Stereoselective synthesis of quaternary center bearing azetines and their beta-amino acid derivatives.
We describe here the use of a stable, four-membered azetine heterocycle for the preparation of highly substituted beta-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 beta2,2,3-amino carbonyl derivatives in good yields.
MacNevin
Christopher J
CJ
Department of Chemistry, Emory University, 1521 Dickey Drive, Atlanta, Georgia 30322, USA.
Moore
Rhonda L
RL
Liotta
Dennis C
DC
D000478:Alkylation; D000596:Amino Acids / Q000737:chemistry*; D001385:Azetines / Q000138:chemical synthesis* / Q000737:chemistry; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization; D013055:Spectrophotometry, Infrared; D013237:Stereoisomerism
D000596:Amino Acids; D001385:Azetines