Theoretical Studies On Mechanism Of Alkenylation Of 8-methyquinoline And Cyclization Of Alkynols And Relevant Experiment

With the help of Gaussian caculation software,not only can we get a reasonable interpretation for some experimental phenomena,but also we can predict the trends to guideline further experiment.The Rh-catalyzed alkenylation of 8-methyquinolines via C(sp3)-H activation and Pd-catalyzed cyclization of alkynols were investigated by using density functional theory(DFT).The energy and geometry optimization calculations of each stationary points in all possible reaction pathways are performed to reasonably explain the reaction mechanism and selectivity.DFT studies on rhodium(?)-catalyzed alkenylation of 8-methyquinolines show that the cleavage of C(sp3)-H bond of 8-methylquinoline prefers to undergo four-membered ring process with free energy barrier of 29.8 kcal/mol,rather than six-membered ring process because of the delocalized electron effect of oxygen atom to Rh center.Alkyne insertion process starts with the cleavage of Rh-N bond to create vacant space to accommodate diphenylacetylene,in which Rh center is more likely to maintain 16e structure rather than 18e structure.Then diphenylacetylene inserts into the Rh-C1 bond with a free energy barrier of 21.2 kcal/mol.The binding of HO Ac process is the premise condition for catalyst regeneration process,in which Rh center is more possible to accommodate HOAc directly instead of going through seven-membered rhodacycle.At last,catalyst was eliminated directly via the H-transfer from HOAc to the carbon of C=C unit to give product and regenerate catalyst to give product with an energy barrier of 12.8 kcal/mol,rather than undergo Rh-mediated H-transfer,which is attributed to the formation of unstable 20e species in the Rh-mediated process.The substituted effect follows the H<F<NMe2 trends,being consistent with its experimental results.The mechanism study on Pd(0)-catalyzed cyclization of alkynols under molecular level shows that alkynols prefer to form endo cyclic ethers in the present of Pd2(dba)3 and Xantphos,which is attributed to the steric hindrance of Xantphos.With the help of the large bulk of metal complexe,reaction point can be regiocontrolled so as to synthesize compounds selectively.The cyclization of alkynols was happened through the following pathways:firstly,the carbon-carbon triple bond of substrate coordinates to Pd complexe.Under the regiocontrolled Pd complexe,the intramolecular nucleophlic addition of alkynols was carried out selectively.The last step is the regeneration of catalyst and the formation of cyclic ethers.In addition,great effort was made to combine computational chemistry with experimental chemistry to study the synthesis of galactopyranosyl azides and galactopyranosyl triazoles and their relevant theory.