Divergent Transformations of Aromatic Esters: Decarbonylative Coupling, Ester Dance, Aryl Exchange, and Deoxygenative Coupling.

ConspectusAromatic esters are cost-effective, versatile, and commonly used scaffolds that are readily synthesized or encountered as synthetic intermediates. While most conventional reactions involving these esters are nucleophilic acyl substitutions or 1,2-nucleophilic additions─where a nucleophile attacks the carbonyl group, decarbonylative transformations offer an alternative pathway by using the carbonyl group as a leaving group. This transition-metal-catalyzed process typically begins with oxidative addition of the C(acyl)-O bond to the metal. Subsequently, the reaction involves the migration of CO to the metal center, the reaction with a nucleophile, and reductive elimination to yield the final product. Pioneering work by Yamamoto on nickel complexes and the development of decarbonylative reactions (such as Mizoroki-Heck-type olefination) using aromatic carboxylic anhydrides catalyzed by palladium were conducted by de Vries and Stephan. Furthermore, reports have surfaced of decarbonylative hydrogenation of pyridyl methyl esters by Murai using ruthenium catalysts as well as Mizoroki-Heck-type reactions of nitro phenyl esters by Gooßen under palladium catalysis. Our group has been at the forefront of developing decarbonylative C-H arylations of phenyl esters with 1,3-azoles and aryl boronic acids using nickel catalysts. The key to this reaction is the use of phenyl esters, which are easy to synthesize, stabilize, and handle, allowing oxidative addition of the C(acyl)-O bond; nickel, which facilitates oxidative addition of the C(acyl)-O bond; and suitable bidentate phosphine ligands that can stabilize the intermediate. By modification of the nucleophiles, esters have been effectively utilized as electrophiles in cross-coupling reactions, encouraging the development of these nucleophiles among researchers. This Account summarizes our advancements in nucleophile development for decarbonylative coupling reactions, particularly highlighting the utilization of aromatic esters in diverse reactions such as alkenylation, intramolecular etherification, α-arylation of ketones, C-H arylation, methylation, and intramolecular C-H arylation for dibenzofuran synthesis, along with cyanation and reductive coupling. We also delve into reaction types that are distinct from typical decarbonylative reactions, including ester dance reactions, aromatic ring exchanges, and deoxygenative transformations, by focusing on the oxidative addition of the C(acyl)-O bond of the aromatic esters to the metal complex. For example, the ester dance reaction is hypothesized to undergo 1,2-translocation starting with oxidative addition to a palladium complex, leading to a sequence of ortho-deprotonation/decarbonylation, followed by protonation, carbonylation, and reductive elimination. The aromatic exchange reaction likely involves oxidative addition of complexes of different aryl electrophiles with a nickel complex. In deoxygenative coupling, an oxidative addition complex with palladium engages with a nucleophile, forming an acyl intermediate that undergoes reductive elimination in the presence of an appropriate reducing agent. These methodologies are poised to captivate the interest of synthetic chemists by offering unconventional and emerging approaches for transforming aromatic esters. Moreover, we demonstrated the potential to transform readily available basic chemicals into new compounds through organic synthesis.

Deoxygenative Hetero- and Carbofunctionalizations of Diarylketones.

Direct transformations of diarylketones to hetero- and carbofunctionalized diarylmethanes have been developed. The reactions involve a phospha-Brook rearrangement of diphenylphosphine oxide with diarylketones, followed by substitutions with various nucleophiles such as amides, amines, phenols, thiols, and diborylmethane under palladium catalysis to afford the corresponding functionalized diarylmethanes in a reductive manner.

Palladium-Catalyzed Denitrative Synthesis of Aryl Nitriles from Nitroarenes and Organocyanides.

A denitrative cyanation of nitroarenes using organocyanides and a palladium catalyst was developed. The key for this reaction was the utilization of an aminoacetonitrile as a cyano source to avoid the generation of stoichiometric metal- and halogen-containing chemical waste. A wide range of nitroarenes, including heteroarenes and pharmaceutical molecules, can be converted into aryl nitriles.