Hydrosilane-Promoted Dehalogenation of Heteroaryl Halides under Air Conditions

Abstract

An efficient dehalogenation reaction of α-substituted halogenated heterocycles catalyzed by Pd/C with triethylsilane (TES) was developed. This study explores the catalytic dehalogenation of N-heteroaryl halides using a Pd/C-K₂CO₃ system, with TES serving as the hydrogen source under air conditions (air and moisture). The reaction conditions are compatible with various functional groups with good to excellent yields.

Keywords

Hydrodehalogenation - N-Heteroaryl halides - Pd/C catalyst - Triethylsilane

Publication History

Received: 02 December 2025

Accepted after revision: 09 February 2026

Accepted Manuscript online:
10 February 2026

Article published online:
19 February 2026

• References

• 1 Alonso F, Beletskaya IP, Yus M. Chem Rev 2002; 102: 4009-4092
• 2 Chioua M, Martínez-Alonso E, Gonzalo-Gobernado R. et al. J Med Chem 2019; 62: 2184-2201
• 3 Cellier PP, Spindler J-F, Taillefer M, Cristau H-J. Tetrahedron Lett 2003; 44: 7191-7195
• 4 Deng J, Feng E, Ma S. et al. J Med Chem 2011; 54: 4508-4522
• 5 Manteau B, Genix P, Brelot L. et al. Eur J Org Chem 2010; 2010: 6043-6066
• 6 Bonnefous C, Payne JE, Roppe J. et al. J Med Chem 2009; 52: 3047-3062
• 7 Kinarivala N, Trippier PC. Tetrahedron Lett 2014; 55: 5386-5389
• 8 Giannouli V, Lougiakis N, Kostakis IK. et al. Bioorg Med Chem Lett 2016; 26: 5229-5233
• 9 Hagui W, Besbes N, Srasra E, Soulé J-F, Doucet H. RSC Adv 2016; 6: 17110-17117
• 10 Grivsky EM, Lee S, Sigel CW, Duch DS, Nichol CA. J Med Chem 1980; 23: 327-329
• 11 Ozturk T, McKillop A. Can J Chem 2000; 78: 1158-1164
• 12 Karakaya I, Karabuga S, Mart M, Altundas R, Ulukanli S. Synthesis 2016; 48: 1719-1726
• 13 Chelucci G, Figus S. J Mol Catal A Chem 2014; 393: 191-209
• 14 Chelucci G. Tetrahedron Lett 2010; 51: 1562-1565
• 15 Sato I, Nakao T, Sugie R, Kawasaki T, Soai K. Synthesis 2004; 2004: 1419-1428
• 16 Nam KY, Damodar K, Lee Y. et al. Molecules 2021; 26: 646
• 17 Cailly T, Fabis F, Legay R, Oulyadi H, Rault S. Tetrahedron 2007; 63: 71-76
• 18 Lefebvre O, Marull M, Schlosser M. Eur J Org Chem 2003; 2003: 2115-2121
• 19 Cottet F, Marull M, Lefebvre O, Schlosser M. Eur J Org Chem 2003; 2003: 1559-1568
• 20 Rauckman BS, Tidwell MY, Johnson JV, Roth B. J Med Chem 1989; 32: 1927-1935
• 21 Korvinson KA, Akula HK, Malinchak CT. et al. Adv Synth Catal 2020; 362: 166-176
• 22 Deng J, Feng E, Ma S. et al. J Med Chem 54: 4508-4522
• 23 Logvinov AA, Casillo E, Jouffroy M, Nolan SP. ACS Med Chem Lett 2025; 16: 1825-1829
• 24 Hirasawa N, Takahashi Y, Fukuda E, Sugimoto O, Tanji K-I. Tetrahedron Lett 2008; 49: 1492-1494
• 25 Jouha J, Khouili M, Hiebel M-A, Guillaumet G, Suzenet F. Tetrahedron Lett 2018; 59: 3108-3111
• 26 Mani NS, Chen P, Jones TK. J Org Chem 1999; 64: 6911-6914
• 27 Jiang F, Wang H-J, Jin Y-H. et al. J Med Chem 2016; 59: 10498-10519
• 28 Perner RJ, DiDomenico S, Koenig JR. et al. J Med Chem 2007; 50: 3651-3660
• 29 Vetrichelvan M, Sankar U, Bokkala V. et al. ChemistrySelect 2023; 8: e202203856
• 30 General procedure for the hydrodehalogenation of α-substituted halogenated heterocycles: α-Substituted halogenated heterocycles (2.0 mmol), 10% Pd/C (4.0 wt%, 13.0 mg), anhydrous K₂CO₃ (3.0 mmol, 414.0 mg, 1.5 equiv), and methanol (MeOH) (4.0 mL) were added to a 50 mL single flask in sequence. TES (4 mmol, 464.0 mg, 2.0 equiv) was slowly injected by syringe. The reaction mixture was stirred at a temperature range of room temperature to 40 °C for a specific period. Upon completion of the reaction, the Pd/C catalyst was removed by Celite. The filtrate was concentrated under reduced pressure using a rotary evaporator and then purified by column chromatography (hexane/ethyl acetate (EtOAc) or dichloromethane (DCM)/methanol as the eluent) to obtain the dehalogenation product