Photochemical Formal (4 + 2)-Cycloaddition of Imine-Substituted Bicyclo[1.1.1]pentanes and Alkenes

Abstract

Amines containing bridged bicyclic carbon skeletons are desirable building blocks for medicinal chemistry. Herein, we report the conversion of bicyclo[1.1.1]pentan-1-amines to a wide range of polysubstituted bicyclo[3.1.1]heptan-1-amines through a photochemical, formal (4 + 2)-cycloaddition of an intermediate imine diradical. To our knowledge, this is the first reported method to convert the bicyclo[1.1.1]pentane skeleton to the bicyclo[3.1.1]heptane skeleton. Hydrolysis of the imine products gives complex, sp 3 -rich primary amine building blocks.

Activation of aminocyclopropanes via radical intermediates

“…The requirement for a sequential ring-opening and nucleophile addition is due to the incompatibility of many nucleophiles with highly oxidizing reaction conditions. In many cases, successful extension to aminocyclobutanes 33,34,[79][80][81] or nitrogen-substituted bicyclo[1.1.1]-pentanes 82 has been realized for synthesizing building blocks by a (4+2) annulation or a 1,4-difunctionlization reaction.…”

Strain Release [2p+2s]-Cycloadditions for the Synthesis of [2.1.1]-Bicyclohexanes Initiated by Energy Transfer

“…13 In one very recent study, the Stephenson group utilized [1.1.1]-bicylopentanes in a strain release cycloaddition with an alkene. 14 After considerable experimentation with thermally induced reactions as well as photoredox processes, no product was observed between a BCB and an alkene. In most cases, polymerization of the BCB was observed.…”

Water-soluble Bioisosteres of the ortho-substituted Phenyl Ring

“…Among all tested solvents (entries 10-13), the best outcome was obtained in acetonitrile. Without irradiation, the reaction did not take took place neither at room temperature nor under heating (entries 14,15).…”