Pd/C Catalyzed Dehalogenation of (Hetero)aryls Using Triethyl­silane as Hydrogen Donor

Abstract

(Hetero)aryl dehalogenation is a classical transformation usually performed using hydrogen gas and a metal supported on carbon, notably palladium (Pd/C). Though efficient, the need for a milder and operationally simple dehalogenation can arise. We found that the combination of Pd/C as catalyst and triethylsilane (TES) as hydrogen donor in THF resulted in a broadly applicable, easy to set up, and scalable debromination and deiodination. Optimization of the reaction showed that 1 mol% of Pd/C and 4 equiv of TES at room temperature were sufficient to obtain full conversion of most synthons of pharmaceutical interest in 4–24 h. The newly found conditions were applied to a large range of aromatic and heteroaromatic substrates, affording the desired targets in good to excellent yields with an exceptional functional group tolerance.

Key words

dehalogenation - triethylsilane - Pd/C - aryl - heteroaryl

Publication History

Received: 09 November 2022

Accepted after revision: 23 January 2023

Article published online:
27 February 2023

• References

• 1 Darnerud PO. Environ. Int. 2003; 29: 841
• 2 Alonso F, Beletskaya IP, Yus M. Chem. Rev. 2002; 102: 4009
• 3 Johnstone RA. W, Wilby AH, Entwistle ID. Chem. Rev. 1985; 85: 129
• 4 Mao Z, Gu H, Lin X. Catalysts 2021; 11: 1078
• 5 Ma X, Liu S, Liu Y, Gu G, Xia C. Sci. Rep. 2016; 6: 25068
• 6 Iranpoor N, Firouzabadi H, Azadi R. J. Organomet. Chem. 2010; 695: 887
• 7 The combination of alkylsilanes and Pd/C was previously reported for the reduction of activated functional groups (azide, imine, nitro, among others), see: Mandal PK, McMurray JS. J. Org. Chem. 2007; 72: 6599
• 8 The lower yield obtained for 17 could be explained by the low solubilities of the compound in the eluting mixtures.
• 9 Ding Y, Mao L, Xu D, Xi H, Yang L, Xu H, Geng W, Gao Y, Xia C, Zangm X, Meng Q, Wu D, Zhao J, Hu W. Bioorg. Med. Chem. Lett. 2015; 25: 2744
• 10 Panda S, Coffin A, Nguyen QN, Tantillo DJ, Ready JM. Angew. Chem. Int. Ed. 2016; 55: 2205
• 11 Kan J, Huang S, Lin J, Zhang M, Su W. Angew. Chem. Int. Ed. 2015; 54: 2199
• 12 Wei B, Zhang D, Chen Y.-H, Lei A, Knochel P. Angew. Chem. Int. Ed. 2019; 58: 15631
• 13 Stokes BJ, Dong H, Leslie BE, Pumphrey AL, Driver TG. J. Am. Chem. Soc. 2007; 129: 7500
• 14 Kudo N, Perseghini M, Fu GC. Angew. Chem. Int. Ed. 2006; 45: 1282
• 15 Amantini D, Beleggia R, Fringuelli F, Pizzo F, Vaccaro L. J. Org. Chem. 2004; 69: 2896
• 16 Kawano T, Hirano K, Satoh T, Miura M. J. Am. Chem. Soc. 2010; 132: 6900
• 17 Alam T, Rakshit A, Dhara HN, Palai A, Patel BK. Org. Lett. 2022; 36: 6619
• 18 Allison BD, Mani NS. ACS Omega 2017; 2: 397
• 19 Chmiel AF, Williams OP, Chernowsky CP, Yeung CS, Wickens ZK. J. Am. Chem. Soc. 2021; 143: 10882
• 20 Greshock TJ, Moore KP, McClain RT, Bellomo A, Chung CK, Dreher SD, Kutchukian PS, Peng Z, Davies IW, Vachal P, Ellwart M, Manolikakes SM, Knochel P, Nantermet PG. Angew. Chem. Int. Ed. 2016; 55: 13714
• 21 Lobo MM, Oliveira SM, Brusco I, Machado P, Timmers LF. S. M, De Souza ON, Martins MA. P, Bonacorso HG, Dos Santos JM, Canova B, Da Silva TV. F, Zanatta N. Eur. J. Med. Chem. 2015; 102: 143
• 22 Spencer J, Rathnam RP, Harvey AL, Clements CJ, Clark RL, Barrett MP, Wong PE, Male L, Coles SJ, Mackay SP. Bioorg. Med. Chem. 2011; 19: 1802