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As a Widely Applicable, Homogeneous Catalyst for Aerobic RESEARCH ARTICLE AEROBIC OXIDATION 2015 © The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. Distributed Silver(I) as a widely applicable, homogeneous under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). catalyst for aerobic oxidation of aldehydes toward 10.1126/sciadv.1500020 carboxylic acids in water—“silver mirror”: From stoichiometric to catalytic Mingxin Liu, Haining Wang, Huiying Zeng, Chao-Jun Li* The first example of a homogeneous silver(I)-catalyzed aerobic oxidation of aldehydes in water is reported. More than 50 examples of different aliphatic and aromatic aldehydes, including natural products, were tested, and all of them successfully underwent aerobic oxidation to give the corresponding carboxylic acids in extremely high yields. The reaction conditions are very mild and greener, requiring only a very low silver(I) catalyst loading, using atmospheric oxygen as the oxidant and water as the solvent, and allowing gram-scale oxidation with only 2 mg of our catalyst. Chromatography is completely unnecessary for purification in most cases. Oxidation is a central task for organic chemists to achieve conversion of We began our investigation by introducing various silver(I) salts or different organic compounds. Among them, oxidation of aldehydes to complexes to benzaldehyde as a standard in air at atmospheric pressure give carboxylic acids is one of the most well-known and most frequently without a balloon in a sealed tube (Table 1). We found the efficiency of used methodologies (1, 2), for example, by stoichiometrically using the the transformation to be strongly affected by the presence of inorganic Cr(IV)-based Jones reagent (3, 4), the Ag(I)-based Tollen’s reaction (5), salt (for example, entries 1 and 2). When the reaction was carried out with- the Cu(II)-based Fehling’s reaction (6), and the permanganate reagents out oxygen, a very low yield was obtained (entry 3), reflecting a stoichi- (7). Although it has long been known that aldehydes are very prone to ometricaldehydeoxidation.Theanionsofthesaltwerethentested. oxidation, methods to achieve a highly efficient and clean transfor- Besides formate, only fluoride and tetrafluoroborate provided the ox- mation of aldehydes to carboxylic acids under mild and greener con- idation product (entries 4 to 7). Considering that tetrafluoroborate ditions are still scarce. Even today, most such oxidations still require might undergo hydrolysis to give fluoride in situ, fluoride was thus chosen stoichiometric amounts of hazardous oxidants (8–25)andoftentake as the standard anion to conduct further investigations. Upon examining place in harmful solvents. the cation, surprisingly, it seemedtobetheonlyoneenablingtheox- With its natural abundance and inherent greener characteristics, idation (entries 8 to 11). Sodium fluoride was therefore selected as the water has been a desirable solvent for chemists (26–28). Although bio- salt for optimizing the conditions. We then tested different ligands logical oxidations in water using enzymes or microorganisms are well (entries 12 to 14) and found that the combination of chelating bipyridine − recognized (29–34), it was only in 2000 that Sheldon established an as a ligand and a noncoordinating PF6 as the counter-ion (entry 14) aqueous-phase homogeneous catalytic aerobic oxidation methodology achieved a quantitative yield of the corresponding oxidation. Switching (35, 36). Yet, the method still requires a precious metal (palladium), a from air to oxygen gas under the same atmospheric pressure also led to high pressure (30 bar), and a large amount of additive (TEMPO). In a quantitative isolated yield (entry 15). As a control experiment, only a 2008, Tian et al. reported a heterogeneous catalytic aqueous-phase trace amount of the product was detected in the absence of the silver oxidation of aldehydes using silver(I)/copper(II) oxide (37), but the catalyst. method suffers from a high catalyst loading, a very limited substrate A series of common aldehydes, including both aliphatic and aro- scope, and side reactions. In 2009, Yoshida and co-workers reported a matic examples with different functional groups, was then chosen to con- water-soluble N-heterocyclic carbene (NHC)–catalyzed oxidation of duct the scope investigation with this catalytic system (Table 2). Besides aldehyde by oxygen (38). However, this method still requires the re- benzaldehyde, which gave a quantitative yield (entry 1, compound 1), action solvent to be a mixture of N,N′-dimethylformamide/H2O in 10:1 aliphatic 1-octanal also gave a quantitative yield of the corresponding acid ratio, which is far from a complete water-phase oxidation. Recently, in (entry 2, compound 38). Hydrocinnamaldehyde and 1-naphthaldehyde 2014, Han and co-workers reported a multifunctional utilization of gave very good yields of 86 and 88% (entries 3 and 4, compounds 49 and silver-NHC complex as catalyst to achieve different oxidation of alco- 4), respectively. With 4-fluorobenzaldehyde, the reaction only gave a hol (39), but the method still relies on organic solvent and anhydrous 34% yield (entry 5, compound 16), whereas 4-chlorobenzaldehyde led to conditions. Here, we wish to report a highly efficient, widely applicable, a 100% recovery of the starting material (entry 6, compound 18). Surpris- homogeneous silver(I)-catalyzed aerobic oxidation of a wide range of ingly, for the unsaturated cinnamaldehyde, even with all the starting ma- aldehydes using only water as solvent, and performed under atmospheric terial consumed, the reaction still did not give any desired product (entry 7, pressurewithoxygengasoroxygenintheairastheoxidantundermild compound 47), whereas the unconjugated 4-allyloxy benzaldehyde led conditions (Fig. 1). to a low conversion of the starting material and no desired product (entry 8, compound 12). p-Anisaldehyde and piperonal, bearing additional oxygen-based functional groups, also led to 100% recovery of the starting Department of Chemistry and FRQNT Centre in Green Chemistry and Catalysis, McGill 6 5 University, 801 Sherbrooke Street West, Montreal, Quebec H3A 0B8, Canada. material (entries 9 and 10, compounds and ). We postulated that *Corresponding author. E-mail: [email protected] those substrates with inferior reactivity might be caused by the competing Liu et al. Sci. Adv. 2015;1:e1500020 27 March 2015 1of9 RESEARCH ARTICLE O2 WATER -Excellent efficiency -1 atm O2 50°C in water -Extremely low [Ag] cat. load capable of doing gram scale with 2 mg of catalyst (in prolonged time) -Chromatography is unnecessary in almost all cases Fig. 1. Highlights of our aerobic oxidation. coordination of oxygen, nitrogen, C=C double bond, and so on, to the With the optimized reaction conditions in hand, a much more di- Lewis acidic silver(I) center within the same molecule as the aldehyde car- verse series of aldehydes were selected to examine the substrate scope bonyl. Thus, we rationalized that a stronger coordinating ligand may be (Table 4). To our satisfaction, excellent yields were obtained with all required to release the Ag(I) center from such coordination. aldehydes that we examined. Aromatic aldehydes where the –Rgroupis Using piperonal, unreactive under the above conditions, as the a hydrocarbon (benzaldehyde, p-tolualdehyde, 5-indancarboxaldehyde, model substrate, phosphorus-based and NHC ligands were examined or 1-naphthaldehyde) were all transformed in quantitative or nearly (Table 3). Unless otherwise noted, all experiments were carried out in quantitative yields (compounds 1 to 4). All of the electron-rich aromatic house-light conditions, without light sheltering. With [(CF3)2CHO]3P, a aldehydes that we tested—mono-, di-, and tri-methoxyl–substituted very electron-poor ligand, we only obtained a 21% yield. Furthermore, benzaldehydes—gave quantitative or nearly quantitative yields (com- some decomposition of the piperonal’s formacetal structure was ob- pounds 6 to 9) regardless of the location of the substituent. Please note served (entry 2). The combination of AgPF6 with more electron-rich that piperonal, which was tested in our investigation of the reaction trifurylphosphine gave a good 66% nuclear magnetic resonance yield conditions (compound 5), also gave almost quantitative yield. The (entry 3); however, some decomposition (ca. 15%) of the acetal was still more hydrophobic 4-(pentyloxy)benzaldehyde and 4-(hexyloxy) observed. The catalyst generated from AgPF6 and the NHC ligand IPr benzaldehyde also gave excellent 94 and 90% yields (compounds 10 gave a much lower yield (entry 4). To our surprise, when we switched and 11), respectively. The 4-allyloxy-benzaldehyde gave quantitative AgPF6 to Ag2O, an almost quantitative yieldwasobtained(entry5).Iso- yield as well, with the terminal C=C double bond intact and no ob- lation of the product from the reactionmixturewasveryeasy:Theaqueous servation of the Claisen rearrangement (compound 12), whereas the reaction mixture was simply washed with common non–water-mixable or- 4-benzyloxy-benzaldehyde resulted in a reduced 65% yield, probably ganic solvent and then acidified, followed by extraction using diethyl due to the cleavage of the benzyloxy group (compound 13). ether. Without needing to perform flash chromatography, the product Other than those electron-rich aldehydes, only slightly reduced with an extremely high purity level was obtained. Meanwhile, a 50% yield yields were obtained with 3-bromo-2,4-dimethoxybenzaldehyde and was achieved when only 0.5
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