Mechanism of the t-BuOM (M = K, Na, Li)/DMEDA-Mediated Direct C–H Arylation of Benzene: A Computational Study

Abstract

Over the past ten years, a combination of organic additive and t-BuOK/t-BuONa has been successfully used for the direct C–H arylation of arenes. Conceptually different from transition-metal-catalyzed cross-coupling reactions, these t-BuOK-mediated reactions have raised significant curiosity among organic chemists. Herein, a systematic computational study of each elementary step of the t-BuOM (M = K, Na, Li)/N ¹,N ²-dimethylethane-1,2-diamine (DMEDA) mediated direct C–H arylation of benzene is detailed. The presented mechanistic proposal relies on the complexation and reaction of t-BuOM with DMEDA (additive), which leads to the formation of different complexes such as SED(M⁺)^…PhI. These complexes mainly involve coordination of the metal ion (from t-BuOM) to the additive and iodobenzene via stabilizing cation–lone pair and cation–π interactions. Such complexation of a metal ion to an additive and iodobenzene not only ensures facile electron transfer to iodobenzene but also provides a lowest energy pathway for the subsequent radical addition and deprotonation step.

Key words

C–H arylation - mechanism - DFT - cross-coupling - potassium tert-butoxide

• References

• 1a Qin Y, Zhu L, Luo S. Chem. Rev. 2017; 117: 9433
• 1b Yang Y, Lan J, You J. Chem. Rev. 2017; 117: 8787
• 1c Sun C.-L, Shi Z.-J. Chem. Rev. 2014; 114: 9219
• 1d Arancon RA. D, Lin CS. K, Vargas C, Luque R. Org. Biomol. Chem. 2014; 12: 10
• 1e Merhritt EA, Olofsson B. Angew. Chem. Int. Ed. 2009; 48: 9052
• 2a Narayan R, Matcha K, Antonchick AP. Chem. Eur. J. 2015; 21: 14678
• 2b Budhwan R, Yadav S, Muraka S. Org. Biomol. Chem. 2019; 17: 6326
• 2c Roscales S, Csáky AG. Chem. Soc. Rev. 2014; 43: 8215
• 2d Bhunia A, Yetra SR, Biju AT. Chem. Soc. Rev. 2012; 41: 3140
• 2e Pan SC. Beilstein J. Org. Chem. 2012; 8: 1374
• 2f Zhang L, Jiao L. Chem. Sci. 2018; 9: 2711
• 3 Nocera G, Murphy JA. Synthesis 2020; 52: 327
• 4a Horton DA, Bourne GT, Smythe ML. Chem. Rev. 2003; 103: 893
• 4b Bringmann G, Price Mortimer AJ, Keller PA, Gresser MJ, Garner J, Breuning M. Angew. Chem. Int. Ed. 2005; 44: 5384
• 4c Frlan R, Kikelj D. Synthesis 2006; 2271
• 5a Yangisawa S, Ueda K, Taniguchi T, Itami K. Org. Lett. 2008; 10: 4673
• 5b Sun C.-L, Li H, Yu D.-G, Yu M, Zhou X, Lu X.-Y, Haung K, Zheng SF, Li BJ, Shi ZJ. Nat Chem. 2010; 2: 1044
• 5c Liu W, Cao H, Zhang H, Chung KH, He C, Wang H, Kwong FY, Lei A. J. Am. Chem. Soc. 2010; 132: 16737
• 5d Shirakawa E, Itoh K, Higashino T, Hayashi T. J. Am. Chem. Soc. 2010; 132: 15537
• 6 Studer A, Curran DP. Angew. Chem. Int. Ed. 2011; 50: 5018
• 7a Cuthbertson J, Gray VJ, Wilden JD. Chem. Commun. 2014; 50: 2575
• 7b Yi H, Jutand A, Lei A. Chem. Commun. 2015; 51: 545
• 8a Zhou S, Anderson GM, Mondal B, Doni E, Ironmonger V, Kranz M, Tuttle T, Murphy JA. Chem. Sci. 2014; 5: 476
• 8b Zhou S, Doni E, Anderson GM, Kane RG, MacDougall SW, Ironmonger VM, Tuttle T, Murphy JA. J. Am. Chem. Soc. 2014; 136: 17818
• 8c Barham JP, Coulthard G, Emery KJ, Doni E, Cumine F, Nocera G, John MP, Berlouis LE. A, McGuire T, Tuttle T, Murphy JA. J. Am. Chem. Soc. 2016; 138: 7402
• 8d Emery KJ, Tuttle T, Murphy JA. Org. Biomol. Chem. 2017; 15: 8810
• 9a Murphy JA. J. Org. Chem. 2014; 79: 3731
• 9b Doni E, Murphy JA. Chem. Commun. 2014; 50: 6073
• 9c Nocera G, Young A, Palumbo F, Emery KJ, Coulthard G, McGuire T, Tuttle T, Murphy JA. J. Am. Chem. Soc. 2018; 140: 9751
• 9d Barham JP, Dalton SE, Allison M, Nocera G, Young A, John MP, McGuire T, Campos S, Tuttle T, Murphy JA. J. Am. Chem. Soc. 2018; 140: 11510
• 10 Patil M. J. Org. Chem. 2016; 81: 632
• 11 Zhang L, Yang H, Jiao L. J. Am. Chem. Soc. 2016; 138: 7151
• 12 Chisholm MH, Drake SR, Naiini AA, Streib WE. Polyhedron 1991; 10: 337
• 13 See Scheme S6 in the Supporting Information for the mechanism of the reaction between [t-BuOK]₄ and DMEDA.
• 14 Liu W, Tian F, Wang X, Yu H, Bi Y. Chem. Commun. 2013; 49: 2983
• 15 Exner JH, Steiner EC. J. Am. Chem. Soc. 1974; 96: 1782
• 16 Optimization of the tert-butoxide ion coordinated to three t-BuOH molecules was not successful at the M062X level. Hence, a single-point energy calculation at the M062X level was performed on the gas-phase geometry optimized at the M062X/ 6-311G** level of theory.
• 17 We have also explored the dissociation of t-BuOK by employing coordination of three DMEDA molecules to the metal ion. It was found that accounting for three DMEDA molecules in the calculations showed a marginal reduction in the endoergicity of the dissociation process. This is mainly because of steric congestion at the metal center and the entropic penalty associated with the formation of an octahedral complex. See Scheme S2 in the Supporting Information for the energetics of dissociation of t-BuOM with coordination of three DMEDA molecules to the metal ion.
• 18 TS-2 was confirmed by intrinsic reaction coordinate (IRC) calculations at the M062X level. Additionally, we optimized the perturbed structures obtained through IRC in the reverse and forward directions to ensure that TS-2 connects the proposed intermediates I-2 and I-3. The IRC plot and the structures of the intermediates are shown in Figure S2 of the Supporting Information.
• 19a Kumpf R, Dougherty DA. Science 1993; 261: 1708
• 19b Dougherty DA. Acc. Chem. Res. 2013; 46: 885
• 19c Lu Q, Oh DX, Lee Y, Jho Y, Hwang DS, Zeng H. Angew. Chem. Int. Ed. 2013; 52: 3944
• 20 For a comparison of various ET pathways, see the Supporting Information (Schemes S3–S5).
• 21 See Scheme S7 in the Supporting Information.
• 22 Yong G.-P, She W.-I, Zhang Y.-M, Li Y.-Z. Chem. Commun. 2011; 47: 11766
• 23a Qiu Y, Lie Y, Yang K, Hong W, Li Z, Wang Z, Yao Z, Jiang S. Org. Lett. 2011; 13: 3556
• 23b Tanimoro K, Ueno M, Takeda K, Kirihata M, Tanimori S. J. Org. Chem. 2012; 77: 7844
• 24 Sun C.-L, Gu Y.-F, Haung W.-P, Shi Z.-J. Chem. Commun. 2011; 47: 9813
• 25 Chen W.-C, Hsu Y.-C, Shih W.-C, Lee C.-Y, Chaung W.-H, Tsai Y.-F, Chen P.-Y, Ong T.-G. Chem. Commun. 2012; 48: 6702
• 26 Dewanji A, Muraka S, Curran DP, Studer A. Org. Lett. 2013; 15: 6102
• 27a De S, Bhunia S, Sheikh JA, Bisai A. Org. Lett. 2012; 14: 4466
• 27b Wu Y, Wong SM, Mao F, Chan TL, Kwong FY. Org. Lett. 2012; 14: 5306
• 27c De S, Mishra S, Kakade BN, Dey D, Bisai A. J. Org. Chem. 2013; 78: 7823
• 27d Zhao H, Shen J, Guo J, Ye R, Zheng H. Chem. Commun. 2013; 49: 2323
• 27e Cumine F, Zhou S, Tuttle T, Murphy JA. Org. Biomol. Chem. 2017; 15: 3324
• 28 Banerjee S, Yang Y.-F, Jenkins ID, Liang Y, Toutov AA, Liu W.-B, Schuman DP, Grubbs RH, Stolz BM, Krenske EH, Houk KN, Zare RN. J. Am. Chem. Soc. 2017; 139: 6880