Nickel-catalyzed cross-couplings via activation of carbon-oxygen and carbon-nitrogen bond

Abstract

This dissertation focuses on nickel-catalyzed cross-couplings via carbon– oxygen and carbon–nitrogen bond activation. These methods transform readily available benzylic alcohol derivatives (in enantioenriched form) and alkyl amine derivatives into high-value products. ☐ Chapter 1 describes a nickel-catalyzed stereospecific vinylation of tertiary benzylic carboxylates. Under our practical conditions, an inexpensive, air-stable nickel precatalyst Ni(acac)2·xH2O is used as the sole catalyst, and exogenous ligand is not required. A variety of styrenyl and alkyl vinyl boronates are tolerated in high yields and stereochemical fidelity. Worth noting, this method works with simple phenyl- substituted benzylic carboxylates, as well as naphthyl-substituted substrates. ☐ Chapter 2 describes a nickel-catalyzed stereospecific arylation of tertiary benzylic carboxylates. In the presence of catalytic Ni(OAc)2·4H2O and a stilbene, phenyl-substituted benzylic carboxylates undergo efficient transformation to highly enantioenriched products with diaryl quaternary stereocenters. This method overcomes the long-standing “Naphthyl Requirement” in this field. All-carbon quaternary stereocenters are formed in high yields and high stereochemical fidelity. ☐ Chapter 3 describes a nickel-catalyzed deaminative cyanation of Katritzky pyridinium salts. A Ni/Xantphos catalyst system was developed to efficiently transform alkyl amines to corresponding alkyl nitriles via C–N bond activation. This method tolerates broad scope, and even performs well in late-stage functionalization, which may give a potentially useful tool in the drug discovery synthesis toolbox.