Studies On The Carbon-Carbon Bond-Forming Reactions Via Activation Of Benzylic Carbon-Oxygen Bonds Catalyzed By Nickel

Cross coupling reactions are one of the most effective methods for constructing C-C bonds. Compounds bearing active C-X or C-B bonds are usually used as the coupling partners, which suffer from some shortcomings like difficulty in preparation, high cost and nonenvironmental friendliness. Compared with transformation of those active bonds, direct activation and functionalization of inert bonds(C-H and C-O bonds) are more straightforward for synthesis of functional molecules, avoiding pre-functionalization of starting materials, featuring high atomic economy and environmental friendliness, and thus meeting the requirements of the modern green chemistry.Benzyloxic compounds are recongnized as one of alternative electrophiles to halocompounds for constructing C-C bonds and C-Z bonds due to their easy avaliability and low toxicity. This paper focuses on functionalization of benzylic ester compounds. A series of facile and efficent methods for constructing C-C bonds by nickel catalyzed cross couplings between benzyloxic compounds and hydrocarbons have been developed. The research contents come as follows:1. Preparation of fluorinated-containing and nitrogen-containing heterocyclic diarylmethanes via nickel catalyzed sp3C-O/sp2C-H cross coupling.A Ni-catalyzed C–O/C–H cross coupling of benzylic alcohol derivatives(pivalates and carbamates) with polyfluoroarenes producing the corresponding fluoroaryl-containing diarylmethanes was described. This transformation has a good functional-group tolerance and various functional group, such as methyl, ester, amine, Me O, CF3 and amide all were tolerated well under this reaction conditions. By employing the present nickel-catalyzed C-O/C-H cross coupling, high molecule-weight linear compounds containing fluorobenzene units which have potential applications as liquid crystal materials were also synthesized. By switching the ligand dppb to strong electron-donating and low steric PEt3, the cross coupling of heteroarenes with benzylic alcohol derivatives was also achieved under the similar reaction conditions, affording the corresponding heteroarenes-contaning diarylmethanes. Kinetic isotope effect(KIE) experiments indicated that C–H activation would not be the rate-determining step in the reaction. A plausible mechanism was also proposed.2. Preparation of α-benzylated arylacetonnitriles via nickel catalyzed sp3C-O/sp3C-H cross couplingA Ni-catalyzed C–O/C–H cross coupling of benzylic alcohol derivatives(pivalates, carbamates and carbonates) with arylacetonitriles to generate α-benzylated arylacetonnitriles in good yields was described. This transformation has a good functional-group tolerance, Me, Ph, Me O, ester, amine, F, CF3, CN and carbonyl all were compatible in this catalytic system. Bulky secondary benzylic esters and secondary arylacetonitriles also served well as the substrates to produce the coupling products bearing quaternary carbon center, which provided a potential way to construct the chiral quaternary carbon center. By switching the ligand binap to strong electron-donating and low steric dcype, the coupling of arylacetonitriles with the benzylic alcohol derivatives also took place efficiently under the similar reaction conditions, readily generating the corresponding α-benzylated arylacetonnitriles.3. Ni-catalyzed α-benzylation of aryl methyl sufones via sp3C-O/sp2C-H cross coupling.A Ni-catalyzed C–O/C–H cross coupling of benzylic alcohol derivatives(pivalates and carbonates) with sulfones generating α-benzylated sulfones under the facile and mild reaction conditions was described. The simple Ni(COD)2 without external ligand enables this transformation to proceed completely in half an hour. This reaction could also be performed at gram scale without decrease of catalytic efficiency. The building block for the bioactive compound eletriptan was synthesized easily by using this strategy. KIE experiments indicated that C–H functionalization would not be the rate-determining step in the reaction. A plausible mechanism was proposed.4. Ni-catalyzed synthesis of(E)-olefins via benzylic C-O activationA Ni-catalyzed selective synthesis of(E)-olefins using the readily available benzylic alcohol derivatives and arylacetonitriles via sp3C-O activation was described. By employing this C-O activation strategy, the precurses of resveratrol and scintillator 1,4-bis((E)-2-methylstyryl)benzene were synthesized. The pharmaceutical adapalene could also be modified. Mechanism studies indicated that this transformation should proceed via a tandem process. α-Alkylated nitriles were firstly generated by nickel-catalyzed cross coupling of benzylic alcohol derivatives with arylacetonitriles via C-O activation. Subsequent stereoselective E2 elimination of the resulting α-alkylated nitriles produced the corresponding product(E)-olefins.