Asymmetric Carbamoyl Anion Additions to Chiral N‑Phosphonyl Imines via the GAP Chemistry Process and Stereoselectivity

ABSTRACT: Carbamoyl anions were found to smoothly react with chiral N-phosphonyl imines in toluene at −78 °C to r.t. using LiHMDS as the base. Group-assisted purification (GAP) has been utilized to give the pure amides without using column chromatography or recrystallization. The asymmetric reaction resulted in chiral N-phosphonyl amino amides with good to excellent yields (71−99%) and good crude diastereoselectivities (dr 84:16−95:5). In this GAP procedure, the crude solids are washed with diethyl ether to afford the pure products, as revealed by 1H NMR analysis; GAP washing consistently increases the diastereopurity of the products, resulting in excellent diaster-eoselectivities, often with final dr> 99:1. Interestingly, the diastereoenriched products can be obtained either in the ether solution or as the suspended solid, depending on the substrate. Chiral amines are ubiquitous throughout natural products an