Homogeneous Catalysis DOI: 10.1002/ange.200902215 Chemoselectivity in Catalytic C  C and C  H Bond Activation: Controlling Intermolecular Carboacylation and Hydroarylation of Alkenes** Michael T. Wentzel, VenkataJaganmohan Reddy, ToddK. Hyster, and Christopher J. Douglas* A major challenge in the development of carbon–carbon s- bond (C C) activation is competitive activation and func- tionalization at C H bonds, [1] which are typically more accessible to metal catalysts (Figure 1). As a result, catalytic C  C activation and functionalization is an under-developed strategy in synthetic organic chemistry. [2] We are aware of only a few prior studies in which competitive C C and C H activation pathways can be controlled. A series of reports from Nakao, Hiyama et al. elegantly demonstrated that nickel-catalyzed aryl C  CN or ortho-C  H activation can be controlled by ligand or substrate choice. [3] In both cases an alkyne was inserted into the activated bond. Jones and co- workers studied competitive C CN and C H activation reactions in allyl cyanides. [4] Milstein and co-workers have extensively studied C C and C H activation in toluene-based pincer systems. [5] As organic substrates for C  C and C  H bond activation become more complex, controlling competing pathways becomes critically important. To this end, we are investigating direct inter- and intramolecular [6] alkene carboacylation with unstrained ketones by C C activation. Herein, we report that C C or ortho-C H activation of ketones is controlled by the appropriate choice of catalyst and solvent. Our success with intramolecular carboacylation [6] led us to contemplate an intermolecular variant (1 + 2 !3 + 4, Scheme 1) for convergent syntheses. Previously, C  C activa- tion of 5 with [{RhCl(C 2 H 4 ) 2 } 2 ] and excess C 2 H 4 yielded fragmentation products 7 and styrene (8) via a Rh-H intermediate (6). [7] This unusual hydroacylation provides the products in good yield, but C 2 H 4 was the only alkene capable of this reaction. [8] We chose [2.2.1]bicycloheptenes for initial study to avoid intermediates with accessible syn-b-hydrides. We heated equimolar amounts of 5 and norbornene for 24 h in the presence of rhodium catalysts (Table 1). Although Wilkin- sons catalyst was ineffective (entry 1), [{RhCl(C 2 H 4 ) 2 } 2 ] resulted in the formation of a new product (10). [9, 10] This C H activation is likely directed by the oxygen atom of the ketone. In CH 3 CN, the conversion decreased, but a small amount of carboacylation product 9 formed (entry 3). [11, 12] A switch to [Rh(cod) 2 ]OTf provided higher conversion, but poor chemoselectivity (entry 5). A solvent screen (entries 6– 9) showed that the product distribution depended on the solvent, with THF providing complete selectivity for 9 (entry 9). It is remarkable that one can select exclusive C C or C  H activation and functionalization by the appropriate choice of catalyst and solvent. The addition of phosphine ligands to the [Rh(cod) 2 ]OTf/THF reactions decreased the yield without affecting the 9/10 ratio (entries 10 and 11). In all cases, 9 and 10 were obtained with good diastereocontrol (>95:5 by 1 H NMR spectroscopy). Excess alkene (10 equiv) Figure 1. C C and C H activation reactions. Scheme 1. Catalytic C C activation reactions with 8-acylquinolines. [*] M.T. Wentzel, V. J. Reddy, T. K. Hyster, [+] Prof. C. J. Douglas Department of Chemistry, University of Minnesota Twin Cities, 207 Pleasant St. SE, Minneapolis, MN 55455 (USA) Fax: (+ 1) 612-626-7541 E-mail: cdouglas@umn.edu [ + ] UMN Undergraduate Research, 2007–2008. [**] We acknowledge the donors of the ACS Petroleum Research Fund for partial support (47565-G1). We thank Dr. Letitia Yao (NMR spectroscopy), Matthew Meyer and Jacob Schmidt (mass spec- trometry), and UMN (start-up funds). Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/anie.200902215. Angewandte Chemie 6237 Angew. Chem. 2009, 121, 6237 –6239  2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim