Part 1
簡單而有效率的從Nitronate生成Nitrile oxide以進行1,3-雙偶極合環反應
β-硝基苯乙烯 (β-nitrostyrenes 1) 系列物可和diethyl allyl malonate anion 進行1,4-加成反應而產生 nitronates 5，當nitronates 5和ethyl chloroformate 以及催化量的 4-dimethylaminopyridine (DMAP).作用反應時，可產生nitrile oxide並進行 INOC (intramolecular nitrile oxide–olefin cycloaddition)形式的合環反應而得到中到高產率 (51–95%) 的五環之碳環化合物 8 和 9。當1a和10的陰離子在相似的反應條件下，可得到高產率 (91%) 的三環化合物11和12。
Part 2
使用Methyl Chloroformate試劑經由一鍋到底的圖途逕來進行INOC 或 IAOC類型的合環反應以合成五環之醚類
β-硝基苯乙烯 (β-nitrostyrenes 6) 系列物和丙烯醇 (allyl alcohol) 以及鹼反應可生成 nitronate 7，當溶液中加入 methyl chloroformate 和催化量的 4-dimethylaminopyridine (DMAP) 以及不同量的三乙基胺 (triethylamine) 時，可將 nitronate 7 轉化成 methoxycarbonyl nitronates 12。反應中間體12可經由IAOC (intramolecular alkoxycarbonyl nitronate-olefin cycloaddition) 的合環路徑生成高立體選擇性的產物 trans-4，或經由INOC (intramolecular nitrile oxide–olefin cycloaddition) 形式的合環路徑生成trans-4 和 cis-4。利用法亦可合成 16和 17 等雜環化合物。
Part 3
用三乙基鋁誘發烷基碘化物產生自由基來和-硝基苯乙烯系列物反應以產生各類型之烯類
硝基苯乙烯系列物 ((E)-β-nitrostyrenes 1) 和三乙基鋁 (triethylaluminum 2) 及烷基碘化物(alkyl iodide) 3, 4, 或 5 於 benzoyl peroxide 的存在的情況下，於室溫的條件下在乙醚溶液中反應能得到60-100% 各種不同之反式的烯類6, 7, 或 8。在相同的條件之下，利用1-iodoadamantane 9 或 5-iodo-2-adamantanone 11和2反應可得到產率95% 之 1-adamantyl-2-(4-methoxyphenyl)ethene 10 或產率 80% 之 1-(4-oxoadamantyl)-2-(4-methoxyphenyl)ethene 12.
Part 4
三乙基鋁或三乙基硼誘發烷基碘化物和α,β-不飽和之烯類進行自由基類型之1,4-加成反應
α,β-不飽和之烯類化合物1a-c、9、13 和 17可進行自由基型態之1,4-加成反應：三乙基硼和空氣中的氧氣 (triethylborane–oxygen in air) 或三乙基鋁 (triethylaluminum) 和benzoyl peroxide可用來誘發烷基碘化物以產生烷基自由基和烯類反應而進行1,4-加成反應。當反應以三乙基硼誘發時，反應通常較乾淨而且易於純化；然而當活性較低的烯類作為反應的受質時，以三乙基鋁誘發之反應在相似的反應條件下，則可得到較高產率的1,4-加成產物以及較少量的副產物。文中 Scheme 1 為此類型反應的反應機構。

Part 1
An Improved, Easy and Efficient Method for the Generation of Nitrile Oxides From Nitronates for in situ 1,3-Dipolar Cycloaddition
The Michael addition of the diethyl allyl malonate anion to β-nitrostyrenes 1 generated nitronates 5. Nitronates 5 could be converted into nitrile oxides 7 to undergo intramolecular nitrile oxide–olefin cycloaddition (INOC) to form medium to high yields (51–95%) of five-membered carbocycles 8 and 9 by using ethyl chloroformate in the presence of a catalytic amount of 4-dimethylaminopyridine (DMAP). High yields (91%) of tricyclic compounds 11 and 12 were obtained when 1a reacted with the anion of 10 under similar experimental conditions and procedures.
Part 2
One-Pot Synthesis of Five-membered Cyclic Ethers via intramolecular Nitrile Oxide-Olefin Cycloaddition (INOC) or Intramolecular Alkoxycarbonyl Nitronate-Olefin Cycloaddition (IAOC) by the Use of Methyl Chloroformate
Reaction of β-nitrostyrenes 6 with allyl alcohol and base generated nitronate 7, which can be converted into methoxycarbonyl nitronates 12 by treating the solution with methyl chloroformate and catalytic amount of 4-dimethylaminopyridine (DMAP) in the presence of different amounts of triethylamine. Intermediates 12 can ethier undergo intramolecular alkoxycarbonyl nitronate-olefin cycloaddition (IAOC) to generate highly stereoselective product trans-4 or undergo INOC to yield trans-4 and cis-4. The application of this improved methodology to synthesize different heterocyclic products 16 and 17 is reported.
Part 3
Triethylaluminum–Induced Free-Radical Reactions of Alkyl Iodides and β-Nitrostyrenes
Reactions of (E)-β-nitrostyrenes 1 with triethylaluminum Et3Al 2 and alkyl iodide RI 3, 4, or 5 in the presence of benzoyl peroxide in diethyl ether solution at room temperature give 60-100% of the different (E)- alkene 6, 7, or 8. Under similar conditions, 95% of 1-adamantyl-2-(4-methoxyphenyl)ethene 10 or 80% 1-(4-oxoadamantyl)-2-(4-methoxyphenyl)ethene 12 also can be easily prepared by using 1-iodoadamantane 9 or 5-iodo-2-adamantanone 11 and 2.
Part 4
Triethylaluminum- or Triethylborane– Induced Free Radical Reaction of Alkyl Iodides and α,β-Unsaturated Compounds
A series of α,β-unsaturated compounds 1a-c, 9, 13, and 17 were used as reactants in free radical conjugate addition reactions with different radicals generated from alkyl iodides such as 3, 4, or 5 in the presence of triethylborane–oxygen in air or via the use of triethylaluminum–benzoyl peroxide as a free radical initiator. When the reactions were carried out using triethylborane–air, the products, in most cases, were clean and were easily purified. However, higher yields of the 1,4-adducts and less side reactions occurred when less reactive substrates were used as a Michael acceptor in reactions with triethylaluminum-benzoyl peroxide and alkyl iodide under similar conditions. A mechanism for this type reaction is proposed in Scheme 1.

(1) (a) Kozikowski, A. P. Acc. Chem. Res. 1984, 17, 410. (b) Torssell, K. B. G. Nitrile Oxides, Nitrones and Nitronates in Organic Synthesis, VCH Publishers; New York, 1988. (c) Carmmella, P.; Grünanger, P. in 1,3-Dipolar Cycloaddition Chemistry, Vol. 1, ed. A. Padwa, Wiley, New York, 1984. (d) Grünanger, P.; Vita-Finzi, P. Isoxazoles Part 1, Vol. 49 of Chemistry of Heterocyclic Compounds, Wiley, New York, 1991 and references cited therein.
(2) (a) Mukaiyama, T.; Hoshino, T. J. Am. Chem. Soc. 1960, 82, 5339. (b) Maugein, N.; Wagner, A.; Mioskowski, C. Tetrahedron Lett. 1997, 38, 1547. (c) Basel, Y.; Hassner, A. Synthesis 1997, 309. (d) Kantorowski, E. J.; Brown, S. P.; Kurth, M. J. J. Org. Chem. 1998, 63, 5272.
(3) (a) Christl, M.; Huisgen, R. Chem. Ber. 1973, 106, 3275, 3345. (b) Liu, L.; Shelton, B.; Howe, R. K. J. Org. Chem. 1980, 45, 3916. (c) Kamaran, G.; Kulkarni, G. H. Tetrahedron Lett. 1994, 35, 5517. (d) Kamaran, G.; Kulkarni, G. H. Tetrahedron Lett.1994, 35, 9099. (e) Kamaran, G.; Kulkarni, G. H. J. Org. Chem. 1997, 62, 1516. (f) Weidner-Wells, M. A.; Fraga-Spano, S. A.; Turch, I. J. J. Org. Chem. 1998, 63, 6319.
(4) (a) Yao, C.-F.; Chen, W.-C.; Lin, Y.-M. Tetrahedron Lett. 1996, 37, 6339. (b) Yao, C.-F.; Kao, K.-H.; Liu, J.-T.; Chu, C.-M.; Wang, Y.; Chen, W.-C.; Lin, Y.-M.; Lin, W.-W.; Yan, M.-C.; Liu, J.-Y.; Chuang, M.-C.; Shiue, J.-L. Tetrahedron 1998, 54, 791. (c) Yao, C.-F.; Yang, C.-S.; Fang, H.-Y. Tetrahedron Lett. 1997, 38, 6419. (d) Kao, K.-H.; Yang, C.-S.; Liu, J.-T.; Lin, W.-W.; Fang, H.-Y.; Yao, C.-F.; Chen, K. Tetrahedron 1998, 54, 13997.
(5) (a) Harada, K.; Kaji, E.; Zen, S. Chem. Pharm. Bull. 1980, 28, 3296; (b) Shimizu, T.; Hayashi, Y.; Shibafuchi, H.; Teramura, K. Bull. Chem. Soc. Jpn. 1986, 59, 2827.
(6) Full crystallographic details, excluding structure factor tables, have been deposited at the Cambridge Crystallographic Data Centre (CCDC). For details of the deposition scheme, see ‘Instructions for Authors’, J. Chem. Soc. Perkin Trans. 1 available via the RSC Web page (http//www.rsc.org/authors). Any request to the CCDC for this material should quote the full literature citation and the reference number 207/308.
Paper 8/09490J
(1) (a) Corey, E. J.; Esteicher, H. J. Am. Chem. Soc. 1978, 100, 6294. (b) Seebach, D.; Colvin, E. W.; Well, T. Chimia 1979, 33, 1. (c) Barrett, A. G. M.; Graboski, G. G. Chem. Rev. 1986, 86, 751. (d) Rosini, G.; Ballini, R. Synthesis 1988, 833. (e) Several articals in tetrahedron Symposia-in Print 41, “Nitroalkanes and Nitroalkenes in Synthesis”, Tetrahedron 1990, 46 (21), Barrett, A. G. M. Ed. (f) Barrett, A. G. M. Chem. Soc. Rev. 1991, 20, 95.
(2) (a) Kozikowski, A. P.; Acc. Chem. Res. 1984, 17, 410. (b) Torsell, K. B. G. Nitrile Oxides, Nitrones and Nitronates in Organic Synthesis. VCH; New York, 1988. (c) Dehaen, W.; Hassner, A. Tetrahedron Lett. 1990, 31, 743. (d) Hassner, A.;Dehaen, W. J. Org. Chem. 1990, 55, 5505. (e) Gottlieb, L.;Hassner, A. J. Org. Chem. 1995, 60, 3759. (f) Narayanan Namboothiri, I. N.; Hassner, A.; Gottlieb, H. E. J. Org. Chem. 1997, 62, 485. (g) Young, D. G. J.; Gomez-Bengoa, E.; Hoveyda, A. H. J. Org. Chem. 1999, 64, 692.
(3) Mukaiyama, T.; Hoshino, T. J. Am. Chem. Soc. 1960, 82, 5339.
(4) (a) Kumaran, G.; Kulkarni, G. H. Tetrahedron Lett. 1994, 35, 5517. (b) Kumaran, G.; Kulkarni, G. H. Tetrahedron Lett. 1994, 35, 9099. (c) Yao. C.-F.; Chen, W.-C.; Lin, Y.-M. Tetrahedron Lett. 1996, 37, 6339. (d) Kumaran, G.; Kulkarni, G. H. J. Org. Chem. 1997, 62, 1516. (e) Yao, C.-F.; Yang, C.-S.; Fang, H.-Y. Tetrahedron Lett. 1997, 38, 6419. (f) Yao, C.-F.; Kao, K.-H.; Liu, J.-T.; Chu, C.-M.; Wang, Y.; Chen, W.-C.; Kao, K.-H.; Yang, C.-S.; Liu, J.-T.; Lin, W.-W.; Fang, H.-Y.; Yao, C.-F.; Chen, K. Tetrahedron 1998, 54, 13997.
(5) (a) Padwa, A. In 1,3-Dipolar Cycloaddition Chemistry; Padwa, A.; Ed. Wiley-Intersceince; New York, 1984; Vol. 2. (b) Curran, D. P. Advances in Cycloaddition; Vol. 1, JAI Press; Greenwich, CT, 1988; p 129-189.
(6) (a) Grigg. R. Chem. Soc. Rev. 1987, 16, 89. (b) Hassner, A.; Maurya, R.; Mesko, E. Tetrahedron Lett. 1988, 29, 5313. (c) Hassner, A.; Maurya, R. Tetrahedron Lett. 1989, 30, 5803. (d) Grigg, R.; Markandu, J.; Perrior, T.; Surendrakumar, S.; Warnock, W. J. Tetrahedron Lett. 1990, 31, 559. (e) Hassner, A.; Maurya, R.; Padwa, A.; Bullock, W. H. J. Org. Chem. 1991, 56, 2775.
(7) (a) Just. G.; Dahl, K. Tetrahedron 1968, 24, 5251. (b) Rai, K. M. L.; Linganna, N.; Hassner, A.; Murthy, C. A. Org. Prep. Proced. Int. 1992, 24, 91.
(8) (a) Grundmann, C.; Dean, J. M. J. Org. Chem. 1965, 30, 2809. (b) Hassner, H.; Rai, K. M. L. Synthesis 1989, 57. (c) Kim, J. N.; Ryu, E. K. Synth. Commun. 1990, 20, 1373.
(9) Shimizu, T.; Hayashi, Y.; Shibafuchi, H.; Teramura, K. Bull. Chem. Soc. Jpn. 1986, 59, 2827.
(10) (a) Liu, J.-Y.; Yan, M. C.; Lin, W.-W.; Wang, L.-Y.; Yao, C.-F. J. C. S. Perkin Trans. 1 1999, 1215. (b) Liu, J.-T.; Lin, W.-W.; Jang, J.-J.; Liu, J. Y.; Yan, M. C.; Hung, C.; Kao, K.-H.; Wang, Y.; Yao, C.-F. Tetrahedron. 1999, 55, 7115.
(11) (a) Padwa, A.; Chiacchio, U.; Dean, D. C.; Schoffstall, A. M.; Hassner, A.; Murthy, K. S. K. Tetrahedron Lett. 1988, 29, 4169. (b) Hassner, A.; Murthy, K. S. K.; Padwa, A.; Chiacchio, U.; Dean, D. C.; Schoffstall, M. J. Org. Chem. 1989, 54, 5277.
(12) (a) Hassner, A.; Dehaen, W. Chem. Ber. 1991, 124, 1181. (b) Kim, H. R.; Kim, H. J.; Duffy, J. L.; Olmstead, M. M.; Ruhlandt-Senge, K.; Kurth, M. J. Tetrahedron Lett. 1991, 32, 4259.
(13) Kantorowski, E. J.; Brown, S. P.; Kurth, M. J. J. Org. Chem. 1998, 63, 5272.
(14) Hassner, A.; Friedman, O.; Dehaen, W. Liebigs Ann. 1997, 587.
(15) Brown, R. K.; Raimondi, L.; Wu, Y.-D.; Houk, K. N. Tetrahedron Lett. 1992, 31, 4405.
(16) Hofle, G.; Steglich, w.; Vorbruggen, H. Angew. Chem. Int. Ed. Engl. 1978, 17, 569.
(17) Bordwell, F. G.; Garbisch, JR. E. W. J. Org. Chem. 1962, 27, 3049.
(18) Bourguignon, J.; Nard, G. L.; Queguiner, G. Can. J. Chem. 1985, 63, 2354.
(1) (a) Corey, E. J.; Estreicher, H. J. Am. Chem. Soc. 1978, 100, 6294. (b) Seebach, D.; Colvin, E. W.; Weller, T. Chimia 1979, 33, 1. (c) Barrett, A. G. M.; Graboski, G. G. Chem. Rev. 1986, 86, 751. (d) Rosini, G.; Ballini, R. Synthesis 1988, 833. (e) Several articles in Tetrahedron Symposia-in-Print 41, “Nitroalkanes and Nitroalkenes in Synthesis”, Tetrahedron 1990, 46 (21), Barrett, A. G. M. Ed. (f) Barrett, A. G. M. Chem. Soc. Rev. 1991, 20, 95.
(2) (a) Seebach, D.; Schafer, H.; Schmidt, B.; Schreiber, M. Angew. Chem., Int. Ed. Engl. 1992, 31, 1587. (b) Hu, Y.; Yu, J.; Yang, S.; Wang, J.-X.; Yin, Y. Synlett. 1998, 1213. (c) Hu, Y.; Yu, J.; Yang , S.; Wang, J.-X.; Yin, Y. Synth. Commun. 1999, 29, 1157.
(3) Russell, G. A.; Yao, C.-F. Heteroatom Chem. 1992, 3, 209.
(4) Namboothiri, I. N. N.; Hassner, A. J. Organomet. Chem. 1996, 518, 69.
(5) Han, Y.; Huang, Y.-Z.; Zhou, C.-M. Tetrahedron Lett. 1996, 37, 3347.
(6) Yao, C.-F.; Chu, C.-M.; Liu, J.-T. J. Org. Chem. 1998, 63, 719.
(7) (a) Kohler, E. P.; Stone, J. R. J. Am. Chem. Soc. 1930, 52, 761. (b) Buckley, G. D. J. Chem. Soc. 1947, 1494. (c) Buckley, G. D.; Ellery, E. J. J. Chem. Soc. 1947, 1497. (c) Ashwood, M. S.; Bell, L. A.; Houghton, P. G.; Wright, S. H. B. Synthesis 1988, 379. (d) Yao, C.-F.; Chen, W.-W.; Lin, Y.-M. Tetrahedron Lett. 1996, 37, 6399. (e) Yao, C.-F.; Kao, K.-H.; Liu, J.-T.; Chu, C.-M.; Wang, Y.; Chen, W.-C.; Lin, Y.-M.; Lin, W.-W.; Yan, M.-C.; Liu, J.-Y.; Chuang, M.-C.; Shiue, J.-L. Tetrahedron 1998, 54, 791. (f) Liu, J.-T.; Lin, W.-W.; Jang, J.-J.; Liu, J.-Y.; Yan, M.-C.; Hung, C.; Kao, K.-H.; Wang, Y.; Yao, C.-F. Tetrahedron 1999, 55, 7115.
(8) (a) Pecunioso, A.; Menicagli, R. Tetrahedron 1987, 43, 5411. (b) Pecunioso, A.; Menicagli, R. J. Org. Chem. 1988, 53, 45. (c) Pecunioso, A.; Menicagli, R. J. Org. Chem. 1989, 54, 2391.
(9) (a) Chu, C.-M.; Liu, J.-T.; Lin, W.-W.; Yao, C.-F. J. Chem. Soc. Perkin Trans. 1, 1999, 47. (b) Maruoka, K.; Sano, H.; Fukutani, Y.; Yamamoto, H. Chem. Lett. 1985,1689.
(10) Smadja, W. Synlett. 1994, 1.
(11) (a) Suzuki, A.; Nozawa, S.; Harada, M.; Itoh, M.; Brown, H. C.; Midland, M. M. J. Am. Chem. Soc. 1971, 93, 1508. (b) Nozaki, K.; Oshima, K.; Utimoto, K. J. Am. Chem. Soc. 1987, 109, 2547. (c) Nozaki, K.; Oshima, K.; Utimoto, K. Tetrahedron Lett. 1988, 29, 1041. (d) Bertrand, M. P.; Feray, L.; Nouguier, R.; Perfetti, P. J. Org. Chem. 1999, 64, 9189. (e) Miyabe, H.; Ushiro, C.; Ueda, M.; Yamakawa, K.; Naito, T. J. Org. Chem. 2000, 65, 176. (f) Wu, B.; Avery, B. A.; Avery, M. A. Tetrahedron Lett. 2000, 41, 3797. (g) Miyabe, H.; Ueda, M.; Naito, T. J. Org. Chem. 2000, 65, 5043. (h) Miyabe, H.; Fujii, K.; Goto, T.; Naito, T. Org. Lett. 2000, 2, 4071. (i) Yorimitsu, H.; Nakamura, T.; Shinokubo, H.; Oshima, K.; Omoto, K.; Fujimoto, H. J. Am. Chem. Soc. 2000, 122, 11041.
(12) Ryu, I.; Araki, F.; Minakata, S.; Komatsu, M. Tetrahedron Lett. 1998, 39, 6335.
(13) (a) Tashtoush, H. I.; Sustmann, R. Chem. Ber. 1992, 125, 287. (b) Tashtoush, H. I.; Sustmann, R. Chem. Ber. 1993, 126, 1759.
(14) Bräse S.; Waegell, B.; de Meijere, A. Synthesis 1998, 148.
(15) Yamataka, H.; Takatsuka, T.; Hanafusa, T. J. Org. Chem. 1996, 61, 722.
(16) (a) Geluk, H. W. Synthesis 1972, 374. (b) Adcock, W.; Trout, N. A. J. Org. Chem. 1991, 56, 3229.
(17) Buss, A. D.; Warren, S. J. Chem. Soc. Perkin Trans. 1 1985, 2307. (b) Kawashima, T.; Ishii, T.; Inamoto, N. Bull. Chem. Soc. Jpn. 1987, 60, 1831. (c) Cahiez, G.; Avedissian, H. Synthesis 1998, 1199.
(18) Barton, D. H. R.; Togo, H.; Zard, S. Z. Tetrahedron 1985, 41, 5507.
(19) (a) Hoshi, M.; Masuda, Y.; Arase, A. Bull. Chem. Soc. Jpn. 1986, 59, 3985. (b) Baudin, J. B.; Hareau, G.; Julia, S. A.; Lorne, R.; Ruel, O. Bull. Soc. Chim. Fr. 1993, 130, 856. (c) Vedejs, E.; Fleck, T. J. J. Am. Chem. Soc. 1989, 111, 5861. (d) Shen, Y.; Yao, J. J. Chem. Research (S) 1996, 394. (e) Xiang, J.; Jiang, W.; Gong, J.; Fuchs, P. L. J. Am. Chem. Soc. 1997, 119, 4123.
(20) Alesso, E. N.; Tombari, D. G.; Moltrasio, G. Y.; Aguirre, J. M. Can. J. Chem. 1987, 65, 2568.
(21) Kashihara, H.; Suemune, H.; Tsunehiro, N.; Sakai, K. Chem. Pharm. Bull. 1990, 38, 2581.
(22) (a) Cahiez, G.; Avedissian, H. Synthesis 1998, 1199. (b) Yuan, T.-M.; Luh, T.-Y. J. Org. Chem. 1992, 57, 4550. (c) Kirmse, W.; Konrad, W.; Schnitzler, D. J. Org. Chem. 1994, 59, 3821. (d) Ishino, Y.; Mihara, M.; Nishihama, S.; Nishiguchi, I. Bull. Chem. Soc. Jpn. 1998, 71, 2669.
(23) (a) Baudin, J. B.; Hareau, G.; Julia, S. A,; Lorne, R.; Ruel, O. Bull. Soc. Chim. Fr. 1993, 130, 856.