Iridium complexes with a new type of N^N′‐donor anionic ligand catalyze the N‐benzylation of amines via borrowing hydrogen

Abstract

The development of efficient and eco‐friendly methods for the synthesis of elaborate amines is highly desired as they are valuable chemicals. The catalytic alkylation of amines using alcohols as alkylating agents, through the so‐called borrowing hydrogen process, satisfies several of the principles of green chemistry. In this paper, four neutral half‐sandwich complexes of Ru(II), Rh(III), and Ir(III) have been synthesized and tested as catalysts in the N‐benzylation of amines with benzyl alcohol. The new derivatives contain a N^N′ anionic ligand derived from 5‐(pyridin‐2‐ylmethylene)hydantoin (Hpyhy) that has never been tested in metal complexes with catalytic applications. In particular, the Ir derivatives, [(Cp*)IrX(pyhy)] (X = Cl or H), exhibit high activity along with good selectivity in the process. Indeed, the scope of the optimized protocol has been proved in the benzylation of several primary and secondary amines. The selectivity towards monoalkylated or dialkylated amines has been tuned by adjusting the amine:alcohol ratio and the reaction time. Experimental results support a mechanism consisting of three consecutive steps, two of which are Ir catalyzed, and a favorable condensation step without the assistance of the catalyst. Moreover, an unproductive competitive pathway can operate when the reaction is performed in open‐air vessels, due to the irreversible release of H2. This route is hampered when the reaction is carried out in close vessels, likely because the release of H2 is reversed through metal‐based heterolytic cleavage. From our viewpoint, these results show the potential of the new catalysts in a very attractive and promising methodology for the synthesis of amines.

Construction of biomass-based amines via Ir-mediated N-alkylation: kinetic analysis

“…All of the r, appearing in the network of 1a/2a-to-5a N-alkylation (Scheme 5b), were then calculated based on the obtained rate equations (eqn ( 26)-( 29), Scheme S3 †) and k (Table 3). The calculated r include the 2a-to-3a dehydrogenation (r 1 , eqn (26), Scheme S3 †), 3a/1a-to-4a condensation (r 2 , eqn (27), Scheme S3 †), 4a-to-5a hydrogenation (r 3 , eqn (28), Scheme S3 †), and 5a-to-4a dehydrogenation (r −3 , eqn (29), Scheme S3 †). Fig.…”

“…Typically, N-alkylation of tetrahydrofurfurylamine (1a, amine) using furfuryl alcohol (2a, alcohol) as an alkylating agent was investigated for the synthesis of 1-(2furanyl)-N-[(2-tetrahydrofuranyl)methyl]methanamine (5a, secondary amine) in this research study (Scheme 1c). Due to the excellent catalytic performance of Ir-based homogeneous catalysts in the previously reported N-alkylation reaction (Table S1, ESI †), [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] Ir complexes immobilized in N,N-bidentate ligandfunctionalized covalent triazine frameworks (CTF, Fig. 1a) were well designed as heterogeneous catalysts (Ir/CTF, Fig.…”

Synthesis and Evaluation of 5-(Heteroarylmethylene)hydantoins as Glycogen Synthase Kinase-3β Inhibitors

“…Four known (15 and 17-19) and ten new 5-(heteroarylmethylene)hydantoins (20)(21)(22)(23)(24)(25)(26)(27)(28)(29) were prepare through the Knovenegel condensation of hydantoin with heteroarylaldhydes (Scheme 1). In most cases, the product precipitated from the ethanol/water reaction mixture; however, in the case of 21, 23, 24, and 25, several drops of conc.…”

“…Compound 28 was chosen as an isomer of 18 in which the hydantoin is attached at a different position of the quinoline ring. Since 5-(pyridine-2-ylmethylene)hydantoin ( 17) is known to form chelated complexes with metals [26], we desired to evaluate the possibility that these compounds might non-specifically inhibit metal-dependent enzymes. Our group's previous experience with evaluating 3-aryl-2-hydroxypropenoic acids as inhibitors for Staphylococcus aureus pyruvate carboxylase (SaPC) [27], including selectivity against matrix metalloproteinase-12 (MMP-12) and human carbonic anhydrase (hCAII) (two proteins in a well-established metalloprotease panel [27]), made these a logical choice for the selectivity studies included here too.…”

A Water/Toluene Biphasic Medium Improves Yields and Deuterium Incorporation into Alcohols in the Transfer Hydrogenation of Aldehydes

“…We tested other halide compounds that could behave like 1, but our efforts so far have been unsuccessful. For example, neutral [58] or cationic [59] [Cp*IrCl (N N')] n + (n = 0, 1) species are able of generating hydride species in the aqueous reaction medium, but these species do not exchange deuterium for D 2 O or do so at an insufficient rate to behave as 1. In principle, according to the proposal of Himeda and our own experience, [53][54][55] the generation of the metal-D group must be fast enough to compete kinetically with the TH process to allow a high level of deuterium incorporation.…”