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DOI: 10.1055/a-2522-6204
Strain Release in Hydrogen Atom Transfer from 1,4-Disubstituted Cyclohexanes to the Cumyloxy Radical
Financial support was provided by the Ministero dell’Università e della Ricerca (MUR) Project PRINPNRR ‘LIGHT CAT’ (P2022RHMCM to MS and MB) supported by the European Commission – NextGenerationEU programme and the National Science Foundation (CHE-2157932 to KNH).
Abstract
A kinetic, product, and computational study on the reactions of the cumyloxyl radical (CumO•) with 1,4-dimethyl- and 1,4-diphenylcyclohexanes is reported. The rate constants for hydrogen atom transfer (HAT) from the C–H bonds of these substrates to CumO•, together with the corresponding oxygenation product distributions reveal the role of strain release on reaction site selectivity. Transition structures and activation barriers obtained by DFT calculations are in excellent agreement with the experimental results. Tertiary/secondary ratios of oxygenation products of 0.6, 1.0, and 3.3 were observed, for trans-1,4-dimethyl-, cis-1,4-dimethyl-, and trans-1,4-diphenylcyclohexane, respectively. With cis-1,4-diphenylcyclohexane, exclusive formation of the diastereomeric tertiary alcohol products was observed. Within the two diastereomeric couples, the tertiary equatorial C–H bond in the cis- isomer is ca. 6 and 27 times more reactive, respectively, than the tertiary axial ones, a behavior that reflects the release of 1,3-diaxial strain in the HAT transition state. The tertiary axial C–H bonds of the four substrates show remarkably similar reactivities in spite of the much greater stabilization of the benzyl radicals resulting from HAT from the 1,4-diphenylcyclohexanes. The lack of benzylic acceleration is discussed in the framework of Bernasconi’s ‘principle of nonperfect synchronization’.
Key words
hydrogen atom transfer - alkoxyl radicals - C–H bond functionalization - strain release - torsional effects - nonperfect synchronizationSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-2522-6204.
- Supporting Information
Publikationsverlauf
Eingereicht: 11. Dezember 2024
Angenommen nach Revision: 22. Januar 2025
Accepted Manuscript online:
22. Januar 2025
Artikel online veröffentlicht:
11. März 2025
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References and Notes
- 1a Davies HM. L, Liao K. Nat. Rev. Chem. 2019; 3: 347
- 1b White MC, Zhao J. J. Am. Chem. Soc. 2018; 140: 13988
- 1c Chu JC. K. Rovis T. Angew. Chem. Int. Ed. 2018; 57: 62
- 1d Hartwig JF. J. Am. Chem. Soc. 2016; 138: 2
- 1e Yamaguchi J, Yamaguchi AD, Itami K. Angew. Chem. Int. Ed. 2012; 51: 8960
- 1f Gutekunst WR, Baran PS. Chem. Soc. Rev. 2011; 40: 1976
- 2 Newhouse T, Baran PS. Angew. Chem. Int. Ed. 2011; 50: 3362
- 3a Galeotti M, Salamone M, Bietti M. Chem. Soc. Rev. 2022; 51: 2171
- 3b Ravelli D, Fagnoni M, Fukuyama T, Nishikawa T, Ryu I. ACS Catal. 2018; 8: 701
- 4 Salamone M, Ortega VB, Bietti M. J. Org. Chem. 2015; 80: 4710
- 5 Martin T, Galeotti M, Salamone M, Liu F, Yu Y, Duan M, Houk KN, Bietti M. J. Org. Chem. 2021; 86: 9925
- 6 Chen K, Eschenmoser A, Baran PS. Nature 2009; 459: 824
- 7 Chen K, Eschenmoser A, Baran PS. Angew. Chem. Int. Ed. 2009; 48: 9705
- 8 Zou L, Paton RS, Eschenmoser A, Newhouse TR, Baran PS, Houk KN. J. Org. Chem. 2013; 78: 4037
- 9 Yang Z, Yu P, Houk KN. J. Am. Chem. Soc. 2016; 138: 4237
- 10a Jana S, Ghosh M, Ambule M, Sen Gupta S. Org. Lett. 2017; 19: 746
- 10b Ma L, Pan Y, Man W.-L, Kwong H.-K, Lam WW. Y, Chen G, Lau K.-C, Lau T.-C. J. Am. Chem. Soc. 2014; 136: 7680
- 10c Prat I, Gómez L, Canta M, Ribas X, Costas M. Chem. Eur. J. 2013; 19: 1908
- 10d Mello R, Fiorentino M, Fusco C, Curci R. J. Am. Chem. Soc. 1989; 111: 6749
- 11 Milan M, Bietti M, Costas M. Org. Lett. 2018; 20: 2720
- 12 Salamone M, Bietti M. Synlett 2014; 25: 1803
- 13 As a matter of comparison, product studies on the reactions of cis-1 and trans-1 with in situ generated ETFDO were also carried out. Full experimental details are
displayed in the Supporting Information.
- 14 Chai JD, Head-Gordon M. Phys. Chem. Chem. Phys. 2008; 10: 6615
- 15 Cossi M, Barone V, Mennucci B, Tomasi J. Chem. Phys. Lett. 1998; 286: 253
- 16 Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Petersson GA, Nakatsuji H, Li X, Caricato M, Marenich AV, Bloino J, Janesko BG, Gomperts R, Mennucci B, Hratchian HP, Ortiz JV, Izmaylov AF, Sonnenberg JL, Williams-Young D, Ding F, Lipparini F, Egidi F, Goings J, Peng B, Petrone A, Henderson T, Ranasinghe D, Zakrzewski VG, Gao J, Rega N, Zheng G, Liang W, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Vreven T, Throssell K, Montgomery JA. Jr, Peralta JE, Ogliaro F, Bearpark MJ, Heyd JJ, Brothers EN, Kudin KN, Staroverov VN, Keith TA, Kobayashi R, Normand J, Raghavachari K, Rendell AP, Burant JC, Iyengar SS, Tomasi J, Cossi M, Millam JM, Klene M, Adamo C, Cammi R, Ochterski JW, Martin RL, Morokuma K, Farkas O, Foresman JB, Fox DJ. Gaussian 16, Revision B.01 . Gaussian, Inc; Wallingford, CT: 2016
- 17a Chang L, An Q, Duan L, Feng K, Zuo Z. Chem. Rev. 2022; 122: 2429
- 17b Wu X, Zhu C. Chem. Commun. 2019; 55: 9747
- 18a Bernasconi CF. Adv. Phys. Org. Chem. 2010; 44: 223
- 18b Bernasconi CF. Acc. Chem. Res. 1992; 25: 9
- 18c Bernasconi CF. Acc. Chem. Res. 1987; 20: 301
For general references on HAT reactions promoted by alkoxyl radicals, see for example: