Photocatalyzed Dowd-Beckwith radical-polar crossover reaction for the synthesis of medium-sized carbocyclic compounds

The Dowd-Beckwith reaction, a ring-expansion of carbonyl compounds via alkoxy radicals, is a powerful approach for synthesizing medium to large-sized carbocyclic scaffolds, which takes advantage of existing ring structures and avoids entropic and enthalpic factors that arise from the end-to-end cyclization strategies. However, the Dowd-Beckwith ring-expansion followed by H-atom abstraction is still the dominating pathway, which hampers its synthetic applications, and there currently exist no reports on the functionalization of ring-expanded radicals using non-carbon based nucleophilic reagents. Herein, we report a redox-neutral decarboxylative Dowd-Beckwith/radical-polar crossover (RPC) sequence that delivers functionalized medium-sized carbocyclic compounds with broad functional group tolerance. The reaction allows one-carbon ring-expansion of 4-, 5-, 6-, 7-, and 8-membered ring substrates and can also be applied to three-carbon chain incorporation, enabling remote functionalization in medium-sized rings.

Automated summary

The Dowd-Beckwith reaction is a powerful method for synthesizing medium to large-sized carbocyclic scaffolds by ring-expansion of carbonyl compounds via alkoxy radicals. However, its synthetic applications are hampered by the dominating pathway of Dowd-Beckwith ring-expansion followed by H-atom abstraction, and there is currently no report on the functionalization of ring-expanded radicals using non-carbon based nucleophilic reagents.