Arylation of Benzylic Amines Using Arylboronates

A Ru-catalyzed direct arylation of benzylic sp carbons of acyclic amines with arylboronates is reported. This highly regioselective and efficient transformation can be performed with various combinations of N-(2-pyridyl) substituted benzylamines and arylboronates. Substitution of the pyridine directing group in the 3-position proved to be crucial in order to achieve high arylation yields. Furthermore, the pyridine directing group can be removed in high yields via a two-step protocol. The direct catalytic cleavage of C H bonds is highly attractive and one of the most investigated, but also most challenging, topics in modern organic synthesis. Within recent years, the field of transition metal catalyzed C H activation reactions is rapidly expanding. Especially, the field of direct functionalization of sp C H bonds has generated many interesting results in previous years. On the other hand, the area of catalytic functionalization of sp C Hbonds hasmatured to a significantly lesser extent and many challenges await to be tackled properly. In 1998, the group of Jun described the first chelation assisted alkylation of benzylamine derivatives by a Ru(0) catalyst. In 2005, Kakiuchi, Chatani, and Murai reported a Ru(0)catalyzed regioselective arylation of aromatic ketones with arylboronates, followed by the discovery of the Sames group to use cyclic imine protecting groups for the arylation of pyrrolidines and piperidine (Scheme 1). Recently, Maes published a pyridine directed arylation of piperidine derivatives (Scheme 1). However, the last two methods (1) For recent reviews on C H activation, see: (a) Ackermann, L. Chem. Rev. 2011, 111, 1315–1345. (b) Yeung, C. S.; Dong, V. M. Chem. Rev. 2011, 111, 1215–1292. (c) Baudoin, O. Chem. Soc. Rev. 2011, 40, 4902–4911. (d) Cho, S. H.; Kim, J. Y.; Kwak, J.; Chang, S. Chem. Soc. Rev. 2011, 40, 5068–5083. (e) Schn€ urch, M.; Dastbaravardeh, N.; Ghobrial, M.; Mrozek, B.; Mihovilovic, M. D. Curr. Org. Chem. 2011, 15, 2694–2730. (f) Colby, D. A.; Bergman, R. G.; Ellman, J. A. Chem. Rev. 2010, 110, 624–655. (g) Daugulis, O. Top. Curr. Chem. 2010, 292, 57–84. (h) Fagnou, K. Top. Curr. Chem. 2010, 292, 35–56. (i) Ackermann, L.; Vicente, R.; Kapdi, A. R. Angew. Chem., Int. Ed. 2009, 48, 9792–9826. (j)McGlacken,G. P.; Bateman, L.M.Chem. Soc. Rev. 2009, 38, 2447–2464. (k) Dyker, G., Ed. Handbook of C H Transformations: Applications in Organic Synthesis; Wiley: 2005; Vol. 2. (2) For recent papers on sp C H bond functionalzation, see: (a) Ackermann, L.; Diers, E.; Manvar, A. Org. Lett. 2012, 14, 1154–1157. (b) Ackermann, L.; Pospech, J.; Graczyk,K.; Rauch,K.Org. Lett. 2012, 14, 930–933. (c) Wencel-Delord, J.; Nimphius, C.; Patureau, F. W.; Glorius, F. Angew. Chem., Int. Ed. 2012, 51, 2247–2251. (d) Tauchert, M. E.; Incarvito, C. D.; Rheingold, A. L.; Bergman, R. G.; Ellman, J. A. J. Am.Chem. Soc. 2012, 134, 1482–1485. (e) Flegeau, E. F.; Bruneau, C.; Dixneuf, P. H.; Jutand, A. J. Am. Chem. Soc. 2011, 133, 10161–10170. (f) Shiota, H.; Ano, Y.; Aihara, Y.; Fukumoto, Y.; Chatani, N. J. Am. Chem. Soc. 2011, 133, 14952–14955. (3) For selected papers on sp C H bond functionalzation, see: (a) Sundararaju, B.; Achard, M.; Sharma, G. V. M.; Bruneau, C. J. Am.Chem.Soc. 2011, 133, 10340–10343. (b) Pan, S.; Endo,K.; Shibata, T. Org. Lett. 2011, 13, 4692–4695. (c) Ghobrial, M.; Harhammer, K.; Mihovilovic, M. D.; Schn€ urch, M. Chem. Commun. 2010, 46, 8836–8838. (d) Rousseaux, S.; Gorelsky, S. I.; Chung, B. K. W.; Fagnou, K. J. Am. Chem. Soc. 2010, 132, 10692–10705. (e) Jazzar, R.; Hitce, J.; Renaudat, A.; Sofack-Kreutzer, J.; Baudoin, O. Chem.;Eur. J. 2010, 16, 2654–2672. (f) Shabashov, D.; Daugulis, O. Org. Lett. 2005, 7, 3657–3659. (4) Kakiuchi, F.; Matsuura, Y.; Kan, S.; Chatani, N. J. Am. Chem. Soc. 2005, 127, 5936–5945. (5) Pastine, S. J.; Gribkov, D. V.; Sames, D. J. Am. Chem. Soc. 2006, 128, 14220–14221. (6) Prokopcova,H.; Bergman, S.D.; Aelvoet,K.; Smout, V.; Herrebout, W.; Van der Veken, B.; Meerpoel, L.; Maes, B. U.W.Chem.;Eur. J. 2010, 16, 13063–13067.