Accessing Substituted Pyrrolidines Via Formal Cycloaddition Of 1,3,5-triazinanes And Donor-acceptor Cyclopropanes

Pyrrolidines are one of the most ubiquitous building blocks for a large number of natural products,pharmaceuticals and biologically active compounds.They are also widely used as the core structure of synthetic catalysts.Consequently,the development of highly efficient strategies to construct pyrrolidine motifs is of great importance.This dissertation focused on the development of an efficient method to synthesize pyrrolidines base on the[3+2]cycloaddition reaction of donor-acceptor cyclopropanes and 1,3,5-triazinanes.Firstly,the reaction conditions were investigated.Various Lewis acids and solvents were screened.In the presence of 20 mol%AlCl3,in dichloromethane,the reaction gave the desired product in 79%yield.Having established the feasibility and optimal conditions,the generality of this formal[3+2]cycloaddition with a range of donor-acceptor cyclopropanes and triazinanes was investigated.Substrates with various electronic nature and hindrance of the substituents were tolerated in this reaction conditions,and 24 examples were obtained in good to excellent yields(55%-99%).Furthermore,the synthetic utility of this reaction was demonstrated under the optimized conditions.Finally,based on the control experiment and the reported results,a plausible mechanism was proposed to explain the reaction.The reaction proceeds through competing SNi and SN2 pathways.In summary,we have developed a formal[3+2]cycloaddition reaction of donor-acceptor cyclopropanes with 1,3,5-triazinanes,leading to the synthesis of highly functionalized pyrrolidines under very mild reaction conditions in moderate to excellent yields(up to 99%).