Synlett 2016; 27(11): 1674-1676
DOI: 10.1055/s-0035-1561944
letter
© Georg Thieme Verlag Stuttgart · New York

Synthesis and Stabilities of 3-Borylated Indoles

Muhannad A. E. Al-Saedy
Department of Chemistry, The University of Sheffield, Brook Hill, Sheffield, S3 7HF, UK   Email: j.harrity@sheffield.ac.uk
,
Joseph P. A. Harrity*
Department of Chemistry, The University of Sheffield, Brook Hill, Sheffield, S3 7HF, UK   Email: j.harrity@sheffield.ac.uk
› Author Affiliations
Further Information

Publication History

Received: 10 February 2016

Accepted after revision: 03 March 2016

Publication Date:
18 March 2016 (online)


Abstract

We report herein that 3-pinacol boronic esters undergo facile protodeborylation in the presence of palladium catalysts and base, and this contributes significantly to the generation of nonborylated indole byproducts in the B2Pin2-mediated palladium-catalysed borylative cyclization of 2-alkynylanilides. Suginome’s reagent provides an alternative method to access 3-borylated indoles as these compounds are less susceptible to protodeborylation.

Supporting Information

 
  • References and Notes

  • 1 Boronic Acids . Hall DG. Wiley-VCH; Weinheim: 2005
  • 4 Kirkham JD, Edeson SJ, Stokes S, Harrity JP. A. Org. Lett. 2012; 14: 5354
  • 7 Cacchi S, Fabrizi G. Chem. Rev. 2005; 105: 2873
  • 8 Iwadate N, Suginome M. J. Am. Chem. Soc. 2010; 132: 2548
  • 9 Cid J, Carbó JJ, Fernández E. Chem. Eur. J. 2014; 20: 3616
  • 10 Amjad M, Knight DW. Tetrahedron Lett. 2004; 45: 539
  • 11 Xu L, Li P. Chem. Commun. 2015; 51: 5656
  • 12 Kaila N, Follows B, Leung L, Thomason J, Huang A, Moretto A, Janz K, Lowe M, Mansour TS, Hubeau C, Page K, Morgan P, Fish S, Xu X, Williams C, Saiah E. J. Med. Chem. 2014; 57: 1299
  • 13 Representative Procedure for the Borylation of N-Tosyl 3-Iodo Indoles – Synthesis of Indole 19 2-Cyclopropyl-3-iodo-1-tosyl-1H-indole (11, 200 mg, 0.455 mmol), Pd2(dba)3 (21 mg, 0.023 mmol), Cs2CO3 (297 mg, 0.910 mmol), PinB-Bdan (268 mg, 0.910 mmol) in MeOH (1 mL) was stirred at reflux under a nitrogen atmosphere for 2 h. The reaction mixture was allowed to cool to r.t., and EtOAc (10 mL) was added. The organic extract was washed with H2O (2 × 5 mL) and brine (5 mL), dried over MgSO4, and the solvents removed under reduced pressure to provide the crude product. Purification of the residue by flash chromatography on silica gel using a solvent gradient of PE–EtOAc (95:5), increasing in polarity to EtOAc gave the target compound 19 as a colorless solid (151 mg, 70%), mp 240–241 °C. 1H NMR (400 MHz, CDCl3): δ = 8.25 (d, J = 8.5 Hz, 1 H), 7.77 (d, J = 8.5 Hz, 2 H), 7.57 (d, J = 7.5 Hz, 1 H, ArH), 7.34–7.29 (m, 1 H, ArH), 7.25–7.20 (m, 3 H, ArH), 7.14 (dd, J = 8.0, 7.5 Hz, 2 H), 7.07 (dd, J = 8.5, 1.0 Hz, 2 H), 6.35 (dd, J = 7.0, 1.0 Hz, 2 H), 5.87 (s, 2 H), 2.39 (s, 3 H), 2.33 (tt, J = 8.5, 5.5 Hz, 1 H), 0.96 (dt, J = 8.5, 3.0 Hz, 2 H), 0.66–0.59 (m, 2 H). 13C NMR (101 MHz, CDCl3): δ = 146.4, 144.6, 140.8, 137.6, 137.0, 136.3, 132.2, 129.7, 127.6, 126.6, 124.3, 123.3, 120.7, 119.8, 117.9, 114.5, 105.9, 21.6, 10.3, 8.9. 11B NMR (128 MHz, CDCl3): δ = 30.9. FTIR: νmax = 3404, 3042, 2963, 2884, 1625, 1600 cm–1. HRMS (ESI-TOF): m/z [M + Na]+ calcd for C28H24BN3O2S: 500.1580; found: 500.1561.