Catalytic\nEnantioselective Nucleophilic Amination\nof α‑Halo Carbonyl Compounds with Free Amines

Catalytic\nenantioselective substitution of the readily available\nracemic α-halo carbonyl compounds by nitrogen nucleophiles represents\none of the most convenient and direct approaches to access enantioenriched\nα-amino carbonyl compounds. Distinct from the two available\nstrategies involving radicals and enolate ions, herein we have developed\na new protocol featuring an electronically opposite way to weaken/cleave\nthe carbon–halogen bond. A suitable chiral anion-based catalyst\nenables effective asymmetric control over the key positively charged\nintermediates. This protocol not only allows free amines to serve\nas nucleophiles but also permits different types of carbonyl compounds\n(ketones, esters, and amides) to participate in the enantioselective\nC–N bond formation, thereby providing a valuable complement\nto the known strategies that are limited to certain carbonyl substrates\nand/or nitrogen nucleophiles. Preliminary studies indicated that an\nS<sub><i>N</i></sub>2 pathway is operational and kinetic\nresolution is involved.