Organophotoredox-Catalyzed Oxidative C(sp²)–H Alkylation of N-Heteroarenes with Dihydroquinazolinones by C–C Cleavage

Dedicated to Professor Matthias Beller on his 60^th birthday

Abstract

We report a visible-light-mediated, organophotoredox-catalyzed, C(sp²)–H alkylation of N-heteroarenes with dihydroquinazolines, prepared from aliphatic ketones, under oxidative conditions. This protocol represents a metal-free approach to the effective construction of C–C bonds through a Minisci-type reaction, formally activating the native C–H bond of the N-heteroarene and an α-C–C bond of a readily available ketone. The mild nature of this method accommodates a wide variety of N-heteroarenes and ketones, tolerating a wide range of functional groups.

Key words

photoredox catalysis - heteroarenes - ketone - C–C bond cleavage - alkylation

Publikationsverlauf

Eingereicht: 24. Dezember 2022

Angenommen nach Revision: 08. Februar 2023

Accepted Manuscript online:
08. Februar 2023

Artikel online veröffentlicht:
09. März 2023

• References and Notes

• 1a Newman DJ, Cragg GM. J. Nat. Prod. 2020; 83: 770
• 1b Michael JP. Nat. Prod. Rep. 2005; 22: 627
• 1c O’Hagan D. Nat. Prod. Rep. 2000; 17: 435
• 2a Heravi MM, Zadsirijan V. RSC Adv. 2020; 10: 44247
• 2b Vitaku ED, Smith T, Njardarson JT. J. Med. Chem. 2014; 57: 10257
• 2c Venditto VJ, Simanek EE. Mol. Pharmaceutics 2010; 7: 307
• 3 Guan A.-Y, Liu C.-L, Sun X.-F, Xie Y, Wang M.-A. Bioorg. Med. Chem. 2016; 24: 342
• 4 Leclerc N, Sanaur S, Galmiche L, Mathevet F, Attias A.-J, Fave J.-L, Roussel J, Hapiot P, Lemaître N, Geffroy B. Chem. Mater. 2005; 17: 502
• 5a Lovering F, Bikker J, Humblet C. J. Med. Chem. 2009; 52: 6752
• 5b Talele TT. J. Med. Chem. 2020; 63: 13291
• 6a Duncton MA. J. Med. Chem. Commun. 2011; 2: 1135
• 6b Procter RS. J, Phipps RJ. Angew. Chem. Int. Ed. 2019; 58: 13666
• 6c Parida SK, Hota SK, Kumar R, Murarka S. Chem. Asian J. 2021; 16: 879
• 6d Ghosh A, Pyne P, Ghosh S, Ghosh D, Majumder S, Hajra A. Green Chem. 2022; 24: 3056
• 7a Minisci F, Bernardi R, Bertini F, Galli R. Tetrahedron 1971; 27: 3575
• 7b Minisci F, Vismara E, Fontana F. Heterocycles 1989; 28: 489
• 8a Juliá F, Constantin T, Leonori D. Chem. Rev. 2022; 122: 2292
• 8b Huang C.-Y, Li J, Li C.-J. Chem. Sci. 2022; 13: 5465
• 8c Liu Q, Huo C, Fu Y, Du Z. Org. Biomol. Chem. 2022; 20: 6721
• 8d Bortolato T, Cuadros S, Simionato G, Dell’Amico L. Chem. Commun. 2022; 58: 1263
• 8e Hota SK, Jinan D, Panda SP, Pan R, Sahoo B. Asian J. Org. Chem. 2021; 10: 1848
• 8f Crespi S, Fagnoni M. Chem. Rev. 2020; 120: 9790
• 9a Santos MS, Cybularczyk-Cecotka M, König B, Giedyk M. Chem. Eur. J. 2020; 26: 15323
• 9b Dong J, Lyu X, Wang Z, Wang X, Song H, Liu Y, Wang Q. Chem. Sci. 2019; 10: 976
• 9c Wang Z, Dong J, Hao Y, Li Y, Liu Y, Song H, Wang Q. J. Org. Chem. 2019; 84: 16245
• 9d Li J, Huang C.-Y, Han J.-T, Li C.-J. ACS Catal. 2021; 11: 14148
• 9e Yan H, Hou Z.-W, Xu H.-C. Angew. Chem. Int. Ed. 2019; 58: 4592
• 9f Ikarashi G, Morofuji T, Kano N. Chem. Commun. 2020; 56: 10006
• 9g Xu F, Lai X.-L, Xu H.-C. Synlett 2021; 32: 369
• 9h Pitre SP, Muuronen M, Fishman DA, Overman LE. ACS Catal. 2019; 9: 3413
• 9i Jin J, MacMillan DW. C. Nature 2015; 525: 87
• 9j Wang X, Shao X, Cao Z, Wu X, Zhu C. Adv. Synth. Catal. 2022; 364: 1200
• 9k Wang Z, Ji X, Zhao J, Huang H. Green Chem. 2019; 21: 5512
• 9l Chen X, Luo X, Wang K, Liang F, Wang P. Synlett 2021; 32: 733
• 9m Lai X, Shu X, Song J, Xu H.-C. Angew. Chem. Int. Ed. 2020; 59: 10626
• 9n Zhang X.-Y, Weng W.-Z, Liang H, Yang H, Zhang B. Org. Lett. 2018; 20: 4686
• 9o Garza-Sanchez RA, Tlahuext-Aca A, Tavakoli G, Glorius F. ACS Catal. 2017; 7: 4057 ; corrigendum: ACS Catal. 2022, 12, 6640
• 9p Li J, Tan SS, Kyne SH, Chan PW. H. Adv. Synth. Catal. 2022; 364: 802
• 9q Procter RS. J, Davis HJ, Phipps RJ. Science 2018; 360: 419
• 9r Chen W.-M, Shang R, Fu M.-C, Fu Y. Chem. Eur. J. 2017; 23: 2537
• 9s Wang K, Liu X, Yang S, Tian Y, Zhou M, Zhou J, Jia X, Li B, Liu S, Chen J. Org. Lett. 2022; 24: 3471
• 9t Li D.-S, Liu T, Hong Y, Cao C.-L, Wu J, Deng H.-P. ACS Catal. 2022; 12: 4473
• 9u Bhakat M, Khatua B, Guin J. Org. Lett. 2022; 24: 5276
• 9v Zhang L, Pfund B, Wenger OS, Hu X. Angew. Chem. Int. Ed. 2022; 61: e202202649
• 9w Tian H, Yang H, Tian C, An G, Li G. Org. Lett. 2020; 22: 7709
• 9x Rammal F, Gao D, Boujnah S, Gaumont AC, Hussein AA, Lakhdar S. Org. Lett. 2020; 22: 7671
• 9y Zhao H, Jin J. Org. Lett. 2019; 21: 6179
• 9z Dong J, Yue F, Song H, Liu Y, Wang Q. Chem. Commun. 2020; 56: 12652
• 10a Kim Y.-S, Shin D.-H. J. Agric. Food Chem. 2004; 52: 781
• 10b Baser KH. C, Özek T, Akgül A, Tümen G. J. Essent. Oil Res. 1993; 5: 215
• 10c Ertl P, Schuhmann T. J. Nat. Prod. 2019; 82: 1258
• 10d Cao S, Foster C, Lazo JS, Kingston DG. I. Bioorg. Med. Chem. 2005; 13: 5830
• 11a Xia Y, Dong G. Nat. Rev. Chem. 2020; 4: 600
• 11b Deng L, Dong G. Trends Chem. 2020; 2: 183
• 11c Fumagalli G, Stanton S, Bower JF. Chem. Rev. 2017; 117: 9404
• 12a Li L, Fang L, Wu W, Zhu J. Org. Lett. 2020; 22: 5401
• 12b Lv X.-Y, Abrams R, Martin R. Nat. Commun. 2022; 13: 2394
• 12c Lee S.-C, Li L.-Y, Tsai Z.-N, Lee Y.-H, Tsao Y.-T, Huang P.-G, Cheng C.-K, Lin H.-B, Chen T.-W, Yang C.-H, Chiu C.-C, Liao H.-H. Org. Lett. 2022; 24: 85
• 12d Cong F, Mega RS, Chen J, Day CS, Martin R. Angew. Chem. Int. Ed. 2022; in press; DOI DOI: 10.1002/anie.202214633.
• 12e Mondal PP, Pal A, Prakash AK, Sahoo B. Chem. Commun. 2022; 58: 13202
• 12f Lv X.-Y, Abrams R, Martin R. Angew. Chem. Int. Ed. 2022; 62: e202217386
• 13 Kaila N, Janz KM, Huang A, Moretto AF, Bedard PW. ; WO 2008121817, 2008
• 14 Shang T.-Y, Lu L.-H, Cao Z, Liu Y, He W.-M, Yu B. Chem. Commun. 2019; 55: 5408
• 15 See the Supporting Information.
• 16 Compounds 3; General Procedure In a heat-gun-dried Schlenk tube equipped with a Teflon-coated stirrer bar, the appropriate N-heteroarene 1 (0.2 mmol, 1.0 equiv), dihydroquinazolinone substrate 2 (0.5 mmol, 2.5 equiv), 4CzIPN (0.004 mmol, 2 mol%), and K₂S₂O₈ (0.4 mmol, 2.0 equiv) were dissolved in anhyd DMF (1 mL) under an inert atmosphere. The mixture was stirred at rt for 18 h in the presence of light from blue LEDs. The reaction was then quenched by the addition of aq Na₂CO₃ (2 mL) and extracted with EtOAc (3 × 5 mL). The combined organic layers were washed with H₂O (5 mL) and brine (5 mL), and the solvents were removed under reduced pressure. The crude residue was purified by flash column chromatography (silica gel, PE–EtOAc).2-Cyclohexyl-4-methylquinoline (3aa)Colorless liquid; yield: 73%. ¹H NMR (500 MHz, CDCl₃): δ = 8.15 (d, J = 8.4 Hz, 1 H), 8.03 (d, J = 8.3 Hz, 1 H), 7.75 (ddd, J = 8.3, 6.9, 1.4 Hz, 1 H), 7.60 (ddd, J = 8.2, 6.9, 1.2 Hz, 1 H), 7.26 (s, 1 H), 2.98 (tt, J = 12.1, 3.4 Hz, 1 H), 2.75 (s, 3 H), 2.10–2.12 (m, 2 H), 1.98 (dt, J = 12.8, 3.0 Hz, 2 H), 1.77–1.81 (m, 1 H), 1.62 (qd, J = 12.6, 3.1 Hz, 2 H), 1.62 (qt, J = 12.8, 3.3 Hz, 2 H), 1.44 (tt, J = 12.8, 3.6 Hz, 1 H). ¹³C NMR (126 MHz, CDCl₃): δ = 166.7, 147.8, 144.4, 129.7, 129.1, 127.2, 125.5, 123.7, 120.4, 47.8, 33.0, 26.7, 26.3, 19.0.4-Methyl-2-(1-phenylcyclopropyl)quinoline (3af)Colorless liquid; yield: 77%. ¹H NMR (500 MHz, CDCl₃): δ = 8.03 (d, J = 8.5 Hz, 1 H), 7.90 (d, J = 8.3 Hz, 1 H), 7.67 (ddd, J = 8.4, 6.9, 1.3 Hz, 1 H), 7.48 (ddd, J = 8.2, 6.9, 1.2 Hz, 1 H), 7.43–7.45 (m, 2 H), 7.36–7.39 (m, 2 H), 7.28–7.30 (m, 1 H), 6.95 (s, 1 H), 2.55 (s, 3 H), 1.81 (dd, J = 6.2, 3.5 Hz, 2 H), 1.36 (dd, J = 6.5, 3.8 Hz, 2 H). ¹³C NMR (126 MHz, CDCl₃): δ = 163.9, 147.8, 144.0, 143.6, 130.3, 129.8, 129.1, 128.7, 126.8, 126.7, 125.5, 123.7, 122.1, 32.3, 18.8, 17.3.(4-Cyclohexylquinolin-2-yl)(piperidin-1-yl)methanon (3da)Colorless liquid; yield: 51%. ¹H NMR (500 MHz, CDCl₃): δ = 8.01–8.31 (m, 2 H), 7.70 (t, J = 7.6 Hz, 1 H), 7.58 (t, J = 7.7 Hz, 1 H), 7.51 (s, 1 H), 3.78–3.80 (m, 2 H), 3.47–3.49 (m, 2 H), 3.30–3.36 (m, 1 H), 2.00–2.02 (m, 2 H), 1.91–1.94 (m, 2 H), 1.82–1.85 (m, 1 H), 1.67–1.74 (m, 4 H), 1.49–1.61 (m, 6 H), 1.29–1.37 (m, 1 H). ¹³C NMR (126 MHz, CDCl₃): δ = 168.3, 154.8, 154.6, 147.2, 130.9, 129.4, 127.0, 126.8, 123.1, 116.8, 48.5, 43.4, 39.3, 33.6, 27.0, 26.7, 26.4, 25.7, 24.8.1-Cyclohexyl-6-(4-methoxyphenyl)isoquinoline (3ha)White solid; yield: 76%; mp 118 °C. ¹H NMR (500 MHz, CDCl₃): δ = 8.48 (d, J = 5.7 Hz, 1 H), 8.26 (d, J = 8.9 Hz, 1 H), 7.93 (d, J = 1.6 Hz, 1 H), 7.80 (dd, J = 8.8, 1.8 Hz, 1 H), 7.66–7.68 (m, 2 H), 7.50 (d, J = 5.7 Hz, 1 H), 7.03–7.05 (m, 2 H), 3.88 (s, 3 H), 3.57 (tt, J = 11.7, 3.2 Hz, 1 H), 1.93–2.01 (m, 4 H), 1.80–1.88 (m, 3 H), 1.50–1.57 (m, 2 H), 1.38–1.44 (m, 1 H). ¹³C NMR (126 MHz, CDCl₃): δ = 165.7, 160.0, 142.5, 141.9, 137.0, 132.8, 128.7, 126.4, 125.5, 125.2, 124.5, 119.2, 114.6, 55.6, 41.8, 32.8, 27.1, 26.4.