DFT Study On The Mechanisms Of The [4+2] Cycloadditions Of Enals And Chalcones Catalyzed By N-heterocyclic Carbene

Cycloaddition reactions are the combinations of two or more unsaturated compounds(or different parts of one compound)to form the cyclic adducts.Among them,the [4 + 2] cycloaddition reactions can be used for the synthesis of six-membered ring,which is also one of the most important methods for the formation of carbon-carbon bond in organic chemistry,and it is one of the favorite reactions in modern organic synthesis.N-heterocyclic carbene-catalyzed [4 + 2] cycloaddition reactions have extensive stereochemical presentations and regional selectivity.Understanding of the mechanism of the cycloaddition reaction deeply is significant for the design of new synthetic pathway,the choice of more efficient catalysts,as well as the choice of a suitable solvent.However,it is very difficult to explore the detailed mechanism of the reactions by experiment,so we need to get more information at the molecular level in theory.This prompts us to study the mechanism of this kind of reactions in detail via theoretical calculations.In this thesis,the possible reaction mechanisms of stereoselective [4 + 2] cycloaddition of enals and chalcones catalyzed by N-heterocyclic carbene(NHC)have been investigated at the B3LYP/6-31G(d,p)level.According to the different orders of the combinations of NHC and two reactants,we suggested two possible reaction pathways.And we considered different proton-transfer channels in each pathway.The calculated results indicate that the most favorable reaction pathway occurs through five steps.The first step is the nucleophilic attack of NHC catalyst on the enal.Then there are two consecutive acid(AcOH)-assisted proton transfer steps.Subsequently,the fourth step is the [4 + 2] cycloaddition process.Finally,it is the dissociation of catalyst NHC and products.Moreover,the computational results demonstrate that the fourth step is the rate-determining step and the stereoselectivity-determining step,in which two chiral centers are formed.And the energy barriers of this step are not high for the experimental condition.SS configurational channel has the lowest energy barrier(17.62 kcal/mol),indicating the SS configuration product should be the main product,which is in good agreement with the experimental results.Furthermore,the calculated enantiomeric excess value is 94%,which is very close to the experimental ee value(98%).The analysis of global reactivity indexes has also been performed to explain the role of catalyst NHC in the [4 + 2] cycloaddition of enals and chalcones.This work should be helpful for people to not only understand the detailed mechanisms and stereoselectivity of the title reaction at the molecular level,but also realize the role of catalyst NHC and the additive AcOH in the reaction,and thus provide valuable insights on the rational design of potential catalyst for this kind of reactions.