Yun
Xu
ab,
Xingbang
Hu
*a,
Jing
Shao
a,
Guoqiang
Yang
a,
Youting
Wu
*a and
Zhibing
Zhang
a
aSchool of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, PR China. E-mail: huxb@nju.edu.cn; ytwu@nju.edu.cn; Fax: +86 2583 336599; Tel: +86 2583 596665
bChina Pharmaceutical University, Nanjing, 211198, PR China
First published on 18th September 2014
An effective method using gold(I) isocyanide complexes as catalysts for the transformation of various alkynes to the corresponding ketones is successfully developed. The hydration process proceeds smoothly at room temperature with quite high yield (up to 99%). The catalytic center is the isocyanide-Au(I)+ cation. Further theoretical research reveals a direct hydration mechanism by H2O, and the rate-determining step has an energy barrier of 23.7 kcal mol−1. These results show a good example to reduce unnecessary steps and achieve milder reaction conditions at the same time for the hydration of alkynes.
To overcome the disadvantages of mercury(II) salts and Brønsted acids, a variety of organometallic catalysts were explored, such as compounds containing Pt,5 Ag,6,7 Ru,8,9 Au, and even biomimetic catalysts.10 Among them, the unique catalytic ability of gold(I) and gold (III) has attracted much attention, because gold centers show high affinity to activate CC triple bonds by nucleophilic attack. Though gold compounds were thought to be potential and excellent catalysts for alkyne hydration,11,12 most of the reactions catalyzed by gold compounds require high reaction temperatures, such as 120 °C for the hydration catalyzed by gold N-heterocyclic carbenes (Au-NHC)/AgSbF6,12,13 Au-NHC/HSbF6,11 and Au-NHC@porous organic polymers,14 100–150 °C for bis(phosphane) gold(I),15 100 °C for NaAuCl4,16 80 °C for Au-NHC17 and Au-SH/SO3H-PMO(Et),8 70 °C for (Ph3P)AuCH3 in the presence of H2SO4,18 65 °C for abnormal Au-NHC,19 and reflux temperature.20–24 Obviously, it is still a challenge to develop more effective gold catalysts for alkyne hydration at room temperature.
In the last decade, an increasing number of studies have focused on the preparation of gold isocyanide complexes (Au-RNC) and the investigation of their structure and properties.25–27 But so far, Au-RNC complexes were mainly used as the starting materials for the synthesis of other novel catalysts.28 Among the complexes obtained via Au-RNC, Au-NHC represents a kind of the most extensively studied compound in organometallic chemistry and catalysis (Scheme 1).29–39 To realize the reported catalytic ability of Au-NHC for the hydration of alkynes, high reaction temperatures are needed to obtain satisfactory conversions.11–14,17,19–23 As far as we know,40 there is almost no report that the Au-RNC complex can be directly used as a catalyst in not only alkyne hydration, but also other reactions.
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Scheme 1 The relationship between Au–RNC and Au–NHC and their catalytic ability for the hydration of alkynes. |
Both experimental and theoretical research studies in this paper show, to our surprise, that Au-RNC has excellent activity in catalyzing the hydration of alkynes at room temperature. It is a good example that avoids the use of complicated catalysts and eliminates harsh reaction conditions in the hydration of alkynes (Scheme 1).
Entry | Catalystb (mol) | Solvent | Conv.c (%) |
---|---|---|---|
a Reaction conditions: phenylacetylene (0.5 mmol), solvent (0.5 ml), H2O (0.5 ml), room temperature, 24 h. b The catalyst amount is based on the molar percent to 1a. c Conversion of 1a determined by GC. d Methanol (0.5 ml) and H2O (1.0 ml). e Methanol (1.0 ml) and H2O (0.5 ml). f Methanol (2.0 ml) and H2O (0.5 ml). | |||
1 | 5% Cat-1 | Methanol | NR |
2 | 5% Cat-1 + 5% AgSbF6 | Methanol | 0.6 |
3 | 5% Cat-1 + 5% KBF4 | Methanol | 3.7 |
4 | 5% Cat-1 + 5% KB(C6H5)4 | Methanol | 1.5 |
5 | 5% Cat-1 + 5% KB(C6F5)4 | Methanol | 99.9 |
6 | 5% KB(C6F5)4 | Methanol | NR |
7d | 5% Cat-1 + 5% KB(C6F5)4 | Methanol | 99.9 |
8e | 5% Cat-1 + 5% KB(C6F5)4 | Methanol | 32.2 |
9f | 5% Cat-1 + 5% KB(C6F5)4 | Methanol | 5.0 |
10 | 1% Cat-1 + 1% KB(C6F5)4 | Methanol | 20.2 |
11f | 1% Cat-1 + 1% KB(C6F5)4 | Methanol | <1.0 |
12 | 5% Cat-1 + 5% KB(C6F5)4 | Ethanol | 27.2 |
13 | 5% Cat-1 + 5% KB(C6F5)4 | Hexane | 25.7 |
14 | 5% Cat-1 + 5% KB(C6F5)4 | Dioxane | 10.1 |
15 | 5% Cat-1 + 5% KB(C6F5)4 | Acetone | 3.4 |
16 | 5% Cat-1 + 5% KB(C6F5)4 | THF | 0.8 |
17 | 5% Cat-1 + 5% KB(C6F5)4 | None | 57.0 |
Using an environmentally preferable solvent is quite important for a green process. The solvents screening experiments on methanol, ethanol, hexane, dioxane, acetone and THF show that the reaction performed in methanol gives the best result (entries 5, 12–16 in Table 1). Using methanol as a solvent is quite green according to the framework for the environmental assessment of solvents,42 Sanofi's solvent selection guide,43 and the EHS assessment for alternative solvents.44 The amount of solvent has an obvious influence on the conversion of phenylacetylene. Comparing with the standard conditions, increasing the amount of methanol results in low conversion of the reactants (entries 5, 7–9).
It has been found that some alkynes can be converted into the vinyl ether intermediate by the addition of methanol to the CC bond, and vinyl ether can then be hydrolyzed into ketone.11,12 The catalysis reported here should not proceed in such a pathway, because no vinyl ethers were detected by GC-MS during the reactions of all the substrates investigated here (Tables 1 and 2). Furthermore, when only H2O was used as both the solvent and the reactant, the reaction conversion still can reach 57.0% in 24 h (entry 17 in Table 1).
Entry | Reactant | Product | Yieldb (%) |
---|---|---|---|
a Reaction conditions: alkyne (1.0 mmol), Cat-1 (0.05 mmol), KB(C6F5)4 (0.05 mmol), H2O (1.0 ml), methanol (1.0 ml), room temperature, 24 h. b Yield determined by GC with biphenyl as the internal standard. Isolated yields are shown in parenthesis. c 10% mol catalyst, 48 h. d Reaction time: 48 h [24 h]. | |||
1 |
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>99 |
2 |
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>99 (96) |
3 |
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>99 |
4 |
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>99 (95) |
5 |
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>99 (97) |
6c |
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63 |
7c |
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8 [5]d |
8 |
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>99 (99) |
9 |
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>99 (95) |
10 |
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>99 (98) |
11 |
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>99 |
12 |
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>99 (99) |
13 |
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>99 (98) |
14 |
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97 |
15 |
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>99 (99) |
16c |
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97 (95) |
17c |
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98 (97) |
In addition to Cat-1, another gold isocyanide (2,6-Me2C6H3-NC)AuCl (Cat-2) was also investigated and its catalytic ability was compared with that of Cat-1 (Fig. 1). Though the activity of Cat-2 is a little weaker than that of Cat-1, the reaction catalyzed by Cat-2 can still proceed quite well at room temperature (Table S1 in ESI†).
Another route to synthesize these ketones is the catalytic aerobic oxidation of alcohols.45–53 It should be noticed that the only by-product is water for an ideal oxidation process, and some of these oxidations can be performed at room temperature.45–49 However, NaNO248,49 or excess amounts of bases45–47,50,51 are usually indispensable in these aerobic oxidations. Though some of the alcohols used in the oxidation routes are cheaper than the alkynes in the hydration routes, the following characteristics of the route reported here make itself a more green choice for the synthesis of ketones: 100% atomic economy, mild reaction conditions, an environmentally preferable solvent, no need of acids or bases.
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Fig. 2 Proposed mechanism of the hydration of phenylacetylene. The values in the reaction pathway are in kcal mol−1. The other values are bond lengths in Å. |
The binding between Cat-1+ and 1a is found to be highly exothermic (−47.3 kcal mol−1). With the assistance of Cat-1+, H2O can attack 1avia a transition state TS1 (Fig. 2). The barrier of TS1 is 23.7 kcal mol−1. The CC triple bond of 1a becomes almost a double bond in TS1 (length increasing from 1.212 to 1.342 Å). An enol form of the intermediate (Int1 or Int1′) can be produced via TS1 (Fig. 2 and 3). After that, enol–keto isomerisation via a proton transfer process (TS2 or TS2′) takes place to generate the final product with a total energy change of −45.0 kcal mol−1. However, the barrier of TS2 or TS2′ is too high (36.5 or 37.6 kcal mol−1) to support the room temperature hydration of 1a. Considering that the microenvironment of the reaction is full of water, a water assisting enol–keto isomerisation process should be more feasible.54–58 In this process, the proton of C–O–H transfers to an explicit H2O, and meanwhile, one proton of this explicit H2O transfers to the terminal carbon of the C
C bond. In this case, the transition from the Int1′ hydrate (Int1′-W) to the final product only needs to overcome a quite low barrier (22.5 kcal mol−1 of TS2′-W). Of course, if there are two or more explicit water molecules to join the process and assist the proton transfer, the barrier should be further reduced to smaller than 22.5 kcal mol−1.54–58 Thus, the rate-determining step of this hydration process should be H2O attacking the C
C triple bond with a barrier of 23.7 kcal mol−1 (Fig. 2).
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Fig. 3 Water-assisted enol–keto isomerisation in the hydration of phenylacetylene. The values in the reaction pathway are in kcal mol−1. The other values are bond lengths in Å. |
Another interesting pathway for the reaction of the terminal alkyne using the gold catalyst as gold(I) may react with the terminal alkyne to produce a gold vinylidene (LAuC
CR2) intermediate and this intermediate can further react with other functional groups, such as the cycloisomerization of alkyne.59,60 The possibility of similar gold vinylidene (Rea″) reacting with H2O was further investigated (Fig. 4). It was found that the addition of H2O to Rea″ is not easy because of a quite high barrier of TS1″ (51.4 kcal mol−1). This energy barrier is 27.7 kcal mol−1 higher than that of TS1. Furthermore, the energy barrier for the proton transfer from C–O–H to the terminal carbon is 45.9 kcal mol−1 (TS2″), which is 9.4 kcal mol−1 higher than that of TS2. Hence, for the hydration of alkynes catalyzed by gold(I) isocyanide compounds, the reaction mechanism is more likely to be the pathway presented in Fig. 2 and 3. The barrier height of the rate-determining step for the pathway in Fig. 2 and 3 is only 23.7 kcal mol−1, and this barrier height is reasonable for the reaction to proceed readily at room temperature.61
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Fig. 4 Reaction between gold vinylidenes and H2O. The values in the reaction pathway are in kcal mol−1. The other values are bond lengths in Å. |
Au-RNC, as a precursor for the synthesis of Au-NHC,29–39 shows comparable catalytic ability to Au-NHC in the hydration of alkynes. This is a rare example that Au-RNC is used as the catalyst directly to obtain satisfactory hydration results. Considering the simple structure and high reactivity of gold isocyanide, it deserves to receive more attention in other reactions. Because gold isocyanide is a homogeneous catalyst, developing a method to recycle it will bring a more green process. Supporting the gold isocyanide on zeolite62 or ionic liquids63–65 will be an effective method to reuse this compound.
Footnote |
† Electronic supplementary information (ESI) available: Experimental details and characterization results (1H-NMR, 13C-NMR, elemental analysis, and MS); hydration of various alkynes catalyzed by Cat-2; computational methods and Cartesians coordinates of the optimized structures. See DOI: 10.1039/c4gc01322k |
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