Anti-Markovnikov Intermolecular Hydroamination of Alkenes and Alkynes: A Mechanistic View

[Image: see text] Hydroamination, the addition of an N–H bond across a C–C multiple bond, is a reaction with a great synthetic potential. Important advances have been made in the last decades concerning catalysis of these reactions. However, controlling the regioselectivity in the amine addition toward the formation of anti-Markovnikov products (addition to the less substituted carbon) still remains a challenge, particularly in intermolecular hydroaminations of alkenes and alkynes. The goal of this review is to collect the systems in which intermolecular hydroamination of terminal alkynes and alkenes with anti-Markovnikov regioselectivity has been achieved. The focus will be placed on the mechanistic aspects of such reactions, to discern the step at which regioselectivity is decided and to unravel the factors that favor the anti-Markovnikov regioselectivity. In addition to the processes entailing direct addition of the amine to the C–C multiple bond, alternative pathways, involving several reactions to accomplish anti-Markovnikov regioselectivity (formal hydroamination processes), will also be discussed in this review. The catalysts gathered embrace most of the metal groups of the Periodic Table. Finally, a section discussing radical-mediated and metal-free approaches, as well as heterogeneous catalyzed processes, is also included.