Cooperative Ruthenium Catalyst for Deaminative Coupling of Primary Amines to Symmetrical Secondary Amines

Abstract

The selective synthesis of secondary amines holds significant importance in organic chemistry, yet the development of an efficient catalytic route remains a challenge. Herein, we report the synthesis, characterization, and application of a well-defined ruthenium (II) catalyst (1) featuring a β-NH pyrazole moiety integrated within a naphthyridine based ligand. This catalyst facilitates the deaminative self-coupling of primary amines to secondary amines through borrowing hydrogen strategy. Notably, the catalyst exhibits exceptional selectivity towards secondary amines, with no formation of overalkylated products or double dehydrogenated nitriles. Moreover, it demonstrates versatility across a wide range of benzylic, heterocyclic, and aliphatic long-chain primary amines. The metal-ligand cooperativity of the catalyst, attributed to the ruthenium metal center and pyrazole unit, enables the concurrent dehydrogenation of primary amines and hydrogenation of secondary imines, thus enhancing the selectivity towards secondary amines, confirmed by DFT calculations. Control experiments revealed the superior performance of β-NH featuring ruthenium complex over its N-methylated counterpart, underscoring the metal-ligand cooperativity in facilitating the deaminative coupling reaction. This study presents a significant advancement in the catalytic synthesis of secondary amines, offering insights into the design of efficient catalytic systems for selective organic transformations.