Development of Tailor-made Organocatalytic Reactions for Total Synthesis of Natural Product

Asymmetric organocatalytic reactions have made significant advancements in recent years. They are cost-effective, safe, and easy to handle, making them a focal point in the realm of green chemistry. These reactions are actively utilized in the total synthesis of natural product. However, when dealing with multifunctional substrates for natural product synthesis, there are instances where conventional methods are not applicable, requiring reoptimization. In this paper, I describe an asymmetric organocatalytic reaction that we have developed for the comprehensive total synthesis of specific natural product we have targeted. We have successfully developed asymmetric organocatalytic formal aza [3+ 3] cycloaddition reactions for the total synthesis of quinine and silicine, both of which possess multi-substituted piperidine rings. Additionally, we have established a dihydropyran ring construction reaction through an enantioselective, anti-selective Michael addition/Fukuyama reduction cascade to prepare secologanin, a pivotal biosynthetic intermediate in the monoterpenoid indole alkaloid biosynthesis. Moreover, I have introduced a trienamine-mediated asymmetric Diels-Alder reaction, utilizing dihydropyridones as substrates, for the total synthesis of Lycopodium alkaloids featuring decahydroquinoline rings. By incorporating these asymmetric reactions with secondary amine-type organocatalysts into our total synthesis approach, we efficiently constructed chiral carbon centers and the natural product scaffolds. All total syntheses were completed in relatively short steps and in high yields.