The Dowd-Beckwith Reaction: History, Strategies, and Synthetic Potential.

Ring-expansion strategies are valuable synthetic tools that take benefit of existing ring structures and evade the unfavorable enthalpic-and entropic effects that arise with end-to-end cyclizations. One potentially important class of such reactions is the Dowd-Beckwith reaction, the ring-expansion of ketones via alkoxy radicals. The exciting advancement in this research area is starting to show its potential, as demonstrated by applying this methodology in strategy-level bond formation to synthesize complex natural products. This Review aims to provide the first comprehensive survey of the development of the Dowd-Beckwith reaction spanning three decades from the initial report to the present day, thus providing the readers with great detail about the contributions of this reaction to organic synthesis. We hope that this review will further disclose the salient features of the Dowd-Beckwith reaction for synthetic applications and encourage the development of new, more advanced applications.

A highly diastereoselective strain-release Doyle-Kirmse reaction: access to functionalized difluoro(methylene)cyclopropanes.

Difluoro(methylene)cyclopropanes (F2MCPs) show better anti-cancer properties and chemical reactivities compared to their nonfluorinated analogues. However, catalytic stereoselective methods to access these privileged motifs still remain a challenging goal. The Doyle-Kirmse reaction is a powerful strategy for the concomitant formation of carbon-carbon and carbon-sulfur bonds. Although the enantioselective variants of this reaction have been achieved with high levels of selectivity, the methods that control the diastereoselectivity have been only moderately successful. Herein, we report a catalytic, highly diastereoselective strain-release Doyle-Kirmse reaction for synthesizing functionalized F2MCPs using an inexpensive copper catalyst. The transformation proceeds under mild conditions and displays excellent functional group compatibility on both diazo compounds and difluorocyclopropenyl methyl sulfane/selane derivatives. Furthermore, the obtained products were efficiently transformed into valuable building blocks, such as functionalized spiroheterocycles, difluorocyclopropanes, and skipped dienes.