Ni-Catalyzed Reductive Cross-Coupling Of Unactivated Alkyl Halides

We have discovered an efficient Ni-catalyzed reductive cross-coupling of alkylelectrophiles for the construction of C(sp~3)–C(sp~3) bonds. The reactions are undermild conditions and exhibit excellent functional group tolerance. Our method alsodisplays high chemoselectivity between two different alkyl electrophiles and providescoupling products in good to excellent yields. The distinctive feautures of this methodare highlighted as follows.1) Use of bis(pinacolato)diboron as the terminal reductant allows efficientNi-catalyzed coupling of unactivated secondary and primary alkyl halides, generatingthe C(sp~3)–C(sp~3) coupling products in good yields. The catalytic conditions are mild,and the combination of NiI2and8a is not essential.2) The present mild, easy-to-handle reductive coupling displays a goodchemoselectivities which require only1.5equiv of alkyl halide as a coupling partner.The reaction conditions are compatible to many functional groups such as ester, acetal,ketone, sulfonamide, siloxane, etc.3) A comparison with Fu’s alkyl borylation procedure indicates that bases (LiOMe vsKOEt) and ligand8a have more profound impact on selecting borylation and couplingpathways than other reaction parameters. Our preliminary studies suggest an in situalkylboronate ester/Suzuki process is less likely. Instead, we propose a mechanisminvolving double oxidative addition of alkyl halides to Ni(I). The formation ofNi–Bpin complexes may be the key in differentiating the coupling alkyl partners.