Scalable DOS-like Strategy to the δ-Amino Acids via Petasis/Cross Metathesis Reactions Sequence

A convenient and scalable approach to N-protected δ,δ-spirosubstituted δ-amino acids and their α,β-unsaturated analogues from bulk ketones was elaborated. The proposed routes include Petasis reaction of starting ketone with allylboronic acid pinacol ester and methanolic ammonia and cross metathesis with methyl acrylate or acrylic acid as key steps. The developed protocols are novel, robust and economically efficient, they avoid tedious separation and purification and were scaled up to 40 g of final compounds from a single synthetic run.