三酮烯烃是一种高度缺电子的不饱和羰基化合物,也是一种重要的合成砌块。在之前的研究中,由于电子效应和空间效应,三酮烯烃通常发生β-选择性的共轭加成或环加成反应。实现三酮烯烃的反常区域选择性共轭加成或环加成反应具有挑战性。我们在前期的工作基础上实现了三酮烯烃与硝酮反常区域选择性[3 + 2]环加成反应,在无催化剂的条件下高效、高立体选择性的合成出一系列异噁唑烷类化合物,收率最高达到95%,非对映选择性达到20:1. 该方法具有绿色环保、操作简便、底物适用范围广的优点,为异噁唑烷类化合物的合成提供了参考. DFT计算显示这种反常的区域选择性环加成反应在能量上是有利的.
Triketone alkenes represent a class of highly electron-deficient unsaturated carbonyl compounds and serve as important and versatile synthetic building blocks. In previous work, triketone enones usually undergo β-selective conjugate addition or cycloaddition. It is challenging to achieve regio-reversed conjugate addition or cycloaddition of triketone enones. Based on our previous work, here, we achieved regio-reversed [3 + 2] cycloaddition of triketone enones with nitrones, and synthesized a series of isoxazolidines effectively and stereoselectively under catalyst-free conditions, up to 95% yield and 20:1 dr. It has the advantages of being green, easy to operate, and having a wide range of substrates, providing a reference for the synthesis of isoxazolidines. DFT study revealed that this regio-reversed [3 + 2] cycloaddition is energetically favorable.
[1] Zhang S.; Neumann H.; Beller M. Chem. Soc. Rev. 2020, 49, 3187-3210.
[2] Wang Z.; Wang C.Green Synth. Catal. 2021, 2, 66-69.
[3] Li X.; Liao J.; Zhuo X.; Wang H.; Chai X.; Zou Y.; Zhao Q.Green Synth. Catal. 2023, 4 , 54-57.
[4] Shen G.; He F.; Yang X.Green Synth. Catal. 2024.
(doi: 10.oi: 10.1016/j.gresc.2024.10.003)
[5] Ren S. C.; Zhang F. L.; Xu A. Q.; Yang Y.; Zheng M.; Zhou X.; Fu Y.; Wang Y. F. Nat. Commun. 2019, 10, 1934.
[6] Zhou F.; Zhu S. ACS Catal. 2021, 11, 8766-8773.
[7] Chen P.; Tan S. Z.; Zhu L.; Ouyang Q.; Jia Z. J.; Du W.; Chen Y. C. Angew. Chem. Int.Ed. 2023, e202301519.
[8] Xu J.; Song Y.; Yang J.; Yang B.; Su Z.; Lin L.; Feng X. Angew. Chem. Int. Ed. 2023, 62, e202217887.
[9] Xiang B.; Wang Y.; Xiao C.; He F.; Huang Y. Chin. Chem. Lett. 2024, 35, 108777.
[10] He C.; Tang X.; He X.; Zhou Y.; Liu X.; Feng X. Chin. Chem. Lett. 2023, 34, 107487.
[11] Liu X.; Kou Y.; Wu H.; Liu T.-X.; Liu Q.; Zhang Z.; Zhang X.; Zhang G. Sci. Adv.2025, 11, eadt2715.
[12] Shu W.-M.; Yang Y.; Zhang D.-X.; Wu L.-M.; Zhu Y.-P.; Yin G.-D.; Wu A.-X. Org. Lett. 2013, 15, 456-459.
[13] Yang Y.; Gao M.; Wu L.-M.; Deng C.; Zhang D.-X.; Gao Y.; Zhu Y.-P.; Wu A.-X. Tetrahedron 2011, 67, 5142-5149.
[14] Gao M.; Yang Y.; Wu Y.-D.; Deng C.; Shu W.-M.; Zhang D.-X.; Cao L.-P.; She N.-F.; Wu A.-X. Org. Lett. 2010, 12, 4026-4029.
[15] Ma J.-R.; Shu W.-M.; Zheng K.-L.; Ni F.; Yin G.-D.; Wu, A.-X. Org. Biomol. Chem. 2015, 13, 4976-4980.
[16] Ni F.; Yang Y.; Shu W.-M.; Ma J.-R.; Wu, A.-X. Org. Biomol. Chem. 2014, 12, 9466-9470.
[17] Han T.-J.; Wang M.-C.; Mei G.-J. Chem. Commun. 2021, 57, 8921-8924.
[18] Fu Y.-D.; Gao X.; Jia S.-K.; Xiao X.; Wang M.-C.; Huang L.; Mei G.-J.Green Chem. 2023, 25, 5692-5697.
[19] Li X. L.; Wang Y. P.; Chen H.; Li Z. W.; Xing C. Y. Chin. J. Org.Chem., 2008, 28, 1750-1755(in Chinese).
(李小六; 王彦坡; 华, 陈.; 李志伟; 邢春勇, 有机化学 2008, 28, 1750-1755.)
[20] Li M.; Cao X.; You J.; Yu Y.; Wu W.; Liu B. Chin.J. Org. Chem., 2019, 39, 1642-1649(in Chinese).
(李明龙, 曹., 由君, 喻艳超, 武文菊, 刘波, 有机化学 2019, 39, 1642-1649.)
[21] Liu X.; Li M.;, You J.; Liu B. Chin. J. Org. Chem., 2017, 37, 86-91(in Chinese).
(刘迅绅, 李., 由君, 刘波, 有机化学 2017, 37, 86-91.)
[22] a) Li, M.-F.; Shi, S.-Q.; Xu, T.; Zhang, Q.; Hao, W.-J.; Wang, S.-L.; Wang, J.; Tu, S.-J.; Jiang, B. Chin. Chem. Lett. 2023, 34, 107751.
b) Yu, L.; Xu, R.; Yao, Y. Y.; Lu, Y.; Liu, F. Y.; Tan, W.; Shi, F. J. Org. Chem., 2023, 88, 3474-3486.
[23] Murahashi S. I.; Imada Y. Chem.Rev. 2019, 119, 4684-4716.
[24] Hashimoto T.; Maruoka K. Chem.Rev. 2015, 115, 5366-5412.
[25] Stanley L. M.; Sibi M. P. Chem. Rev. 2008, 108, 2887-2902.
[26] Berthet M.; Cheviet T.; Dujardin G.; Parrot I.; Martinez J. Chem.Rev. 2016, 116, 15235-15283.
[27] Cornil J.; Gonnard L.; Bensoussan C.; Serra-Muns, A.; Gnamm, C.; Commandeur, C.; Commandeur, M.; Reymond, S.; Guérinot, A.; Cossy, J. Acc. Chem. Res. 2015, 48, 761-773.
[28] Tyrrell E.; Allen J.; Jones K.; Beauchet R. Synthesis 2005, 2393-2399.
[29] Gao M.; Yang Y.; Wu Y. D.; Deng C.; Cao L. P.; Meng X.-G.; Wu A.-X. Org. Lett. 2010, 12, 1856-1859.
[30] Zhao Y.; Truhlar D. G. Theor. Chem. Acc., 2008, 120, 215-241.
[31] (a) Hariharan, P. C.; Pople, J. A. Theor. Chim. Acta., 1973, 28, 213-222.
(b) Francl, M. M.; Pietro, W. J.; Hehre, W. J.; Binkley, J. S.; Gordon, M. S.; DeFrees, D. J.; Pople, J. A. J. Chem. Phys., 1982, 77, 3654-3665.
[32] McLean, A. D.; Chandler, G. S. J. Chem. Phys., 1980, 72, 5639.
[33] Mennucci B.; Tomasi J. J. Chem. Phys., 1997, 106, 5151-5158.
[34] Legault C. Y.;CYL view, 1.0b; Université de Sherbrooke, 2009.
