Current Green Chemistry   Send Orders for Reprints to reprints@benthamscience.net 78 Current Green Chemistry, 2019, 6, 78-95 REVIEW ARTICLE Carbonylation of Aryl Halides in the Presence of Heterogeneous Catalysts Béla Urbán 1 , Máté Papp 1 and Rita Skoda-Földes 1,* 1 Department of Organic Chemistry, Institute of Chemistry, University of Pannonia, Veszprém, Hungary Abstract: Palladium-catalyzed carbonylation in the presence of organic and organometallic nucleo- philes serves as a powerful tool for the conversion of aryl/alkenyl halides or halide equivalents to car- bonyl compounds and carboxylic acid derivatives. To circumvent the difficulties in product separation and recovery and reuse of the catalysts, associated with homogeneous reactions, supported counter- parts of the homogeneous palladium catalysts were developed. The review intends to summarize the huge development that has been witnessed in recent years in the field of heterogeneous carbonylation. A great plethora of supports, organic modifiers on solid surfaces stabilizing metal particles, transition metal precursors, as well as alternative sources for CO was investigated. In most cases, careful optimi- zation of reaction conditions was carried out. Besides simple model reactions, the synthesis of carbon- yl compounds and carboxylic acid derivatives from substrates with different functionalities was per- formed. In some cases, causes of palladium leaching were clarified with detailed investigations. The advantages of immobilized catalysts were shown by several examples. The possibility of catalyst- recycling was proved besides proving that metal contamination of the products could often be kept be- low the detection limit. At the same time, detailed investigations should be carried out to gain a better insight into the real nature of these processes. A R T I C L E H I S T O R Y Received: January 24, 2019 Revised: February 22, 2019 Accepted: March 13, 2019 DOI: 10.2174/2213346106666190321141550 Keywords: Immobilization, supported catalyst, palladium complexes, palladium nanoparticles, catalyst recycling, palladium leaching. 1. INTRODUCTION Since the first example on the synthesis of esters and amides by palladium-catalyzed carbonylation of aryl halides reported by Heck in 1974 [1], the methodology has emerged as a powerful tool for the synthesis of aldehydes, ketones, carboxylic acids and their derivatives, lactones, lactams, etc. [2-6]. It can be used to produce a wide range of substances such as heterocycles [7, 8] pharmaceutical ingredients [9] or natural products [10]. Palladium-catalyzed carbonylations lead to the desired products in good yield and with high se- lectivity usually under very mild conditions. In addition, they are compatible with many functional groups and therefore can be more advantageous for the synthesis of these deriva- tives than conventional methods. However, they suffer from common drawbacks of homogeneous catalytic reactions such as the problem of catalyst recovery and recycling as well as metal-contamination of the crude products. Especially the latter reduces the chances of industrial implementation, since metal contamination in the final products strictly regulated especially in pharmaceuticals [11]. *Address correspondence to this author at the Department of Organic Chemistry, Institute of Chemistry, University of Pannonia, P.O. Box: 158, Veszprém, Hungary; Tel: +36-88-624719; Fax: +36-88-624469; E-mail: skodane@almos.uni-pannon.hu A great variety of methodologies were developed to cir- cumvent these drawbacks, such as the use of polymeric or dendritic ligands, self-supported catalysts, biphasic catalysis [12, 13] or application of ionic liquids as solvents [14, 15]. Heterogeneous catalysts, prepared by anchoring metal com- plexes on solid materials or depositing metal nanoparticles on surfaces modified with stabilizing organic moieties, may ensure easy separation of products as well as an efficient catalyst recycling [16, 17]. As another advantage, they are also suitable for continuous flow applications [18]. Although several heterogeneous catalysts were developed in the past decades for C-C coupling reactions [13], their application in carbonylations has come to the forefront only in the last 10-15 years. In the latter case, the catalytic situa- tion is much more complex. Heterogeneous carbonylations are three-phase reactions, highly influenced by the solubility of CO in the solvent as well as by its adsorption on the sur- face of the catalyst. Moreover, the presence of a high excess of CO compared to palladium is the first step of the catalytic cycle, making the oxidative addition of aryl halides onto the metal, less facile. Its presence may also induce aggregation of palladium leading to catalytically inactive species. As alkoxy- and aminocarbonylation reactions, as well as phosphine free carbonylative Sonogashira- and Suzuki cou- plings were reviewed in 2014 [17], except for some particu- larly interesting results, only the most recent achievements 2213-347X/19 $58.00+.00 © 2019 Bentham Science Publishers