Toward the continuous-flow synthesis of chiral tertiary alcohols by enantioselective addition of organozinc reagents to ketones using nanosize isoborneol ligands

The catalytic enantioselective addition of different organozinc reagents, such as alkyl or in situ generated phenylzinc derivatives to simple aryl ketones, was accomplished using titanium tetraisopropoxide and chiral ligands derived from trans-1-arenesulfonylamino-2-isoborneolsulfonylamidocyclohexane and Fréchet-type dendrons with up to 2.5 nm of diameter, giving the corresponding tertiary alcohols with enantioselectivities up to >99%. A simple and efficient procedure for the synthesis of the ligands used is also described, involving the radical addition of the corresponding thiol dendron to the chiral styryl-isoborneol derivative.

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N-{2-(2-Hydroxy-7,7-dimethylbicyclo[2.2.1]hept-1-ylmethanesulfonylamino)cyclohexyl}-4-(2-benzylsulfanylethyl)benzenesulfonamideC31H46N2O6S3Ee = 100%[α]D25=+13.8 (c 1.1 CHCl3)Source of chirality: (+)-10-camphorsulfonyl chloride and (−)-diaminocyclohexane

N-{2-(2-Hydroxy-7,7-dimethylbicyclo[2.2.1]hept-1-ylmethanesulfonylamino)cyclohexyl}-4-[2-(3,5-bisbenzyloxybenzylsulfanylethyl)benzenesulfonamideC45H56N2O7S3Ee = 100%[α]D25=+14.0 (c 1.1 CHCl3)Source of chirality: (+)-10-camphorsulfonyl chloride and (−)-diaminocyclohexane

N-{2-(2-Hydroxy-7,7-dimethylbicyclo[2.2.1]hept-1-ylmethanesulfonylamino)cyclohexyl}-4-{2-[3,5-bis(3,5-bisbenzyloxy-benzyloxy)benzylsulfanylethyl)benzenesulfonamideC73H80N2O11S3Ee = 100%[α]D25=+4.5 (c 1.1 CHCl3)Source of chirality: (+)-10-camphorsulfonyl chloride and (−)-diaminocyclohexane