Singha Tushar, Kadam Ganesh Arjun, Hari Durga Prasad
Department of Organic Chemistry, Indian Institute of Science Bangalore 560012 India
Chem Sci. 2023 May 25;14(25):6930-6935. doi: 10.1039/d3sc01908j. eCollection 2023 Jun 28.
The Dowd-Beckwith reaction, a ring-expansion of carbonyl compounds 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.
多德-贝克威思反应，即羰基化合物与烷氧基自由基的扩环反应，是合成中大型碳环骨架的有效方法，该反应利用现有的环结构，避免了端到端环化策略中出现的熵和焓因素。然而，多德-贝克威思扩环反应随后的氢原子提取仍然是主要途径，这阻碍了其合成应用，目前尚无关于使用非碳基亲核试剂对扩环自由基进行官能化的报道。在此，我们报道了一种氧化还原中性的脱羧多德-贝克威思/自由基-极性交叉（RPC）序列，该序列可提供具有广泛官能团耐受性的官能化中型碳环化合物。该反应允许4、5、6、7和8元环底物进行单碳扩环，也可应用于三碳链的引入，从而实现中型环的远程官能化。
