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Article Cite This: ACS Omega 2019, 4, 8465−8471
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Chemoselective Transformations of Aromatic Methoxymethyl Ethers Using Trialkylsilyl Triflate and 2,2′-Bipyridyl Mizushi Yanagihara, Reiya Ohta, Kenichi Murai, Mitsuhiro Arisawa, and Hiromichi Fujioka* Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan
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ABSTRACT: Aromatic methoxymethyl (MOM) ethers behave differently from aliphatic MOM ethers upon treatment with trialkylsilyl triflate (R3SiOTf) and 2,2′-bipyridyl. The aromatic MOM ethers are first converted to silyl ethers and subsequently deprotected by hydrolysis to give the mother alcohols when the R3SiOTf used is trimethylsilyl triflate (TMSOTf). Conversely, direct conversion of aromatic MOM ethers to aromatic triethylsilyl (TES) ethers is possible when the R3SiOTf used is triethylsilyl triflate (TESOTf).
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INTRODUCTION Protecting the hydroxyl group plays an important role in the multistep synthesis of natural products. A number of protecting groups for hydroxyl functions have been developed, such as the methoxymethyl (MOM) group, which is a widely used one due to the MOM ether’s resistance in strongly basic to weakly acidic conditions. Therefore, the deprotection of the MOM group generally needs strong acidic conditions. Then, the substrates with acid-labile functional groups usually need other protective groups, whose deprotection does not need such acidic conditions. However, development of a new mild deprotection method of MOM ether, which does not effect the substrates having labile functional groups, can broaden the range of the use of the MOM group.1 We have recently reported that aliphatic MOM ethers form bipyridinium salt intermediates upon treatment with trimethylsilyl triflate (TMSOTf) or triethylsilyl triflate (TESOTf) and 2,2′-bipyridyl in CH2Cl2.2 Because these intermediates are cationic species, they are susceptible to nucleophilic attack by H2O, which affords the corresponding deprotected products via hemiacetal intermediates.2a The reaction proceeds under mild, nonacidic conditions, allowing this method to be applied even to substrates bearing acid- and base-labile functional groups. A further application of this method is the easy and direct replacement of MOM ethers with benzyloxymethyl (BOM) or 2-(trimethylsilyl)ethoxymethyl (SEM) ethers in a one-pot procedure (Scheme 1).2b However, aromatic MOM ethers have reduced reactivity under the same conditions compared with that of aliphatic MOM ethers. We then explored the reaction of aromatic MOM ethers with trialkysilyl triflate and 2,2′-bipyridyl in detail and found the remarkable effect of CH3CN as a reaction solvent and that the reaction mechanism of aromatic MOM ethers is completely different from that of aliphatic ones. Thus, treatment of aromatic MOM ethers with TMSOTf and 2,2′bipyridyl gives deprotected phenols, whereas the use of © 2019 American Chemical Society
TESOTf in place of TMSOTf results in direct conversion of MOM ethers to TES ethers. These observations also allowed us to develop a chemoselective transformation on molecules containing both aromatic and aliphatic MOM ethers.
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RESULTS AND DISCUSSION We first examined the effect of solvents on the reaction using phenol methoxymethyl ether (1a) as a model substrate for reaction with TMSOTf and 2,2′-bipyridyl at 0 °C to room temperature for the first treatment and at room temperature for the work-up (Table 1). The starting material 1a was not completely consumed even after 14 h of reaction time in CH2Cl2 (entry 1). The reaction did not proceed in toluene, a nonpolar solvent, and only 1a was recovered (entry 2). Although the deprotected product 2a was obtained in 41% yield in AcOEt, 1a did not react completely after 27 h (entry 3). Even in more polar solvents, such as 1,4-dioxane or tetrahydrofuran (THF), 1a was not completely consumed (entries 4 and 5). However, to our delight, the use of CH3CN greatly improved the reaction and 1a disappeared within 15 min and gave 2a in a high yield of 91% (entry 6). In every reaction except entry 2, the TMS ether was formed first,3 based on thin-layer chromatography (TLC), and the mother alcohol was formed by adding H2O for work-up, the details of which will be discussed later (see Scheme 2). Although the reason why the reaction time is greatly shortened in CH3CN is not clear, TMSOTf may be activated in CH3CN by the formation of a complex between TMSOTf and CH3CN as reported previously.4 In fact, when 1H NMR and 13C NMR studies were conducted for the reaction mixture of 2,2′-bipyridyl and TMSOTf in various deuterated solvents (CD3CN, CD2Cl2, THF-d8), remarkable movement of signals was observed only Received: March 7, 2019 Accepted: April 25, 2019 Published: May 14, 2019 8465
DOI: 10.1021/acsomega.9b00643 ACS Omega 2019, 4, 8465−8471
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Scheme 1. Reaction of Aliphatic MOM Ethers with TMSOTf (or TESOTf) and 2,2′-Bipyridyl
Table 1. Effect of Solvents on the Reaction
entry
solvent
1 2 3 4 5 6
CH2Cl2 toluene AcOEt THF 1,4-dioxane CH3CN
time 14 21 27 17 17 15
h h h h h min
yield (%) 52 N.R.a 41 57 53 91
The first stage of the reaction did not proceed.
a
Scheme 2. Plausible Deprotection Mechanism of Aromatic MOM Ethers by TMSOTf-2,2′-Bipyridyl
in CD3CN.5 This shows that CH3CN has a strong effect with the complex ([Bpy·TMS]+−OTf) formed by the reaction of 2,2′-bipyridyl and TMSOTf. Previously, we have already proposed the formation of the complex from 2,4,6-collidine and TMSOTf.6 In this case, it is expected that a similar complex is also formed (see Table 1). Next, we examined the generality of this reaction in CH3CN by screening different substrates (Table 2). In the case of aromatic MOM ethers having an electron-donating group such as a methyl group (1b) or a methoxy group (1c), the reaction proceeded well to give the corresponding products 2b and 2c in high yields without any problems. However, substrate 1e with an electron-withdrawing nitro group required a longer reaction time and heating, although the yield of 2e was still high. This reaction proceeded satisfactorily even with sterically hindered substrate 1d, which had a bulky moiety next to the MOM group. Substrate 1f, with an ester group, gave the deprotected product 2f in good yield. The MOM ether 1g, which had an acid-labile functional group, namely, triphenylmethyl (Tr) ether, was also deprotected without any undesired reactions to give 2g in high yield. This result indicated that this
Table 2. Reaction of Aromatic MOM Ethers with TMSOTf and 2,2′-Bipyridyl in CH3CN
a
The first stage of the reaction was carried out at 50 °C for 4 h.
reaction is very mild and nonacidic. In addition, this method is also applicable to the MOM ether of naphthol 1h. 8466
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considered to be a factor. This reaction mechanism reflects the difference in reactivity depending on the substituents such as when the substrate with a nitro group required longer reaction time and heating relative to other substrates. This is probably because it was difficult for the complex ([Bpy·TMS]+−OTf) to coordinate to the electron-deficient oxygen atom. In addition, it can be said that the presence of 2,2′-bipyridyl is important because this reaction did not proceed with TMSOTf alone. Since the binding energy between the aromatic oxygen and trimethylsilyl group is not so high,8 it was readily hydrolyzed to give the phenol products. Therefore, if we could form a stronger O−Si bond, a stable silyl ether could be obtained. We then conducted an experiment using TESOTf in place of TMSOTf and succeeded in directly obtaining aromatic TES ethers, which is not possible with aliphatic MOM ethers as shown in Scheme 1. The reactivity profile of the TESOTf reaction was found to be similar to that of the TMSOTf (Table 3). Almost all the substrates 1a−h afforded the corresponding
The mechanism of this deprotection reaction was found to be different from that of the aliphatic MOM ether deprotection, as shown by TLC behavior (Figure 1). The
Table 3. Reaction of Aromatic MOM Ethers with TESOTf and 2,2′-Bipyridyl
Figure 1. TLC behaviors of aliphatic MOM ethers (A) and aromatic MOM ethers (B) in the deprotection reaction.
The reaction was carried out at 0−80 °C. bThe reaction was carried out at 0−40 °C. a
aliphatic MOM ether is first converted to a highly polar compound, a salt intermediate, and then the deprotected alcohol forms upon addition of H2O (eq A). On the other hand, the aromatic MOM ether first gives a less polar compound accompanied by a more polar one, presumably a salt intermediate. When water was added, the less polar compound disappeared and phenol, which was identified by comparison to be a standard phenol, appeared (eq B). The less polar compound was unambiguously determined to be the TMS ether of phenol, as revealed by NMR spectroscopy in CD3CN.3 Based on these results, we proposed that the mechanism of this deprotection reaction proceeded as shown in Scheme 2. The complex ([Bpy·TMS]+−OTf) coordinates to the oxygen atom next to the aromatic ring and compound A and salt intermediate C are formed.7 Then, compound A is hydrolyzed to give phenol. In the case of aromatic MOM ethers, it is thought that the complex ([Bpy·TMS]+−OTf) preferentially coordinates to the more highly Lewis basic oxygen atom on the methyl side of the acetal. But because of the equilibrium reaction, it is presumed that some complex ([Bpy· TMS]+−OTf) is also coordinated to the oxygen atom on the aromatic ring side, and the reaction proceeds only when the complex is coordinated to the aromatic side oxygen. Compared with aliphatic MOM ethers, the difference in electron density between two oxygen atoms of an aromatic MOM ether is
TES ethers 3a−h in excellent yields; substrate 1e, which has an electron-withdrawing nitro group that required a longer reaction time and heating, still afforded TES ether 3e in moderate yield (63%). To the best of our knowledge, such a direct conversion of MOM ethers to TES ethers has not been reported so far. This interesting difference in reactivity between aromatic and aliphatic MOM ethers was exploited by performing the reaction on substrate 4, which has both types of MOM groups (Table 4). The aromatic MOM ether was converted to the corresponding TES ether, and after the addition of H2O, the aliphatic MOM ether was deprotected via the salt intermediate to give hydroxyl TES ether 5a in 88% yield (entry 1). When benzyl alcohol was added in place of H2O, product 5b, which had benzyloxymethyl (BOM) and TES ethers in the same molecule was obtained in 81% yield (entry 2). Furthermore, the use of trimethylsilylethanol as ROH gave product 5c, which contains both trimethylsilylethoxymethyl (SEM) and TES ethers in 78% yield (entry 3). Because many multistep reactions utilize MOM ethers, we believe that this method will be useful and practical.
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CONCLUSIONS We found that aromatic MOM ethers have different reaction pathways than aliphatic MOM ethers under the conditions of 8467
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Table 4. Substrate with Aromatic and Aliphatic MOM Ethers
s), 3.48 (3H, s), 3.10 (2H, t, J = 6.3 Hz), 2.68 (2H, t, J = 7.7 Hz), 1.94−1.85 (2H, m); 13C NMR (75 MHz, CDCl3) δ 155.4, 144.5, 135.8, 129.5, 128.8, 127.9, 127.0, 116.3, 94.7, 86.5, 62.8, 56.1, 32.1, 31.8; HRMS (MALDI-TOF) m/z [M + Na]+ calcd for C30H30O3Na 461.2087, found 461.2085. General Procedure for Deprotection of MOM Ether (1a) in Combination with TMSOTf-2,2′-bipyridyl (Table 1). TMSOTf (0.18 mL, 1.0 mmol) was added dropwise to a solution of MOM ether 1a (0.5 mmol) and 2,2′-bipyridyl (234.3 mg, 1.5 mmol) in a solvent (5.0 mL) at 0 °C under N2 atmosphere. The solution was stirred for the time indicated in Table 1 at room temperature. H2O was added to the solution, and the resulting solution was stirred at room temperature until the low polar compound disappeared from the TLC plate. The organic compounds were extracted with AcOEt, and the combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel to give 2a. General Procedure for Deprotection of MOM Ether in Combination with TMSOTf-2,2′-bipyridyl (Table 2). TMSOTf (0.18 mL, 1.0 mmol) was added dropwise to a solution of MOM ether 1 (0.5 mmol) and 2,2′-bipyridyl (234.3 mg, 1.5 mmol) in CH3CN (5.0 mL) at 0 °C under N2 atmosphere. The solution was stirred at room temperature until the MOM ether disappeared from the TLC plate. H2O was added to the solution and the resulting solution was stirred at room temperature until the TMS ether disappeared from the TLC plate. The organic compounds were extracted with AcOEt, and the combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel to give a phenol 2. 2a, 2b, 2c, 2d, 2e, 2f, and 2h are commercially available. Phenol (2a). According to the general procedure, 1a (71.8 mg, 0.52 mmol) gave 2a (44.7 mg, 0.47 mmol, 91%). Colorless oil; 1H NMR (400 MHz, CDCl3) δ 7.28−7.23 (2H, m), 6.97− 6.96 (1H, m), 6.86−6.42 (2H, m); 13C NMR (100 MHz, CDCl3) δ 155.5, 129.8, 121.0, 115.4.
TMSOTf (or TESOTf) and 2,2′-bipyridyl. In other words, the aromatic MOM ether was deprotected via TMS ethers rather than via salt intermediates. This difference in reactivity also allowed us to develop an unprecedented conversion of an aromatic MOM ether directly to a TES ether. These are very mild conditions, so it can also retain the trityl ether, which is removed under normal acidic conditions. Additionally, we showed that the difference in reactivity could be exploited by performing a chemoselective reaction on a substrate containing both aliphatic and aromatic MOM ethers.
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EXPERIMENTAL SECTION General Procedure for the Preparation of MOM Ethers 1a−1f, 1h, and 4. Chloromethyl methyl ether was added to a solution of a phenol (6.0 mmol) and diisopropylethylamine (12.0 mmol) in dimethylformamide (12.0 mL) at 0 °C under N2 atmosphere, and the mixture was stirred overnight at room temperature. The resulting solution was quenched with H2O and extracted with a mixture of AcOEt/hexane = 1:4. The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on a silica gel to give a MOM ether 1. 1a,9 1b,10 1c,11 1d,12 1e,13 1f,14 1h,15 and 416 are known compounds. Preparation of MOM Ethers 1g. MOM ether 1g was prepared from 3-(4-(methoxymethoxy)phenyl)propan-1-ol.1a Trityl chloride (493.4 mg, 1.8 mmol) was added to a solution of 3-(4-(methoxymethoxy)phenyl)propan-1-ol (316.0 mg, 1.6 mmol), trietylamine (0.39 mL, 2.8 mmol), and 4-dimethylaminopyridine (7.9 mg, 0.06 mmol) at room temperature under N2 atmosphere. After stirring overnight at room temperature, the resulting solution was quenched with H2O and extracted with CH2Cl2. The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel to give 1g (644.7 mg, 1.5 mmol, 91%). Colorless oil; 1H NMR (300 MHz, CDCl3) δ 7.47−7.43 (6H, m), 7.33−7.20 (9H, m), 7.06−7.03 (2H, m), 6.93−6.89 (2H, m), 5.14 (2H, 8468
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1.00 (9H, t, J = 8.0 Hz), 0.74 (6H, q, J = 8.0 Hz); 13C NMR (125 MHz, CDCl3) δ 155.7, 129.5, 121.4, 120.1, 6.8, 5.1. Triethyl(o-tolyloxy)silane (3b). According to the general procedure, 1b (77.5 mg, 0.51 mmol) gave 3b (100.0 mg, 0.45 mmol, 88%). Colorless oil; 1H NMR (500 MHz, CDCl3) δ 7.12 (1H, d, J = 7.3 Hz), 7.07−7.03 (1H, m), 6.85 (1H, t, J = 7.3 Hz), 6.77 (1H, d, J = 8.1 Hz), 2.21 (3H, s), 1.00 (9H, t, J = 8.0 Hz), 0.76 (q, J = 8.0 Hz, 6H); 13C NMR (125 MHz, CDCl3) δ 154.1, 131.0, 128.9, 126.7, 121.1, 118.5, 16.8, 6.8, 5.5. Triethyl(4-methoxyphenoxy)silane (3c). According to the general procedure, 1c (84.3 mg, 0.50 mmol) gave 3c (118.7 mg, 0.50 mmol, 99%). Colorless oil; 1H NMR (400 MHz, CDCl3) δ 7.02 (2H, d, J = 6.9 Hz), 6.96−6.92 (1H, m), 4.97 (2H, s), 3.62 (3H, s), 2.30 (6H, s); 13C NMR (75 MHz, CDCl3) δ 154.9, 131.2, 129.0, 124.3, 99.2, 57.5, 17.0. (2,6-Dimethylphenoxy)triethylsilane (3d). According to the general procedure, 1d (80.2 mg, 0.48 mmol) gave 3d (111.0 mg, 0.47 mmol, 97%). Colorless oil; 1H NMR (400 MHz, CDCl3) δ 6.96 (2H, d, J = 7.4 Hz), 6.78 (1H, t, J = 7.4 Hz), 2.22 (6H, s), 0.98 (9H, t, J = 8.0 Hz), 0.76 (6H, q, J = 8.0 Hz); 13C NMR (125 MHz, CDCl3) δ 153.0, 128.6, 128.5, 121.3, 17.7, 7.0, 5.9. Triethyl(4-nitrophenoxy)silane (3e). According to the general procedure (except the reaction temperature), 1e (90.4 mg, 0.49 mmol) gave 3e (79.1 mg, 0.31 mmol, 63%). Colorless oil; 1H NMR (400 MHz, CDCl3) δ 8.15 (2H, m), 6.90 (2H, m), 1.01 (9H, t, J = 7.9 Hz), 0.79 (6H, q, J = 7.9 Hz); 13C NMR (125 MHz, CDCl3) δ 161.8, 142.0, 126.0, 120.0, 6.6, 5.1. Methyl 2-(4-((Triethylsilyl)oxy)phenyl)acetate (3f). According to the general procedure (except the reaction temperature), 1f (104.6 mg, 0.50 mmol) gave 3f (131.9 mg, 0.47 mmol, 94%). Colorless oil; 1H NMR (400 MHz, CDCl3) δ 7.14−7.11 (2H, m), 6.81−6.78 (2H, m), 3.69 (3H, s), 3.55 (2H, s), 0.99 (9H, t, J = 7.9 Hz), 0.73 (6H, q, J = 7.9 Hz); 13C NMR (100 MHz, CDCl3) δ 172.5, 154.8, 130.4, 126.7, 120.1, 52.1, 40.5, 6.8, 5.1; HRMS (MALDI-TOF) m/z [M + Na]+ calcd for C15H24O3NaSi 303.1387, found 303.1380. Triethyl(4-(3-trityloxy)phenoxy)silane (3g). According to the general procedure, 1g (219.4 mg, 0.50 mmol) gave 3g (247.5 mg, 0.49 mmol, 97%). Colorless oil; 1H NMR (500 MHz, CDCl3) δ 7.46−7.44 (6H, m), 7.31−7.28 (6H, m), 7.25−7.21 (3H, m), 6.98−6.96 (2H, m), 6.72−6.70 (2H, m), 3.08 (2H, t, J = 6.3 Hz), 2.66 (2H, t, J = 7.8 Hz), 1.93−1.87 (2H, m), 0.99 (9H, t, J = 7.9 Hz), 0.72 (6H, q, J = 7.9 Hz); 13C NMR (125 MHz, CDCl3) δ 153.6, 144.6, 134.89, 129.4, 128.8, 127.8, 127.0, 119.7, 86.5, 62.9, 32.0, 31.8, 6.8, 5.1; HRMS (MALDI-TOF) m/z [M + Na]+ calcd for C34H40O2NaSi 531.2690, found 531.2692. Triethyl(naphthalen-1-yloxy)silane (3h). According to the general procedure, 1h (93.7 mg, 0.50 mmol) gave 3h (108.8 mg, 0.42 mmol, 85%). Colorless oil; 1H NMR (400 MHz, CDCl3) δ 8.21−8.19 (1H, m), 7.81−7.78 (1H, m), 7.49−7.44 (3H, m), 7.32 (1H, t, J = 7.8 Hz), 6.88−6.86 (1H, m), 1.04 (9H, t, J = 7.9 Hz), 0.86 (6H, q, J = 7.9 Hz); 13C NMR (100 MHz, CDCl3) δ 151.8, 135.1, 128.0, 127.7, 126.3, 126.1, 125.2, 122.7, 121.0, 112.5, 6.9, 5.4. Reaction of Substrate with Aromatic and Aliphatic MOM Ethers (Table 4). (Entry 1) TESOTf (0.45 mL, 2.0 mmol) was added dropwise to a solution of MOM ether 4 (119.8 mg, 0.50 mmol) and 2,2′-bipyridyl (390.5 mg, 2.5 mmol) in CH3CN (5.0 mL) at 0 °C under N2 atmosphere.
o-Cresol (2b). According to the general procedure, 1b (75.9 mg, 0.50 mmol) gave 2a (50.1 mg, 0.46 mmol, 93%). Colorless oil; 1H NMR (400 MHz, CDCl3) δ 7.14−7.07 (2H, m), 6.88− 6.84 (1H, m), 6.78 (1H, d, J = 8.2 Hz), 2.26 (3H, s); 13C NMR (100 MHz, CDCl3) δ 153.9, 131.1, 127.3, 123.8, 120.8, 115.0, 15.9. 4-Methoxyphenol (2c). According to the general procedure, 1c (88.4 mg, 0.53 mmol) gave 2c (quantitative). White crystal; 1 H NMR (400 MHz, CDCl3) δ 6.81−6.76 (4H, m), 3.77 (3H, s); 13C NMR (100 MHz, CDCl3) δ 153.8, 149.6, 116.2, 115.0, 55.9. 2,6-Dimethylphenol (2d). According to the general procedure, 1d (83.4 mg, 0.50 mmol) gave 2d (45.1 mg, 0.37 mmol, 74%). Pale yellow crystal; 1H NMR (400 MHz, CDCl3) δ 6.99 (2H, d, J = 7.3 Hz), 6.77 (1H, t, J = 7.3 Hz), 4.61 (1H, br d), 2.26 (6H, s); 13C NMR (100 MHz, CDCl3) δ 152.3, 128.7, 123.1, 120.3, 16.0. 4-Nitrophenol (2e). According to the general procedure (except the reaction temperature), 1e (91.4 mg, 0.50 mmol) gave 2e (58.3 mg, 0.42 mmol, 84%). Pale yellow solid; 1H NMR (300 MHz, CDCl3) δ 8.21−8.15 (2H, m), 6.95−6.90 (2H, m), 5.93 (1H, br d); 13C NMR (100 MHz, CDCl3) δ 161.6, 141.6, 126.5, 115.9. Methyl 2-(4-Hydroxyphenyl)acetate (2f). According to the general procedure, 1f (105.4 mg, 0.50 mmol) gave 2f (69.5 mg, 0.42 mmol, 83%). White solid; 1H NMR (300 MHz, CDCl3) δ 7.11 (2H, d, J = 8.3 Hz), 6.75 (2H, d, J = 8.3 Hz), 3.70 (3H, s), 3.56 (3H, s); 13C NMR (75 MHz, CDCl3) δ 173.1, 155.0, 130.6, 125.9, 115.7, 52.3, 40.4. 4-(3-(Trityloxy)propyl)phenol (2g). According to the general procedure, 1g (213.9 mg, 0.49 mmol) gave 2a (178.2 mg, 0.45 mmol, 93%). Colorless oil; 1H NMR (300 MHz, CDCl3) δ 7.41 (6H, d, J = 7.6 Hz), 7.28−7.17 (9H, m), 6.96 (2H, d, J = 8.3 Hz), 6.66 (2H, d, J = 8.3 Hz), 4.56 (1H, br d), 3.06 (2H, t, J = 6.2 Hz), 2.62 (2H, t, J = 7.7 Hz), 1.90−1.80 (2H, m); 13C NMR (75 MHz, CDCl3) δ 153.6, 144.5, 134.5, 129.6, 128.8, 127.9, 127.0, 115.2, 86.5, 62.8, 32.1, 31.8; HRMS (MALDI-TOF) m/z [M + Na]+ calcd for C28H26O2Na 417.1825, found 417.1823. 1-Naphthol (2h). According to the general procedure, 1h (95.0 mg, 0.50 mmol) gave 2a (quantitative). Pale brown solid; 1H NMR (300 MHz, CDCl3) δ 8.20−8.16 (1H, m), 7.85−7.80 (1H, m), 7.53−7.44 (3H, m), 7.32 (1H, t, J = 7.8 Hz), 6.82 (1H, d, J = 7.8 Hz), 5.28 (1H, br d); 13C NMR (100 MHz, CDCl3) δ 151.5, 134.9, 127.8, 126.6, 126.0, 125.4, 124.4, 121.7, 120.8, 108.7. General Procedure for Conversion of MOM Ether to TES Ether in Combination with TESOTf-2,2′-bipyridyl (Table 3). TESOTf (0.23 mL, 1.0 mmol) was added dropwise to a solution of MOM ether 1 (0.5 mmol) and 2,2′-bipyridyl (234.3 mg, 1.5 mmol) in CH3CN (5.0 mL) at 0 °C under N2 atmosphere. After stirring at room temperature until the MOM ether disappeared from the TLC plate, the solution was quenched with H2O, and extracted with AcOEt. The combined organic layers were dried over Na 2SO4 , filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel to give TES ether 3. 3a,17 3b,17 3c,17 3d,18 3e,17 and 3h19 are known compounds. Triethyl(phenoxy)silane (3a). According to the general procedure, 1a (68.7 mg, 0.50 mmol) gave 3a (93.4 mg, 0.45 mmol, 90%). Colorless oil; 1H NMR (500 MHz, CDCl3) δ 7.24−7.20 (2H, m), 6.96−6.93 (1H, m), 6.86−6.84 (2H, m), 8469
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The solution was stirred for 1.5 h at room temperature. Saturated NaHCO3 aq (4.0 mL) was added to the reaction mixture and the resulting solution was stirred for 4 h at 50 °C. The organic compounds were then extracted with AcOEt, and the combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel to give 5a (117.3 mg, 0.44 mmol, 88%). 5a20 is a known compound. 3-(4-((Triethylsilyl)oxy)phenyl)propan-1-ol (5a). Colorless oil; 1H NMR (400 MHz, CDCl3) δ 7.06−7.02 (2H, m), 6.79− 6.75 (2H, m), 3.66 (2H, t, J = 6.4 Hz), 2.64 (2H, t, J = 7.6 Hz), 1.89−1.82 (2H, m), 0.99 (9H, t, J = 8.0 Hz), 0.73 (6H, q, J = 8.0 Hz); 13C NMR (100 MHz, CDCl3) δ 153.8, 134.5, 129.4, 119.9, 62.5, 34.5, 31.4, 6.8, 5.1. (Entries 2 and 3) TESOTf (0.45 mL, 2.0 mmol) was added dropwise to a solution of MOM ether 4 (0.5 mmol) and 2,2′bipyridyl (390.5 mg, 2.5 mmol) in CH3CN (5.0 mL) at 0 °C under N2 atmosphere. The solution was stirred for 1.5 h at room temperature. The alcohol (5.0 mmol) was added to the solution and the resulting solution was stirred at 50 °C until the salt intermediate disappeared from the TLC plate. The organic compounds were then extracted with AcOEt, and the combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel to give TES ether 5. (4-(3-((Benzyloxy)methoxy)propyl)phenoxy)triethylsilane (5b). According to the above procedure, 4 (121.5 mg, 0.51 mmol), benzyl alcohol (0.52 mL, 5.0 mmol) gave 5b (159.3 mg, 0.41 mmol, 81%). Colorless oil; 1H NMR (400 MHz, CDCl3) δ 7.35−7.27 (6H, m), 7.05−7.02 (2H, m), 6.78−6.74 (2H, m), 4.77 (2H, s), 4.61 (2H, s), 3.59 (2H, t, J = 6.4 Hz), 2.64 (2H, t, J = 7.6 Hz), 1.93−1.86 (2H, m), 0.99 (9H, t, J = 7.8 Hz), 0.73 (6H, q, J = 7.8 Hz); 13C NMR (100 MHz, CDCl3) δ 153.7, 138.1, 134.6, 129.4, 128.6, 128.0, 127.8, 119.9, 94.8, 69.5, 67.4, 13.7, 31.6, 6.8, 5.1; HRMS (MALDITOF) m/z [M + Na]+ calcd for C23H34O3NaSi 409.2169, found 409.2170. Triethyl(4-(3-(((trimethylsilyl)methoxy)methoxy)propyl)phenoxy)silane (5c). According to the above procedure, 4 (122.4 mg, 0.51 mmol), 2-(trimethylsilyl)ethan-1-ol (0.63 mL, 5.0 mmol) gave 5c (157.4 mg, 0.40 mmol, 78%). Colorless oil; 1 H NMR (300 MHz, CDCl3) δ 7.03 (2H, d, J = 8.7 Hz), 6.76 (2H, d, J = 8.7 Hz), 4.67 (2H, s), 3.62 (2H, m), 3.54 (2H, t, J = 6.4 Hz), 2.63 (2H, t, J = 7.8 Hz), 1.92−1.83 (2H, m), 0.99 (9H, t, J = 7.9 Hz), 0.73 (6H, q, J = 7.9 Hz), 0.02 (9H, s); 13C NMR (101 MHz, CDCl3) δ 153.7, 134.6, 129.4, 119.9, 95.0, 67.2, 65.1, 31.7, 31.7, 18.3, 6.8, 5.1, −1.3; HRMS (MALDITOF) m/z [M + Na]+ calcd for C21H40O3NaSi2 419.2408, found 419.2408.
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AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. ORCID
Reiya Ohta: 0000-0003-4932-9440 Kenichi Murai: 0000-0002-1689-6492 Mitsuhiro Arisawa: 0000-0002-7937-670X Hiromichi Fujioka: 0000-0002-9970-4248 Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS This work was financially supported by Grant-in-Aid for Scientific Research (C) (18K065760) from JSPS and Platform for Drug Discovery, Informatics, and Structural Life Science from MEXT. We thank Ramon Francisco Bernardino Avena for calibration of this manuscript.
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REFERENCES
(1) (a) Schelhaas, M.; Waldmann, H. Protecting Group Strategies in Organic Synthesis. Angew. Chem., Int. Ed. 1996, 35, 2056−2083. (b) Wuts, P. G. M. Green’s Protective Groups in Organic Synthesis, 5th ed.; John Wiley & Sons: Hoboken, New Jersey, 2014. (2) (a) Fujioka, H.; Kubo, O.; Senami, K.; Minamitsuji, Y.; Maegawa, T. Remarkable Effect of 2,2′-Bipyridyl: Mild and Highly Chemoselective Deprotection of Methoxymethyl (MOM) Ethers in Combination with TMSOTf (TESOTf)−2,2’-Bipyridyl. Chem. Commun. 2009, 4429−4431. (b) Fujioka, H.; Minamitsuji, Y.; Kubo, O.; Senami, K.; Maegawa, T. The Reaction of Acetal-type Protective Groups for Hydroxy Group in Combination with TMSOTf and 2,2′-Bipyridyl; Mild and Chemoselective Deprotection and Direct Conversion to Other Protective Groups. Tetrahedron 2011, 67, 2949−2960. (c) Maegawa, T.; Koutani, Y.; Senami, K.; Yahata, K.; Fujioka, H. Selective Deprotection of Methylene Acetal and MOM ether in the presence of Ketal-type Protective Groups: Remarkable Effect of TBSOTf. Heterocycles 2012, 86, 455−467. (d) Minamitsuji, Y.; Kawaguchi, A.; Kubo, O.; Ueyama, Y.; Maegawa, T.; Fujioka, H. A Mild and Versatile Method for the Synthesis of Alkyl Ethers from MOM Ethers and Application to the Preparation of Sterically Crowded Ethers. Adv. Synth. Catal. 2012, 354, 1861−1866. (3) See Supporting Information; 1H NMR of TMS ether of phenol was based on this paper: Rajagopal, G.; Lee, H.; Kim, S. S. Nafion SAC-13: Heterogeneous and Reusable Catalyst for the Activation of HMDS for Efficient and Selective O-Silylation Reactions under Solvent-Free Condition. Tetrahedron 2009, 65, 4735−4741. (4) Arshadi, M.; Johnels, D.; Edlund, U.; Ottosson, C. H.; Cremer, D. Solvated Silylium Cations: Structure Determination by Nmr Spectroscopy and the Nmr/Ab Initio/Iglo Method. J. Am. Chem. Soc. 1996, 118, 5120−5131. (5) See Supporting Information. (6) TMSOTf in the presence of base must in situ form TMSOTf/ base complex. See: Ohta, R.; Matsumoto, N.; Ueyama, Y.; Kuboki, Y.; Aoyama, H.; Murai, K.; Arisawa, M.; Maegawa, T.; Fujioka, H. Highly Discriminative and Chemoselective Transformations of Acetals with the Combination of Trialkylsilyl Triflate/2,4,6-Collidine. J. Org. Chem. 2018, 83, 6432−6443. (7) The reaction mechanism, concerted manner or stepwise one, for the formation of salt intermediate C is not clear. But for the assistance of understanding the salt formation C the oxonium ion B was depicted here. (8) Luo, Y. R. Comprehensive Handbook of Chemical Bond Energies; CRC Press: Boca Raton, FL, 2007. (9) Vo, C. V. T.; Mitchell, T. A.; Bode, J. W. Expanded Substrate Scope and Improved Reactivity of Ether-Forming Cross-Coupling Reactions of Organotrifluoroborates and Acetals. J. Am. Chem. Soc. 2011, 133, 14082−14089.
ASSOCIATED CONTENT
S Supporting Information *
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsomega.9b00643. 1
H and 13C NMR spectra of newly synthesized substrates and compounds, 1H NMR spectrum of the reaction mixture in Figure 1b, and 1H and 13C NMR spectra of the mixture of TMSOTf and 2,2′-bipyridyl in CD3CN, THF-d8, and CD2Cl2 compared with that of 2,2′-bipyridyl only (PDF) 8470
DOI: 10.1021/acsomega.9b00643 ACS Omega 2019, 4, 8465−8471
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(10) Dal Molin, M.; Gasparini, G.; Scrimin, P.; Rastrelli, F.; Prins, L. J. 13C-Isotope Labelling for the Facilitated NMR Analysis of a Complex Dynamic Chemical System. Chem. Commun. 2011, 47, 12476−12478. (11) Bouzbouz, S.; Goujon, J. Y.; Deplanne, J.; Kirschleger, B. Enantioselective Synthesis of Cordiachromene. Eur. J. Org. Chem. 2000, 3223−3228. (12) Kaufman, T. S.; Sindelar, R. D.; Jürgens, A. R. 13C NMR chemical shifts of the carbon atoms of the methoxymethyl group of diortho-substituted aromatic methoxymethyl ethers. Magn. Reson. Chem. 1989, 27, 1178−1181. (13) Peng, T.; Wong, N. K.; Chen, X.; Chan, Y. K.; Ho, D. H. H.; Sun, Z.; Hu, J. J.; Shen, J.; El-Nezami, H.; Yang, D. Molecular Imaging of Peroxynitrite with HKGreen-4 in Live Cells and Tissues. J. Am. Chem. Soc. 2014, 136, 11728−11734. (14) Büttner, A.; Cottin, T.; Xu, J.; Tzagkaroulaki, L.; Giannis, A. Serotonin Derivatives as a New Class of Non-ATP-Competitive Receptor Tyrosine Kinase Inhibitors. Bioorg. Med. Chem. 2010, 18, 3387−3402. (15) Ogata, T.; Yoshida, T.; Shimizu, M.; Tanaka, M.; Fukuhara, C.; Ishii, J.; Nishiuchi, A.; Inamoto, K.; Kimachi, T. Unusual, Chemoselective Etherification of 2-Hydroxy-1,4-Naphthoquinone Derivatives Utilizing Alkoxymethyl Chlorides: Scope, Mechanism and Application to the Synthesis of Biologically Active Natural Product (±)-Lantalucratin C. Tetrahedron 2016, 72, 1423−1432. (16) Agharahimi, M. R.; Lebel, N. A. Synthesis of (-)-Monoterpenylmagnolol and Magnolol. J. Org. Chem. 1995, 60, 1856−1863. (17) Delucia, N. A.; Das, N.; Vannucci, A. K. Mild Synthesis of Silyl Ethers: Via Potassium Carbonate Catalyzed Reactions between Alcohols and Hydrosilanes. Org. Biomol. Chem. 2018, 16, 3415−3418. (18) Gevorgyan, V.; Rubin, M.; Benson, S.; Liu, J. X.; Yamamoto, Y. A Novel B(C6F5)3-Catalyzed Reduction of Alcohols and Cleavage of Aryl and Alkyl Ethers with Hydrosilanes. J. Org. Chem. 2000, 65, 6179−6186. (19) Yoshii, E.; Takeda, K. Triethylsilylation of hydroxyl groups with a ketene triethylsilyl acetal. 2-Methyl-1-triethylsilyloxy-1-methoxypropene. Chem. Pharm. Bull. 1983, 31, 4586−4588. (20) Dakhili, S. Y. T.; Caslin, S. A.; Faponle, A. S.; Quayle, P.; de Visser, S. P.; Wong, L. S. Recombinant Silicateins as Model Biocatalysts in Organosiloxane Chemistry. Proc. Natl. Acad. Sci. U.S.A. 2017, 114, E5285−E5291.
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