Chiral N-phosphonylimine chemistry: Asymmetric synthesis of N-phosphonyl β-amino Weinreb amides

Various chiral N-phosphonyl β-amino Weinreb amides were synthesized by treating chiral N-phosphonyl imines with the lithium enolate of N-methoxy-N-methylacetamide. The N,N-protection groups on chiral N-phosphonyl imines and the types of deprotonation bases for enolate generation were found to be crucial for the successful synthesis. Eleven Weinreb amides were obtained in excellent chemical yields (92 to 98%) and good to excellent diastereoselectivities (up to dr = 99:1). The absolute structures were unambiguously determined by converting the products into authentic samples and by comparing their optical rotation values.