Potassium Alkoxide/Disilane-Mediated Dehalogenative Deuteration

Abstract

Deuterated compounds are of great importance in chemistry and pharmaceuticals. Reductive dehalogenation is one of the most useful methods to incorporate deuterium into molecules. This article briefly discusses the historical development of dehalogenative deuteration reactions that involve transition-metal catalysis, radical halogen abstraction, alkali-metal reductive deuteration, and the recently developed potassium methoxide/hexamethyldisilane-mediated dehalogenation of aryl halides.

Key words

deuteration - dehalogenation - aryl halides - Transition-metal-free - potassium base - disilane

• References

• 1 Miyashita M, Sasaki M, Hattori I, Sakai M, Tanino K. Science 2004; 305: 495
• 2a Simmons EM, Hartwig JF. Angew. Chem. Int. Ed. 2012; 51: 3066
• 2b Wiberg KB. Chem. Rev. 1955; 55: 713
• 3a Timmins GS. Expert Opin. Ther. Pat. 2014; 24: 1067
• 3b Harbeson SL, Tung RD. MedChem News 2014; 8
• 3c Mullard A. Nat. Rev. Drug Discovery 2016; 15: 219
• 3d Harbeson SL, Tung RD. Annu. Rep. Med. Chem. 2011; 46: 403
• 3e Gant TG. J. Med. Chem. 2014; 57: 3595
• 3f Katsnelson A. Nat. Med. 2013; 19: 656
• 3g Atzrodt J, Derdau V, Kerr WJ, Reid M. Angew. Chem. Int. Ed. 2018; 57: 1758
• 4 Belleau B, Burba J, Pindell M, Reiffenstein J. Science 1961; 133: 102
• 5 Schmidt C. Nat. Biotechnol. 2017; 35: 493
• 6 For a review of metal-mediated/catalyzed reductive hydrodehalogenations, see: Alonso F, Beletskaya IP, Yus M. Chem. Rev. 2002; 102: 4009

Selected examples:
• 7a Spiegel DA, Wiberg KB, Schacherer LN, Medeiros MR, Wood JL. J. Am. Chem. Soc. 2005; 127: 12513
• 7b Soulard V, Villa G, Vollmar DP, Renaud P. J. Am. Chem. Soc. 2018; 140: 155
• 7c Zhang M, Yuan XA, Zhu C, Xie J. Angew. Chem. Int. Ed. 2019; 57: 312
• 7d Grainger R, Nikmal A, Cornella J, Larrosa I. Org. Biomol. Chem. 2012; 10: 3172

Selected recent examples:
• 8a Yu RP, Hesk D, Rivera N, Pelczer I, Chirik PJ. Nature 2016; 529: 195
• 8b Li W, Wang M.-M, Hu Y, Werner T. Org. Lett. 2017; 19: 5768
• 8c Loh YY, Nagao K, Hoover AJ, Hesk D, Rivera NR, Colletti SL, Davies IW, MacMillan DW. C. Science 2017; 358: 1182
• 8d Koniarczyk J, Hesk D, Overgard A, Davies IW, McNally A. J. Am. Chem. Soc. 2018; 140: 1990

For selected reviews, see:
• 8e Junk T, Catallo WJ. Chem. Soc. Rev. 1997; 26: 401
• 8f Atzrodt J, Derdau V, Kerr WJ, Reid M. Angew. Chem. Int. Ed. 2018; 57: 3022
• 9a Mongin F, Fourquez J, Rault S, Levacher V, Godard A, Trecourt F, Queguiner G. Tetrahedron Lett. 1995; 36: 8415
• 9b Koketsu K, Oguri H, Watanabe K, Oikawa H. Org. Lett. 2006; 8: 4719
• 9c For an example of hydrodehalogenation using NaH/LiI, see: Ong DY, Tejo C, Xu K, Hirao H, Chiba S. Angew. Chem. Int. Ed. 2017; 56: 1840
• 10a Inoue A, Kitagawa K, Shinokubo H, Oshima K. J. Org. Chem. 2001; 66: 4333
• 10b Salinger D, Bruckner R. Chem. Eur. J. 2009; 15: 6688
• 10c Weldon LH. P, Wilson CL. J. Chem. Soc. 1946; 235
• 10d Hall GE, Piccolini R, Roberts JD. J. Am. Chem. Soc. 1955; 77: 4540
• 11 Rathman TL, Bailey WF. Org. Process Res. Dev. 2009; 13: 144
• 12 Donald CS, Moss TA, Noonan GM, Roberts B, Durham CE. Tetrahedron Lett. 2014; 55: 3305
• 13 Oba M. J. Labelled Compd. Radiopharm. 2015; 58: 215
• 14a Janni M, Peruncheralathan S. Org. Biomol. Chem. 2016; 14: 3091
• 14b Kuriyama M, Hamaguchi N, Yano G, Tsukuda K, Sato K, Onomura O. J. Org. Chem. 2016; 81: 8934
• 15a Desmarets C, Kuhl S, Schneider R, Fort Y. Organometallics 2002; 21: 1554
• 15b For an example using 4,4′-di-tert-butylbiphenyl as the catalyst, stoichiometric NiCl₂·D₂O and an excess of lithium powder as reducing agents for dehalogenative deuteration, see: Alonso F, Radivoy G, Yus M. Tetrahedron 1999; 55: 4441
• 16 Landvatter SW, Schauer DJ, Garnes KT, Mack JF, Killmer LB. Jr. J. Labelled Compd. Radiopharm. 2001; 44: 1025

For selected examples, see:
• 17a Lockley WJ. S, Jones JR, Wilkinson DJ. J. Labelled Compd. Radiopharm. 2007; 50: 505
• 17b Kurita T, Aoki F, Mizumoto T, Maejima T, Esaki H, Maegawa T, Monguchi Y, Sajiki H. Chem. Eur. J. 2008; 14: 3371
• 17c Pyo A, Kim S, Kumar MR, Byeun A, Eom MS, Han MS, Lee S. Tetrahedron Lett. 2013; 54: 5207
• 17d Johansen SK, Sørensen L, Martiny L. J. Labelled Compd. Radiopharm. 2005; 48: 569
• 17e Gevorgyan A, Mkrtchyan S, Grigoryan T, Iaroshenko VO. ChemPlusChem 2018; 83: 375

Selected recent examples:
• 18a Dewanji A, Muck-Lichtenfeld C, Studer A. Angew. Chem. Int. Ed. 2016; 55: 6749
• 18b Hokamp T, Dewanji A, Lubbesmeyer M, Muck-Lichtenfeld C, Wurthwein E, Studer A. Angew. Chem. Int. Ed. 2017; 56: 13275
• 19a Miura Y, Oka H, Yamano E, Morita M. J. Org. Chem. 1997; 62: 1188
• 19b For an early example of the preparation of deuterated phenols using Raney Cu-Al alloy in 10% NaOD/D₂O solution, see: Tashiro M, Iwasaki A, Fukata G. J. Org. Chem. 1978; 43: 196
• 20a Zhang B, Li H, Ding Y, Yan Y, An J. J. Org. Chem. 2018; 83: 6006

For recent examples using alkali metal/EtOD for deuterium incorporation, see:
• 20b Ding Y, Luo S, Adijiang A, Zhao H, An J. J. Org. Chem. 2018; 83: 12269
• 20c Han M, Ding Y, Yan Y, Li H, Luo S, Adijiang A, Ling Y, An J. Org. Lett. 2018; 20: 3010
• 21 Yorimitsu H, Shinokubo H, Oshima K. Bull. Chem. Soc. Jpn. 2001; 74: 225
• 22a Mutsumi T, Iwata H, Maruhashi K, Monguchi Y, Sajiki H. Tetrahedron 2011; 67: 1158
• 22b Mutsumi T, Maruhashi K, Monguchi Y, Sajiki H. Synlett 2008; 18: 2811
• 23 A radical dehalogenative deuteration mediated by ^t BuOK using THF-d ₈ as a deuterium source was reported recently with only one substrate, see: Liu W, Hou F. Tetrahedron 2017; 73: 931
• 24a Davidson RS, Goodin JW. Tetrahedron Lett. 1981; 22: 163
• 24b Kimura M, Miyahara H, Moritani N, Sawaki Y. J. Org. Chem. 1990; 55: 3897
• 24c Liu C, Chen Z, Su C, Zhao X, Gao Q, Ning G.-H, Zhu H, Tang W, Leng K, Fu W, Tian B, Peng X, Li J, Xu Q.-H, Zhou W, Loh KP. Nat. Commun. 2018; 9: 80
• 25 Wang X, Zhu MH, Schuman DP, Zhong D, Wang WY, Wu LY, Liu W, Stoltz BM, Liu WB. J. Am. Chem. Soc. 2018; 140: 10970

For recent examples of the preparation of deuterated alkenes, see:
• 26a Puleo TR, Strong AJ, Bandar JS. J. Am. Chem. Soc. 2019; 141: 1467
• 26b Yabe Y, Sawama Y, Monguchi Y, Sajiki H. Chem. Eur. J. 2013; 19: 484 ; and references 20b and 20c
• 27 Song S, Sun X, Li X, Yuan Y, Jiao N. Org. Lett. 2015; 17: 2886