Metal-Free Directed C–H Borylation of Indoles at the Sterically Congested C2 Position

Wang Jiang; Jingyi Bai; Jiahang Lv; Yue Zhao; Chaoguo Yan; Zhuangzhi Shi

doi:10.1055/a-2126-1750

Synlett, Table of Contents

Synlett 2023; 34(18): 2220-2226
DOI: 10.1055/a-2126-1750

cluster

Modern Boron Chemistry: 60 Years of the Matteson Reaction

Metal-Free Directed C–H Borylation of Indoles at the Sterically Congested C2 Position

Wang Jiang

^aCollege of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou, P. R. of China

^bState Key Laboratory of Coordination Chemistry, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, P. R. of China

,

Jingyi Bai

^bState Key Laboratory of Coordination Chemistry, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, P. R. of China

,

Jiahang Lv

^bState Key Laboratory of Coordination Chemistry, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, P. R. of China

,

Yue Zhao

^bState Key Laboratory of Coordination Chemistry, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, P. R. of China

,

Chaoguo Yan∗

^aCollege of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou, P. R. of China

,

Zhuangzhi Shi∗

^aCollege of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou, P. R. of China

^bState Key Laboratory of Coordination Chemistry, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, P. R. of China

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Abstract

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Abstract

During the past few decades, transition metal-catalyzed C–H borylation has been one of the most notable advances in synthetic chemistry and has been widely employed in the preparation of organoboron reagents. Due to economic and heavy-metal-residue concerns, there is significant interest in the development of metal-free processes to mimic metallic systems. Here, we disclose a highly efficient metal-free approach for the directed C–H borylation of C3-substituted indoles at the sterically congested C2 position that uses the inexpensive boron reagent BBr₃. Compared with the conventional methods using transition metals, this practical protocol provides an ideal pathway to obtain numerous C2-borylated indoles. The benefit of the synthesis of complex molecules and their applicability to medicinal chemistry is also shown through the construction of key intermediates of (–)-goniomitine and bazedoxifene and by a total synthesis of the drug fluvastatin. Mechanistic experiments demonstrate the site selectivity of this C–H borylation process.

Key words

C–H bond activation - borylation - indoles - BBr₃ - site selectivity - metal-free reaction

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References

References and Notes

1a Indoles, Part 4: The Monoterpenoid Indole Alkaloids: Saxton J. E. The Chemistry ofHeterocyclic Compounds. Vol. 25 Wiley; Chichester: 1983
1b Indoles, The Monoterpenoid Indole Alkaloids: Supplement to Part 4 . Saxton JE. The Chemistry of Heterocyclic Compounds, Vol. 25; Wiley; Chichester: 1994
1c Sundberg RJ. Indoles . Academic; London: 1996
1d Kawasaki T, Higuchi K. Nat. Prod. Rep. 2005; 22: 761
1e Miller KA, Williams RM. Chem. Soc. Rev. 2009; 38: 3160
1f Kochanowska-Karamyan AJ, Hamann MT. Chem. Rev. 2010; 110: 4489
1g Xu Z, Wang Q, Zhu J. Chem. Soc. Rev. 2018; 47: 7882
1h Nagarajua K, Ma D. Chem. Soc. Rev. 2018; 47: 8018

2a Robinson B. Chem. Rev. 1969; 69: 227
2b Cacchi S, Fabrizi G. Chem. Rev. 2005; 105: 2873
2c Humphrey GR, Kuethe JT. Chem. Rev. 2006; 106: 2875
2d Cacchi S, Fabrizi G. Chem. Rev. 2011; 111: PR215
2e Shi Z, Glorius F. Angew. Chem. Int. Ed. 2012; 51: 9220
2f Bartoli G, Dalpozzo R, Nardi M. Chem. Soc. Rev. 2014; 43: 4728

3a Bandini M, Eichholzer A. Angew. Chem. Int. Ed. 2009; 48: 9608
3b Joucla L, Djakovitch L. Adv. Synth. Catal. 2009; 351: 673
3c Ping L, Chung DS, Bouffard J, Lee S.-g. Chem. Soc. Rev. 2017; 46: 4299
3d Leitch JA, Bhonoah Y, Frost CG. ACS Catal. 2017; 7: 5618
3e Prabagar B, Yang Y, Shi Z. Chem. Soc. Rev. 2021; 50: 11249

4a Hall DG. Boronic Acids: Preparation and Applications in Organic Synthesis, Medicine and Materials, 2nd ed., Vols. 1 and 2. Wiley–VCH; Weinheim: 2011
4b Suzuki A. Angew. Chem. Int. Ed. 2011; 50: 6722
4c Neeve EC, Geier SJ, Mkhalid IA. I, Westcott SA, Marder TB. Chem. Rev. 2016; 116: 9091
4d Collins BS. L, Wilson CM, Myers EL, Aggarwal VK. Angew. Chem. Int. Ed. 2017; 56: 11700
4e Cuenca AB, Shishido R, Ito H, Fernández E. Chem. Soc. Rev. 2017; 46: 415
4f Wang M, Shi Z. Chem. Rev. 2020; 120: 7348

5a Paul S, Chotana GA, Holmes D, Reichle RC, Maleczka RE, Smith MR. J. Am. Chem. Soc. 2006; 128: 15552
5b Stahl T, Müther K, Ohki Y, Tatsumi K, Oestreich M. J. Am. Chem. Soc. 2013; 135: 10978
5c Robbins DW, Boebel TA, Hartwig JF. J. Am. Chem. Soc. 2010; 132: 4068
5d Huang J, Macdonald SJ. F, Harrity JP. A. Chem. Commun. 2010; 46: 8770
5e Feng Y, Holte D, Zoller J, Umemiya S, Simke LR, Baran PS. J. Am. Chem. Soc. 2015; 137: 10160
5f Yuan K, Wang S. Org. Lett. 2017; 19: 1462
5g Lv J, Zhao B, Liu L, Han Y, Yuan Y, Shi Z. Adv. Synth. Catal. 2018; 360: 4054
5h Tian Y.-M, Guo X.-N, Wu Z, Friedrich A, Westcott SA, Braunschweig H, Radius U, Marder TB. J. Am. Chem. Soc. 2020; 142: 13136

6 Nicolaou KC, Dalby SM, Majumder U. J. Am. Chem. Soc. 2008; 130: 14942
7 Wooleb H, Wooleb A, van der Schaaf PA, Kolly R, End N. WO 2003018555 2003

8a Ishiyama T, Murata M, Miyaura N. J. Org. Chem. 1995; 60: 7508
8b Ishiyama T, Miyaura N. Chem. Rec. 2004; 3: 271
8c Pilarski LT, Szabó KJ. Angew. Chem. Int. Ed. 2011; 50: 8230
8d Kubota K, Iwamoto H, Ito H. Org. Biomol. Chem. 2017; 15: 285

9 Zhang Y, Lu BZ, Li G, Rodriguez S, Tan J, Wei H, Liu J, Roschangar F, Ding F, Zhao W, Qu B, Reeves D, Grinberg N, Lee H, Heckmann G, Niemeier O, Brenner M, Tsantrizos Y, Beaulieu PL, Hossain A, Yee N, Farina V, Senanayake CH. Org. Lett. 2014; 16: 4558

10a Mkhalid IA. I, Barnard JH, Marder TB, Murphy JM, Hartwig JF. Chem. Rev. 2010; 110: 890
10b Hartwig JF. Chem. Soc. Rev. 2011; 40: 1992
10c Hartwig JF. Acc. Chem. Res. 2012; 45: 864
10d Ros A, Fernández R, Lassaletta JM. Chem. Soc. Rev. 2014; 43: 3229

11 Jia Y, Zhou S. Org. Lett. 2014; 16: 3416
12 Han S, Movassaghi M. J. Am. Chem. Soc. 2011; 133: 10768

13a Sun C.-L, Shi Z.-J. Chem. Rev. 2014; 114: 9219
13b Li Y, Wu X.-F. Angew. Chem. Int. Ed. 2020; 59: 1770
13c Ingleson MJ. Sci. China Chem. 2019; 62: 1547
13d Zhong Q, Qin S, Yin Y, Hu J, Zhang H. Angew. Chem. Int. Ed. 2018; 57: 14891

14a Legare M.-A, Courtemanche M.-A, Rochette E, Fontaine F.-G. Science 2015; 349: 513
14b Lavergne JL, Jayaraman A, Castro LC. M, Rochette É, Fontaine F.-G. J. Am. Chem. Soc. 2017; 139: 14714
14c Rochette É, Desrosiers V, Soltani Y, Fontaine F.-G. J. Am. Chem. Soc. 2019; 141: 12305

15a Lv J, Chen X, Xue X.-S, Zhao B, Liang Y, Wang M, Jin L, Yuan Y, Han Y, Zhao Y, Lu Y, Zhao J, Sun W.-Y, Houk KN, Shi Z. Nature 2019; 575: 336
15b Wang Z.-J, Chen X, Wu L, Wong JJ, Liang Y, Zhao Y, Houk KN, Shi Z. Angew. Chem. Int. Ed. 2021; 60: 8500

16 Iqbal SA, Cid J, Procter RJ, Uzelac M, Yuan K, Ingleson MJ. Angew. Chem. Int. Ed. 2019; 58: 15381

17a Lv J, Zhao B, Han Y, Yuan Y, Shi Z. Chin. Chem. Lett. 2021; 32: 691
17b Wang D, Xue X.-S, Houk KN, Shi Z. Angew. Chem. Int. Ed. 2018; 57: 16861

18 CCDC 2053493 and 2053494 contains the supplementary crystallographic data for compounds 1b and 1c. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures.
19 Brown H, Rao BC. J. Org. Chem. 1957; 22: 1137
20 Zhang F, Spring DR. Chem. Soc. Rev. 2014; 43: 6906
21 Lv J, Zhao B, Yuan Y, Han Y, Shi Z. Nat. Commun. 2020; 11: 1316
22 Shang Y, Jonnada K, Yedage SL, Tu H, Zhang X, Lou X, Huang S, Su W. Chem. Commun. 2019; 55: 9547
23 Fuenfschiling PC, Hoehn P, Muetz J.-P. Org. Process Res. Dev. 2007; 11: 13
24 1-(1-Adamantylcarbonyl)-3-methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (1c); Typical Procedure A flame-dried 25-mL Schlenk tube was flushed with argon and then charged with indole 1a (58.6 mg, 0.2 mmol, 1.0 equiv) and dry DCM (1 mL, 0.2 M). A 1.0 M solution of BBr₃ in DCM, (0.22 mL, 1.1 equiv) was added slowly under argon. Pyridine (2.0 mmol) and pinacol (0.30 mmol) were then added sequentially, and the resulting mixture was stirred at rt for another 2 h until the reaction was complete (TLC). The solvent was removed directly under vacuum, and the crude product was purified by flash column chromatography [silica gel, EtOAc–PE (1:20)] to give a white solid; yield: 64.9 mg (77%). ATR-FTIR: 3023, 2976, 1685, 1352, 952, 728 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.59 (d, J = 8.3 Hz, 1 H), 7.52–7.50 (m, 1 H), 7.28–7.24 (m, 1 H), 7.19–7.15 (m, 1 H), 2.42 (s, 3 H), 2.16 (d, J = 3.0 Hz, 6 H), 2.10–2.08 (m, 3 H), 1.76–1.74 (m, 6 H), 1.36 (s, 12 H). ¹³C NMR (126 MHz, CDCl₃): δ = 183.2, 136.4, 132.5, 125.9, 124.1, 121.6, 119.7, 113.8, 83.1, 44.1, 38.0, 36.3, 28.0, 25.1, 9.9. HRMS (ESI): m/z [M + H]⁺ calcd for C₂₆H₃₅BNO₃: 420.2705; found: 420.2708.

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