Azocarboxamide-enabled enantioselective regiodivergent unsymmetrical 1,2-diaminations
Yun-Dong Fu, Han Zhang, Beibei Li, Li‐Hua Huang, Xiao Xiao, Min‐Can Wang, Donghui Wei, Guang‐Jian Mei
Abstract
Enantioenriched unsymmetrical vicinal diamines are important basic structural motifs. While catalytic asymmetric intermolecular 1,2-diamination of carbon–carbon double bonds represents the most straightforward approach for preparing enantioenriched vicinal-diamine-containing heterocycles, these reactions are often limited to the installation of undifferentiated amino functionalities through metal catalysis and/or the use of stoichiometric amounts of oxidants. Here, we report organocatalytic enantioselective unsymmetrical 1,2-diaminations based on the rational design of a bifunctional 1,2-diamination reagent, namely, azocarboxamides (ACAs). Under the catalysis of chiral phosphoric acid, unsymmetrical 1,2-diaminations of ACAs with various electron-rich double bonds readily occur in a regiodivergent manner. Indoles prefer dual hydrogen-bonding mode to give dearomative (4 + 2) products, and 3-vinylindoles and azlactones are inclined to undergo unsymmetrical 1,2-diamination via the (3 + 2) process. DFT calculations are performed to reveal the reaction mechanism and the origin of the regio- and enantioselectivity. Guided by computational design, we are able to reverse the regioselectivity of the dearomative unsymmetrical 1,2-diamination of indoles using Lewis acid catalysis. 1,2-diaminations of double bonds represent a fundamental transformation in organic synthesis, the progress of which has largely been limited to symmetrical delivery of equivalent amine species. Here, the authors report a protocol using azocarboxamides to differentiate carbons of some double bonds, resulting in unsymmetrical diaminations, proceeding under organocatalytic conditions.