Why do thioureas and squaramides slow down the Ireland-Claisen rearrangement?

Beilstein J Org Chem. 2019 Dec 10:15:2948-2957. doi: 10.3762/bjoc.15.290. eCollection 2019.

Abstract

A range of chiral hydrogen-bond-donating organocatalysts was tested in the Ireland-Claisen rearrangement of silyl ketene acetals. None of these organocatalysts was able to impart any enantioselectivity on the rearrangements. Furthermore, these organocatalysts slowed down the Ireland-Claisen rearrangement in comparison to an uncatalyzed reaction. The catalyst-free reaction proceeded well in green solvents or without any solvent. DFT calculations showed that the activation barriers are higher for reactions involving hydrogen-donating organocatalysts and kinetic experiments suggest that the catalysts bind stronger to the starting silyl ketene acetals than to transition structures thus leading to inefficient rearrangement reactions.

Keywords: DFT calculations; H-bonding catalysts; Ireland–Claisen rearrangement; green solvents; silyl ketene acetals.