Theoretical Investigation on Ni-Catalyzed C(sp3)–F Activation and Ring Contraction of Tetrahydropyrans: Exploration of an SN2 Pathway

DFT calculations were conducted to elucidate the mechanistic details of a recently reported cross-electrophile coupling (i.e., XEC) reaction, in which a stable C(sp3)–F bond was successfully cleaved and a ring contraction from six-membered tetrahydropyran to three-membered cyclopropane was realized. Our theoretical investigation highlights the critical role that the Grignard reagents play. Despite being a reducing agent, the RMgX also helps to promote the C(sp3)–O cleavage while breaking the tetrahydropyran ring and to activate the C(sp3)–F bond to furnish the final recyclization. The cleavage of the C(sp3)–F bond follows an SN2-type reaction, so that a chirality inversion of the carbon can be ensured. Regarding the details of the cross-coupling between two electrophiles, the pathway involving radicals is not possible for this system. According to our calculations, this reaction in fact follows an unconventional Tsuji–Trost reaction, which means that, rather than being attacked by a nucleophile, the termi...