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

• Main Author: Adsool, Shubhangi V., 1979-
• Other Authors: Memorial University of Newfoundland. Dept. of Chemistry
• Format: Thesis
• Language: English
• Published: 2010
• Subjects: Acetone; Addition reactions; Amino acids > Synthesis; Cyclohexanones > Synthesis; Nitroalkenes; Newfoundland studies; University of Newfoundland
• Online Access: http://collections.mun.ca/cdm/ref/collection/theses4/id/84623

Thesis (M.Sc.)--Memorial University of Newfoundland, 2010. Chemistry Includes bibliographical references. 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).* -- 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.* *Please refer to dissertation for diagrams.