Transition Metal-catalyzed Heck-type Reactions Of Non-activated Olefins With Controllable Regioselectivit

The Mizoroki-Heck reaction is considered as one of the most important methods for constructing C-C bonds,which is widely used in the synthesis of natural products,pharmaceuticals,daily necessities,and advanced materials over the last few decades.Professor R.F.Heck shared the 2010 Nobel Prize in Chemistry for his fundamental contribution in this reaction.The traditional Heck reaction generally refers to the coupling of activated alkenes such as styrene,acrylate,and alkenyl ethers with aryl/alkenyl(pseudo)halides in the presence of transition metal catalysts.In contrast,the intermolecular Heck reaction of unactivated alkenes and alkyl(pseudo)halides has been far less explored,being attributed to the intrinsic low reactivity of electronically unbiased olefins as well as the difficulty in controlling the regioselectivity with several detachable hydrogens in β-H elimination step,which will lead to the formation of several inseparable regioisomers.In our preliminary work,a strategy combining directing group and the radical chemistry was successfully utilized to achieve the first intermolecular Heck-type reaction of unactivated alkenes and alkyl electrophilic reagents,and single regioisomer was obtained.The aim of this thesis is to conduct more comprehensive research on the factors influencing regioselective control in Heck-type reaction and obtain different types of internal alkenes compounds.The major challenge lies in completely distinguishing the multiple detachable hydrogen atoms at the β position of the reaction intermediate,which requires extremely precise control of the reaction conditions.In this thesis,the β-hydrogen elimination process of directing groups-stablized trivalent copper intermediate is well controlled by simply varying the external additives,while a combination strategy has been successfully utilized to control the selective H-X elimination of the atom transfer radical addition(ATRA)adduct;both ultimately lead to the regioselective Heck-type reaction between unactivated alkenes and alkyl electrophilic reagents.The main chapters of this paper are divided as following:In Chapter 1,the author will give a thorough overview of the significant advancements in Heck-type reaction of unactivated alkenes,including the intramolecular Heck-type reactions of unactivated alkenes,the intermolecular Heck-type reactions of unactivated alkenes and aryl reagents,as well as the intermolecular Heck-type reactions of unactivated alkenes and alkyl reagents.In Chapter 2,on the basis of previous work,the addition of different external additives and a combination strategy have been proposed,respectively,to overcome the difficulty in distinguishing the multiple detachable β-hydrogens,which would eventually fill the gap in regiodivergent Heck-type reaction of unactivated alkenes and alkyl electrophilic reagents.In Chapter 3,divergent regioselective intermolecular Heck-type reaction of unactivated alkenes and alkyl electrophilic reagents has been enabled by directing-group-based strategy.With the assistance of copper catalyst and directing group,N-fluorosulfonamides were utilized as the alkyl electrophilic reagents to efficiently couple with unactivated alkenes and conveniently obtain allylation or allylation coupling products by varying the external additives.In Chapter 4,cobalt-catalyzed regiodivergent Heck-type reaction of unactivated alkenes has been reported.Further extending the regiocontrollable intermolecular Heck-type reaction to simple unactivated alkenes can effectively avoid the use of directing groups.By employing cobalt catalyst and fluoroalkyl bromides as the alkyl electrophilic reagents,the electronically distinct β-hydrogen atoms of ATRA adduct allowed for subsequent tunable H-Br elimination via a portfolio strategy,wherein the external base promoted thermal E2 elimination of acidic H atom to generate vinyl product,while with an external ligand,β-H elimination of cobalt(III)-alkyl species preferred electron-rich H atom to deliver unprecedented contra-thermodynamic allylic product.In Chapter 5,a facile synthesis of α,β-unsaturated imines via palladium-catalyzed successive dehydrogenation has been realized.During the study of Heck-type reactions using N-fluorosulfonamide as the alkyl electrophilic reagents,an unexpected palladium-catalyzed successive dehydrogenation of N-fluorosulfonamide has been discovered for the efficient construction ofα,β-unsaturated imines.This is the first case to employ palladium catalyst in the functionalization of N-fluoro-sulfonamides.It is remarkable that through a two-step strategy combining pre-fluorination and this successive dehydrogenation reaction,the abundant simple aliphatic amides are allowed for the rapid construction of complex molecular architectures to forge versatile α,β-unsaturated imines.The synthetic utility of this transformation was further demonstrated by a diversity-oriented derivatization and a concise formal synthesis of(±)-alloyohimbane.