Cobalt Macrocycle-Catalyzed Electrochemical Coupling Reactions

在亲电性试剂存在下，双卤化物的电化学还原对于合成单取代和双取代材料有几个缺点(化学选择性和立体选择性较差)。这一过程将由钴(I)大环络合物催化，包括维生素B12、双水杨基乙二胺钴和钴肟。该策略是将钴物种还原到活性钴(I)状态，预计该状态将与介质中的双卤化物进行快速氧化加成。生成的加合物，一种Co(III)物种，将被原位还原，以喷射所需的碳负离子，以便与介质中的电泳体反应。实际上，钴大循环将催化将双卤化物还原为相应的α-卤代碳离子。催化过程的立体选择性和化学选择性比直接电化学过程高得多，并允许通过直接过程进行根本不可能的转化。此外，通过在Co(I)发生氧化加成但Co(III)加合物稳定的电位下进行电解，可以通过后者的热或光化学分解来生成自由基。根据这些原理，将进行一些合成应用，包括双卤化物(包括开链和环状体系)上的还原亲电取代，取代环丙烷、芳烃和多环体系的合成，以及烯烃的合成。这些原理将进一步扩展到从烷基卤化物以外的底物中电催化生成碳负离子。有机合成计划支持这项研究，以发展钴大环催化的电化学偶联反应。这项研究将导致一条合成有用的活性中间体的新的新途径，这些中间体可以用来合成我们经济所需的日益复杂的物质。

The electrochemical reduction of geminal dihalides in the presence of electrophilic reagents has several disadvantages (poor chemoselectivity and stereoselectivity) for the synthesis of mono-and bis-substituted materials. The process will be catalyzed with cobalt (I) macrocyclic complexes, including vitamin B12, cobalt bis-salicylideneethylenediamine, and cobaloximes. The strategy is to reduce the cobalt species to the reactive Co(I) state, which is expected to undergo rapid oxidative addition with a geminal dihalide in the medium. The resulting adduct, a Co(III) species, will be reduced in situ to eject the desired carbanion for reaction with an electrophile in the medium. In effect, the cobalt macrocycle will catalyze the reduction of the geminal halide to the corresponding alpha-halocarbanion. The catalytic process is expected to occur in far higher stereoselectivity and chemoselectivity than the direct electrochemical process, and permit conversions not possible at all by the direct process. Furthermore, by carrying out the electrolysis at potentials where oxidative addition to Co(I) takes place but the Co(III) adduct is stable, it will be possible to make radicals by thermal or photochemical decomposition of the latter. A number of synthetic applications, including reductive electrophilic substitution on geminal dihalides (including both open chain and cyclic systems), synthesis of substituted cyclopropanes, arenes, and polycyclic systems, and synthesis of alkenes, based on these principles, will be undertaken. These principles will be further extended to electrocatalytic generation of carbanions from substrates other than alkyl halides. The Organic Synthesis Program is supporting this research to develop cobalt macrocycle-catalyzed electrochemical coupling reactions. This research will lead to a new and novel route to synthetically useful reactive intermediates that can be used to synthesize the increasingly complex substances needed in our economy.