Synthesis, Table of Contents Synthesis 2019; 51(07): 1649-1654DOI: 10.1055/s-0037-1611938 paper © Georg Thieme Verlag Stuttgart · New YorkSelective ortho-Metalation of a Fluoroarene with Knochel–Hauser Base and Reactions with Various Electrophiles Authors Author Affiliations Markus Baenziger* a Novartis Pharma AG, GDD/TRD/Chemical & Analytical Development, 4056 Basel, Switzerland Email: markus.baenziger@novartis.com Sumesh Eswaran b Anthem Biosciences Private Limited, No 49, Canara Bank Road, Bommasandra, 560 099 Karnataka, India Yifan Jiang c Department of Chemistry, University College London, 20 Gordon Street, London, WC1H 0AJ, UK Gopu Kasinathan b Anthem Biosciences Private Limited, No 49, Canara Bank Road, Bommasandra, 560 099 Karnataka, India Recommend Article Abstract Buy Article(opens in new window) All articles of this category(opens in new window) Abstract Selective ortho-metalation of 1-bromo-2-(1,1-difluoroethyl)-4-fluorobenzene was achieved with the Knochel–Hauser base (TMPMgCl·LiCl) in position 5 of the aromatic ring. The magnesiated intermediate was reacted with a variety of electrophiles to obtain the products in good yields. The work was successfully extended to a Negishi coupling, after transmetalation with ZnCl2 and Pd-catalyzed reaction with 4-iodotoluene. Key words Key words ortho-metalation - TMPMgCl·LiCl - Knochel–Hauser base - Negishi coupling - fluoroaromatic Full Text References References 1 Tria GS, Abrams T, Baird J, Burks HE, Firestone B, Gaither LA, Hamann LG, He G, Kirby CA, Kim S, Lombardo F, Macchi KJ, McDonnell DP, Mishina Y, Norris JD, Nunez J, Springer C, Sun Y, Thomsen NM, Wang C, Wang J, Yu B, Tiong-Yip C.-L, Peukert S. J. Med. Chem. 2018; 61: 2837 2a Krasovskiy A, Krasovskaya V, Knochel P. Angew. Chem. Int. Ed. 2006; 45: 2958 2b Lin W, Baron O, Knochel P. Org. Lett. 2006; 8: 5673 3 Unsinn A, Rohbogner CJ, Knochel P. Adv. Synth. Catal. 2013; 355: 1553 4a The Chemistry of Organolithium Compounds . Rappoport Z, Marek I. Wiley-VCH; Weinheim: 2004 4b Clayden J. Organolithiums: Selectivity for Synthesis. In Tetrahedron Organic Chemistry. Vol. 23. Pergamon; Oxford: 2002 4c Hartung CG, Snieckus V. Modern Arene Chemistry . Astruc D. Wiley-VCH; Hoboken: 2002: 330-367 5 Organometallics in Synthesis: A Manual . Schlosser M. Wiley-VCH; Weinheim: 1994 6a Choppin S, Gros P, Fort Y. Org. Lett. 2000; 2: 803 6b Cuperly D, Gros P, Fort Y. J. Org. Chem. 2002; 67: 238 6c Gros P, Fort Y, Caubère P. J. Chem. Soc., Perkin Trans. 1 1997; 3071 7a Sakurada I, Hirabayashi T, Maeda Y, Nagasue H, Mizuno T. WO 2015160636, 2015 7b Batista JH. C, dos Santos FM, Bozzini LA, Vessecchi R, Oliveira AR. M, Clososki GC. Eur. J. Org. Chem. 2015; 967 7c Dong Z, Clososki GC, Wunderlich SH, Unsinn A, Li J, Knochel P. Chem.–Eur. J. 2009; 15: 457 8 Blangetti M, Fleming P, O’Shea DF. J. Org. Chem. 2012; 77: 2870 9a Balkenhohl M, Salgues B, Hirai T, Karaghiosoff K, Knochel P. Org. Lett. 2018; 20: 3114 9b Haas D, Hammann JM, Greiner R, Knochel P. ACS Catal. 2016; 6: 1540 10 Farina V, Krishnan B. J. Am. Chem. Soc. 1991; 113: 9585 11 For a review on halogen dance reactions: Schnürch M, Spina M, Khan AF, Mihovilovic MD, Stanetty P. Chem. Soc. Rev. 2007; 36: 1046 Supplementary Material Supplementary Material Supporting Information (PDF)
