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A new arylation of silyl enol ethers by quinone monoacetal substitution
Tetrahedron Letters 56 (2015) 3046–3051
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A new arylation of silyl enol ethers by quinone monoacetal substitution Toshifumi Dohi, Tohru Kamitanaka, Hitoho Takamuro, Yusuke Mishima, Naohiko Washimi, Yasuyuki Kita ⇑ College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577, Japan
a r t i c l e
i n f o
Article history: Received 9 October 2014 Revised 14 November 2014 Accepted 17 November 2014 Available online 24 November 2014 Dedicated to the memory of Professor Harry H. Wasserman
a b s t r a c t Quinone monoacetals (QMAs) were found to be convenient substrates for a unique arylation reaction of enol silyl ethers. This arylation process of QMAs typically proceeds through the acetal activation of the QMAs by a hydrogen-bond donor solvent, such as a fluoroalcohol, for the initiating step. The silyl transfer from silyl enol ethers to the carbonyl oxygen of the QMAs appears to be involved in the C–C coupling step, followed by QMA aromatization. By this method, valuable a-aryl carbonyl compounds containing o-phenol moieties can be obtained directly under mild conditions without lactone formation. Ó 2014 Elsevier Ltd. All rights reserved.
Keywords: Arylation Silyl enol ether Quinone monoacetal Substitution a-Aryl carbonyl compound
Ketene acetal derivatives such as silyl enol ethers1a–c and alkoxy vinyl esters1d,e belong to the family of O-functionalized enols of esters. Upon nucleophilic attack on the silyl or acyl group, they easily revert to the stable original ester. By taking advantage of this powerful driving force and the attractiveness of having only the ester as a coproduct, these ketene acetal derivatives have been used since the 1970s as efficient and clean silyl and acyl group transfer agents in organic synthesis, as first reported by our research group.2–8 Indeed, more than 40 years ago our research group first pioneered the silyl transfer chemistry for the direct and efficient silylations of alcohols, carboxylic acids, mercaptans, and amides under very mild conditions by utilizing O-silylated ketene acetals.3,4 These silyl group transfer processes were further applied to carbon–carbon bond-forming reactions, that is, 1,4addition to a,b-unsaturated ketones,5 1,2-additions to aldehydes,6 and 1,3-additions to nitrones,7 all of which involved activation of the enolate through the transfer of the silyl group to the nucleophilic oxygen of the coupling partner. These addition reactions proceed even without the presence of an external activator or catalyst (Scheme 1). Thanks to advances in the synthetic routes to alkoxy vinyl esters,9 these compounds have become more
⇑ Corresponding author. Tel./fax: +81 (77)5615829. E-mail address: [email protected] (Y. Kita). http://dx.doi.org/10.1016/j.tetlet.2014.11.085 0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.
R1 XH (X = heteroatom)
R1 X[Si] O[Si]
O R2 CHR3 O R
4
R
O[Si]
R'
OMe
R7 + ON R
R
R
CO2Me R'
O[Si]
[Si] = TMS, TBS H silyl ketene acetals
5
R2 R3HC
R4 R R7
N
CO2 Me R' O[Si]
6 5
R
R6
R
CO2Me R'
Scheme 1. Ketene silyl acetals as versatile silyl transfer agent in organic transformations. (TMS = trimethylsilyl, TBS = tert-butyldimethylsilyl).
readily available. Similarly, we have also reported the acyl group transfer ability of alkoxy vinyl esters in the 1980s and applied this process to organic syntheses.8 As a continuation of our research, we became interested in the possibility of new carbon–carbon forming reactions of these ketene silyl acetals and silyl enol ethers and the synthetic applications of this chemistry. We focused our efforts on a new a-arylating
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aryl equivalent
Table 1 Screening of the conditions for arylation using QMA 1a
O
TMSO
O R MeO
OTMS
+
OMe
QMA (electrophile)
TMSO
CO2Me
MeO OMe 1a
OTMS OMe 2a
HFIP solvent conditions
CO2Me 3aa
OMe
R OMe and other silyl enol ether (nucleophile)
catalyst-free arylation OMe α-aryl carbonyl compound
Scheme 2. A new a-arylation strategy by quinone monoacetal (QMA) substitution utilizing silyl enol ethers.
method of carbonyl compounds under mild and metal catalyst-free conditions, following our recent studies of the substitution chemistry of quinone monoacetals (QMAs).10 These quinone derivatives have been found to react as powerful and regiospecific electrophiles, their reaction being followed by rapid rearomatization.11,12 Accordingly, we now report the first results of an extended study of a new coupling reaction of silyl enol ether nucleophiles with QMAs, facilitated by a strong hydrogen-bond donor solvent, that is, a fluoroalcohol, under mild conditions (Scheme 2).13 Since the discovery of the Mukaiyama-aldol reaction, the use of silyl enol ethers has greatly expanded beyond the scope of the aldol reaction to form new complex products.14 As part of these efforts, the a-arylation of carbonyl compounds utilizing silyl enol ethers has emerged as a powerful synthetic process.15 Since a-aryl carbonyl motifs are present in a large number of nature-made molecules and fine chemicals, introducing aryl moieties to keto compounds, or rather to a form of the corresponding metal enolates, has been intensively studied. In particular, the transition metal-catalyzed coupling strategies employing aryl halides and related electrophiles were the focus of much attention during the early stages of research in this area.16 New synthetic developments for this reaction have involved the uses of silyl enol ethers as convenient equivalents of these basic enolates, because of their characteristics as stable, neutral, and regiocontrolling nucleophiles.17 These silyl nucleophiles have been found to be effective in several metal catalyst-free approaches for providing a-arylated carbonyl compounds,18 though the methods were limited only to specific types of aryl substrates, that is, activated aryl electrophiles, such as diaryl iodonium salts, arylbismuth agents,19 among others.20,21 We recently developed conditions for the substitution reactions of QMAs promoted by Brønsted acids in a specific solvent, hexafluoroisopropanol (HFIP), for the coupling reactions with aromatic and alkene nucleophiles.11,12 QMAs are readily available, mono-protected quinone derivatives, which have recently attracted interest due to their broad utility in selective organic transformations, effectively acting as desymmetrized quinones.10 Hence, we started our QMA arylation study of silyl enol ethers in order to establish a new arylation process for the production of a-arylated carbonyl compounds under metal catalyst-free conditions by examining our reported reaction conditions, that is, the use of perfluorinated benzoic acids in HFIP (Table 1).22 As expected, the coupling of the representative QMA 1a with ketene silyl acetal 2a proceeded smoothly under our standard conditions in the fluoroalcohol solvent in the presence of a catalytic amount of phthalic acids (5 mol %),12c producing the a-aryl ester 3aa,23 accompanied by silylation of the phenol group, in 72% yield (entry 1). Interestingly, the corresponding lactone was prevented by the O-silylation of the phenol. This coupling rapidly proceeded at room
Entrya
Acid (equiv)
Time (h)
Yieldb of 3aa (%)
1 2 3 4 5 6c 7d 8e
Perfluoroterephthalic acid (0.05) Perfluoroterephthalic acid (0.5) Pentafluorobenzoic acid (1) Acetic acid (1) None None None None
1.5 1.5 3 3 24 24 24 24
72 Complex 45 81 91 95 89 43
a The reactions were examined using QMA 1a (1 equiv) and silyl enol ether 2a (2 equiv) in a mixture of hexafluoroisopropanol (10 mL relative to 1 mmol of QMA 1a) and dichloromethane (1 mL relative to 1 mmol of QMA 1a) at 0 °C unless otherwise noted. b Isolated yield based on QMA 1a used. c HFIP/DCM = 5.5 mL/5.5 mL. d HFIP/DCM = 1 mL/10 mL. e Dichloromethane (1a: 0.10 M) was used as solvent together with 2 equiv of HFIP.
temperature, and the reaction went to completion in 1.5 h. Consistent with our previous observations,11,12 the nucleophile 2a attacked the QMA 1a selectively at the a-position of the carbonyl group and did not touch the other electrophilic ring carbons of QMA 1a.24 To further improve the yield, we then examined the stoichiometric use of acid activators. However, this attempt to use perfluorinated terephthalic and benzoic acids12a,b failed, resulting in drastic decreases in product yields, despite the complete consumption of both reaction substrates 1a and 2a (entries 2 and 3). Based on these experiments, we concluded that the low yields were probably caused by the degradation of the acid-labile ketene silyl acetal 2a by the action of the acids, thereby preventing the desired coupling reaction of QMA 1a and silyl nucleophile 2a. This situation prompted us to study a milder reaction system with a weaker Brønsted acid. Hence, acetic acid was used as the activator instead of the above-mentioned stronger acids, and to our delight, we observed complete consumption of QMA 2a after stirring in HFIP for 3 hours and the product was obtained in good yield (entry 4). At that time, we were also aware of the formation of some product 3aa in the absence of catalyst, presumably promoted by the hydrogen-bond donating fluoroalcohol medium, HFIP. The reaction progress in the absence of the acid additives was thus monitored by TLC. We reasoned that the fluoroalcohol as a solvent or possibly even as an additive could act as a promoter for the coupling of the silyl enol ether 2a with QMA 1a. In the event, using HFIP either as a solvent or additive, with QMA 1a concentrations ranging from 0.10 to 0.01 M, provided the product 3aa in good yields (entries 5 and 6), however decreasing the proportion of HFIP with respect to the dichloromethane solvent caused the yield to significantly drop (entry 7). Needless to say, no reaction was observed in the absence of HFIP. Other reaction factors, such as concentration (doubling and halving the amount of the solvents) and temperature (0 °C), had little influence on product formation and yield. However, as in the reported metal-catalyzed reactions,17 this metal catalyst-free method was similarly sensitive to the stoichiometry of the silyl enol ether 2a, and the product 3aa was obtained in very low yield when employing an equimolar amount of the ketene silyl acetal 2a with QMA 1a. According to our careful examinations, the use of other activators (Et2AlCl, SnCl4, PtBr4, BF3Et2O, TMS-triflate)
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Table 2 A series of QMAs 1 for arylation of silyl enol ether 2aa Entry
QMA
Yieldb (%)
Arylation product
O
TMSO
C O2 Me 87
1
MeO
OMe
3ba
1b OMe TMSO
O 2
CO 2 Me 81
t Bu
1c
MeO
t
3ca
Bu
OMe
OMe TMSO
O
CO 2 Me 66
3
Br MeO
1d OMe
3da
Br OMe TMSO
O
CO 2 Me 34 68c
4
MeO MeO
1e
3ea
MeO
OMe
OMe
TMSO
O
CO 2 Me
5
Trace
1f MeO
OMe
3fa OMe TMSO
O
C O2 M e 54
6
1g MeO
OMe
3ga OMe OH
O
C O2 Me 77d,e
7
1h MeO a b c d e
OMe
3ha OMe
The reactions were examined under the optimized conditions of Table 1, entry 6. Isolated yield based on QMAs 1b–h used after reaction for 24 h. 5 equiv of silyl enol ether 2a was used. 3 equiv of silyl enol ether 2a. Including very small amount of the corresponding lactone form.
positions of the substituents determined the regioselectivity of the products 3ba–ea, the a-arylation proceeding cleanly to the less crowded a-position to the carbonyl group of QMAs 1b–e. Consistent with this strong steric regiocontrol by the substituent, dimethyl QMA 1f did not react at all with the ketene silyl acetal 1a (entry 5). Overall, the reaction behaviors of these QMAs 1b–f in the present system generally followed the known reactivity profiles of the QMAs toward other p-nucleophiles under the acidic conditions previously reported by us.11,12 Meanwhile, a clear difference was found for the reactivity of QMA 1g having a ring substituent at the a-position of the carbonyl group: at this position, even the small methyl group created steric interaction severe enough to strongly hinder the coupling reaction with the ketene silyl acetal 2a (entry 6).28 This drop in the reactivity of QMAs 1g is quite unique and was only observed in the present case of the nucleophile 2a. On the other hand, a smooth arylation occurred with the reactive naphthalene-based QMA 1h, and the coupling product 3ha was produced in good yield in the free phenol form (entry 7).29 Turning to the coupling partners for the QMAs, several silyl nucleophiles were tested. Ketene silyl acetals 2b–e were used for the reactions, although the relative instability of these silyl compounds toward acids forced the use of an excess of the nucleophile (2 equiv).30 As shown in Scheme 3, the ketene silyl acetals 2b–e derived from propionate (2b), a-aryl acetate (2c), cyclic ester (2d), and phenyl ester (2e), reacted with QMA 1a to afford the aarylated esters 3ab–ae in moderate yields, respectively (Eqs. 1–4). For the coupling of the QMAs 1 with silyl nucelophiles 2, a typical experimental procedure for the reaction listed in Table 1, entry 6 is as follows: to a stirred solution of the QMA 1a (77.1 mg, 0.50 mmol) in dichloromethane (2.5 mL) and 1,1,1,3,3,3-hexafluoro-2-propanol, HFIP (2.5 mL, dehydrated), was added the ketene silyl acetal 2a (174 mg, 1.0 mmol) at 0 °C. After completion of the reaction, as checked by TLC, the solvent was removed by rotary evaporator. The resulting crude residue containing the arylation product 3aa was subjected to column chromatography on silica-gel (hexanes/ethyl acetate = 15/1). By this simple operation, the a-arylated ester 3aa (136 mg, 92%) was obtained as a pure colorless oil. The product was obtained as the TMS-protected form
OTMS OMe
2b
TMSO CO2Me OMe
resulted in low yields of the product 3aa (0–37%) under the reported conditions. These activators, which have been useful in other types of substitutions of QMAs,25,26 do not appear to be useful for this arylation process. In order to extend our arylation method to additional QMAs, a brief survey was conducted with several QMAs 127 under the optimized reaction conditions (Table 2). Both QMAs 1b and 1c having a methyl and bulky tert-butyl group near the acetal sites of the QMA rings reacted with the ketene silyl acetal 2a without any problem, producing the expected a-aryl esters, 3ba and 3ca, in good yields (entries 1 and 2), respectively. Thus, the QMA activation and the silyl transfer to the phenol oxygen of the product were not affected by the presence of the bulky substituent. QMA 1d, containing a bromo group at the same position, led to the product 3da, albeit in somewhat lower yield (entry 3). Furthermore, the reaction of the less reactive QMA 1e having a methoxy group resulted in the partial formation of a-arylated product 3ea with low product conversion and a large amount of recovered starting QMA 1e. Fortunately, this product yield can be increased by using a larger amount of the silyl nucleophile 2a (entry 4). In these cases, the
Ph
OTMS OMe
QMA 1a
TMSO
Ph
2c CO2Me OMe
optimized conditions
(1)
3ab (57%)
(2)
3ac (40%)
OTMS OMe
2d
TMSO CO2Me OMe
OTMS OPh
(3)
3ad (31%)
TMSO 2e CO2Ph OMe
3ae (47%)
Scheme 3. Other silyl enol ethers (2 equiv of 2b–e relative to QMA 1a).
(4)
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OTMS O
O
OMe 2a
δ+
R (CF3)2CHOH (HFIP) OMe
MeO
R
δ+
MeO
1
intra- or intermolecular silyl transfer
TMSO
CO2Me
R
- H+
a
OMe
CF3
OMe
R
- MeOH
O HO Me F3C
QMAs
TMS O O H
3 OMe
- H+ TMSO OMe O
cyclization
intra- or intermolecular silyl transfer
R 3' OMe Scheme 4. Proposed roles of fluoroalcohol and silyl enol ether 2.
3aa, while the apparent formation of the corresponding O-free phenol during this reaction was not detected. In this unique arylation reaction of silyl enol ethers 2, we have shown that QMAs 1 selectively add to the a-position of the carbonyl group, that is, the allylic position of the allyl acetal moiety of the QMAs 1. Thus, the reaction produces a-aryl carbonyl compounds having an o-phenol or naphthol moiety as the coupling product. The mechanistic outline of this QMA arylation of silyl enol ethers is proposed in Scheme 4 for a representative case. It is assumed that the hydrogen-bond donor fluoroalcohol, HFIP,31 increases the partial positive charge of the QMAs 1 at the ring carbons a to the carbonyl group, and the activation for the allyl acetal functionalities helps the attack of the silyl enol ether 2a to the less crowded position of the electrophilic rings. This step seems to smoothly proceed even in the absence of external catalysts11,12 presumably because of the high nucleophilicity of the silyl enol ether 2a and other p-nucleophiles.32 The resulting putative intermediate a would be directly aromatized into the a-arylated carbonyl products 3, the intramolecular silyl transfer to the phenolic oxygen or some other intermolecular silylium shuttle step serving as the driving force.2–7 The unique effects of substituents displayed in Table 1 on the selectivity of the reaction with respect to the aposition to the carbonyl group, as shown for QMA having a tertbutyl group,28 seem to argue for the importance of the silyl transfer toward the carbonyl oxygens during the coupling reaction. An alternative pathway is the transient cyclization of intermediate a into dihydrobenzofuran 30 , which subsequently collapses to the a-aryl product 3 by silyl group transfer. The intermediacy of the cyclic intermediate 30 is suggested by the detection of this type of cyclic coproduct 30 af in the specific case of silyl enol ether 2f33 (Scheme 5) as well as previous observations in the couplings of QMAs 1 with alkenes.12 Thus, when cyclic silyl enol 2f was treated with QMA 1a under the standard conditions, the production of the a-arylated cyclopentanone 3af was accompanied by the formation of a small amount of the [3+2] coupling product, dihydrobenzofuran 30 af, which was isolated from the reaction mixture.34 The in situ formed cyclized 30 af eventually degraded into the a-aryl
TMSO O
OTMS O
2f
TMSO O
optimized condition MeO OMe 1a
OMe 3af (50%)
TMS O
O
δ+
R
pseudo-intramolecular silyl transfer
OMe
δ+
MeO
Scheme 6. Possible transition state for concerted silyl transfer and coupling.
carbonyl product 3af during the workup, which implies the possible intermediacy of the dihydrobenzofuran 30 af in the arylation processes. In our previous studies, the silyl group transfer from the ketene silyl acetals such as 2a, toward the carbonyl or nitrone oxygen during the silyl enol formations and addition reaction was assumed to take place via a six- or eight-membered cyclic bimolecular transition state.2–6 Based on this insight, a concerted mechanism for the formation of products 3 is proposed that proceeds via the transition state TS-a (Scheme 6). Obviously, the high affinity of the silicon atom toward oxygen is a key component. Indeed, this arylation using silyl nucleophiles 2 did not work with the related iminoquinone acetals,35 in stark contrast to the reactions between QMAs and silyl enol ethers 2 or other p-nucleophiles,11,12 a result which is consistent with the weaker bond energy between the silicon and nitrogen atoms. However, it is still difficult to make a unified conclusion for the reaction mechanism, as 2-[(trimethylsilyl)oxy]furan 2g was found to react with QMA 1a without the transfer of the silyl group, and the product 3ag not having the TMS moiety was obtained in good yield by the reaction of the nucleophile 2g at the remote conjugated carbon of the silyl enol ether function (Scheme 7). Consequently, one can assume that the silyl transfer and concerted transition state are not the essential events for the carbon–carbon bond-forming step during the arylation processes in some cases of the reactive nucleophiles.
OTMS O
O
2g
OH
(3 equiv.)
3'af
Scheme 5. Isolation of dihydrobenzofuran-type product 30 af.
3 OMe
CF3
TS-a
+
OMe
CO2Me
R
- H+
O HO Me F3C
TMSO
MeO OMe 1a
optimized condition
O OMe 3ag
O
O workup
column chromatography
Scheme 7. Alernative c-reactive silyl enol ether 2g.
O O
OMe 3'ag (85%)
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In summary, we have developed a new coupling reaction between QMAs 1 and silyl enol ethers 2, effectively promoted by the hydrogen-bond donor fluoroalcohol, HFIP, under mild conditions. This activation strategy allows QMAs 1 to selectively react with the nucleophiles in a regioselective, sterically controlled manner at the a-position of the carbonyl group as the only reacting center among the six electrophilic ring carbons, thereby providing via rearomatization a series of a-arylated o-phenol compounds that are difficult to obtain by other metal-free coupling methods without lactone formation. Along with the development of this unique substitution chemistry, this work demonstrates the use of QMAs 1 as a new entry to the arylation platform for the metal catalyst-free method for obtaining valuable a-arylated carbonyl products. We expect these substrates to be useful for the preparation of other compounds, as will be demonstrated in future studies.
10.
11.
12.
13.
Acknowledgments 14.
We acknowledge financial support from a Grant-in-Aid for Scientific Research (A) and Encouragement of Young Scientists (A) from JSPS, a Grant-in-Aid for Scientific Research on Innovative Areas ‘Advanced Molecular Transformations by Organocatalysts’ from MEXT. T.D. thanks Mitsubishi Gas Chemical Company research award from the Society of Synthetic Organic Chemistry, Japan, and research fund from the Asahi Glass Foundation and the Industrial Technology Research Grant Program from NEDO of Japan.
15.
16.
References and notes 17. 1. For early reports, see: (a) Petrov, A. D.; Sadykh-Zade, S. I.; Filatova, E. I. Zh. Obshch. Khim. 1959, 29, 2936; (b) Baukov, J. I.; Burlachenko, G. S.; Lutsenko, I. F. J. Organomet. Chem. 1965, 3, 478; (c) Lutsenko, I. F.; Baukor, Y. I.; Burlachenko, G. S.; Khasapor, B. N. J. Organomet. Chem. 1966, 5, 20; (d) Arth, G. E.; Poos, G. I.; Lukes, R. M.; Robinson, F. M.; Johns, W. F.; Feurer, M.; Sarett, L. H. J. Am. Chem. Soc. 1954, 76, 1715; (e) Arens, J. F. Recl. Trav. Chim. Pays-Bas 1955, 74, 769. 2. For background information about our chemistry on silyl and acyl transfer agents, see the following accounts and reviews: (a) Kita, Y. Yakugaku Zasshi 1986, 106, 269; (b) Kita, Y.; Tamura, O.; Tamura, Y. J. Synth. Org. Chem. Jpn. 1986, 44, 1118; (c) Tamura, Y.; Kita, Y. J. Synth. Org. Chem. Jpn. 1988, 46, 205; (d) Kita, Y.; Shibata, N. J. Synth. Org. Chem. Jpn. 1994, 52, 746; (e) Kita, Y.; Shibata, N. Synlett 1996, 289; (f) Kita, Y. Yakugaku Zasshi 1997, 117, 282; (g) Kita, Y.; Akai, S. Chem. Rec. 2004, 4, 363. 3. (a) Kita, Y.; Haruta, J.; Segawa, J.; Tamura, Y. Tetrahedron Lett. 1979, 20, 4311; (b) Kita, Y.; Haruta, J.; Fujii, T.; Segawa, J.; Tamura, Y. Synthesis 1981, 451; (c) Kita, Y.; Yasuda, H.; Sugiyama, Y.; Fukada, F.; Haruta, J.; Tamura, Y. Tetrahedron Lett. 1983, 24, 1273. 4. (a) Kita, Y.; Segawa, J.; Haruta, J.; Tamura, Y. Tetrahedron Lett. 1980, 21, 3779; (b) Kita, Y.; Segawa, J.; Haruta, J.; Yasuda, H.; Tamura, Y. J. Chem. Soc., Perkin Trans. 1 1982, 1099. 5. (a) Kita, Y.; Yasuda, H.; Haruta, J.; Segawa, J.; Tamura, Y. Synthesis 1982, 1089; (b) Kita, Y.; Yasuda, H.; Tamura, O.; Itoh, F.; Tamura, Y. Tetrahedron Lett. 1984, 25, 4681; (c) Kita, Y.; Tamura, O.; Yasuda, H.; Itoh, F.; Tamura, Y. Chem. Pharm. Bull. 1985, 33, 4235; (d) Kita, Y.; Tohma, H.; Inagaki, M.; Hatanaka, K.; Yakura, T. J. Am. Chem. Soc. 1992, 114, 2175; (e) Kita, Y.; Shibata, N.; Kawano, N.; Tohjo, T.; Fujimori, C.; Ohishi, H. J. Am. Chem. Soc. 1994, 116, 5116; For our recent report including the use of silyl transfer agent, see: (f) Dohi, T.; Uchiyama, T.; Yamashita, D.; Washimi, N.; Kita, Y. Tetrahedron Lett. 2011, 52, 2212. in the Special Issue published in honor of Professor Harry H. Wasserman on the occasion of his 90th birthday. 6. (a) Kita, Y.; Yasuda, H.; Tamura, O.; Itoh, F.; Ke, Y. Y.; Tamura, Y. Tetrahedron Lett. 1985, 26, 5777; (b) Kita, Y.; Tamura, O.; Itoh, F.; Yasuda, H.; Kishino, H.; Ke, Y. Y.; Tamura, Y. J. Org. Chem. 1988, 53, 554. 7. (a) Kita, Y.; Ito, F.; Tamura, O.; Ke, Y. Y.; Tamura, Y. Tetrahedron Lett. 1987, 28, 1431; (b) Kita, Y.; Tamura, O.; Itoh, F.; Kishino, H.; Miki, T.; Kohno, M.; Tamura, Y. J. Chem. Soc., Chem. Commun. 1988, 761; (c) Kita, Y.; Itoh, F.; Tamura, O.; Ke, Y. Y.; Miki, T.; Tamura, Y. Chem. Pharm. Bull. 1989, 37, 1446. 8. (a) Kita, Y.; Haruta, J.; Tagawa, H.; Tamura, Y. J. Org. Chem. 1980, 45, 4519; (b) Tamura, Y.; Inoue, M.; Wada, A.; Fujita, M.; Kita, Y. Chem. Pharm. Bull. 1981, 29, 3226; (c) Kita, Y.; Haruta, J.; Yasuda, H.; Fukunaga, K.; Shirouchi, Y.; Tamura, Y. J. Org. Chem. 1982, 47, 2697; (d) Kita, Y.; Akai, S.; Yoshigi, M.; Nakajima, Y.; Yasuda, H.; Tamura, Y. Tetrahedron Lett. 1984, 25, 6027; (e) Kita, Y.; Akai, S.; Ajimura, N.; Yoshigi, M.; Tsugoshi, T.; Yasuda, H.; Tamura, Y. J. Org. Chem. 1986, 51, 4150; (f) Kita, Y.; Akai, S.; Yamamoto, M.; Taniguchi, M.; Tamura, Y. Synthesis 1989, 334. for other applications, see accounts in Ref. 2. 9. For early preparations, see: (a) Broekema, R.; van der Werf, S.; Arens, J. F. Recl. Trav. Chim. Pays-Bas 1958, 77, 258; (b) Sheehan, J. C.; Hlavka, J. J. J. Org. Chem.
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27.
1958, 23, 635; Preparations by using mercury salts: (c) Wasserman, H. H.; Wharton, P. S. Tetrahedron 1958, 3, 321; (d) Wasserman, H. H.; Wharton, P. S. J. Am. Chem. Soc. 1960, 82, 661; (e) Tamura, Y.; Haruta, J.; Okuyama, S.; Kita, Y. Tetrahedron Lett. 1978, 19, 3737; Later, we have developed a practical and highyielding route to alkoxy vinyl esters avoiding the use of mercury salts: (f) Kita, Y.; Maeda, H.; Omori, K.; Okuno, T.; Tamura, Y. J. Chem. Soc., Perkin. Trans. 1 1993, 2999. For summarizations of preparations and utilities of QMAs, see: (a) Magdziak, D.; Meek, S. J.; Pettus, T. R. R. Chem. Rev. 2004, 104, 1383; (b) Dohi, T.; Kita, Y. In Quinones: Occurrence, Medicinal Uses and Physiological Importance; Price, E. R., Johnson, S. C., Eds.; NOVA Science Publisher: New York, 2013; pp 85–140. (a) Dohi, T.; Washimi, N.; Kamitanaka, T.; Fukushima, K.; Kita, Y. Angew. Chem., Int. Ed. 2011, 50, 6142; (b) Dohi, T.; Kamitanaka, T.; Watanabe, S.; Hu, Y.; Washimi, N.; Kita, Y. Chem. Eur. J. 2012, 18, 13614. (a) Dohi, T.; Hu, Y.; Kamitanaka, T.; Washimi, N.; Kita, Y. Org. Lett. 2011, 13, 4814; (b) Dohi, T.; Hu, Y.; Kamitanaka, T.; Kita, Y. Tetrahedron 2012, 68, 8424; (c) Hu, Y.; Kamitanaka, T.; Mishima, Y.; Dohi, T.; Kita, Y. J. Org. Chem. 2013, 78, 5530. A related strategy using quinones as the arylating source was reported for few cases of b-keto esters. However, this method accompanied the formation of aryl quinone products by overoxidation after the arylations: Aleman, J.; Richter, B.; Jørgensoen, K. A. Angew. Chem., Int. Ed. 2007, 46, 5515. Several reviews and accounts: (a) Brownbridge, P. Synthesis 1983, 1; (b) Brownbridge, P. Synthesis 1983, 85; (c) Kuwajima, I.; Nakamura, E. Acc. Chem. Res. 1985, 18, 181; (d) Carreira, E. M. In Comprehensive Asymmetric Catalysis I– III; Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer: New York, 1999; Vol. 3, pp 997–1065; (e) Kobayashi, S.; Manabe, K.; Ishitani, H.; Matsuo, J.-I. In Science of Synthesis; Fleming, I., Ed.; Thime: Stuttgart, 2002; Vol. 4, pp 317–369; (f) Kobayashi, S.; Yoo, W.-J.; Yamashita, Y. In Comprehensive Chirality; Carreira, E. M., Yamamoto, H., Eds.; Elsevier: Amsterdam, 2012; Vol. 4, pp 168–197; (g) Matsuo, J.-I.; Murakami, M. Angew. Chem., Int. Ed. 2013, 52, 9109. See the reported works referenced in: Schlummer, B.; Scholz, U. In Modern Arylation Methods; Ackermann, L., Ed.; Wiley-VCH: Weinheim, 2009; pp 69– 120. Reviews and highlights: (a) Culkin, D. A.; Hartwig, J. F. Acc. Chem. Res. 2003, 36, 234; (b) Lloyd-Jones, G. C. Angew. Chem., Int. Ed. 2002, 41, 953; (c) Johansson, C. C. C.; Colacot, T. J. Angew. Chem., Int. Ed. 2010, 49, 676; (d) Prim, D.; Marque, S.; Gaucher, A.; Campagne, J.-M. Org. React. 2012, 76, 49. For selected examples, see: (a) Kuwajima, I.; Urabe, H. J. Am. Chem. Soc. 1982, 104, 6831. this method involves in situ generation of tin enolates; (b) Carfagna, C.; Musco, A.; Sallese, G.; Santi, R.; Fiorani, T. J. Org. Chem. 1991, 56, 261; (c) Galarini, R.; Musco, A.; Pontellini, R.; Santi, R. J. Mol. Catal. 1992, 72, L11; (d) Agnelli, F.; Sulikowski, G. A. Tetrahedron Lett. 1998, 39, 8807; (e) Liu, X.; Hartwig, J. F. J. Am. Chem. Soc. 2004, 126, 5182; (f) Huang, Z.; Liu, Z.; Zhou, J. J. Am. Chem. Soc. 2011, 133, 15582; (g) Bigot, A.; Williamson, A. E.; Gaunt, M. J. J. Am. Chem. Soc. 2011, 133, 13778; (h) Harvey, J. S.; Simonovich, S. C.; Jamison, C. R.; MacMillan, D. W. C. J. Am. Chem. Soc. 2011, 133, 13782. By photoactivation: (a) Fraboni, A.; Fagnoni, M.; Albini, A. J. Org. Chem. 2003, 68, 4886; (b) Dichiarante, V.; Fagnoni, M.; Albini, A. J. Org. Chem. 2010, 75, 1271. (a) Chen, K.; Koser, G. F. J. Org. Chem. 1991, 56, 5764; (b) Iwama, T.; Birman, V. B.; Kozmin, S. A.; Rawal, V. H. Org. Lett. 1999, 1, 673; (c) Ooi, T.; Goto, R.; Maruoka, K. J. Am. Chem. Soc. 2003, 125, 10494. Oxidative methods: (a) RajanBabu, T. V.; Fukunaga, T. J. Org. Chem. 1984, 49, 4571; (b) Makosza, M.; Surowiec, M. Tetrahedron 2003, 59, 6261. Aryne trappings: Hamura, T.; Chuda, Y.; Nakatsuji, Y.; Suzuki, K. Angew. Chem., Int. Ed. 2012, 51, 3368. As a part of the preliminary study on the reactivity of QMAs toward different types of nucleophiles, we examined the reactions of a few silyl enol ethers with QMA 1a under unoptimized conditions. See Ref. 12b 5-Methoxy-2-silyloxy-a,a-dimethylbenzeneacetic acid methylester (3aa): Colorless oil. IR (KBr) cm1: 2950, 2833, 1737, 1497, 1 1424,1255,1234,1215,1145,1078,1049, 915, 883, 843, 763; H NMR (400 MHz, CDCl3) d 0.02 (s, 9H), 1.23 (s, 6H), 3.36 (s, 3H), 3.61 (s, 3H), 6.41– 6.62 (m, 3H) ppm; 13C NMR (100 MHz, CDCl3) d 0.0, 25.3, 43.9, 51.5, 55.2, 110.6, 112.8, 116.8, 136.3, 146.4, 153.0, 177.4 ppm. HRMS (EI) calcd for C15H24O4Si [M]+: 296.1444, found: 296.1446. The arylated position of QMA 1a was determined by converting the obtained product 3aa to a corresponding lactone, 5-methoxy-3,3-dimethyl-2(3H)benzofuranone, after TMS deprotection under acidic conditions followed by dehydrative lactonization. (a) Sartori, G.; Maggi, R.; Bigi, F.; Giacomelli, S.; Porta, C.; Arienti, A.; Bocelli, G. J. Chem. Soc., Perkin Trans. 1 1995, 2177; (b) Mohr, A. L.; Lombardo, M. L.; Arisco, T. M.; Morrow, G. W. Synth. Commun. 2009, 39, 3845; (c) Sloman, D. L.; Mitasev, B.; Scully, S. S.; Beutler, J. A.; Porco, J. A., Jr. Angew. Chem., Int. Ed. 2011, 50, 2511; (d) Reddy Parumala, S. K.; Peddinti, R. K. Org. Lett. 2013, 15, 3546. (a) Büchi, G.; Chu, P.-S. J. Org. Chem. 1978, 43, 3717; (b) Kerns, M. L.; Conroy, S. M.; Swenton, J. S. Tetrahedron Lett. 1994, 41, 7529; (c) Collins, J. L.; Grieco, P. A.; Walker, J. K. Tetrahedron Lett. 1997, 38, 1321; (d) Goodell, J. R.; McMullen, J. P.; Zaborenko, N.; Maloney, J. R.; Ho, C.-X.; Jensen, K. F.; Porco, J. A., Jr.; Beeler, A. B. J. Org. Chem. 2009, 74, 6169; (e) Liu, Y.; Liu, J.; Wang, M.; Liu, J.; Liu, Q. Adv. Synth. Catal. 2012, 354, 2678. These QMAs 1 can be readily prepared from corresponding phenols or pmethoxy phenols by utilizing hypervalent iodine-mediated oxidations in methanol solvent: (a) Tamura, Y.; Yakura, T.; Haruta, J.; Kita, Y. J. Org. Chem. 1987, 52, 3927; (b) Kita, Y.; Tohma, H.; Kikuchi, K.; Inagaki, M.; Yakura, T. J. Org. Chem. 1991, 56, 435.
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T. Dohi et al. / Tetrahedron Letters 56 (2015) 3046–3051 28. The substrate replacing the ring methyl substituent to tert-butyl group did not couple with ketene silyl acetal 2a. 29. We consider that this deprotection probably occurred during workup due to the instability of the TMS-protected 1-naphthol 3ha. 30. The requirements of excess amounts of silyl nucleophiles 2a–g are due to their instability under the acidic reaction medium. See the additional discussion in the following contents. 31. For characteristics of fluoroalcohols, see: (a) Eberson, L.; Hartshorn, M. P.; Persson, O.; Radner, F. Chem. Commun. 1996, 2105; (b) Bégué, J.-P.; Bonnetdelpon, D.; Crousse, B. Synlett 2004, 18; (c) Dohi, T.; Yamaoka, N.; Kita, Y. Tetrahedron 2010, 66, 5775. 32. (a) Mayr, H.; Kempf, B.; Ofial, A. R. Acc. Chem. Res. 2003, 36, 66; (b) Burfeindt, J.; Patz, M.; Mueller, M.; Mayr, H. J. Am. Chem. Soc. 1998, 120, 3629; (c) Mayr, H.; Bug, T.; Gotta, M. F.; Hering, N.; Irrgang, B.; Janker, B.; Kempf, B.; Loos, R.; Ofial, A. R.; Remennikov, G.; Schimmel, H. J. Am. Chem. Soc. 2001, 123, 9500. 33. In these silyl enol ethers, we detected their competitive decompositions into the corresponding aldol dimers, thus lowering the product yields compared to the ketene silyl acetals. 34. Characterization data of 30 ag: Colorless oil. IR (KBr) cm1: 2958, 2870, 1488, 1252, 1211, 844; 1H NMR (400 MHz, CDCl3) d 0.08 (s, 9H), 1.47–1.53 (m, 1H),
1.65–1.69 (m, 2H), 1.88 (td, 1H, J = 12.7, 6.4 Hz), 2.10–2.21 (m, 2H), 3.37 (d, 1H, J = 9.8 Hz), 3.73 (s, 3H), 6.60–6.68 (m, 3H); 13C NMR (100 MHz, CDCl3) d 1.3, 24.3, 33.5, 41.1, 53.5, 55.9, 108.7, 110.9, 112.2, 122.2, 131.9, 152.9, 154.3. See a similar compound, in: Saraswathy, V. G.; Sankararaman, S. J. Org. Chem. 1995, 60, 5024. 35. We set up the reaction of imino-QMA 4 for the same arylation with ketene silyl acetal 2a aimed at appending the o-anilide group to the obtainable product array of our metal-free a-arylating method. However, it was found that the reaction giving the corresponding a-arylated product 5 did not proceed at all in this case.
NTs
TMSNTs
CO2 Me
H NTs
or MeO
OMe 4 (Ts = p-toluenesulfonyl)
OMe 5
OMe
CO2Me
Contents lists available at ScienceDirect
Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet
A new arylation of silyl enol ethers by quinone monoacetal substitution Toshifumi Dohi, Tohru Kamitanaka, Hitoho Takamuro, Yusuke Mishima, Naohiko Washimi, Yasuyuki Kita ⇑ College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577, Japan
a r t i c l e
i n f o
Article history: Received 9 October 2014 Revised 14 November 2014 Accepted 17 November 2014 Available online 24 November 2014 Dedicated to the memory of Professor Harry H. Wasserman
a b s t r a c t Quinone monoacetals (QMAs) were found to be convenient substrates for a unique arylation reaction of enol silyl ethers. This arylation process of QMAs typically proceeds through the acetal activation of the QMAs by a hydrogen-bond donor solvent, such as a fluoroalcohol, for the initiating step. The silyl transfer from silyl enol ethers to the carbonyl oxygen of the QMAs appears to be involved in the C–C coupling step, followed by QMA aromatization. By this method, valuable a-aryl carbonyl compounds containing o-phenol moieties can be obtained directly under mild conditions without lactone formation. Ó 2014 Elsevier Ltd. All rights reserved.
Keywords: Arylation Silyl enol ether Quinone monoacetal Substitution a-Aryl carbonyl compound
Ketene acetal derivatives such as silyl enol ethers1a–c and alkoxy vinyl esters1d,e belong to the family of O-functionalized enols of esters. Upon nucleophilic attack on the silyl or acyl group, they easily revert to the stable original ester. By taking advantage of this powerful driving force and the attractiveness of having only the ester as a coproduct, these ketene acetal derivatives have been used since the 1970s as efficient and clean silyl and acyl group transfer agents in organic synthesis, as first reported by our research group.2–8 Indeed, more than 40 years ago our research group first pioneered the silyl transfer chemistry for the direct and efficient silylations of alcohols, carboxylic acids, mercaptans, and amides under very mild conditions by utilizing O-silylated ketene acetals.3,4 These silyl group transfer processes were further applied to carbon–carbon bond-forming reactions, that is, 1,4addition to a,b-unsaturated ketones,5 1,2-additions to aldehydes,6 and 1,3-additions to nitrones,7 all of which involved activation of the enolate through the transfer of the silyl group to the nucleophilic oxygen of the coupling partner. These addition reactions proceed even without the presence of an external activator or catalyst (Scheme 1). Thanks to advances in the synthetic routes to alkoxy vinyl esters,9 these compounds have become more
⇑ Corresponding author. Tel./fax: +81 (77)5615829. E-mail address: [email protected] (Y. Kita). http://dx.doi.org/10.1016/j.tetlet.2014.11.085 0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.
R1 XH (X = heteroatom)
R1 X[Si] O[Si]
O R2 CHR3 O R
4
R
O[Si]
R'
OMe
R7 + ON R
R
R
CO2Me R'
O[Si]
[Si] = TMS, TBS H silyl ketene acetals
5
R2 R3HC
R4 R R7
N
CO2 Me R' O[Si]
6 5
R
R6
R
CO2Me R'
Scheme 1. Ketene silyl acetals as versatile silyl transfer agent in organic transformations. (TMS = trimethylsilyl, TBS = tert-butyldimethylsilyl).
readily available. Similarly, we have also reported the acyl group transfer ability of alkoxy vinyl esters in the 1980s and applied this process to organic syntheses.8 As a continuation of our research, we became interested in the possibility of new carbon–carbon forming reactions of these ketene silyl acetals and silyl enol ethers and the synthetic applications of this chemistry. We focused our efforts on a new a-arylating
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T. Dohi et al. / Tetrahedron Letters 56 (2015) 3046–3051
aryl equivalent
Table 1 Screening of the conditions for arylation using QMA 1a
O
TMSO
O R MeO
OTMS
+
OMe
QMA (electrophile)
TMSO
CO2Me
MeO OMe 1a
OTMS OMe 2a
HFIP solvent conditions
CO2Me 3aa
OMe
R OMe and other silyl enol ether (nucleophile)
catalyst-free arylation OMe α-aryl carbonyl compound
Scheme 2. A new a-arylation strategy by quinone monoacetal (QMA) substitution utilizing silyl enol ethers.
method of carbonyl compounds under mild and metal catalyst-free conditions, following our recent studies of the substitution chemistry of quinone monoacetals (QMAs).10 These quinone derivatives have been found to react as powerful and regiospecific electrophiles, their reaction being followed by rapid rearomatization.11,12 Accordingly, we now report the first results of an extended study of a new coupling reaction of silyl enol ether nucleophiles with QMAs, facilitated by a strong hydrogen-bond donor solvent, that is, a fluoroalcohol, under mild conditions (Scheme 2).13 Since the discovery of the Mukaiyama-aldol reaction, the use of silyl enol ethers has greatly expanded beyond the scope of the aldol reaction to form new complex products.14 As part of these efforts, the a-arylation of carbonyl compounds utilizing silyl enol ethers has emerged as a powerful synthetic process.15 Since a-aryl carbonyl motifs are present in a large number of nature-made molecules and fine chemicals, introducing aryl moieties to keto compounds, or rather to a form of the corresponding metal enolates, has been intensively studied. In particular, the transition metal-catalyzed coupling strategies employing aryl halides and related electrophiles were the focus of much attention during the early stages of research in this area.16 New synthetic developments for this reaction have involved the uses of silyl enol ethers as convenient equivalents of these basic enolates, because of their characteristics as stable, neutral, and regiocontrolling nucleophiles.17 These silyl nucleophiles have been found to be effective in several metal catalyst-free approaches for providing a-arylated carbonyl compounds,18 though the methods were limited only to specific types of aryl substrates, that is, activated aryl electrophiles, such as diaryl iodonium salts, arylbismuth agents,19 among others.20,21 We recently developed conditions for the substitution reactions of QMAs promoted by Brønsted acids in a specific solvent, hexafluoroisopropanol (HFIP), for the coupling reactions with aromatic and alkene nucleophiles.11,12 QMAs are readily available, mono-protected quinone derivatives, which have recently attracted interest due to their broad utility in selective organic transformations, effectively acting as desymmetrized quinones.10 Hence, we started our QMA arylation study of silyl enol ethers in order to establish a new arylation process for the production of a-arylated carbonyl compounds under metal catalyst-free conditions by examining our reported reaction conditions, that is, the use of perfluorinated benzoic acids in HFIP (Table 1).22 As expected, the coupling of the representative QMA 1a with ketene silyl acetal 2a proceeded smoothly under our standard conditions in the fluoroalcohol solvent in the presence of a catalytic amount of phthalic acids (5 mol %),12c producing the a-aryl ester 3aa,23 accompanied by silylation of the phenol group, in 72% yield (entry 1). Interestingly, the corresponding lactone was prevented by the O-silylation of the phenol. This coupling rapidly proceeded at room
Entrya
Acid (equiv)
Time (h)
Yieldb of 3aa (%)
1 2 3 4 5 6c 7d 8e
Perfluoroterephthalic acid (0.05) Perfluoroterephthalic acid (0.5) Pentafluorobenzoic acid (1) Acetic acid (1) None None None None
1.5 1.5 3 3 24 24 24 24
72 Complex 45 81 91 95 89 43
a The reactions were examined using QMA 1a (1 equiv) and silyl enol ether 2a (2 equiv) in a mixture of hexafluoroisopropanol (10 mL relative to 1 mmol of QMA 1a) and dichloromethane (1 mL relative to 1 mmol of QMA 1a) at 0 °C unless otherwise noted. b Isolated yield based on QMA 1a used. c HFIP/DCM = 5.5 mL/5.5 mL. d HFIP/DCM = 1 mL/10 mL. e Dichloromethane (1a: 0.10 M) was used as solvent together with 2 equiv of HFIP.
temperature, and the reaction went to completion in 1.5 h. Consistent with our previous observations,11,12 the nucleophile 2a attacked the QMA 1a selectively at the a-position of the carbonyl group and did not touch the other electrophilic ring carbons of QMA 1a.24 To further improve the yield, we then examined the stoichiometric use of acid activators. However, this attempt to use perfluorinated terephthalic and benzoic acids12a,b failed, resulting in drastic decreases in product yields, despite the complete consumption of both reaction substrates 1a and 2a (entries 2 and 3). Based on these experiments, we concluded that the low yields were probably caused by the degradation of the acid-labile ketene silyl acetal 2a by the action of the acids, thereby preventing the desired coupling reaction of QMA 1a and silyl nucleophile 2a. This situation prompted us to study a milder reaction system with a weaker Brønsted acid. Hence, acetic acid was used as the activator instead of the above-mentioned stronger acids, and to our delight, we observed complete consumption of QMA 2a after stirring in HFIP for 3 hours and the product was obtained in good yield (entry 4). At that time, we were also aware of the formation of some product 3aa in the absence of catalyst, presumably promoted by the hydrogen-bond donating fluoroalcohol medium, HFIP. The reaction progress in the absence of the acid additives was thus monitored by TLC. We reasoned that the fluoroalcohol as a solvent or possibly even as an additive could act as a promoter for the coupling of the silyl enol ether 2a with QMA 1a. In the event, using HFIP either as a solvent or additive, with QMA 1a concentrations ranging from 0.10 to 0.01 M, provided the product 3aa in good yields (entries 5 and 6), however decreasing the proportion of HFIP with respect to the dichloromethane solvent caused the yield to significantly drop (entry 7). Needless to say, no reaction was observed in the absence of HFIP. Other reaction factors, such as concentration (doubling and halving the amount of the solvents) and temperature (0 °C), had little influence on product formation and yield. However, as in the reported metal-catalyzed reactions,17 this metal catalyst-free method was similarly sensitive to the stoichiometry of the silyl enol ether 2a, and the product 3aa was obtained in very low yield when employing an equimolar amount of the ketene silyl acetal 2a with QMA 1a. According to our careful examinations, the use of other activators (Et2AlCl, SnCl4, PtBr4, BF3Et2O, TMS-triflate)
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Table 2 A series of QMAs 1 for arylation of silyl enol ether 2aa Entry
QMA
Yieldb (%)
Arylation product
O
TMSO
C O2 Me 87
1
MeO
OMe
3ba
1b OMe TMSO
O 2
CO 2 Me 81
t Bu
1c
MeO
t
3ca
Bu
OMe
OMe TMSO
O
CO 2 Me 66
3
Br MeO
1d OMe
3da
Br OMe TMSO
O
CO 2 Me 34 68c
4
MeO MeO
1e
3ea
MeO
OMe
OMe
TMSO
O
CO 2 Me
5
Trace
1f MeO
OMe
3fa OMe TMSO
O
C O2 M e 54
6
1g MeO
OMe
3ga OMe OH
O
C O2 Me 77d,e
7
1h MeO a b c d e
OMe
3ha OMe
The reactions were examined under the optimized conditions of Table 1, entry 6. Isolated yield based on QMAs 1b–h used after reaction for 24 h. 5 equiv of silyl enol ether 2a was used. 3 equiv of silyl enol ether 2a. Including very small amount of the corresponding lactone form.
positions of the substituents determined the regioselectivity of the products 3ba–ea, the a-arylation proceeding cleanly to the less crowded a-position to the carbonyl group of QMAs 1b–e. Consistent with this strong steric regiocontrol by the substituent, dimethyl QMA 1f did not react at all with the ketene silyl acetal 1a (entry 5). Overall, the reaction behaviors of these QMAs 1b–f in the present system generally followed the known reactivity profiles of the QMAs toward other p-nucleophiles under the acidic conditions previously reported by us.11,12 Meanwhile, a clear difference was found for the reactivity of QMA 1g having a ring substituent at the a-position of the carbonyl group: at this position, even the small methyl group created steric interaction severe enough to strongly hinder the coupling reaction with the ketene silyl acetal 2a (entry 6).28 This drop in the reactivity of QMAs 1g is quite unique and was only observed in the present case of the nucleophile 2a. On the other hand, a smooth arylation occurred with the reactive naphthalene-based QMA 1h, and the coupling product 3ha was produced in good yield in the free phenol form (entry 7).29 Turning to the coupling partners for the QMAs, several silyl nucleophiles were tested. Ketene silyl acetals 2b–e were used for the reactions, although the relative instability of these silyl compounds toward acids forced the use of an excess of the nucleophile (2 equiv).30 As shown in Scheme 3, the ketene silyl acetals 2b–e derived from propionate (2b), a-aryl acetate (2c), cyclic ester (2d), and phenyl ester (2e), reacted with QMA 1a to afford the aarylated esters 3ab–ae in moderate yields, respectively (Eqs. 1–4). For the coupling of the QMAs 1 with silyl nucelophiles 2, a typical experimental procedure for the reaction listed in Table 1, entry 6 is as follows: to a stirred solution of the QMA 1a (77.1 mg, 0.50 mmol) in dichloromethane (2.5 mL) and 1,1,1,3,3,3-hexafluoro-2-propanol, HFIP (2.5 mL, dehydrated), was added the ketene silyl acetal 2a (174 mg, 1.0 mmol) at 0 °C. After completion of the reaction, as checked by TLC, the solvent was removed by rotary evaporator. The resulting crude residue containing the arylation product 3aa was subjected to column chromatography on silica-gel (hexanes/ethyl acetate = 15/1). By this simple operation, the a-arylated ester 3aa (136 mg, 92%) was obtained as a pure colorless oil. The product was obtained as the TMS-protected form
OTMS OMe
2b
TMSO CO2Me OMe
resulted in low yields of the product 3aa (0–37%) under the reported conditions. These activators, which have been useful in other types of substitutions of QMAs,25,26 do not appear to be useful for this arylation process. In order to extend our arylation method to additional QMAs, a brief survey was conducted with several QMAs 127 under the optimized reaction conditions (Table 2). Both QMAs 1b and 1c having a methyl and bulky tert-butyl group near the acetal sites of the QMA rings reacted with the ketene silyl acetal 2a without any problem, producing the expected a-aryl esters, 3ba and 3ca, in good yields (entries 1 and 2), respectively. Thus, the QMA activation and the silyl transfer to the phenol oxygen of the product were not affected by the presence of the bulky substituent. QMA 1d, containing a bromo group at the same position, led to the product 3da, albeit in somewhat lower yield (entry 3). Furthermore, the reaction of the less reactive QMA 1e having a methoxy group resulted in the partial formation of a-arylated product 3ea with low product conversion and a large amount of recovered starting QMA 1e. Fortunately, this product yield can be increased by using a larger amount of the silyl nucleophile 2a (entry 4). In these cases, the
Ph
OTMS OMe
QMA 1a
TMSO
Ph
2c CO2Me OMe
optimized conditions
(1)
3ab (57%)
(2)
3ac (40%)
OTMS OMe
2d
TMSO CO2Me OMe
OTMS OPh
(3)
3ad (31%)
TMSO 2e CO2Ph OMe
3ae (47%)
Scheme 3. Other silyl enol ethers (2 equiv of 2b–e relative to QMA 1a).
(4)
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OTMS O
O
OMe 2a
δ+
R (CF3)2CHOH (HFIP) OMe
MeO
R
δ+
MeO
1
intra- or intermolecular silyl transfer
TMSO
CO2Me
R
- H+
a
OMe
CF3
OMe
R
- MeOH
O HO Me F3C
QMAs
TMS O O H
3 OMe
- H+ TMSO OMe O
cyclization
intra- or intermolecular silyl transfer
R 3' OMe Scheme 4. Proposed roles of fluoroalcohol and silyl enol ether 2.
3aa, while the apparent formation of the corresponding O-free phenol during this reaction was not detected. In this unique arylation reaction of silyl enol ethers 2, we have shown that QMAs 1 selectively add to the a-position of the carbonyl group, that is, the allylic position of the allyl acetal moiety of the QMAs 1. Thus, the reaction produces a-aryl carbonyl compounds having an o-phenol or naphthol moiety as the coupling product. The mechanistic outline of this QMA arylation of silyl enol ethers is proposed in Scheme 4 for a representative case. It is assumed that the hydrogen-bond donor fluoroalcohol, HFIP,31 increases the partial positive charge of the QMAs 1 at the ring carbons a to the carbonyl group, and the activation for the allyl acetal functionalities helps the attack of the silyl enol ether 2a to the less crowded position of the electrophilic rings. This step seems to smoothly proceed even in the absence of external catalysts11,12 presumably because of the high nucleophilicity of the silyl enol ether 2a and other p-nucleophiles.32 The resulting putative intermediate a would be directly aromatized into the a-arylated carbonyl products 3, the intramolecular silyl transfer to the phenolic oxygen or some other intermolecular silylium shuttle step serving as the driving force.2–7 The unique effects of substituents displayed in Table 1 on the selectivity of the reaction with respect to the aposition to the carbonyl group, as shown for QMA having a tertbutyl group,28 seem to argue for the importance of the silyl transfer toward the carbonyl oxygens during the coupling reaction. An alternative pathway is the transient cyclization of intermediate a into dihydrobenzofuran 30 , which subsequently collapses to the a-aryl product 3 by silyl group transfer. The intermediacy of the cyclic intermediate 30 is suggested by the detection of this type of cyclic coproduct 30 af in the specific case of silyl enol ether 2f33 (Scheme 5) as well as previous observations in the couplings of QMAs 1 with alkenes.12 Thus, when cyclic silyl enol 2f was treated with QMA 1a under the standard conditions, the production of the a-arylated cyclopentanone 3af was accompanied by the formation of a small amount of the [3+2] coupling product, dihydrobenzofuran 30 af, which was isolated from the reaction mixture.34 The in situ formed cyclized 30 af eventually degraded into the a-aryl
TMSO O
OTMS O
2f
TMSO O
optimized condition MeO OMe 1a
OMe 3af (50%)
TMS O
O
δ+
R
pseudo-intramolecular silyl transfer
OMe
δ+
MeO
Scheme 6. Possible transition state for concerted silyl transfer and coupling.
carbonyl product 3af during the workup, which implies the possible intermediacy of the dihydrobenzofuran 30 af in the arylation processes. In our previous studies, the silyl group transfer from the ketene silyl acetals such as 2a, toward the carbonyl or nitrone oxygen during the silyl enol formations and addition reaction was assumed to take place via a six- or eight-membered cyclic bimolecular transition state.2–6 Based on this insight, a concerted mechanism for the formation of products 3 is proposed that proceeds via the transition state TS-a (Scheme 6). Obviously, the high affinity of the silicon atom toward oxygen is a key component. Indeed, this arylation using silyl nucleophiles 2 did not work with the related iminoquinone acetals,35 in stark contrast to the reactions between QMAs and silyl enol ethers 2 or other p-nucleophiles,11,12 a result which is consistent with the weaker bond energy between the silicon and nitrogen atoms. However, it is still difficult to make a unified conclusion for the reaction mechanism, as 2-[(trimethylsilyl)oxy]furan 2g was found to react with QMA 1a without the transfer of the silyl group, and the product 3ag not having the TMS moiety was obtained in good yield by the reaction of the nucleophile 2g at the remote conjugated carbon of the silyl enol ether function (Scheme 7). Consequently, one can assume that the silyl transfer and concerted transition state are not the essential events for the carbon–carbon bond-forming step during the arylation processes in some cases of the reactive nucleophiles.
OTMS O
O
2g
OH
(3 equiv.)
3'af
Scheme 5. Isolation of dihydrobenzofuran-type product 30 af.
3 OMe
CF3
TS-a
+
OMe
CO2Me
R
- H+
O HO Me F3C
TMSO
MeO OMe 1a
optimized condition
O OMe 3ag
O
O workup
column chromatography
Scheme 7. Alernative c-reactive silyl enol ether 2g.
O O
OMe 3'ag (85%)
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T. Dohi et al. / Tetrahedron Letters 56 (2015) 3046–3051
In summary, we have developed a new coupling reaction between QMAs 1 and silyl enol ethers 2, effectively promoted by the hydrogen-bond donor fluoroalcohol, HFIP, under mild conditions. This activation strategy allows QMAs 1 to selectively react with the nucleophiles in a regioselective, sterically controlled manner at the a-position of the carbonyl group as the only reacting center among the six electrophilic ring carbons, thereby providing via rearomatization a series of a-arylated o-phenol compounds that are difficult to obtain by other metal-free coupling methods without lactone formation. Along with the development of this unique substitution chemistry, this work demonstrates the use of QMAs 1 as a new entry to the arylation platform for the metal catalyst-free method for obtaining valuable a-arylated carbonyl products. We expect these substrates to be useful for the preparation of other compounds, as will be demonstrated in future studies.
10.
11.
12.
13.
Acknowledgments 14.
We acknowledge financial support from a Grant-in-Aid for Scientific Research (A) and Encouragement of Young Scientists (A) from JSPS, a Grant-in-Aid for Scientific Research on Innovative Areas ‘Advanced Molecular Transformations by Organocatalysts’ from MEXT. T.D. thanks Mitsubishi Gas Chemical Company research award from the Society of Synthetic Organic Chemistry, Japan, and research fund from the Asahi Glass Foundation and the Industrial Technology Research Grant Program from NEDO of Japan.
15.
16.
References and notes 17. 1. For early reports, see: (a) Petrov, A. D.; Sadykh-Zade, S. I.; Filatova, E. I. Zh. Obshch. Khim. 1959, 29, 2936; (b) Baukov, J. I.; Burlachenko, G. S.; Lutsenko, I. F. J. Organomet. Chem. 1965, 3, 478; (c) Lutsenko, I. F.; Baukor, Y. I.; Burlachenko, G. S.; Khasapor, B. N. J. Organomet. Chem. 1966, 5, 20; (d) Arth, G. E.; Poos, G. I.; Lukes, R. M.; Robinson, F. M.; Johns, W. F.; Feurer, M.; Sarett, L. H. J. Am. Chem. Soc. 1954, 76, 1715; (e) Arens, J. F. Recl. Trav. Chim. Pays-Bas 1955, 74, 769. 2. For background information about our chemistry on silyl and acyl transfer agents, see the following accounts and reviews: (a) Kita, Y. Yakugaku Zasshi 1986, 106, 269; (b) Kita, Y.; Tamura, O.; Tamura, Y. J. Synth. Org. Chem. Jpn. 1986, 44, 1118; (c) Tamura, Y.; Kita, Y. J. Synth. Org. Chem. Jpn. 1988, 46, 205; (d) Kita, Y.; Shibata, N. J. Synth. Org. Chem. Jpn. 1994, 52, 746; (e) Kita, Y.; Shibata, N. Synlett 1996, 289; (f) Kita, Y. Yakugaku Zasshi 1997, 117, 282; (g) Kita, Y.; Akai, S. Chem. Rec. 2004, 4, 363. 3. (a) Kita, Y.; Haruta, J.; Segawa, J.; Tamura, Y. Tetrahedron Lett. 1979, 20, 4311; (b) Kita, Y.; Haruta, J.; Fujii, T.; Segawa, J.; Tamura, Y. Synthesis 1981, 451; (c) Kita, Y.; Yasuda, H.; Sugiyama, Y.; Fukada, F.; Haruta, J.; Tamura, Y. Tetrahedron Lett. 1983, 24, 1273. 4. (a) Kita, Y.; Segawa, J.; Haruta, J.; Tamura, Y. Tetrahedron Lett. 1980, 21, 3779; (b) Kita, Y.; Segawa, J.; Haruta, J.; Yasuda, H.; Tamura, Y. J. Chem. Soc., Perkin Trans. 1 1982, 1099. 5. (a) Kita, Y.; Yasuda, H.; Haruta, J.; Segawa, J.; Tamura, Y. Synthesis 1982, 1089; (b) Kita, Y.; Yasuda, H.; Tamura, O.; Itoh, F.; Tamura, Y. Tetrahedron Lett. 1984, 25, 4681; (c) Kita, Y.; Tamura, O.; Yasuda, H.; Itoh, F.; Tamura, Y. Chem. Pharm. Bull. 1985, 33, 4235; (d) Kita, Y.; Tohma, H.; Inagaki, M.; Hatanaka, K.; Yakura, T. J. Am. Chem. Soc. 1992, 114, 2175; (e) Kita, Y.; Shibata, N.; Kawano, N.; Tohjo, T.; Fujimori, C.; Ohishi, H. J. Am. Chem. Soc. 1994, 116, 5116; For our recent report including the use of silyl transfer agent, see: (f) Dohi, T.; Uchiyama, T.; Yamashita, D.; Washimi, N.; Kita, Y. Tetrahedron Lett. 2011, 52, 2212. in the Special Issue published in honor of Professor Harry H. Wasserman on the occasion of his 90th birthday. 6. (a) Kita, Y.; Yasuda, H.; Tamura, O.; Itoh, F.; Ke, Y. Y.; Tamura, Y. Tetrahedron Lett. 1985, 26, 5777; (b) Kita, Y.; Tamura, O.; Itoh, F.; Yasuda, H.; Kishino, H.; Ke, Y. Y.; Tamura, Y. J. Org. Chem. 1988, 53, 554. 7. (a) Kita, Y.; Ito, F.; Tamura, O.; Ke, Y. Y.; Tamura, Y. Tetrahedron Lett. 1987, 28, 1431; (b) Kita, Y.; Tamura, O.; Itoh, F.; Kishino, H.; Miki, T.; Kohno, M.; Tamura, Y. J. Chem. Soc., Chem. Commun. 1988, 761; (c) Kita, Y.; Itoh, F.; Tamura, O.; Ke, Y. Y.; Miki, T.; Tamura, Y. Chem. Pharm. Bull. 1989, 37, 1446. 8. (a) Kita, Y.; Haruta, J.; Tagawa, H.; Tamura, Y. J. Org. Chem. 1980, 45, 4519; (b) Tamura, Y.; Inoue, M.; Wada, A.; Fujita, M.; Kita, Y. Chem. Pharm. Bull. 1981, 29, 3226; (c) Kita, Y.; Haruta, J.; Yasuda, H.; Fukunaga, K.; Shirouchi, Y.; Tamura, Y. J. Org. Chem. 1982, 47, 2697; (d) Kita, Y.; Akai, S.; Yoshigi, M.; Nakajima, Y.; Yasuda, H.; Tamura, Y. Tetrahedron Lett. 1984, 25, 6027; (e) Kita, Y.; Akai, S.; Ajimura, N.; Yoshigi, M.; Tsugoshi, T.; Yasuda, H.; Tamura, Y. J. Org. Chem. 1986, 51, 4150; (f) Kita, Y.; Akai, S.; Yamamoto, M.; Taniguchi, M.; Tamura, Y. Synthesis 1989, 334. for other applications, see accounts in Ref. 2. 9. For early preparations, see: (a) Broekema, R.; van der Werf, S.; Arens, J. F. Recl. Trav. Chim. Pays-Bas 1958, 77, 258; (b) Sheehan, J. C.; Hlavka, J. J. J. Org. Chem.
18. 19.
20. 21. 22.
23.
24.
25.
26.
27.
1958, 23, 635; Preparations by using mercury salts: (c) Wasserman, H. H.; Wharton, P. S. Tetrahedron 1958, 3, 321; (d) Wasserman, H. H.; Wharton, P. S. J. Am. Chem. Soc. 1960, 82, 661; (e) Tamura, Y.; Haruta, J.; Okuyama, S.; Kita, Y. Tetrahedron Lett. 1978, 19, 3737; Later, we have developed a practical and highyielding route to alkoxy vinyl esters avoiding the use of mercury salts: (f) Kita, Y.; Maeda, H.; Omori, K.; Okuno, T.; Tamura, Y. J. Chem. Soc., Perkin. Trans. 1 1993, 2999. For summarizations of preparations and utilities of QMAs, see: (a) Magdziak, D.; Meek, S. J.; Pettus, T. R. R. Chem. Rev. 2004, 104, 1383; (b) Dohi, T.; Kita, Y. In Quinones: Occurrence, Medicinal Uses and Physiological Importance; Price, E. R., Johnson, S. C., Eds.; NOVA Science Publisher: New York, 2013; pp 85–140. (a) Dohi, T.; Washimi, N.; Kamitanaka, T.; Fukushima, K.; Kita, Y. Angew. Chem., Int. Ed. 2011, 50, 6142; (b) Dohi, T.; Kamitanaka, T.; Watanabe, S.; Hu, Y.; Washimi, N.; Kita, Y. Chem. Eur. J. 2012, 18, 13614. (a) Dohi, T.; Hu, Y.; Kamitanaka, T.; Washimi, N.; Kita, Y. Org. Lett. 2011, 13, 4814; (b) Dohi, T.; Hu, Y.; Kamitanaka, T.; Kita, Y. Tetrahedron 2012, 68, 8424; (c) Hu, Y.; Kamitanaka, T.; Mishima, Y.; Dohi, T.; Kita, Y. J. Org. Chem. 2013, 78, 5530. A related strategy using quinones as the arylating source was reported for few cases of b-keto esters. However, this method accompanied the formation of aryl quinone products by overoxidation after the arylations: Aleman, J.; Richter, B.; Jørgensoen, K. A. Angew. Chem., Int. Ed. 2007, 46, 5515. Several reviews and accounts: (a) Brownbridge, P. Synthesis 1983, 1; (b) Brownbridge, P. Synthesis 1983, 85; (c) Kuwajima, I.; Nakamura, E. Acc. Chem. Res. 1985, 18, 181; (d) Carreira, E. M. In Comprehensive Asymmetric Catalysis I– III; Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer: New York, 1999; Vol. 3, pp 997–1065; (e) Kobayashi, S.; Manabe, K.; Ishitani, H.; Matsuo, J.-I. In Science of Synthesis; Fleming, I., Ed.; Thime: Stuttgart, 2002; Vol. 4, pp 317–369; (f) Kobayashi, S.; Yoo, W.-J.; Yamashita, Y. In Comprehensive Chirality; Carreira, E. M., Yamamoto, H., Eds.; Elsevier: Amsterdam, 2012; Vol. 4, pp 168–197; (g) Matsuo, J.-I.; Murakami, M. Angew. Chem., Int. Ed. 2013, 52, 9109. See the reported works referenced in: Schlummer, B.; Scholz, U. In Modern Arylation Methods; Ackermann, L., Ed.; Wiley-VCH: Weinheim, 2009; pp 69– 120. Reviews and highlights: (a) Culkin, D. A.; Hartwig, J. F. Acc. Chem. Res. 2003, 36, 234; (b) Lloyd-Jones, G. C. Angew. Chem., Int. Ed. 2002, 41, 953; (c) Johansson, C. C. C.; Colacot, T. J. Angew. Chem., Int. Ed. 2010, 49, 676; (d) Prim, D.; Marque, S.; Gaucher, A.; Campagne, J.-M. Org. React. 2012, 76, 49. For selected examples, see: (a) Kuwajima, I.; Urabe, H. J. Am. Chem. Soc. 1982, 104, 6831. this method involves in situ generation of tin enolates; (b) Carfagna, C.; Musco, A.; Sallese, G.; Santi, R.; Fiorani, T. J. Org. Chem. 1991, 56, 261; (c) Galarini, R.; Musco, A.; Pontellini, R.; Santi, R. J. Mol. Catal. 1992, 72, L11; (d) Agnelli, F.; Sulikowski, G. A. Tetrahedron Lett. 1998, 39, 8807; (e) Liu, X.; Hartwig, J. F. J. Am. Chem. Soc. 2004, 126, 5182; (f) Huang, Z.; Liu, Z.; Zhou, J. J. Am. Chem. Soc. 2011, 133, 15582; (g) Bigot, A.; Williamson, A. E.; Gaunt, M. J. J. Am. Chem. Soc. 2011, 133, 13778; (h) Harvey, J. S.; Simonovich, S. C.; Jamison, C. R.; MacMillan, D. W. C. J. Am. Chem. Soc. 2011, 133, 13782. By photoactivation: (a) Fraboni, A.; Fagnoni, M.; Albini, A. J. Org. Chem. 2003, 68, 4886; (b) Dichiarante, V.; Fagnoni, M.; Albini, A. J. Org. Chem. 2010, 75, 1271. (a) Chen, K.; Koser, G. F. J. Org. Chem. 1991, 56, 5764; (b) Iwama, T.; Birman, V. B.; Kozmin, S. A.; Rawal, V. H. Org. Lett. 1999, 1, 673; (c) Ooi, T.; Goto, R.; Maruoka, K. J. Am. Chem. Soc. 2003, 125, 10494. Oxidative methods: (a) RajanBabu, T. V.; Fukunaga, T. J. Org. Chem. 1984, 49, 4571; (b) Makosza, M.; Surowiec, M. Tetrahedron 2003, 59, 6261. Aryne trappings: Hamura, T.; Chuda, Y.; Nakatsuji, Y.; Suzuki, K. Angew. Chem., Int. Ed. 2012, 51, 3368. As a part of the preliminary study on the reactivity of QMAs toward different types of nucleophiles, we examined the reactions of a few silyl enol ethers with QMA 1a under unoptimized conditions. See Ref. 12b 5-Methoxy-2-silyloxy-a,a-dimethylbenzeneacetic acid methylester (3aa): Colorless oil. IR (KBr) cm1: 2950, 2833, 1737, 1497, 1 1424,1255,1234,1215,1145,1078,1049, 915, 883, 843, 763; H NMR (400 MHz, CDCl3) d 0.02 (s, 9H), 1.23 (s, 6H), 3.36 (s, 3H), 3.61 (s, 3H), 6.41– 6.62 (m, 3H) ppm; 13C NMR (100 MHz, CDCl3) d 0.0, 25.3, 43.9, 51.5, 55.2, 110.6, 112.8, 116.8, 136.3, 146.4, 153.0, 177.4 ppm. HRMS (EI) calcd for C15H24O4Si [M]+: 296.1444, found: 296.1446. The arylated position of QMA 1a was determined by converting the obtained product 3aa to a corresponding lactone, 5-methoxy-3,3-dimethyl-2(3H)benzofuranone, after TMS deprotection under acidic conditions followed by dehydrative lactonization. (a) Sartori, G.; Maggi, R.; Bigi, F.; Giacomelli, S.; Porta, C.; Arienti, A.; Bocelli, G. J. Chem. Soc., Perkin Trans. 1 1995, 2177; (b) Mohr, A. L.; Lombardo, M. L.; Arisco, T. M.; Morrow, G. W. Synth. Commun. 2009, 39, 3845; (c) Sloman, D. L.; Mitasev, B.; Scully, S. S.; Beutler, J. A.; Porco, J. A., Jr. Angew. Chem., Int. Ed. 2011, 50, 2511; (d) Reddy Parumala, S. K.; Peddinti, R. K. Org. Lett. 2013, 15, 3546. (a) Büchi, G.; Chu, P.-S. J. Org. Chem. 1978, 43, 3717; (b) Kerns, M. L.; Conroy, S. M.; Swenton, J. S. Tetrahedron Lett. 1994, 41, 7529; (c) Collins, J. L.; Grieco, P. A.; Walker, J. K. Tetrahedron Lett. 1997, 38, 1321; (d) Goodell, J. R.; McMullen, J. P.; Zaborenko, N.; Maloney, J. R.; Ho, C.-X.; Jensen, K. F.; Porco, J. A., Jr.; Beeler, A. B. J. Org. Chem. 2009, 74, 6169; (e) Liu, Y.; Liu, J.; Wang, M.; Liu, J.; Liu, Q. Adv. Synth. Catal. 2012, 354, 2678. These QMAs 1 can be readily prepared from corresponding phenols or pmethoxy phenols by utilizing hypervalent iodine-mediated oxidations in methanol solvent: (a) Tamura, Y.; Yakura, T.; Haruta, J.; Kita, Y. J. Org. Chem. 1987, 52, 3927; (b) Kita, Y.; Tohma, H.; Kikuchi, K.; Inagaki, M.; Yakura, T. J. Org. Chem. 1991, 56, 435.
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T. Dohi et al. / Tetrahedron Letters 56 (2015) 3046–3051 28. The substrate replacing the ring methyl substituent to tert-butyl group did not couple with ketene silyl acetal 2a. 29. We consider that this deprotection probably occurred during workup due to the instability of the TMS-protected 1-naphthol 3ha. 30. The requirements of excess amounts of silyl nucleophiles 2a–g are due to their instability under the acidic reaction medium. See the additional discussion in the following contents. 31. For characteristics of fluoroalcohols, see: (a) Eberson, L.; Hartshorn, M. P.; Persson, O.; Radner, F. Chem. Commun. 1996, 2105; (b) Bégué, J.-P.; Bonnetdelpon, D.; Crousse, B. Synlett 2004, 18; (c) Dohi, T.; Yamaoka, N.; Kita, Y. Tetrahedron 2010, 66, 5775. 32. (a) Mayr, H.; Kempf, B.; Ofial, A. R. Acc. Chem. Res. 2003, 36, 66; (b) Burfeindt, J.; Patz, M.; Mueller, M.; Mayr, H. J. Am. Chem. Soc. 1998, 120, 3629; (c) Mayr, H.; Bug, T.; Gotta, M. F.; Hering, N.; Irrgang, B.; Janker, B.; Kempf, B.; Loos, R.; Ofial, A. R.; Remennikov, G.; Schimmel, H. J. Am. Chem. Soc. 2001, 123, 9500. 33. In these silyl enol ethers, we detected their competitive decompositions into the corresponding aldol dimers, thus lowering the product yields compared to the ketene silyl acetals. 34. Characterization data of 30 ag: Colorless oil. IR (KBr) cm1: 2958, 2870, 1488, 1252, 1211, 844; 1H NMR (400 MHz, CDCl3) d 0.08 (s, 9H), 1.47–1.53 (m, 1H),
1.65–1.69 (m, 2H), 1.88 (td, 1H, J = 12.7, 6.4 Hz), 2.10–2.21 (m, 2H), 3.37 (d, 1H, J = 9.8 Hz), 3.73 (s, 3H), 6.60–6.68 (m, 3H); 13C NMR (100 MHz, CDCl3) d 1.3, 24.3, 33.5, 41.1, 53.5, 55.9, 108.7, 110.9, 112.2, 122.2, 131.9, 152.9, 154.3. See a similar compound, in: Saraswathy, V. G.; Sankararaman, S. J. Org. Chem. 1995, 60, 5024. 35. We set up the reaction of imino-QMA 4 for the same arylation with ketene silyl acetal 2a aimed at appending the o-anilide group to the obtainable product array of our metal-free a-arylating method. However, it was found that the reaction giving the corresponding a-arylated product 5 did not proceed at all in this case.
NTs
TMSNTs
CO2 Me
H NTs
or MeO
OMe 4 (Ts = p-toluenesulfonyl)
OMe 5
OMe
CO2Me