Enantioselective α-Amination of 1,3-Dicarbonyl Compounds in Batch and Flow with Immobilized Thiourea Organocatalysts

Abstract

<p> A polymer-supported bifunctional thiourea organocatalyst (<strong>PS</strong>-<strong>TU</strong>) has been prepared and successfully used in the enantioselective a-amination of 1,3-dicarbonyl compounds with azodicarboxylates. In contrast with homogeneous thioureas, <strong>PS</strong>-<strong>TU</strong> is not irreversibly deactivated by the azodicarboxylate reagents, and simple washing with triethylamine between runs has allowed the repeated reuse (9 cycles) of the <strong>PS</strong>-<strong>TU</strong> catalyst. The a-amination mediated by <strong>PS</strong>-<strong>TU</strong> has also been adapted to perform the enantioselective amination (93% ee) of ethyl 2-oxocyclopentanecarboxylate in continuous flow (7.5 h operation, 21 min residence time, TON = 37).</p>