A theoretical study of the regioselectivity of the reaction of six-membered and five-membered nitrones with a series of substituted alkenes

Year 2024, Volume: 8 Issue: 3, 23 - 43, 19.09.2024

Boulanouar Messaoudı

https://doi.org/10.33435/tcandtc.1275208

Abstract

The experimentally observed regioselectivity of a series of alkenes reactions with some nitrones has been thoroughly investigated theoretically using density functional theory (DFT) B3lyp/6-31G(d) level of theory. Both Fukui and Parr indices have been calculated to explain and show the most reactive sites. The electrostatic surface potential has also been studied and analyzed in order to show the positive and negative regions responsible of the possible interaction between the two studied reactants. The theoretical results are in good agreement with the experimental findings.

Keywords

Nitrones, alkene, regioselectivity, Fukui and Parr functions, B3lyp.

References

• [1] P. Albert, H. P. William, Synthetic applications of 1,3-dipolar cycloaddition chemistry toward heterocycles and natural products, John Wiley & Sons, (2003).
• [1] P. Albert, H. P. William, Synthetic applications of 1,3-dipolar cycloaddition chemistry toward heterocycles and natural products, John Wiley & Sons, (2003).
• [2] F.R. Thomas, Advances in synthetic organic chemistry and methods reported in US patents, Elsevier, (2006).
• [2] F.R. Thomas, Advances in synthetic organic chemistry and methods reported in US patents, Elsevier, (2006).
• [3] B. Messaoudi, S. M. Mekelleche Elucidation of the chemo- and regioselectivity of polar Diels-Alder reactions involving thiophene-1,1-dioxides using DFT-based reactivity indexes. Letters in Organic Chemistry 8 (2011) 95-103.
• [3] B. Messaoudi, S. M. Mekelleche Elucidation of the chemo- and regioselectivity of polar Diels-Alder reactions involving thiophene-1,1-dioxides using DFT-based reactivity indexes. Letters in Organic Chemistry 8 (2011) 95-103.
• [4] N. Nishiwaki, Methods and applications of cycloaddition reactions in organic syntheses, Wiley, (2014).
• [4] N. Nishiwaki, Methods and applications of cycloaddition reactions in organic syntheses, Wiley, (2014).
• [5] P. Quadrelli, Modern applications of cycloaddition chemistry, Elsevier Science, (2019).
• [5] P. Quadrelli, Modern applications of cycloaddition chemistry, Elsevier Science, (2019).
• [6] D. Margetic, Cycloaddition reactions: advances in research and applications, Nova Science Publishers, Incorporated, (2019).
• [6] D. Margetic, Cycloaddition reactions: advances in research and applications, Nova Science Publishers, Incorporated, (2019).
• [7] J. Zhu, J. Mo, H. Z. Lin, et al., The recent progress of isoxazole in medicinal chemistry. Bioorganic & Medicinal Chemistry 26 (2018) 3065-3075.
• [7] J. Zhu, J. Mo, H. Z. Lin, et al., The recent progress of isoxazole in medicinal chemistry. Bioorganic & Medicinal Chemistry 26 (2018) 3065-3075.
• [8] A. Thakur, M. Verma, R. Bharti, et al., Oxazole and isoxazole: from one-pot synthesis to medical applications. Tetrahedron 119 (2022) 1-30.
• [8] A. Thakur, M. Verma, R. Bharti, et al., Oxazole and isoxazole: from one-pot synthesis to medical applications. Tetrahedron 119 (2022) 1-30.
• [9] A. Sysak, B. Obmińska-Mrukowicz, Isoxazole ring as a useful scaffold in a search for new therapeutic agents. European Journal of Medicinal Chemistry 137 (2017) 292-309.
• [9] A. Sysak, B. Obmińska-Mrukowicz, Isoxazole ring as a useful scaffold in a search for new therapeutic agents. European Journal of Medicinal Chemistry 137 (2017) 292-309.
• [10] X. Wang, Q. Hu, H. Tang, et al., Isoxazole/isoxazoline skeleton in the structural modification of natural products: a review. Pharmaceuticals 16 (2023) 1-35.
• [10] X. Wang, Q. Hu, H. Tang, et al., Isoxazole/isoxazoline skeleton in the structural modification of natural products: a review. Pharmaceuticals 16 (2023) 1-35.
• [11] C. P. Pandhurnekar, H. C. Pandhurnekar, A. J. Mungole, et al., A review of recent synthetic strategies and biological activities of isoxazole. Journal of Heterocyclic Chemistry 60 (2023) 537-565.
• [11] C. P. Pandhurnekar, H. C. Pandhurnekar, A. J. Mungole, et al., A review of recent synthetic strategies and biological activities of isoxazole. Journal of Heterocyclic Chemistry 60 (2023) 537-565.
• [12] V. Basavanna, S. Doddamani, M. Chandramouli, et al., Green approaches for the synthesis of pharmacologically enviable isoxazole analogues: a comprehensive review. Journal of Iran Chemical Society 19 (2022) 3249-3283.
• [12] V. Basavanna, S. Doddamani, M. Chandramouli, et al., Green approaches for the synthesis of pharmacologically enviable isoxazole analogues: a comprehensive review. Journal of Iran Chemical Society 19 (2022) 3249-3283.
• [13] Y. Walunj, P. Mhaske, P. Kulkarni, Application, reactivity and synthesis of isoxazole derivatives. Mini-Reviews in Organic Chemistry 18 (2021) 55-77.
• [13] Y. Walunj, P. Mhaske, P. Kulkarni, Application, reactivity and synthesis of isoxazole derivatives. Mini-Reviews in Organic Chemistry 18 (2021) 55-77.
• [14] R. Huisgen, Kinetics and mechanism of 1,3-dipolar cycloadditions. Angewandte Chemie International Edition 2 (1963) 633-645.
• [14] R. Huisgen, Kinetics and mechanism of 1,3-dipolar cycloadditions. Angewandte Chemie International Edition 2 (1963) 633-645.
• [15] P. N. Confalone, E. M. Huie, The [3 + 2] nitrone–olefin cycloaddition reaction. Organic Reactions 36 (1988) 1-173.
• [15] P. N. Confalone, E. M. Huie, The [3 + 2] nitrone–olefin cycloaddition reaction. Organic Reactions 36 (1988) 1-173.
• [16] K. V. Gothelf, K. A. Jorgensen, Asymmetric 1,3-dipolar cycloaddition reactions. Chemical Reviews 98 (1998) 863-910.
• [16] K. V. Gothelf, K. A. Jorgensen, Asymmetric 1,3-dipolar cycloaddition reactions. Chemical Reviews 98 (1998) 863-910.
• [17] H. Pellissier, Asymmetric 1,3-dipolar cycloadditions. Tetrahedron 63 (2007) 3235-3285.
• [17] H. Pellissier, Asymmetric 1,3-dipolar cycloadditions. Tetrahedron 63 (2007) 3235-3285.
• [18] S. Akai, K. Tanimoto, Y. Kanao, et al., Lipase-catalyzed domino kinetic resolution of α-hydroxynitrones/intramolecular 1,3-dipolar cycloaddition: a concise asymmetric total synthesis of (−)-rosmarinecine. Chemical Communications 18 (2005) 2369-2371.
• [18] S. Akai, K. Tanimoto, Y. Kanao, et al., Lipase-catalyzed domino kinetic resolution of α-hydroxynitrones/intramolecular 1,3-dipolar cycloaddition: a concise asymmetric total synthesis of (−)-rosmarinecine. Chemical Communications 18 (2005) 2369-2371.
• [19] J. Shimokawa, K. Shirai, A. Tanatani, et al., Enantioselective total synthesis of batzelladine A. Angewandte Chemie International Edition 43 (2004) 1559-1562.
• [19] J. Shimokawa, K. Shirai, A. Tanatani, et al., Enantioselective total synthesis of batzelladine A. Angewandte Chemie International Edition 43 (2004) 1559-1562.
• [20] Y. C. Moon, Inter- and intramolecular [4+2] cycloaddition reactions and tandem inter- and intramolecular [4+2]/intramolecular [3+2] cycloaddition reactions of nitroalkenes. University of Illinois at Urbana-Champaign, (1991).
• [20] Y. C. Moon, Inter- and intramolecular [4+2] cycloaddition reactions and tandem inter- and intramolecular [4+2]/intramolecular [3+2] cycloaddition reactions of nitroalkenes. University of Illinois at Urbana-Champaign, (1991).
• [21] J. J. Tufariello, Nitrones in 1,3-dipolar cycloaddition chemistry. Padwa, A., Ed., New York, Wiley, (1984).
• [21] J. J. Tufariello, Nitrones in 1,3-dipolar cycloaddition chemistry. Padwa, A., Ed., New York, Wiley, (1984).
• [22] S. J. Wendy, J. M. W. John, W. C. M. David, New strategies for organic catalysis: the first enantioselective organocatalytic 1,3-dipolar cycloaddition. Journal of the American Chemical Society 122 (2000) 9874-9875.
• [22] S. J. Wendy, J. M. W. John, W. C. M. David, New strategies for organic catalysis: the first enantioselective organocatalytic 1,3-dipolar cycloaddition. Journal of the American Chemical Society 122 (2000) 9874-9875.
• [23] Y. Ito, Y. Kimura, S. Terashima, Nitrone cycloaddition route to the 1β-methylcarbapenem key intermediate. Bulletin of the Chemical Society of Japan 60 (1987) 3337-3340.
• [23] Y. Ito, Y. Kimura, S. Terashima, Nitrone cycloaddition route to the 1β-methylcarbapenem key intermediate. Bulletin of the Chemical Society of Japan 60 (1987) 3337-3340.
• [24] T. Junji, K. Shuji, Ab initio study of Lewis acid catalyzed nitrone cycloaddition to electron deficient alkenes. Does a Lewis acid catalyst change the reaction mechanism? Tetrahedron 57 (2001) 899-905.
• [24] T. Junji, K. Shuji, Ab initio study of Lewis acid catalyzed nitrone cycloaddition to electron deficient alkenes. Does a Lewis acid catalyst change the reaction mechanism? Tetrahedron 57 (2001) 899-905.
• [25] D. Wanapun, K. A. Van Gorp, N. J. Mosey, et al., The mechanism of 1,3-dipolar cycloaddition reactions of cyclopropanes and nitrones. A theoretical study. Canadian Journal of Chemistry 83 (2005) 1752-1767.
• [25] D. Wanapun, K. A. Van Gorp, N. J. Mosey, et al., The mechanism of 1,3-dipolar cycloaddition reactions of cyclopropanes and nitrones. A theoretical study. Canadian Journal of Chemistry 83 (2005) 1752-1767.
• [26] A. J. Hodges, J. P. Adams, A. D. Bond, et al., Intramolecular nitrone dipolar cycloadditions: control of regioselectivity and synthesis of naturally-occurring spirocyclic alkaloids. Organic and Biomolecular Chemistry 10 (2012) 8963-8974.
• [26] A. J. Hodges, J. P. Adams, A. D. Bond, et al., Intramolecular nitrone dipolar cycloadditions: control of regioselectivity and synthesis of naturally-occurring spirocyclic alkaloids. Organic and Biomolecular Chemistry 10 (2012) 8963-8974.
• [27] P. Merino, R. Majer, O. Konechnaya, et al., ChemInform abstract: highly diastereoselective 1,3-dipolar cycloadditions of chiral non-racemic nitrones to 1,2-diaza-1,3-dienes: an experimental and computational investigation. Organic and Biomolecular Chemistry 12 (2014) 8888-8901.
• [27] P. Merino, R. Majer, O. Konechnaya, et al., ChemInform abstract: highly diastereoselective 1,3-dipolar cycloadditions of chiral non-racemic nitrones to 1,2-diaza-1,3-dienes: an experimental and computational investigation. Organic and Biomolecular Chemistry 12 (2014) 8888-8901.
• [28] S. B. Joyann, D. S. Evan, V. P. Hung, et al., Nitrone cycloadditions of 1,2-cyclohexadiene. Journal of the American Chemical Society 138 (2016) 2512-2515.
• [28] S. B. Joyann, D. S. Evan, V. P. Hung, et al., Nitrone cycloadditions of 1,2-cyclohexadiene. Journal of the American Chemical Society 138 (2016) 2512-2515.
• [29] H. Hazhazi, Y. Boumedjane, B. Messaoudi, Theoretical study of the regio- and stereoselectivity of the 1,3-DC reaction of 2,3,4,5-tetrahydropyridine-l-oxide with methyl crotonate. Moroccan Journal of Chemistry 4 (2016) 1106-1116.
• [29] H. Hazhazi, Y. Boumedjane, B. Messaoudi, Theoretical study of the regio- and stereoselectivity of the 1,3-DC reaction of 2,3,4,5-tetrahydropyridine-l-oxide with methyl crotonate. Moroccan Journal of Chemistry 4 (2016) 1106-1116.
• [30] J. S. Cannon, A Nitrone dipolar cycloaddition strategy toward an enantioselective synthesis of massadine. Organic Letters 20 (2018) 3883-3887.
• [30] J. S. Cannon, A Nitrone dipolar cycloaddition strategy toward an enantioselective synthesis of massadine. Organic Letters 20 (2018) 3883-3887.
• [31] P. N. Gunawardene, W. Luo, A. M. Polgar, et al., Highly electron-deficient pyridinium-nitrones for rapid and tunable inverse-electron-demand strain-promoted alkyne-nitrone cycloaddition. Organic Letters 21 (2019) 5547-5551.
• [31] P. N. Gunawardene, W. Luo, A. M. Polgar, et al., Highly electron-deficient pyridinium-nitrones for rapid and tunable inverse-electron-demand strain-promoted alkyne-nitrone cycloaddition. Organic Letters 21 (2019) 5547-5551.
• [32] M. Bakthadoss, M. Mushaf, Intramolecular [3 + 2] nitrone cycloaddition reaction: highly regio and diastereoselective synthesis of bicyclo[3.2.1]octane scaffolds. Organic and Biomolecular Chemistry 18 (2020) 9653-9659.
• [32] M. Bakthadoss, M. Mushaf, Intramolecular [3 + 2] nitrone cycloaddition reaction: highly regio and diastereoselective synthesis of bicyclo[3.2.1]octane scaffolds. Organic and Biomolecular Chemistry 18 (2020) 9653-9659.
• [33] P. M. Alexander, M. L. Valentina, M.E. Mariia, et al., The 1,3-dipolar cycloaddition of adamantine-derived nitrones with maleimides. Synthetic Communications 50 (2020) 1367-1374.
• [33] P. M. Alexander, M. L. Valentina, M.E. Mariia, et al., The 1,3-dipolar cycloaddition of adamantine-derived nitrones with maleimides. Synthetic Communications 50 (2020) 1367-1374.
• [34] S. Thakur, A. Das, T. Das, 1,3-Dipolar cycloaddition of nitrones: synthesis of multisubstituted, diverse range of heterocyclic compounds. New Journal of Chemistry 45 (2021) 11420-11456.
• [34] S. Thakur, A. Das, T. Das, 1,3-Dipolar cycloaddition of nitrones: synthesis of multisubstituted, diverse range of heterocyclic compounds. New Journal of Chemistry 45 (2021) 11420-11456.
• [35] S. A. Ali, J. H. Khan, M.I. Wazeer, et al., The 1, 3-dipolar cycloaddition of cyclic nitrones with 1, 2-disubstituted alkenes. Tetrahedron 45 (1989) 5979-5986.
• [35] S. A. Ali, J. H. Khan, M.I. Wazeer, et al., The 1, 3-dipolar cycloaddition of cyclic nitrones with 1, 2-disubstituted alkenes. Tetrahedron 45 (1989) 5979-5986.
• [36] M. J. Frisch, G. W. Trucks, H. B. Schlegel, et al., Gaussian 09, Inc., Wallingford CT, (2009).
• [36] M. J. Frisch, G. W. Trucks, H. B. Schlegel, et al., Gaussian 09, Inc., Wallingford CT, (2009).
• [37] X. Li, M. J. J. Frisch, Energy-represented DIIS within a hybrid geometry optimization method. Journal of Chemical Theory and Computation 2 (2006) 835-839.
• [37] X. Li, M. J. J. Frisch, Energy-represented DIIS within a hybrid geometry optimization method. Journal of Chemical Theory and Computation 2 (2006) 835-839.
• [38] C. Peng, P. Y. Ayala, H. B. Schlegel, et al., Using redundant internal coordinates to optimize equilibrium geometries and transition states. Journal of Computational Chemistry 17 (1996) 49-56.
• [38] C. Peng, P. Y. Ayala, H. B. Schlegel, et al., Using redundant internal coordinates to optimize equilibrium geometries and transition states. Journal of Computational Chemistry 17 (1996) 49-56.
• [39] J. Luo, Z. Q. Xue, W. M. Liu, et al., Koopmans' theorem for large molecular systems within density functional theory. The Journal of Physical Chemistry A 110 (2006) 12005-12009.
• [39] J. Luo, Z. Q. Xue, W. M. Liu, et al., Koopmans' theorem for large molecular systems within density functional theory. The Journal of Physical Chemistry A 110 (2006) 12005-12009.
• [40] D. A. McQuarrie, J. D. Simon, Physical chemistry: a molecular approach (Vol. 1), Sausalito, CA: University science books, (1997).
• [40] D. A. McQuarrie, J. D. Simon, Physical chemistry: a molecular approach (Vol. 1), Sausalito, CA: University science books, (1997).
• [41] J. M. Jacob, M. P. Kurup, K. Nisha, et al., Mixed ligand copper (II) chelates derived from an O, N, S-donor tridentate thiosemicarbazone: Synthesis, spectral aspects, FMO, and NBO analysis. Polyhedron 189 (2020) 114736.
• [41] J. M. Jacob, M. P. Kurup, K. Nisha, et al., Mixed ligand copper (II) chelates derived from an O, N, S-donor tridentate thiosemicarbazone: Synthesis, spectral aspects, FMO, and NBO analysis. Polyhedron 189 (2020) 114736.
• [42] H. A. Hussein, G. F. Fadhil, Theoretical investigation of para amino-dichloro chalcone isomers. Part II: a DFT structure–stability study of the FMO and NLO Properties. American Chemical Society omega 8 (2023) 4937-4953.
• [42] H. A. Hussein, G. F. Fadhil, Theoretical investigation of para amino-dichloro chalcone isomers. Part II: a DFT structure–stability study of the FMO and NLO Properties. American Chemical Society omega 8 (2023) 4937-4953.
• [43] R. G. Parr, L. V. Szentpály, S. Liu, Electrophilicity index. Journal of the American Chemical Society 121 (1999) 1922-1924.
• [43] R. G. Parr, L. V. Szentpály, S. Liu, Electrophilicity index. Journal of the American Chemical Society 121 (1999) 1922-1924.
• [44] L. R. Domingo, P. Pérez, The nucleophilicity N index in organic chemistry. Organic & Biomolecular Chemistry 9 (2011) 7168-7175.
• [44] L. R. Domingo, P. Pérez, The nucleophilicity N index in organic chemistry. Organic & Biomolecular Chemistry 9 (2011) 7168-7175.
• [45] F. A. Bulat, E. Chamorro, P. Fuentealba, et al. Condensation of frontier molecular orbital Fukui functions. The Journal of Physical Chemistry A 108 (2004) 342-349.
• [45] F. A. Bulat, E. Chamorro, P. Fuentealba, et al. Condensation of frontier molecular orbital Fukui functions. The Journal of Physical Chemistry A 108 (2004) 342-349.
• [46] M. S. M. Ahmed, A. E. Mekky, S. M. Sanad, Regioselective [3+ 2] cycloaddition synthesis and theoretical calculations of new chromene-pyrazole hybrids: A DFT-based Parr Function, Fukui Function, local reactivity indexes, and MEP analysis. Journal of Molecular Structure 1267 (2022) 133583.
• [46] M. S. M. Ahmed, A. E. Mekky, S. M. Sanad, Regioselective [3+ 2] cycloaddition synthesis and theoretical calculations of new chromene-pyrazole hybrids: A DFT-based Parr Function, Fukui Function, local reactivity indexes, and MEP analysis. Journal of Molecular Structure 1267 (2022) 133583.
• [47] T. G. B. Suelen, B. Fernanda, O. Ednilson, et al., Photodynamic efficiency of xanthene dyes and their phototoxicity against a carcinoma cell line: a computational and experimental study. Journal of Chemistry 2017 (2017) 1-9.
• [47] T. G. B. Suelen, B. Fernanda, O. Ednilson, et al., Photodynamic efficiency of xanthene dyes and their phototoxicity against a carcinoma cell line: a computational and experimental study. Journal of Chemistry 2017 (2017) 1-9.
• [48] D. Sarkar, K. Ray, M. Sengupta, Structure-function correlation analysis of connexin50 missense mutations causing congenital cataract: electrostatic potential alteration could determine intracellular trafficking fate of mutants. Biomed Research International 2014 (2014) 1-10.
• [48] D. Sarkar, K. Ray, M. Sengupta, Structure-function correlation analysis of connexin50 missense mutations causing congenital cataract: electrostatic potential alteration could determine intracellular trafficking fate of mutants. Biomed Research International 2014 (2014) 1-10.
• [49] A. Bendjeddou, T. K. Abbaz, A. Gouasmia, et al., Molecular structure, HOMO-LUMO, MEP and Fukui function analysis of some TTF-donor substituted molecules using DFT (B3LYP) calculations. International Research Journal of Pure and Applied Chemistry 12 (2016) 1-9.
• [49] A. Bendjeddou, T. K. Abbaz, A. Gouasmia, et al., Molecular structure, HOMO-LUMO, MEP and Fukui function analysis of some TTF-donor substituted molecules using DFT (B3LYP) calculations. International Research Journal of Pure and Applied Chemistry 12 (2016) 1-9.
• [50] L. R. Domingo, P. Pérez, J. A. Sáez, Understanding the local reactivity in polar organic reactions through electrophilic and nucleophilic Parr functions. RSC Advances 3 (2013) 1486-1494.
• [50] L. R. Domingo, P. Pérez, J. A. Sáez, Understanding the local reactivity in polar organic reactions through electrophilic and nucleophilic Parr functions. RSC Advances 3 (2013) 1486-1494.