Compatibility Assessment of Unactivated Internal Alkynes in Rhodium-Catalyzed [2+2+2] Cycloadditions

Functionalized 1,2,4,5-tetrasubstituted benzenes are syn-thetically difficult or laborious to access. The Rh-catalyzed [2+2+2] cyc-loaddition of a diyne and internal alkyne offers a seemingly straightfor-ward route to these scaffolds; however, this has been largely restrictedto alkynes bearing activating (coordinating) functional groups, withvery few examples of unactivated alkynes. In this work, we disclose anassessment of Rh-catalyzed [2+2+2] cycloadditions employing unacti-vated internal alkynes, focusing on the structural diversity and compat-ibility of both alkyne and diyne components. The limitations of thismethod are disclosed, with exceptionally bulky alkynes and specificfunctional groups undergoing side reactions. Furthermore, the practi-calities of gram-scale reactions and catalyst recovery/reuse are demon-strated