Lewis Base Activation of Lewis Acids

Although the concepts of Lewis acid-base interactions have been developed and understood for nearly 80 years, the implications for catalysis of organic reactions have still not been fully realized. In recent years we have outlined the conceptual framework for the counter-intuitive ability of electron-pair donors (Lewis bases) to enhance the electrophilic character of the electron-pair acceptors (Lewis acids) along with the unique opportunities for enantioselective reactions promoted by the catalytically active species thus generated. The main themes of this program are the conceptual development, structural basis, and preparative application of chiral Lewis base catalysis in the main group of the Periodic Table.

This project encompasses three major components of research: methodology, mechanism, and total synthesis. Methodologically, we are investigating the scope of reactions that can be catalyzed by a combination of weak Lewis acids (in Groups 14, 16, and 17) and a chiral Lewis base donor. Good success has been recorded for activation of silicon tetrachloride in directed aldol reactions of enoxysilane derivatives of esters, nitriles, cyanohydrins, ketones, chiral ketones, aldehydes and unsaturated esters, amides and ketones in combination with aldehyde electrophiles. Also, the addition of allyltin reagents and isocyanides (Passerini reaction) to aldehydes has been successful. Total synthesis of selected natural products is frequently undertaken as a vehicle to illustrate and test the limits of a newly developed method.

In recent years we have extended the application of this concept to the Lewis base activation of Lewis acidic reagents in Groups 16 and 17. These reagents are particularly useful for the vicinal functionalization of alkenes initiated by chalcogens and halogens with capture of the putative onium ions by various nucleophiles both inter- and intramolecularly with oxygen, nitrogen and carbon-based nucleophiles. The ability of various Lewis basic moieties to activate the electrophilic functionalization of double bonds has been demonstrated for S, Se, Cl, Br and I. Extensive mechanistic investigations have established the intermediacy and configurational stability of thiiranium and seleniranium ions as well the corresponding halonium ions. These studies have led to the development of catalytic enantioselective chalcogeno- and halofunctionalization reactions.

We actively employ the tools of physical organic chemistry to investigate the foundations of these reactions. We have described structural (X-ray, multinuclear NMR) and mechanistic investigations (kinetics, stereochemistry and computations) on the origin of catalysis and stereoselection in a number of Lewis-base catalyzed processes. In addition, we have constructed a unique Rapid Injection NMR system to allow for in-situ monitoring of fast reactions directly at any temperature, for any combination of reactants, and observing any nucleus.

Read the most recent review: 245, 285, 318, 355

Chiral Lewis Base-Activation of Lewis Acids (Group 14)


Chiral Lewis Base-Activation of Lewis Acids (Group 16)


Chiral Lewis Base-Activation of Lewis Acids (Group 17)


Catalytic Cycle for Enantioselective Sulfenofunctionalization of Alkenes


X-ray Crystal Structure of Catalytically Active Sulfenylating Agent