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A novel and efficient approach to 3-allyl-chromones from arylynones and allylic alcohols via a tandem Michael addition/Claisen rearrangement/O-arylation reactions has been developed.
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Tandem Synthesis of 3-Allyl-chromones from Alkynones and Allylic Alcohols under Metal-free Conditions† Xuesong Wang, Guolin Cheng and Xiuling Cui* 5
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Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX DOI: 10.1039/b000000x A novel and efficient approach to 3-allyl-chromones from alkynones and allylic alcohols via a tandem Michael addition/Claisen rearrangement/O-arylation reaction has been developed. Diversely structural 3-allyl-chromones were afforded in up to 93% yield for 24 examples. This synthetic strategy features with regiospecificity, high efficiency, environmental friendliness and metal-free. Chromones are important structural motifs, exist in numerous natural products 1 and exhibit a wide range of biological activities 2, such as biocide, 3 pharmacology, 4 and antioxidant. 5 Of the numerous chromone derivatives, 3-allyl-chromone is a privileged structural scaffold for drug discovery6 due to its significant biological activities in vitro and in vivo, 7 which results in the importance of efficient synthetic methods to build such structure. 8 Conventionally, introducing C3 allyl groups into preformed chromone was via Stille coupling reaction of 3bromochromones with allyltributyltin (Scheme 1, eq 1). 9 Bromation of chromone and a Pd-catalyzed Stille coupling reaction were involved in this process using toxic organic tin reagent. Recently, a gold-catalyzed intramolecular addition of alkoxy-arylalkynone has been investigated, generating 3-allylchromone in only 38% yield (Scheme 1, eq 2). 10 In this procedure, noble metal (gold) is necessary, and the substrate scope is limited since the starting materials are difficult to prepare. 11 Lack of efficient protocol to 3-allyl-chromones has limited its applications in industries and academic research. Therefore, a more straightforward and cost-effective procedure for such structure with higher yields and good functional group tolerance is highly desirable. Herein, we design a concise and efficient strategy for the synthesis of 3-
Scheme 1 Synthesis of 3-allyl-chromone derivatives.
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Engineering Research Center of Molecular Medicine, Ministry of Education, Key Laboratory of Xiamen Marine and Gene Drugs, Institutes of Molecular Medicine and School of Biomedical Sciences, Huaqiao University, Xiamen, 361021 E-mail: [email protected] † Electronic Supplementary Information (ESI) available: Experimental details. See DOI:10.1039/b000000x/
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allyl-chromones via tandem reaction including Michael addition 12/Claisen rearrangement 13/O-arylation14 in one pot under metal-free conditions (Scheme 1, eq 3). At the outset of the study, the condensation of obromophenylynone 1a and allyl alcohol 2a were chosen as a model reaction to screen the reaction parameters (Table 1). To our delight, the desired product 3a was obtained in 82% yield when the tandem reaction was conducted at 120ºC in the presence of 10 mol % PBu315 and 1.0 equiv K 2CO3 (based on 1a) as base in DMF under air atmosphere (entry 1). The yield was improved to 87% when the transformation was conducted under nitrogen atmosphere (entry 2). Further studies focused on the reaction time and temperature (entries 3-5). 89% yield could be provided at 100ºC for 8 hours (entry 4). Then the amount of PBu 3 was investigated. The yield of the desired product was decreased with reducing the catalyst loading of PBu 3 (entries 6-7). Only a trace amount of product 3a was obtained in the presence of 1 mol % PBu 3 (entry 8). Other inorganic bases were also screened (entries 9-13). Cs2CO3, K3PO4, and Na2CO3 could provide reasonable yields (entries 9-11). The product 3a was not observed in the presence of NaOH. However, 3-unsubstituted chromone 16 was obtained in 65% yield (entry 12). The product of Michael addition reaction of 1a with allyl alcohol 2a was perhaps hydrolyzed into 1-(2-bromophenyl)-3-phenylpropane-1,3-dione in the presence of NaOH, which transformed into 2-phenyl-4Hchromen-4-one sequentially. 17 The solvent also played a [journal], [year], [vol], 00–00 | 1
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Table 2 Scope of substrates.a
Table 1 Screening the reaction parameters for the tandem reaction of obromophenylynone 1a with allyl alcohol 2aa.
entry
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PBu3 base solvent T t Yield (equiv) (ºC) (h) (%)b 1 0.1 K2CO3 DMF 120 12 82c 2 0.1 K2CO3 DMF 120 12 87 3 0.1 K2CO3 DMF 120 8 88 0.1 4 K2CO3 DMF 100 8 89 5 0.1 K2CO3 DMF 80 12 84 6 0.08 K2CO3 DMF 100 24 81 7 0.05 K2CO3 DMF 100 24 50 8 0.01 K2CO3 DMF 100 24 trace 9 0.1 Cs2CO3 DMF 100 8 88 10 0.1 K3PO4 DMF 100 8 85 11 0.1 Na2CO3 DMF 100 8 84 12 0.1 NaOH DMF 100 12 n.d.d 13 0.1 NaH DMF 100 12 69 14 0.1 K2CO3 DMSO 100 8 86 15 0.1 K2CO3 NMP 100 8 82 16 0.1 K2CO3 dioxane 100 24 trace 17 0.1 K2CO3 toluene 100 24 trace 18 0.1 K2CO3 EtOH 70 24 trace 19 0.1 K2CO3 H2O 100 24 trace 20 0.1 K2CO3 THF 60 24 trace a Reaction conditions: o-bromophenylynone 1a (0.5 mmol), allyl alcohol 2a (0.6 mmol), base (0.5 mmol), solvent (2 mL), under nitrogen. b Isolated yield based on 1a. c Under air. d 2-phenyl-4H-chromen-4-one was obtained.
crucial role in this transformation (entries 4 and 14-20). DMF, DMSO and NMP afforded the desired product 3a in 89%, 86% and 82% yields, respectively. Only a trace amount of 3a was observed for other solvents, such as dioxane, toluene, EtOH, THF and water (entries 16-20). On the basis of above results obtained, the optimal reaction conditions were identified as follows: 10 mol% PBu 3 as a catalyst, K 2CO3 as a base and DMF as the solvent under nitrogen atmosphere at 100ºC. With the optimized conditions in hand, the generality and scope of the substrates were investigated as illustrated in Table 2. The X substituent on 1 was firstly investigated. The identical product 3a was acquired in 80%, 84% and 89% yields, respectively, when X was F, Cl and Br. Pseudohalide, o-methoxyarylynone, could proceed smoothly and give 3a in 75% yield. It is worth noting that crotyl alcohol, 2-methyl allyl alcohol and cinnamyl alcohol were also suitable substrates, affording the corresponding products 3b, 3c and 3d in 85%, 81% and 75% yields, respectively. When 3-buten-2-ol was involved in the catalytic system, only 25% yield of the target product 3e was obtained, probably due to the steric hindrance of the secondary alcohol, which blocked the Michael addition process. These results indicated that Michael addition was the key step for this tandem reaction. This reaction system was applied to both of aryl (3f-i) and aliphatic group (3j-k) as R2 substituent on 1. The former could give the products in higher yields compared to the later. Moreover, either electron-donating groups (such as -Me, -OMe) (3f-g) or electron-withdrawing groups (such as -F, -Cl) 2 | Journal Name, [year], [vol], 00–00
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Under the optimized conditions. b Isolated yield. c 125 ºC. d Allyl alcohol as substrate. e Crotyl alcohol as substrate. f 2-Methylprop-2-en-1ol as substrate. g Cinnamyl alcohol as substrate. h 3-Buten-2-ol as substrate.
(3h-i) in R2 substituent could react smoothly with allyl alcohol, affording the corresponding 3-allyl-charomones in good to excellent yields. The scope of substrates were extended to various alkynones reacting with crotyl alcohol and 2-methyl allyl alcohol. Diversely structural 3-allyl- charomones were provided in 75% to 93% yields (3l-s). Generally, when crotyl alcohol was involved in the tandem reaction (3l – o), the corresponding products were afforded in slight higher yields compared to 2-methyl allyl alcohol (3p – s). Additionally, chloroarylynones were also investigated under the standand reaction conditions. The good yields of the target products This journal is © The Royal Society of Chemistry [year]
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5
were obtained (3t–u). To explore the reaction mechanism, an experiment was performed as demonstrated in Scheme 2. The intermediate C was firstly synthesized from the tandem transformation of ochlorophenylynone 1b with allyl alcohol 2a. Subsequently, the intermediate C was treated by 1 equiv K2CO3 at 100 ºC in DMF for 2 hours. The target product 3a was obtained in 86% yield.
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Scheme 2 Synthesis of 3a by two steps.
According to the literature 18 and the results obtained above, a plausible reaction mechanism was proposed and shown in scheme 3. First, PBu3-promoted Michael addition of allyl alcohol 2a with o-halo/methoxyaryl-containing alkynone 1 afforded enyne adduct B (E/Z). Then, Claisen rearrangement thermally induced the transformation of enyne adduct B into intermediate C. Subsequently, enolization of the α-carbonyl group in C formed D in the presence of K 2CO3. And the species of E was generated via intramolecular cyclization of D. Finally, rearomatization of E by elimination of KX provided the target product 3a.
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Scheme 3 Plausible mechanism.
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In summary, we have developed an efficient protocol to 3allyl-chromones from o-halo/methoxyarylynone and allylic alcohol in one pot. The Michael addition, Claisen rearrangement and Ullmann-type O-arylation reactions were involved in this tandem procedure. This strategy features with regio-specificity, high efficiency, environmental friendliness, and metal-free.
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Acknowledgment
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Financial support was provided by NSF of China (21202048), Program for Minjiang Scholar program (10BS216), Science Research Item of Science and Technology of Xiamen City (3502z201014) and NSF of Fujian Province, China (2013J01050).
Notes and references 1 2 40
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Rice-Evans, N. J. Miller and G. Paganga, Free radic. Boil. Med., 1996, 20, 933. 3 (a) K. V. Rao, S. K. Chattopadhyay and G. C. Reddy, J. Agric. Food Chem., 1990, 38, 1427; (b) M. W. Örner and H. C. Jha, Pestic. Sci., 1993, 38, 347; (c) A. M. S. Silva, M. W. ÖRner and J. A. S. Cavaleiro, Mycol. Res., 1998, 102, 638. 4 (a) E. S. C. Wu, J. T. Loch III, B. H. Toder, A. R. Borrelli, D. Gawlak, L. A. Radov and N. P. Gensmantel, J. Med. Chem., 1992, 35, 3519; (b) C. Wolfman, H. Viola, M. Marder, C. Wasowski, P. Ardenghi, I. Izquierdo, A. C. Paladini and J. H. Medina, Eur. J. Pharmacol., 1996, 318, 23; (c) J. A. Manthey, N. Guthrie and K. Grohmann, Curr. Med. Chem., 2001, 8, 135; (d) M. i n-Saxin, T. Seifert, M. R. Landergren, T. Suuronen, M. Lahtela-Kakkonen, E. M. Jarho and K. Luthman, J. Med. Chem., 2012, 55, 7104. 5 (a) C. Kandaswami and E. Middleton Jr, In Free radicals in diagnostic medicine, 1994, 351; (b) C. A. Rice-Evans, N. J. Miller, and G. Paganga, Free Rad. Boil. Med., 1996, 20, 933; (c) K. E. Heim, A. R. Tagliaferro and D. J. Bobilya, J. Nutr. Biochem. Chem., 2002, 13, 572; (d) A. Gaspar, T. Silva, M. ez, D. Vina, F. Orallo, F. Ortuso, E. Uriarte, S. Alcaro and F. Borges, J. Med. Chem., 2011, 54, 5165. 6 (a) D. A. Horton, G. T. Bourne and M. L. Smythe, Chem. Rev., 2003, 103, 893; (b) C. K. Ghosh, Heterocycles, 2004, 63, 2875. 7 (a) Y. S. Chi, H. G. Jong, K. H. Son, H. W. Chang, S. S. Kang and H. P. Kim, Biochem. Pharmacol., 2001, 62, 1185; (b) H. -Y. Sohn, K. H. Son, C. -S. Kwon, G. -S. Kwon and S. S. Kang, Phytomedicine, 2004, 11, 666; (c) A. R. Han, Y. J. Kang, T. Windono, S. K. Lee and E. K. Seo, J. nat. prod. 2006, 69, 719. 8 K. Dahle´n, E. A. A. Walle´n, M. Grøtli and K. Luthman, J. Org. Chem., 2006, 71, 6863. 9 T. T. Dao, J. W. Oh, Y. S. Chi, H. P. Kim, K. S. Sin and H. Park, Arch. Pharm. Res., 2003, 26, 581. 10 J. Renault, Z. Qian, P. Uriac and N. Gouault, Tetrahedron Lett., 2011, 52, 2476. 11 K. Tangdenpaisal, S. Sualek, S. Ruchirawat and P. Ploypradith, Tetrahedron, 2009, 65, 4316. 12 For select tandem Michael addition, see: (a) F. Liang, S. Lin and Y. Wei, J. Am. Chem. Soc., 2011, 133, 1781; (b) G. Chai, S. Wu, C. Fu and S. Ma, J. Am. Chem. Soc., 2011, 133, 3740; (c) Q. G. Wang, X. M. Deng, B. H. Zhu, L. W. Ye, X. L. Sun, C. Y. Li, C. Y. Zhu, Q. Shen and Y. Tang, J. Am. Chem. Soc., 2008, 130, 5408; (d) H. L. Teng, F. L. Luo, H. Y. Tao and C. J. Wang, Org. Lett., 2011, 13, 5600; (e) H. S. Yoon, X. H. Ho, J. Jang, H. J. Lee, S. J. Kim and H. Y. Jang, Org. Lett., 2012, 14, 3272. 13 For select tandem Claisen rearrangement, see: (a) H. M. L. Davies and Y. Lian, Acc. Chem. Res., 2012, 45, 923; (b) P. Wipf and S. Ribe, Org. Lett., 2001, 3, 1503; (c) X. Li, R. E. Kyne and T. V. Ovaska, J. Org. Chem., 2007, 72, 6624; (d) H. Yoshida, K. Hiratani, T. Ogihara, Y. Kobayashi, K. Kinbara and K. Saigo, J. Org. Chem., 2003, 68, 5812; (e) K. Hiratani and M. Albrecht, Chem. Soc. Rev., 2008, 37, 2413. 14 For recent examples, see: (a) Y. Fang and C. Li, J. Org. Chem., 2006, 71, 6427; (b) S. L. Buchwald and C. Bolm, Angew. Chem. Int. Ed., 2009, 48, 5586; (c) G. Evindar and R. A. Batey, J. Org. Chem., 2006, 71, 1802; (d) Q. Shelby, N. Kataoka, G. Mann and J. Hartwig, J. Am. Chem. Soc., 2000, 122, 10718; (e) K. E. Torraca, S. I. Kuwab and S. L. Buchwald, J. Am. Chem. Soc., 2000, 122, 12907. 15 H. Jiang, W. Yao, H. Cao, H. Huang and D. Cao, J. Org. Chem., 2010, 75, 5347. 16 (a) M. Yoshida, Y. Fujino, K. Saito and T. Doi, Tetrahedron, 2011, 67, 9993; (b) Z. Du, H. Ng, K. Zhang, H. Zeng and J. Wang, Org. Biomol. Chem., 2011, 9, 6930; (c) G. W. Kabalka and A. R. Mereddy, Tetrahedron Lett., 2005, 46, 6315. 17 (a) P. A. Turner, E. M. Griffin, J. L. Whatmore and M. Shipman, Org. Lett., 2011, 13, 1056; (b) J. Zhao, Y. Zhao and H. Fu, Angew. Chem. Int. Ed., 2011, 50, 3769. 18 J. Zhao, Y. Zhao and H. Fu, Org. Lett., 2012, 14, 2710.
(a) P. J. Houghton, Alkaloids, 1987, 31, 67; (b) P. J. Houghton, Stud. Nat. Prod. Chem., 2000, 21, 123. (a) M. L. Borges, O. C. Matos, I. Pais, J. S. De Melo, C. P. Ricardo, A. MacAnita and R. S. Becker, Pestic. Sci., 1995, 44, 155; (b) C. A.
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Accepted Manuscript This article can be cited before page numbers have been issued, to do this please use: X. Wang, G. Cheng and X. Cui, Chem. Commun., 2013, DOI: 10.1039/C3CC48259F.
Volume 46 | Number 32 | 2010
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This is an Accepted Manuscript, which has been through the RSC Publishing peer review process and has been accepted for publication. Chemical Communications www.rsc.org/chemcomm
Volume 46 | Number 32 | 28 August 2010 | Pages 5813–5976
ChemComm
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Accepted Manuscripts are published online shortly after acceptance, which is prior to technical editing, formatting and proof reading. This free service from RSC Publishing allows authors to make their results available to the community, in citable form, before publication of the edited article. This Accepted Manuscript will be replaced by the edited and formatted Advance Article as soon as this is available. To cite this manuscript please use its permanent Digital Object Identifier (DOI®), which is identical for all formats of publication.
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COMMUNICATION J. Fraser Stoddart et al. Directed self-assembly of a ring-in-ring complex
FEATURE ARTICLE Wenbin Lin et al. Hybrid nanomaterials for biomedical applications
1359-7345(2010)46:32;1-H
Please note that technical editing may introduce minor changes to the text and/or graphics contained in the manuscript submitted by the author(s) which may alter content, and that the standard Terms & Conditions and the ethical guidelines that apply to the journal are still applicable. In no event shall the RSC be held responsible for any errors or omissions in these Accepted Manuscript manuscripts or any consequences arising from the use of any information contained in them.
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A novel and efficient approach to 3-allyl-chromones from arylynones and allylic alcohols via a tandem Michael addition/Claisen rearrangement/O-arylation reactions has been developed.
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Tandem Synthesis of 3-Allyl-chromones from Alkynones and Allylic Alcohols under Metal-free Conditions† Xuesong Wang, Guolin Cheng and Xiuling Cui* 5
10
15
20
25
30
35
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX DOI: 10.1039/b000000x A novel and efficient approach to 3-allyl-chromones from alkynones and allylic alcohols via a tandem Michael addition/Claisen rearrangement/O-arylation reaction has been developed. Diversely structural 3-allyl-chromones were afforded in up to 93% yield for 24 examples. This synthetic strategy features with regiospecificity, high efficiency, environmental friendliness and metal-free. Chromones are important structural motifs, exist in numerous natural products 1 and exhibit a wide range of biological activities 2, such as biocide, 3 pharmacology, 4 and antioxidant. 5 Of the numerous chromone derivatives, 3-allyl-chromone is a privileged structural scaffold for drug discovery6 due to its significant biological activities in vitro and in vivo, 7 which results in the importance of efficient synthetic methods to build such structure. 8 Conventionally, introducing C3 allyl groups into preformed chromone was via Stille coupling reaction of 3bromochromones with allyltributyltin (Scheme 1, eq 1). 9 Bromation of chromone and a Pd-catalyzed Stille coupling reaction were involved in this process using toxic organic tin reagent. Recently, a gold-catalyzed intramolecular addition of alkoxy-arylalkynone has been investigated, generating 3-allylchromone in only 38% yield (Scheme 1, eq 2). 10 In this procedure, noble metal (gold) is necessary, and the substrate scope is limited since the starting materials are difficult to prepare. 11 Lack of efficient protocol to 3-allyl-chromones has limited its applications in industries and academic research. Therefore, a more straightforward and cost-effective procedure for such structure with higher yields and good functional group tolerance is highly desirable. Herein, we design a concise and efficient strategy for the synthesis of 3-
Scheme 1 Synthesis of 3-allyl-chromone derivatives.
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Engineering Research Center of Molecular Medicine, Ministry of Education, Key Laboratory of Xiamen Marine and Gene Drugs, Institutes of Molecular Medicine and School of Biomedical Sciences, Huaqiao University, Xiamen, 361021 E-mail: [email protected] † Electronic Supplementary Information (ESI) available: Experimental details. See DOI:10.1039/b000000x/
This journal is © The Royal Society of Chemistry [year]
70
allyl-chromones via tandem reaction including Michael addition 12/Claisen rearrangement 13/O-arylation14 in one pot under metal-free conditions (Scheme 1, eq 3). At the outset of the study, the condensation of obromophenylynone 1a and allyl alcohol 2a were chosen as a model reaction to screen the reaction parameters (Table 1). To our delight, the desired product 3a was obtained in 82% yield when the tandem reaction was conducted at 120ºC in the presence of 10 mol % PBu315 and 1.0 equiv K 2CO3 (based on 1a) as base in DMF under air atmosphere (entry 1). The yield was improved to 87% when the transformation was conducted under nitrogen atmosphere (entry 2). Further studies focused on the reaction time and temperature (entries 3-5). 89% yield could be provided at 100ºC for 8 hours (entry 4). Then the amount of PBu 3 was investigated. The yield of the desired product was decreased with reducing the catalyst loading of PBu 3 (entries 6-7). Only a trace amount of product 3a was obtained in the presence of 1 mol % PBu 3 (entry 8). Other inorganic bases were also screened (entries 9-13). Cs2CO3, K3PO4, and Na2CO3 could provide reasonable yields (entries 9-11). The product 3a was not observed in the presence of NaOH. However, 3-unsubstituted chromone 16 was obtained in 65% yield (entry 12). The product of Michael addition reaction of 1a with allyl alcohol 2a was perhaps hydrolyzed into 1-(2-bromophenyl)-3-phenylpropane-1,3-dione in the presence of NaOH, which transformed into 2-phenyl-4Hchromen-4-one sequentially. 17 The solvent also played a [journal], [year], [vol], 00–00 | 1
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Table 2 Scope of substrates.a
Table 1 Screening the reaction parameters for the tandem reaction of obromophenylynone 1a with allyl alcohol 2aa.
entry
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PBu3 base solvent T t Yield (equiv) (ºC) (h) (%)b 1 0.1 K2CO3 DMF 120 12 82c 2 0.1 K2CO3 DMF 120 12 87 3 0.1 K2CO3 DMF 120 8 88 0.1 4 K2CO3 DMF 100 8 89 5 0.1 K2CO3 DMF 80 12 84 6 0.08 K2CO3 DMF 100 24 81 7 0.05 K2CO3 DMF 100 24 50 8 0.01 K2CO3 DMF 100 24 trace 9 0.1 Cs2CO3 DMF 100 8 88 10 0.1 K3PO4 DMF 100 8 85 11 0.1 Na2CO3 DMF 100 8 84 12 0.1 NaOH DMF 100 12 n.d.d 13 0.1 NaH DMF 100 12 69 14 0.1 K2CO3 DMSO 100 8 86 15 0.1 K2CO3 NMP 100 8 82 16 0.1 K2CO3 dioxane 100 24 trace 17 0.1 K2CO3 toluene 100 24 trace 18 0.1 K2CO3 EtOH 70 24 trace 19 0.1 K2CO3 H2O 100 24 trace 20 0.1 K2CO3 THF 60 24 trace a Reaction conditions: o-bromophenylynone 1a (0.5 mmol), allyl alcohol 2a (0.6 mmol), base (0.5 mmol), solvent (2 mL), under nitrogen. b Isolated yield based on 1a. c Under air. d 2-phenyl-4H-chromen-4-one was obtained.
crucial role in this transformation (entries 4 and 14-20). DMF, DMSO and NMP afforded the desired product 3a in 89%, 86% and 82% yields, respectively. Only a trace amount of 3a was observed for other solvents, such as dioxane, toluene, EtOH, THF and water (entries 16-20). On the basis of above results obtained, the optimal reaction conditions were identified as follows: 10 mol% PBu 3 as a catalyst, K 2CO3 as a base and DMF as the solvent under nitrogen atmosphere at 100ºC. With the optimized conditions in hand, the generality and scope of the substrates were investigated as illustrated in Table 2. The X substituent on 1 was firstly investigated. The identical product 3a was acquired in 80%, 84% and 89% yields, respectively, when X was F, Cl and Br. Pseudohalide, o-methoxyarylynone, could proceed smoothly and give 3a in 75% yield. It is worth noting that crotyl alcohol, 2-methyl allyl alcohol and cinnamyl alcohol were also suitable substrates, affording the corresponding products 3b, 3c and 3d in 85%, 81% and 75% yields, respectively. When 3-buten-2-ol was involved in the catalytic system, only 25% yield of the target product 3e was obtained, probably due to the steric hindrance of the secondary alcohol, which blocked the Michael addition process. These results indicated that Michael addition was the key step for this tandem reaction. This reaction system was applied to both of aryl (3f-i) and aliphatic group (3j-k) as R2 substituent on 1. The former could give the products in higher yields compared to the later. Moreover, either electron-donating groups (such as -Me, -OMe) (3f-g) or electron-withdrawing groups (such as -F, -Cl) 2 | Journal Name, [year], [vol], 00–00
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Under the optimized conditions. b Isolated yield. c 125 ºC. d Allyl alcohol as substrate. e Crotyl alcohol as substrate. f 2-Methylprop-2-en-1ol as substrate. g Cinnamyl alcohol as substrate. h 3-Buten-2-ol as substrate.
(3h-i) in R2 substituent could react smoothly with allyl alcohol, affording the corresponding 3-allyl-charomones in good to excellent yields. The scope of substrates were extended to various alkynones reacting with crotyl alcohol and 2-methyl allyl alcohol. Diversely structural 3-allyl- charomones were provided in 75% to 93% yields (3l-s). Generally, when crotyl alcohol was involved in the tandem reaction (3l – o), the corresponding products were afforded in slight higher yields compared to 2-methyl allyl alcohol (3p – s). Additionally, chloroarylynones were also investigated under the standand reaction conditions. The good yields of the target products This journal is © The Royal Society of Chemistry [year]
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were obtained (3t–u). To explore the reaction mechanism, an experiment was performed as demonstrated in Scheme 2. The intermediate C was firstly synthesized from the tandem transformation of ochlorophenylynone 1b with allyl alcohol 2a. Subsequently, the intermediate C was treated by 1 equiv K2CO3 at 100 ºC in DMF for 2 hours. The target product 3a was obtained in 86% yield.
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Scheme 2 Synthesis of 3a by two steps.
According to the literature 18 and the results obtained above, a plausible reaction mechanism was proposed and shown in scheme 3. First, PBu3-promoted Michael addition of allyl alcohol 2a with o-halo/methoxyaryl-containing alkynone 1 afforded enyne adduct B (E/Z). Then, Claisen rearrangement thermally induced the transformation of enyne adduct B into intermediate C. Subsequently, enolization of the α-carbonyl group in C formed D in the presence of K 2CO3. And the species of E was generated via intramolecular cyclization of D. Finally, rearomatization of E by elimination of KX provided the target product 3a.
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Scheme 3 Plausible mechanism.
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In summary, we have developed an efficient protocol to 3allyl-chromones from o-halo/methoxyarylynone and allylic alcohol in one pot. The Michael addition, Claisen rearrangement and Ullmann-type O-arylation reactions were involved in this tandem procedure. This strategy features with regio-specificity, high efficiency, environmental friendliness, and metal-free.
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Acknowledgment
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Financial support was provided by NSF of China (21202048), Program for Minjiang Scholar program (10BS216), Science Research Item of Science and Technology of Xiamen City (3502z201014) and NSF of Fujian Province, China (2013J01050).
Notes and references 1 2 40
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