Late-Stage Carbonyl Removal via Sequential Double Carbon-Carbon Bond Cleavage

The direct removal of carbonyl groups from cyclic ketones offers a nonintuitive but straightforward route to access multisubstituted saturated structural motifs via late-stage modification. However, such transformations have been challenging to achieve, especially in a chemoselective manner. Here we report reductive and annulative carbonyl removal methods, enabled by the N'-alkyl hydrazonamide (NAHA) reagents, via sequential double C-C bond cleavage. These transformations efficiently convert diverse cyclic ketones to the corresponding ring-opened and ring-contracted analogues with broad functional group tolerance. Besides late-stage modification of complex bioactive compounds, this carbonyl-removal strategy can also be applied to the synthesis of all-carbon quaternary centers lacking polar functional groups, terminal deuteration, and iterative ring contraction.