Development of Highly Acidic Conjugate-Base-Stabilized Bronsted Acid Organocatalysts and Their Application to Enantioselective Intramolecular 6p-Electrocyclizations of Hydrazones

摘要

Chiral Bronsted acids have found widespread applications as organocatalysts in the past two decades. We recently introduced a new class of chiral Bronsted acid catalysts that comprise carboxylic acids with a covalently connected anion-recognition site such as a thiourea moiety. These catalysts are thought to derive their acidity largely from stabilization of their respective conjugate bases through anion binding. Carboxylic-acid-thiourea catalysts were found to facilitate a number of enantioselective transformations such as Povarov reactions with secondary amines, Pictet-Spengler reactions with unmodified tryptamine, intramolecular Type-1 aza-Diels-Alder reactions, and A3 reactions with secondary amines. While a more widespread use of our first-generation catalysts has been hampered by their still limited acidity, we now disclose newly developed conjugate-base-stabilized Bronsted acids with significantly increased activity.