DOI: 10.1002/adsc.201200876 Phosphine-Free Palladium-Catalyzed Decarboxylative Coupling of Alkynylcarboxylic Acids with Aryl and Heteroaryl Halides Police Vishnuvardhan Reddy, a Pottabathula Srinivas, a,b Manne Annapurna, a Suresh Bhargava, b,d Jorg Wagler, c Nedaossadat Mirzadeh, d and Mannepalli Lakshmi Kantam a, * a I & PC Division, CSIR – Indian Institute of Chemical Technology, Hyderabad – 500607, India Fax: : (+ 91)-40-271-93510; phone: (+ 91)-40-271-93510; e-mail: mlakshmi@iict.res.in b RMIT-IICT Research Centre, CSIR – Indian Institute of Chemical Technology, Hyderabad –500607, India c Institut für Anorganische Chemie, Technische Universität, Bergakademie Freiberg, D-09596 Freiberg, Germany d Advanced Materials & Industrial Chemistry Group, School of Applied Sciences, RMIT University, Melbourne, Australia Received: September 29, 2012; Revised: December 10, 2012; Published online: February 22, 2013 Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201200876. Abstract: We herein report the design and develop- ment of a carboxyamido/carbene ligand and its Pd- complex for the decarboxylative coupling of alky- nylcarboxylic acids with aryl and heteroaryl halides to afford arylalkynes. Keywords: alkynylcarboxylic acids; aryl and hetero- aryl halides; decarboxylative coupling reaction; ho- mogeneous conditions; phosphine-free reaction The alkyne moiety is a widely occurring motif of nat- ural products, molecular materials and pharmaceuti- cals. [1] Despite the many methods developed for the formation of arylalkynes and conjugated enynes, the Sonogashira coupling of nucleophilic terminal acety- lenes with aryl halides [2] has almost completely re- placed other classical methods of arylalkyne synthe- sis. [3] However, the formation of the homocoupled by- product from the terminal acetylenes is a drawback to this method, limiting its usage in industrial applica- tions. Remarkable advances have been made in this type of transformation over the past several de- cades. [4,5] Yet there is still much scope for improve- ment in the straightforward synthesis of internal al- kynes from other readily available sources rather than terminal alkynes. As an alternative approach, Pd-cata- lyzed decarboxylative cross-coupling of alkynylcar- boxylic acids with aryl halides and phenylboronic acids have provided attractive protocols [6] with the two main features being the low level by-products and the high reactivity. The use of carboxylic acids as directing groups in different C À C bond forming reactions represents a major breakthrough [7] in modern organic synthesis. Compared with terminal alkynes, carboxylic acids are more readily available, easy to store and simple to handle: they also exhibit higher reactivity. Especially noteworthy are Heck-type couplings by Myers et al., [8] the coupling of a variety of benzoic acids with aryl halides and triflates by Gooßen et al., [9] the direct arylation of benzoic acids by Yu et al. and Daugulis et al., [10] and decarboxylative arylations of activated aliphatic carboxylic acids with aryl halides and tri- flates by Liu et.al. [11] The decarboxylative cross-cou- pling of alkynylcarboxylic acids with aryl halides is another notable decarboxylative C À C bond forming reaction. [12] Recently, pioneering work has established that the Pd-catalyzed decarboxylative couplings of alkACHTUNGTRENNUNGynylcarboxylic acids with aryl halides, [6] arylboronic acids [13] or benzyl halides [14] afford internal alkynes. Still these methods suffer the limitations of the need for highly expensive, toxic and sensitive bulky phos- phines, and additives such as [NBu 4 ]F, silver and/or lithium salts. The copper-catalyzed decarboxylative coupling of alkynylcarboxylic acids with aryl halides has been reported under phosphine-free conditions. [15] However, the scope of these approaches is limited to aryl iodides only. Therefore, a collective methodology able to carry out the decarboxylative coupling of alk- ACHTUNGTRENNUNGynylcarboxylic acids with the aryl and heteroaryl hal- ides under phosphine-free conditions would be highly desirable. In recent years, carbocyclic carbenes have emerged as versatile phosphine-free ligands for homogeneous catalysis. [16] We were intrigued by the concept of using anionic carbocyclic carbenes derived from aromatic nitrones, particularly for the strong sigma-donor abili- ty and anionic nature of the carbene ligand. [16a] More- over, it was shown by us that the amidate donor func- Adv. Synth. Catal. 2013, 355, 705 – 710  2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 705 COMMUNICATIONS