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Vol. 35 No. 12 (2023): Vol 35 Issue 12, 2023

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Geometrical Optimization and Natural Bond Orbital Analysis of Relevant Structures in the Diastereoselective Cuprate Conjugate Addition Reaction of α,β-Unsaturated Lactams using Density Functional Theory

https://doi.org/10.14233/ajchem.2023.30725
Anan Arisha
1Department of Organic Chemistry, School of Chemistry, Faculty of Exact Sciences, Tel Aviv University, Tel Aviv 6997801, Israel 2Department of Education, Beit Berl College, Beit Berl, Israel 3Al-Qasemi Academic College, Baqa El-Gharbia 3010000, Israel
https://orcid.org/0000-0003-4943-1808

Corresponding Author(s) : Anan Arisha

ananarisha@gmail.com

Asian Journal of Chemistry, Vol. 35 No. 12 (2023): Vol 35 Issue 12, 2023

Abstract

In this study, density functional theory calculations at the wB97XD/Def2TZVPP level were performed to analyze the mechanism underlying the cuprate conjugate addition reaction of α,β-unsaturated lactams. The calculation results were well-aligned with those obtained experimentally–the keto-aminal and aldo-aminal, i.e. 2 and 1a, yield the syn- and anti-products, respectively. The diastereoselectivity reversal originates from the small differences in the structure of the reactants. The pyramidalization and C7N3C2 angle between the aminal carbon, nitrogen and carbonyl carbon are large in 2. The dihedral angle of the aminal oxygen, aminal  carbon, nitrogen and carbonyl carbon, O8C7N3C2, is closer to 180º in 2 than in 1a. The NBO analysis revealed string interactions between the lone pair of N3 and carbonyl π*(O1–C2) bond. These results validate the assumption—the planarity around nitrogen in molecule 2 increases the nucleophilicity of the carbonyl oxygen, thereby driving the reaction between molecule 2 and trimethylsilyl  chloride (TMSCl), which yields a siloxyiminium cation 5b and this 5b propels the syn addition of dimethylcuprate, leading to the  formation of complex 7. The π(C5–C6) (HOMO) and π*(C2–N3) (LUMO) interactions in the siloxyiminium cation explain the increased  C5–C6 double bond electrophilicity. The aldo-aminal 1a directly reacts with dimethylcuprate under steric control and yields the anti  complex 6a, whose π character is stronger than that of the syn complex 7 and this weak π characteristics of 7 increases its stability to  compensate for the trimethylsilyl disturbance. The bicyclic α,β-unsaturated lactam 8 does not contain aminal oxygen and thus remains  unreactive during the cuprate conjugate addition reaction. Moreover, its pyramidalization is higher than that of the keto-aminal 2 and  its dihedral angle of C8C7N3C2 is closer to 180º. Finally, a thermodynamic anti product is obtained, which is more stable than the syn- product because of less torsional strain. 

Keywords

Diastereoselectivity Conjugate addition α,β-Unsaturated lactams Density functional theory Natural bond orbital
Arisha, A. (2023). Geometrical Optimization and Natural Bond Orbital Analysis of Relevant Structures in the Diastereoselective Cuprate Conjugate Addition Reaction of α,β-Unsaturated Lactams using Density Functional Theory. Asian Journal of Chemistry, 35(12), 3071–3080. https://doi.org/10.14233/ajchem.2023.30725
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References
  1. E.J. Corey and N.W. Boaz, Tetrahedron Lett., 26, 6019 (1985); https://doi.org/10.1016/S0040-4039(00)95114-1
  2. E.J. Corey and N.W. Boaz, Tetrahedron Lett., 26, 6015 (1985); https://doi.org/10.1016/S0040-4039(00)95113-X
  3. Y. Horiguchi, S. Matsuzawa, E. Nakamura and I. Kuwajima, Tetrahedron Lett., 27, 4025 (1986); https://doi.org/10.1016/S0040-4039(00)84901-1
  4. S.H. Bertz and R.A.J. Smith, Tetrahedron, 46, 4091 (1990); https://doi.org/10.1016/S0040-4020(01)90543-5
  5. B.H. Lipshutz, S.H. Dimock and B. James, J. Am. Chem. Soc., 115, 9283 (1993); https://doi.org/10.1021/ja00073a052
  6. S.H. Bertz, G. Miao, B.E. Rossiter and J.P. Snyder, J. Am. Chem. Soc., 117, 11023 (1995); https://doi.org/10.1021/ja00149a032
  7. S.W. Wright, C. Choi, Y. Kawamata and P.S. Baran, J. Org. Chem., 88, 4387 (2023); https://doi.org/10.1021/acs.joc.2c02993
  8. S.W. Wright, C. Choi, S. Chung, B.P. Boscoe, S.E. Drozda, J.J. Mousseau and J.D. Trzupek, Org. Lett., 17, 5204 (2015); https://doi.org/10.1021/acs.orglett.5b02533
  9. S.W. Wright, B. Li, Z. Peng, L. Wei, E. McInturff, D. Place, D.B. Damon and R.A. Singer, Org. Process Res. Dev., 22, 1835 (2018); https://doi.org/10.1021/acs.oprd.8b00386
  10. C. Jorand-Lebrun and R. Boivin, Preparation of Quinoline Compounds as IRAK Inhibitors and Uses Thereof, WO Patent 149522A1 (2019).
  11. Y. Xie and L.E. Babiss, Preparation of Heterocyclic Compounds as IRAK4 Inhibitors. WO Patnet 089422A1 (2019).
  12. Y. Jie, P. Livant, H. Li, M. Yang, W. Zhu, V. Cammarata, P. Almond, T. Sullens, Y. Qin and E. Bakker, J. Org. Chem., 75, 4472 (2010); https://doi.org/10.1021/jo100628v
  13. I.V. Alabugin, L. Kuhn, N.V. Krivoshchapov, P. Mehaffy and M.G. Medvedev, Chem. Soc. Rev., 50, 10212 (2021); https://doi.org/10.1039/D1CS00564B
  14. S.A. Glover and A.A. Rosser, J. Org. Chem., 77, 5492 (2012); https://doi.org/10.1021/jo300347k
  15. K.W. Bowers, R.W. Giese, J. Grimshaw, H.O. House, N.H. Kolodny, K. Kronberger and D.K. Roe, J. Am. Chem. Soc., 92, 2783 (1970); https://doi.org/10.1021/ja00712a032
  16. H.O. House, Acc. Chem. Res., 9, 59 (1976); https://doi.org/10.1021/ar50098a003
  17. M. J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman, G. Scalmani, V. Barone, G.A. Petersson, H. Nakatsuji, X. Li, M. Caricato, A.V. Marenich, J. Bloino, B.G. Janesko, R. Gomperts, B. Mennucci, H.P. Hratchian, J.V. Ortiz, A.F. Izmaylov, J.L. Sonnenberg, D. Williams-Young, F. Ding, F. Lipparini, F. Egidi, J. Goings, B. Peng, A. Petrone, T. Henderson, D. Ranasinghe, V.G. Zakrzewski, J. Gao, N. Rega, G. Zheng, W. Liang, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven, K. Throssell, J.A. Montgomery, Jr., J.E. Peralta, F. Ogliaro, M.J. Bearpark, J.J. Heyd, E.N. Brothers, K.N. Kudin, V.N. Staroverov, T.A. Keith, R. Kobayashi, J. Normand, K. Raghavachari, A.P. Rendell, J.C. Burant, S.S. Iyengar, J. Tomasi, M. Cossi, J.M. Millam, M. Klene, C. Adamo, R. Cammi, J.W. Ochterski, K. Morokuma, R.L. Martin, O. Farkas, J.B. Foresman and D.J. Fox, Gaussian 16. Wallingford, CT: Gaussian, Inc. (2016).
  18. R. Dennington, T.A. Keith and J.M. Millam, GaussView (Version 6.0). Shawnee, KS: Semichem Inc. (2016).
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