Asymmetric aminohydroxylation of substituted styrenes: applications in the synthesis of enantiomerically enriched arylglycinols and a diamine

Abstract

The catalytic asymmetric aminohydroxylation of a variety of styrene derivatives and vinyl aromatics using osmium tetroxide in conjunction with alkaloid-derived ligands [e.g. (DHQ)₂PHAL or (DHQD)₂PHAL] and haloamine salts of alkyl carbamates (e.g. ethyl carbamate or tert-butyl carbamate) has been investigated. By observing the effect of different aromatic substituents and alkyl carbamates on the regioselectivity, yield and enantioselectivity of the aminohydroxylation reactions, a number of conclusions have been reached: (i) the 1-aryl-2-hydroxyethylamine regioisomers were obtained as the major products in reasonable yield and high (87%) enantiomeric excess; (ii) tert-butyl carbamate was superior to ethyl carbamate in terms of yield, enantioselectivity and ease of removal of the N-protecting group; (iii) high (96%) enantioselectivity was observed with a 4-methoxy-substituted styrene whereas ortho-substituted styrenes gave lower enantioselectivities; (iv) chiral ligands (DHQ)₂PHAL and (DHQD)₂PHAL gave essentially equal and opposite senses and degrees of asymmetric induction; (v) regioselectivity was ligand dependent with better regioselectivity (and therefore higher isolated yields) obtained with (DHQ)₂PHAL than with (DHQD)₂PHAL. The products of the aminohydroxylation reactions were used to prepare enantiomerically enriched arylglycinols and a chiral diamine.