Nickel-Catalyzed anti-Markovnikov Hydroalkylation of Trifluoromethylalkenes

Transition-metal-catalyzed difunctionalization of olefins constitutes a fertile synthetic platform for rapid access to complex molecules from bulk chemicals. However, substrates featuring fluoroalkyl substituents are rarely employed because of facile beta-fluoride elimination pathways. Herein, we report a hydroalkylation of trifluoromethylalkenes with alkyl halides under nickel catalysis that enables the rapid construction of 1,1,1-trifluoropropane derivatives. The common beta-fluoride elimination pathway is suppressed by identifying a competent proton donor that favors a protonolysis process. Also, unactivated alkenes could be readily employed as the alkyl donor when using a Ni/hydrosilane catalytic system.

Automated summary

Transition-metal-catalyzed difunctionalization of olefins is a powerful method to access complex molecules from bulk chemicals. In this study, a hydroalkylation reaction of trifluoromethylalkenes with alkyl halides under nickel catalysis was developed, leading to the efficient construction of 1,1,1-trifluoropropane derivatives. The commonly observed beta-fluoride elimination pathway was suppressed by using a competent proton donor, enabling the use of substrates featuring fluoroalkyl substituents.