LIGAND-ACCELERATED CROSS-COUPLING AND MECHANISTIC INVESTIGATIONS

Abstract

Pd-catalyzed cross-coupling, initially developed in the 1970s, has now become an

indispensable tool in synthetic chemistry. To extend the current capability of crosscoupling

can immensely benefit the practice of organic synthesis. In recent years, ligandaccelerated

catalysis has been discovered as an effective strategy to enable challenging

cross-coupling reactions. To this end, tri(1-adamantyl)phosphine has been designed and

synthesized. The new ligand enabled the development of more sustainable synthetic

protocols for industrial chemicals, pharmaceuticals, and materials and the mechanistic

investigations of several important catalytic intermediates.

Specifically, Chapter 2 describes the synthesis of tri(1-adamantyl)phosphine and

detailed characterization of its properties (e.g., stability against cyclometalation, steric, and

electronic parameters). Ligand-accelerated Suzuki-Miyaura coupling was demonstrated

and found to be generally applicable to many classes of substrates. Results on ligand

structure-property relationships inspired the later development of diamondoid phosphines

in our laboratory.

Chapter 3 details the synthesis of tri(1-adamantyl)phosphine-ligated organopalladium

cations, key intermediates in unconventional base-free transmetalation of boronic acids.

By decoupling the role of base from transmetalation, we circumvented the

protodeboronation of sensitive boron reagents and demonstrated the first general

polyfluoroarylation methods of aryl halides and diazonium salts using commercial reagents.

These methods enabled rapid access to a wide range of material-like polyfluoroaromatic

scaffolds.

Finally, in Chapter 4, the first experimental evidence of monoligated palladium(0)

complexes in solution is discussed. The generation and structural characterization of such

intermediates lend strong credence to previous mechanistic hypothesis and paved the way

to more detailed investigations of highly unsaturated “12 e-” palladium(0) species in

stoichiometric and catalytic reactions.