NiH-Catalyzed Asymmetric1,2-Reduction Of α,β-Unsaturated Ketones,Reductive Migratory Arylation And Defluorinative Allylation Of Olefins

The first-row transition metals are cheap and readily available.Over the past two decades,their metal hydride chemistry has attracted the increasing attention of synthetic chemists.Metal hydride such as Fe H,Co H,Cu H has developed rapidly.In contrast,Ni H chemistry is a new field yet to be developed with rich chemistry and potential application value.This thesis focuses on Ni H chemistry,the content of this thesis includes three parts:asymmetric 1,2-reduction ofα,β-unsaturated ketone,reductive migratory arylation and defluorinative allylation of olefins catalyzed by Ni H.In the first part,we have developed a reductive Ni H system for the enantioselective1,2-reduction ofα,β-unsaturated ketones to produce chiral allylic alcohols,a privileged scaffold in natural products and drug molecules.This mild process,which makes use of easily prepared ~tBu-Pmrox ligand and abundant nickel catalyst,represents a general method to access a wide variety of structurally diversea-chiral allylic alcohols in excellent yields and enatioselectivity,as well as very high levels of ambidoselectivity for 1,2-over 1,4-reduction.Our system can also easily achieve gram scale-up experiments with low catalyst loading(0.5 mol%).In the second part,we reported a Ni H-catalyzed reductive migratory cross-electrophile-coupling between alkyl bromides and aryl bromides.Chain-walking is promoted by Ni H generated in situ from alkyl bromide.When stoichiometric amount of ~nPr Br and manganese powder are used as hydride source,olefins could be used instead of alkyl bromides to achieve remote hydroarylation with benzylic selectivity.Finally,preliminary mechanism studies show that:a)olefin isomerization and arylation are two independent processes;b)Ni H can dissociate during the process of olefin isomerization;C)benzylic Ni(Ⅲ)species exists in rapid equilibrium with the Ni(Ⅱ)complex and the benzylic radical before reductive elimination.In the third part,we developed a nickel hydride catalyzed migratory defluorinative coupling between two electronically-differentiated olefins.A broad scope of unactivated donor olefins can be joined directly to acceptor olefins containing an electron-deficient trifluoromethyl-substituent in both intra-and intermolecular fashions to form gem-difluoroalkenes.This migratory coupling has both site-and chemoselectivity under mild conditions,with the formation of a tertiary or quaternary carbon center.Finally,preliminary mechanistic studies show that:a)Ni H does not dissociate from olefins during the chain-walking process,which is different from our previously reported migratory arylation;c)The regioselectivity depends on the stability of the alkyl radical intermediates.