Synthesis of Unsymmetrical Vicinal Diamines via Directed Hydroamination

Abstract

Vicinal diamines are a common motif found in biologically active molecules. The hydroamination of allyl amine derivatives is a powerful approach for the synthesis of substituted 1,2-diamines. Herein, the rhodium-catalyzed hydroamination of primary and secondary allylic amines using diverse amine nucleophiles, including primary, secondary, acyclic, and cyclic aliphatic amines to access a wide range of unsymmetrical vicinal diamines, is presented. The utility of this methodology is further demonstrated through the rapid synthesis of several bioactive molecules and analogs.

Cobalt-catalyzed amination of aziridines and azetidines toward 1,2- and 1,3-diamines

“…4 Particularly, in the presence of a transition-metal catalyst, such as [Rh], [Cu], [Fe], [Pd], etc. , alkenes 5 or aziridines 6 react with amines to form 1,2-diamines. Unlike their 1,2-diamine counterparts, only a few methods for the synthesis of 1,3-diamines have been described.…”

Palladium-Catalyzed anti-Michael-Type (Hetero)arylation of Acrylamides

“…In recent years, transition-metal-catalyzed substrate-directed hydrofunctionalization of unactivated alkenes has emerged as a prominent tool in synthetic organic chemistry. − Particularly, the use of bidentate directing groups, such as an aminoquinoline group, − promotes a regioselective nucleometalation process with various carbon and heteroatom nucleophiles by suppressing undesired β-hydrogen elimination. − While these reactions established the regioselective addition of nucleophiles to unactivated alkenes (i.e., electronically unbiased alkenes) by generating a five-membered metallacycle, the efficiency of the strategy in an inverse electron-demand nucleophilic addition is unclear . We envisioned that introducing an appropriate bidentate directing group would determine the regioselectivity of the addition step beyond the electronic bias of α,β-unsaturated carbonyl compounds.…”

Ring Opening of Aziridines by Pendant Sulfamates Allows for Regioselective and Stereospecific Preparation of Vicinal Diamines

“…Vicinal diamines (1,2-diamines) are well represented in molecules of value, including those used as medicines, ligands, and agrochemicals. − Given their importance to multiple areas of synthetic chemistry, it is no surprise that numerous protocols have been invented for their construction. − Diamination of olefins − and untethered (intermolecular) aminolysis − of aziridines are common strategies for accessing these motifs (Scheme ). The direct diamination of olefins is a powerful approach for the construction of vicinal diamines as it installs both nitrogens in a single synthetic step; some limitations of existing protocols include harsh reaction conditions, limited substrate scope, and issues with regioselectivity and stereoselectivity.…”