Stereoselective synthesis of highly functionalized spirocyclic compounds based on claisen rearrangement and its application to the synthesis of natural products

Spirocyclic scaffolds are embedded in many biologically active natural compounds, including candidates for medicines, perfumes and agricultural chemicals. Therefore, a development of efficient synthetic methods directed at those structures is strongly demanded. To this end, we have recently developed synthetic methodologies for two different spirocyclic frameworks, spiro[4.5]decanes and spirocyclic oxindoles, based on Claisen rearrangement. We have developed the Claisen rearrangement protocol by which bicyclic 2-(alkenyl)dihydropyrans with functionality at C 4 can be transformed to 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 be also achieved. Thus, a one-pot intramolecular Ullmann coupling/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 pyrrolidinoindoline alkaloids.