Highly Chemoselective Reductive Amination of Carbonyl Compounds Promoted by InCl₃/Et₃SiH/MeOH System

Abstract

A new strategy has been developed for reductive amination of aldehydes and ketones with the InCl3/Et3SiH/MeOH system, which is a nontoxic system with highly chemoselective and nonwater sensitive properties. The methodology can be applied to a variety of cyclic, acyclic, aromatic, and aliphatic amines. Functionalities including ester, hydroxyl, carboxylic acid, and olefin are found to be stable under our conditions. The reaction shows a first-order kinetics profile with respect to both InCl3 and Et3SiH. Spectroscopic techniques such as NMR and ESI-MS have been employed to probe the active and resulting species arising from InCl3 and Et3SiH in MeOH, which are important in deriving a mechanistic proposal. In the ESI-MS studies, we have first discovered the existence of stable methanol-coordinated indium(III) species which are presumably responsible for the gentle generation of indium hydride at room temperature. The solvent attribution was crucial in tuning the reactivity of [In-H] species, leading to the establishment of mild reaction conditions. The system is superior in flexible tuning of hydride reactivity, resulting in the system being highly chemoselective.

Efficient and Highly Chemoselective Direct Reductive Amination of Aldehydes using the System Silane/Oxorhenium Complexes

“…In contrast, organosilanes are mild and environmentally benign reducing agents, and in recent years, several reagent systems containing silanes such as Et 3 SiH/InCl 3 , [6] [7] PhSiH 3 / Bu 2 SnCl 2 , [8] PhSiH 3 /MoO 2 Cl 2 , [9] polymethylhydrosiloxane (PMHS)/TiA C H T U N G T R E N N U N G (O-i-Pr) 4 , [10] and polymethylhydrosil-A C H T U N G T R E N N U N G oxane (PMHS)/trifluoroacetic acid (TFA) [11] have also been employed in reductive amination.…”

Programmed Synthesis Palladium Supported on Fe3O4@C: An Efficient and Heterogeneous Recyclable Catalyst for One-Pot Reductive Amination of Aldehydes with Nitroarenes in Aqueous Reaction Medium

“…We also found that salicylaldehyde, o-chlorobenzaldehyde and 2-chlorobenzaldehyde had low yields (entries 9, 10, 12), those probably due to the intramolecular hydrogen bond, electron withdrawing and steric effects for the aromatic aldehydes during this reaction. Besides, aliphatic aldehydes, regardless of whether they were linear or R-branched, underwent the reductive amination rapidly and gave the products in excellent yields nearly without the formation of any side products (entries [13][14][15]. Table 3 shows the results obtained for reactions carried using benzaldehyde with different nitrobenzenes.…”

“…Due to their importance, several methods have been developed for the preparation of amines, such as direct base-promoted N-alkylation and direct reductive amination [3,4]. However, it's still a challenge to control the monoalkylation of primary amines [5], the synthesis of a wide variety of substituted amines relies heavily on the reductive amination of the carbonyl compounds [6,7], but the method is usually carried out with hydride-based reagents such as NaBH 4 [8], pyridine-BH 3 [9], Zn-AcOH [10], Et 3 SiH-CF 3 CO 2 H [11], Bu 3 SnHDMF [12], InCl 3 -Et 3 SiH [13], and various modified borohydride derivatives [14]. These reagents have certain limitations such as the dependence of a stoichiometric amount of reductant, poor functional group tolerance, side reactions, overalkylation, toxic waste, thermal instability, handling risks, and rigorous reaction conditions [15].…”

Practical One-Pot Synthesis of Secondary Amines by Zinc-Catalyzed Reductive Amination

“…Although hydrogenation and transfer hydrogenation of C=N bonds in the presence of catalytic amounts of metal precursors are the most developed ways, catalytic hydrosilylation is a desirable choice because of mild reaction conditions and straightforwardness [17][18][19]. Indeed, during the last decades several reductive amination protocols based on transition metals or metal free catalysts have been reported [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35]. A number of catalysts rely on precious metals such as rhodium, ruthenium, and iridium.…”