HOMO活化的2-吡喃酮与2,5-二烯酮反电子需求的不对称Diels-Alder反应
收稿日期: 2018-04-05
网络出版日期: 2018-05-09
基金资助
国家自然科学基金（No.21772126）和四川大学优秀青年学者科研基金（No.2017SCU04A15）资助项目.
Asymmetric Inverse-Electron-Demand Diels-Alder Reaction of 2-Pyrone and 2,5-Dienones via HOMO-Activation
Received date: 2018-04-05
Online published: 2018-05-09
Supported by
Project supported by the National Natural Science Foundation of China (No. 21772126) and Sichuan University Distinguished Young Scientist Program (No. 2017SCU04A15).
2-吡喃酮的不对称Diels-Alder（DA）反应可以高效、高立体选择性地构建多官能团化的双环内酯手性骨架.目前贫电子的2-吡喃酮多依赖于手性Lewis酸通过降低LUMO能量与富电子烯烃发生反电子需求环加成反应，活化机制相对单一，因此发展新的活化模式合成此类骨架尤为重要.报道了在金鸡纳碱衍生的伯胺作用下，环状2，5-二烯酮能形成延伸型三烯胺中间体，从而活化远端δ，e-双键，与3-甲氧羰基-2-吡喃酮发生反电子需求不对称DA反应.该方法能够以中等到良好的收率（46%～82%）、优异立体选择性（93%～99%ee，>19∶1 dr）高效构建含有多个连续手性中心的双环内酯化合物.通过内酯醇解开环，能高收率进一步转化为手性环己烯醇化合物.我们发展的经HOMO活化的不对称反电子需求DA反应可以为构建手性双环内酯骨架提供一种较为实用的新方法.
关键词： 三烯胺; 不对称催化; 反电子需求Diels-Alder反应; 双环内酯化合物; HOMO活化
周远春 , 周志 , 杜玮 , 陈应春 . HOMO活化的2-吡喃酮与2,5-二烯酮反电子需求的不对称Diels-Alder反应[J]. 化学学报, 2018 , 76(5) : 382 -386 . DOI: 10.6023/A18040131
The bicyclic lactones possess multiple reactive sites, and are usually employed as the key intermediates in the synthesis of natural products and bioactive substances. Among the methods for the construction of these chiral skeletons, the asymmetric Diels-Alder (DA) reaction with 2-pyrone substrates represents one of the most straightforward protocols, generally with high stereocontrol. However, in regard to the electron-deficient 2-pyrone substrates, the corresponding asymmetric DA reactions usually rely on LUMO-activation by chiral Lewis acids, suffering from relatively narrow substitutions and functional group limitations. As a result, the development of new activation modes for this type of DA reactions is in high demand. Here we report an asymmetric inverse-electron-demand Diels-Alder (IEDDA) reaction of 3-methoxycarbonyl-2-pyrone and cyclic 2,5-dienones in the presence of a primary amine derived from cinchona alkaloid, through the in situ generation of extended trienamine species. In this case, the remote δ,e-C=C bond of 2,5-dienone substrates is activated via a HOMO-raising strategy. A variety of bicyclic lactones with contiguous stereogenic centers were produced in moderate to good yields (46%~82%) with excellent diastereo-and enantioselectivity (>19:1 dr, 93%~99% ee). In addition, the cycloadduct underwent the ring-opening reaction with methanol, affording a cyclohexenol derivative with dense substitutions in an excellent yield with a retained ee value. Therefore, the current method supplies an efficient tool to construct chiral bicyclic lactones with high molecular complexity under mild aminocatalytic conditions, which might have potential application in organic synthesis and medicinal chemistry. A representative procedure for the asymmetric IEDDA reaction is as follows:3-Methoxycarbonyl-2-pyrone 1 (0.1 mmol), cyclic 2,5-dienone 2 (0.2 mmol), amine catalyst C2 (0.02 mmol) and acid A4 (0.04 mmol) were added into an oven-dried vial equipped with a magnetic stirbar. p-Xylene (1.0 mL) was added and the mixture was stirred at 60℃ and monitored by TLC. After completion, the residue was purified by flash chromatography on silica gel eluting with petroleum ether/ethyl acetate (8:1 to 4:1) to afford the product 3.
[1] (a) Luxenburger, A. Tetrahedron 2003, 59, 3297.
(b) Huang, C.; Li, W.; Ma, F.; Li, Q.; Asada, Y.; Koike, K. Chem. Pharm. Bull. 2012, 60, 1324.
[2] (a) Posner, G. H.; Ishihara, Y. Tetrahedron Lett. 1994, 35, 7545.
(b) Nicolaou, K. C.; Liu, J. J.; Yang, Z.; Ueno, H.; Sorensen, E. J.; Claiborne, C. F.; Guy, R. K.; Hwang, C. K.; Nakada, M.; Nantermet, P. G. J. Am. Chem. Soc. 1995, 117, 634.
(c) Stigers, K. D.; Mar-Tang, R.; Bartlett, P. A. J. Org. Chem. 1999, 64, 8409.
(d) Burch, P.; Binaghi, M.; Scherer, M.; Wentzel, C.; Bossert, D.; Eberhardt, L.; Neuburger, M.; Scheiffele, P.; Gademann, K. Chem. Eur. J. 2013, 19, 2589.
(e) Zhao, Y. M.; Maimone, T. J. Angew. Chem., Int. Ed. 2015, 54, 1223.
(f) Shimizu, H.; Okamura, H.; Iwagawa, T.; Nakatani, M. Tetrahedron 2001, 57, 1903.
(g) Lee, J.-H.; Cho, C.-G. Org. Lett. 2016, 18, 5126.
[3] (a) Afarinkia, K.; Vinader, V.; Nelson, T. D.; Posner, G. H. Tetrahedron 1992, 48, 9111.
(b) Corey, E. J. Angew. Chem., Int. Ed. 2002, 41, 1650.
(c) Heravi, M. M.; Vavsari, V. F. RSC Adv. 2015, 5, 50890.
[4] (a) Wang, Y.; Li, H.; Wang, Y.-Q.; Liu, Y.; Foxman, B. M.; Deng, L. J. Am. Chem. Soc. 2007, 129, 6364.
(b) Singh, R. P.; Bartelson, K.; Wang, Y.; Su, H.; Lu, X.; Deng, L. J. Am. Chem. Soc. 2008, 130, 2422.
(c) Bartelson, K. J.; Singh, R. P.; Foxman, B. M.; Deng, L. Chem. Sci. 2011, 2, 1940.
[5] Soh, J. Y.-T.; Tan, C.-H. J. Am. Chem. Soc. 2009, 131, 6904.
[6] Shi, L.-M.; Dong, W.-W.; Tao, H.-Y.; Dong, X.-Q.; Wang, C.-J. Org. Lett. 2017, 19, 4532.
[7] For a comprehensive review, see:Jiang, X.; Wang, R. Chem. Rev. 2013, 113, 5515.
[8] (a) Markó, I. E.; Evans, G. R. Tetrahedron Lett. 1994, 35, 2771.
(b) Markó, I. E.; Evans, G. R.; Declercq, J.-P. Tetrahedron 1994, 50, 4557.
(c) Posner, G. H.; Carry, J.-C.; Kyoo Lee, J.; Bull, D. S.; Dai, H. Tetrahedron Lett. 1994, 35, 1321.
(d) Posner, G. H.; Eydoux, F.; Lee, J. K.; Bull, D. S. Tetrahedron Lett. 1994, 35, 7541.
[9] For a review, see:Li, J.-L.; Liu, T.-Y.; Chen, Y.-C. Acc. Chem. Res. 2012, 45, 1491.
[10] (a) Ramachary, D. B.; Reddy, Y. V. Eur. J. Org. Chem. 2012, 2012, 865.
(b) Kano, T.; Maruoka, K. Chem. Sci. 2013, 4, 907;
(d) Duan, J.; Li, P. Catal. Sci. Technol. 2014, 4, 311.
(c) Donslund, B. S.; Johansen, T. K.; Poulsen, P. H.; Halskov, K. S.; Jørgensen, K. A. Angew. Chem., Int. Ed. 2015, 54, 13860.
(d) Reddy, U. V. S.; Chennapuram, M.; Seki, C.; Kwon, E.; Okuyama, Y.; Nakano, H. Eur. J. Org. Chem. 2016, 2016, 4124.
(d) Jiang, K.; Chen, Y. Prog. Chem. 2015, 27, 137. (蒋坤, 陈应春, 化学进展, 2015, 27, 137.)
[11] (a) Feng, X.; Zhou, Z.; Ma, C.; Yin, X.; Li, R.; Dong, L.; Chen, Y.-C. Angew. Chem., Int. Ed. 2013, 52, 14173.
(b) Feng, X.; Zhou, Z.; Yin, X.; Li, R.; Chen, Y.-C. Eur. J. Org. Chem. 2014, 2014, 5906.
(c) Zhou, Z.; Feng, X.; Yin, X.; Chen, Y.-C. Org. Lett. 2014, 16, 2370.
(d) Wei, X.-Z.; Zhou, Z.; Du, W. Chin. J. Synth. Chem. 2016, 7, 565. (韦学振, 周志, 杜玮, 合成化学, 2016, 7, 565.)
[12] For other examples, see:
(a) Chen, P.-Q.; Xiao, Y.-C.; Yue, C.-Z.; Chen, Y.-C. Org. Chem. Front. 2014, 1, 490.
(b) Zhan, G.; He, Q.; Yuan, X.; Chen, Y.-C. Org. Lett. 2014, 16, 6000.
(c) Shi, M.-L.; Zhan, G.; Zhou, S.-L.; Du, W.; Chen, Y.-C. Org. Lett. 2016, 18, 6480.
(d) He, X.-L.; Zhao, H.-R.; Duan, C.-Q.; Du, W.; Chen, Y.-C. Org. Lett. 2018, 20, 804.
(e) Prieto, L.; Talavera, G.; Uria, U.; Reyes, E.; Vicario, J. L.; Carrillo, L. Chem. Eur. J. 2014, 20, 2145.
[13] For a review, see:Melchiorre, P. Angew. Chem., Int. Ed. 2012, 51, 9748.
[14] For a review of additive effect, see:Hong, L.; Sun, W.; Yang, D.; Li, G.; Wang, R. Chem. Rev. 2016, 116, 4006.
[15] For more details, see the Supporting Information.
[16] CCDC-1834913(3g) contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from the Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif
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