The evaluation of chemoselectivity in multicomponent domino Knoevenagel/Diels–Alder reaction: A DFT study Scientific paper

Main Article Content

Mina Attarbashi
Nader Zabarjad Shiraz
Marjaneh Samadizadeh


Herein, the chemoselectivity of the multicomponent domino Kno­eve­nagel/Diels–Alder reaction is investigated in terms of theoretical calcu­lations. The structures of reagents, transition states, intermediates and products are optimized at the M062X/6-31+G(d,p) level of theory. The reaction mechanism involves processes of bond rotation, isomerization, asymmetric cycloaddition, acid–base and nucleophile–electrophile competitions, which are studied for the purpose of delivering a clear information of the mechanism in terms of chemo­selectivity considerations. Accordingly, the chemoselectivity of the reaction is controlled by the releasing acetone during the decomposition of Meldrum acid in the presence of methanol and l-proline (DG# = 61.45 kcal** mol-1). Com­paring calculated results (gas and solvent phase) with the experimental ones showed that using these reagents are the kinetical favourite path for the chemo­selective multicomponent cascade Knoevenagel/Diels–Alder reaction to pro­duce the predominant product (>95 %). The results suggest that the creation of cis-spiro cyclohexanone is the predominant chemoselective product under kin­etic control of the desired enone.

Article Details

How to Cite
M. Attarbashi, N. Z. Shiraz, and M. . Samadizadeh, “The evaluation of chemoselectivity in multicomponent domino Knoevenagel/Diels–Alder reaction: A DFT study: Scientific paper”, J. Serb. Chem. Soc., vol. 86, no. 11, pp. 1053-1065, Nov. 2021.
Theoretical Chemistry


L. Reguera, D. G. Rivera, Chem. Rev. 119 (2019) 9836 (

U. K. Sharma, P. Ranjan, E. V. Van der Eycken, S.-L. You, Chem. Soc. Rev. 49 (2020) 8721 (

R. C. Cioc, E. Ruijter, R. V. Orru, Green Chem. 16 (2014) 2958 (

H. Pellissier, Adv. Synth. Catal. 358 (2016) 2194 (

M. Ashe, Master Thesis, University of Southampton, Faculty of Natural and Environmental Sciences, Southampton, 2016 (

S. M. Xu, L. Wei, C. Shen, L. Xiao, H. Y. Tao, C. J. Wang, Nat. Commun. 10 (2019) 5553 (

M. Wang, Z. Shi, Chem. Rev. 120 (2020) 7348 (

H. A. Younus, M. Al. Rashida, A. Hameed, M. Uroos, U. Salar, S. Rana, K. M. Khan, Expert Opin. Ther. Pat. 31 (2021) 267 (

X. Xiao, T. R. Hoye, Nat. Chem. 10 (2018) 838 (

M. H. Cao, N. J. Green, S. Z. Xu, Org. Biomol. Chem. 15 (2017) 3105 (

X. Ji, C. Zhou, K. Ji, R. E. Aghoghovbia, Z. Pan, V. Chittavong, B. Ke, B. Wang, Angew. Chem. Int. Ed. 55 (2016) 15846 (

Y. Yamashita, T. Yasukawa, W. J. Yoo, T. Kitanosono, S. Kobayashi, Chem. Soc. Rev. 47 (2018) 4388 (

J. Hu, M. Bian, H. Ding, Tetrahedron Lett. 57 (2016) 5519 (

J. F. Allochio Filho, B. C. Lemos, A. S. de Souza, S. Pinheiro, S. J. Greco, Tetrahedron 73 (2017) 6977 (

B. L. Oliveira, Z. Guo, G. J. L. Bernardes, Chem. Soc. Rev. 46 (2017) 4895 (

P. L. Wang, S. Y. Ding, Z. C. Zhang, Z. P. Wang, W. Wang, J. Am. Chem. Soc. 141 (2019) 18004 (

W. Gati, H. Yamamoto, Acc. Chem. Res. 49 (2016) 1757 (

C. He, J. Hu, Y. Wu, H. Ding, J. Am. Chem. Soc. 139 (2017) 6098 (

E. Sánchez-Larios, J. M. Holmes, C. L. Daschner, M. Gravel, Org. Lett. 12 (2010) 5772 (

J. Wang, H. Li, H. Xie, L. Zu, X. Shen, W. Wang, Angew. Chem. 119 (2007) 9208 (

B. C. Hong, R. Y. Nimje, A. A. Sadani, J. H. Liao, Org. Lett. 10 (2008) 2345 (

W. Notz, F. Tanaka, C. F. Barbas, Acc. Chem. Res. 37 (2004) 580 (

A. Cordova, C. F. Barbas, Tetrahedron Lett. 44 (2003) 1923 (

F. Tanaka, C. F. Barbas III, J. Syn. Org. Chem. Jpn. 63 (2005) 709 (

S. Mukherjee, J. W. Yang, S. Hoffmann, B. List, Chem. Rev. 107 (2007) 5471 (

N. Campillo, J. A. Paez, P. Goya, Helv. Chim. Acta 86 (2003) 139 (

D. B. Ramachary, K. Anebouselvy, N. S. Chowdari, C. F. Barbas, J. Org. Chem. 69 (2004) 5838 (

R. Thayumanavan, B. Dhevalapally, K. Sakthivel, F. Tanaka, C. F. Barbas III, Tetrahedron Lett. 43 (2002) 3817 (

N. S. Chowdari, C. F. Barbas, Org. Lett. 7 (2005) 867 (

E. M. Carreira, T. C. Fessard, Chem. Rev. 114 (2014) 8257 (

L. Hong, R. Wang, Adv. Synth. Catal. 355 (2013) 1023 (

J. Tellenbröker, D. Kuck, Eur. J. Org. Chem. 2001 (2001) 1483 (<1483::AID-EJOC1483>3.0.CO;2-U)

A. Boudhar, M. Charpenay, G. Blond, J. Suffert, Angew. Chem. Int. Ed. 52 (2013) 12786 (

L. Porcelli, D. Stolfa, A. Stefanachi, R. Di Fonte, M. Garofoli, R. Iacobazzi, N. Silvestris, A. Guarini, S. Cellamare, A. Azzariti, Cancer Lett. 445 (2019) 1 (

D. B. Ramachary, C. F. Barbas III, Chem. Eur. J. 10 (2004) 5323 (

M. W. Schmidt, K. Baldridge, J. A. Boatz, S. T. Elbert, M. S. Gordon, J. H. Jensen, S. Koseki, N. Matsunaga, K. A. Nguyen, S. Su, T. L. Windus, M. Dupuis, J. A. Montomery, J. Comput. Chem. 14 (1993) 1347 (

Y. Zhao, D. G. Truhlar, Theor. Chem. Acc. 120 (2008) 215 (

A. Castro-Alvarez, H. Carneros, D. Sanchez, J. Vilarrasa, J. Org. Chem. 80 (2015) 11977 (

M. Head-Gordon, J. A. Pople, M. J. Frisch, J. Chem. Phys. Lett. 153 (1988) 503 (

Y. Zhao, N. E. Schultz, D. G. Truhlar, J. Chem. Phys. 123 (2005) 161103 (

S. B. Trickey, Int. J. Quantum Chem. 59 (1996) 259 (

M. Attarbashi, N. Zabarjad Shiraz, M. Samadizadeh, J. Theor. Comput. Chem. 19 (2020) 2050005 (

M. Girod, B. Grammaticos, Nucl. Phys., A 330 (1979) 40 (