Type of Document	Dissertation
Author	Jo, Sunjin
URN	etd-04102008-145338
Title	Asymmetric Michael Additions of Lithium Propionate Enolates to ?,?-Unsaturated Esters: A Study towards the Total Synthesis of Lonomycin A
Degree	Doctor of Philosophy
Department	Chemistry and Biochemistry, Department of
Advisory Committee	Advisor Name Title ARMEN ZAKARIAN Committee Member MARIE E. KRAFFT Committee Member MICHAEL BLABER Committee Member ROBERT A. HOLTON Committee Member ROBERT H. REEVES Committee Member
Keywords	Lonomycin A Asymmetric Michael Addition Synthesis
Date of Defense	2008-04-08
Availability	unrestricted
Abstract The Michael addition of lithium enolates to ?,??unsaturated esters is considered to be one of the powerful and widely used C-C bond forming methods in organic synthesis. We investigated the Michael addition of lithium propionate enolates using the various chiral auxiliaries to ?,??unsaturated esters, methyl 2-bromo-3-methoxy acrylate and dioxinones. Various chiral propionates were prepared from the optically pure and commercially available terpenes in several steps. Michael additions using the chiral auxiliary introduced moderate to high stereoselectivities, and the factors that influence the stereoselection were examined. These results are consistent with a chelated transition state. The stereochemistry of Michael adducts was determined by the Mosher’s esterification and NMR experiments. Lonomycin A, which was isolated from Streptomyces ribosidificus in 1975, is a polycyclic ether constituted of six highly functionalized rings and 23 stereocenters. Our synthetic strategy relying on the asymmetric Michael addition of lithium propionate enolate to ?,??unsaturated esters introduced stereoselectively the contiguous and alternating methyl and methoxy moieties. This attractive methodology gave an easy access to the crucial intermediates in the synthetic approach towards the right-half fragment of Lonomycin A.
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