Lactams, preparation from pyrrolines

Another synthetic route to ( )-retronecine (27) has been developed by Vedejs and Martinez.11 The protected hydroxy-lactam (22) was prepared from 2-methoxy-1-pyrroline by known methods. The key ylide intermediate (24) was then generated from the salt (23) by desilylation with caesium fluoride (Scheme 6). This ylide (24) reacted with methyl acrylate in a 1,3-dipolar cycloaddition to afford the unsaturated pyrrolizidine (25) in 57% yield from the lactam (22). Catalytic hydrogenation of the ester (25) gave an unstable endo-product, which epimerized to the exo-form (26). Introduction of the 1,2-double-bond into (26) was carried out by insertion and thermal elimination of a phenylseleno-group.12 Reduction then yielded ( )-retronecine (27). 

Starting from readily available substrates, a new one-pot procedure has been devised to prepare polycyclic lactams and sultams. 2-Pyrrolines 48 were obtained... 

Enaminones were obtained from lactam acetals by reaction with active methylene compounds610. Heterocyclic / -enaminoesters are synthons in the preparation of condensed systems611. Acylated alkyl aminoisobutyrylmalonates (145) can be converted to 3-oxo-2-pyrrolines (146)612,613. 

VaUee and coworkers found that Zn-mediated reduction of y-hydrox-ylaminoynoate esters gives intermediate y-aminoesters that subsequendy cyclize into 3-pyrrolin-2-ones (Scheme 12 1997TL5503, 1999SL602). This transformation involves the reduction of the hydroxylamine functionality, stereoselective reduction of the ynoate ester, and subsequent cycliza-tion to the lactam. Hydroxylamine 93 was prepared by the addition of the anion derived from ethyl propiolate (91) to nitrone 92. Treatment of 93 with zinc in acetic acid led to reduction of both the hydroxylamine... 

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