Difunctional­ization of C–C σ‑Bonds Enabled by the Reaction of Bicyclo[1.1.0]butyl Boronate Complexes with Electrophiles: Reaction Development, Scope, and Stereochemical Origins

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 C–C σ-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.