Photocatalytic reductive carboxylation of unactivated hydrazones with CO₂

Carboxylation with CO₂ is one of the most sustainable strategies for synthesizing carboxylic acids. Particularly, the reductive carboxylation of carbonyl derivatives with CO₂ offers a promising route to valuable α-hydroxy acids, α-amino acids and relatives. However, catalytic methods for this transformation remain underexplored and predominantly limited to carboxylation of activated carbonyl derivatives, which rely on the generation of stabilized organometallic intermediates or carbanions to react with CO₂. In this study, we report a reductive carboxylation of unactivated hydrazones with CO₂ via visible-light photocatalysis. Diverse unactivated hydrazones, such as dialkyl substituted ketone hydrazones, cyclic ketone hydrazones and alkyl aldehyde hydrazones, are all suitable for such a carboxylation. The process enables the efficient synthesis of diverse valuable α-hydrazino acids in good yields via selective cleavage of C = N π bond, distinguishing it from prior hydrazone carboxylation methods, which typically involve C = N double bond cleavage. Moreover, this protocol exhibits mild reaction conditions, good functional group tolerance, easy scale up and facile derivatization of products into α-amino acids. Mechanistic investigations and density functional theory (DFT) calculations support the radical addition of CO₂ radical anion to C = N bonds, which represents a unique umpolung strategy for reductive carboxylation with CO₂.