Aryl/heteroaryl pentafluorobenzenesulfonates (ArOPFBs): new electrophilic coupling partners for room temperature Suzuki–Miyaura cross-coupling reactions Jayan T. Joseph a,b , Ayyiliath M. Sajith b , Revanna C. Ningegowda b , Archana Nagaraj b , K. S. Rangappa a , Sheena Shashikanth a,⇑ a Department of Studies in Chemistry, Manasagangothri, University of Mysore, Mysore 570006, India b Syngene International Ltd, Biocon Park, Bommasandra IV Phase, Jigani Link Road, Bangalore 560099, India article info Article history: Received 29 June 2015 Revised 9 July 2015 Accepted 10 July 2015 Available online 16 July 2015 Keywords: Pentafluorobenzenesulfonates Cross-coupling Palladium Suzuki–Miyaura cross-coupling abstract The first cross-coupling reaction between aryl/heteroaryl pentafluorobenzenesulfonates and aryl/heteroaryl boronic acids under mild conditions is described. The successful synthesis of highly ortho substituted biaryls and high chemoselectivity of these bench stable intermediates over tosylates, triflates, mesylates, and chlorides increases its scope as a valuable cross-coupling partner. The generality of this protocol was further extended to other boron containing nucleophiles (boronates, trifluoroborates) and alkyl boronic acids. Ó 2015 Elsevier Ltd. All rights reserved. Introduction The Suzuki–Miyaura cross-coupling methodology is, debatably, one of the most malleable method, employed in the area of organic synthesis for carbon–carbon bond forming reactions. 1 The pres- ence of biaryls and heterobiaryls in advanced materials, 2 molecules of biological importance, 3 and natural products, 1 highlights the sig- nificance of developing efficient protocols for their synthesis. Over the decades, the use of aryl/heteroaryl bromides and iodides as electrophilic cross-coupling partners has been well documented in the literature. 1 Activated aryl/heteroaryl chlorides, as cross- coupling partners are also well studied by various researchers across the globe. 4 Efforts to utilize pseudo halides (triflates, tosylates, mesylates, nonaflates, phosphates, diaryl sulfates, fluorosulfates) 5,6 have expanded the substrate scope for these transformations, thereby, making it widely applicable in the field of diversity oriented syn- thesis (DOS). Despite these advances in pseudo halides as cross- coupling partners, the necessity to use highly demanding catalytic systems 5–7 opens the room for developing new coupling partners, which can effect these transformations under mild conditions. Considering the utility of carbon–carbon bonds, we shifted our focus on developing a new electrophilic cross-coupling partner for the Suzuki–Miyaura reaction. Results/discussion At the outset of our studies, we were interested in developing an efficient protocol which allows the use of aryl/heteroaryl pentafluorobenzenesulfonates in carbon–carbon bond forming reaction under mild conditions. By doing so, the phenolic group can be used as a means to introduce the desired functionality in the aromatic/heteroaromatic ring and then be converted into a carbon–carbon bond via a pentafluorobenzenesulfonate intermedi- ate. 8 To the best of our knowledge, this is the first Letter on Suzuki–Miyaura cross-coupling process employing aryl/heteroaryl pentafluorobenzenesulfonates. For this study, a wide range of activated and deactivated aryl/heteroaryl pentafluorobenzenesulfonates (ArOPFBs) were synthesized from the corresponding phenols (Fig. 1). These inter- mediates were obtained as crystalline solids and can be stored under normal lab conditions for long periods of time. Literature studies indicate that, electrophiles containing an electron donating group are often difficult coupling partners in Suzuki–Miyaura reaction. 9 Accordingly, we used a deactivated 3,5-dimethoxyphenyl pentafluorobenzenesulfonate and 4-meth- oxyphenyl boronic acid as the model substrate for optimization http://dx.doi.org/10.1016/j.tetlet.2015.07.033 0040-4039/Ó 2015 Elsevier Ltd. All rights reserved. ⇑ Corresponding author. E-mail address: shashis1956@gmail.com (S. Shashikanth). Tetrahedron Letters 56 (2015) 5106–5111 Contents lists available at ScienceDirect Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet