Weinreb amides, Wittig reaction

This is a Wittig reaction. The stable ylide is prepared from 29 prior to the reaction. Only the ketone reacts to form the corresponding olefin via the oxaphosphetane intermediate, as the Weinreb amide is not reactive enough. Owing to the use of a stable phosphonium ylide, only the product with the -configured double bond is obtained in 90 % yield ( /Z 99 1). 

The monomers are prepared by the homologation of N-protected amino acid aldehydes. Boc-protected amino aldehyde was synthesized in solution via Weinreb amide reduction with LiAlH4.Then, using a Wittig reaction, it was transformed into an olefin bearing an ethyl ester group, which was subsequently saponified. 

Wacker oxidation, 237 Weinreb amide, 117, 188 Weinreb s oxazolidinone, 377 Wittig olefination, 250, 258, 368 Wittig reaction, 46, 50, 164,... 

Aldol 307 became the central starting material for three advanced intermediates. Thus, tret-butyldimethyl-silyl (TBS) protection followed by Red-Al reduction of "Weinreb amide produced aldehyde 308, which underwent "Wittig reaction. The latter gave mediocre 30% yield and was one of the most difficult reactions to scale up (Scheme 10.59). 

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