Insights into Ag(i)-catalyzed addition reactions of amino alcohols to electron-deficient olefins: competing mechanisms, role of catalyst, and origin of chemoselectivity.

The competing mechanisms of Ag(i)-catalyzed chemoselective addition reactions of amino alcohols and electron-deficient olefins leading to the O -adduct or N -adduct products were systematically studied with density functional theory methods. Calculations indicate that the AgHMDS/dppe versus AgOAc/dppe catalytic systems can play different roles and thereby generate two different products. The AgHMDS/dppe system works as a Brønsted base to deprotonate the amino alcohol OH to form the Ag-O bond, which leads to formation of the O -adduct. In contrast, the AgOAc/dppe system mainly acts as a Lewis acid to coordinate with O and N atoms of the amino alcohol, but it cannot act as the Brønsted base to further activate the OH group because of its weaker basicity. Therefore, the AgOAc/dppe catalyzed reaction has a mechanism that is similar to the non-catalyzed reaction, and generates the same N -adduct. The obtained insights will be important for rational design of the various kinds of cooperatively catalyzed chemoselective addition reactions, including the use of the less nucleophilic hydroxyl groups of unprotected amino alcohols.