Potassium tert-Butoxide Promoted Intramolecular Mizoroki–Heck-Type Radical Cyclization: Photoluminescence Properties and Application in Live Cancer-Cell Imaging

Mahalingam Sivaraman; Sivakalai Mayakrishnan; Chandrasekar Balachandran; Shin Aoki; Narayanan Uma Maheswari; Paramasivan T. Perumal

doi:10.1055/a-1782-7150

Synlett, Table of Contents

Synlett 2022; 33(08): 785-790
DOI: 10.1055/a-1782-7150

letter

Potassium tert-Butoxide Promoted Intramolecular Mizoroki–Heck-Type Radical Cyclization: Photoluminescence Properties and Application in Live Cancer-Cell Imaging

Authors

Mahalingam Sivaraman∗

^aOrganic & Bioorganic Chemistry, CSIR- Central Leather Research Institute, Chennai-600020, India
Sivakalai Mayakrishnan

^aOrganic & Bioorganic Chemistry, CSIR- Central Leather Research Institute, Chennai-600020, India
Chandrasekar Balachandran

^bFaculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda 278-8510, Japan

^cResearch Institute for Biomedical Sciences (RIBS), Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan
Shin Aoki

^bFaculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda 278-8510, Japan

^cResearch Institute for Biomedical Sciences (RIBS), Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan
Narayanan Uma Maheswari∗

^aOrganic & Bioorganic Chemistry, CSIR- Central Leather Research Institute, Chennai-600020, India
Paramasivan T. Perumal∗

^aOrganic & Bioorganic Chemistry, CSIR- Central Leather Research Institute, Chennai-600020, India

Abstract

All articles of this category

Abstract

Privileged indole-fused phenanthridinones were synthesized by an inexpensive potassium tert-butoxide-promoted intramolecular Mizoroki–Heck-type radical cyclization. This method offers high atom- and step-economic C–C bond formation. An array of the synthesized compounds showed good photoluminescence properties, and could be successfully applied as fluorescent bioprobes for imaging of living cancer cells.

Key words

transition-metal-free reaction - C–H bond functionalization - potassium tert-butoxide - Mizoroki–Heck reaction - phenanthridinones - indoles

Full Text

References

References and Notes

1a Yamaguchi J, Muto K, Itami K. Eur. J. Org. Chem. 2013; 19
1b Ball CJ, Willis MC. Eur. J. Org. Chem. 2013; 425
1c Vlaar T, Ruijter E, Orru RV. A. Adv. Synth. Catal. 2011; 353: 809
1d Johansson C. C. C., Colacot T. J.; Angew. Chem. Int. Ed.; 2010, 49, 676.
1e Cahiez G, Moyeux A. Chem. Rev. 2010; 110: 1435
1f Yin L, Liebscher J. Chem. Rev. 2007; 107: 133
1g Corbet J.-P, Mignani G. Chem. Rev. 2006; 106: 2651
1h Bellina F, Rossi R. Chem. Rev. 2010; 110: 1082
1i Yang Y, Lan J, You J. Chem. Rev. 2017; 117: 8787

For ligand drawbacks, see:

2a Fleckenstein CA, Plenio H. Organometallics 2008; 27: 3924
2b Snelders DJ. M, van Koten G, Gebbink RJ. M. K. J. Am. Chem. Soc. 2009; 131: 11407
2c Wang D, Weinstein AB, White PB, Stahl SS. Chem. Rev. 2018; 118: 2636
2d Zhao T, Ghosh P, Martinez Z, Liu X, Meng X, Darensbourg MY. Organometallics 2017; 36: 1822
2e Würtz S, Glorius F. Acc. Chem. Res. 2008; 41: 1523 For the prices of various transition metals, see
2f www.metalprices.com (accessed Mar 16, 2022).

3a Garrett CE, Prasad K. Adv. Synth. Catal. 2004; 346: 889
3b Chatterjee S, Sarkar S, Bhattacharya S. Chem. Res. Toxicol. 2014; 27: 1887
3c Egorova KS, Ananikov VP. Organometallics 2017; 36: 4071
3d Banik A, Paira R, Shaw BK, Vijaykumar G, Mandal SK. J. Org. Chem. 2018; 83: 3236
3e Bera K, Sarkar S, Jalal S, Jana U. J. Org. Chem. 2012; 77: 8780
3f Duval JF. L, Paquet N, Lavoie M, Fortin C. Environ. Sci. Technol. 2015; 49: 6625

4 Sun C.-L, Shi Z.-J. Chem. Rev. 2014; 114: 9219

5a Rueping M, Leiendecker M, Das A, Poisson T, Bui L. Chem. Commun. 2011; 47: 10629
5b Kumar S, Rathore V, Verma A, Prasad CD, Kumar A, Yadav A, Jana S, Sattar M, Meenakshi Meenakshi, Kumar S. Org. Lett. 2015; (17) 82
5c Bhakuni BS, Kumar A, Balkrishna SJ, Sheikh JA, Konar S, Kumar S. Org. Lett. 2012; 14: 2838
5d Cuthbertson J, Gray VJ, Wilden JD. Chem. Commun. 2014; 50: 2575
5e Liu Y, Xu J, Zhang J, Xu X, Jin Z. Org. Lett. 2017; 19: 5709
5f Nocera G, Young A, Palumbo F, Emery KJ, Coulthard G, McGuire TM, Tuttle T, Murphy JA. J. Am. Chem. Soc. 2018; 140: 9751
5g Chan TL, Wu Y, Choy PY, Kwong FY. Chem. Eur. J. 2013; 19: 15802
5h De S, Mishra S, Kakde BN, Dey D, Bisai A. J. Org. Chem. 2013; 78: 7823
5i Patil M. J. Org. Chem. 2016; 81: 632
5j Mehta VP, Punji B. RSC Adv. 2013; 3: 11957
5k Rowlands GJ. Annu. Rep. Prog. Chem., Sect. B: Org. Chem. 2012; 108: 15
5l Zhang L, Yang H, Jiao L. J. Am. Chem. Soc. 2016; 138: 7151

6 Yanagisawa S, Ueda K, Taniguchi T, Itami K. Org. Lett. 2008; 10: 4673

7a Sun C.-L, Li H, Yu D.-G, Yu M, Zhou X, Lu X.-Y, Huang K, Zheng S.-F, Li B.-J, Shi Z.-J. Nat. Chem. 2010; 2: 1044
7b Shirakawa E, Itoh K.-i, Higashino T, Hayashi T. J. Am. Chem. Soc. 2010; 132: 15537
7c Sun C.-L, Gu Y.-F, Wang B, Shi Z.-J. Chem. Eur. J. 2011; 17: 10844
7d Chen W.-C, Hsu Y.-C, Shih W.-C, Lee C.-Y, Chuang W.-H, Tsai Y.-F, Chen PP.-Y, Ong T.-G. Chem. Commun. 2012; 48: 6702
7e Roman DS, Takahashi Y, Charette AB. Org. Lett. 2011; 13: 3242
7f Shirakawa E, Zhang X, Hayashi T. Angew. Chem. Int. Ed. 2011; 50: 4671

8a Studer A, Curran DP. Angew. Chem. Int. Ed. 2011; 50: 5018
8b Zhou S, Anderson GM, Mondal B, Doni E, Ironmonger V, Kranz M, Tuttle T, Murphy JA. Chem. Sci. 2014; 5: 476
8c Barham JP, Coulthard G, Emery KJ, Doni E, Cumine F, Nocera G, John MP, Berlouis LE. A, McGuire T, Tuttle T, Murphy JA. J. Am. Chem. Soc. 2016; 138: 7402
8d Drapeau MP, Fabre I, Grimaud L, Ciofini I, Ollevier T, Taillefer M. Angew. Chem. Int. Ed. 2015; 54: 10587

9a Ning X.-S, Liang X, Hu K.-F, Yao C.-Z, Qu J.-P, Kang Y.-B. Adv. Synth. Catal. 2018; 360: 1590
9b Li S.-S, Xia Y.-Q, Hu F.-Z, Liu C.-F, Su F, Dong L. Chem. Asian J. 2016; 11: 3165
9c Ning X.-S, Wang M.-M, Qu J.-P, Kang Y.-B. J. Org. Chem. 2018; 83: 13523
9d Shan X.-H, Zheng H.-X, Yang B, Tie L, Fu J.-L, Qu J.-P, Kang Y.-B. Nat. Commun. 2019; 10: 908
9e Shan X.-H, Yang B, Zheng H.-X, Qu J.-P, Kang Y.-B. Org. Lett. 2018; 20: 7898
9f Zhang Z, Liu K, Chen X, Su S.-J, Deng Y, Zeng W. RSC Adv. 2017; 7: 30554
9g Lee HK, Dao PD. Q, Kim Y.-s, Cho CS. Synthesis 2018; 50: 3243
9h Guo X, Han Q, Tang Z, Su L, Zhang X, Zhang X, Lin S, Huang Q. Tetrahedron Lett. 2018; 59: 1568

10a Park GY, Wilson JJ, Song Y, Lippard SJ. Proc. Natl. Acad. Sci. U.S.A. 2012; 109: 11987
10b Rajagopalan R, Lin T.-S, Karwa AS, Poreddy AR, Asmelash B, Dorshow RB. ACS Med. Chem. Lett. 2012; 3: 284
10c Abdel-Halim OB, Morikawa T, Ando S, Matsuda H, Yoshikawa M. J. Nat. Prod. 2004; 67: 1119
10d Berkov S, Cuadrado M, Osorio E, Viladomat F, Codina C, Bastida J. Planta Med. 2009; 75: 1351
10e Suna Q, Shen Y.-H, Tiana J.-M, Tanga J, Sua J, Liua R.-H, Lia H.-L, Xua X.-K, Zhang W.-D. Chem. Biodiversity 2009; 6: 1751
10f Miao F, Yang X.-J, Ma Y.-N, Zheng F, Song X.-P, Zhou L. Chem. Pharm. Bull. 2012; 60: 1508
10g Alawode OE, Naganaboina V, Liyanage T, Desper J, Rayat S. Org. Lett. 2014; 16: 1494
10h Dubost E, Dumas N, Fossey C, Magnelli R, Butt-Gueulle S, Ballandonne C, Caignard DH, Dulin F, de-Oliveira Santos JS, Millet P, Charnay Y, Rault S, Cailly T, Fabis F. J. Med. Chem. 2012; 55: 9693

11a Chen C, Shang G, Zhou J, Yu Y, Li B, Peng J. Org. Lett. 2014; 16: 1872
11b Yan L, Zhao D, Lan J, Cheng Y, Guo Q, Li X, Wu N, You J. Org. Biomol. Chem. 2013; 11: 7966

12a Sivaraman M, Muralidharan D, Perumal PT. Tetrahedron Lett. 2012; 53: 6039
12b Sivaraman M, Perumal PT. Org. Biomol. Chem. 2014; 12: 1318
12c Sivaraman M, Perumal PT. RSC Adv. 2014; 4: 52060

13 CCDC: 1519207 contains the supplementary crystallographic data for compound 3a. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures.

14a Mayakrishnan S, Arun Y, Balachandran C, Awale S, Maheswari NU, Perumal PT. ACS Omega 2017; 2: 2694
14b Mayakrishnan S, Arun Y, Balachandran C, Emi N, Muralidharan D, Perumal PT. Org. Biomol. Chem. 2016; 14: 1958
14c Nandakumar A, Perumal PT. Org. Lett. 2013; 15: 382
14d Mayakrishnan S, Arun Y, Maheswari NU, Perumal PT. Chem. Commun. 2018; 54: 11889

15a Wang W, Chen C, Li X, Wang S, Luo X. Chem. Commun. 2015; 51: 9109
15b Miao J, Cui H, Jin J, Lai F, Wen H, Zhang X, Ruda GF, Chen X, Yin D. Chem. Commun. 2015; 51: 881
15c Abeywickrama CS, Baumann HJ, Alexander N, Shriver LP, Konopka M, Pang Y. Org. Biomol. Chem. 2018; 16: 3382
15d Cheng Y, Li G, Liu Y, Shi Y, Gao G, Wu D, Lan J, You J. J. Am. Chem. Soc. 2016; 138: 4730

16a Lu Y.-J, Deng Q, Hu D.-P, Wang Z.-Y, Huang B.-H, Du Z.-Y, Fang Y.-X, Wong W.-L, Zhang K, Chow C.-F. Chem. Commun. 2015; 51: 15241
16b Shaikh AC, Shalini S, Vaidhyanathan R, Mane MV, Barui AK, Patra CR, Venkatesh Y, Bangal PR, Patil NT. Eur. J. Org. Chem. 2015; 4860
16c Hyun JY, Park S.-H, Park CW, Kim HB, Cho JW, Shin I. Org. Lett. 2019; 21: 4439

17 3-(2-(2-Bromophenyl)-1H-indol-1-yl)-5,5-dimethylcyclohex-2-en-1-ones 2a–n; General ProcedureA suspension of the appropriate cyclohexanone 1 (1.0 equiv), CuI (0.2 equiv), l-proline (0.4 equiv), and K₂CO₃ (2.0 equiv) in DMSO under N₂ was stirred at 100 °C for 3 h. The mixture was then diluted with H₂O and extracted with EtOAc. The combined organic phases were washed with brine, dried (Na₂SO₄), and concentrated under reduced pressure. The residue was purified by column chromatography [silica gel, PE–EtOAc (7:3)].3-[2-(2-Bromophenyl)-1H-indol-1-yl]-5,5-dimethylcyclohex-2-en-1-one (2a)Yellow viscous liquid; yield: 276 mg (92%). ¹H NMR (400 MHz, CDCl₃): δ = 7.67 (t, J = 7.7 Hz, 2 H), 7.50 (d, J = 8.2 Hz, 1 H), 7.37 (d, J = 6.3 Hz, 2 H), 7.31–7.22 (m, 3 H), 6.76 (s, 1 H), 6.26 (s, 1 H), 2.28 (s, 2 H), 2.21 (s, 2 H), 0.87 (s, 6 H). ¹³C NMR (100 MHz, CDCl₃): δ = 199.21, 155.61, 137.65, 136.61, 134.22, 133.30, 132.47, 130.31, 128.64, 127.39, 124.43, 124.35, 123.46, 121.70, 121.25, 111.25, 108.42, 50.96, 44.14, 33.22, 27.94.7,7-Dimethyl-7,8-dihydroindolo[1,2-f]phenanthridin-5(6H)-ones 3a–m; General ProcedureA solution of the appropriate cyclohexanone 2 (1.0 equiv), t-BuOK (2.0 equiv), and 1,10-phen (0.5 equiv) in DMF was stirred at 120 °C under N₂ until the reaction was complete (TLC). The mixture was then diluted with H₂O and extracted with EtOAc. The combined organic phases were washed with brine, dried (Na₂SO₄), and concentrated under reduced pressure. The residue was purified by column chromatography [silica gel, PE–EtOAc (8:2)].7,7,12-Trimethyl-7,8-dihydroindolo[1,2-f]phenanthridin-5(6H)-one (3d)Yellow solid; yield: 50 mg (63%); mp 159–161 °C. ¹H NMR (400 MHz, CDCl₃): δ = 9.24 (d, J = 8.3 Hz, 1 H), 7.97 (d, J = 7.8 Hz, 1 H), 7.84 (d, J = 8.7 Hz, 1 H), 7.53–7.39 (m, 3 H), 7.08 (d, J = 8.7 Hz, 1 H), 7.04 (s, 1 H), 3.29 (s, 2 H), 2.53 (s, 2 H), 2.51 (s, 3 H), 1.16 (s, 6 H). ¹³C NMR (100 MHz, CDCl₃): δ = 197.82, 149.09, 136.48, 133.08, 131.88, 131.85, 128.29, 127.12, 126.77, 125.80, 124.46, 123.25, 123.00, 120.79, 116.15, 112.00, 96.62, 52.32, 44.00, 32.29, 28.62, 21.49. HRMS (ESI): m/z [M + H]⁺ calcd for C₂₃H₂₂NO: 328.1701; found: 328.1700.

Supplementary Material

Supporting Information (PDF)