Enantioselective synthesis of the C1-C11 fragment of bafilomycin A(1) using non-Wittig and desymmetrization strategies

The synthesis of the C1-C11 fragment 33 of bafilomycin A, was achieved. Intermediate ketone 16 was prepared in six steps from 4-oxopimelate 13. Desymmetrization of this ketone using Koga's chiral base followed by TMSCl quench furnished silyl enol ether 17 with excellent enantioselectivity. Furt...

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Bibliographic Details
Published inJournal of organic chemistry Vol. 68; no. 12; pp. 4700 - 4707
Main Authors Poupon, JC, Demont, E, Prunet, J, Ferezou, JP
Format Journal Article
LanguageEnglish
Published WASHINGTON Amer Chemical Soc 13.06.2003
Subjects
Chemistry
Chemistry, Organic
Physical Sciences
Science & Technology
FUNCTIONALIZATION
SEGMENT
REAGENTS
REDUCTION
STEREOCHEMISTRY
ALDOL REACTIONS
ALDEHYDES
STEREOSELECTIVE-SYNTHESIS
CHIRAL LITHIUM AMIDE
DIMETHYL (DIAZOMETHYL)PHOSPHONATE
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Summary:The synthesis of the C1-C11 fragment 33 of bafilomycin A, was achieved. Intermediate ketone 16 was prepared in six steps from 4-oxopimelate 13. Desymmetrization of this ketone using Koga's chiral base followed by TMSCl quench furnished silyl enol ether 17 with excellent enantioselectivity. Further elaboration led to C5-C11 aldehyde 24, which was coupled with sulfone 3 to give lactone 25 in very good yield. The subsequent reductive elimination created the E-trisubstituted C4-C5 olefin with a 13:1 selectivity. The E C2-C3 double bond was then installed by methanol elimination, and compound 33 was obtained after a few functional group manipulations and a Negishi methyl zirconation.
ISSN:0022-3263
1520-6904
DOI:10.1021/jo034018e