An enantioselective HAT for diols

Abstract

The research team explored how the catalyst, in the presence of photocatalyst 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene (4CzIPN) and blue light irradiation, generates a radical intermediate on cis-1,2-cyclohexanediol that can be trapped by 1-dodecanethiol as hydrogen atom donor, to produce trans-1,2-cyclohexanediol. Use of epi-NHBoc-dihydrocinchonidine yields the opposite enantiomer.

The reaction is tolerant of cyclic diols of different sizes, with fused rings or bearing acetonide, ester or benzylic groups; it was also successfully applied to acyclic diols, such as meso-hexane-3,4-diol, as well as meso-1,3-diols, and pentane-2,4-diol. The team also demonstrated that the catalyst can control the enantioselection in the Giese addition of acrylamide or vinyl sulfone to the radical generated on the diol substrates. Mechanistic investigations confirmed that the photoexcited 4CzIPN is quenched by the catalyst, producing a radical cation that desymmetrizes the diol, forming a radical intermediate, placing the reaction under kinetic control. This intermediate undergoes a nonselective hydrogen atom delivery from the thiol to produce the entioenriched chiral diol.