Stereocontrolled Synthesis of Functionalized Spirocyclic Compounds Based on Claisen Rearrangement and its Application to the Synthesis of Spirocyclic Sesquiterpenes and Pyrrolidinoindoline Alkaloids

摘要

Spirocyclic scaffolds are embedded in many biologically active natural compounds, including candidates for medicines, per-fumes and agricultural chemicals. Therefore, the development of ef-ficient synthetic methods directed at those structures is strongly in demand. To this end, we have recently developed synthetic method-ologies for two different spirocyclic frameworks, spiro[4.5]decanes and spirocyclic oxindoles, based on the Claisen rearrangement. We have developed the Claisen rearrangement protocol by which bicyclic 2-(alkenyl)dihydropyrans with functionality at the 4-posi-tion can be transformed into spiro[4.5]decanes in good-to-excellent yields with excellent stereoselectivities. We applied this method to a concise total synthesis of several biologically active spirocyclic sesquiterpenes. Related Claisen rearrangement in alkenyl pyranoindole systems can also be achieved, Thus, a one-pot intramolecular Ullmann coupling (IUC)/Claisen rearrangement sequence from 2-iodoindoles was found to provide spirocyclic oxindoles in good yields with excellent stereoselectivities. We applied this sequence to the synthesis of pyr-rolidinoindoline alkaloids.