Late-Stage Carbonyl Removal via Sequential Double Carbon–Carbon Bond Cleavage
Abstract
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.
Fields of Study & Subjects
Chemical Reactions and Isotopes
Advanced Synthetic Organic Chemistry
Catalytic C–H Functionalization Methods
Publication details
- Journal / source
- Journal of the American Chemical Society
- Publisher
- American Chemical Society (ACS)
- Volume
- 148
- Issue
- 27
- Pages
- 28061–28067
- Publication date
- 4 July 2026
- Language
- EN