Studies on an organocatalytic synthesis of functionalized nitrocyclohexanones and (+)-lycoperdic acid

Adsool, Shubhangi V. (2010) Studies on an organocatalytic synthesis of functionalized nitrocyclohexanones and (+)-lycoperdic acid. Masters thesis, Memorial University of Newfoundland.

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Abstract

A strategy for enantioselective double Michael addition reactions of acetone to nitroalkene 1 has been investigated. The feasibility of employing an enamine-mediated, organocatalytic route to functionalized cyclohexanones 2 was examined in this study (Scheme 1). -- [special characters omitted] -- Scheme 1: Synthesis of functionalized nitrocyclohexanones. -- Simultaneously, in continuation with the Pansare group's interest in organocatalytic conjugate addition reactions, an organocatalytic, conjugate addition based synthesis of (+)-lycoperdic acid (10) was examined. Lycoperdic acid is an unusual amino acid isolated from a mushroom (lycoperdon perlatum ). Its unique structure and potential glutamate receptor activity, makes it a challenging synthetic target. Our approach to lycoperdic acid is based on the enantioselective organocatalytic Mukaiyama-Michael addition of furan 5 to acrolein, mediated by catalysts 11 and 12 to provide the key butyrolactone 6 (Scheme 2). It is noteworthy that only a few examples of enantioselective organocatalytic Mukaiyama-Michael conjugate additions of furans related to 5 and β-substituted α,β-unsaturated aldehydes are known, and the use of acrolein as a Michael acceptor in these reactions has not previously been reported. Conversion of 6 to (S)-homocitric acid lactone (8) not only provided a new synthesis of this natural product enantiomer, and also established the stereochemistry of the Michael addition of 5 to 6. An organocatalytic α-amination of 6 using catalyst 12 provided 9 which is an advanced intermediate to lycoperdic acid. -- [special characters omitted] -- Scheme 2: Organocatalytic synthesis of (+) lycoperdic acid.

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