The Role of Proton Donors in SmI2-Mediated Ketone Reduction: New Mechanistic Insights

Abstract

The effects of proton donors (alcohols and water) on the rate of reduction of acetophenone by SmI₂ have been examined utilizing stopped-flow spectrophotometric studies. The rate orders with respect to proton source and the kinetic isotope effects were determined as well. The reaction was first-order in phenol, 2,2,2-trifluoroethanol, methanol, and ethanol and zero-order in 2-propanol and 2-methyl-2-propanol when 25 equiv of proton source were used in the reduction. Methanol, ethanol, 2,2,2-trifluoroethanol, and phenol also showed a direct correlation between the pK_a of the alcohol and the rate of reduction. Under the same conditions, water had a fractional rate order of 1.4. Further studies showed that water has a rate order of 1 at lower concentrations (80 equiv). These results clearly indicate that the nature of the proton donor and its concentration affects the rates of reduction. Water has a high affinity for SmI₂ (compared to that of the alcohols), and the onset of coordination at relatively low concentrations channels the reaction through a mechanistically distinct pathway.