Studies of Azetidin-2-one as a Reactive Enolate Synthon of β‑Alanine for Condensations with Aldehydes and Ketones

Studies describe formation of the lithium enolate of N-(4-methoxybenzyloxy)­azetidin-2-one (1) and characterization of representative aldol reactions with aldehydes and ketones. Diastereoselectivity features the production of anti-aldol adducts from α,β-unsaturated ketones and α-branched aliphatic aldehydes. The stereoselectivity is rationalized via closed, six-membered transition-state arrangements leading to the formation of Felkin–Anh and anti-Felkin products. Examples illustrate the direct incorporation of monocyclic β-lactams into a variety of molecular architectures. The utility of 1 as an enolate synthon of homoglycine (β-alanine) is illustrated by the efficient synthesis of novel β-amino acid derivatives, including complex 4-hydroxy-2-pyridinones.