Diastereo- and Enantioselective Synthesis of Tetracyclic Cycloheptanols through (4+3) Annulation via C-C/C-H Activation Cascade

Transition metal-catalyzed annulations of four-membered rings via C-C activation are powerful tools to construct complex fused and bridged ring systems. Despite significant progress in (4+1), (4+2) and (4+4) annulations, the (4+3) annulation remains unexplored. Herein, we develop an asymmetric Rh-catalyzed intramolecular (4+3) annulation of alpha-arylalkene-tethered benzocyclobutenols for the synthesis of dihydrofuran-annulated dibenzocycloheptanols with two discontinuous chiral carbon centers via a C-C and C-H activation cascade. The reaction features excellent diastereo- and enantioselectivities and 100 % atom economy, and is applicable to late-stage modification of complex molecules. A Rhodium-catalyzed intramolecular (4+3) annulation of alpha-arylalkene-benzocyclobutenols has been developed, which proceeds through sequential beta-carbon elimination of alcohols, migratory insertion with alkenes, 1,4-Rh shift, and nucleophilic addition to the in situ formed ketones. The protocol offers a diastereo- and enantioselective approach to dihydrofuran-annulated dibenzocycloheptanols with two discontinuous chiral carbon centers built.+image