London Dispersion Stabilizes Chloro-Substituted cis-Double Bonds

Abstract

We present a combined experimental and computational study on the thermodynamic stability of cis- and trans-alkenes substituted with dispersion energy donor (DED) groups. To investigate the role of noncovalent interactions on equilibrium of cis- and trans-alkenes we utilized hydrochlorination reactions. While the general assumption is that increasing steric bulk favors the trans-alkene, we observe an equilibrium shift towards the more crowded cis-alkene with increasing substituent size. With the aim to quantify noncovalent interactions, we performed a double mutant cycle to experimentally gauge the attractive potential of bulky substituents. Additionally, we utilized local energy decomposition analysis at the DLPNO-CCSD(T)/def2-TZVP level of theory. We found LD interactions and Pauli exchange repulsion to be the most dominant components to influence cis- and trans-alkene equilibria.

Key words

double mutant cycle - equilibrium - hydrohalogenation - London dispersion - Pauli repulsion

• References and Notes

• 1 Kwasniewski SP, Claes L, François J.-P, Deleuze MS. J. Chem. Phys. 2003; 118: 7823
• 2a Malhotra SK, Johnson F. J. Am. Chem. Soc. 1965; 87: 5493
• 2b Johnson F, Malhotra SK. J. Am. Chem. Soc. 1965; 87: 5492
• 2c Johnson F. Chem. Rev. 1968; 68: 375
• 3a Gotō H, Ōsawa E, Yamato M. Tetrahedron 1993; 49: 387
• 3b Scott RA, Scheraga HA. J. Chem. Phys. 1966; 44: 3054
• 3c Hoffmann RW, Stahl M, Schopfer U, Frenking G. Chem. Eur. J. 1998; 4: 559
• 4a Winstein S, Holness NJ. J. Am. Chem. Soc. 1955; 77: 5562
• 4b Jensen FR, Bushweller CH, Beck BH. J. Am. Chem. Soc. 1969; 91: 344
• 5a London F. Z. Phys. 1930; 63: 245
• 5b London F. Trans. Faraday Soc. 1937; 33: 8b
• 6a Wagner JP, Schreiner PR. Angew. Chem. Int. Ed. 2015; 54: 12274
• 6b Solel E, Ruth M, Schreiner PR. J. Org. Chem. 2021; 86: 7701
• 6c Solel E, Ruth M, Schreiner PR. J. Am. Chem. Soc. 2021; 143: 20837
• 7a Rösel S, Balestrieri C, Schreiner PR. Chem. Sci. 2017; 8: 405
• 7b Rösel S, Becker J, Allen WD, Schreiner PR. J. Am. Chem. Soc. 2018; 140: 14421
• 7c Rummel L, Schümann JM, Schreiner PR. Chem. Eur. J. 2021; 27: 13699
• 7d Rösel S, Schreiner PR. Isr. J. Chem. 2022; 62: e202200002
• 8a Rösel S, Quanz H, Logemann C, Becker J, Mossou E, Cañadillas-Delgado L, Caldeweyher E, Grimme S, Schreiner PR. J. Am. Chem. Soc. 2017; 139: 7428
• 8b Maué D, Strebert PH, Bernhard D, Rösel S, Schreiner PR, Gerhards M. Angew. Chem. Int. Ed. 2021; 60: 11305
• 9a Wong DP, Fink WH, Allen LC. J. Chem. Phys. 1970; 52: 6291
• 9b Schmittel M, Ruechardt C. J. Am. Chem. Soc. 1987; 109: 2750
• 10 Schweighauser L, Strauss MA, Bellotto S, Wegner HA. Angew. Chem. Int. Ed. 2015; 54: 13436
• 11 Grimme S, Huenerbein R, Ehrlich S. ChemPhysChem 2011; 12: 1258
• 12a Kropp PJ, Daus KA, Crawford SD, Tubergen MW, Kepler KD, Craig SL, Wilson VP. J. Am. Chem. Soc. 1990; 112: 7433
• 12b Kropp PJ, Daus KA, Tubergen MW, Kepler KD, Wilson VP, Craig SL, Baillargeon MM, Breton GW. J. Am. Chem. Soc. 1993; 115: 3071
• 12c Pienta NJ, Crawford SD, Kropp PJ. J. Chem. Educ. 1993; 70: 682
• 12d Kropp PJ, Crawford SD. J. Org. Chem. 1994; 59: 3102
• 12e Kropp PJ, Breton GW, Craig SL, Crawford SD, Durland WF, Jones JE, Raleigh JS. J. Org. Chem. 1995; 60: 4146
• 13 Saltiel J, Ganapathy S, Werking C. J. Phys. Chem. 1987; 91: 2755
• 14 Williams RB. J. Am. Chem. Soc. 1942; 64: 1395
• 15 Fischer G, Muszkat KA, Fischer E. J. Chem. Soc. B 1968; 1156
• 16 Adrian FJ. J. Chem. Phys. 1958; 28: 608
• 17 General Procedure for the Coupling Reactions Pd(PPh₃)₂Cl₂ (0.1 equiv.), 1,4-bis(diphenylphosphino)butane (0.1 equiv.), aryl halides (2 equiv.), and 2-butynedioic acid (1 equiv.) were combined with DBU (2 equiv.) in a small round-bottomed flask. DMSO (15.0 mL) was added, and the flask was sealed with a septum. The resulting mixture was placed in an oil bath at 110 °C for 4 h. The reaction was poured into 25 mL of saturated aqueous ammonium chloride and extracted with Et₂O (4 × 20 mL). The combined ether extracts were washed with brine (90 mL), dried over MgSO₄, and filtered. The solvent was removed under reduced pressure, and the resulting crude product was purified by flash chromatography (n-hexane) on silica gel Bis(3,5-di-tert-butylphenyl)acetylene (1- ^t Bu₂) ¹H NMR (400 MHz, CDCl₃): δ = 1.22 (s, 36 H, 1), 7.51 (t, 2 H, 2), 7.77 (d, 4 H, 3) ppm. ¹³C NMR {¹H} (101 MHz, CDCl₃): δ = 31.4, 34.9, 90.4, 122.8, 123.7, 126.7, 151.3 ppm.
• 18a Eschmann C, Song L, Schreiner PR. Angew. Chem. Int. Ed. 2021; 60: 4823
• 18b Shi F, Shen JK, Chen D, Fog K, Thirstrup K, Hentzer M, Karlsson J.-J, Menon V, Jones KA, Smith KE, Smith G. ACS Med. Chem. Lett. 2011; 2: 303
• 19 Park K, Bae G, Moon J, Choe J, Song KH, Lee S. J. Org. Chem. 2010; 75: 6244
• 20 General Procedure for the Hydrochlorination Reaction A round-bottomed flask was charged with substituted diphenylacetylene (1 equiv.) and 10 g alumina. 20 mL DCM were added, and the mixture was stirred vigorously. To start the reaction oxalyl chloride (8 equiv.) was added via a syringe and the mixture sealed with a septum. The reaction procedure and product ratio was monitored via GC–MS.
• 21 Liu T, Schneider H.-J. Angew. Chem. Int. Ed. 2002; 41: 1368
• 22 Pracht P, Bohle F, Grimme S. Phys. Chem. Chem. Phys. 2020; 22: 7169
• 23 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 Rev. C.01 . Gaussian; Wallingford: 2016
• 24a Lee C, Yang W, Parr RG. Phys. Rev. B 1988; 37: 785
• 24b Becke AD. J. Chem. Phys. 1993; 98: 5648
• 25a Grimme S, Antony J, Ehrlich S, Krieg H. J. Chem. Phys. 2010; 132: 154104
• 25b Grimme S, Ehrlich S, Goerigk L. J. Comput. Chem. 2011; 32: 1456
• 26 Schäfer A, Huber C, Ahlrichs R. J. Chem. Phys. 1994; 100: 5829
• 27a Miertuš S, Scrocco E, Tomasi J. Chem. Phys. 1981; 55: 117
• 27b Tomasi J, Mennucci B, Cammi R. Chem. Rev. 2005; 105: 2999
• 28 Chai J.-D, Head-Gordon M. Phys. Chem. Chem. Phys. 2008; 10: 6615
• 29a Riplinger C, Neese F. J. Chem. Phys. 2013; 138: 034106
• 29b Liakos DG, Sparta M, Kesharwani MK, Martin JM. L, Neese F. J. Chem. Theory Comput. 2015; 11: 1525
• 30 Pollice R, Bot M, Kobylianskii IJ, Shenderovich I, Chen P. J. Am. Chem. Soc. 2017; 139: 13126
• 31a Pollice R, Fleckenstein F, Shenderovich I, Chen P. Angew. Chem. Int. Ed. 2019; 58: 14281
• 31b Schümann JM, Wagner JP, Eckhardt AK, Quanz H, Schreiner PR. J. Am. Chem. Soc. 2021; 143: 41
• 32a Johnson ER, Keinan S, Mori-Sánchez P, Contreras-García J, Cohen AJ, Yang W. J. Am. Chem. Soc. 2010; 132: 6498
• 32b Contreras-García J, Johnson ER, Keinan S, Chaudret R, Piquemal J.-P, Beratan DN, Yang W. J. Chem. Theory Comput. 2011; 7: 625
• 33a Carter PJ, Winter G, Wilkinson AJ, Fersht AR. Cell 1984; 38: 835
• 33b Adams H, Carver FJ, Hunter CA, Morales JC, Seward EM. Angew. Chem., Int. Ed. Engl. 1996; 35: 1542
• 33c Yang L, Adam C, Nichol GS, Cockroft SL. Nat. Chem. 2013; 5: 1006
• 34 Rummel L, Domanski MH. J, Hausmann H, Becker J, Schreiner PR. Angew. Chem. Int. Ed. 2022; 134: e202204393
• 35 Strauss MA, Wegner HA. Angew. Chem. Int. Ed. 2019; 58: 18552
• 36 Van Craen D, Rath WH, Huth M, Kemp L, Räuber C, Wollschläger JM, Schalley CA, Valkonen A, Rissanen K, Albrecht M. J. Am. Chem. Soc. 2017; 139: 16959