Organic chemistry

Combinatorial chemistry

Ring (chemistry)

Radical

Catalysis

Medicinal chemistry

Stereoselectivity

Chemistry

Stereospecificity

Cyclobutane

Cyclobutanes

Alkyl

Photochemistry

Journal of the American Chemical Society

While radical additions to π-bonds are well established, additions to σ-bonds are far less explored. We have found that electron deficient radicals derived from alkyl iodides under visible light irradiation add to the central strained bond of bicyclobutyl (BCB)-boronate complexes and lead to 1,3-alkyl disubstituted cyclobutyl boronic esters in high yields, with full stereospecificity and high levels of stereoselectivity. Novel cyclobutyl-substituted structures, including peptide and steroid boronic ester derivatives can be accessed. Additionally, although the use of electron-rich alkyl iodides as radical precursors was found to be ineffective, an alternative route involving alkylsulfonylation of the BCB-boronate followed by reductive desulfonylation provided access to simple alkyl substituted cyclobutane products.

Radical Addition to Strained σ-Bonds Enables the Stereocontrolled Synthesis of Cyclobutyl Boronic Esters