Synthesis of Aryl Alkynes via Copper Catalyzed Decarboxylative Alkynylation of 2-Nitrobenzoic Acids

Abstract

An efficient protocol for the synthesis of internal aryl alkynes was achieved via Cu-catalyzed decarboxylative cross-coupling reactions, and to the best of our knowledge, this is the first example of a Cu-catalyzed decarboxylative alkynylation of benzoic acids with terminal alkynes. This approach utilizes simple Cu salt as catalyst and O, an abundant, clean, and green material, as the oxidant. The reaction tolerates various functional groups, and a variety of internal aryl alkynes were synthesized in 46-83% yields.

Decarboxylative Arylation of α,β‐Unsaturated Carboxylic Acids Using Aryl Triazenes by Copper/Ionic Liquid Combination in PEG‐400

“…Based on the existing literature, control experiments and isolation of products, a plausible mechanism is outlined in Figure . The reaction is assumed to proceed via a copper carboxylate intermediate I , which undergoes decarboxylation to provide the organo‐copper intermediate II .…”

Palladium-Catalyzed Decarbonylative Sonogashira Coupling of Terminal Alkynes with Carboxylic Acids

“…Notably, compared with the oxidative decarboxylative alkynylation, − the scope of carboxylic acids was also rather general. Both electron-rich and electron-deficient benzoic acids underwent decarbonylative coupling with terminal alkynes under the similar reaction conditions.…”

“…During the past decades, great progress has been made. As for the synthesis of internal alkynes, decarboxylative coupling has been achieved by Su, Tan, and Jana dependently (Scheme C); however, the three reactions were conducted under the oxidative conditions with the use of NBS, dioxygen and Ag 2 CO 3 /CuI as the oxidant, which also lead to the production of byproduct 1,3-diynes through homocoupling of terminal alkynes. In addition, steric and (or) electron-deficient carboxylic acids were required in order to facilitate the decarboxylation.…”

“…Herein, we reported a redox-neutral reaction of carboxylic acids with terminal alkynes through decarbonylative coupling . This reaction overcame those issues such as the use of overstoichiometric oxidants, homocouplings of terminal alkynes, and the narrow substrate scope of carboxylic acids encountered in the oxidative decarboxylative couplings. − High tolerance of functional groups was also demonstrated, i.e., alkyl, MeO, CF 3 O, TMS, F, Cl, CF 3 , CN, carbonyl, sulfonamide, and heterocycles all survived well under the reaction conditions. These advantages are also the embodiment of sustainable chemical principles …”

Facile Conversion of Molecularly Complex (Hetero)aryl Carboxylic Acids into Alkynes for Accelerated SAR Exploration

“…[9] The direct transformation of carboxylic acids into the corresponding alkynes is also described in the literature. [10][11][12] However, the reported transformations suffer from a highly limited substrate scope, likely because of the harsh reaction conditions and temperatures (far above the boiling point of the corresponding solvents), significantly limiting their applicability and scalability. Therefore, we envisioned to develop an alternative method for converting an available (hetero)aryl carboxylic acid, originally designed for the formation of a given amide, into the corresponding alkyne derivative.…”