Theoretical Mechanism Of Copper-catalyzed Alkyne Coupling Reaction

The C-C coupling reaction of alkynes and organic electrophiles catalyzed by transition metals has been greatly developed.Among them,the transition metal copper has become a research hotspot because of its surprisingly similar working mode to palladium and its advantages such as low price,environmental protection and non-toxicity.Alkynes can be used as internal oxidants in the reaction to achieve atomic economy,so they are widely used.In order to synthesize the target product,its site selectivity has always been the focus of our attention.Therefore,exploring the regioselectivity of the reaction to control the reaction site to synthesize the target product is the problem we should solve.In recent years,the versatile reactivity of Cu-catalyzed hydrocarbonylative coupling of alkynes with alkyl halides has drawn a wide range of attention.In this paper,we explored in detail the origin of regioselectivity for alkynes coupling with primary,secondary and tertiary alkyl halides by using density functional theory(DFT)calculation.The present results reveal that the dominant factor of high C_α-regioselectivity in alkyne insertion is mainly the electron effect for 1-decyne,in which the higher electron density of terminal carbon making electrophilic attack more favorable.For internal alkyne 1-phenyl-1-hexyne,d orbital in Cu which is able to conjugated with HOMO of the benzene ring plays a dominate role in C_α-selective formation of alkenylcopper.Moreover,we also confirmed that enones was formed by C-C concerted coupling of alkenylcopper with acyl bromide instead of the oxidation addition suggested in the literature.Notably,the origin of regioselectivity of 1,2-reduction over 1,4-reduction is mainly the steric effect,whether for the terminal alkyne or the internal alkyne case.Alkynes are important part of transition metal-catalyzed C-C bond formation reactions.The reductive coupling of alkynes with unsaturated substrates,such as olefins,alkynes,aldehydes,ketones,imines,and epoxy compounds,provide effective routes to functionalize products.Alkynes are also commonly used in transition metal-catalyzed cycloadducts to build carbocyclic rings.Controlling regioselectivity is essential for intermolecular reactions of asymmetric alkynes.Therefore,the second work is to investigate the effect of alkynes on Cu-catalyzed C-C coupling sites selectivity and to extend alkynes to olefins.Significant deviations in the size or electronic properties of the alkynyl substituents of alkynes can achieve high regioselectivity,such as terminal alkynes,conjugated alkynes,etc.It is found through analysis that anti-Markovnikovis better than Markovnikov selectivity addition for alkyl alkynes,and the main factor affecting regioselectivity is the electronic effect.But for aromatic phenyl or carbonylalkynes and alkenes,Markovnikov is better than anti-Markovnikov selectivity addition and this is controlled by orbital interaction.