Design of Novel Uncharged Organic Superbases: Merging Basicity and Functionality.

ConspectusOne of the constant challenges of synthetic chemistry is the molecular design and synthesis of nonionic, metal-free superbases as chemically stable neutral organic compounds of moderate molecular weight, intrinsically high thermodynamic basicity, adaptable kinetic basicity, and weak or tunable nucleophilicity at their nitrogen, phosphorus, or carbon basicity centers. Such superbases can catalyze numerous reactions, ranging from C-C bond formation to cycloadditions and polymerization, to name just a few. Additional benefits of organic superbases, as opposed to their inorganic counterparts, are their solubility in organic reaction media, mild reaction conditions, and higher selectivity. Approaching such superbasic compounds remains a continuous challenge. However, recent advances in synthetic methodology and theoretical understanding have resulted in new design principles and synthetic strategies toward superbases. Our computational contributions have demonstrated that the gas-phase basicity region of 350 kcal mol-1 and even beyond is easily reachable by organosuperbases. However, despite record-high basicities, the physical limitations of many of these compounds become quickly evident. The typically large molecular weight of these molecules and their sensitivity to ordinary reaction conditions prevent them from being practical, even though their preparation is often not too difficult. Thus, obviously structural limitations with respect to molecular weight and structural complexity must be imposed on the design of new synthetically useful organic superbases, but strategies for increasing their basicity remain important.The contemporary design of novel organic superbases is illustrated by phosphazenyl phosphanes displaying gas-phase basicities (GB) above 300 kcal mol-1 but having molecular weights well below 1000 g·mol-1. This approach is based on a reconsideration of phosphorus(III) compounds, which goes along with increasing their stability in solution. Another example is the preparation of carbodiphosphoranes incorporating pyrrolidine, tetramethylguanidine, or hexamethylphosphazene as a substituent. With gas-phase proton affinities of up to 300 kcal mol-1, they are among the top nonionic carbon bases on the basicity scale. Remarkably, the high basicity of these compounds is achieved at molecular weights of around 600 g·mol-1. Another approach to achieving high basicity through the cooperative effect of multiple intramolecular hydrogen bonding, which increases the stabilization of conjugate acids, has recently been confirmed.This Account focuses on our efforts to produce superbasic molecules that embody many desirable traits, but other groups' approaches will also be discussed. We reveal the crucial structural features of superbases and place them on known basicity scales. We discuss the emerging potential and current limits of their application and give a general outlook into the future.