Stereoselective Synthesis of Quaternary Center Bearing Azetines and Their β-Amino Acid Derivatives

We describe here the use of a stable, four-membered azetine heterocycle for the preparation of highly
substituted β-amino acid derivatives. Imidazolidinone chiral auxiliaries were found to eliminate a
competitive reaction pathway that had been present under previously reported conditions for azetine
synthesis. The ephedrine derived imidazolidin-2-one 21 was allowed to react as its chlorotitanium enolate
with O-methyl or -benzyl oximes under optimized conditions to gain improved access to azetines at the
gram scale. The azetines were further found to undergo alkylation with complete diastereocontrol, affording
the creation of a quaternary center. Subsequent ring opening with benzoyl chloride and auxiliary cleavage
provided the corresponding β2,2,3-amino carbonyl derivatives in good yields.