Highly Enantiodelective Intramolecular Reductive Cyclization Catalyzed By Ni/P-Chiral Ligand

The structure of allyl alcohol is an important part of organic synthesis.This structure fragment is widely used in natural products and medicines with its biological activity,and it is also a common intermediate in various synthetic transformations.Transition metal-catalyzed intramolecular reductive coupling and cyclization of alkynone compounds is an effective method to construct cycloallyl alcohol in current organic chemical synthesis.The earliest research in reductive coupling of alkynone mainly focused on expensive and heavily polluted precious metals such as Pd and Rh,whose shortcomings limited its large-scale application in industry.However,transition metals such as Ni and Cu have abundant reserves with lower prices,which are always been regarded as the ideal substitutes for precious metals such as Pd.In this work,we have exploited a Ni/P-chiral ligand catalyzed high enantioselective synthesis of tetrahydrofuran and chroman structure with a chiral tertiary allyl alcohol（silyl ether）structure that has important application values in biology and medicine areas.The first part of this work reported the Ni/（S,S）-DI-BIDIME catalyzed intramolecular reductive cyclization of highly enantioselective O-alkynone compounds with a separation yield parameter reach up to 99%and over 99:1er which have synthesized a variety of tetrahydrofuran derivatives containing chiral tertiary allyl alcohol.The study of the mechanism shows that the transition state of the dimer Ni（II）ring in the cycloaddition stage is the key step in determining the enantioselectivity,and the ligand（S,S）-DI-BIDIME play an important role in providing a largeπ-conjugated system and spatial interaction.At the same time,the new reaction that we discovered in this study also achieved a moderate yield parameter and 98:2 er enantioselectivity under the catalysis of this catalytic system.The second part of this work reported the high-efficiency and high enantioselective synthesis of Ni/（R）-Ant Phos catalyzed with the chroman of chiral tertiary allylic siloxanes structure for the first time.The reaction has a good general applicability,and it has a good tolerance ability in different electrical properties,different positions,different steric hindrances,and heterocyclic substituents.The yield parameter of this reaction reached 98%,and over 99:1 er enantioselectivity have been accomplished at the same time.It has no effect on the high-efficiency with expand the reaction in a gram scale and remove the triethylsilyl enantioselectivity.Finally,by trying different types of reducing agents,the author found that the commonly used reducing agent Zn Et₂was inactive.When HBpin was used as a reducing agent,a better yield parameter and 90:10 er were obtained,which shows that if change the reducing agents,it will have a great influence on the reaction.In general,we developed Ni/P-chiral ligand catalyzed high enantioselective intramolecular reductive coupling to synthesize tetrahydrofuran and chroman with chiral tertiary allyl alcohol（silyl ether）structure with the use of cheap and easily available raw materials.This reaction has an excellent substrate compatibility,high activity and excellent enantioselectivity and it can be widely used in the synthesis of biologically active natural products and drugs.Besides,this reaction has important research significance in medicine and biology fields.We have also discovered new reactions in our work,and then we will further study them in depth.