Categories: C-C Bond Formation > Oxygen-containing molecules, Alkynes >

Synthesis of alkynyl ketones, carboxylic acids and derivatives

Related:

---

Recent Literature

A highly efficient copper(I) iodide/N,N,N′,N′-tetramethylethylenediamine (CuI/TMEDA) catalytic system enables the coupling of various terminal alkynes, including 4-iodophenylacetylene, with acid chlorides to afford the corresponding ynones in very good yields in a short time. It is noteworthy that the reaction is conducted under solvent-free conditions at room temperature.
W. Yin, H. He, Y. Zhang, D. Luo, H. He, Synthesis, 2014, 46, 2617-2621.

A polystyrene-supported zinc bromide-ethylenediamine complex is a useful, recyclable heterogeneous catalyst for the rapid and efficient synthesis of α,β-acetylenic ketones in very good yields by cross coupling of acid chlorides with terminal alkynes. The catalyst is easily prepared, stable, reusable, and efficient under the reaction conditions.
A. Keivanloo, M. Bakherad, B. Bahramian, M. Rahmani, S. A. N. Taheri, Synthesis, 2011, 325-329.

A selective coupling of alkynylsilanes and allyltrimethylsilane is catalyzed by 5 mol% of indium tribromide under mild conditions to afford the corresponding α,β-acetylenic ketones and β,γ-unsaturated ketones in excellent yields.
J. S. Yadav, B. V. S. Reddy, M. Sridhar Reddy, G. Parimala, Synthesis, 2003, 2390-2394.

The presence of magnesium chloride, cyanuric chloride, and triethylamine enables a highly efficient copper- and palladium-free cross-coupling of terminal alkynes with structurally diverse sodium carboxylate salts to furnish the corresponding ynones in very good yields at room temperature.
M. N. S. Rad, S. Behrouz, Synlett, 2011, 2562-2566.

A general method for the synthesis of α-alkyl ynones is based on the strategy of electrophilic activation of amides. Its distinctive advantages are attributed to the use of air-stable 1-copper(I) alkynes as mild nucleophiles without any exogeneous ligand.
Y. Weng, L. Min, X. Zeng, L. Shan, X. Wang, Y. Hu, Org. Lett., 2020, 22, 8296-8301.

4-Acyl-1,4-dihydropyridines (DHPs) can be converted into ynones under mild, electrochemical conditions. The reaction proceeds via the homolysis of acyl-DHP under electron activation. The resulting acyl radicals are alkynylated with hypervalent iodine(III) reagents to form the target ynones or ynamides in acceptable yields. The reaction tolerates halides, carboxylates, or alkenes.
X. Luo, P. Wang, Org. Lett., 2021, 23, 4960-4965.

Electrochemical Palladium-Catalyzed Oxidative Sonogashira Carbonylation of Arylhydrazines and Alkynes to Ynones
Y. Wu, L. Zeng, H. Li, Y. Cao, J. Hu, M. Xu, R. Shi, H. Yi, A. Lei, J. Am. Chem. Soc., 2021, 143, 12460-12466.

An efficient palladium-catalyzed reaction of terminal alkynes with triazine esters as carbonyl electrophiles provides a broad array of ynones under CO-, Cu-, ligand-, and base-free conditions. The superior reactivity of these triazine "super-active esters" was rationalized by the strong electron-withdrawing ability and the unique affinity of triazine on palladium via N-Pd coordination, that plays a crucial role for the highly efficient C-O activation.
B. Yu, H. Sun, Z. Xie, G. Zhang, L.-W. Xu, W. Zhang, Z. Gao, Org. Lett., 2015, 17, 3298-3301.

Divalent lanthanide amide complexes catalyze an efficient addition of terminal alkynes to aromatic nitriles at room temperature under solvent-free conditions without any additives to give conjugated ynones in very good yields.
H. Ding, C. Lu, X. Hu, B. Zhao, B. Wu, Y. Yao, Synlett, 2013, 24, 1269-1274.

The reaction of nitriles and alkynyldimethylaluminum reagents, derived from trimethylaluminum and alkynes, provides a simple and efficient access to a wide range of α,β-alkynyl ketones with aliphatic, aromatic, and heteroaromatic substituents in good yield. In the cases of aryl-substituted nitriles, α,β-alkynyl N-H ketimines can also be obtained in high yield.
B. L. Korbad, S.-H. Lee, Synlett, 2013, 24, 1856-1860.

tert-Butyl isocyanide insertion enables a simple and efficient palladium-catalyzed carbonylative Sonogashira coupling. This methodology demonstrates the utility of isocyanides in intermolecular C-C bond construction and provides a novel pathway for the synthesis of alkynyl imines which can undergo simple silica gel catalyzed hydrolysis to afford alkynones. The approach is tolerant of a wide range of substrates and applicable to library synthesis.
T. Tang, X.-D. Fei, Z.-Y. Ge, Z. Chen, Y.-M. Zhu, S.-J. Ji, J. Org. Chem., 2013, 78, 3170-3175.

A palladium-catalyzed carbonylative Sonogashira coupling of aryl bromides using near stoichiometric amounts of carbon monoxide converts a broad substrate scope in good yields. The formed alkynone motive serves as a platform for the synthesis of various heterocyclic structures, including pyrimidines. Furthermore, the presented strategy allows effective ¹³C labeling.
K. T. Neumann, S. R. Laursen, A. T. Lindhardt, B. Bang-Andersen, T. Skrydstrup, Org. Lett., 2014, 16, 2216-2219.

Carbonylative coupling of terminal alkynes with aryliodides in the presence of PdCl₂(PPh₃)₂ as catalyst in 2 eq. of 0.5 M aqueous ammonia, and CO (1 atm) gives the corresponding α,β-alkynyl ketones in good yields.
M. S. M. Ahmed, A. Mori, Org. Lett., 2003, 5, 3057-3060.

A Pd-catalyzed copper-free carbonylative Sonogashira coupling reaction at room temperature was achieved by using water as a solvent under balloon pressure of CO with Et₃N as a base.
B. Liang, M. Huang, Z. You, Z. Xiong, K. Lu, R. Fathi, J. Chen, Z. Yang, J. Org. Chem., 2005, 70, 6097-6100.

Alkynyldimethylaluminum reagents react efficiently with various aromatic and aliphatic acid chlorides without any transition metal as a catalyst to give ynones in good yields.
B. Wang, M. Bonin, L. Micouin, J. Org. Chem., 2005, 70, 6126-6128.

A gold catalyst and a secondary amine work synergistically to produce trisubstituted allenyl aldehydes from readily available aldehydes and hypervalent alkynyl iodides. A subsequent oxidation leads to the desired ynone through an in situ C-C bond oxidative cleavage in the presence of molecular oxygen.
Z. Wang, L. Li, Y. Huang, J. Am. Chem. Soc., 2014, 136, 12161-12165.

The use of a bifunctional organocatalyst and Cs₂CO₃ enables a direct carboxylation of terminal alkynes with CO₂ at atmospheric pressure under mild temperatures to provide a range of propiolic acid derivatives in high yields with broad substrate scope. This work has demonstrated that this organocatalytic method offers a competitive alternative to metal catalysis.
J.-B. Shi, Q. Bu, B.-Y. Liu, B. Dai, N. Liu, J. Org. Chem., 2021, 86, 1850-1860.

The reactivity of sodium methyl carbonate with Grignard and organolithium reagents enables selective syntheses of carboxylic acids, symmetrical ketones, and unsymmetrical ketones.
T. E. Hurst, J. A. Deichert, L. Kapeniak, R. Lee, J. Harris, P. G. Jessop, V. Snieckus, Org. Lett., 2019, 21, 3882-3885.

Pd/C-catalyzed oxidative alkoxycarbonylation of terminal alkynes using alcohols in the presence of tetrabutylammonium iodide under CO/O₂ gave α,β-alkynyl esters and unsymmetrical maleate esters in very good yields depending on the reaction conditions. The protocols eliminate the use of phosphine ligands and offer catalyst recovery. The catalyst was recycled up to six times without significant loss of catalytic activity.
S. T. Gadge, B. M. Bhanage, Synlett, 2013, 24, 981-986.

Tetrabutylammonium fluoride (TBAF) catalyzes a cross-coupling of carbamoyl fluorides with alkynylsilanes to provide alkynamides. C-F bond cleavage is achieved under exceptionally mild conditions (room temperature, low catalyst loadings, and short reaction times) without the need for strongly nucleophilic reagents and/or catalysts. This method tolerates aryl halide moieties.
D. Cadwallader, D. Shevchuk, T. R. Tiburcio, C. M. Le, Org. Lett., 2023, 25, 7369-7373.

An operationally simple, palladium-catalyzed three-component reaction between terminal alkynes, isonitriles, and sodium carboxylates provides N-acyl propiolamide derivatives under mild conditions.
Y. He, Y. Wang, X. Liang, B. Huang, H. Wang, Y.-M. Pan, Org. Lett., 2018, 20, 7117-7120.

2-Oxo-3-butynoates and 2-oxo-3-butynoamides were synthesized by a general, efficient and mild Cu(I)-catalyzed cross-coupling of terminal alkynes and monooxalyl chloride derivatives. Readily available starting materials, mild reaction conditions, wide functional group tolerance, and the obviation of stoichiometric organometallic reagents combine to highlight this reaction.
M. Guo, D. Li, Z. Zhang, J. Org. Chem., 2003, 68, 10172-10174.

Related

A highly efficient oxidation of propargylic alcohols to ynones is catalyzed by copper nanoparticles (Cu Nps) with TBHP or air as oxidants. With bipyridine as the ligand, the reaction was accelerated significantly and led in good to excellent yields to a variety of propargylic alcohols.
C. Han, M. Yu, W. Sun, Y. Yao, Synlett, 2011, 2363-2368.