Regioselective Benzoylation Of Diols And Polyols By Benzoate Catalysis

Owing to a large number of functional groups, protecting groups and protection strategies of hydroxyl groups are important components of carbohydrate chemistry. Because of many reactive hydroxyl sites, it is generally difficult to derivatize monosaccharide. Developing environment-friendly, convenient, efficient and high regioselective carbohydrate protection methods is one of the most prominent challenges in carbohydrate chemistry. Regioselective benzoylation plays an important role in oligosaccharide synthesis. We developed an efficient method for regioselective benzoylation of diols and polyols. The research was trying to explore in the following aspects:1. Our team recently developed a highly regioselective acetylation method where acetylation is enabled by only a catalytic amount of acetate. The method is based on an H-bonding activation mechanism where H-bonding between hydroxyl groups and anions can activate acetylation in the absence of a pyridine catalyst and lead to higher regioselectivities. Based on the above outcome, we apply tetrabutylammonium benzoate as catalysis to the regioselective benzoylation of diols and polys. To the best of our knowledge, this approach to regioselective benzoylation offers the most environmentally friendly, convenient and efficient method to date. The best experiment conditions are as follows: 0.2 equiv.-0.4 equiv. of TBAOBz, 12 h of reaction time, benzoic anhydride as acylation reagents.2. Selective protection of vicinal dio l and its derivatives have been the focus of syntheses of oligosaccharide. The catalysis was applied to the benzoylation of 1,2- and 1,3-diols. The isolated yields of the major product are 64%-94%. For diols with a primary hydroxyl, the primary hydroxyl groups were selective benzoylated due to their minimum steric effect. For diols without primary hydroxyl, the selectivities are poor.3. The catalysis was also applied to the benzoylation of polyols. For glycoside polyols with the primary hydroxyl groups, the 6-OH groups and the 3-OH were selective benzoylated due to their steric effect. For glycoside polyols in which the 6-OH groups have been protected, 3-OH groups have the minimum steric effects since they neighbored two hydroxyl groups whereas 2- and 4-OH groups neighbored a bulky group separately except for 3-OH, leading to good selectivities to 3-OH. The acidity of hydroxyl group for substrates should also play an important role on the regioselectivity. We proposed the regioselectivities should be mainly controlled by steric effect of substrates.