Mechanistic Basis for Divergent Stereoselectivity in Intramolecular Ni-Catalyzed Cross-Electrophile Coupling Reactions

Nickel-catalyzed asymmetric coupling reactions are known
to proceed
through both stereospecific and stereoablative mechanisms. Herein,
we report a mechanistic investigation of a previously reported Ni-catalyzed
cross-electrophile coupling reaction that proceeds via divergent mechanisms
with different stereochemical outcomes. Depending on the benzylic
substituent, from the same organonickel intermediate, competing rates
of transmetalation or single electron transfer shunt the reaction
to either pathway. For one substrate, the formation of an arylzinc
intermediate dominates. This intermediate subsequently participates
in intramolecular Negishi coupling, which is an enantiospecific reaction.
For another substrate, single electron transfer outcompetes transmetalation,
triggering a sequential reduction mechanism, a stereoablative pathway.

已知镍催化不对称偶联反应可通过立体专一性与立体消旋化两种机制进行。本文针对此前已报道的镍催化交叉亲电偶联反应开展机理研究，该反应可通过不同机理进行，且呈现不同的立体化学结果。根据苄位取代基的不同，同一有机镍中间体可通过转金属化与单电子转移的竞争速率，将反应分流至两条不同路径。对于一类底物，芳基锌中间体的形成占主导地位，该中间体随后参与分子内根岸偶联（Negishi coupling）反应，该过程为对映专一性反应。而对于另一类底物，单电子转移的速率超过转金属化，从而触发分步还原机制，即立体消旋化路径。