Enantioselective Nickel-Electrocatalyzed Cross-Dehydrogenative α- and γ-Nitroalkylation

J Am Chem Soc. 2024 Nov 22. doi: 10.1021/jacs.4c13109. Online ahead of print.

Abstract

Asymmetric catalytic versions of electricity-driven processes hold immense potential for the sustainable preparation of chiral compounds. However, the involvement of anodic oxidative cross-dehydrogenative coupling events between two distinct nucleophiles makes it challenging for a chiral catalyst to regulate the stereochemistry of the products. Our current electrocatalytic strategy for enantioconvergent cross-dehydrogenative α- and γ-nitroalkylation via radical-based pathways produces an array of enantioenriched nitroesters without supplementary stoichiometric oxidants. Mechanistic investigations reveal that the nickel catalyst plays a key role in both the electrochemical activation of the substrates and the stereoselectivity-defining events, affording the electrochemically generated Lewis acid-bound α-carbonyl radicals to interact with in situ-generated nitronate anions in a stereoselective manner. This electrocatalytic approach enables transformations that are highly challenging under thermal conditions, such as umpolung reactivity with readily available substrates, all-carbon quaternary stereocenter creation, and the control of remote stereochemistry.