver.caltech.edu/CaltechETD:etd-06132005-145346

Abstract

An improved imidazolidinone catalyst for the LUMO-lowering activation of [alpha],[beta]-unsaturated aldehydes has been designed, synthesized and evaluated. This new catalyst allows hitherto infeasible reactions to proceed with high fidelity. A new strategy for the synthesis of C-3 chiral indoles has been developed. This strategy employs the use of the aforementioned imidazolidinone catalyst to activate [alpha], [beta]-unsaturated aldehydes toward a Friedel-Crafts reaction with a variety of indoles. This is the first and only example in the literature were an indole is alkylated by an [alpha], [beta]-unsaturated aldehyde enantioselectively and catalytically. This methodology allows for the rapid synthesis of this priviledged pharmacophore. By exploiting the indolium ion intermediate produced during the asymmetric Friedel-Crafts alkylation of indoles, a cascade cyclization was found to occur in the first enantioselectivive catalytic construction of the pyrroloindoline architecture. This direct route provides rapid access to this valuable core motif. This research has led to interesting observances in terms of indole facial selectivity that can be rationalized by an understanding of the cation-[pi] interaction. After numerous unsuccessful attempts to apply the direct pyrroloindoline construction to the synthesis of vicinally quaternary adducts, exploration of the higher reactivity of oxindoles was undertaken. This study has led to the first construction of vicinally quaternary stereogenic carbons via an organocatalyzed protocol.

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