Nobel Prize Awarded for Catalysis

Abstract

Finally, Richard Heck, Ei-ichi Negishi, and Akira Suzuki (pictured) have been awarded the Nobel Prize in Chemistry for palladium-catalyzed cross-coupling in organic synthesis, a long-awaited award that has been celebrated by all organic and organometallic chemists. The impact of the Heck reaction and palladium-catalyzed cross-couplings has been enormous, having totally changed the practice of organic synthesis in research laboratories and in industry. Along with (π-allyl)palladium chemistry, cross-coupling reactions have made palladium the most important transition metal in organic synthesis.1 Although the scope of the palladium-catalyzed alkenylation of aryl, heteroaryl, and alkenyl halides was well established by Heck’s highly detailed experimental work, published in the late 1960s and early 1970s, the importance of this reaction for the synthesis of natural products was not immediately recognized by the community of organic chemists. However, applications of the Heck reaction in total synthesis flourished in the 1980s and nowadays it is one of the methods of choice to create complex organic architectures, as exemplified by Köhler et al. on page 1467 ff. Heck also made seminal contributions in (π-allyl)palladium chemistry and other areas of organometallic chemistry. The development of metal-catalyzed cross-coupling reactions of aryl and alkenyl halides can be traced back to the pioneering work of Kharasch and, later, Kochi, Kumada, Tamao, Corriu, and Sonogashira, among others. However, the full importance of these palladium-catalyzed processes became fully appreciated after contributions made by the late Stille, Negishi, and Suzuki in the 1970s and early 1980s. These discoveries were soon followed by the use of organosilanes as coupling partners by the group of Hiyama. It is important to note that, although Negishi’s work in this area is now associated to the cross-coupling of organozinc reagents, a reaction that carries his name, a perusal of the early literature reveals that Negishi’s group had already examined a wide variety of organometallic nucleophiles as coupling partners, including alanes, zirconium reagents, boron derivatives, and stannanes. The Suzuki cross-coupling of organoboron compounds (also known as the Suzuki–Miyaura reaction, as employed by Klein Gebbink et al. on page 1425 ff.) and the Stille reaction of organostannanes were initially established as the most general and selective palladium-catalyzed cross-coupling reactions. A particularly significant advance was made by the use of triflates and other sulfonates as organic electrophiles in couplings with organostannanes and in Heck alkenylations, which allowed the use of phenols and carbonyl compounds as starting materials. The field matured further thanks to the more in-depth understanding of the mechanisms of these reactions, which led to the development of palladium complexes with very bulky ligands that enable the coupling of alkyl halides and many other organic electrophiles with a wide variety of mild organometallic reagents. The latest flourishing advance in cross-coupling chemistry has been the incorporation of nickel and copper as alternative catalysts and the use of alcohols and amines as the nucleophiles (Buchwald–Hartwig reactions), which has revolutionized heterocyclic synthesis. Needless to say, without the contributions made by Heck, Negishi, and Suzuki, the field of organic chemistry today would look somewhat different, and I, on behalf of ChemCatChem, would like to congratulate them on their achievements.1