ISHC2015

Since nitrogen-containing heterocyclic rings are common structural motifs in biologically important natural products, development of new synthetic methodologies for construction of these structures have been one of the important research topics in synthetic chemistry. In this lecture, our recently completed total syntheses of polycyclic alkaloids featuring new synthetic strategies will be discussed. We investigated a reductive ring expansion of cyclic ketoximes and applied to a concise total synthesis of (–)-mersicarpine.1 For formation of substituted indolines, we developed a benzyne-mediated cyclization-functionalization sequence and applied this reaction to total syntheses of dictyodendrins A-E.2 A protective group free total synthesis of (–)-rhazinicine was accomplished based on the development of a gold-catalyzed double cyclization cascade.3 In the first total synthesis of (+)-haplophytine, we constructed the characteristic spiroaminal by an oxidative semi-pinacol type rearrangement.4 Dihydrooxepin rings in (–)-acetylaranotin was formed by combination of the vinylogous Rubottom oxidation and the Baeyer-Villiger ring expansion of an enone intermediate.

In general, the synthesis of complex biologically active molecules are problematic but the problems, encountered during the syntheses, can be a good source of inspiration to develop methods. One major challenge is the design of concise strategies as well as chemoselective and efficient methods that rapidly lead to the skeleton framework of natural and/or biologically active heterocyclic compounds.

In this context, we have explored the construction of heterocycles using catalytic reactions involving transition metal catalysts and heat. Metal catalysts and heat can induce rearrangements, cyclizations, functionalizations which can be highly diastereoselective and enantioselective if a chiral ligand is added in the reaction media. These reactions and their applications to the synthesis of heterocyclic natural and non-natural products will be presented