Asymmetric Synthesis of α-Alkyl-ω-amino Acids and α-Alkyllactams

A versatile access to optically active α-branched ω-amino acids 8 and 9 and corresponding lactams 11 was developed allowing the synthesis of either enantiomer of these products. This asymmetric synthesis is based on amino alcohols 3 as chiral auxiliaries, which were converted to 2-(ω-benzenesulfonylaminoalkyl)oxazolines 4 by reaction with ω-amino-imido esters 2 or derivatives of lactams 1. The 2-(ω-benzenesulfonylaminoalkyl)oxazolines 4 were deprotonated by LDA and α-alkylated by alkyl halides 5. Final hydrolytic cleavage of the oxazoline ring afforded the amino acids 8 and 9 or lactams 11. The method does not follow Meyers model of α-alkylation of 2-alkyloxazolines and requires BEt₃ as additive in order to achieve complete stereoselectivity.

Asymmetric α-alkylation of 2-(ω-aminoalkyl)-oxazolines and hydrolysis affords enantiomerically pure ω-aminoacids or lactams