Article pubs.acs.org/Organometallics
Copper(I)-Catalyzed Halogenation and Acyloxylation of Aryl Triflates through a Copper(I)/Copper(III) Catalytic Cycle Chao Long,† Liang Zhao,‡ Jing-Song You,† and Mei-Xiang Wang*,‡ †
Key Laboratory of Green Chemistry and Technology (MOE), College of Chemistry, Sichuan University, Chengdu 610064, People’s Republic of China ‡ Key Laboratory of Organic Phosphorus Chemistry and Chemistry Biology (MOE), Department of Chemistry, Tsinghua University, Beijing 100084, People’s Republic of China S Supporting Information *
ABSTRACT: Catalyzed by CuOTf under very mild conditions, aryl triflates which are embedded in the azacalix[1]arene[3]pyridine macrocycle underwent coupling reactions with metal halides and acetates to afford respectively halogenated and acyloxylated arene products in moderate to excellent yields. The unprecedented CuOTf-catalyzed transformations of aryl triflates proceeded through an oxidative addition of intramolecularly chelated Cu(I) into the C−O bond of aryl triflates to form arylcopper(III) intermediates which underwent anion exchange and reductive elimination reactions with nucleophiles to yield functionalized macrocyclic products.
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INTRODUCTION Organocopper compounds constitute an important and indispensable area of organometallic chemistry.1−3 This has been manifested by the well-known examples of organocuprates: their syntheses, intriguing structures, and extensive applications in organic synthesis.4 Organocopper species with different oxidative states, either structurally defined or hypothesized, play an important role in the widely used cross-coupling reactions, including the Ullmann reaction,5 the Ullmann and Goldberg reaction,6 the Chan−Lam−Evans reaction,7 the Castro−Stephens reaction,8 the Rosenmund− von Braun reaction, 9 the Glaser−Hay reaction,10 etc. Admittedly, copper was displaced from the leading position by palladium in the mid-1980s. After the domination by palladium and other noble metals in organometallic chemistry for more than three decades, there has been a revival of organocopper chemistry in recent years.3,11−13 In comparison to precious metals, copper is naturally abundant, cost-effective, and eco-friendly. In addition, recent studies have shown that, as a surrogate of precious-metal catalysts, copper salts exhibit unexpected versatility in catalyzing or mediating various carbon−carbon and carbon−heteroatom bond forming reactions. More importantly, the novel structures and reactivity associated with high-valent organocopper compounds offer great opportunities in synthetic organic chemistry.3,11,12 Copper salts are able to catalyze or mediate various coupling reactions to synthesize carbon−carbon and carbon−heteroatom bonds. The reaction substrates are mainly confined to preactivated chemical entities such as aryl halides.5−10 Alkenyl14 and alkynyl15 halides have also been used as reactants. In 2006, Yu16 reported in a seminal study that, with the aid of a © 2014 American Chemical Society
neighboring pyridine-2-yl chelating group, arenes underwent Cu(OAc)2-catalyzed C−H functionalization reactions using oxygen as an terminal oxidant. Since then, a number of chelating-group-bearing arene substrates have been successfully utilized in copper-catalyzed oxidative aryl C−H bond transformations.12 Among the copper-catalyzed or -mediated arene C−H bond transformations reported, reactions of arene substrates embedded in polyazamacrocycles appeared interesting because high-valent Ar−CuIII compounds were isolated and structurally well characterized.3,17−19 As the intermediates in the process of arene C−H bond functionalizations, Ar−CuIII compounds are able to couple with various nucleophilic reagents.18,20,21 Surprisingly, copper-catalyzed cross-coupling reactions employing activated phenol derivatives such as aryl triflates and tosylates have never been reported until now, although phenol derivatives are cheap and readily available.22 In the study of the transition metal ion binding ability of azacalix[1]arene[3]pyridine, a member of a new generation of synthetic macrocyclic host molecules, viz. heteracalixaromatics,23 we discovered serendipitously the efficient formation of an arylcopper(III) compound from aryl C−H bond activation18 (Scheme 1). Very recently, we21b have found that an arylcopper(III) compound is also readily obtained from the reaction of iodobenzene embedded in the macrocycle with CuOTf (Scheme 1). The resulting arylcopper(III) compounds, which are stable and structurally well-defined, are able to react with a number of nucleophiles to afford functionalized macrocycles.21 The facile oxidative addition of copper(I) into Received: January 15, 2014 Published: February 6, 2014 1061
dx.doi.org/10.1021/om500046g | Organometallics 2014, 33, 1061−1067
Organometallics
Article
Scheme 1. Formation of Arylcopper(III) Compounds by Two Methods
the C−I bond encouraged us to undertake the current study. We envisioned that, as a model system, macrocyclic azacalix[1]arene[3]pyridines would be a unique testing ground for the study of cross-coupling reactions or functionalization reactions. We report herein for the first time the unprecedented example of copper(I)-catalyzed functionalizations of aryl triflates through a Cu(I)/Cu(III) catalytic cycle. The method provides an efficient and straightforward synthetic route to halogenated and acyloxylated azacalix[1]arene[3]pyridines that are valuable in the study of host−guest chemistry.
Table 1. Optimization of the Reaction of 2a with KI
RESULTS AND DISCUSSION All starting materials 2, namely azacalix[1]arene[3]pyridines that contain a substituted aryl triflate moiety, were synthesized conveniently by means of straightforward sulfonation of phenols 1, which were obtained from hydroxylation of azacalix[1]arene[3]pyridines.21e Thus, treatment of 1 with Tf2O in the presence of dimethlaminopyridine (DMAP) at room temperature led to the formation of the desired compounds 2 in 60−82% yields (Scheme 2).
entry
amt of Cu (x)
1
50
CH3CN
2 3 4 5 6 7
50 50 50 50 50 50
TsOH TfOH TfOH TfOH
CH3CN CH3CN CH3CN CH3CN dioxane dioxane
8
50
TFA
dioxane
9
50
HClO4
dioxane
10 11
50 50
12
20
13
20
14
20
15
20
16 17
20 20
18
20
19
20
20
20
21
10
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Scheme 2. Synthesis of Reactants 2
additivea
solvent
dioxane dioxane/MeOH (10/1) dioxane/MeOH (10/1) dioxane/MeOH (20/1) dioxane:MeOH (50:1) dioxane/MeOH (100/1) dioxane dioxane/MeOH (50/1) dioxane/MeOH (50/1) dioxane/MeOH (50/1) dioxane/MeOH (50/1) dioxane/MeOH (50/1)
amt of 3a (%)b
T (°C)
t (h)
room temp 60 reflux reflux reflux reflux room temp room temp room temp 60 60
12
c
12 12 12 24 12 46
c c c 36d 33d 36d
12
40d
46
36d
24 11
86 92
60
24
78e
60
6
86
60
6
92
60
6
90
60 room temp 80
6 30
86f 29d
3.5
96
reflux
3
67
60
10
74g
60
24
73h
a
One equivalent was used. bIsolated yield. cStarting material was recovered. dA large amount of reactant 2a was isolated. eReactant 2a was isolated in 17% yield. fReactant 2a was isolated in 11% yield. gOne equivalent of KI was used. hReactant 1a was isolated in 10% yield.
We commenced our study with the examination of the reaction between the triflate derivative 2a and KI. To facilitate the transformation, a substoichiometric amount of CuOTf (50 mol %) and 2 equiv of KI were used initially. As indicated by the results compiled in Table 1, when the reaction was performed at room temperature or in refluxing acetonitrile, no reaction was observed and the starting material was recovered (entries 1−3, Table 1). While the presence of 1 equiv of p-
toluenesulfonic acid did not promote the reaction (entry 4, Table 1), trifluoromethylsulfonic acid (TfOH), trifluoroacetic acid (TFA), or perchloric acid (HClO4) was found to effect the reaction. Unfortunately, the conversion was only moderate in 1062
dx.doi.org/10.1021/om500046g | Organometallics 2014, 33, 1061−1067
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Article
either acetonitrile or 1,4-dioxane (entries 5−9, Table 1). We were then surprised to discover that the reaction proceeded effectively in warm 1,4-dioxane, giving the desired product 3a in 86% isolated yield after 24 h (entry 10, Table 1). Pleasingly, the reaction become highly efficient in a mixture of 1,4-dioxane and methanol (10/1). Complete conversion was achieved in 11 h to afford product 3a in an almost quantitative yield (entry 11, Table 1). The catalyst loading was then decreased, and the effect of the mixed solvents on the reaction was investigated. In the presence of 20 mol % of CuOTf, the same reaction took place slowly in a mixture of 1,4-dioxane and methanol (10/1), producing compound 3a in 78% yield with recovery of 17% of the reactant 2a in 24 h (entry 12, Table 1). Gratifyingly, the chemical yield of product 2a was improved to 86% and to 92% when the ratio of 1,4-dioxane to methanol was increased to 20/ 1 and to 50/1, respectively (entries 13 and 14, Table 1). A further increase of the ratio of 1,4-dioxane to methanol to 100/ 1 or the use of pure 1,4-dioxane as solvent did not have a beneficial effect. In contrast, a decreased velocity of the transformation was observed and product 3a was isolated in a diminished yield in 1,4-dioxane (entry 16, Table 1). It is worth noting that the optimal reaction temperature was in the range of 60−80 °C, at which the rapid conversion and excellent yield of the product were guaranteed (entries 14 and 18, Table 1). Either a lower or a higher reaction temperature had a detrimental effect on both the reaction rate and the chemical yield of product (entries 17 and 19, Table 1). To ensure an efficient transformation, the employment of 2 equiv of the nucleophile appeared necessary (entry 20, Table 1). It should also be addressed that a catalyst loading as low as 10 mol % was found to be effective in catalyzing the transformation, although an prolonged reaction time was required (entry 21, Table 1). It is very interesting to emphasize that the use of methanol as a cosolvent did not lead to the formation of phenyl methyl ether, a possible product from coupling between phenyl triflate and methanol.20b,21a Under the optimized conditions, the scopes and limitations of the CuOTf-catalyzed functionalization of triflate were tested. First of all, all trfilate derivatives 2b−e, which contain either an electron-withdrawing group or an electron-donating group at the para position, underwent an efficient iodination reaction with KI to afford the corresponding products 3b−e in good yields. The presence of a para-substituted electron-withdrawing group such as cyano or chlorine seemed to accelerate the reaction (entries 1−5, Table 2). The reaction of triflate 2f, which bears a methyl group at the meta position, proceeded equally well to give product 3f in 65% yield (entry 6, Table 1). The outcomes indicate clearly that CuOTf-catalyzed iodination of aryl triflates 2 takes place efficiently in general, irrespective of the nature of the substituent or the pattern of the substitution on the benzene ring. Second, in addition to KI, both KCl and KBr acted as effective nucleophiles to react analogously with triflates under the CuOTf-catalyzed conditions to furnish the formation of chlorobenzene product 3g and bromobenzene compound 3h in 72% and 86% yields, respectively (entries 7 and 8, Table 2). In addition, as summarized in Table 2, triflate 2a underwent a CuOTf-catalyzed acyloxylation reaction with sodium carboxylates smoothly to generate O-acylated phenol compounds. For example, treatment of 2a with sodium acetate or sodium benzoate under the identical catalytic conditions led to, within 31−36 h, the formation of 3i,j in good yields (entries 9 and 10, Table 2). Furthermore, sodium carboxylates containing a long lipophilic alkyl chain such as C11H23 or
Table 2. CuOTf-Catalyzed Transformations of Triflates 2
entry
2
R1
R2
MX
t (h)
3 (amt (%))a
1 2 3 4 5 6 7 8 9 10 11 12 13 14
2a 2b 2c 2d 2e 2f 2a 2a 2a 2a 2c 2c 2a 2a
H H H H H Me H H H H H H H H
H Cl CN MeO Me H H H H H CN CN H H
KI KI KI KI KI KI KCl KBr MeCO2Na PhCO2Na C11H23CO2Na C13H27CO2Na NaSCN PhSNab
6 1 1 1.5 6.5 6.5 22 13 31 36 50 50 33 13
3a (92) 3b (80) 3c (78) 3d (84) 3e (74) 3f (65) 3g (72) 3h (86) 3i (62) 3j (70) 3k (45) 3l (56) 3m (
