Directed Copper-catalyzed Intermolecular Heck-type Reaction Of Alkyl Halides And Unactivated Olefins

The Mizoroki-Heck reaction is one of the most efficient methods for constructing carbon-carbon bonds,and has been widely used in the synthesis of pharmaceutical active molecules and natural products,preparation of fine chemicals,agricultural chemicals as well as advanced materials in the past few decades.However,the Heck reaction is still limited to the coupling of C(sp~2)-X compounds(X is a halogen or sulfonate,etc.)with activated olefins such as styrenes and electron-withdrawing or electron donating olefins.The intermolecular Heck type reaction of alkyl halides with non-activated olefins has not been reported due to the following problems:1)the slow oxidation addition rates of C(sp~3)-X(X=halogen,sulfonate)compounds with transition metal catalysts and the carbon metal complex formed is easy to go throughβ-H elimination,2)the regioselectivity and stereoselectivity is difficult to control during theβ-H elimination step.In this paper,a single electron transfer(SET)process of alkyl halides with transition metal catalyst is used to generate alkyl radical,thus inhibiting theβ-H elimination.On the other hand,installation of a suitable directing group on the unactivated alkenes makes it possible to simulate the intermolecular reaction as an intramolecular version and to enhance the chemical reactivity of the non-activated olefins.Moreover,the directing-group-coordinated metallacyclic intermediate might result in a conformationally strained intermediate,which would distinguish the adjacentβ-hydrogen atoms during theβ-hydride elimination event to realize the Heck type coupling reaction of alkyl halides with olefins with high regioselectivity and stereoselectivity.Meanwhile,this essay also explains the mechanism for high regioselectivity through density functional theory calculation(DFT),and reveals the assisting effect of solvent molecules in theβ-H elimination process.This thesis will be focused on the Heck reactions of alkyl halides and how to realize the intermolecular Heck type reaction of alkyl halides and unactivated olefins.In chapter one,recent advances in the Heck reactions of alkyl halides and alkenes was summarized,as well as the directing group increasing reactivity of alkenes strategy to realize a variety of hydrofunctionnalization and difunctionalization of unactivated alkens.In chapter two,the background,conditions optimization,substrates scope and mechanism were illustrated.In the end,the derivatations of the alkylated olefins products was developed.