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Difunctionalization reactions of C-C σ bonds have the potential to streamline access to molecules that would otherwise be difficult to prepare. However, the development of such reactions is challenging because C-C σ bonds are typically unreactive. Exploiting the high ring-strain energy of polycyclic carbocycles is a common strategy to weaken and facilitate the reaction of C-C σ bonds, but there are limited examples of highly strained C-C σ bonds being used in difunctionalization reactions. We demonstrate that highly strained bicyclo[1.1.0]butyl boronate complexes (strain energy: ca. 65 kcal/mol), which were prepared by reacting boronic esters with bicyclo[1.1.0]butyl lithium, react with electrophiles to achieve the diastereoselective difunctionalization of the strained central CC -bond of the bicyclo[1.1.0]butyl unit. The reaction shows broad substrate scope, with a range of different electrophiles and boronic esters being successfully employed to form a diverse set of 1,1,3-trisubstituted cyclobutanes (>50 examples) with high diastereoselectivity. The high diastereoselectivity observed has been rationalized based on a combination of experimental data and DFT calculations, which suggests that separate concerted and stepwise reaction mechanisms are operating depending upon the migrating substituent and electrophile used.
Bibliographical noteprovisional acceptance date added to record, based on publicaiton information
Changing the Synthesis Landscape with Boron at the Helm: from Chiral Organometallics to Assembly Line Synthesis
14/05/12 → 13/01/18