A General Solid-Phase Synthesis Strategy for the Preparation of 2-PyrroHdinemethanol Ligands

摘要

The development of asymmetric catalysts generally requires the time-consuming screening of a large number of chiral liganda, metals, and reaction conditions. For many asymmetric reactions, optimization of ligand structures for each substrate class must be performed. To expedite these processes, we have worked to apply combinatorial strategies to asymmetric catalyst development and optimization. As progress toward this goal, we report a general approach for the solid-phase synthesis of the 2-pyrrolidinemethanol ligand class (Figure 1) and demonstrate that the ligands can be directly evaluated in dialkylzinc addition reactions without purification. This ligand class, as well as other ligands based on pro-line, have been used extensively to prepare asymmetric catalysts for a number of reactions including dialkylzinc additions to aldehydes, enantioselective reductions of ketones, and asymmetric Diels-Alder reactions.