Nickel-Catalyzed Reductive Ring Opening Reactions

Being one of the most important organic reactions,ring opening reactions of cyclic compounds enable the efficient conversion of simple and readily available cyclic molecules into various types of multifunctional compounds,providing building blocks for the synthesis of compounds with more complex structures.On the other hand,transition metal-catalyzed cross-electrophile coupling reactions are bestowed with the merits of high functional group tolerance and mild reaction conditions,and have experienced a surge of developments in recent years.Combining cross-electrophile coupling and ring opening reactions of cyclic compounds under reducing conditions represents a novel ring-opening strategy with numerous advantages.The implementation of this strategy can avoid the use of pregenerated organometallics in the construction of carbon-carbon bonds,leading to high compatiblity with electrophilic functional groups.Therefore,contributions to develop this ring opening strategy is of high significance.Unlike the well-established traditional nucleophilic ring opening reactions,the development of reductive ring opening reactions lags behind due to lacking reliable activation modes to overturn the intrinsic nature of the precursors.To date,the substrates for reductive ring opening reactions are mainly limited to small heterocycles,while the carbocycles and heterocycles are rarely employed as the precurors.In the first chapter of this paper,we will introduce the develepment of reductive ring opening reactions of small heterocycles.Cyclobutanone oxime esters and cyclobutanones are susceptible to ring-opening reactions via carbon-carbon bond cleavage due to their high strain energy.However,all the reported ring-opening reactions involving cycloketone oxime esters or cyclobutanones proceed in redox-neutral pathways.In this dissertation,we achieved the reductive ring-opening reaction of cyclobutanone oxime esters with aryl chlorides in high yield and regioselectivity under nickel catalysis as well as the asymmetric reductive ring-opening reaction of cyclobutanone in high enantioselectivity,which provides a novel approach to carbon-carbon bond cleavage and reassembly.Two classes of heterocyclic compounds,benzofurans and oxa-and azabicyclic alkenes,can undergo ring-opening reactions through β-heteroatom elimination,giving various useful styrene derivatives.Therefore,they are very commonly used building blocks in organic synthesis.In this context,we used alkyl halides as electrophilies under nickel catalysis to achieve reductive ring opening of benzofurans in good yields and asymmetric reductive ring opening of oxa-and azabicyclic alkenes in high yields and enantioselectivity.This method further expands the variety of cyclic compounds in reductive ring opening reactions.We successfully used nickel catalysis to extend the scope of cyclic compounds in reductive ring opening reactions to carbocycles and unstrained heterocycles.In addition,different kinds of electrophilic reagents,such as aroyl chlorides,alkyl halides,and aryl halides were introduced into our reductive ring-opening reactions to further enrich the arsenal of this strategy.The preliminary mechanistic study provides us more insight into the reductive ring-opening reaction and laid the foundation for the further development of the strategy.