Recent advances in chiral phosphoric acids for asymmetric organocatalysis: a catalyst design perspective

Asymmetric catalysis, as a core technique in organic synthetic chemistry, can efficiently and precisely construct organic compounds with specific stereochemical structures and plays an indispensable role in many fields such as drug research and development, materials science, and total synthesis of natural products. Chiral phosphoric acid catalysts (CPA) have ascended to become a preeminent category of organic small-molecule catalysts within the precincts of asymmetric catalysis. Their bifunctional nature as both a chiral Brønsted acid and a Lewis base bequeaths them with prodigious catalytic prowess. In a copious number of asymmetric synthesis reactions, they have invariably demonstrated extraordinary efficacy, constituting an inestimable boon for the streamlined synthesis of chiral compounds. Notwithstanding the presence of several review articles on CPA catalysis, the preponderant majority have focused on chemical reactions. By contrast, this review adopts a vantage point of catalyst design. As a Brønsted acid, CPA can be demarcated into three discrete classifications predicated on acidity: common chiral phosphoric acid, chiral phosphoramide, and chiral superacid. The augmentation in acidity corresponds with a concomitant increment in catalytic activity, facilitating a more profound apprehension of reaction mechanisms and application under varying conditions and offering substantial assistance for catalyst design. This review will meticulously analyze the characteristics of these three types of chiral phosphoric acid catalysts and review the representative research achievements from 2004 to 2025, thereby presenting the development path and research status of this active field.