Over the last two decades, transition metal catalyzed C–H bond activation reactions have emerged as a vibrant area of research, allowing functionalization of otherwise unactivated C–H bonds and offering unconventional disconnection approach for the synthesis of complex molecules.1 Directing group (DG) plays pivotal role in this strategy in controlling the regioselectity. The use of common organic functional groups as DGs obviates the problem of installation and removal of DGs, and thereby boosts up step-economy and versatility of the reaction.1c In this aspect, the use of amine functionality as a DG is highly challenging as it makes strong chelation with metal catalysts. Also high nucleophilic reactivity of amines leads to many undesired side reactions.2 With judicious tuning of reaction conditions, we have successfully engaged free amine DG in C H activation reactions with diverse coupling partners like activated olefins 3a, maleimides 3b and vinyl cyclopropanes under ruthenium and cobalt catalysis, giving succinct access to high value scaffolds. Another class of organic functionalities that have garnered much focus as DG’s in recent years are weakly coordinating amide functionality. In this context, N OMe benzamides were also engaged with allenes for regioselective (4+2) annulation reactions under ruthenium catalysis. In this research colloquium, detailed report on literature background, substrate scope, synthetic utilities and post-functionalizations along with mechanistic investigations of the aforementioned reactions will be presented.












Scheme 1: Amine and amide directed C−H bond activation and functionalization of arenes.

References:

1. (a) Handbook of C–H Transformations: Applications in Organic Synthesis, ed. G. Dyker, Wiley-VCH, Weinheim, 2005;

(b) C–H Activation: Topics in Current Chemistry, ed. J.-Q. Yu and Z. Shi, Springer, Berlin, vol. 292, 2010. (c) Mandal, A.; Dana, S.; Chowdhury, D.; Baidya, M. Chem. Asian. J. 2019, 14, 4074.

2. (a) Alberico, D.; Scott, M. E.; Lautens, M. Chem. Rev. 2007, 107, 174. (b) Arockiam, P. B.; Bruneau, C.; Dixneuf, P. H.; Chem. Rev. 2012, 112, 5879. (c) He, C.; Whitehurst, W; Gaunt, M.J. Chem. 2019, 5, 1.

3. (a) Chowdhury, D.; Dana, S.; Mandal, A.; Baidya, M. Chem. Commun. 2019, 55, 11908. (b) Chowdhury, D.; Dana, S.; Maity, S.; Baidya, M. Org. Lett. 2020, 22, 6760.