Dearomatization of Halonaphthols via an Intermolecular [4＋1] Spiroannulation with in situ Formed Aza-ortho-quinone Methides

doi:10.6023/cjoc202303029

Abstract

A base promoted dearomatization strategy for [4＋1] spiroannulation of halonaphthols with N-(o-chloromethyl) aryl amides is reported, which is used to efficiently synthesize azaspirocycles. A range of azaspirocycles were obtained in satisfactory to excellent yield with high diastereoselectivity under mild conditions. Variety functional groups including aldehyde and free hydroxyl group, and different N-protecting groups, such as Bz and Ts are compatibility. The transformation of the product and a possible mechanism were also provided.

Key words: azaspirocyclic compound, [4＋1] cycloaddition reaction, dearomatization, spiroannulation

Cite this article

Junxiu Liang, Yazhou Liu, Amu Wang, Yanchao Wu, Xiaofeng Ma, Huijing Li. Dearomatization of Halonaphthols via an Intermolecular [4＋1] Spiroannulation with in situ Formed Aza-ortho-quinone Methides[J]. Chinese Journal of Organic Chemistry, 2023, 43(11): 3888-3899.

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Fig. & Tab. 9

Figure 1. Representative molecules containing azaspirocycles

Figure 2. Construction of azaspirocycles by dearomatization

Entry	Base	Solvent	T/℃	Yield^b/%
1	Cs₂CO₃	DCE	25	83
2	MeONa	DCE	25	60
3	K₂CO₃	DCE	25	93 (92)
4	DBU	DCE	25	0
5	DIPEA	DCE	25	0
6	K₂CO₃	DCM	25	85
7	K₂CO₃	THF	25	82
8	K₂CO₃	DMF	25	0
9	K₂CO₃	Toluene	25	90
10	K₂CO₃	DCE	40	92
11	K₂CO₃	DCE	50	92
12	K₂CO₃	DCE	10	90

Table 1. Optimization of the reaction conditionsa

Scheme 1. Scope of o-chloromethylanilines

Scheme 2. Scope of 1-halo-2-naphthols

Scheme 3. Gram-scale reaction and synthetic applications

Scheme 4. Control experiments and proposed mechanism

Scheme 5. Synthesis of compound 1

Scheme 6. Synthesis of compound 2

References 22

[1]	(a) Zhao, Y.; Xia, W. Chem. Soc. Rev. 2018, 47, 2591. doi: 10.1039/C7CS00572E
	(b) Ju, M.; Schomaker, J. M. Nat. Rev. Chem. 2021, 5, 580. doi: 10.1038/s41570-021-00291-4
[2]	(a) Powell, R. G.; Weisleder, D.; Smith, C. R. J. Pharm. Sci. 1972, 61, 1227. doi: 10.1002/jps.2600610812
	(b) Iizuka, H.; Irie, H.; Masaki, N.; Osaki, K.; Uyeo, S. J. Chem. Soc., Chem. Commun. 1973, 125.
	(c) Inubushi, Y.; Ishii, H.; Yasui, B.; Hashimoto, M.; Harayama, T. Chem. Pharm. Bull. 1968, 16, 82. doi: 10.1248/cpb.16.82
	(d) Zhang, Y.; Tice, C. M.; Singe, S. B. Bioorg. Med. Chem. Lett. 2014, 24, 3673. doi: 10.1016/j.bmcl.2014.06.081
[3]	(a) Dou, Q.; Tu, Y.; Zhang, Y.; Tian, J.; Zhang, F.; Wang, S. Adv. Synth. Catal. 2016, 358, 874. doi: 10.1002/adsc.v358.6
	(b) Chen, S.; Ma, W.; Yan, Z.; Zhang, F.; Wang, S.; Tu, Y.; Zhang, X.; Tian, J. J. Am. Chem. Soc. 2018, 140, 10099. doi: 10.1021/jacs.8b05386
	(c) Yuan, Y.; Han, X.; Zhu, F.; Tian, J.; Zhang, F.; Zhang, X.; Tu, Y.; Wang, S.; Guo, X. Nat. Commun. 2019, 10, 3394. doi: 10.1038/s41467-019-11382-8
	(d) Jing, Z.; Liang, D.; Tian, J.; Zhang, F.; Tu, Y. Org. Lett. 2021, 23, 1258. doi: 10.1021/acs.orglett.0c04241
[4]	(a) Zheng, Y.; Tice, C. M.; Singh, S. B. Bioorg. Med. Chem. Lett. 2014, 24, 3673. doi: 10.1016/j.bmcl.2014.06.081 pmid: 33381970
	(b) Hiesinger, K.; Dar'in, D.; Proschak, E.; Krasavin, M. J. Med. Chem. 2021, 64, 150. doi: 10.1021/acs.jmedchem.0c01473 pmid: 33381970
	(c) Yanagimoto, A.; Uwabe, Y.; Wu, Q.; Muto, K.; Yamaguchi, J. ACS Catal. 2021, 11, 10429. doi: 10.1021/acscatal.1c02627 pmid: 33381970
[5]	(a) Shin, K.; Kim, H.; Chang, S. Acc. Chem. Res. 2015, 48, 1040. doi: 10.1021/acs.accounts.5b00020 pmid: 31072095
	(b) Zheng, C.; You, S. Chem 2016, 1, 830. doi: 10.1016/j.chempr.2016.11.005 pmid: 31072095
	(c) Adams, K.; Ball, A. K.; Sweeney, J. B. Nat. Chem. 2017, 9, 396. doi: 10.1038/nchem.2670 pmid: 31072095
	(d) Wertjes, W. C.; Southgate, E. H.; Sarlah, D. Chem. Soc. Rev. 2018, 47, 7996. doi: 10.1039/C8CS00389K pmid: 31072095
	(e) Wang, Y.; Bode, J. W. J. Am. Chem. Soc. 2019, 141, 9739. doi: 10.1021/jacs.9b05074 pmid: 31072095
	(f) Saito, F.; Trapp, N.; Bode, J. W. J. Am. Chem. Soc. 2019, 141, 5544. doi: 10.1021/jacs.9b01537 pmid: 31072095
	(g) Flodén, N. J.; Trowbridge, A.; Willcox, D.; Walton, S. M.; Kim, Y.; Gaunt, M. J. J. Am. Chem. Soc. 2019, 141, 8426. doi: 10.1021/jacs.9b03372 pmid: 31072095
	(h) Shennan, B. D. A.; Smith, P. W.; Ogura, Y.; Dixon, D. J. Chem. Sci. 2020, 11, 10354. doi: 10.1039/D0SC03676E pmid: 31072095
	(i) Xia, Z.-L.; Xu-Xu, Q.-F.; Zheng, C.; You, S.-L. Chem. Soc. Rev. 2020, 49, 286. doi: 10.1039/C8CS00436F pmid: 31072095
	(j) Yang, W.; Zhang, M.; Feng, J. Adv. Synth. Catal. 2020, 362, 4446. doi: 10.1002/adsc.v362.21 pmid: 31072095
	(k) Zhang, C.; Bu, F.; Zeng, C.; Wang, D.; Lu, L.; Zhang, H.; Lei, A. CCS Chem. 2022, 4, 1199. doi: 10.31635/ccschem.021.202100860 pmid: 31072095
[6]	(a) Zhuo, C.; Zhang, W.; You, S. L. Angew. Chem., Int. Ed. 2012, 51, 12662. doi: 10.1002/anie.v51.51
	(b) Zhuo, C.; Liu, W.; Wu, Q.; You, S. L. Chem. Sci. 2012, 3, 205. doi: 10.1039/C1SC00517K
	(c) Zhuo, C.; Cheng, Q.; Liu, W.; Zhao, Q.; You, S. L. Angew. Chem., Int. Ed. 2015, 54, 8475. doi: 10.1002/anie.v54.29
	(d) Chen, J. B.; Jia, Y. X. Org. Biomol. Chem. 2017, 15, 3550. doi: 10.1039/C7OB00413C
	(e) Li, X.; Zhou, B.; Yang, R.; Yang, M.; Liang, X.; Liu, R.; Jia, Y, X. J. Am. Chem. Soc. 2018, 140, 13945. doi: 10.1021/jacs.8b09186
	(f) Liang, R. X.; Xu, D. Y.; Yang, F. M.; Jia, Y. X. Chem. Commun. 2019, 55, 7711. doi: 10.1039/C9CC03566D
[7]	(a) Ciufolini, M. A.; Braun, N. A.; Canesi, S.; Ousmer, M.; Chang, J.; Chai, D. Synthesis 2007, 3759.
	(b) Dohi, T.; Maruyama, A.; Minamitsuji, Y.; Takenaga, N.; Kita, Y. Chem. Commun. 2007, 1224.
	(c) Dohi, T.; Takenaga, N.; Fukushima, K.; Uchiyama, T.; Kato, D.; Motoo, S.; Fujioka, H.; Kita, Y. Chem. Commun. 2010, 46, 7697. doi: 10.1039/c0cc03213a
	(d) Palmer, L. I.; Read de Alaniz, J. Angew. Chem., Int. Ed. 2011, 50, 7167. doi: 10.1002/anie.v50.31
	(e) Xu, Z.; Xing, P.; Jiang, B. Org. Lett. 2017, 19, 1028. doi: 10.1021/acs.orglett.6b03853
	(f) Tang, W.; Cao, K.; Meng, S.; Zheng, W. Synthesis 2017, 49, 3670. doi: 10.1055/s-0036-1589040
	(g) Singh, F. V.; Kole, P. B.; Mangaonkar, S. R.; Shetgaonkar, S. E. Beilstein J. Org. Chem. 2018, 14, 1778. doi: 10.3762/bjoc.14.152
[8]	(a) Zhang, Z.; Song, X.; Zhang, G.; Liu, L. Chin. Chem. Lett. 2021, 32, 1423. doi: 10.1016/j.cclet.2020.11.001
	(b) Zhang, Z.; Cao, X.; Zhang, G.; Liu, L. Chin. Chem. Lett. 2023, 34, 107779. doi: 10.1016/j.cclet.2022.107779
[9]	(a) Kusama, H.; Uchiyama, K.; Yamashita, Y.; Narasaka, K. Chem. Lett. 1995, 24, 715. doi: 10.1246/cl.1995.715 pmid: 28953364
	(b) Tanaka, K.; Mori, Y.; Narasaka, K. Chem. Lett. 2004, 33, 26. doi: 10.1246/cl.2004.26 pmid: 28953364
	(c) Ma, X., Farndon, J. J.; Young, T. A.; Fey, N.; Bower, J. F. Angew. Chem., Int. Ed. 2017, 56, 14531. doi: 10.1002/anie.v56.46 pmid: 28953364
	(d) Farndon, J. J.; Ma, X.; Bower, J. F. J. Am. Chem. Soc. 2017, 139, 14005. doi: 10.1021/jacs.7b07830 pmid: 28953364
	(e) Zhang, C.; Bu, F.; Zeng, C.; Wang, D.; Lu, L.; Zhang, H.; Lei, A. CCS Chem. 2022, 4, 1199. doi: 10.31635/ccschem.021.202100860 pmid: 28953364
[10]	Ge, Y.; Qin, C.; Bai, L.; Hao, J.; Liu, J.; Luan, X. Angew. Chem., Int. Ed. 2020, 59, 18985. doi: 10.1002/anie.v59.43
[11]	(a) Yang, B. C.; Gao, S. H. Chem. Soc. Rev. 2018, 47, 7926. doi: 10.1039/C8CS00274F pmid: 28809505
	(b) Happy, S.; Junaid, M.; Yadagiri, D. Chem. Commun. 2023, 59, 29. doi: 10.1039/D2CC05623B pmid: 28809505
	(c) Hsiao, C. C.; Liao, H. H.; Rueping, M. Angew. Chem., Int. Ed. 2014, 53, 13258. doi: 10.1002/anie.v53.48 pmid: 28809505
	(d) Gebauer, K.; F. Reuß, F.; Spanka, M.; Schneider, C. Org. Lett. 2017, 19, 4588. doi: 10.1021/acs.orglett.7b02185 pmid: 28809505
	(e) Zhang, X.; Pan, Y.; Liang, P.; Ma, X.; Jiao, W.; Shao, H. W. Adv. Synth. Catal. 2019, 361, 5552. doi: 10.1002/adsc.v361.24 pmid: 28809505
	(f) Zhou, F.; Cheng, Y.; Liu, X. P.; Chen, J. R.; Xiao, W. J. Chem. Commun. 2019, 55, 3117. doi: 10.1039/C9CC00727J pmid: 28809505
[12]	(a) Jian, Y.; Liang, P.; Li, X.; Shao, H.; Ma, X. Org. Biomol. Chem. 2023, 21, 179. doi: 10.1039/D2OB01951E pmid: 35166547
	(b) Liang, P.; Zhao, H.; Zhou, T.; Zeng, K.; Jiao, W.; Pan, Y.; Liu, Y.; Fang, D.; Ma, X.; Shao, H. Adv. Synth. Catal. 2021, 363, 3532. doi: 10.1002/adsc.v363.14 pmid: 35166547
	(c) Wang, A.; Liu, Y.-Z.; Shen, Z.; Qiao, Z.; Ma, X. Org. Lett. 2022, 24, 1454. doi: 10.1021/acs.orglett.2c00035 pmid: 35166547
	(d) Ma, X.; Liu, Y.; Du, L.; Zhou, J.; Markó, I. E. Nat. Commun. 2020, 11, 914. doi: 10.1038/s41467-020-14522-7 pmid: 35166547
[13]	During our preparation of this manuscript, a similar process was disclosed in a patent, in which 2.5 equiv. of 1 and 4.0 equiv. of Na₂CO₃ were employed in toxic CH₃NO₂ to maintain high yield with limited functional group tolerance, see: Zhang, J; He, Z; Cheng, X. CN 114835630, 2022.
[14]	(a) Lei, L.; Liang, Y.-F.; Liang, C.; Qin, J.-K.; Pan, C.-X.; Su, G.-F.; Mo, D.-L. Org. Biomol. Chem. 2021, 19, 3379. doi: 10.1039/d1ob00319d pmid: 33899889
	(b) Lu, D.-L.; Yao, Y.-Y.; Liang, Y.-F.; Liang, C.; Lei, L.; Ma, L.; Mo, D.-L. J. Org. Chem. 2023, 88, 690. doi: 10.1021/acs.joc.2c02140 pmid: 33899889
[15]	Bram, G.; Loupy, A.; Sansoulet, J.; Vaziri, Z. F. Tetrahedron Lett. 1984, 25, 5035. doi: 10.1016/S0040-4039(01)91111-6
[16]	(a) Izzo, I.; Scioscia, M.; Gaudio, P. D.; Riccardis, F. D. Tetrahedron Lett. 2001, 42, 5421. doi: 10.1016/S0040-4039(01)01048-6
	(b) Song, X.; Song, A.; Zhang, F.; Li, H.; Wang, W. Nat. Commun. 2011, 2, 524. doi: 10.1038/ncomms1541
	(c) Wang, L.; Yang, D.; Li, D.; Wang, P.; Wang, K.; Wang, J.; Jiang, X.; Wang, R. Chem.-Eur. J. 2016, 22, 8483. doi: 10.1002/chem.v22.25
	(d) Zhou, B.; Yuan, Z.; Yu, J.; Luan, X. Org. Lett. 2022, 24, 837. doi: 10.1021/acs.orglett.1c04065
[17]	Rossi, R. A.; Pierini, A. B.; Penenory, A. B. Chem. Rev. 2003, 103, 71. doi: 10.1021/cr960134o
[18]	Boal, B. W.; Schammel, A. W.; Garg, N. K. Org. Lett. 2009, 11, 3458. doi: 10.1021/ol901383j pmid: 19601608
[19]	Chen, L.; Yang, G. M.; Wang, J.; Jia, Q. F.; Wei, J.; Du, Z. Y. RSC Adv. 2015, 5, 76696. doi: 10.1039/C5RA15903B
[20]	Jiang, F.; Wu, Z.; Zhang, W. Tetrahedron Lett. 2010, 51, 5124. doi: 10.1016/j.tetlet.2010.07.084
[21]	Kumar, P.; Shirke, R. P.; Yadav, S.; Ramasastry, S. S. V. Org. Lett. 2021, 23, 4909. doi: 10.1021/acs.orglett.1c01671
[22]	Lee, E.; Hwang, Y.; Kim, Y. B.; Kim, D.; Chang, S. J. Am. Chem. Soc. 2021, 143, 6363. doi: 10.1021/jacs.1c02550

基于原位形成的氮杂邻亚甲基苯醌和卤代萘酚的分子间[4＋1]螺环化/去芳香化反应