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In vivo antibacterial activity and pharmacological properties of the membrane-active glycopeptide antibiotic YV11455
G Model
CCLET-3248; No. of Pages 3 Chinese Chemical Letters xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Chinese Chemical Letters journal homepage: www.elsevier.com/locate/cclet
Original article
Phosphine-promoted [3 + 2] cycloaddition between nonsubstituted MBH carbonates and trifluoromethyl ketones Hong-Yu Duan a, Juan Ma a, Zhe-Zhe Yuan a, Ri-Sheng Yao a,*, Wei Tao a, Fang Xu a, Hua Xiao a,b,**, Gang Zhao b a
School of Medical Engineering, Hefei University of Technology, Hefei 230009, China Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China
b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 14 January 2015 Received in revised form 3 February 2015 Accepted 4 March 2015 Available online xxx
A phosphine-promoted [3 + 2] cycloaddition from readily accessible MBH (Morita–Baylis–Hillman) carbonate and aryl trifluoromethyl ketone is described. The use of methyl vinyl ketone-derived allylic carbonate rather than common acrylate-derived counterpart renders the reaction pathway exclusive for 5-endo process, which enables the expeditious preparation of a range of trifluoromethylated 2, 3-dihydrofuran in a chemospecific manner. ß 2015 Ri-Sheng Yao and Hua Xiao. Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. All rights reserved.
Keywords: Cycloaddition Allylic carbonate Ylides Trifluoromethyl ketones
1. Introduction The trifluoromethylated 2,3-dihydrofuran is a privileged structural motif present in some agrochemical candidates and bioactive compounds [1], thus their synthetic methodologies would be of potential application interest. The past decade has witnessed a significant advance on efficient construction of 2, 3-dihydrofuran structure [2], however, direct and convenient synthetic approaches for trifluoromethyl substituted dihydrofuran analogs from readily accessible starting materials and reagents under ambient conditions remain highly desirable [3]. Recently, nucleophilic phosphine or tertiary amine promoted cyclization reactions had proved themselves as a powerful tool to access synthetically valuable functionalized carbon or heterocycles [4]. When differently substituted allenoates reacted with CF3 aryl ketone, various trifluoromethylated oxygen heterocycles including dihydrofuran, dihydropyran and tetrahydrofuran can be synthesized respectively [3a,5]. On the other hand, MBH carbonate has also been identified as versatile coupling partner in lieu of allenic
ester to generate reactive zwitterion upon treatment of tertiary phosphine [6]. Very recently, we developed a chemoselective tandem reaction between g-nonsubstituted acrylate-derived MBH carbonates and trifluoromethyl aryl ketones (Scheme 1), whereas the tandem reaction sequence is terminated by a Wittig olefination. The reaction favored 5-exo-trig lactonization to give mono- or bicyclic vinyl g-butenolide products [7]. Under certain circumstances, a small amount of CF3-bearing 2,3-dihydrofuran was also separated as byproduct concomitantly, which resulted from alternative 5-endo-trig ring-closing process. Conceivably, changing methyl ester group in MBH carbonates into acetyl group would enforce the reaction pathway toward 5-endo process, resulting in 2,3-dihydrofuran exclusively (Scheme 1). Herein we disclosed a phosphine-promoted [3 + 2] cyclization of nonsubstituted MVK (methyl vinyl ketone)-derived MBH carbonates and trifluoromethyl ketones to produce potentially useful CF3-containing 2, 3-dihydrofurans with completely controlled chemoselectivity in moderate yields. 2. Experimental
* Corresponding author. ** Corresponding author at: School of Medical Engineering, Hefei University of Technology, Hefei 230009, China. E-mail addresses: [email protected] (R.-S. Yao), [email protected] (H. Xiao).
MVK-derived MBH carbonate 2 was prepared according to literature [8]. Aryl CF3 ketones used in this work were purchased from commercial suppliers and were used without further purification. 1H NMR, 19F and 13C NMR were recorded on Bruker
http://dx.doi.org/10.1016/j.cclet.2015.03.019 1001-8417/ß 2015 Ri-Sheng Yao and Hua Xiao. Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. All rights reserved.
Please cite this article in press as: H.-Y. Duan, et al., Phosphine-promoted [3 + 2] cycloaddition between nonsubstituted MBH carbonates and trifluoromethyl ketones, Chin. Chem. Lett. (2015), http://dx.doi.org/10.1016/j.cclet.2015.03.019
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CCLET-3248; No. of Pages 3 H.-Y. Duan et al. / Chinese Chemical Letters xxx (2015) xxx–xxx
2
for the present cyclization. It should be mentioned that the standard conditions also produced some unidentified dark compound with high polarity inevitably. 3. Results and discussion
Scheme 1. Phosphine-promoted reactions of g-nonsubstituted MBH carbonates and a-CF3 ketones.
600 MHz or 400 MHz spectrometers in CDCl3 solution, using TMS as an internal standard. HRMS were performed using electrospray ionization (ESI) with Waters Synapt G2 Si. Melting points were determined on a SGW X-4 melting point apparatus and were uncorrected. Initially, MVK-derived allylic carbonate 2 was exposed to 2 equiv. phenyl trifluoromethyl ketone 1a in the presence of various phosphine promoters with different electronic properties in CH2Cl2 at room temperature (Table 1). The anticipated 2, 3-dihydrofuran cycloadduct was isolated as the sole product in all cases and trialkylphosphine gave the best result, producing the corresponding product 3a in 57% isolated yield with excellent regioselectivity (Table 1, entries 1–4). Subsequent variation of reaction parameters, including ketone/carbonate molar ratio (Table 1, entries 5–7), phosphine loading (Table 1, entries 8–10) and temperature (Table 1, entry 12), did not avail further significant improvement for reaction efficiency. The cyclization seems to rely on the use of substoichiometric amount of Bu3P to maintain moderate conversion. In addition, the screening of solvents revealed that polar solvent DMF and protonic solvent ethanol resulted in either a small amount or trace of the desired cycloadduct, toluene was identified as the most suitable medium
With the optimized reaction conditions in hand, we next attempted to briefly investigate the reaction scope (Scheme 2). CF3-activated ketones with either electron-donating, electronneutral or electron-withdrawing substituents at p- or m-position on aryl group all reacted uneventfully, affording a series of CF3bearing 2,3-dihydrofuran in modest yields with excellent chemoand regioselectivities. In general, ketones with electron-donating and -neutral substituents usually delivered higher chemical yields than those with electron-withdrawing substituents. The sterically demanding 2-subtituted ketone 1f and heteroaryl ketone 1j were compatible with this cycloaddition protocol as well. However, aliphatic substrates were totally unsuitable (1,1,1-trifluoropropan2-one generally remained intact under our conditions). All new compounds were characterized by 1H, 13C, 19F NMR and HRMS spectra (Supporting information). The mechanistic proposal for the exclusive formation of dihydrofuran is outlined in Scheme 3. The cyclization begins with the conversion of MVK-derived MBH carbonate 2 and PBu3 to allylic phosphorus ylide A via a well-defined SN20 addition/ deprotonation process. Then the in situ generated zwitterion A undergoes sterically favorable g-addition to a-CF3 ketone to furnish intermediate B, otherwise the a-addition of allylic phosphorus ylide would lead to a Wittig olefination (g-substituted allylic ylide would undergo a-addition, see Ref. [7b]). Subsequently, the betaine B cyclized exclusively in a 5-endo-trig fashion to produce 2,3-dihydrofuran 3a since the appendant acetyl group was not susceptible to alternative 5-exo lactonization.
Table 1 Optimization of reaction conditions.a
Entry
PR3
Solvent
2/1a
PR3 loading (mol%)
3a (%)b
1 2 3 4 5 6 7 8 9 10 11 12c 13 14 15d 16 17 18 19 20 21
PPh3 P(p-FC6H4)3 P(p-MeOC6H4)3 P(n-Bu)3 P(n-Bu)3 P(n-Bu)3 P(n-Bu)3 P(n-Bu)3 P(n-Bu)3 P(n-Bu)3 P(n-Bu)3 P(n-Bu)3 P(n-Bu)3 P(n-Bu)3 P(n-Bu)3 P(n-Bu)3 P(n-Bu)3 P(n-Bu)3 P(n-Bu)3 P(n-Bu)3 P(n-Bu)3
CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 Toluene Toluene EtOAc THF CHCl3 DMF Et2O Acetone EtOH ClCH2CH2Cl n-Hexane
2/1 2/1 2/1 2/1 1/1 1/2 3/1 2/1 2/1 2/1 2/1 2/1 2/1 2/1 2/1 2/1 2/1 2/1 2/1 2/1 2/1
50 50 50 50 50 50 50 20 75 100 50 50 50 50 50 50 50 50 50 50 50
39 45 27 57 38 29 46 37 61 63 66 64 52 51 51 23 47 47 Trace 41 34
a b c d
Unless otherwise noted, reaction conditions: Ketone 1a and tert-butyl (2-methylene-3-oxobutyl) carbonate 2 were stirred in the presence of phosphine at r.t. for 12 h. Yields of isolated products. Reaction was carried out at 100 8C. A small amount of uncharacterized compound was observed concurrently.
Please cite this article in press as: H.-Y. Duan, et al., Phosphine-promoted [3 + 2] cycloaddition between nonsubstituted MBH carbonates and trifluoromethyl ketones, Chin. Chem. Lett. (2015), http://dx.doi.org/10.1016/j.cclet.2015.03.019
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CCLET-3248; No. of Pages 3 H.-Y. Duan et al. / Chinese Chemical Letters xxx (2015) xxx–xxx
3
Acknowledgments This work was supported by the National Natural Science Foundation of China (No. 21302034), and the Fundamental Research Funds for the Central Universities (No. 2013HGQC0028).
Appendix A. Supplementary data Supplementary material related to this article can be found, in the online version, at http://dx.doi.org/10.1016/j.cclet.2015.03.019. References
Scheme 2. Substrate scope of [3 + 2] annulation reaction of MBH carbonate 2 and a-CF3 ketones 1. Reaction conditions: ketone 1 (0.1 mmol) and tert-butyl(2methylene-3-oxobutyl)carbonate 2 (0.2 mmol) were stirred in the presence of nBu3P (0.05 mmol) in toluene at r.t. for 8–12 h. Yields refer to isolated yield. A small amount of uncharacterized compound was observed concurrently in the case of 3b, 3c or 3j.
Scheme 3. Proposed reaction mechanism.
4. Conclusion In conclusion, we disclosed a phosphine-promoted [3 + 2] cycloaddition reaction between MVK-derived MBH carbonate and aryl trifluoromethyl ketone, which provided a facile entry to CF3substituted 2,3-dihydrofurans under ambient and metal-free conditions. The presented work demonstrated the reaction pattern of allylic phosphorus ylide with carbonyl compound can be successfully modulated to bypass their intrinsic tendency toward Wittig olefination.
[1] (a) J.C. Toueg, T. Smejkal, S.V. Wendeborn, et al., Preparation of dihydrofuran derivatives as insecticidal compounds, PCT Int. Appl. WO 2013026724 A1 20130228 (2013). (b) Y Shishido, H. Wakabayashi, H. Koike, et al., Discovery and stereoselective synthesis of the novel isochroman neurokinin-1 receptor antagonist ‘CJ-17,493’, Bioorg. Med. Chem. 16 (2008) 7193–7205. [2] (a) T.G. Kilroy, T.P. O’Sullivan, P.J. Guiry, Synthesis of dihydrofurans substituted in the 2-position, Eur. J. Org. Chem. 23 (2005) 4929–4949; (b) F.L. Zhu, Y.H. Wang, D.Y. Zhang, et al., Enantioselective synthesis of highly functionalized dihydrofurans through copper-catalyzed asymmetric formal [3 + 2] cycloaddition of b-ketoesters with propargylic esters, Angew. Chem. Int. Ed. Engl. 53 (2014) 10223–10227; (c) M. Li, S. Lin, Z. Dong, et al., Organocatalyzed anion relay leading to functionalized 2,3-dihydrofurans, Org. Lett. 15 (2013) 3978–3981. [3] (a) T. Wang, S. Ye, Phosphine-catalyzed [3 + 2] cycloaddition of allenoates with trifluoromethylketones: synthesis of dihydrofurans and tetrahydrofurans, Org. Biomol. Chem. 9 (2011) 5260–5265; (b) H. Yu, J. Han, J. Chen, et al., Preparation of (E)-4-Aryl-1,1,1-trifluoro-3-tosylbut3-en-2-ones as fluorinated building blocks and their application in ready and highly stereoselective routes to trans-2,3-dihydrofurans substituted with trifluoromethyl and sulfonyl groups, Eur. J. Org. Chem. 16 (2012) 3142–3150. [4] (a) Z.M. Wang, X.Z. Xu, O. Kwon, Phosphine catalysis of allenes with electrophiles, Chem. Soc. Rev. 43 (2014) 2927–2940; (b) L.Y. Cui, S.H. Guo, B. Li, et al., Synthesis of cyclopentenyl and cyclohexenyl ketones via [3 + 2] and [4 + 2] annulations of 1,2-allenic ketones, Chin. Chem. Lett. 25 (2014) 55–57; (c) M.H. Mosslemina, N. Shamsa, H. Esteghamata, H. Anaraki-Ardakanib, An efficient synthesis of functionalized tetrahydro-1H-indeno[2,1-c]pyridine derivatives by a PPh3-promoted condensation reaction between acetylene esters and 1, 3-dioxo-N-aryl-2,3-dihydro-1H-indene-2-carboxamides, Chin. Chem. Lett. 24 (2013) 1095–1098. [5] (a) T. Wang, S. Ye, Diastereoselective synthesis of 6-trifluoromethyl-5,6-dihydropyrans via phosphine-catalyzed [4 + 2] annulation of alpha-benzylallenoates with ketones, Org. Lett. 12 (2010) 4168–4171; (b) L.B. Saunders, S.J. Miller, Divergent reactivity in amine- and phosphine-catalyzed C-C bond-forming reactions of allenoates with 2,2,2-trifluoroacetophenones, ACS Catal. 1 (2011) 1347–1350. [6] (a) Y. Du, X. Lu, C. Zhang, A catalytic carbon-phosphorus ylide reaction: phosphane-catalyzed annulation of allylic compounds with electron-deficient alkenes, Angew. Chem. Int. Ed. 42 (2003) 1035–1037; (b) R. Zhou, C.Z. Wang, H.B. Song, Z.J. He, Wittig olefination between phosphine, aldehyde, and allylic carbonate: a general method for stereoselective synthesis of trisubstituted 1,3-dienes with highly variable substituents, Org. Lett. 12 (2010) 976–979. [7] (a) H. Xiao, H. Duan, J. Ye, et al., Chemoselective synthesis of trifluoromethylated g-butenolide derivatives via phosphine-promoted tandem reaction of allylic carbonates and trifluoromethyl ketones, Org. Lett. 16 (2014) 5462–5465; (b) T. Wang, L.T. Shen, S. Ye, Wittig olefination of trifluoromethyl ketones and allylic carbonates mediated by phosphines synthesis 20 (2011) 3359–3363. [8] B.C.III Gerwick, S.C. Fields, P.R. Graupner, et al., Isolation and preparation of herbicidal methylidenemevalonates, Can. Pat. Appl. 2527439 (2006).
Please cite this article in press as: H.-Y. Duan, et al., Phosphine-promoted [3 + 2] cycloaddition between nonsubstituted MBH carbonates and trifluoromethyl ketones, Chin. Chem. Lett. (2015), http://dx.doi.org/10.1016/j.cclet.2015.03.019
CCLET-3248; No. of Pages 3 Chinese Chemical Letters xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Chinese Chemical Letters journal homepage: www.elsevier.com/locate/cclet
Original article
Phosphine-promoted [3 + 2] cycloaddition between nonsubstituted MBH carbonates and trifluoromethyl ketones Hong-Yu Duan a, Juan Ma a, Zhe-Zhe Yuan a, Ri-Sheng Yao a,*, Wei Tao a, Fang Xu a, Hua Xiao a,b,**, Gang Zhao b a
School of Medical Engineering, Hefei University of Technology, Hefei 230009, China Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China
b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 14 January 2015 Received in revised form 3 February 2015 Accepted 4 March 2015 Available online xxx
A phosphine-promoted [3 + 2] cycloaddition from readily accessible MBH (Morita–Baylis–Hillman) carbonate and aryl trifluoromethyl ketone is described. The use of methyl vinyl ketone-derived allylic carbonate rather than common acrylate-derived counterpart renders the reaction pathway exclusive for 5-endo process, which enables the expeditious preparation of a range of trifluoromethylated 2, 3-dihydrofuran in a chemospecific manner. ß 2015 Ri-Sheng Yao and Hua Xiao. Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. All rights reserved.
Keywords: Cycloaddition Allylic carbonate Ylides Trifluoromethyl ketones
1. Introduction The trifluoromethylated 2,3-dihydrofuran is a privileged structural motif present in some agrochemical candidates and bioactive compounds [1], thus their synthetic methodologies would be of potential application interest. The past decade has witnessed a significant advance on efficient construction of 2, 3-dihydrofuran structure [2], however, direct and convenient synthetic approaches for trifluoromethyl substituted dihydrofuran analogs from readily accessible starting materials and reagents under ambient conditions remain highly desirable [3]. Recently, nucleophilic phosphine or tertiary amine promoted cyclization reactions had proved themselves as a powerful tool to access synthetically valuable functionalized carbon or heterocycles [4]. When differently substituted allenoates reacted with CF3 aryl ketone, various trifluoromethylated oxygen heterocycles including dihydrofuran, dihydropyran and tetrahydrofuran can be synthesized respectively [3a,5]. On the other hand, MBH carbonate has also been identified as versatile coupling partner in lieu of allenic
ester to generate reactive zwitterion upon treatment of tertiary phosphine [6]. Very recently, we developed a chemoselective tandem reaction between g-nonsubstituted acrylate-derived MBH carbonates and trifluoromethyl aryl ketones (Scheme 1), whereas the tandem reaction sequence is terminated by a Wittig olefination. The reaction favored 5-exo-trig lactonization to give mono- or bicyclic vinyl g-butenolide products [7]. Under certain circumstances, a small amount of CF3-bearing 2,3-dihydrofuran was also separated as byproduct concomitantly, which resulted from alternative 5-endo-trig ring-closing process. Conceivably, changing methyl ester group in MBH carbonates into acetyl group would enforce the reaction pathway toward 5-endo process, resulting in 2,3-dihydrofuran exclusively (Scheme 1). Herein we disclosed a phosphine-promoted [3 + 2] cyclization of nonsubstituted MVK (methyl vinyl ketone)-derived MBH carbonates and trifluoromethyl ketones to produce potentially useful CF3-containing 2, 3-dihydrofurans with completely controlled chemoselectivity in moderate yields. 2. Experimental
* Corresponding author. ** Corresponding author at: School of Medical Engineering, Hefei University of Technology, Hefei 230009, China. E-mail addresses: [email protected] (R.-S. Yao), [email protected] (H. Xiao).
MVK-derived MBH carbonate 2 was prepared according to literature [8]. Aryl CF3 ketones used in this work were purchased from commercial suppliers and were used without further purification. 1H NMR, 19F and 13C NMR were recorded on Bruker
http://dx.doi.org/10.1016/j.cclet.2015.03.019 1001-8417/ß 2015 Ri-Sheng Yao and Hua Xiao. Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. All rights reserved.
Please cite this article in press as: H.-Y. Duan, et al., Phosphine-promoted [3 + 2] cycloaddition between nonsubstituted MBH carbonates and trifluoromethyl ketones, Chin. Chem. Lett. (2015), http://dx.doi.org/10.1016/j.cclet.2015.03.019
G Model
CCLET-3248; No. of Pages 3 H.-Y. Duan et al. / Chinese Chemical Letters xxx (2015) xxx–xxx
2
for the present cyclization. It should be mentioned that the standard conditions also produced some unidentified dark compound with high polarity inevitably. 3. Results and discussion
Scheme 1. Phosphine-promoted reactions of g-nonsubstituted MBH carbonates and a-CF3 ketones.
600 MHz or 400 MHz spectrometers in CDCl3 solution, using TMS as an internal standard. HRMS were performed using electrospray ionization (ESI) with Waters Synapt G2 Si. Melting points were determined on a SGW X-4 melting point apparatus and were uncorrected. Initially, MVK-derived allylic carbonate 2 was exposed to 2 equiv. phenyl trifluoromethyl ketone 1a in the presence of various phosphine promoters with different electronic properties in CH2Cl2 at room temperature (Table 1). The anticipated 2, 3-dihydrofuran cycloadduct was isolated as the sole product in all cases and trialkylphosphine gave the best result, producing the corresponding product 3a in 57% isolated yield with excellent regioselectivity (Table 1, entries 1–4). Subsequent variation of reaction parameters, including ketone/carbonate molar ratio (Table 1, entries 5–7), phosphine loading (Table 1, entries 8–10) and temperature (Table 1, entry 12), did not avail further significant improvement for reaction efficiency. The cyclization seems to rely on the use of substoichiometric amount of Bu3P to maintain moderate conversion. In addition, the screening of solvents revealed that polar solvent DMF and protonic solvent ethanol resulted in either a small amount or trace of the desired cycloadduct, toluene was identified as the most suitable medium
With the optimized reaction conditions in hand, we next attempted to briefly investigate the reaction scope (Scheme 2). CF3-activated ketones with either electron-donating, electronneutral or electron-withdrawing substituents at p- or m-position on aryl group all reacted uneventfully, affording a series of CF3bearing 2,3-dihydrofuran in modest yields with excellent chemoand regioselectivities. In general, ketones with electron-donating and -neutral substituents usually delivered higher chemical yields than those with electron-withdrawing substituents. The sterically demanding 2-subtituted ketone 1f and heteroaryl ketone 1j were compatible with this cycloaddition protocol as well. However, aliphatic substrates were totally unsuitable (1,1,1-trifluoropropan2-one generally remained intact under our conditions). All new compounds were characterized by 1H, 13C, 19F NMR and HRMS spectra (Supporting information). The mechanistic proposal for the exclusive formation of dihydrofuran is outlined in Scheme 3. The cyclization begins with the conversion of MVK-derived MBH carbonate 2 and PBu3 to allylic phosphorus ylide A via a well-defined SN20 addition/ deprotonation process. Then the in situ generated zwitterion A undergoes sterically favorable g-addition to a-CF3 ketone to furnish intermediate B, otherwise the a-addition of allylic phosphorus ylide would lead to a Wittig olefination (g-substituted allylic ylide would undergo a-addition, see Ref. [7b]). Subsequently, the betaine B cyclized exclusively in a 5-endo-trig fashion to produce 2,3-dihydrofuran 3a since the appendant acetyl group was not susceptible to alternative 5-exo lactonization.
Table 1 Optimization of reaction conditions.a
Entry
PR3
Solvent
2/1a
PR3 loading (mol%)
3a (%)b
1 2 3 4 5 6 7 8 9 10 11 12c 13 14 15d 16 17 18 19 20 21
PPh3 P(p-FC6H4)3 P(p-MeOC6H4)3 P(n-Bu)3 P(n-Bu)3 P(n-Bu)3 P(n-Bu)3 P(n-Bu)3 P(n-Bu)3 P(n-Bu)3 P(n-Bu)3 P(n-Bu)3 P(n-Bu)3 P(n-Bu)3 P(n-Bu)3 P(n-Bu)3 P(n-Bu)3 P(n-Bu)3 P(n-Bu)3 P(n-Bu)3 P(n-Bu)3
CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 Toluene Toluene EtOAc THF CHCl3 DMF Et2O Acetone EtOH ClCH2CH2Cl n-Hexane
2/1 2/1 2/1 2/1 1/1 1/2 3/1 2/1 2/1 2/1 2/1 2/1 2/1 2/1 2/1 2/1 2/1 2/1 2/1 2/1 2/1
50 50 50 50 50 50 50 20 75 100 50 50 50 50 50 50 50 50 50 50 50
39 45 27 57 38 29 46 37 61 63 66 64 52 51 51 23 47 47 Trace 41 34
a b c d
Unless otherwise noted, reaction conditions: Ketone 1a and tert-butyl (2-methylene-3-oxobutyl) carbonate 2 were stirred in the presence of phosphine at r.t. for 12 h. Yields of isolated products. Reaction was carried out at 100 8C. A small amount of uncharacterized compound was observed concurrently.
Please cite this article in press as: H.-Y. Duan, et al., Phosphine-promoted [3 + 2] cycloaddition between nonsubstituted MBH carbonates and trifluoromethyl ketones, Chin. Chem. Lett. (2015), http://dx.doi.org/10.1016/j.cclet.2015.03.019
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CCLET-3248; No. of Pages 3 H.-Y. Duan et al. / Chinese Chemical Letters xxx (2015) xxx–xxx
3
Acknowledgments This work was supported by the National Natural Science Foundation of China (No. 21302034), and the Fundamental Research Funds for the Central Universities (No. 2013HGQC0028).
Appendix A. Supplementary data Supplementary material related to this article can be found, in the online version, at http://dx.doi.org/10.1016/j.cclet.2015.03.019. References
Scheme 2. Substrate scope of [3 + 2] annulation reaction of MBH carbonate 2 and a-CF3 ketones 1. Reaction conditions: ketone 1 (0.1 mmol) and tert-butyl(2methylene-3-oxobutyl)carbonate 2 (0.2 mmol) were stirred in the presence of nBu3P (0.05 mmol) in toluene at r.t. for 8–12 h. Yields refer to isolated yield. A small amount of uncharacterized compound was observed concurrently in the case of 3b, 3c or 3j.
Scheme 3. Proposed reaction mechanism.
4. Conclusion In conclusion, we disclosed a phosphine-promoted [3 + 2] cycloaddition reaction between MVK-derived MBH carbonate and aryl trifluoromethyl ketone, which provided a facile entry to CF3substituted 2,3-dihydrofurans under ambient and metal-free conditions. The presented work demonstrated the reaction pattern of allylic phosphorus ylide with carbonyl compound can be successfully modulated to bypass their intrinsic tendency toward Wittig olefination.
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Please cite this article in press as: H.-Y. Duan, et al., Phosphine-promoted [3 + 2] cycloaddition between nonsubstituted MBH carbonates and trifluoromethyl ketones, Chin. Chem. Lett. (2015), http://dx.doi.org/10.1016/j.cclet.2015.03.019