Synthesis through C(sp)-C(sp) Bond Scission in Alkenes and Ketones.

ConspectusThe homolytic cleavage of C-C bonds adjacent to functional groups has recently become a popular strategy for restructuring the skeletons of complex organic molecules. In contrast to the traditional reactivity profiles of polar bond disconnections, homolytic scission furnishes carbon-centered free radicals primed for controlled termination with a diverse range of radicophiles. Beyond standard radical capture, transition-metal catalysis facilitates sophisticated C-C and C-heteroatom bond-forming reactions. Intensive efforts have been focused over many years into the cleavage of the neighboring C-C bonds of carboxylic acids and alcohols. Despite the ubiquity of alkenes and ketones in natural products, feedstock chemicals, and common synthetic intermediates, much less attention has been paid to exploiting their potential in diversifying chiral pool materials, such as terpenes and terpenoids. Defunctionalization in this manner is a powerful approach for synthesizing high-value chemicals and advanced synthetic intermediates because of the possibility to reconstruct and further decorate chirality-bearing carbon skeletons. Motivated by synthetic necessity, since 2018 our group has focused on developing ozonolysis-based dealkenylative molecular diversification, and we expanded into deacylation in 2025. In this Account, we chronicle our initial motivation, describe the historical background, and summarize our research into dealkenylative and deacylative synthesis. Our dealkenylative approach capitalizes on the ozonolysis of alkenes in MeOH to generate α-methoxyhydroperoxides primed for a reaction with reducing agents. Their reduction through single electron transfer, mediated by a transition metal, leads to the formation of an alkoxyl radical that undergoes rapid β-scission, furnishing both a carbon-centered free radical and an ester group derived from the acetal carbon atom. The produced free radical can be strategically terminated by radicophiles, thereby delivering remodeled chiral molecules. Using this concept, we have developed hydrodealkenylation (through hydrogen atom transfer from benzenethiol), dealkenylative thiylation (through thiyl group transfer from diaryl disulfides), alkenylation (through addition/elimination with nitrostyrenes), and oxodealkenylation (through treatment with TEMPO followed by oxidation). Furthermore, kinetic analysis has enabled the development of a catalytic Fe/vitamin C system for dealkenylative alkynylation and halodealkenylation. Synergizing ozonolysis and copper catalysis has recently enabled aminodealkenylation through net-redox-neutral C-C cleavage followed by C-N bond formation. Although the high oxidation potential of ozone relative to organic compounds makes alkene-to-peroxide conversion possible, it also limits the applicability of dealkenylative techniques for substrates featuring ozone-sensitive functional groups. We recently overcame this constraint by first applying Isayama-Mukayiama peroxidation to olefins and then using a novel catalytic system─catalytic Fe and PhSH with stoichiometric γ-terpinene─for ozone-free hydrodealkenylation. Beyond alkenes, we have developed a straightforward methodology for the homolytic deacylative cleavage of ketones as well, including cycloalkanones. This process is applicable in total syntheses and in the late-stage modifications of complex ketone-containing natural products.