The mechanism of cleavage of Evans chiral auxiliaries by LiOOH: origins of the different regioselectivities obtained with LiOH, LiOOH, LiOBn and LiSBn
Ka Ho Chow A , Ronald J. Quinn
B , Ian D. Jenkins B * and Elizabeth H. Krenske A *
A School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Qld 4072, Australia.
B Griffith Institute for Drug Discovery, Griffith University, Nathan, Qld 4111, Australia.
Abstract
Oxazolidinones are widely used as chiral auxiliaries in asymmetric synthesis. The chiral auxiliary can be selectively removed using LiOOH, LiOBn or LiSBn, but not LiOH, which instead favours endocyclic cleavage with opening of the oxazolidinone ring. Although Evans originally suggested that the regioselectivity of HO−-mediated hydrolysis may be governed by the relative rates of formation of the two tetrahedral intermediates, whereas the regioselectivity of HOO− cleavage might be determined by their relative breakdown rates, it was not clear why this should be the case. Since then, there appear to have been no mechanistic studies that account for the differing selectivities of LiOH v. LiOOH, and the reason for this difference in selectivity has remained somewhat of an enigma in organic chemistry for many years. Herein, we report DFT computations with M06-2X-D3//B3LYP-D3 to examine the origins of the regioselectivities. The computations predict that all four nucleophiles prefer to attack at the endocyclic carbonyl group, which is less hindered. The barrier for decomposition of the initially formed tetrahedral intermediate determines whether or not the reaction continues all the way to the endocyclic cleavage products. For LiOH, the barrier for decomposition of the intermediate is small and the endocyclic cleavage products are formed. For LiOOH, LiOBn and LiSBn, the decomposition barrier is large, and the exocyclic cleavage pathway instead becomes preferred. An alternative mechanism involving formation of a novel cyclic peroxide intermediate was found to involve a relatively high energy pathway and has been excluded.
Keywords: buttressing effect, chiral auxiliaries, Curtin–Hammett, density functional calculations, exocyclic cleavage, lithium hydroperoxide, N-acyloxazolidinones, nucleophilic substitution, reaction mechanisms, regioselectivity, steric acceleration.
References
1 Heravi MM, Zadsirjan V. Oxazolidinones as chiral auxiliaries in asymmetric aldol reactions applied to total synthesis. Tetrahedron Asymmetry 2013; 24: 1149-1188.
| Crossref | Google Scholar |
2 Ager DJ, Prakash I, Schaad DR. 1,2-Amino alcohols and their heterocyclic derivatives as chiral auxiliaries in asymmetric synthesis. Chem Rev 1996; 96: 835-876.
| Crossref | Google Scholar |
3 Evans DA, Britton TC, Ellman JA. Contrasteric carboximide hydrolysis with lithium hydroperoxide. Tetrahedron Lett 1987; 28: 6141-6144.
| Crossref | Google Scholar |
4 Evans DA, Carter PH, Dinsmore CJ, Barrow JC, Katz JL, Kung DW. Mild nitrosation and hydrolysis of polyfunctional amides. Tetrahedron Lett 1997; 38: 4535-4538.
| Crossref | Google Scholar |
5 Evans DA, Wood MR, Trotter BW, Richardson TI, Barrow JC, Katz JL. Total syntheses of vancomycin and eremomycin aglycons. Angew Chem Int Ed 1998; 37: 2700-2704.
| Crossref | Google Scholar |
6 Evans DA, Kim AS, Metternich R, Novack VJ. General strategies toward the syntheses of macrolide antibiotics. The total syntheses of 6-deoxyerythronolide B and oleandolide. J Am Chem Soc 1998; 120: 5921-5942.
| Crossref | Google Scholar |
7 Evans DA, Britton TC, Ellman JA, Dorow RL. The asymmetric synthesis of α-amino acids. Electrophilic azidation of chiral imide enolates, a practical approach to the synthesis of (R)- and (S)-α-azido carboxylic acids. J Am Chem Soc 1990; 112: 4011-4030.
| Crossref | Google Scholar |
8 Tallmadge EH, Collum DB. Evans enolates: solution structures of lithiated oxazolidinone-derived enolates. J Am Chem Soc 2015; 137: 13087-13095.
| Crossref | Google Scholar |
9 Tallmadge EH, Jermaks J, Collum DB. Structure–reactivity relationships in lithiated Evans enolates: influence of aggregation and solvation on the stereochemistry and mechanism of aldol additions. J Am Chem Soc 2016; 138: 345-355.
| Crossref | Google Scholar |
10 Lee C, Yang W, Parr RG. Development of the Colle–Salvetti correlation-energy formula into a functional of the electron density. Phys Rev B 1988; 37: 785-789.
| Crossref | Google Scholar |
11 Becke AD. A new mixing of Hartree–Fock and local density-functional theories. J Chem Phys 1993; 98: 1372-1377.
| Crossref | Google Scholar |
12 Becke AD. Density-functional thermochemistry. III. The role of exact exchange. J Chem Phys 1993; 98: 5648-5652.
| Crossref | Google Scholar |
13 Stephens PJ, Devlin FJ, Chabalowski CF, Frisch MJ. Ab initio calculation of vibrational absorption and circular dichroism spectra using density functional force fields. J Phys Chem 1994; 98: 11623-11627.
| Crossref | Google Scholar |
14 Grimme S, Antony J, Ehrlich S, Krieg H. A consistent and accurate ab initio parametrization of density functional dispersion correction (DFT-D) for the 94 elements H-Pu. J Chem Phys 2010; 132: 154104.
| Crossref | Google Scholar |
15 Zhao Y, Truhlar DG. The M06 suite of density functionals for main group thermochemistry, thermochemical kinetics, noncovalent interactions, excited states, and transition elements: two new functionals and systematic testing of four M06-class functionals and 12 other functionals. Theor Chem Acc 2008; 120: 215-241.
| Crossref | Google Scholar |
16 Goerigk L, Grimme S. A thorough benchmark of density functional methods for general main group thermochemistry, kinetics, and noncovalent interactions. Phys Chem Chem Phys 2011; 13(14): 6670.
| Crossref | Google Scholar |
17 Marenich AV, Cramer CJ, Truhlar DG. Universal solvation model based on solute electron density and on a continuum model of the solvent defined by the bulk dielectric constant and atomic surface tensions. J Phys Chem B 2009; 113: 6378-6396.
| Crossref | Google Scholar |
18 Beutner GL, Cohen BM, DelMonte AJ, Dixon DD, Fraunhoffer KJ, Glace AW, Lo E, Stevens JM, Vanyo D, Wilbert C. Revisiting the cleavage of Evans oxazolidinones with LiOH/H2O2. Org Process Res Dev 2019; 23: 1378-1385.
| Crossref | Google Scholar |
19 Evans DA, Ennis MD, Mathre DJ. Asymmetric alkylation reactions of chiral imide enolates. A practical approach to the enantioselective synthesis of α-substituted carboxylic acid derivatives. J Am Chem Soc 1982; 104: 1737-1739.
| Crossref | Google Scholar |
20 Damon RE, Coppola GM. Cleavage of N-acyl oxazolidones. Tetrahedron Lett 1990; 31: 2849-2852.
| Crossref | Google Scholar |
21 Brown HC, Okamoto Y. Electrophilic substituent constants. J Am Chem Soc 1958; 80: 4979-4987.
| Crossref | Google Scholar |
22 Plata RE, Singleton DA. A case study of the mechanism of alcohol-mediated Morita Baylis–Hillman reactions. The importance of experimental observations. J Am Chem Soc 2015; 137: 3811-3826.
| Crossref | Google Scholar |
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, Revision C.01. Wallingford, CT, USA: Gaussian, Inc.; 2019.
24 Zhao Y, Truhlar DG. Computational characterization and modeling of buckyball tweezers: density functional study of concave–convex π⋯π interactions. Phys Chem Chem Phys 2008; 10: 2813-2818.
| Crossref | Google Scholar |
25 Gonzalez C, Schlegel HB. An improved algorithm for reaction path following. J Chem Phys 1989; 90: 2154-2161.
| Crossref | Google Scholar |
26 Gonzalez C, Schlegel HB. Reaction path following in mass-weighted internal coordinates. J Phys Chem 1990; 94(14): 5523-5527.
| Crossref | Google Scholar |
