Iterative Synthesis of Unsymmetrical Diaryl Cyclobutenes by Monoselective Bromodesilylation and Suzuki-Miyaura Cross-Coupling

The synthesis of heavily decorated cyclobutenes can be particularly challenging due to the strain associated with these species. Particularly, the monoselective cross-coupling of dibromocyclobutenes is unsuccessful, leading to only double arylated products. To combat this problem, an iterative functionalization strategy was developed to selectively facilitate subsequent Suzuki-Miyaura cross-couplings with bromocyclobutenes. This method employs a high yielding monobromodesilyation to furnish the desired bromosilylcyclobutene, which can be derivatized through Suzuki-Miyaura cross-coupling. The same conditions could also be implemented a second time, enabling the iterative and selective arylation of a tetrasubstituted cyclobutene. This method is complementary to the direct [2+2] photocycloaddition approach to tetrasubstituted cyclobutenes as it was found to tolerate photosensitive functional groups.