Article Cite This: J. Org. Chem. 2018, 83, 2274−2281
pubs.acs.org/joc
Transfer Hydrogenation of Aldehydes and Ketones with Isopropanol under Neutral Conditions Catalyzed by a Metal−Ligand Bifunctional Catalyst [Cp*Ir(2,2′-bpyO)(H2O)] Rongzhou Wang, Yawen Tang, Meng Xu, Chong Meng, and Feng Li* School of Chemical Engineering, Nanjing University of Science & Technology, Nanjing 210094, People’s Republic of China S Supporting Information *
ABSTRACT: A Cp*Ir complex bearing a functional bipyridonate ligand [Cp*Ir(2,2′-bpyO)(H2O)] was found to be a highly efficient and general catalyst for transfer hydrogenation of aldehydes and chemoselective transfer hydrogenation of unsaturated aldehydes with isopropanol under neutral conditions. It was noteworthy that many readily reducible or labile functional groups such as nitro, cyano, ester, and halide did not undergo any change under the reaction conditions. Furthermore, this catalytic system exhibited high activity for transfer hydrogenation of ketones with isopropanol. Notably, this research exhibited new potential of metal−ligand bifunctional catalysts for transfer hydrogenation.
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based on the concept of ligand-promoted dehydrogenation.8 More recently, we demonstrated that such complexes are highly effective metal−ligand bifunctional catalysts for the Nalkylation of sulfonamides with alcohols based on hydrogen autotransfer process9 and acceptorless dehydrogenative coupling for the construction of quinazolinones and quinolines.10 As a continuing effort to develop iridium-catalyzed environmentally benign transformations,9−11 we herein explored the feasibility of transfer hydrogenation of aldehydes and chemoselective transfer hydrogenation of unsaturated aldehydes with isopropanol under neutral conditions catalyzed by a metal− ligand bifunctional catalyst. Furthermore, transfer hydrogenation of ketones with isopropanol was also investigated.
INTRODUCTION The reduction of aldehydes to primary alcohols represents one of the most fundamental reactions in organic synthesis both on laboratory and industry scale.1 Traditionally, such transformations were performed in the presence of stoichiometric amount of metal hydrides such as NaBH4 and LiAlH4 with the generation of a large amount of side products. Along with increasing environmental awareness, transition metal-catalyzed hydrogenation reactions of aldehydes with hydrogen gas2 and transfer hydrogenation with HCOOM (M = Na,3 NH4,4 H5) have been developed in recent years. In past decades, transition metal-catalyzed transfer hydrogenation of ketones to secondary alcohols with isopropanol as a hydrogen source has attracted much attention due to isopropanol being inexpensive and easy available; the moderate boiling point eases the separation from reaction products with high efficiency.6 However, the use of isopropanol as a hydrogen source for transfer hydrogenation of aldehydes remains less explored.7 It may be attributed to such transfer hydrogenation usually requiring the presence of base for the activation of isopropanol, and aldehydes are far more sensitive than ketones; thus, self-aldol side reactions unavoidably occurred under basic conditions. From both synthetic and environmental points of view, the development of an efficient and general organometallic catalyst for transfer hydrogen of aldehydes to primary alcohols with isopropanol under neural condition is highly desirable. Recently, Fujita, Yamaguchi, and coworkers reported a series of Cp*Ir complexes bearing a functional bipyridine or a bipyridonate ligand, which exhibited highly catalytic activity for acceptorless dehydrogenation of alcohols and N-heterocycles © 2018 American Chemical Society
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RESULTS AND DISCUSSION In our initial experiment, the transfer hydrogenation of benzaldehyde (1a) with isopropanol was selected as a model reaction (Scheme 1). In the presence of [Cp*IrCl2]2 (Cp* = pentamethylcyclopentadienyl) (cat. 1), [Cp*Ir(2-phenylpyridine-kC,N)]Cl (cat. 2), [Cp*Ir(bpy)Cl)][Cl] (cat. 3), and [Cp*Ir(bpy)(H2O)][OTf]2 (cat. 4) (0.2 mol %), the reaction was carried out for 6 h at 82 °C, and the product 2a was obtained in ≤18% yield. When a series of Cp*Ir complexes bearing a functional bipyridine or bipyridonate ligand such as [Cp*Ir(2-(OH)py)]Cl2 (cat. 5), Cp*Ir[2-(2-(2-(OH)py)phenyl]Cl (cat. 6), [Cp*Ir(6,6′-(OH)2-2,2′-bpy)(H2O)][OTf]2 (cat. 7), and [Cp*Ir(2,2′-bpyO)(H2O)] (cat. 8) were Received: December 17, 2017 Published: January 13, 2018 2274
DOI: 10.1021/acs.joc.7b03174 J. Org. Chem. 2018, 83, 2274−2281
Article
The Journal of Organic Chemistry
rated aldehydes (3) with isopropanol (Table 2). The transformation of cinnamaldehyde afforded cinnamylalcohol (4a) in 92% yield with complete chemoselectivity (Table 2, entry 1). Similarly, cinnamaldehydes bearing an electrondonating group or an electron-withdrawing group were converted to the corresponding products 4b−4e in 94−96% yields (Table 2, entries 2−5). High catalytic activities were also observed when cinnamaldehydes bearing a substituent on the α-position were used, and the desired products 4f−4h were obtained in 93−97% yields (Table 2, entries 6−8). Furthermore, 3-(9-anthryl)acrylaldehyde and 3-(2-furyl)acrylaldehyde were hydrogenated to give the corresponding products 4i and 4j in 98 and 92% yields, respectively (Table 2, entries 9 and 10). In the case of aliphatic α,β-unsaturated aldehydes, the desired products 4k and 4l were obtained in 80 and 91% yields, respectively (Table 2, entries 11 and 12). Interestingly, nonconjugated unsaturated aldehydes such as 3cyclohexene-1-carboxaldehyde and 5-norbornene-2-carboxaldehyde were also successfully converted to the corresponding products 4m and 4n in 93 and 96% yields, respectively (Table 2, entries 13 and 14). When 3,7-dimethyl-2,6-octadienal served as a substrate, only the carbonyl group was hydrogenated, and two CC bonds remained unreacted (Table 2, entry 15). A plausible mechanism was proposed for the present transfer hydrogenation of aldehydes or chemoselective transfer hydrogenation of unsaturated aldehydes with isopropanol (Scheme 2). The initial stage of reaction involved the elimination of H2O from cat. 8 to give an unsaturated species A bearing a 2,2′bipyridonate ligand.8f In the step of the activation of isopropanol, the ligand accepted a proton, resulting in the generation of alkoxy iridium species B, which underwent βhydrogen elimination to give iridium hydride species C and acetone.13 Accompanied by the process of ligand-promoted simultaneous transfer of the hydride on iridium and the hydroxy proton on the bpy ligand of species C to the CO bond of aldehydes or unsaturated aldehydes, the desirable alcohols were released as final products, and the catalytic species A was regenerated. To demonstrate the practical potential of this methodology, the large-scale reaction was undertaken. The hydrogenation of 1a (20 mmol) was carried out in the presence of cat. 8 (0.05 mol %) to give the corresponding product 2a in 92% yield (Scheme 3). Furthermore, transfer hydrogenation of glucose, which is a unit of cellulose and exists an equilibrium between its hemiacetal and aldehyde forms in water, was represented. The reaction of 5 with isopropanol was performed at 120 °C in the presence of cat. 8 (0.2 mol %) for 12 h to afford the desired product sorbitol 6 in 80% yield (Scheme 4). The present catalytic system was also expanded to transfer hydrogenation of ketones with isopropanol. As outlined in Table 3, reactions of a series of ketones (7) proceeded smoothly to give the desired products 8 in high yields. In summary, we demonstrated that a Cp*Ir complex bearing a functional bipyridonate ligand [Cp*Ir(2,2′-bpyO)(H2O)] is a highly efficient and general catalyst for transfer hydrogenation of aldehydes and chemoselective transfer hydrogenation of unsaturated aldehydes with isopropanol under neutral conditions. It was noteworthy that many readily reducible or labile functional groups such as nitro, cyano, ester, and halide did not undergo any change under present reaction conditions. Furthermore, this catalytic system exhibited high activity for transfer hydrogenation of ketones with isopropanol. Notably,
Scheme 1. Transfer Hydrogenation of Benzaldehyde with Isopropanol Using a Range of Catalystsa,b
a
Reaction conditions: 1a (1 mmol), isopropanol (5 mL), catalyst (0.2 mol %), 82 °C, under N2, 6 h. bYield was determined based on the 1H NMR spectrum of the crude reaction. cIsolated yield.
screened, yields of 2a were obviously enhanced. Apparently, the presence of functional units in the ligand is crucially important for the activity of catalysts. Among them, cat. 8 exhibited the highest activity, and the product 2a was obtained in >98% yield.12 Using rhodium analogues [Cp*Rh(2,2′-bpyO)(H2O)] (cat. 9) as an alternative catalysts, the product 2a was obtained in 40% yield. However, only
