Parameterization of Arynophiles: Experimental Investigations towards a Quantitative Understanding of Aryne Trapping Reactions

Abstract

Arynes are highly reactive intermediates that may be used strategically in synthesis by trapping with arynophilic reagents. However, ‘arynophilicity’ of such reagents is almost completely anecdotal and predicting which ones will be efficient traps is often challenging. Here, we describe a systematic study to parameterize the arynophilicity of a wide range of reagents known to trap arynes. A relative reactivity scale, based on one-pot competition experiments, is presented by using furan as a reference arynophile and 3-chlorobenzyne as a the aryne. More than 15 arynophiles that react in pericyclic reactions, nucleophilic addition, and σ-bond insertion reactions are parameterized with arynophilicity (A) values, and multiple aryne precursors are applicable.

Key words

LFER - aryne - arynophile - percyclic reaction - δ-bond insertion - nucleophilic addition

Publikationsverlauf

Eingereicht: 31. März 2022

Angenommen nach Revision: 06. Mai 2022

Accepted Manuscript online:
06. Mai 2022

Artikel online veröffentlicht:
20. Juni 2022

• References

• 1a Tadross PM, Stoltz BM. Chem. Rev. 2012; 112: 3550
• 1b Gample CM, Carreira EM. Angew. Chem. Int. Ed. 2012; 51: 3766
• 1c Modern Aryne Chemistry . Biju A. Wiley-VCH; Weinheim: 2021
• 2 Hoffmann R, Imamura A, Hehre WJ. J. Am. Chem. Soc. 1968; 90: 1499
• 3a Stephens D, Zhang Y, Cormier M, Chavez G, Arman H, Larionov OV. Chem. Commun. 2013; 49: 6558
• 3b Thangaraj M, Bhojgude SS, Mane MV, Biju AT. Chem. Commun. 2016; 52: 1665
• 3c Suh S.-E, Chenoweth DM. Org. Lett. 2016; 18: 4080
• 4 Biehl ER, Nieh E, Hsu KC. J. Org. Chem. 1969; 34: 3595
• 5 Fine NF, Lucas NA, Mayr HM, Garg NK. J. Am. Chem. Soc. 2016; 138: 10402
• 6a Mayr H, Kempf B, Ofial AR. Acc. Chem. Res. 2003; 36: 66
• 6b Ammer J, Nolte C, Mayr H. J. Am. Chem. Soc. 2012; 134: 13902
• 7 Nilova A, Metze BE, Stuart DR. Org. Lett. 2021; 23: 4813
• 8 See the Supporting Information for stacked NMR plots from competition experiments.
• 9 Kanzian T, Nigst TA, Maier A, Pichl S, Mayr H. Eur. J. Org. Chem. 2009; 6379
• 10 Fukui K. Acc. Chem. Res. 1971; 4: 57
• 11 Jung ME, Gervay J. J. Am. Chem. Soc. 1989; 111: 5469
• 12 Vogel AI, Furniss BS, Hannaford AJ, Rogers V, Smith PW. G, Tatchell AR. Vogel’s Textbook of Practical Organic Chemistry, 4th Ed. Longman; London: 1978: 308
• 13 Seidl TL, Sundalam SK, McCullough B, Stuart DR. J. Org. Chem. 2016; 81: 1998
• 14 Sundalam SK, Nilova A, Seidl TL, Stuart DR. Angew. Chem. Int. Ed. 2016; 55: 8431
• 15 Medina JM, Mackey JL, Garg NK, Houk KN. J. Am. Chem. Soc. 2014; 136: 15798
• 16 Asua JM, Leiza JR. Regulators for controlling linear and pseudo-ring expansion polymerization of vinyl monomers Van Es J. J. G. S. PCT Int. Appl 2017076992, 11.05.2017
• 17 Xu ZL, Li HX, Ren ZG, Du WY, Xu WC, Lang JP. Tetrahedron 2011; 67: 5282
• 18 Miura T, Morimoto M, Murakami M. Org. Lett. 2012; 14: 5214
• 19 Duan Y.-N, Zhang Z, Zhang C. Org. Lett. 2016; 18: 6176
• 20 Masson E, Schlosser M. Eur. J. Org. Chem. 2005; 4401
• 21 Suguru Y, Akira Y, Keisuke U, Takamitsu H. Chem. Lett. 2017; 46: 733
• 22 Liu F, Hu Y.-Y, Li D, Zhou Q, Lu J.-M. Tetrahedron 2018; 74: 5683
• 23 Tran VH, La MT, Kang S, Kim HK. Org. Biomol. Chem. 2020; 18: 5008
• 24 He Y, Zheng Z, Liu Y, Qiao J, Zhang Y, Fan X. Org. Lett. 2019; 21: 1676
• 25 Mesgar M, Daugulis O. Org. Lett. 2016; 18: 3910
• 26 Tian ZY, Ming XX, Teng HB, Hu YT, Zhang CP. Chem. Eur. J. 2018; 24: 13744
• 27 MacNeil SL, Wilson BJ, Snieckus V. Org. Lett. 2006; 8: 1133
• 28 Arava VR, Bandatmakuru SR. Pharma Chem. 2013; 5: 12
• 29 Heng S, Harris KM, Kantrowitz ER. Eur. J. Med. Chem. 2010; 45: 1478
• 30 Sun KX, Zhou JH, He QW, Shao LX, Lu JM. Tetrahedron 2020; 76: 130944
• 31 Wang M, Huang Z. Org. Biomol. Chem. 2016; 14: 10185