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. 2018 Sep 13;9(43):8253-8259.
doi: 10.1039/c8sc03339k. eCollection 2018 Nov 21.

Redox-triggered cascade dearomative cyclizations enabled by hexafluoroisopropanol

Shuai-Shuai Li  1 , Xintong Lv  1 , Didi Ren  1 , Chang-Lun Shao  2 , Qing Liu  3 , Jian Xiao  1
Affiliations

Redox-triggered cascade dearomative cyclizations enabled by hexafluoroisopropanol

Shuai-Shuai Li et al. Chem Sci. .

Abstract

An unprecedented cascade dearomative cyclization through hydrogen-bonding-assisted hydride transfer is realized. The aggregate effect of HFIP enables the rapid buildup of polycyclic amines directly from phenols and o-aminobenzaldehydes via a cascade dearomatization/rearomatization/dearomatization sequence. This unique transformation addressed the drawbacks of hydride transfer-involved redox-neutral reactions.

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Figures

Scheme 1
Scheme 1. Cascade dearomative cyclizations via a dearomatization/rearomatization/dearomatization sequence.
Scheme 2
Scheme 2. Substrate scope: o-aminobenzaldehydes. aReaction conditions: 1a (0.13 mmol) and 2 (0.1 mmol) in 2.0 mL HFIP at room temperature under air; isolated yield; dr > 20 : 1; dr was determined by 1H NMR spectroscopy. bAt 40 °C. cIn 1.0 mL toluene and 1.0 mL HFIP at 120 °C. d1a (0.13 mmol), 2 (0.1 mmol), and 2.0 equiv. of piperidine were added to 1.0 mL toluene with stirring for 12 h at 120 °C, and then cooled to room temperature followed by the addition of 1.0 mL HFIP and stirred for another 10 min.
Scheme 3
Scheme 3. Substrate scope: phenols. Reaction conditions: 1 (0.13 mmol) and 2 (0.1 mmol) in 2.0 mL of HFIP at room temperature under air; isolated yield; dr > 20 : 1; dr was determined by 1H NMR spectroscopy.
Scheme 4
Scheme 4. Substrate scope for the formation of para-spirocyclic ketenes. 4 (0.13 mmol), 2 (0.1 mmol), and piperidine (2.0 equiv.) were added to 1.0 mL toluene with stirring for 12 h at 120 °C, and then cooled to room temperature followed by the addition of 1.0 mL HFIP and stirred for another 10 min; isolated yield.
Scheme 5
Scheme 5. Gram scale reaction.
Scheme 6
Scheme 6. Derivatization of products.
Scheme 7
Scheme 7. Deuterium labeling experiments.
Scheme 8
Scheme 8. Control experiments.
Scheme 9
Scheme 9. Plausible reaction mechanism.
See this image and copyright information in PMC

References

    1. Campos K. R. Chem. Soc. Rev. 2007;36:1069. - PubMed
    2. Baudoin O. Chem. Soc. Rev. 2011;40:4902. - PubMed
    3. Shi L., Xia W. Chem. Soc. Rev. 2012;41:7687. - PubMed
    4. Mitchell E. A., Peschiulli A., Lefevre N., Meerpoel L., Maes B., Chem U. W. Chem.–Eur. J. 2012;18:10092. - PubMed
    5. Vo C. V. T., Bode J. W. J. Org. Chem. 2014;79:2809. - PubMed
    6. Seidel D. Acc. Chem. Res. 2015;48:317. - PMC - PubMed
    7. Mahato S., Jana C. K. Chem. Rec. 2016;16:1477. - PubMed
    1. Tobisu M., Chatani N. Angew. Chem., Int. Ed. 2006;45:1683. - PubMed
    2. Peng B., Maulide N. Chem.–Eur. J. 2013;19:13274. - PubMed
    3. Wang L., Xiao J. Adv. Synth. Catal. 2014;356:1137.
    4. Wang L., Xiao J. Top. Curr. Chem. 2016;374:17. - PubMed
    5. Wang L., Xiao J. Org. Chem. Front. 2016;3:635.
    6. Pan S. C. Beilstein J. Org. Chem. 2012;8:1374. - PMC - PubMed
    7. Haibach M. C., Seidel D. Angew. Chem., Int. Ed. 2014;53:5010. - PubMed
    8. Xiao M., Zhu S., Shen Y., Wang L., Xiao J. Chin. J. Org. Chem. 2018;38:328.
    9. Kwon S. J., Kim D. Y. Chem. Rec. 2016;16:1191. - PubMed

    1. For examples of electrophilic alkenes, see:

    2. Pastine S. J., McQuaid K. M., Sames D. J. Am. Chem. Soc. 2005;127:12180. - PubMed
    3. Murarka S., Zhang C., Konieczynska M. D., Seidel D. Org. Lett. 2009;11:129. - PubMed
    4. Han Y., Han W., Hou X., Zhang X., Yuan W. Org. Lett. 2012;14:4054. - PubMed
    5. Yoshida T., Mori K. Chem. Commun. 2017;53:4319. - PubMed
    6. Ruble J. C., Hurd A. R., Johnson T. A., Sherry D. A., Barbachyn M. R., Toogood P. L., Bundy G. L., Graber D. R., Kamilar G. M. J. Am. Chem. Soc. 2009;131:3991. - PubMed
    7. Mori K., Ehara K., Kurihara K., Akiyama T. J. Am. Chem. Soc. 2011;133:6166. - PubMed
    8. Suh C. W., Kim D. Y. Org. Lett. 2014;16:5374. - PubMed
    9. Mori K., Kurihara K., Yabe S., Yamanaka M., Akiyama T. J. Am. Chem. Soc. 2014;136:3744. - PubMed
    10. Mori K., Isogai R., Kamei Y., Yamanaka M., Akiyama T. J. Am. Chem. Soc. 2018;140:6203. - PubMed

    1. For representative examples, see:

    2. Jurberg I. D., Peng B., Woestefeld E., Wasserloos M., Maulide N. Angew. Chem., Int. Ed. 2012;51:1950. - PubMed
    3. Chen D., Han Z., He Y., Yu J., Gong L.-Z. Angew. Chem., Int. Ed. 2012;51:12307. - PubMed
    4. Vadola P. A., Sames D. J. Am. Chem. Soc. 2009;131:16525. - PMC - PubMed
    5. Barluenga J., Fananas-Mastral M., Aznar F., Valdes C. Angew. Chem., Int. Ed. 2008;47:6594. - PubMed
    6. Sugiishi T., Nakamura H. J. Am. Chem. Soc. 2012;134:2504. - PubMed
    7. Theunissen C., Metayer B., Henry N., Compain G., Marrot J., Martin-Mingot A., Thibaudeau S., Evano G. J. Am. Chem. Soc. 2014;136:12528. - PubMed
    8. Cui L., Peng Y., Zhang L. M. J. Am. Chem. Soc. 2009;131:8394. - PubMed
    9. Kang Y. K., Kim S. M., Kim D. Y. J. Am. Chem. Soc. 2012;132:11847. - PubMed

    1. For recently developed hydride acceptors, see:

    2. Chang Y.-Z., Li M.-L., Zhao W.-F., Wen X., Sun H., Xu Q.-L. J. Org. Chem. 2015;80:9620. - PubMed
    3. Suh C. W., Kwon S. J., Kim D. Y. Org. Lett. 2017;19:1334. - PubMed
    4. Liu S., Qu J., Wang B. Chem. Commun. 2018;54:7928. - PubMed
    5. Li S.-S., Zhou L., Wang L., Zhao H., Yu L., Xiao J. Org. Lett. 2018;20:138. - PubMed
    6. Idiris F. I. M., Majesté C. E., Craven G. B., Jones C. R., Chem. Sci., 2018, 9 , 2873 , ; For an intermolecular hydride transfer, see: . - PMC - PubMed
    7. Chen W., Ma L., Paul A., Seidel D. Nat. Chem. 2018;10:165. - PMC - PubMed