Imidazolidinone chiral auxiliaries for the stereoselective synthesis of azetines and β-amino carbonyl derivatives bearing a quaternary center

ORGN 643

Christopher J. MacNevin, cmacnev@emory.edu and Dennis C. Liotta. Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, GA 30322
Addition of chlorotitanium enolates of N-propionyl oxazolidinone and thiazolidinethione chiral auxiliaries to oxime ethers provides substituted azetines with high diastereoselectivity. The reaction also gives a pyrimidinone byproduct as the result of a competitive reaction pathway involving intramolecular cyclization to the carbonyl of the auxiliary. The alternative use of imidazolidinone chiral auxiliaries under similar reaction conditions has been shown to eliminate this alternative pathway and allow improved access to the azetine substrates. The further addition of electrophiles to the azetine enolate achieves stereoselective quaternary center formation due to the mutually reinforcing directing groups present in the azetine-auxiliary complex. The functionalized azetine can be subsequently ring opened upon treatment with benzoyl chloride to give the corresponding β-amino carbonyl derivative.