Enantioenriched unnatural amino acids
represent a prevalent motif
in organic chemistry, with profound applications in biochemistry,
medicinal chemistry, and materials science. Herein, we report a cobalt-catalyzed
aza-Barbier reaction of dehydroglycines with unactivated alkyl halides
to afford unnatural α-amino esters with high enantioselectivity.
This catalytic reductive alkylative addition protocol circumvents
the use of moisture-, air-sensitive organometallic reagents, and stoichiometric
chiral auxiliaries, enabling the conversion of a variety of primary,
secondary, and even tertiary unactivated alkyl halides to α-alkyl-amino
esters under mild conditions, thus leading to broad functional group
tolerance. The expedient access to biologically active motifs demonstrates
the practicality of this protocol by reducing the number of synthetic
steps and enhancing the reaction efficiency.