Size-Induced Inversion of Selectivity in the Acylation of 1,2-Diols

Relative rates for the Lewis base-catalyzed acylation of aryl-substituted 1,2-diols with anhydrides differing in size have been determined by turnover-limited competition experiments and absolute kinetics measurements. Depending on the structure of the anhydride reagent, the secondary hydroxyl group of the 1,2-diol reacts faster than the primary one. This preference towards the secondary hydroxyl group is boosted in the second acylation step from the monoesters to the diester through size and additional steric effects. In absolute terms the first acylation step is found to be up to 35 times faster than the second one for the primary alcohols due to neighboring group effects.

Automated summary

The relative rates of Lewis base-catalyzed acylation of aryl-substituted 1,2-diols with anhydrides of varying sizes have been determined. Depending on the anhydride reagent structure, the secondary hydroxyl group of the 1,2-diol reacts faster than the primary one. This preference is further enhanced in the second acylation step from monoesters to diesters through size and additional steric effects. The first acylation step is found to be up to 35 times faster than the second one for primary alcohols due to neighboring group effects.