Dirhodium(ii)-catalyzed regio- and stereoselective cycloisomerization towards 6,5,3-tricyclic skeletons containing vicinal all-carbon quaternary stereocenters

Abstract

The construction of multicyclic frameworks and all-carbon quaternary stereocenters is among the most important and challenging tasks in organic synthesis. Therefore, the development of an efficient catalytic method for the direct and stereoselective construction of multicyclic frameworks bearing vicinal all-carbon quaternary stereocenters is highly desirable. Herein, we report a Rh₂(II)-catalyzed regio- and stereoselective cycloisomerization of benzo-fused 1,6-enynes, which enables rapid construction of 6,5,3-tricyclic skeletons containing two consecutive all-carbon quaternary stereocenters with high efficiency (up to 98% yield) and excellent enantioselectivity (up to 99% ee). In this process, an exclusive cis-olefin and a unique alkenyl cyclopropane motif are constructed in one step. Mechanistic studies and the crystal structures of alkyne–dirhodium complexes reveal that the cooperative weak hydrogen bonding between the substrates and the dirhodium catalyst may enable the occurrence of cycloisomerization. Further control experiments indicated that the selectivity of 5-exo or 6-endo cyclization could be regulated by changing the reactive site of 1,2-hydride migration.