The asymmetric bromohydroxylation of 2-aryl-2-propen-1-ols catalyzed by quinine-derived bifunctional catalyst has been developed. The regioselectivity was controlled by employing a boronate ester as tether which was formed in situ and enantioselectivity was introduced by taking advantage of a quinine-derived bifunctional catalyst which activated the boronate ester and N-bromosuccinimide (NBS) at the same time. Chiral bromohydrin, which is a useful feedstock in organic synthesis, was produced in moderate to excellent enantioselectivity in a two-step reaction sequence.Halohydroxylation of the C=C double bond is an important transformation in organic chemistry for providing a direct method to bifunctionalized C=C double bonds. [1] The halohydroxylation products are versatile feedstocks in organic synthesis since both halogen atom and hydroxy group offer a good handle for further derivatization (e.g., nucleophilic substitution of halogen atoms). [2] Although a few direct asymmetric halohydroxylation reactions of C=C double bonds have been reported to date, the reactions suffered from low enantioselectivity, limited substrate scope, high catalyst loadings and the need for metal catalysts. [3] Organocatalyzed reactions have attracted much attention from the chemical community for their environmentally benign, and operationally friendly advantages over transition metal-catalyzed reactions and have witnessed great progresses over the past decade. [4] However, the development of an organocatalyzed halogenation of olefins fell far behind the other types of organocatalyzed reactions (e.g., Michael addition reactions, a-fucntionalization of aldehydes). [5a] Just recently, asymmetric halogenpromoted nucleophilic addition reactions of olefins catalyzed by organocatalysts have emerged as a powerful tool for the construction of optically active lactones and other heterocyclic compounds, but those reactions were limited to intramolecular processes (for example, halolactonization [5c-j] and haloetherification [5k-m] ). The organocatalyzed asymmetric halohydroxylation of isolated C=C double bonds has remained a challenge due to the difficulties in controlling the regioselectivity and enantioselectivity of the reaction from the lack of interactions between substrates and catalysts.Chiral bromohydrin 4 is a common synthetic intermediate of triazole antifungal reagents such as ZD0870 and Sch45450. [6] Although Sharpless asymmetric dihydroxylation of allyl halide, [7a] or enzymatic resolution of diols [7b] provided a direct way to synthesize bromohydrin 4, moderate enantioselectivity or low yields of the desired enantiomer retards their practical application. Other stepwise protocols initiated with the Sharpless asymmetric epoxidation of allyl alcohol, [7c] or asymmetric cyanosilylation [7d] suffer from long synthetic steps and a need for transition metals. Herein we would like to report the first asymmetric bromohydroxylation of 2-aryl-2-propen-1-ols 1 catalyzed by a quinine-derived bifunctional catalyst to provide bromohydrin ...
