Expedient Cobalt-Catalyzed C-H Alkynylation of (Enantiopure) Benzylamines Vinod G. Landge, †,§ Siba P. Midya, †,§ Jagannath Rana, †,§ Dinesh R. Shinde, ‡ and Ekambaram Balaraman* ,†,§ † Catalysis Division and ‡ Central NMR Facility, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411008, India § Academy of Scientific and Innovative Research, New Delhi 110 025, India * S Supporting Information ABSTRACT: A unified strategy for cobalt-catalyzed ortho-C- H bond alkynylation of benzylamines is reported. Simple, commercially available CoBr 2 was used as a cobalt source. The developed alkynylation strategy is robust and efficient and has a broad substrate scope including 1°,2°, and 3° benzylamines. The mechanistic study shows that C-H bond cleavage is reversible, and the kinetic study illustrates that the rate of reaction depends solely on the catalyst. T ransition-metal-catalyzed ubiquitous C-H bond activation circumvents the necessity of prefunctionalization of an organic molecule and has great demand in chemical synthesis, pharmaceuticals, and the development of functional materials. 1 In particular, C-H bond alkynylations have been identified as increasingly powerful alternatives to the classical palladium- catalyzed cross-coupling reaction. 2 Until recently, a majority of C-H bond alkynylation strategies have relied on precious and less abundant 4d and 5d transition metals. 3 However, the development of catalysts based on the naturally more abundant and economical first-row transition metals 4-6 for similar or better reactivity is still rare. On the other hand, after Daugulis’s promising work 7 on bidentate directing-group assisted tran- sition-metal-catalyzed activation of inert C-H bonds, several groups have been extensively exploiting this strategy. It is well recognized that the bidentate directing-group stabilizes tran- sition metals in high oxidation states and is able to deliver the active catalytic site to a proximal C-H bond, typically via the formation of a five- or a six-membered metallacycle intermediate, and entails the C-H bond activation. In this context, the directing group assisted C-H bond activation of arenes catalyzed by inexpensive, benign first-row transition metals has gained considerable momentum with great potential applications to emulate the selectivity and reactivity of precious-metal catalysts. 8 In recent times, a notable progress in C-H bond functionaliza- tion has been accomplished using air-stable, inexpensive cobalt catalysts. 8k,9 Despite notable efforts in bidentate group directed C-H bond alkynylation catalyzed by cobalt(II)- and nickel(II)-based systems, previous reports have been limited to electron-deficient benzamide derivatives. 4d-h,6c,d Moreover, Cp*Co(III)-catalyzed C 2 -selective C-H bond alkynylation of indole derivatives was also reported using hypervalent iodine-alkyne reagents 6a and bromoalkynes. 6b However, the activation of the ortho-C(sp 2 )-H bond located further away from the coordinating functional group (or directing group; DG) remains a noteworthy challenge. To the best of our knowledge, there is no report on C-H bond activation of the ortho-C(sp 2 )-H bond of benzylamines catalyzed by first-row transition metals except one pioneering example of cobalt-catalyzed alkenylation developed by Daugulis and co-workers. 8g This is due to the geometric flexibility of the substrate, which does not permit cyclometalation (Scheme 1b). Benzylamines constitute important synthetic precursors and are ubiquitous in agrochemical, peptide, pharmaceutical, and functional materials. 10 Various effective, practical methods have been developed to access benzylamines. Indeed, the stereo- chemistry at the benzylic position of α-substituted benzylamines can also be readily introduced using well-explored asymmetric synthesis technologies. Herein, we disclose a versatile and Received: August 26, 2016 Scheme 1. Directed-Group-Assisted Cobalt-Catalyzed C-H Bond Activation Letter pubs.acs.org/OrgLett © XXXX American Chemical Society A DOI: 10.1021/acs.orglett.6b02549 Org. Lett. XXXX, XXX, XXX-XXX