Next Article in Journal
Production and Surfactant Properties of Tert-Butyl α-d-Glucopyranosides Catalyzed by Cyclodextrin Glucanotransferase
Next Article in Special Issue
Kinetic Monte-Carlo Simulation of Methane Steam Reforming over a Nickel Surface
Previous Article in Journal
Enhanced Ni-Al-Based Catalysts and Influence of Aromatic Hydrocarbon for Autothermal Reforming of Diesel Surrogate Fuel
Previous Article in Special Issue
Iridium-Catalyzed Transfer Hydrogenation of Ketones and Aldehydes Using Glucose as a Sustainable Hydrogen Donor
Open AccessArticle

PPh3-Assisted Esterification of Acyl Fluorides with Ethers via C(sp3)–O Bond Cleavage Accelerated by TBAT

1
Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushimanaka, Kita-ku, Okayama 700-8530, Japan
2
Research Institute for Interdisciplinary Science, Okayama University, 3-1-1 Tsushimanaka, Kita-ku, Okayama 700-8530, Japan
*
Author to whom correspondence should be addressed.
Catalysts 2019, 9(7), 574; https://doi.org/10.3390/catal9070574
Received: 23 May 2019 / Revised: 21 June 2019 / Accepted: 26 June 2019 / Published: 28 June 2019
(This article belongs to the Special Issue Catalysis and Fine Chemicals)

Abstract

We describe the (triphenylphosphine (PPh3)-assisted methoxylation of acyl fluorides with cyclopentyl methyl ether (CPME) accelerated by tetrabutylammonium difluorotriphenysilicate (TBAT) via regiospecific C–OMe bond cleavage. Easily available CPME is utilized not only as the solvent, but a methoxylating agent in this transformation. The present method is featured by C–O and C–F bond cleavage under metal-free conditions, good functional-group tolerance, and wide substrate scope. Mechanistic studies revealed that the radical process was not involved.
Keywords: Acyl fluorides; cyclopentyl methyl ether (CPME); tetrabutylammonium difluorotriphenysilicate (TBAT); carbon-oxygen bond cleavage; esterification Acyl fluorides; cyclopentyl methyl ether (CPME); tetrabutylammonium difluorotriphenysilicate (TBAT); carbon-oxygen bond cleavage; esterification

1. Introduction

The C−O bond cleavage in ethers is one of the most fundamental transformations in organic synthesis and has been widely applied in the manufacturing of fine chemicals as well as the synthesis of polyfunctional molecules [1,2,3,4,5]. Particularly, the preparation and degradation of ethers have often been considered important synthetic strategies for the protection/deprotection of hydroxyl groups. Although numerous studies on demethylation in aromatic methyl ethers have been reported [6,7,8,9,10], demethylation of viable aliphatic surrogates has been relatively less explored. Typically, various reagents have been utilized to convert aliphatic methyl ethers into the corresponding alcohols via demethylation (Scheme 1a), employing BF3·Et2O/(CH3CO)2O [11], BCl3 [12], BBr3 [13], BF3·Et2O/EtSH [14], Me3SiI [15], hydrobromic acid/phase-transfer-catalysts [16], BBr3/NaI/15-crown-5 [17], (CH3)2BBr [18], AlCl3/NaI/CH3CN [19], or BI3/N,N-diethylaniline [20].
On the other hand, since 2005, cyclopentyl methyl ether (CPME) [21,22] has become the common solvent in organic reactions [23,24,25]. Compared with other conventional ethereal solvents such as diethyl ether (Et2O), tetrahydrofuran (THF), 1,2-dimethoxyethane (DME), 1,4-dioxane, methyl tert-butyl ether (MTBE), and 2-MeTHF, CPME displays many advantages, such as low cost, high-boiling point (106 °C), low polarity, lower miscibility with water (1.1 g/100 g), low tendency to form peroxides, narrow explosion range, and stability under strong acidic and basic conditions. With these characteristics of CPME in mind, the utility of CPME as a potential reactant in various organic transformations are attractive. However, to the best of our knowledge, the selective C−O bond cleavage in CPME [26] and the utilization of released methoxy group as a methoxylating agent [27] has been unexplored.
Numerous examples for utilization of acyl fluorides in synthetic organic chemistry have been reported [28], while recently, unique reactivity of acyl fluorides has been extensively disclosed due to their strong electrophilicity and high stability [29,30]. Transformations of acyl fluorides into other valuable molecules have been well demonstrated by others [31,32,33,34,35,36] and our group [37,38,39,40]. As a part of our ongoing interest in the functionalization of acyl halides, we herein report the nucleophilic methoxylation of acyl fluorides with CPME assisted by PPh3 via both C−OMe and C−F bonds cleavage under metal-free conditions (Scheme 1b).

2. Results and Discussion

When we conducted the reaction of benzoyl fluoride (1a) with CPME (2a), giving rise to methyl benzoate (3a) in the presence of a catalytic amount of PPh3, various additives were screened. As shown in Table, tetrabutylammonium difluorotriphenylsilicate (TBAT) [41] as the additive sufficiently increased the yield of 3a in 74% yield (Table 1, entry 1). PPh3 showed superior result than other monodentate phosphine ligands (entries 2–5). Compared to TBAT, several tetrabutylammonium halides such as tetrabutylammonium fluoride, -chloride, -bromide, and -iodide were tested, but they were found to be inferior (entries 6–9). Markedly, tetrabutylammonium trifluoromethanesulfonate (NBu4OTf) did not work at all (entry 10). With regard to other fluoride sources, poor results were obtained when potassium fluoride (KF) or cesium fluoride (CsF) was employed (entries 11–12). Interestingly, in the presence of 18-crown-6, KF gave 34% of 3a (entry 13), which might prove the importance of a naked fluoride ion. Notably, no trace of 3a was detected with fluorotriphenysilane (entry 14) or without TBAT (entry 15), indicating that TBAT uniquely accelerated this methoxylation event (Table S1). Careful control experiments resulted in an unexpected accelerating effect on methoxylation with 30 mol % of PPh3 (entry 1 vs entry 16), suggesting that an addition of PPh3 can enhance the electrophilicity of acyl fluorides, to some extents (Table S2) [42]. It is noteworthy that the identical reaction with benzoyl chloride afforded the lower yield of 3a (entry 17), suggesting a unique feature of acyl fluoride in this transformation.
With the optimized reaction conditions in hand, we investigated the scope and limitation of the methoxylation of an array of acyl fluorides 1 with CPME. As shown in Figure 1, this protocol displayed remarkable tolerance towards the substitution pattern and a steric effect. Both electron-donating and sterically encumbering substituents in any positions of the aryl ring gave good results. Another interesting feature of this reaction is that alkyl aryl ethers such as 3c and 3d were inert under the conditions. Acyl fluorides bearing electron-donating groups provided the corresponding products 3e3g in 64–90% isolated yields. When acyl fluorides with electron-withdrawing groups were employed, except for 4-nitrobenzoyl fluoride (1i), the desired products 3h, 3j, and 3k were obtained in good yields. Particularly, an ester group can also be tolerated, affording the target product 3l in 75% yield, which is noteworthy because the esters are known to be incompatible with Me3SiI [15]. Either more sterically hindered (3n) or more electron-rich (3o) products were successfully formed in this transformation. Polyaromatic products including naphthalenes (3p3q) and anthracene (3r) motifs also exhibited moderate to good levels of reactivity. Moreover, oxygen- (3s and 3t), sulfur-containing heterocycles (3u) did not interfere toward the ester formation. To our delight, the primary and tertiary alkylated acyl fluorides also could accommodate under optimal conditions, afforded corresponding ester 3v and 3w in moderate yields.
Given a regiospecific cleavage of C−O bond in CPME, we reasoned that other ethers could also be applied in alkoxylation of acyl fluorides (Scheme 2). Dibenzyl ether (2b) was also a good substrate, resulting in the formation of 3bb in 78% yield (Scheme 2a). When benzyl propargyl ether (2c) was employed, a propargyl group was installed preferentially into the product to afford 3bc in 50% yield, along with 18% of 3bb (Scheme 2b). Subsequently, unsymmetrical benzyl methyl ether (2d) smoothly gave 3a in 84% yield with a high regiospecificity (Scheme 2c). In a sharp contrast, n-hexyl methyl ether failed to undergo the reaction, leading to only 6% of 3a and no competitive product 3ae was detected (Scheme 2d). Although the cleavage patterns highly depend on the reagents added [1,2,3,4,5], the regiospecific C−O bond cleavage in this transformation can be explained by the stability of the resulting carbocations.
To clarify the reaction mechanism, we performed the methoxylation in the presence of radical scavengers (Scheme 3). Consequently, in the presence of equimolar amount of 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO), 2,6-di-tert-butyl-4-methylphenol (BHT), or 9,10-dihydroanthracene (DHA), the reaction proceeded with comparable efficiency to that without a radical scavenger, ruling out a radical pathway of this transformation.
Next, we hypothesized that this PPh3-assisted transformation might proceed via methoxytriphenylsilane (Ph3SiOMe) as the intermediate [43]. When we carried out the reaction using Ph3SiOMe instead of CPME under the optimized conditions (Scheme 4), no desired product 3a was formed in the absence of TBAT, along with the recovered 1a (91%) and Ph3SiOMe (95%). In a sharp contrast, the reaction of 1a with Ph3SiOMe in the presence of TBAT, 91% of 3a was obtained. These results indicate that the reaction of TBAT with CPME generates many nucleophilic pentacoordinate silicates [44]. Hypervalent silicates are the key organosilicon species to promote the nucleophilic substitution step, which is normally reluctant with less nucleophilic tetracoordinate organosilicon compounds [45].
A plausible reaction mechanism is outlined in Scheme 5. Initially, CPME (2a) interacts with TBAT to form a hypervalent silicate A, which is supposed to cleave C−OMe bond, affording silicate [Ph3FSiOMe]. Meanwhile, acyl fluorides 1 react with PPh3 to generate phosphonium B which can be more electrophilic to participate in methoxylation by nucleophilic attack of a methoxide ion to a carbonyl group, giving the desired product 3 and Ph3SiF which was confirmed by 19F{1H} nuclear magnetic resonance (NMR) spectrum. Although a role of a catalytic amount of PPh3 has not been clarified, the formation of phosphonium might accelerate a nucleophilic attack of a methoxide to 1.

3. Experimental Sections

3.1. General

Unless otherwise noted, all the reactions were carried out under an argon atmosphere using standard Schlenk techniques. Glassware was dried in an oven (150 °C) and heated under reduced pressure prior to use. Solvents were employed as eluents for all other routine operation, as well as dehydrated solvent were purchased from commercial suppliers and employed without any further purification. For thin layer chromatography (TLC) analyses throughout this work, Merck precoated TLC plates (silica gel 60 GF254, 0.25 mm) were used. Silica gel column chromatography was carried out using Silica gel 60 N (spherical, neutral, 40–100 μm) from Kanto Chemicals Co., Inc. (Tokyo, Japan) NMR spectra (1H and 19F{1H}) were recorded on Varian INOVA-600 (600 MHz) or Mercury-400 (400 MHz) spectrometers (Agilent Technologies International Japan, Ltd., Tokyo, Japan). Chemical shifts (δ) are in parts per million relative to CDCl3 at 7.26 ppm for 1H. The 19F{1H} NMR spectra were measured by using CCl3F (=0.00 ppm) as an external standard. The NMR yields were determined using dibromomethane as an internal standard. The GC yields were determined by GC analysis of the crude mixture, using n-dodecane as an internal standard.

3.2. Experimental Method

3.2.1. Representative Procedure for the Synthesis of Acyl Fluorides from Acyl Chlorides

To a 50 mL of Schlenk tube charged with a magnetic stir bar, were successively added acyl chlorides (4 mmol), 18-crown-6 (52.9 mg, 0.2 mmol, 5 mol %), KF (2.32 g, 40 mmol, 10 equivalents), and THF (20 mL). After the reaction mixture was stirred at 40 °C for 24 h, insoluble inorganic solid (KF or KCl) was filtered, and the volatiles were removed using a rotary evaporator. The crude product was purified by bulb-to-bulb distillation to afford the corresponding acyl fluorides 1 [46].

3.2.2. Representative Procedure for the Synthesis of Acyl Fluorides from Carboxylic Acids

To a 20 mL of Schlenk tube charged with a magnetic stir bar, were successively added carboxylic acids (3.0 mmol) and CH2Cl2 (15 mL). After the mixture was stirred at 0 °C for 30 min, Deoxo-Fluor® reagent (608 μL, 1.1 equivalents, 3.3 mmol) was slowly added to the reaction mixture. After the reaction mixture was stirred at 0 °C for 30 min, the solution was slowly poured into saturated NaHCO3, extracted with CH2Cl2 (3 × 15 mL), and dried over MgSO4. The crude product was purified by flash chromatography on silica gel to afford the corresponding acyl fluorides 1 [47].

3.2.3. Synthesis of Methoxytriphenylsilane

To methanol (2 mL), were added chlorotriphenylsilane (1.179 g, 4 mmol) and triethylamine (607.1 mg, 6 mmol, 1.5 equiv). The reaction mixture was stirred under argon for 72 h until full conversion. Next, the reaction mixture was evaporated to dryness, dissolved in diethyl ether (100 mL), and washed with H2O (1 × 5 mL, 2 × 2.5 mL). Organic phase was dried over sodium sulfate and evaporated. The crude product was purified by flash chromatography (n-hexane: EtOAc = 40:1) to afford methoxytriphenylsilane in 95% yield [48].

3.2.4. General Methods for the Synthesis of Benzyl Ethers 2b2d

To a solution of the corresponding alcohol (20 mmol) in DMF (20 mL), was added sodium hydride (1.2 g, 30 mmol, 60% in paraffin oil, 1.5 equivalents) at 0 °C under argon. After the reaction mixture was stirred for 30 min, benzyl bromide (2.95 mL, 30 mmol, 1.5 equivalents) was added to the reaction mixture at 0 °C and the solution was stirred at room temperature for 5 h. Then the reaction mixture was quenched with H2O (10 mL) and extracted with Et2O (20 mL × 2). The combined organic layers were dried over MgSO4 and concentrated under vacuum. The residue was purified by silica-gel column chromatography (n-hexane: EtOAc = 40:1) to give the corresponding benzyl ether derivatives 2b2d [49].

3.2.5. Representative Procedure for Methoxylation of Acyl Fluorides 1 with CPME (2a)

To a 20 mL Schlenk tube containing PPh3 (15.7 mg, 0.06 mmol, 30 mol %,) and TBAT (108 mg, 0.2 mmol, 1 equivalents), were added [1,1′-biphenyl]-4-carbonyl fluoride (1b) (40.0 mg, 0.2 mmol,) and CPME (2.0 mL). Subsequently, the resulting mixture was heated at 130 °C. After 24 h, cyclopentyl methyl ether (2a) was removed by a rotary evaporator (for the high-boiling-point ethers were removed by bulb-to-bulb distillation), and the residue was purified by column chromatography (n-hexane: EtOAc = 20:1) to afford methyl [1,1′-biphenyl]-4-carboxylate (3b) (39 mg, 0.184 mmol) in 92% yield. Spectroscopic data for methyl esters matched with those previously reported in the literature, and 1H and 19F{1H} NMR spectra of representative starting materials and the prepared products are shown in Supplementary Materials.

3.3. Characterization Data of Starting Materials and Products

Methoxytriphenylsilane [48]. Yield: 95% (1.1 g); white solid; 1H NMR (400 MHz, CDCl3) δ 3.65 (s, 3H), 7.37–7.47 (m, 9H), 7.60–7.67 (m, 6H).
((Prop-2-yn-1-yloxy)methyl)benzene (2c) [49]. Yield: 80% (2.34 g); colorless oil; 1H NMR (600 MHz, CDCl3) δ 2.47 (s, 1H), 4.18 (d, J = 2.4 Hz, 2H), 4.62 (s, 2H), 7.29–7.33 (m, 1H), 7.34–7.39 (m, 4H).
Methyl benzoate (3a) [50]. Yield: 74% (20.2 mg); colorless oil; 1H NMR (400 MHz, CDCl3) δ 3.92 (s, 3H), 7.42-7.47 (m, 2H), 7.53–7.58 (m, 1H), 8.02-8.07 (m, 2H).
Methyl [1,1′-biphenyl]-4-carboxylate (3b) [51]. Yield: 92% (39.1 mg); white solid; 1H NMR (400 MHz, CDCl3) δ 3.94 (s, 3H), 7.40 (t, J = 7.3 Hz, 1H), 7.47 (t, J = 7.5 Hz, 2H), 7.61–7.68 (m, 4H), 8.11 (d, J = 8.2 Hz, 2H).
Methyl 4-methoxybenzoate (3c) [50]. Yield: 88% (29.2 mg); colorless oil; 1H NMR (400 MHz, CDCl3) δ 3.85 (s, 3H), 3.88 (s, 3H), 6.91 (d, J = 8.9 Hz, 2H), 7.99 (d, J = 9.0 Hz, 2H).
Methyl 4-butoxybenzoate (3d) [52]. Yield: 78% (32.5 mg); colorless oil; 1H NMR (600 MHz, CDCl3) δ 0.98 (t, J = 7.4 Hz, 3H), 1.46–1.53 (m, 2H), 1.78 (ddt, J = 9.1, 7.7, 6.5 Hz, 2H), 3.88 (s, 3H), 4.01 (s, 2H), 6.90 (d, J = 8.9 Hz, 2H), 7.92–8.03 (m, 2H).
Methyl 4-butylbenzoate (3e) [53]. Yield: 64% (24.6 mg); colorless oil; 1H NMR (400 MHz, CDCl3) δ 0.92 (t, J = 7.3 Hz, 3H), 1.31–1.40 (m, 2H), 1.55–1.67 (m, 2H), 2.63–2.68 (m, 2H), 3.90 (s, 3H), 7.24 (dt, J = 8.6, 0.6 Hz, 2H), 7.90–7.98 (m, 2H).
Methyl 4-methylbenzoate (3f) [50]. Yield: 90% (27.0 mg); colorless oil; 1H NMR (400 MHz, CDCl3) δ 2.41 (s, 3H), 3.90 (s, 3H), 7.24 (dt, J = 8.0, 0.6 Hz, 2H), 7.89–7.97 (m, 2H).
Methyl 2-methylbenzoate (3g) [54]. Yield: 87% (26.2 mg); colorless oil; 1H NMR (400 MHz, CDCl3) δ 2.60 (s, 3H), 3.89 (s, 3H), 7.22–7.26 (m, 2H), 7.39 (td, J = 7.5, 1.3 Hz, 1H), 7.91 (dd, J = 8.2, 1.2 Hz, 1H).
Methyl 4-chlorobenzoate (3h) [50]. Yield: 92% (31.4 mg); white solid; 1H NMR (400 MHz, CDCl3) δ 3.92 (s, 3H), 7.41 (d, J = 8.5 Hz, 2H), 7.95–8.00 (m, 2H).
Methyl 4-nitrobenzoate (3i) [55]. Yield: 31% (11.3 mg); white solid; 1H NMR (400 MHz, CDCl3) δ 3.98 (s, 3H), 8.19–8.23 (m, 2H), 8.26–8.31 (m, 2H).
Methyl 4-cyanobenzoate (3j) [56]. Yield: 80% (25.8 mg); white solid; 1H NMR (400 MHz, CDCl3) δ 3.96 (s, 3H), 7.71–7.77 (m, 2H), 8.10–8.17 (m, 2H).
Methyl 4-(trifluoromethyl)benzoate (3k) [50]. Yield: 78% (32.0 mg); colorless oil; 1H NMR (400 MHz, CDCl3) δ 3.96 (s, 3H), 7.69–7.73 (m, 2H), 8.11–8.18 (m, 2H).
Dimethyl terephthalate (3l) [55]. Yield: 75% (29.0 mg); colorless oil; 1H NMR (400 MHz, CDCl3) δ 3.94 (s, 6H), 8.10 (s, 4H).
Methyl 2,3-dihydrobenzo[b][1,4]dioxine-6-carboxylate (3m) [57]. Yield: 93% (36.1 mg); colorless oil; 1H NMR (400 MHz, CDCl3) δ 3.87 (s, 3H), 4.25–4.28 (m, 2H), 4.29–4.32 (m, 2H), 6.86–6.90 (m, 1H), 7.52–7.58 (m, 2H).
Methyl 2,4,6-trimethylbenzoate (3n) [58]. Yield: 61% (21.8 mg); white solid; 1H NMR (400 MHz, CDCl3) δ 2.28 (s, 9H), 3.89 (s, 3H), 6.85 (s, 2H).
Methyl 3,4,5-trimethoxybenzoate (3o) [59]. Yield: 70% (31.7 mg); white solid; 1H NMR (400 MHz, CDCl3) δ 3.90 (d, J = 1.0 Hz, 12H), 7.29 (s, 2H).
Methyl 1-naphthoate (3p) [54]. Yield: 73% (27.2 mg); white solid; 1H NMR (400 MHz, CDCl3) δ 4.01 (s, 3H), 7.48–7.56 (m, 2H), 7.62 (ddd, J = 8.6, 6.8, 1.5 Hz, 1H), 7.89 (ddd, J = 8.2, 1.4, 0.7 Hz, 1H), 8.02 (ddd, J = 8.3, 1.4, 0.7 Hz, 1H), 8.19 (dd, J = 7.3, 1.3 Hz, 1H), 8.89–8.95 (m, 1H).
Methyl 2-naphthoate (3q) [60]. Yield: 83% (31.0 mg); white solid; 1H NMR (400 MHz, CDCl3) δ 3.99 (s, 3H), 7.57 (dddd, J = 19.6, 8.1, 6.9, 1.4 Hz, 2H), 7.88 (dt, J = 8.0, 1.2 Hz, 2H), 7.95 (ddt, J = 8.0, 1.4, 0.7 Hz, 1H), 8.07 (dd, J = 8.6, 1.7 Hz, 1H), 8.62 (dd, J = 1.6, 0.8 Hz, 1H).
Methyl anthracene-9-carboxylate (3r) [54]. Yield: 52% (24.6 mg); white solid; 1H NMR (400 MHz, CDCl3) δ 4.19 (s, 3H), 7.47-7.57 (m, 4H), 8.03 (dd, J = 8.4, 4.1 Hz, 4H), 8.54 (s, 1H).
Methyl benzofuran-2-carboxylate (3s) [61]. Yield: 42% (14.8 mg); white solid; 1H NMR (400 MHz, CDCl3) δ 3.98 (s, 3H), 7.31 (ddd, J = 7.9, 7.2, 0.8 Hz, 1H), 7.46 (ddd, J = 8.4, 7.1, 1.3 Hz, 1H), 7.54 (t, J = 0.7 Hz, 1H), 7.59 (dq, J = 8.3, 0.8 Hz, 1H), 7.69 (ddd, J = 7.9, 1.4, 0.7 Hz, 1H).
Methyl furan-2-carboxylate (3t) [62]. Yield: 80% (20.2 mg); colorless oil; 1H NMR (400 MHz, CDCl3) δ 3.86 (s, 3H), 6.47 (dd, J = 3.5, 1.8 Hz, 1H), 7.14 (dd, J = 3.5, 0.9 Hz, 1H), 7.54 (dd, J = 1.7, 0.9 Hz, 1H).
Methyl thiophene-2-carboxylate (3u) [54]. Yield: 70% (20 mg); colorless oil; 1H NMR (400 MHz, CDCl3) δ 3.89 (s, 3H), 7.10 (dd, J = 5.0, 3.7 Hz, 1H), 7.55 (dd, J = 5.0, 1.3 Hz, 1H), 7.80 (dd, J = 3.7, 1.3 Hz, 1H).
Methyl dodecanoate (3v) [63]. Yield: 45% (19.4 mg); colorless oil; 1H NMR (400 MHz, CDCl3) δ 0.85–0.90 (m, 3H), 1.23–1.30 (m, 16H), 1.62 (td, J = 7.1, 3.0 Hz, 2H), 2.27–2.32 (m, 2H), 3.66 (s, 3H).
Methyl (3r,5r,7r)-adamantane-1-carboxylate (3w) [64]. Yield: 56% (21.8 mg); white solid; 1H NMR (600 MHz, CDCl3) δ 1.68–1.73 (m, 6H), 1.88–1.89 (m, 6H), 1.99–2.02 (m, 3H), 3.64 (s, 3H).
Benzyl [1,1′-biphenyl]-4-carboxylate (3bb) [65]. Yield: 78% (45.1 mg); white solid; 1H NMR (600 MHz, CDCl3) δ 5.40 (s, 2H), 7.33–7.43 (m, 4H), 7.45–7.49 (m, 4H), 7.61–7.64 (m, 2H), 7.65–7.68 (m, 2H), 8.13–8.17 (m, 2H).
Prop-2-yn-1-yl [1,1′-biphenyl]-4-carboxylate (3bc) [66]. Yield: 50% (23.6 mg); white solid; 1H NMR (600 MHz, CDCl3) δ 2.54 (t, J = 2.4 Hz, 1H), 4.96 (d, J = 2.5 Hz, 2H), 7.39–7.43 (m, 1H), 7.45–7.50 (m, 2H), 7.61–7.64 (m, 2H), 7.66–7.70 (m, 2H), 8.12–8.18 (m, 2H).

4. Summary

In summary, we report the PPh3-assisted methoxylation via the regiospecific cleavage of the inert C−OMe bond in CPME. This protocol demonstrated the utility of CPME as a methoxylating reagent, good functional group tolerance, and metal-free conditions. Furthermore, the regiospecific cleavage of aliphatic ethers, even in the presence of aromatic ethers, is quite difficult to achieve by conventional reagents. We believe that our study constitutes an important contribution towards a more practical use of readily available aliphatic ethers as coupling partners. Further explorations of related transformations via C−O scission are currently underway in our laboratory.

Supplementary Materials

The following are available online at https://www.mdpi.com/2073-4344/9/7/574/s1. Details of screening the amounts of TBAT and PPh3 (Table S1), the effect of PPh3 (Table S2), and 1H and 19F{1H} NMR spectra of representative starting materials and final products.

Author Contributions

Z.W. developed above reactions and wrote the manuscript; Z.W. and X.W. prepared starting materials and expanded the substrates scope; Y.N. supervised the project and revised the manuscript.

Funding

This research received no external funding.

Acknowledgments

We gratefully thank the SC-NMR Laboratory (Okayama University) for the NMR spectral measurements.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Burwell, R.L., Jr. The Cleavage of Ethers. Chem. Rev. 1954, 54, 615–685. [Google Scholar] [CrossRef]
  2. Maercker, A. Ether Cleavage with Organo-Alkali-Metal Compounds and Alkali Metals. Angew. Chem. Int. Ed. Engl. 1987, 26, 972–989. [Google Scholar] [CrossRef]
  3. Bhatt, M.V.; Kulkarni, S.U. Cleavage of Ethers. Synthesis 1983, 1983, 249–282. [Google Scholar] [CrossRef]
  4. Tiecco, M. Selective Dealkylations of Aryl Alkyl Ethers, Thioethers, and Selenoethers. Synthesis 1988, 1988, 749–759. [Google Scholar] [CrossRef]
  5. Ranu, B.C.; Bhar, S. Dealkylation of Ethers. A Review. Org. Prep. Proced. Int. 1996, 28, 371–409. [Google Scholar] [CrossRef]
  6. Minamikawa, J.; Brossi, A. Selective o-demethylation of an aromatic methylether in the presence of an aromatic methylenedioxy group with trimethylisilyl iodide in quinoline. Tetrahedron Lett. 1978, 19, 3085–3086. [Google Scholar] [CrossRef]
  7. McCarthy, J.R.; Moore, J.L.; Cregge, R.J. A convenient new method for converting aromatic methyl ethers to phenols with sodium cyanide-dimethyl sulfoxide. Tetrahedron Lett. 1978, 19, 5183–5186. [Google Scholar] [CrossRef]
  8. Kamal, A.; Gayatri, N.L. An efficient method for 4-β-anilino-4′-demethylepipodophyllotoxins: Synthesis of NPF and W-68. Tetrahedron Lett. 1996, 37, 3359–3362. [Google Scholar] [CrossRef]
  9. Brooks, P.R.; Wirtz, M.C.; Vetelino, M.G.; Rescek, D.M.; Woodworth, G.F.; Morgan, B.P.; Coe, J.W. Boron Trichloride/Tetra-n-Butylammonium Iodide:  A Mild, Selective Combination Reagent for the Cleavage of Primary Alkyl Aryl Ethers. J. Org. Chem. 1999, 64, 9719–9721. [Google Scholar] [CrossRef]
  10. Chakraborti, A.K.; Nayak, M.K.; Sharma, L. Diphenyl Disulfide and Sodium in NMP as an Efficient Protocol for in Situ Generation of Thiophenolate Anion:  Selective Deprotection of Aryl Alkyl Ethers and Alkyl/Aryl Esters under Nonhydrolytic Conditions. J. Org. Chem. 2002, 67, 1776–1780. [Google Scholar] [CrossRef]
  11. Narayanan, C.R.; Iyer, K.N. Regeneration of Steroid Alcohols from Their Methyl Ethers. J. Org. Chem. 1965, 30, 1734–1736. [Google Scholar] [CrossRef]
  12. Géro, S.D. The preparation of 1-0-tosyl-(-)-inositol from quebrachitol. Tetrahedron Lett. 1966, 7, 591–595. [Google Scholar] [CrossRef]
  13. Ayer, W.A.; Bowman, W.R.; Joseph, T.C.; Smith, P. Synthesis of dl-lycopodine. J. Am. Chem. Soc. 1968, 90, 1648–1650. [Google Scholar] [CrossRef] [PubMed]
  14. Node, M.; Hori, H.; Fujita, E. Demethylation of aliphatic methyl ethers with a thiol and boron trifluoride. J. Chem. Soc. Perkin Trans. 1 1976, 1, 2237–2240. [Google Scholar] [CrossRef]
  15. Jung, M.E.; Lyster, M.A. Quantitative dealkylation of alkyl ethers via treatment with trimethylsilyl iodide. A new method for ether hydrolysis. J. Org. Chem. 1977, 42, 3761–3764. [Google Scholar] [CrossRef]
  16. Landani, D.; Montanari, F.; Rolla, F. Cleavage of Dialkyl and Aryl Alkyl Ethers with Hydrobromic Acid in the Presence of Phase-Transfer Catalysts. Synthesis 1978, 1978, 771–773. [Google Scholar] [CrossRef]
  17. Niwa, H.; Hida, T.; Yamada, K. A new method for cleavage of aliphatic methyl ethers. Tetrahedron Lett. 1981, 22, 4239–4240. [Google Scholar] [CrossRef]
  18. Guindon, Y.; Yoakim, C.; Morton, H.E. Cleavage of carbonoxygen bonds. Dimethylboron bromide. A new reagent for ether cleavage. Tetrahedron Lett. 1983, 24, 2969–2972. [Google Scholar] [CrossRef]
  19. Node, M.; Ohta, K.; Kajimoto, T.; Nishide, K.; Fujita, E.; Fuji, K. Selective Demethylation of Aliphatic Methyl Ether in the Presence of Aromatic Methyl Ether with the Aluminum Chloride-Sodium Iodide-Acetonitrile System. Chem. Pharm. Bull. 1983, 31, 4178–4180. [Google Scholar] [CrossRef]
  20. Narayana, C.; Padmanabhan, S.; Kabalka, G.W. Cleavage of ethers and geminal diacetates using the boron triiodide-N,N-diethylaniline complex. Tetrahedron Lett. 1990, 31, 6977–6978. [Google Scholar] [CrossRef]
  21. Watanabe, K.; Yamagiwa, N.; Torisawa, Y. Cyclopentyl Methyl Ether as a New and Alternative Process Solvent. Org. Process. Res. Dev. 2007, 11, 251–258. [Google Scholar] [CrossRef]
  22. Antonucci, V.; Coleman, J.; Ferry, J.B.; Johnson, N.; Mathe, M.; Scott, J.P.; Xu, J. Toxicological Assessment of 2-Methyltetrahydrofuran and Cyclopentyl Methyl Ether in Support of Their Use in Pharmaceutical Chemical Process Development. Org. Process. Res. Dev. 2011, 15, 939–941. [Google Scholar] [CrossRef]
  23. Ochiai, H.; Uetake, Y.; Niwa, T.; Hosoya, T. Rhodium-Catalyzed Decarbonylative Borylation of Aromatic Thioesters for Facile Diversification of Aromatic Carboxylic Acids. Angew. Chem. Int. Ed. 2017, 56, 2482–2486. [Google Scholar] [CrossRef] [PubMed]
  24. Majdanski, T.C.; Vitz, J.; Meier, A.; Brunzel, M.; Schubert, S.; Nischang, I.; Schubert, U.S. “Green” ethers as solvent alternatives for anionic ring-opening polymerizations of ethylene oxide (EO): In-situ kinetic and advanced characterization studies. Polymer 2018, 159, 86–94. [Google Scholar] [CrossRef]
  25. Wang, Z.; Guo, C.-Y.; Yang, C.; Chen, J.-P. Ag-Catalyzed Chemoselective Decarboxylative Mono- and gem-Difluorination of Malonic Acid Derivatives. J. Am. Chem. Soc. 2019, 141, 5617–5622. [Google Scholar] [CrossRef]
  26. Atienza, B.J.P.; Truong, N.; Williams, F.J. Reliably Regioselective Dialkyl Ether Cleavage with Mixed Boron Trihalides. Org. Lett. 2018, 20, 6332–6335. [Google Scholar] [CrossRef] [PubMed]
  27. Bhar, S.; Ranu, B.C. Zinc-Promoted Selective Cleavage of Ethers in Presence of Acyl Chloride. J. Org. Chem. 1995, 60, 745–747. [Google Scholar] [CrossRef]
  28. Craig, R.; Litvajova, M.; Cronin, S.A.; Connon, S.J. Enantioselective acyl-transfer catalysis by fluoride ions. Chem. Commun. 2018, 54, 10108–10111. [Google Scholar]
  29. Blanchard, N.; Bizet, V. Acid Fluorides in Transition-Metal Catalysis: A Good Balance between Stability and Reactivity. Angew. Chem. Int. Ed. 2019, 58, 6814–6817. [Google Scholar] [CrossRef] [PubMed]
  30. Ogiwara, Y.; Sakai, N. Acyl Fluorides in Late Transition-Metal Catalysis. Angew. Chem. Int. Ed. 2019. [Google Scholar] [CrossRef]
  31. Zhang, Y.D.; Rovis, T. A Unique Catalyst Effects the Rapid Room-Temperature Cross-Coupling of Organozinc Reagents with Carboxylic Acid Fluorides, Chlorides, Anhydrides, and Thioesters. J. Am. Chem. Soc. 2004, 126, 15964–15965. [Google Scholar] [CrossRef] [PubMed]
  32. Ogiwara, Y.; Sakino, D.; Sakurai, Y.; Sakai, N. Acid Fluorides as Acyl Electrophiles in Suzuki-Miyaura Coupling. Eur. J. Org. Chem. 2017, 4324–4327. [Google Scholar] [CrossRef]
  33. Ogiwara, Y.; Sakurai, Y.; Hattori, H.; Sakai, N. Palladium-Catalyzed Reductive Conversion of Acyl Fluorides via Ligand-Controlled Decarbonylation. Org. Lett. 2018, 20, 4204–4208. [Google Scholar] [CrossRef]
  34. Keaveney, S.T.; Schoenebeck, F. Palladium-Catalyzed Decarbonylative Trifluoromethylation of Acid Fluorides. Angew. Chem. Int. Ed. 2018, 57, 4073–4077. [Google Scholar] [CrossRef] [PubMed]
  35. Malapit, C.A.; Bour, J.R.; Brigham, C.E.; Sanford, M.S. Base-free nickel-catalysed decarbonylative Suzuki-Miyaura coupling of acid fluorides. Nature 2018, 563, 100–104. [Google Scholar] [CrossRef] [PubMed]
  36. Sakurai, S.; Yoshida, T.; Tobisu, M. Iridium-catalyzed Decarbonylative Coupling of Acyl Fluorides with Arenes and Heteroarenes via C–H Activation. Chem. Lett. 2019, 48, 94–97. [Google Scholar] [CrossRef]
  37. Okuda, Y.; Xu, J.; Ishida, T.; Wang, C.; Nishihara, Y. Nickel-Catalyzed Decarbonylative Alkylation of Aroyl Fluorides Assisted by Lewis-Acidic Organoboranes. ACS Omega 2018, 3, 13129–13140. [Google Scholar] [CrossRef]
  38. Wang, Z.; Wang, X.; Nishihara, Y. Nickel-catalysed decarbonylative borylation of aroyl fluorides. Chem. Commun. 2018, 54, 13969–13972. [Google Scholar] [CrossRef] [PubMed]
  39. Wang, X.; Wang, Z.; Asanuma, Y.; Nishihara, Y. Synthesis of 2-Substituted Propenes by Bidentate Phosphine Assisted Methylenation of Acyl Fluorides and Acyl Chlorides with AlMe3. Org. Lett. 2019, 21, 3640–3643. [Google Scholar] [CrossRef]
  40. Wang, X.; Wang, Z.; Liu, L.; Asanuma, Y.; Nishihara, Y. Nickel-Catalyzed Decarbonylative Stannylation of Acyl Fluorides under Ligand-Free Conditions. Molecules 2019, 24, 1671. [Google Scholar] [CrossRef]
  41. Pilcher, A.S.; Ammon, H.L.; DeShong, P. Utilization of Tetrabutylammonium Triphenylsilyldifluoride as a Fluoride Source for Nucleophilic Fluorination. J. Am. Chem. Soc. 1995, 117, 5166–5167. [Google Scholar] [CrossRef]
  42. Gazizov, T.K.; Belyalov, R.U.; Pudovik, A.N. Reaction of phosphorus acid esters with carboxylic acid chlorides and fluorides. Chem. Inf. 1982, 52, 776–780. [Google Scholar]
  43. Bou, V.; Vilarrasa, J. New synthetic ‘tricks’. Trimethylsilyl triflate mediated cleavage of hindered silyl ethers. Tetrahedron Lett. 1990, 31, 567–568. [Google Scholar] [CrossRef]
  44. Tamao, K.; Yoshida, J.; Takahashi, M.; Yamamoto, H.; Kakui, T.; Matsumoto, H.; Kurita, A.; Kumada, M. Organofluorosilicates in organic synthesis. 1. A novel general and practical method for anti-Markownikoff hydrohalogenation of olefins via organopentafluorosilicates derived from hydrosilylation products. J. Am. Chem. Soc. 1978, 100, 290–292. [Google Scholar] [CrossRef]
  45. Nakao, Y.; Hiyama, T. Silicon-based cross-coupling reaction: An environmentally benign version. Chem. Soc. Rev. 2011, 40, 4893–4901. [Google Scholar] [CrossRef] [PubMed]
  46. Lee, L.; Shim, C.S.; Chung, S.Y.; Kim, H.Y.; Lee, H.W. Cross-interaction constants as a measure of the transition-state structure. Part 1. The degree of bond formation in nucleophilic substitution reactions. J. Chem. Soc. Perkin Trans. 2 1988, 11, 1919–1923. [Google Scholar] [CrossRef]
  47. Lal, G.S.; Pez, G.P.; Pesaresi, R.J.; Prozonic, F.M.; Cheng, H.S. Bis(2-methoxyethyl)aminosulfur Trifluoride: A New Broad-Spectrum Deoxofluorinating Agent with Enhanced Thermal Stability. J. Org. Chem. 1999, 64, 7048–7054. [Google Scholar] [CrossRef]
  48. Savela, R.; Zawartka, W.; Leino, R. Iron-Catalyzed Chlorination of Silanes. Organometallics 2012, 31, 3199–3206. [Google Scholar] [CrossRef]
  49. Yasukawa, N.; Kanie, T.; Kuwata, M.; Monguchi, Y.; Sajiki, H.; Sawama, Y. Palladium on Carbon-Catalyzed Benzylic Methoxylation for Synthesis of Mixed Acetals and Orthoesters. Chem. Eur. J. 2017, 23, 10974–10977. [Google Scholar] [CrossRef]
  50. Zhou, H.; Zhang, J.; Yang, H.; Xia, C.; Jiang, G. Rhodium-Catalyzed Double Alkyl-Oxygen Bond Cleavage: An Alkyl Transfer Reaction from Bis/Tris(o-alkyloxyphenyl)phosphine to Aryl Acids. Organometallics 2016, 35, 3406–3412. [Google Scholar] [CrossRef]
  51. Riggleman, S.; DeShong, P. Application of Silicon-Based Cross-Coupling Technology to Triflates. J. Org. Chem. 2003, 68, 8106–8109. [Google Scholar] [CrossRef] [PubMed]
  52. Torraca, K.E.; Huang, X.; Parrish, C.A.; Buchwald, S.L. An Efficient Intermolecular Palladium-Catalyzed Synthesis of Aryl Ethers. J. Am. Chem. Soc. 2001, 123, 10770–10771. [Google Scholar] [CrossRef] [PubMed]
  53. Ebert, G.W.; Rieke, R.D. Preparation of aryl, alkynyl, and vinyl organocopper compounds by the oxidative addition of zerovalent copper to carbon-halogen bonds. J. Org. Chem. 1988, 53, 4482–4488. [Google Scholar] [CrossRef]
  54. Mane, R.S.; Sasakib, T.; Bhanage, B.M. Silica supported palladium-phosphine as a reusable catalyst for alkoxycarbonylation and aminocarbonylation of aryl and heteroaryl iodides. RSC Adv. 2015, 5, 94776–94785. [Google Scholar] [CrossRef]
  55. Chng, L.L.; Yang, J.; Ying, J.Y. Efficient Synthesis of Amides and Esters from Alcohols under Aerobic Ambient Conditions Catalyzed by a Au/Mesoporous Al2O3 Nanocatalyst. ChemSusChem 2015, 8, 1916–1925. [Google Scholar] [CrossRef]
  56. Leduc, A.B.; Jamison, T.F. Continuous Flow Oxidation of Alcohols and Aldehydes Utilizing Bleach and Catalytic Tetrabutylammonium Bromide. Org. Process. Res. Dev. 2012, 16, 1082–1089. [Google Scholar] [CrossRef]
  57. Sun, J.; Ren, S.-Z.; Lu, X.-Y.; Li, J.-J.; Shen, F.-Q.; Xu, C.; Zhu, H.-L. Discovery of a series of 1,3,4-oxadiazole-2(3H)-thione derivatives containing piperazine skeleton as potential FAK inhibitors. Bioorg. Med. Chem. 2017, 25, 2593–2600. [Google Scholar] [CrossRef]
  58. Zhang, N.; Yang, R.; Negrerie, D.Z.; Du, Y.; Zhao, K. Direct Conversion of N-Alkoxyamides to Carboxylic Esters through Tandem NBS-Mediated Oxidative Homocoupling and Thermal Denitrogenation. J. Org. Chem. 2013, 78, 8705–8711. [Google Scholar] [CrossRef]
  59. Hirose, T.; Takai, H.; Watabe, M.; Minamikawa, H.; Tachikawa, T.; Kodama, K.; Yasutake, M. Effect of alkoxy terminal chain length on mesomorphism of 1,6-disubstituted pyrene-based hexacatenar liquid crystals: Columnar phase control. Tetrahedron 2014, 70, 5100–5108. [Google Scholar] [CrossRef]
  60. Zhu, Y.; Yan, H.; Lu, L.; Liu, D.; Rong, G.; Mao, J. Copper-Catalyzed Methyl Esterification Reactions via C–C Bond Cleavage. J. Org. Chem. 2013, 78, 9898–9905. [Google Scholar] [CrossRef]
  61. Marco, P.; Elisa, A.; Nicoletta, B.; Silvia, P.; Michal, Z.; Claudia, B.; Giannamaria, A.; Agostino, B.; Federica, V.; Gabriele, C. Accepting the Invitation to Open Innovation in Malaria Drug Discovery: Synthesis, Biological Evaluation, and Investigation on the Structure–Activity Relationships of Benzo[b]thiophene-2-carboxamides as Antimalarial Agents. J. Med. Chem. 2017, 60, 1959–1970. [Google Scholar]
  62. Liu, C.; Wang, J.; Meng, L.; Deng, Y.; Li, Y.; Lei, A. Palladium-Catalyzed Aerobic Oxidative Direct Esterification of Alcohols. Angew. Chem. Int. Ed. 2011, 50, 5144–5148. [Google Scholar] [CrossRef] [PubMed]
  63. Hatano, M.; Tabata, Y.; Yoshida, Y.; Toh, K.; Yamashita, K.; Ogura, Y.; Ishihara, K. Metal-free transesterification catalyzed by tetramethylammonium methyl carbonate. Green Chem. 2018, 20, 1193–1198. [Google Scholar] [CrossRef]
  64. Rodriguez, A.; Nomen, M.; Spur, B.W.; Godfroid, J.J. A selective method for the preparation of aliphatic methyl esters in the presence of aromatic carboxylic acids. Tetrahedron Lett. 1998, 39, 8563–8566. [Google Scholar] [CrossRef]
  65. Rout, S.K.; Guin, S.; Ghara, K.K.; Banerjee, A.; Patel, B.K. Copper Catalyzed Oxidative Esterification of Aldehydes with Alkylbenzenes via Cross Dehydrogenative Coupling. Org. Lett. 2012, 14, 3982–3985. [Google Scholar] [CrossRef] [PubMed]
  66. Ramanjaneyulu, B.T.; Reddy, V.; Arde, P.; Mahesh, S.; Anand, R.V. Combining Oxidative N-Heterocyclic Carbene Catalysis with Click Chemistry: A Facile One-Pot Approach to 1,2,3-Triazole Derivatives. Chem. Asian J. 2013, 8, 1489–1496. [Google Scholar] [CrossRef] [PubMed]
Scheme 1. C−O cleavage in alkyl methyl ethers. (a) Conventional demethylation of aliphatic methyl ethers (deprotection), (b) This work.
Scheme 1. C−O cleavage in alkyl methyl ethers. (a) Conventional demethylation of aliphatic methyl ethers (deprotection), (b) This work.
Catalysts 09 00574 sch001
Figure 1. Methoxylation of acyl fluorides 1 with CPME (2a) a,b. a Reaction conditions: acyl fluorides 1 (0.2 mmol), 2a (2 mL), PPh3 (0.06 mmol), TBAT (0.2 mmol), 130 °C, 24 h. b Isolated yields.
Figure 1. Methoxylation of acyl fluorides 1 with CPME (2a) a,b. a Reaction conditions: acyl fluorides 1 (0.2 mmol), 2a (2 mL), PPh3 (0.06 mmol), TBAT (0.2 mmol), 130 °C, 24 h. b Isolated yields.
Catalysts 09 00574 g001aCatalysts 09 00574 g001b
Scheme 2. (a) Alkoxylation of 1b with dibenzyl ether (2b). (b) Alkoxylation of acyl fluorides 1b with benzyl propargyl ether (2c). (c) Alkoxylation of acyl fluorides 1a with benzyl methyl ether (2d). (d) Alkoxylation of acyl fluorides 1a with hexyl methyl ether (2e).
Scheme 2. (a) Alkoxylation of 1b with dibenzyl ether (2b). (b) Alkoxylation of acyl fluorides 1b with benzyl propargyl ether (2c). (c) Alkoxylation of acyl fluorides 1a with benzyl methyl ether (2d). (d) Alkoxylation of acyl fluorides 1a with hexyl methyl ether (2e).
Catalysts 09 00574 sch002
Scheme 3. Methoxylation of 1a with 2a in the presence of radical scavengers.
Scheme 3. Methoxylation of 1a with 2a in the presence of radical scavengers.
Catalysts 09 00574 sch003
Scheme 4. Methoxylation of 1a with Ph3SiOMe.
Scheme 4. Methoxylation of 1a with Ph3SiOMe.
Catalysts 09 00574 sch004
Scheme 5. Proposed mechanism.
Scheme 5. Proposed mechanism.
Catalysts 09 00574 sch005
Table 1. Optimization of the reaction conditions.
Table 1. Optimization of the reaction conditions.
Catalysts 09 00574 i001
Entry[P]AdditiveYield of 3a (%) 1
1PPh3TBAT74 (74)
2P(OPh)3TBAT40
3PCy3TBAT50
4PtBu3TBAT45
5P(4-F-C6H4)3TBAT55
6PPh3NBu4F46
7PPh3NBu4Cl30
8PPh3NBu4Br14
9PPh3NBu4I25
10PPh3NBu4OTf 0
11PPh3KF12
12PPh3CsF14
13PPh318-crown-6/KF34
14PPh3Ph3SiF0
15PPh3-0
16-TBAT53
17 2PPh3TBAT50
1 Determined by gas chromatography (GC) analysis of the crude mixture using n-dodecane as an internal standard. An isolated yield is given in parentheses. 2 Benzoyl chloride was employed instead of 1a.
Back to TopTop