Asymmetric hydroboration and Matteson homologation for the preparation of fluorinated α-phenethanols

The asymmetric catalytic hydroboration–oxidation of ring-fluorinated styrenes (F-PhCHCH2) was achieved with catecholborane along with a combination of [Rh(COD)2]+BF4− and (R)-BINAP providing 81–96% enantioselectivities for the product alcohols for ortho-unhindered styrenes. A deleterious effect of a 2,6-disubstitution on the enantioselectivity of the product alcohol was observed. 2-Trifluoromethylstyrene also provides only 53% ee, probably due to the steric bulk of the CF3 group at the ortho-position of styrene. Asymmetric homologation of fluorophenylmetals (magnesium bromide or lithium) with pinanediol α-chloroethylboronate, followed by oxidation readily furnished the desired 1-(2,6-difluorophenyl)- and 1-(perfluorophenyl)ethanols in 94–95% ee.

Graphical abstractThe catalytic hydroboration–oxidation of ring-fluorinated styrenes (F-PhCHCH2) was achieved with catecholborane along with a combination of [Rh(COD)2]+BF4− and (R)-BINAP providing 81–96% enantioselectivities for the product alcohols for ortho-unhindered styrenes. A deleterious effect of a 2,6-disubstitution on the enantioselectivity of the product alcohol was observed. 2-Trifluoromethylstyrene also provides only 53% ee, probably due to the steric bulk of the CF3 group at the ortho-position of styrene. Asymmetric homologation of fluorophenylmetals (magnesium bromide or lithium) with pinanediol α-chloroethylboronate, followed by oxidation readily furnished the desired 1-(2,6-difluorophenyl)- and 1-(perfluorophenyl)ethanols in 94–95% ee.Figure optionsDownload full-size imageDownload as PowerPoint slide