TEMPO-Based Organocatalyst Design

Abstract

Recently there has been an increased interest in the development of small molecule electrooxidation catalysts such as (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO), for multistep electrochemical alcohol oxidation. Several TEMPO derivatives have long been used to electrochemically oxidize short chain alcohols and various sugars to the corresponding aldehydes and carboxylic acids under physiological aqueous conditions. However, many nitroxyl radical-containing species decompose rapidly in an oxidized state and are therefore ineffective as alcohol oxidation catalysts. Furthermore, building libraries of such a catalyst is difficult due to the limited number of commercially available TEMPO derivatives and the lack of modular synthetic pathways for more complicated TEMPO structures. A promising alternative to the physical preparation of such libraries is the use of computational modeling to allow for in silico catalytic screening of a much wider range of TEMPO compounds. We have recently developed a descriptive model that correlates the electrocatalytic activity of nitroxyl radical catalysts to their redox potentials under aqueous conditions. Based on fundamental insights derived from this model, we have designed several highly active and promiscuous catalytic materials in the form of redox polymers capable of oxidizing a wide range of primary and secondary alcohols as well as several amines. In addition, we have recently aimed at enhancing the selectivity of nitroxyl radical catalysts by incorporating highly active TEMPO derivatives into the active site of an artificial thermostable protein.