Abstract
Hydrogen bonding‐mediated cooperative catalysis is the most prevalent mode of catalysis by enzymes. How to mimic enzymes with small molecules as catalysts to afford general yet selective hydrogen bonding‐mediated cooperative catalysis was a fascinating but unanswered question. The advances in acid and base organocatalysis by chiral organic molecules prompted a search of bifunctional organocatalysts to afford cooperative catalysis. The discovery of synthetically accessible, tunable, yet powerful bifunctional catalysts based on modified cinchona alkaloids greatly facilitated the discovery and development of new activities and selectivities. This in turn enabled the invention of numerous asymmetric transformations, thereby changing hydrogen bonding‐based cooperative catalysis from an unproven idea into a widely applied strategy in asymmetric synthesis. In this chapter, key studies in catalyst discovery and reaction development using modified cinchona alkaloids are presented to illustrate the emerging, continuing rapid evolution, and the current “state of the art” of hydrogen bonding‐based cooperative organocatalysis.