Mechanism-Driven Development of Group 10 Metal-Catalyzed Decarbonylative Coupling Reactions.

Transition-metal-catalyzed cross-coupling reactions are widely used in both academia and industry for the construction of carbon-carbon and carbon-heteroatom bonds. The vast majority of cross-coupling reactions utilize aryl (pseudo)halides as the electrophilic coupling partner. Carboxylic acid derivatives (RC(O)X) represent a complementary class of electrophiles that can engage in decarbonylative couplings to produce analogous products.

Decarbonylative Fluoroalkylation at Palladium(II): From Fundamental Organometallic Studies to Catalysis.

This Article describes the development of a decarbonylative Pd-catalyzed aryl-fluoroalkyl bond-forming reaction that couples fluoroalkylcarboxylic acid-derived electrophiles [RC(O)X] with aryl organometallics (Ar-M'). This reaction was optimized by interrogating the individual steps of the catalytic cycle (oxidative addition, carbonyl de-insertion, transmetalation, and reductive elimination) to identify a compatible pair of coupling partners and an appropriate Pd catalyst. These stoichiometric organometallic studies revealed several critical elements for reaction design.

Nickel-Catalyzed Decarbonylative Synthesis of Fluoroalkyl Thioethers.

This report describes the development of a nickel-catalyzed decarbonylative reaction for the synthesis of fluoroalkyl thioethers (RSR) from the corresponding thioesters. Readily available, inexpensive, and stable fluoroalkyl carboxylic acids (RCOH) serve as the fluoroalkyl (R) source in this transformation. Stoichiometric organometallic studies reveal that R-S bond-forming reductive elimination is a challenging step in the catalytic cycle.

Nickel-Catalyzed Decarbonylative Amination of Carboxylic Acid Esters.

The reaction of carboxylic acid derivatives with amines to form amide bonds has been the most widely used transformation in organic synthesis over the past century. Its utility is driven by the broad availability of the starting materials as well as the kinetic and thermodynamic driving force for amide bond formation. As such, the invention of new reactions between carboxylic acid derivatives and amines that strategically deviate from amide bond formation remains both a challenge and an opportunity for synthetic chemists.

Base-free nickel-catalysed decarbonylative Suzuki-Miyaura coupling of acid fluorides.

The Suzuki-Miyaura cross-coupling of organoboron nucleophiles with aryl halide electrophiles is one of the most widely used carbon-carbon bond-forming reactions in organic and medicinal chemistry. A key challenge associated with these transformations is that they generally require the addition of an exogenous base, the role of which is to enable transmetallation between the organoboron nucleophile and the metal catalyst. This requirement limits the substrate scope of the reaction because the added base promotes competitive decomposition of many organoboron substrates.