Synthesis 2020; 52(03): 424-432
DOI: 10.1055/s-0039-1691490
paper
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Spirofluorenyl-1,2,4-oxadiazinan-5-ones through Metal-Free [3+3] Cycloaddition of N-Vinyl Fluorenone Nitrones with Aza-oxyallyl Cations

Yan Luo
,
Chun-Hua Chen
,
Jin-Qi Zhang
,
Cui Liang
,
State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Ministry of Science and Technology of China, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, 15 Yu Cai Road, Guilin 541004, P. R. of China   Email: moeastlight@mailbox.gxnu.edu.cn
› Author Affiliations
Financial support from the National Natural Science Foundation of China (21602037), the Natural Science Foundation of Guangxi Province (2016GXNSFFA380005), the Ministry of Education (IRT_16R15), the ‘Overseas 100 Talents Program’ of Guangxi Higher Education, and the ‘One Thousand Young and Middle-Aged College and University Backbone Teachers Cultivation Program’ of Guangxi are greatly appreciated.
Further Information

Publication History

Received: 27 October 2019

Accepted after revision: 31 October 2019

Publication Date:
13 November 2019 (online)

Yan Luo and Chun-Hua Chen contributed equally to this work.

Abstract

Spirofluorenyl-1,2,4-oxadiazinan-5-ones are prepared in good to excellent yields through metal-free [3+3] cycloaddition of N-vinyl fluorenone nitrones and aza-oxyallyl cations under mild reaction conditions. Detailed studies reveal that N-vinyl fluorenone nitrones show greater reactivity in [3+3] cycloadditions with aza-oxyallyl cations compared to N-alkyl/aryl fluorenone nitrones. The spirofluorenyl-1,2,4-oxadiazinan-5-ones are easily prepared on gram scale. The present method features mild reaction conditions, broad substrate scope, good functional group tolerance and efficient [3+3] cycloadditions of 9-fluorenone nitrones.

Supporting Information

 
  • References


    • For some recent reviews on nitrones, see:
    • 1a Shi W.-M, Ma X.-P, Su G.-F, Mo D.-L. Org. Chem. Front. 2016; 3: 116
    • 1b Anderson LL. Asian J. Org. Chem. 2016; 5: 9
    • 1c Huple DB, Ghorpade S, Liu R.-S. Adv. Synth. Catal. 2016; 358: 1348
    • 1d Rück-Braun K, Freysoldt TH. E, Wierschem F. Chem. Soc. Rev. 2005; 34: 507
    • 1e Chiacchio U, Padwa A, Romeo G. Curr. Org. Chem. 2009; 13: 422
    • 1f Yang J. Synlett 2012; 23: 2293
    • 1g Merino P. Product Class 13: Nitrones and Cyclic Analogues . In Science of Synthesis, Vol. 27. Bellus D, Padwa A. Thieme; Stuttgart: 2004: 511-580
    • 1h Merino P. Nitrones and Cyclic Analogues. In Science of Synthesis, Vol. 4. Schaumann E. Thieme; Stuttgart: 2011: 325-403

      For examples of the use of a fluorenyl group in pharmaceuticals, dyes, and materials, see:
    • 2a Ma G, Zhao H, Wang J, Le Y, Jiang H, Deng H, Hao J, Wan W. Dyes Pigm. 2018; 158: 420
    • 2b Xin Y, Wen G.-A, Zeng W.-J, Zhao L, Zhu X.-R, Fan Q.-L, Feng J.-C, Wang L.-H, Wei W, Peng B, Cao Y, Huang W. Macromolecules 2005; 38: 6755
    • 2c Fan S, Lai J, Burn PL, Shaw PE. ACS Sens. 2019; 4: 134
    • 2d Kumar AG, Singh A, Komber H, Voit B, Tiwari BR, Noori MT, Ghangrekar MM, Banerjee S. ACS Appl. Mater. Interfaces 2018; 10: 14803
    • 3a Denmark SE, Montgomery JI. J. Org. Chem. 2006; 71: 6211
    • 3b Michael RE, Chando KM, Sammakia T. J. Org. Chem. 2015; 80: 6930
    • 3c Chen C.-H, Liu Q.-Q, Ma X.-P, Feng Y, Liang C, Pan C.-X, Su G.-F, Mo D.-L. J. Org. Chem. 2017; 82: 6417
    • 4a Mo D.-L, Wink DJ, Anderson LL. Org. Lett. 2012; 14: 5180
    • 4b Kontokosta D, Muller DS, Mo D.-L, Pace WH, Simpson RA, Anderson LL. Beilstein J. Org. Chem. 2015; 11: 2097
    • 5a Son J, Kim KH, Mo D.-L, Wink DJ, Anderson LL. Angew. Chem. Int. Ed. 2017; 56: 3059
    • 5b Reidl TW, Son J, Wink DJ, Anderson LL. Angew. Chem. Int. Ed. 2017; 56: 11579
    • 5c Nakamura I, Okamoto M, Sato Y, Terada M. Angew. Chem. Int. Ed. 2012; 51: 10816
    • 5d Chen C.-H, Wu Q.-Y, Wei C, Liang C, Su G.-F, Mo D.-L. Green Chem. 2018; 20: 2722
    • 5e Zou N, Jiao J.-W, Feng Y, Pan C.-X, Liang C, Su G.-F, Mo D.-L. Org. Lett. 2019; 21: 481
    • 5f Ma X.-P, Li L.-G, Zhao H.-P, Du M, Liang C, Mo D.-L. Org. Lett. 2018; 20: 4571
    • 5g Zou N, Jiao J.-W, Feng Y, Chen C.-H, Liang C, Su G.-F, Mo D.-L. Adv. Synth. Catal. 2017; 359: 3545
    • 6a Wei C, Zhu J.-F, Zhang J.-Q, Deng Q, Mo D.-L. Adv. Synth. Catal. 2019; 361: 3965
    • 6b Ma X.-P, Zhu J.-F, Wu S.-Y, Chen C.-H, Zou N, Liang C, Su G.-F, Mo D.-L. J. Org. Chem. 2017; 82: 502
  • 7 Pecak WH, Son J, Burnstine AJ, Anderson LL. Org. Lett. 2014; 16: 3440

    • For recent reviews on aza-oxyallyl cations, see:
    • 8a Li H, Wu J. Synthesis 2015; 47: 22
    • 8b Barnes KL, Koster AK, Jeffrey CS. Tetrahedron Lett. 2014; 55: 4690
    • 8c Xuan J, Cao X, Cheng X. Chem. Commun. 2018; 54: 5154
  • 9 For an example of [3+1] cycloaddition, see: Li C, Jiang K, Ouyang Q, Liu T.-Y, Chen Y.-C. Org. Lett. 2016; 18: 2738

    • For selected examples of [3+2] cycloaddition, see:
    • 10a Dipoto MC, Wu J. Org. Lett. 2018; 20: 499
    • 10b Ji D, Sun J. Org. Lett. 2018; 20: 2745
    • 10c Shao P.-L, Li Z.-R, Wang Z.-P, Zhou M.-H, Wu Q, Hu P, He Y. J. Org. Chem. 2017; 82: 10680

      For selected examples of [3+3] cycloaddition, see:
    • 11a Cheng X, Cao X, Zhou S.-J, Cai B.-G, He X.-K, Xuan J. Adv. Synth. Catal. 2019; 361: 1230
    • 11b Zhang K, Xu X, Zheng J, Yao H, Huang Y, Lin A. Org. Lett. 2017; 19: 2596
    • 11c Xu X, Zhang K, Li P, Yao H, Lin A. Org. Lett. 2018; 20: 1781

      For selected examples of [4+3] cycloaddition, see:
    • 12a Jeffrey CS, Barnes KL, Eickhoff JA, Carson CR. J. Am. Chem. Soc. 2011; 133: 7688
    • 12b Acharya A, Eickhoff JA, Jeffrey CS. Synthesis 2013; 45: 1825
    • 13a Zhao H.-W, Zhao Y.-D, Liu Y.-Y, Zhao L.-J, Feng N.-N, Pang H.-L, Chen X.-Q, Song X.-Q, Du J. RSC Adv. 2017; 7: 12916
    • 13b Chen R, Sun S, Wang G, Guo H. Tetrahedron Lett. 2018; 59: 1916
  • 14 An Y, Xia H, Wu J. Chem. Commun. 2016; 52: 10415
  • 15 Jia Q, Li D, Lang M, Zhang K, Wang J. Adv. Synth. Catal. 2017; 359: 3837

    • For reviews of N,O-heterocycles, see:
    • 16a Pattenden G. J. Heterocycl. Chem. 1992; 29: 607
    • 16b Corey EJ, Czakó B, Kürti L. Molecules and Medicine . John Wiley & Sons; Hoboken: 2007
    • 16c Comprehensive Heterocyclic Chemistry III, Vol. 4 and 8. Katritzky AR, Ramsden CA, Scriven EF. V, Taylor RJ. K. Elsevier; Amsterdam: 2008

    • For selected examples of six-membered N,O-heterocycles, see:
    • 16d Ye C, Kou X, Xia J, Yang G, Kong L, Wei Q, Zhang W. Chem. Asian J. 2018; 13: 1897
    • 16e Tran CB, To TA, Vo YH, Do TT. L, Nguyen QT. P, Nguyen AT, Nguyen TT, Phan NT. S. ChemistrySelect 2019; 4: 880
    • 16f Zhao D, Fañanás-Mastral M, Chang M.-C, Otten E, Feringa BL. Chem. Sci. 2014; 5: 4216
    • 17a Weller HN, Miller AV, Dickinson KE. J, Hedberg SA, Delaney CL, Serafino RP, Moreland S. Heterocycles 1993; 36: 1027
    • 17b Huang X, Zhou W, Liu X, Li H, Sun G, Mandal M, Vicarel M, Zhu X, Bennett C, McCraken T, Pissarnitski D, Zhao Z, Cole D, Gallo G, Zhu Z, Palani A, Aslanian R, Clader J, Czarniecki M, Greenlee W, Burnett D, Cohen-Williams M, Hyde L, Song L, Zhang L, Chu I, Buevich A. ACS Med. Chem. Lett. 2012; 3: 931
    • 17c Bernstein J, Losee KA. US Patent 3438985, 1969
    • 17d Koenig KH, Steinbrunn G, Zschocke A. US Patent 3625968, 1971
  • 18 CCDC 1938291 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.
  • 19 K2CO3 is not soluble in MeCN at room temperature but dissolves completely after adding the α-bromohydroxamate and stirring for about 2 h. White solid KBr was observed after stirring for about 5 h. The insolubility of KBr might shift the equilibrium.

    • An alkoxy donor group on the nitrogen atom could potentially stabilize aza-oxyallylic cation intermediates, see:
    • 20a Kikugawa Y. Heterocycles 2009; 78: 571
    • 20b Kikugawa Y, Shimada M, Kato M, Sakamoto T. Chem. Pharm. Bull. 1993; 41: 2192
  • 21 N-Vinyl fluorenone nitrone 1a easily decomposed to give 9-fluorenone in the presence of K2CO3 in HFIP; N-Me/Ph fluorenone nitrones 1n and 1o were stable in HFIP. However, N-vinyl fluorenone nitrone 1a was stable in the presence of K2CO3 in MeCN.

    • Hexafluoroisopropanol (HFIP) was proved to increase the yield of reactions proceeding through reactive oxyallyl cationic intermediates, see:
    • 22a Myers AG, Barbay JK. Org. Lett. 2001; 3: 425
    • 22b Harmata M, Huang C, Rooshenas P, Schreiner PR. Angew. Chem. Int. Ed. 2008; 47: 8696