Theoretical Study Of Gold-catalyzed Cyclization Reactions

In this thesis,with the M06 and B3 LYP level of density functional theory,we have studied the mechanisms of the following two works.The purpose of our study is to gain deeper insights into the reaction mechanism and the associated experimental observations and the experimental results,and offer guidance for further study of related reactions.Two specific work is as follows:(1)Gold-catalyzed cyclization of 2-alkynyl-N-propargylanilines provides a step-economic method for the construction of three-dimensional indolines.In the third chapterof thisthesis,M06 functional of density functional theory was employed to gain deeper insights into the reaction mechanism and the associated intriguing experimental observations.The reaction was found to first undergo Au(I)-induced cyclization to form a indole intermediate,1,3-propargyl migration,and substitution with the substrate 2-alkynyl-N-propargylaniline(R1)to generate the intermediate product P1,an allene species.Subsequently,Au(I)-catalyzed conversion of P1 into the final product P2,an indoline compound,occurs first through direct cyclization.Thereafter,water-assisted oxygen heterocycle formation and proton transfer generate the final product.The calculated activation free energiesindicate that P1 formation is 5.9 times slower than P2 formation,which confirms that P1 formation is rate-limiting.Futhermore,the intriguing experimental phenomenon presented by experimental authors that P2 can be accessed only after almost all the substrate R1 converts to P1 although P1 formation is rate-limiting was rationalized by employing energetic span model.We found the initial facile cyclization to form a highly stable indole intermediate in the forming of P1 is the key to the intriguing experimental phenomenon.In non-catalytic reactions,such an observation is impossible,but in some catalytic reactions,this seemly impossible observation becomes feasible.Our theoretical study reasonably rationalized the experimental observations and therefore enriches the contents of consecutive reactions involved in the textbook of Physical Chemistry.(2)With the aid of density functional theory calculations,we have investigated the mechanism of the cyclization reaction of gold-catalyzed oxidation of diacetylene compounds and the feasibility of 1,6-carbene migration(Chapter 4).Based on theoretical calculations,we used a reasonable reaction mechanism to explain the experimental response.As proposed in our study,The process proceeds through a more readily 1,2-methyl shift to obtain a more stable intermediate 9,which is then subjected to 1,2-gold shift to the final product.The 1,6-carbene migration in the reaction proposed by the experimental authors can be ruled out.In summary,we have carried out theoretical research and analysis to examine the feasibility of the preliminary reaction mechanism of the experiment,and provided more reasonable alternative reaction mechanism to guide future research.