Despite the fact that metal-catalyzed asymmetric alkylative
cross-couplings
have been well-established, enantioselective alkylative substitution
of an unactivated C–O bond remains a challenge due to the lack
of strategies to cleave the C–O bond and suppress β-H
elimination as well as control stereochemistry simultaneously. Herein,
the enantioselective alkylative activation of an unactivated C–O
bond with β-H-containing alkylating reagents was described using
a chiral nickel catalyst, and versatile axially chiral biaryls bearing
alkyl moieties with different chain lengths were delivered in good
yields and with high ee. Control experiments demonstrated the significant
role of the solvent tetrahydrofuran to facilitate this transformation.
DFT calculations revealed that the coordination of THF to Mg(II) is
pivotal for suppressing β-H elimination during reductive elimination,
thus unlocking how the solvent molecule affects the competing β-H
elimination and reductive elimination dynamics in transition-metal-catalyzed
alkylative cross-coupling reactions.