Ru(II)-Catalyzed Oxidative Heck-Type Olefination of Aromatic Carboxylic Acids with Styrenes through Carboxylate-Assisted C-H Bond Activation Suman Dana, Anup Mandal, Harekrishna Sahoo, Sumitava Mallik, Gowri Sankar Grandhi, and Mahiuddin Baidya* Department of Chemistry, Indian Institute of Technology Madras, Chennai 600036, Tamil Nadu, India * S Supporting Information ABSTRACT: A straightforward synthesis of 2-styrylbenzoic acids from aryl carboxylic acids is disclosed through a carboxylate-assisted coupling under Ru(II) catalysis. This protocol is simple and exhibits broad scope with high tolerance of common organic functional groups, providing good to excellent yields of diverse olefinated products. The efficacy of this protocol has been showcased through sequential syntheses of isochromanone, isocoumarin, and formal synthesis of anacardic acid derivative in good yields. A lkenyl aromatic carboxylic acids, such as 2-styrylbenzoic acid and derivatives thereof, have profound synthetic importance in light of their existence in many natural products, agrochemicals, pharmaceuticals, and functional materials (Figure 1). 1 They are also high-value synthons for the production of a large number of commodity chemicals and complex molecular architectures including clinical drug candidates. 2 Consequently, devising synthetic protocols toward these scaffolds has remained the focus of general interest. Traditionally, they have been accessed through multistep Wittig and Peterson olefination processes. 2j-l Although hydroarylation of alkynes 3 and Mizor- oki-Heck coupling 1b of aryl halides are predominant for the synthesis of vinyl arenes, the requirement of prefunctionalized starting materials limits their scope toward this pivotal framework. A straightforward route would be the direct coupling of styrenes with benzoic acids. This approach is advantageous because benzoic acids are inexpensive chemicals with diverse substitution patterns, and styrenes are easily accessible reaction partners. Further, the carboxylic acid functionality can be easily manipulated into various functional groups and also tracelessly removed through protodecarboxylation. 4 In the past two decades, synthetic chemists have witnessed a radical shift beyond the conventional synthesis toward direct use of otherwise unactivated C-H bonds for the functionalization of organic molecules. 5 In this context, Ru(II)-catalyzed reactions turned out to be very promising. 6 A series of new trans- formations, particularly oxidative Heck-type coupling, have been developed by exploiting the complex-induced proximity effect with weakly coordinating and synthetically valuable common organic functional groups. 6b,c While significant advancements on Ru(II)-catalyzed oxidative Heck-type coupling have been accomplished using aromatic amides, esters, anilides, carbamates, and phenol derivatives, 7,8 similar examples with aromatic carboxylic acids are limited (Scheme 1). 9 Furthermore, in a majority of the cases, the choice of coupling partners is largely limited to activated acrylates and only a handful of examples are known with styrene derivatives. 7 There are no reports for the synthesis of 2-styrylbenzoic acids using Ru(II) catalysis. In our program on the development of ruthenium-catalyzed C-H bond activation protocols with the aid of weakly Received: December 9, 2017 Figure 1. Biologically important 2-styrylbenzoic acid derivatives. Scheme 1. Ru-Catalyzed Direct Styrenylation of Benzoic Acids Letter pubs.acs.org/OrgLett Cite This: Org. Lett. XXXX, XXX, XXX-XXX © XXXX American Chemical Society A DOI: 10.1021/acs.orglett.7b03852 Org. Lett. XXXX, XXX, XXX-XXX