FULL PAPER DOI: 10.1002/ejoc.201403644 Palladium-Catalyzed Oxidative Aminocarbonylation by Decarboxylative Coupling: Synthesis of Alkynyl Amides Jinil Hwang, [a] Jinseop Choi, [a] Kyungho Park, [a] Wonyoung Kim, [a] Kwang Ho Song,* [b] and Sunwoo Lee* [a] Keywords: Synthetic methods / Palladium / Carbonylation / Alkynes / Amides Alkynyl amides were synthesized from a palladium-cata- lyzed coupling reaction of alkynyl carboxylic acids and amines under carbon monoxide. The reaction was conducted with palladium(II) acetate (5 mol-%) and silver(I) oxide Introduction Transition-metal-catalyzed carbonylations, which are coupling reactions in the presence of carbon monoxide, have been developed and widely used for the synthesis of a number of carbonyl compounds such as ketones, aldehydes, amides, and esters. These reactions with carbon monoxide are valued because of their simplicity and atom economy. [1] In addition, a variety of reactions such as Heck, [2] Suzuki, [3] Stille, [4] and Sonogashira [5] coupling reactions have been employed as carbonylative couplings to produce desired ketones. We were first to report the palladium-catalyzed de- carboxylative carbonylation for the synthesis of alkynyl ketones from the coupling reactions of alkynyl carboxylic acids and aryl halides in the presence of carbon mon- oxide. [6] Although many kinds of decarboxylative coupling reactions have been developed by our group and others, [7] a decarboxylative oxidative carbonylation has never been reported. Therefore, we have focused on developing the syn- thesis of alkynyl amides by using a decarboxylative oxidat- ive carbonylation. In the pharmaceutical industry, the amide functionality is one of the most important building blocks for the synthe- sis of bioactive compounds. [8] Alkynyl amides are also im- portant building blocks. Among the numerous methods to prepare alkynyl amides, the coupling reaction between a carbamoyl chloride and a terminal alkyne has most often [a] Department of Chemistry and Institute of Basic Science, Chonnam National University, Gwangju 500-757, Republic of Korea E-mail: sunwoo@chonnam.ac.kr [b] Department of Chemical & Biological Engineering, Korea University, Seoul, 1360713, Republic of Korea E-mail: khsong@korea.ac.kr Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/ejoc.201403644. Eur. J. Org. Chem. 2015, 2235–2243 © 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 2235 (1.0 equiv.) in acetonitrile at 80 °C for 1 h. This method pro- vides good to moderate product yields and good functional group tolerance towards ketone, ester, and nitrile groups. been used [Scheme 1 (a)]. [9] However, this method has some drawbacks, as there are limited types of carbamoyl chlor- ides commercially available and they are moisture sensitive. A similar reaction type, the reaction of propiolic acid derivatives with amines, has also been employed [Scheme 1 (b)]. [10] However, this process requires multiple reaction steps to transform the acid into an active func- tional group such as an ester and acid chloride. Recently, Zhu and co-workers reported the copper-catalyzed direct oxidative coupling of propiolic acid and formamide, but only one example was described. [11] An alternative method, the transition-metal-mediated or -catalyzed oxidative carb- onylation of terminal alkynes and amines in the presence of carbon monoxide has been reported, but there are few published papers [Scheme 1 (c)]. Hoberg and co-workers re- ported a noncatalytic system with a nickel complex for an oxidative aminocarbonylation. [12] Gabriele and co-workers first reported a PdI 2 -catalyzed oxidative aminocarbon- ylation, [13] and the Yamamoto group employed PdCl 2 /PPh 3 as a catalytic system in the synthesis of an alkynyl amide. [14] Recently, Bhanage’s research group developed a hetero- geneous reusable palladium catalytic system for an oxidat- ive aminocarbonylation. [15] However, these methods employ only four or five types of aryl alkynes in their coupling reac- Scheme 1. Synthesis of alkynyl amides.