Synthesis of Carboranyl Alkyl Sulfide via Radical Thiol-Ene "Click" Reaction

Synthetic methods that feature mild reaction conditions and broad functional group tolerance are highly desired for the development of third-generation boron delivery agents, which are highly significant for boron neutron capture therapy (BNCT), a selective cancer treatment technique. Molecules containing carborane are promising candidates as boron delivery compounds for BNCT. Herein, we report an efficient radical thiol-ene "click" reaction involving carboranyl thiols and unactivated alkenes under photoredox conditions. This reaction affords moderate to excellent isolated yields. The current methodology allows for the incorporation of carborane, a valuable moiety with a high boron content, into molecules under mild reaction conditions. The outstanding functional group tolerance of this method makes it suitable for the late-stage introduction of boron into bioactive molecules. The radical addition reactivity of carboranyl thiol radical was investigated by DFT calculations to uncover the impact of the 3D aromaticity of carborane on the stabilization of a sulfur centered radical.