Iminium Catalysis For The Systhesis Of3-substituted Pyrrolidine-based Natural Products

Iminium catalysis has recently emerged as a powerful tool for the construction of carbon-carbon and carbon-heteroatom bonds in asymmetric synthesis and thus, becomes one of the most competitive research areas in synthetic organic chemistry. Particularly, iminium catalysis has also been widely used in the synthesis of natural products.Based on the highly efficient organocatalytic asymmetric Michael reaction, the main task of this PhD thesis is the synthesis of3-substituted pyrrolidine-based amino acid derivatives and natural products. Accordingly, the obtained results could be divided into three parts:1. Using diarylprolinol silyl ether as the organocatalyst, the asymmetric organocatalytic Michael addition of nitro esters to α, β-unsaturated aldehydes was achieved in high yields and excellent enantioselectivity. Furthermore, we developed a facile five-step strategy for the enantioselective synthesis of trans-3-substituted proline derivatives with high biological activities.2. On the basis of the organocatalytic Michael addition to construct the C4stereogenic center, and of the challenging method for the imine-bond formation via the one-pot approach containing the deprotection of both N-Boc and acetal groups, a concise synthesis of L-pyrrolysine was accomplished in six steps.3. Using the organocatalytic Michael addition reaction as the key step, we have also conducted the studies towards the asymmetric synthesis of the3-substituted pyrrolidine-based natural product (-)-kainic acid.In addition, inspired by the unique spirobicyclo[4.5]decane skeleton of the natural product (-)-erythrodiene, which was isolated from Caribbean gorgonian octocoral erythropodium caribaeorum, we designed a facile organocatalytic cascade strategy for the construction of this unique skeleton in the asymmetric synthesis of (-)-erythrodiene.