A General\nEnantioselective α‑Alkyl Amino\nAcid Derivatives Synthesis Enabled by Cobalt-Catalyzed Reductive Addition

Enantioenriched unnatural amino acids\nrepresent a prevalent motif\nin organic chemistry, with profound applications in biochemistry,\nmedicinal chemistry, and materials science. Herein, we report a cobalt-catalyzed\naza-Barbier reaction of dehydroglycines with unactivated alkyl halides\nto afford unnatural α-amino esters with high enantioselectivity.\nThis catalytic reductive alkylative addition protocol circumvents\nthe use of moisture-, air-sensitive organometallic reagents, and stoichiometric\nchiral auxiliaries, enabling the conversion of a variety of primary,\nsecondary, and even tertiary unactivated alkyl halides to α-alkyl-amino\nesters under mild conditions, thus leading to broad functional group\ntolerance. The expedient access to biologically active motifs demonstrates\nthe practicality of this protocol by reducing the number of synthetic\nsteps and enhancing the reaction efficiency.