Synthetic studies toward paraherquamides E and F and related 13C-labeled putative biosynthetic intermediates: stereocontrolled synthesis of the α-alkyl-β-methylproline ring system

A substituted 2R-allyl-3S-methylproline ethyl ester suitable for elaboration to paraherquamides E, F and related 13C-labeled putative biosynthesis intermediates have been prepared efficiently in six steps and 24% overall yield. The key steps are a 5-exo-trig cyclization of a zinc enolate on an unactivated alkene and a stereocontrolled alkylation of the enolate formed from 3S-methyl-pyrrolidine-1,2R-dicarboxylic acid 1-tert-butyl ester 2-ethyl ester.