Access to Optically Active 7‑Membered Rings by a 2‑Step Synthetic Sequence: Cu-Catalyzed Stereoselective Cyclopropanation of Branched 1,3-Dienes/Rh-Catalyzed Stereoconvergent [5 + 2] Cycloaddition

We report a 2-step
cyclopropanation/cycloaddition catalytic sequence
that provides access to optically active 7-membered rings with a carboxyl-bearing
tertiary stereocenter. In the first step, the Cu-catalyzed cyclopropanation
of branched dienes generates vinylcyclopropanes in high yields, regioselectivity
and enantioselectivity, albeit in modest cis/trans diastereoselectivity.
The stereoconvergent nature of the subsequent Rh-catalyzed [5 + 2]
cycloaddition with alkynes overrides this apparent limitation and
affords preferentially one 7-membered ring out of the 8 or 16 possible
stereoisomers that can be theoretically generated. The final regioselectivity
and enantioselectivity are high in the majority of cases. The method
is versatile and tolerates a broad range of functional groups.