Halogen-Radical-Promoted Dearomative Aza-Spirocyclization of Alkynylimines: An Efficient Approach to 3-Halo-Spirocyclohexadienones

Abstract

A novel halogen-radical-promoted dearomative aza-spiro­cyclization of alkynylimines for the synthesis of 3-halo-spirocyclohexadienones is described. In this process, it is believed that a radical addition, 5-exo-trig cyclization, and dearomative aza-spirocyclization are involved. Easily available starting materials, mild conditions, and a wide substrate scope make this approach potentially useful.

Key words

halogen radical - dearomative aza-spirocyclization - alkynylimine - 3-halo-spirocyclohexadienone - 5-exo-trig cyclization

• References

• 1a Müller G, Berkenbosch T, Benningshof JC. J, Stumpfe D, Bajorath J. Chem. Eur. J. 2017; 23: 703
• 1b Koswatta PB, Das J, Yousufuddin M, Lovely CJ. Eur. J. Org. Chem. 2015; 2603
• 1c Ball-Jones NR, Badillo JJ, Franz AK. Org. Biomol. Chem. 2012; 10: 5165
• 1d Marson C. Chem. Soc. Rev. 2011; 40: 5514
• 1e Gravel E, Poupon E. Nat. Prod. Rep. 2010; 27: 32
• 2a Jia M, You S. Chem. Commun. 2012; 48: 6363
• 2b Zhuo C, Zhang W, You S. Angew. Chem. Int. Ed. 2012; 51: 12662
• 2c Barradas S, Hernández-Torres G, Urbano A, Carreño MC. Org. Lett. 2012; 14: 5952
• 2d Roche ST, Porco JA. Angew. Chem. Int. Ed. 2011; 50: 4068
• 3a Huang M, Hao W, Li G, Tu S, Jiang B. Chem. Commun. 2018; 54: 10791
• 3b Huang M, Hao W, Jiang B. Chem. Asian J. 2018; 13: 2958
• 3c Reddy CR, Prajapti SK, Warudikar K, Ranjan R, Rao BB. Org. Biomol. Chem. 2017; 15: 3130
• 3d Wu W, Zhang L, You S. Chem. Soc. Rev. 2016; 45: 1570
• 3e D’yakonov VA, Trapeznikova OA, de Meijere A, Dzhemilev UM. Chem. Rev. 2014; 114: 5775
• 3f Rios R. Chem. Soc. Rev. 2012; 41: 1060
• 4a Chabaud L, Hromjakova T, Rambla M, Retailleau P, Guillou C. Chem. Commun. 2013; 49: 11542
• 4b Liang H, Ciufolini MA. Chem. Eur. J. 2010; 16: 13262
• 4c Zhdankin VV, Stang PJ. Chem. Rev. 2008; 108: 5299
• 5a Nemoto T, Zhao Z, Yokosaka T, Suzuki Y, Hamada RW. Y. Angew. Chem. Int. Ed. 2013; 52: 2217
• 5b Unsworth WP, Cuthbertson JD, Taylor RJ. K. Org. Lett. 2013; 15: 3306
• 5c Tnay YL, Chen C, Chua YY, Zhang L, Chiba S. Org. Lett. 2012; 14: 3550
• 5d Likhar PR, Subhas MS, Roy S, Kantam ML, Sridhar B, Seth RK, Biswas S. Org. Biomol. Chem. 2009; 7: 85
• 6a Tang B, Zhang Y, Song R, Tang D, Deng G, Wang Z, Xie Y, Xia Y, Li J. J. Org. Chem. 2012; 77: 2837
• 6b Godoi B, Schumacher RF, Zeni G. Chem. Rev. 2011; 111: 2937
• 6c Crone B, Kirsch SF, Umland KD. Angew. Chem. Int. Ed. 2010; 49: 4661
• 7a Yang Z, Jiang R, Zheng C, You S. J. Am. Chem. Soc. 2018; 140: 3114
• 7b Liebov BK, Harman WD. Chem. Rev. 2017; 117: 13721
• 7c Ouyang XH, Song R, Liu B, Li J. Chem. Commun. 2016; 52: 2573
• 7d Wu W, Xu R, Zhang L, You S. Chem. Sci. 2016; 7: 3427
• 7e Wang L, Wang A, Xia Y, Wu X, Liu X, Liang Y. Chem. Commun. 2014; 50: 13998
• 7f Aparece MD, Vadola PA. Org. Lett. 2014; 16: 6008
• 7g Zhang J, Hu B, Ji M, Ye S, Zhu G. Org. Lett. 2018; 20: 2988
• 7h Li J, Zhang W, Wei X, Liu F, Hao W, Wang S, Li G, Tu S, Jiang B. J. Org. Chem. 2017; 82: 6621
• 7i Dong W, Yuan Y, Gao X, Keranmu M, Li W, Xie X, Zhang Z. Org. Lett. 2018; 20: 5762
• 7j Wu J, Ma D, Tang G, Zhao Y. Org. Lett. 2019; 21: 7674
• 8a Zhang L, Ma L, Zhou H, Yao J, Li X, Qiu G. Org. Lett. 2018; 20: 2407
• 8b Liu R, Li M, Xie W, Zhou H, Zhang Y, Qiu G. J. Org. Chem. 2019; 84: 11763
• 8c Qiu G, Chen Z.-F, Xie W, Zhou H. Eur. J. Org. Chem. 2019; 4327
• 8d Zheng Y, Liu M, Qiu G, Xie W, Wu J. Tetrahedron 2019; 75: 1663
• 8e Wang Y.-H, Qiu G, Zhou H, Xie W, Liu J.-B. Tetrahedron 2019; 75: 3850
• 8f Wang Y.-H, Ouyang B, Qiu G, Xie W, Liu J.-B. Org. Biomol. Chem. 2019; 17: 4335
• 8g Yang M, Hu X, Ouyang B, Xie W, Liu J.-B. Tetrahedron 2019; 75: 3516
• 8h Wang Y.-C, Wang R.-X, Qiu G, Zhou H, Xie W, Liu J.-B. Org. Chem. Front. 2019; 6: 2471
• 9a Feng S, Li J, Liu Z, Sun H, Shi H, Wang X, Xie X, She X. Org. Biomol. Chem. 2017; 15: 8820
• 9b Qiu G, Liu T, Ding Q. Org. Chem. Front. 2016; 3: 510
• 9c Dutta U, Deb A, Lupton D, Maiti D. Chem. Commun. 2015; 51: 17744
• 9d Moriyama K, Nakamura Y, Togo H. Org. Lett. 2014; 16: 3812

For selected examples on Oxone chemistry, see:
• 9e Lu L.-H, Zhou S.-J, Sun M, Chen J.-L, Xia W, Yu X, Xu X, He W.-M. ACS Sustaniable Chem. Eng. 2019; 7: 1574
• 9f Xie LY, Peng S, Liu F, Chen G.-R, Xia W, Yu X, Li W.-F, Cao Z, He W.-M. Org. Chem. Front. 2018; 5: 2604
• 9g Lu L.-H, Zhou S.-J, He W.-B, Xia W, Chen P, Yu X, Xu X, He W.-M. Org. Biomol. Chem. 2018; 16: 9064
• 9h Xie L.-Y, Peng S, Fan T.-G, Liu Y.-F, Sun M, Jiang L.-L, Wang X.-X, Cao Z, He W.-M. Sci. China Chem. 2019; 62: 460
• 10a Hegmann N, Prusko L, Heinrich MR. Org. Lett. 2017; 19: 2222
• 10b Bansode AH, Shaikh SR, Gonnade RG, Patil NT. Chem. Commun. 2017; 53: 9081
• 10c Yuan Z, Gai K, Wu Y, Wu J, Lin A, Yao H. Chem. Commun. 2017; 53: 3485
• 10d Reddy CR, Ranjan R, Prajapti SK, Warudikar K. J. Org. Chem. 2017; 82: 6932
• 10e He Y, Qiu G. Org. Biomol. Chem. 2017; 15: 3485
• 10f Jin D, Gao P, Chen D, Chen S, Wang J, Liu X, Yong Y. Org. Lett. 2016; 18: 3486
• 10g Ni S, Cao J, Mei H, Han J, Li S, Pan Y. Green Chem. 2016; 18: 3935
• 10h Yang X, Long Y, Chen F, Han B. Org. Chem. Front. 2016; 3: 184
• 10i Wen J, Wei W, Xue S, Yang D, Lou Y, Gao C, Wang H. J. Org. Chem. 2015; 80: 4966
• 10j Yang X, Ouyang X, Wei W, Song R, Li J. Adv. Synth. Catal. 2015; 357: 1161

For examples on alkynylimines, see:
• 11a Chen D, Shan Y, Li J, You J, Sun X, Qiu G. Org. Lett. 2019; 21: 4044
• 11b Ge G, Ding C, Hou X. Org. Chem. Front. 2014; 1: 382

For other dual-functionalized synthons, see:
• 11c Wu C, Wang Z, Hu Z, Zeng F, Zhang X.-Y, Cao Z, Tang Z, He W.-M, Xu X.-H. Org. Biomol. Chem. 2018; 16: 3177
• 11d Xie L.-Y, Peng S, Liu F, Yi J.-Y, Wang M, Tang Z, Xu X, He W.-M. Adv. Synth. Catal. 2018; 360: 4259
• 11e Wu C, Lu L.-H, Peng A.-Z, Jia G.-K, Peng C, Cao Z, Tang Z, He W.-M, Xu X. Green Chem. 2018; 20: 3683
• 11f Gong X, Chen J, Li X, Xie W, Wu J. Chem. Asian J. 2018; 13: 2543
• 11g Zhao Y, Luo Y, Zhu Y, Wang H, Zhou H, Tan H, Zhou Z. Synlett 2018; 29: 773
• 11h Zhao Y.-H, Li Y, Luo M, Tang Z, Deng K. Synlett 2016; 27: 2597
• 11i Zhao Y, Li Y, Guo T, Tang Z, Xie W, Zhao G. Tetrahedron Lett. 2016; 57: 2257
• 11j Guo T, Liu Y, Zhao Y.-H, Zhang P.-K, Han S.-L, Liu H.-M. Tetrahedron Lett. 2016; 57: 4629
• 11k Guo T, Liu Y, Zhao Y.-H, Zhang P.-K, Han S.-L, Liu H.-M. Tetrahedron Lett. 2016; 57: 3920
• 11l Zhen L, Fang C, Zheng Y, Qiu G, Li X, Zhou H. Tetrahedron Lett. 2018; 59: 3934
• 11m Xie W, Wu Y, Zhang J, Mei Q, Zhang Y, Zhu N, Liu R, Zhang H. Eur. J. Med. Chem. 2018; 145: 35
• 11n Zhang J, Li X, Xie W, Ye S, Wu J. Org. Lett. 2019; 21: 4950
• 11o Zong Y, Lang L, Yang M, Li X, Fan X, Wu J. Org. Lett. 2019; 21: 1935
• 11p Wang X, Yang M, Xie W, Fan X, Wu J. Chem. Commun. 2019; 55: 6010
• 12a Liu T, Myers MC, Yu Y. Angew. Chem. Int. Ed. 2017; 56: 306
• 12b Dutta U, Deb A, Lupton D, Maiti D. Chem. Commun. 2015; 51: 17744
• 12c Schmidt VA, Quinn RK, Brusoe AT, Alexanian EJ. J. Am. Chem. Soc. 2014; 136: 14389
• 12d Moriyama K, Nkamura Y, Togo H. Org. Lett. 2014; 16: 3812
• 13 CCDC 1949292 contains the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.
• 14a Zhang L, Lu P, Wang Y. Org. Biomol. Chem. 2015; 13: 8322
• 14b Wen Q, Jin J, Mei Y, Lu P, Wang Y. Eur. J. Org. Chem. 2013; 4032
• 15a Becker P, Duhamel T, Martínez C, Muñiz K. Angew. Chem. Int. Ed. 2018; 57: 5166
• 15b Natarajan P, Priya P, Chuskit D. Green Chem. 2017; 19: 5854
• 16a Liu L, Chen D, Yao J, Zong Q, Wang J, Zhou H. J. Org. Chem. 2017; 82: 4625
• 16b Ali S, Zhu H, Xia X, Ji K, Yang Y, Song X, Liang Y. Org. Lett. 2011; 13: 2598
• 17 Kandepi VV. K. M, Narender N. Synthesis 2012; 44: 15