Gold Particles Supported on Amino‐Functionalized Silica Catalyze Transfer Hydrogenation of N‐Heterocyclic Compounds

Abstract

In this work we demonstrate that exceptionally small gold particles (d = 0.6 AE 0.2 nm) supported on amino-functionalized mesoporous silicate SBA-15 are highly active in transfer hydrogenation of structurally diverse unsaturated N-heterocyclic compounds. The heterocyclic ring is reduced selectively. The gold particles aggregate to a diameter of 4-5 nm in the presence of formic acid/triethylamine (hydrogen donor) during the first catalytic run. In subsequent cycles the nanoparticles maintain their size, yielding a very stable catalytic system that was recycled more than five times. In contrast, analogous SBA catalysts featuring larger (~5-35 nm) gold particles are not active. Excess formic acid also leads to the formation of formamide derivatives of the products of hydrogenation, which can be deformylated quantitatively. Fifteen structurally different substrates, including the scaffolds of quinoline, isoquinoline, quinoxaline, acridine, phenanthroline, quinazoline, and phenanthridine are hydrogenated and deformylated to give the amine products in > 90% overall yield. Deuterium labeling experiments indicate that 1,2-addition with subsequent disproportionation of the formed intermediate is the preferred reaction path over the 1,4addition one, suggesting the participation of a gold hydride species. . [4] However, their excellent reactivity and selectivity are accompanied by difficult or impossible catalyst separation and recycling -issues typically resolved by heterogeneous catalysis. [5] The reported heterogeneous catalytic systems include catalysts based on Ru (supported on SiO 2 , [6,7] hectorite, [8] glucose-derived carbon spheres, [9] poly(4-vinylpyridine), [10] MgO, [11] and RuÀCu nanocages and nanocrystals [12] ), Rh (on Al 2 O 3 , [13] ionic liquid, [14] various metal oxides, [15] MgO, [16] and PEG [17] ), Pd (on hydroxyapatite, [18] methacrylic polymer; [19] tannin- [20] and metal-carbon stabilized [21] ), Pt (unsupported, [22,23] on various metal oxides [15] ), Co (on nitrogendopedgraphene [24,25] ), and Au (unsupported nanoporous, [26] on TiO 2 support [27][28][29] ). The reductions have been performed with pressurized gaseous hydrogen in most cases. [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25]27] On the other hand, transfer hydrogenation reactions [30] employing hydrogen donors such as PhMe 2 SiH/H 2 O, [26] PhMe 2 SiH/EtOH, [29] and HCOOH/triethylamine [28] are often preferred owing to the use of simple reactors, without the need of hazardous gaseous hydrogen. The scope of unsaturated N-heterocycles that were reduced in the aforementioned studies comprises for instance derivatives of quinoline isoquinoline, [7,9,16,23,[25][26][27][28] quinoxaline, [7,9,19,25,29] acridine, [6,11,[23][24][25]27] and phenanthroline. [23] Hydrogenation catalyzed by supported gold clusters is still largely underdeveloped. The main advancement occurred around 2000, when many reports on the regioselective hydrogenation of alkenes, alkynes, aldehydes and ketones emerged. [31] However, the area of...

A decennary update on applications of metal nanoparticles (MNPs) in the synthesis of nitrogen- and oxygen-containing heterocyclic scaffolds

“…The hydrogenation of N-heterocyclic compounds such as isoquinolines (39a), quinolines (35b), quinoxalines (38b), and quinazoline (42a) was proven to be successful using AuNPs supported on 3-aminopropyl-functionalized silica (AuNPs/NH 2 -SBA-15) as the catalyst in anhydrous DMF in formic acid (Scheme 15). 75 The scope of the reaction was also extended for the reduction of acridine, 1,10-phenanthroline, phenanthridine and benzo[h]quinoline. The authors also extended it for the reductive formylation of the above heterocycles using an excess amount of formic acid and deuteration of 2-methyl quinolines using deuterated formic acid and DMF-d 7 .…”

General and Efficient Copper-Catalyzed Oxazaborolidine Complex in Transfer Hydrogenation of Isoquinolines under Mild Conditions

“…Then, products were deformylated with NaOH in H 2 O/EtOH at 100 °C to give the THIQs. 35 In other literature, only one case of transfer hydrogenation of isoquinoline was reported. 19 − 28 They have not studied the functional group tolerance.…”

Recent advances in heterogeneous catalytic hydrogenation and dehydrogenation of N-heterocycles

“…The synthesis of functionalized 1,2,3,4-tetrahydroquinolines (py-THQ) has attracted more and more attention due to their immense utility as biologically active building blocks and key intermediates in the manufacture of pharmaceuticals, alkaloids, agrochemicals, and other fine chemicals [1]. For example, well-known prescription and potential drugs, such as oxamniquine, nicainoprol, viratmycin, and diclofensine, all contain py-THQ units [2,3]. Currently, conventional synthesis methods used to prepare py-THQ derivatives involve catalytic cyclization [4,5], Beckman rearrangement [6], and chemoselective hydrogenation of N-heterocycles (Scheme 1(a)).…”