Rhodium-Catalyzed Asymmetric Hydroamination of Allyl Amines

Abstract

A Rh-catalyzed enantioselective hydroamination of allylamines using a chiral BIPHEP-type ligand is reported. Enantioenriched 1,2-diamines are formed in good yields and with excellent enantioselectivities. A diverse array of nucleophiles and amine directing groups are demonstrated, including deprotectable motifs. Finally, the methodology was demonstrated toward the rapid synthesis of 2-methyl-moclobemide.

Ligand-promoted cobalt-catalyzed radical hydroamination of alkenes

“…Metal-catalyzed hydrofunctionalization of readily available alkenes with nitrogen sources is one of the most efficient methods for the synthesis of nitrogen-containing molecules; however, to achieve the high regio-and enantioselectivities of this transformation is still a challenge ( Fig. 2a) [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] . Among several activation strategies for alkene hydroamination, metal-catalyzed hydrogen atom transfer (HAT) reaction exhibits great Markovnikov selectivity and chemoselectivity (Fig.…”

Regio‐ and Enantioselective Formal Hydroamination of Enamines for the Synthesis of 1,2‐Diamines

“…[11] Theh ydroamination of as uitable pre-cursor appeared to be an attractive solution to these problems.T ot he best of our knowledge,o nly two examples of the application of hydroamination for the synthesis of chiral 1,2-diamines have been documented:inthe first achiral aldehyde is used to tether ah ydroxylamine and an allylic amine which is then followed by an intramolecular retro-Cope elimination to install the 1,2-diamine moiety (Scheme 1a), [12] while the other relies on an asymmetric Rh I -MeO-BIPHEP-catalyzed asymmetic hydroamination of secondary allyl amines (Scheme 1b). [13] In 2013, the groups of Hirano,Miura, [14] and Buchwald [15] independently developed an efficient copper(I) hydride protocol for the regio-and enantioselective formal hydroamination of olefins.Since then, this approach has been well demonstrated for av ariety of substrates,a nd has established its broad generality and applicability. [7d,e,g, 16] We speculated that this approach could be extended to the regio-and enantioselective formal hydroamination of enamines,t hus allowing ready access to 1,2-diamines,a nd herein report our results (Scheme 1c).…”

Cobalt-Catalyzed Hydroamination of Alkenes with 5-Substituted Tetrazoles: Facile Access to 2,5-Disubstituted Tetrazoles and Asymmetric Intermolecular Hydroaminations

“…We then explored the possibility of asymmetric hydroamination by using optically active cobalt complexes (Table 2). In particular, the asymmetric intermolecular hydroamination of nonactivated olefins still remains one of the unsolved challenges in modern synthetic organic chemistry, 19) with reported reactions resulting in low enantioselectivity 20) or requiring activated olefin substrates, such as styrenes, 20-28) allenes, 5) dienes, 29,30) allylamines, [31][32][33] etc. [6][7][8][9][10][11][34][35][36][37][38][39][40][41][42] We chose 1a, 1g, and 1l as test substrates for the asymmetric reaction.…”