A highly efficient diastereoselective synthesis of cyclohexadiene epoxide derivatives with a multi-stereocenter has been developed via a tandem ylide Michael addition/epoxidation. By employing a chiral sulfonium ylide, up to 96% ee can be achieved in good yields

Deng, Xian-Ming

Li, Chuan-Ying

Shen, Qi

Sun, Xiu-Li

Tang, Yong

Wang, Qing-Gang

Ye, Long-Wu

Zhu, Ben-Hu

Zhu, Chun-Yin

叶龙武

Journal of the American Chemical Society

Xiamen University Institutional Repository

Tandem Michael Addition/Ylide Epoxidation for the Synthesisof Highly Functionalized Cyclohexadiene Epoxide DerivativesQing-Gang Wang,† Xian-Ming Deng,† Ben-Hu Zhu,‡ Long-Wu Ye,† Xiu-Li Sun,†Chuan-Ying Li,† Chun-Yin Zhu,† Qi Shen,‡ and Yong Tang*,†State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry,354 FengLin Lu, Shanghai 200032, China, and School of Chemistry and Chemical Engineering,Suzhou UniVersity, Suzhou 215123, ChinaReceived January 30, 2008; E-mail: tangy@mail.sioc.ac.cnYlide reactions have been developed as one of the powerfulapproaches for the synthesis of small ring compounds.1 Re-cently, much attention has been paid to the synthesis of fusedbicyclic compounds via ylide routes.2 During our study on ylidechemistry,3 we developed a tandem reaction of allylic ylide withR,-unsaturated ketones for the rapid construction of function-alized multisubstituted cyclohexadiene epoxides with multiplestereogenic centers. In particular, optically active cyclohexadieneepoxides could be easily prepared with high enantiomericexcesses in good yields by remote control of enantioselectivityvia chiral sulfur ylides. In this communication, we will reportour preliminary results.The reactions of allylic sulfur ylides with chalcone were reportedto give vinylcyclopropanes.4 In the presence of K2CO3, unexpect-edly, we found that the reaction of crotonate-derived sulfoniumsalt 1 with chalcone only gave the cyclohexadiene epoxides ratherthan cyclopropanes (Scheme 1). Further studies showed that both-aryl- and -alkyl-substituted R,-unsaturated ketones are goodsubstrates, affording the cyclohexadiene epoxide derivatives withexcellent diastereoselectivities (>99/1) in good to high yields(60-93%). In all cases examined, cyclopropanes were not ob-served. As shown in Table 1, both electron-donating and electron-withdrawing substituents on the aryl ring proved to be well-toleratedbut influenced slightly the yields (entries 1-4). Trifluoromethyl-substituted ketone 2e gave cyclohexadiene epoxide 4e in 86% yield(entry 5, Table 1). Propenylphenylketone 2f furnished the desiredproduct in 85% yield (entry 6). The reaction of ketone 2g alsoproceeded well to afford product 4g with high chemoselectivity(entry 7). (E)-Methyl-2-oxo-4-phenylbut-3-enoate and (E)-ethyl-2-oxopent-3-enoate also gave the desired epoxides in good yields(entries 9 and 10).Encouraged by this tandem reaction, we also investigated itsintramolecular version and found it proceeded very well (Table2), giving the desired tricyclic cyclohexadiene epoxides withexcellent diastereoselectivities (>99/1) in good to high yields (upto 85%). For example, allylic sulfonium salt 5a was treated withK2CO3 to afford cyclohexadiene epoxide 6a as a single product in69% yield (entry 1, Table 2). Other sulfonium salts such as 5b-f,which are readily available from crotonate, proved to be quite goodfor this cyclization (Table 2). This method provides a good wayto prepare tricyclic compounds with a cyclohexadiene epoxide unit.The present reaction makes it readily accessible to highlyfunctionalized cyclohexadiene epoxide derivatives6 with excel-lent diastereoselectivity and chemoselectivity, prompting us todevelop its asymmetric version using chiral sulfur ylides. Usingcamphor-derived sulfonium salts 7 and 8,4b,c,8 fortunately, wefound that both the intermolecular and the intramolecularreactions worked very well, furnishing the desired epoxides withhigher than 91% ee in moderate to good yields (Scheme 2).5Thus, the current reaction proVides an excellent example forremote control of enantioselectiVity.7The absolute configuration of epoxide 6d was determined byX-ray ananlysis.5 The stereochemical model, as shown in Figure1, could explain the enantioselection,4b in which the first Michaeladdition attacked from the re face of the enone. A clearmechanism waits further investigation.The functionalized epoxide derivatives9 prepared by the currentmethod are potentially useful. As shown in Scheme 3, for example,compound 4b was found to react with sodium methoxide to givethe corresponding ring opening product 9 with high regiospecificity.Interestingly, treatment of 4b with LiBEt3H afforded bicycliccompound 1011 stereospecifically in 87% yield.In summary, we have developed a tandem10 Michael addition/ylide epoxidation for the rapid creation of highly functionalizedcyclohexadiene epoxide skeletons with three stereocenters.† Shanghai Institute of Organic Chemistry.‡ Suzhou University.Scheme 1. An Unexpected Cyclization Reaction of 1Table 1. Tandem Michael Addition/Ylide Epoxidation Reaction5a Conditions: sulfonium salt 1 (145 mg, 0.6 mmol), ketone (0.3mmol), CH3CN (3.0 mL), K2CO3 (166 mg, 1.2 mmol). b Cyclopropanederivative was not detected and dr >99/1 (by 1H NMR). c Isolated yield.d Five equivalents of 1 was used.Published on Web 04/01/200810.1021/ja800747m CCC: $40.75  2008 American Chemical Society5408 9 J. AM. CHEM. SOC. 2008, 130, 5408–5409Although, its asymmetric version involving the remote controlof selectivities, high enantioselectivity, and high diastereose-lectivity could be obtained. The readily accessible startingmaterial, mild reaction conditions, high selectivities, andrecoverable chiral sulfide made the present reaction potentiallyuseful in organic synthesis. Further studies on the mechanismare under investigation in our laboratory.Acknowledgment. We are grateful for the financial supportfrom the Natural National Sciences Foundation of China, theMajor State Basic Research Development Program (Grant No.2006CB806105), and The Chinese Academy of Sciences. Thispaper is dedicated to Professor Xiyan Lu on the occasion ofhis 80th birthday.Supporting Information Available: Detailed experimental pro-cedures, characterization data for all new compounds (PDF), and ciffiles of single crystals 4a, 6c, 6d, and 10 are available. This materialis available free of charge via the Internet at http://pubs.acs.org.References(1) For reviews, please see: (a) McGarrigle, E. M.; Myers, E. L.; Illa, O.; Shaw,M. A.; Riches, S. L.; Aggarwal, V. K. Chem. ReV. 2007, 107, 5841. (b)Tang, Y.; Ye, S.; Sun, X.-L. Synlett 2005, 2720. (c) Aggarwal, V. K.; Winn,C. L. Acc. Chem. Res. 2004, 37, 611. (d) Lebel, H.; Marcouxv, J. F.;Molinnaro, C.; Charette, A. B. Chem. ReV. 2003, 103, 977. (e) Dai, L.-X.;Hou, X.-L.; Zhou, Y.-G. Pure Appl. Chem. 1999, 71, 369. (f) Li, A.-H.;Dai, L.-X.; Aggarwal, V. K. Chem. ReV. 1997, 97, 2341.(2) For leading references, see: (a) Unthank, M. G.; Hussain, N.; Aggarwal,V. K. Angew. Chem., Int. Ed. 2006, 45, 7066. (b) Kokotos, C. G.; Aggarwal,V. K. Chem. Commun. 2006, 2156. (c) Johansson, C. C. C.; Bremeyer, N.;Ley, S. V.; Owen, D. R.; Smith, S. C.; Gaunt, M. J. Angew. Chem., Int.Ed. 2006, 45, 6024. (d) Papageorgiou, C. D.; Cubillo de Dios, M. A.; Ley,S. V.; Gaunt, M. J. Angew. Chem., Int. Ed. 2004, 43, 4641. (e) Bremeyer,N.; Smith, S. C.; Ley, S. V.; Gaunt, M. J. Angew. Chem., Int. Ed. 2004,43, 2681. (f) Gais, H. J.; Reddy, L. R.; Babu, G. S.; Raabe, G. J. Am.Chem. Soc. 2004, 126, 4859. (g) Koep, S.; Gais, H. J.; Raabe, G. J. Am.Chem. Soc. 2003, 125, 13243. (h) Wang, L.-C.; Krische, M. J. Angew.Chem., Int. Ed. 2003, 42, 5855. (i) Wang, L.-C.; Ng, S. S.; Krische, M. J.J. Am. Chem. Soc. 2003, 125, 3682.(3) (a) Li, C.-Y.; Wang, X.-B.; Sun, X.-L.; Tang, Y.; Zheng, J.-C.; Xu, Z.-H.;Zhou, Y.-G.; Dai, L.-X. J. Am. Chem. Soc. 2007, 129, 1494. (b) Ye, L.-W.; Sun, X.-L.; Wang, Q.-G.; Tang, Y. Angew. Chem., Int. Ed. 2007, 46,5951. (c) Zheng, J.-C.; Liao, W.-W.; Tang, Y.; Sun, X.-L.; Dai, L.-X. J. Am.Chem. Soc. 2005, 127, 12222. (d) Liao, W.-W.; Li, K.; Tang, Y. J. Am.Chem. Soc. 2003, 125, 13030.(4) (a) Neff, J. R.; Gruetzmacher, R. R.; Nordlander, J. E. J. Org. Chem. 1974,39, 3814. (b) Deng, X.-M.; Cai, P.; Ye, S.; Sun, X.-L.; Liao, W.-W.; Li,K.; Tang, Y.; Wu, Y.-D.; Dai, L.-X. J. Am. Chem. Soc. 2006, 128, 9730.(c) Ye, S.; Huang, Z.-Z.; Xia, C.-A.; Tang, Y.; Dai, L.-X. J. Am. Chem.Soc. 2002, 124, 2432. (d) Tang, Y.; Huang, Y.-Z.; Dai, L.-X.; Sun, J.; Xia,W. J. Org. Chem. 1997, 62, 954.(5) For details, please see the Supporting Information, and ee values weredeterminded by chiral HPLC.(6) For selected examples for the synthesis of cyclohexadiene epoxide, see:(a) Inoue, M.; Yokota, W.; Murugesh, M. G.; Izuhara, T.; Katoh, T. Angew.Chem., Int. Ed. 2004, 43, 4207. (b) Wood, J. L.; Thompson, B. D.; Yusuff,N.; Pflum, D. A.; Matthäus, M. S. P. J. Am. Chem. Soc. 2001, 123, 2097.(c) Nicolaou, K. C.; Vassilikogiannakis, G.; Simonsen, K. B.; Baran, P. S.;Zhong, Y.-L.; Vidali, V. P.; Pitsinos, E. N.; Couladouros, E. A. J. Am.Chem. Soc. 2000, 122, 3071.(7) For recent remote asymmetric induction, please see: (a) Belostotskii, A. M.;Albeck, A.; Hassner, A. Eur. J. Org. Chem. 2007, 4837. (b) Judd, W. R.;Ban, S.; Aube, J. J. Am. Chem. Soc. 2006, 128, 13736. (c) Malkov, A. V.;Stewart Liddon, A. J. P.; Ramirez-Lopez, P.; Bendova, L.; Haigh, D.;Kocovsky, P. Angew. Chem., Int. Ed. 2006, 45, 1432. (d) Paton, R. S.;Goodman, J. M. Org. Lett. 2006, 8, 4299.(8) For camphor-derived sulfonium in organic synthesis, please see: (a)Aggarwal, V. K.; Charmant, J. P. H.; Fuentes, D.; Harvey, J. N.; Hynd,G.; Ohara, D.; Picoul, W.; Robiette, R.; Smith, C.; Vasse, J. L.; Winn,C. L. J. Am. Chem. Soc. 2006, 128, 2105. (b) Aggarwal, V. K.; Hynd, G.;Picoul, W.; Vasse, J. L.; Winn, C. L. J. Am. Chem. Soc. 2002, 124, 9964.(c) Zhou, Y.-G.; Hou, X.-L.; Dai, L.-X.; Xia, L.-J.; Tang, M.-H. J. Chem.Soc., Perkin Trans. 1 1999, 77. (d) Li, A.-H.; Dai, L.-X.; Hou, X.-L.; Huang,Y.-Z.; Li, F.-W. J. Org. Chem. 1996, 61, 489.(9) For recent reviews on cyclohexadiene epoxides in organic synthesis, pleasesee: (a) Marco-Contelles, J.; Molina, M. T.; Anjum, S. Chem. ReV. 2004,104, 2857. For recent examples, please see: (b) Shoji, M.; Imai, H.;Mukaida, M.; Sakai, K.; Kakeya, H.; Osada, H.; Hayashi, Y. J. Org. Chem.2005, 70, 79. (c) Lorbach, V.; Franke, D.; Nieger, M.; Müller, M. Chem.Commun. 2002, 494. (d) Block, O.; Klein, G.; Altenbach, H. J.; Brauer,D. J. J. Org. Chem. 2000, 65, 716.(10) For leading reviews on tandem reaction, see: (a) Enders, D.; Grondal, C.;Hüttl, M. R. M. Angew. Chem., Int. Ed. 2007, 46, 1570. (b) Pellissier, H.Tetrahedron 2006, 62, 2143. (c) Guo, H.-C.; Ma, J.-A. Angew. Chem., Int.Ed. 2006, 45, 354. (d) Ramon, D. J.; Yus, M. Angew. Chem., Int. Ed. 2005,44, 1602. (e) Tietze, L. F. Chem. ReV. 1996, 96, 115.(11) The structures of 4a, 6c, 6d, and 10 were determined by X-ray analysis.JA800747MTable 2. Intramolecular Michael Addition/Ylide Epoxidation5entrya n R yieldb,c1 1 Ph (5a) 692 1 p-BrC6H4 (5b) 693 2 Ph (5c) 854 2 p-BrC6H4 (5d) 785 2 p-ClC6H4 (5e) 836 2 p-OMeC6H4 (5f) 78a Conditions: 5 (0.2 mmol), CH3CN (3.0 mL), K2CO3 (56 mg, 0.40mmol), room temperature. b Cyclopropanes were not observed and dr>99/1 (by 1H NMR). c Isolated yield.Scheme 2. Asymmetric Michael Addition/Ylide Epoxidationaa See ref 5. Reaction conditions: a7 (0.2 mmol), K2CO3 (56 mg, 0.4mmol), CH3CN (3 mL), 0-50 °C and a trace amount of de-epoxidationproduct was observed; b8 (dr >20/1, 171 mg, 0.45 mmol), Cs2CO3 (180mg, 0.55 mmol), ketone (0.15 mmol), CH3CN (4 mL), 0 °C.Figure 1. Stereochemical model.Scheme 3. Product ElaborationJ. AM. CHEM. SOC. 9 VOL. 130, NO. 16, 2008 5409C O M M U N I C A T I O N S

Tandem Michael addition/ylide epoxidation for the synthesis of highly functionalized cyclohexadiene epoxide derivatives

https://dspace.xmu.edu.cn/bitstream/2288/61390/1/Tandem%20Michael%20AdditionYlide%20Epoxidation%20for%20the%20Synthesis%20of%20Highly%20Functionalized%20Cyclohexadiene%20Epoxide%20Derivatives.pdf

Tandem Michael addition/ylide epoxidation for the synthesis of highly functionalized cyclohexadiene epoxide derivatives

Abstract

Similar works

Full text

Available Versions

Xiamen University Institutional Repository