We recently had the pleasure of collaborating with the group of Daniel Seidel (University of Florida) in the field of enantioselective acidic catalysis. Prof. Seidel and his co-workers have developed Highly Acidic Conjugate‐Base‐Stabilized Enantioselective Carboxylic Acid Catalysts that are able to catalyze oxa‐Pictet–Spengler Reactions with Ketals. Our task in this endeavor was determining the acidity of the catalysts involved and elucidating the effect of the different elements of its substitution scheme on acidity. The main outcome is summarized in the scheme on the left. As can be seen, the most acidifying element is the substituted thiourea moiety, leading to one of the catalysts – the rightmost molecule. The findings strongly suggest that a key to the high acidity is the intramolecular hydrogen bond stabilizing the anion of the acid catalyst. These same substituents are also instrumental in the enantioselective catalytic ability of these catalysts.
This work has been published in Angew. Chem. Int. Edit. 2019.