CHAPTER 3. Catalysis by Networks of Cooperative Hydrogen Bonds

Abstract

The main paradigm of today's chemistry is sustainability. In pursuing sustainability, we need to learn from chemical processes carried out by Nature and realize that Nature does not use either strong acids, or strong bases or fancy reagents to achieve outstanding chemical processes. Instead, enzyme activity leans on the cooperation of several chemical entities to avoid strong acids or bases or to achieve such an apparently simple goal as transferring a proton from an NuH unit to an E unit (NuH + E → Nu–EH). Hydrogen bond catalysis emerged strongly two decades ago in trying to imitate Nature and avoid metal catalysis. Now to mount another step in pursuing the goal of sustainability, the focus is upon cooperativity between the different players involved in catalysis. This chapter looks at the concept of cooperativity and, more specifically, (a) examines the role of cooperative hydrogen bonded arrays of the general type NuH⋯(NuH)n⋯NuH (i.e. intermolecular cooperativity) to facilitate general acid–base catalysis, not only in the solution phase but also under solvent-free and catalyst-free conditions, and, most important, (b) analyzes the capacity of designer chiral organocatalysts displaying intramolecular networks of cooperative hydrogen bonds (NCHBs) to facilitate enantioselective synthesis by bringing conformational rigidity to the catalyst in addition to simultaneously increasing the acidity of key hydrogen atoms so to achieve better complementarity in the highly polarized transition states.