Highly Efficient Synthesis of Hindered 3-Azoindoles via Metal-Free C–H Functionalization of Indoles

Published as part of the Bürgenstock Special Section 2019 Future Stars in Organic Chemistry

Abstract

Although 3-azoindoles have recently emerged as an appealing family of photoswitch molecules, the synthesis of such compounds has been poorly covered in the literature. Herein a high-yielding and operationally simple protocol is reported allowing the synthesis of 3-azoindoles, featuring important steric hindrance around the azo motif. Remarkably, this C–H coupling is characterized by excellent atom economy and occurs under metal-free conditions, at room temperature, and within few minutes, delivering the expected products in excellent yields (quantitatively in most of the cases). Accordingly, a library of new molecules, with potential applications as photochromic compounds, is prepared.

Key words

azoindole - C–H functionalization of indoles - azoswitches - diazenylation

• References


For selected reviews, see:
• 1a Brieke C, Rohrbach F, Gottschalk A, Mayer G, Heckel A. Angew. Chem. Int. Ed. 2012; 51: 8446
• 1b Russew M.-M, Hecht S. Adv. Mater. 2010; 22: 3348
• 1c Pianowski ZL. Chem. Eur. J. 2019; 25: 5128
• 1d Mutlu H, Geiselhart CM, Barner-Kowollik C. Mater. Horiz. 2018; 5: 162
• 1e Bléger D, Hecht S. Angew. Chem. Int. Ed. 2015; 54: 11338
• 2 Baroncini M, d’Agostino S, Bergamini G, Ceroni P, Comotti A, Sozzani P, Bassanetti I, Grepioni F, Hernandez TM, Silvi S, Venturi M, Credi A. Nat. Chem. 2015; 7: 634
• 3 Hirshberg Y. J. Am. Chem. Soc. 1956; 78: 2304
• 4 Roke D, Stuckhardt C, Danowski W, Wezenberg SJ, Feringa BL. Angew. Chem. Int. Ed. 2018; 57: 10515
• 5a Barber RW, McFadden ME, Hu X, Robb MJ. Synlett 2019; 30: 1725
• 5b Ihrig SP, Eisenreich F, Hecht S. Chem. Commun. 2019; 55: 4290
• 6a Beauté L, McClenaghan N, Lecommandoux S. Adv. Drug Deliv. Rev. 2019; 138: 148
• 6b Jia S, Fong W.-K, Graham B, Boyd B. J. Chem. Mater. 2018; 30: 2873
• 7 Borowiak M, Nahaboo W, Reynders M, Nekolla K, Jalinot P, Hasserodt J, Rehberg M, Delattre M, Zahler S, Vollmar A, Trauner D, Thorn-Seshold O. Cell 2015; 162: 403
• 8 Andréasson J, Pischel U, Straight SD, Moore TA, Moore AL, Gust D. J. Am. Chem. Soc. 2011; 133: 11641
• 9a Goldau T, Murayama K, Brieke C, Asanuma H, Heckel A. Chem. Eur. J. 2015; 21: 17870
• 9b Nakasone Y, Ooi H, Kamiya Y, Asanuma H, Terazima M. J. Am. Chem. Soc. 2016; 138: 9001
• 9c Rullo A, Reiner A, Reiter A, Trauner D, Isacoff EY, Woolley GA. Chem. Commun. 2014; 50: 14613
• 9d Goldau T, Murayama K, Brieke C, Steinwand S, Mondal P, Biswas M, Burghardt I, Wachtveitl J, Asanuma H, Heckel A. Chem. Eur. J. 2015; 21: 2845
• 9e Zhang F, Zarrine-Afsar A, Al-Abdul-Wahid MS, Prosser RS, Davidson AR, Woolley GA. J. Am. Chem. Soc. 2009; 131: 2283
• 10 García-Amorós J, Velasco D. Beilstein J. Org. Chem. 2012; 8: 1003

For selected examples, see:
• 11a Kienzler MA, Reiner A, Trautman E, Yoo S, Trauner D, Isacoff EY. J. Am. Chem. Soc. 2013; 135: 17683
• 11b Schönberger M, Althaus M, Fronius M, Clauss W, Trauner D. Nat. Chem. 2014; 6: 712
• 12 Klajn R. Chem. Soc. Rev. 2014; 43: 148
• 13a Frolova SR, Gorbunov VS, Shubina NS, Perepukhov AM, Romanova SG, Agladze KI. Biosci. Rep. 2019; 39: BSR20181849
• 13b Schmidt D, Rodat T, Heintze L, Weber J, Horbert R, Girreser U, Raeker T, Bußmann L, Kriegs M, Hartke B, Peifer C. ChemMedChem 2018; 13: 2415
• 14a Matsuda K, Higashiguchi K. In Supramolecular Soft Matter . Nakanishi T. Wiley; Hoboken: 2011: 215
• 14b Matsuda K. Pure App. Chem. 2008; 80: 555
• 15a Xu W.-C, Sun S, Wu S. Angew. Chem. Int. Ed. 2019; 58: 9712
• 15b Amrutha AS, Sunil Kumar KR, Tamaoki N. ChemPhotoChem 2019; 3: 337
• 16 Petermayer C, Dube H. Acc. Chem. Res. 2018; 51: 1153
• 17a Zulfikri H, Koenis MA. J, Lerch MM, Di Donato M, Szymański W, Filippi C, Feringa BL, Buma WJ. J. Am. Chem. Soc. 2019; 141: 7376
• 17b Lerch MM, Wezenberg SJ, Szymanski W, Feringa BL. J. Am. Chem. Soc. 2016; 138: 6344
• 18a For a review see: Crespi S, Simeth NA, König B. Nat. Rev. Chem. 2019; 3: 133
• 18b For a selected recent example, see: Saba S, Dos Santos CR, Zavarise BR, Naujorks AA. S, Franco MS, Schneider AR, Scheide MR, Affeldt RF, Rafique J, Braga AL. Chem. Eur. J. 2019; 25 in press: DOI:
• 19 For early examples of phenylazoindole dyes, see: Seferoğlu Z, Yalçın E, Babür B, Seferoğlu N, Hökelek T, Yılmaz E, Şahin E. Spectrochim. Acta, Part A 2013; 113: 314

For an early report, see:
• 20a Albar HA, Shawali AS, Abdaliah MA. Can. J. Chem. 1993; 71: 2144

Recently, synthesis of 3-(phenyl)diazenyl)-1,2-dimethyl-1H-indole was described as side reaction while developing base-free C–H arylation of indoles:
• 20b Gemoets HP. L, Kalvet I, Nyuchev AV, Erdmann N, Hessel V, Schoenebeck F, Noël T. Chem. Sci. 2017; 8: 1046
• 21a Cao D, Zhang Y, Liu C, Wang B, Sun Y, Abdukadera A, Hu H, Liu Q. Org. Lett. 2016; 18: 2000
• 21b Liu Y, Ma X, Wu G, Liu Z, Yang X, Wang B, Liu C, Zhang Y, Huang Y. New J. Chem. 2019; 43: 9255
• 22 Barak DS, Dighe SU, Avasthi I, Batra S. J. Org. Chem. 2018; 83: 3537
• 23a Simeth NA, Crespi S, Fagnoni M, König B. J. Am. Chem. Soc. 2018; 140: 2940
• 23b Crespi S, Simeth NA, Bellisario A, Fagnoni M, König B. J. Phys. Chem. A 2019; 123: 1814
• 23c Simeth NA, Bellisario A, Crespi S, Fagnoni M, König B. J. Org. Chem. 2019; 84: 6565

For an example of a synthesis of ortho-ortho′-substituted azoarenes via C–H activation, see:
• 24a Hubrich J, Himmler T, Rodefeld L, Ackermann L. ACS Catal. 2015; 5: 4089
• 24b Himmler T, Rodefeld L, Hubrich J, Ackermann L. Patent WO 2016071249 A1 20160512, 2016