Abstract
Both intramolecular [4 + 2] and intermolecular [3 + 2] cycloaddition reactions for the synthesis of 1,3-dioxoepoxyisoindole and epoxypyrrolo[3,4-g]indazoles, respectively, experimentally explored by Alizadeh and co-workers, were studied theoretically at the M06-2X/6-311G(d,p) computational level in both gaseous and solution (acetonitrile, benzene and DMSO) phases. In the first stage, it was studied the intramolecular [4 + 2] cycloaddition reaction generating potentially two diastereomeric adducts and it was confirmed the formation of experimentally reported product, 1,3-dioxoepoxyisoindole DEI-1 by the local reactivity indices as well as potential energy surface analysis. In the second stage, the [3 + 2] cycloaddition reaction of DEI-1 with three nitrilimines including NI–H, NI-C and NI–N, which generates potentially four possible regio- and stereoisomeric adducts was studied. The local reactivity indices described satisfactorily the experimentally observed regioselectivities. The results of potential energy surface analysis indicated that among the four possible products, only two exo regioisomeric adducts (namely, epoxypyrrolo[3,4-g]indazoles, CA-x1 and CA-x2) can be formed. In fact, for the reaction of DEI-1 with NI–H, NI-C and NI–H, the ratio of CA-x1:CA-x2 was estimated to be 57:43, 86:14 and 39:61, respectively, which is in satisfactory agreement with the experimental outcomes. The structural variations during the reactions were also studied and the results indicated that the transition states are not completely synchronous.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Alizadeh A, Asalemi KAA, Halvagar M (2019) Intramolecular Diels-Alder and [3+ 2] Cycloaddition reactions in the one-pot synthesis of epoxypyrrolo [3, 4-g] indazoles. Synthesis 51:2936–2944. https://doi.org/10.1055/s-0037-1612426
Barone V, Cossi M (1998) Quantum calculation of molecular energies and energy gradients in solution by a conductor solvent model. J Phys Chem A 102:1995–2001. https://doi.org/10.1021/jp9716997
Bazian A, Beyramabadi SA, Davoodnia A, Pordel M, Bozorgmehr MR (2016) Kinetics and mechanism of the 1, 3-dipolar cycloaddition of nitrilimine with thione-containing dipolarophile: a detailed DFT study. Res Chem Intermed 42:6125–6141. https://doi.org/10.1007/s11164-016-2449-3
Berski S, Andrés J, Silvi B, Domingo LR (2006) New findings on the Diels−Alder reactions. An analysis based on the bonding evolution theory. J Phys Chem A 110:13939–13947. https://doi.org/10.1021/jp068071t
Bertini I, Calderone V, Fragai M, Luchinat C, Talluri E (2009) Structural basis of serine/threonine phosphatase inhibition by the archetypal small molecules cantharidin and norcantharidin. J Med Chem 52:4838–4843. https://doi.org/10.1021/jm900610k
Brieger G, Bennett JN (1980) The intramolecular Diels-Alder reaction. Chem Rev 80:63–97. https://doi.org/10.1021/cr60323a004
Brion F (1982) On the lewis acid catalyzed diels-alder reaction of furan. regio-and stereospecific synthesis of substituted cyclohexenols and cyclohexadienols. Tetrahedron Lett 23:5299–5302. https://doi.org/10.1016/S0040-4039(00)85823-2
Chamorro E, Pérez P, Domingo LR (2013) On the nature of Parr functions to predict the most reactive sites along organic polar reactions. Chem Phys Lett 582:141–143. https://doi.org/10.1016/j.cplett.2013.07.020
Chiu P, Lautens M (1997) Using ring-opening reactions of oxabicyclic compounds as a strategy in organic synthesis, Stereoselective Heterocyclic Synthesis II. Springer, Berlin, pp 1–85
Diels O (1929) The Diels-Alder Reaction. Ber Dtsch Chem Ges 62:554–562
Domingo LR, Aurell MJ, Pérez P, Contreras R (2002) Quantitative characterization of the global electrophilicity power of common diene/dienophile pairs in Diels-Alder reactions. Tetrahedron 58:4417–4423. https://doi.org/10.1016/S0040-4020(02)00410-6
Domingo LR, Pérez P, Ortega DE (2013a) Why do five-membered heterocyclic compounds sometimes not participate in polar diels-alder reactions? J Org Chem 78:2462–2471. https://doi.org/10.1021/jo3027017
Domingo LR, Pérez P, Sáez JA (2013b) Understanding the local reactivity in polar organic reactions through electrophilic and nucleophilic Parr functions. RSC Adv 3:1486–1494. https://doi.org/10.1039/C2RA22886F
Domingo LR, Emamian S, Salami M, Ríos-Gutiérrez M (2016) Understanding the molecular mechanism of the [3+ 2] cycloaddition reaction of benzonitrile oxide toward electron-rich N-vinylpyrrole: a DFT study. J Phys Org Chem 29:368–376. https://doi.org/10.1002/poc.3544
Emamian S (2016) How the mechanism of a [3+ 2] cycloaddition reaction involving a stabilized N-lithiated azomethine ylide toward a π-deficient alkene is changed to stepwise by solvent polarity? What is the origin of its regio-and endo stereospecificity? A DFT study using NBO, QTAIM, and NCI analyses. RSC Adv 6:75299–75314. https://doi.org/10.1039/C6RA13913B
Emamian S, Soleymani M, Moosavi SS (2019) Copper (i)-catalyzed asymmetric aza Diels-Alder reactions of azoalkenes toward fulvenes: a molecular electron density theory study. New J Chem 43:4765–4776. https://doi.org/10.1039/C9NJ00269C
Frisch MJTG, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Mennucci B, Petersson GA, Nakatsuji H, Caricato M, Li X, Hratchian HP, Izmaylov AF, Bloino J, Zheng G, Sonnenberg JL, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Vreven T, Montgomery JA Jr, Peralta JE, Ogliaro F, Bearpark M, Heyd JJ, Brothers E, Kudin KN, Staroverov VN, Kobayashi R, Normand J, Raghavachari K, Rendell A, Burant JC, Iyengar SS, Tomasi J, Cossi M, Rega N, Millam JM, Klene M, Knox JE, Cross JB, Bakken V, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Martin RL, Morokuma K, Zakrzewski VG, Voth GA, Salvador P, Dannenberg JJ, Dapprich S, Daniels AD, Farkas Ö, Foresman JB, Ortiz JV, Cioslowski J, Fox DJ (2013) Gaussian 09, Revision E.01. Gaussian Inc., Wallingford CT
Geerlings P, De Proft F, Langenaeker W (2003) Conceptual density functional theory. Chem Rev 103:1793–1874. https://doi.org/10.1021/cr990029p
Gonzalez C, Schlegel HB (1989) An improved algorithm for reaction path following. J Chem Phys 90:2154–2161. https://doi.org/10.1063/1.456010
Gonzalez C, Schlegel HB (1990) Reaction path following in mass-weighted internal coordinates. J Phys Chem 94:5523–5527. https://doi.org/10.1021/j100377a021
Hill TA, Stewart SG, Gordon CP, Ackland SP, Gilbert J, Sauer B, Sakoff JA, McCluskey A (2008) Norcantharidin analogues: synthesis, anticancer activity and protein phosphatase 1 and 2A inhibition. ChemMedChem 3:1878–1892. https://doi.org/10.1002/cmdc.200800192
Huisgen R (1984) 1, 3-Dipolar cycloaddition chemistry. Wiley, New York, pp 55–92
Huyen CTT, Luyen BTT, Khan GJ, Oanh HV, Hung TM, Li H-J, Li P (2018) Chemical constituents from Cimicifuga dahurica and their anti-proliferative effects on MCF-7 breast cancer cells. Molecules 23:1083. https://doi.org/10.3390/molecules23051083
Jaramillo P, Domingo LR, Chamorro E, Pérez P (2008) A further exploration of a nucleophilicity index based on the gas-phase ionization potentials. J Mol Struct-THEOCHEM 865:68–72. https://doi.org/10.1016/j.theochem.2008.06.022
Lee C, Yang W, Parr RG (1988) Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys Rev B 37:785. https://doi.org/10.1103/physrevb.37.785
McCluskey A, Walkom C, Bowyer MC, Ackland SP, Gardiner E, Sakoff JA (2001) Cantharimides: a new class of modified cantharidin analogues inhibiting protein phosphatases 1 and 2A. Bioorg Med Chem Lett 11:2941–2946. https://doi.org/10.1016/S0960-894X(01)00594-7
Molteni G, Ponti A (2017) The nitrilimine-alkene cycloaddition regioselectivity rationalized by density functional theory reactivity indices. Molecules 22:202. https://doi.org/10.3390/molecules22020202
Norman RO (1982) Principles of organic synthesis, 2nd edn. Chapman and Hall, London, pp 270–298
Opoku E, Arhin G, Pipim GB, Adams AH, Tia R, Adei E (2020) Site-, enantio-and stereo-selectivities of the 1, 3-dipolar cycloaddition reactions of oxanorbornadiene with C, N-disubstituted nitrones and dimethyl nitrilimines: a DFT mechanistic study. Theor Chem Acc 139:1–15. https://doi.org/10.1007/s00214-019-2529-8
Parr RG, Pearson RG (1983) Absolute hardness: companion parameter to absolute electronegativity. J Am Chem Soc 105:7512–7516. https://doi.org/10.1021/ja00364a005
Parr RG, Weitao Y (1989) Density-functional theory of atoms and molecules. Oxford University Press, Oxford
Parr RG, Lv S, Liu S (1999) Electrophilicity index. J Am Chem Soc 121:1922–1924. https://doi.org/10.1021/ja983494x
Reymond J-L, Vogel P (1990) New chiral auxiliaries and new optically pure ketene equivalents derived from tartaric acids. Improved synthesis of (−)-7-oxabicyclo [2.2. 1] hept-5-en-2-one. Tetrahedron Asymmetry 1:729–736. https://doi.org/10.1016/S0957-4166(00)82385-X
Saleem M, Ali MS, Hussain S, Jabbar A, Ashraf M, Lee YS (2007) Marine natural products of fungal origin. Nat Prod Rep 24:1142–1152. https://doi.org/10.1039/B607254M
Schindler CS, Carreira EM (2009) Rapid formation of complexity in the total synthesis of natural products enabled by oxabicyclo [2.2. 1] heptene building blocks. Chem Soc Rev 38:3222–3241. https://doi.org/10.1039/B915448P
Smith MB (2020) March's advanced organic chemistry: reactions, mechanisms, and structure. John Wiley & Sons, New Jersey
Soleymani M (2018) DFT study of double 1, 3-dipolar cycloaddition of nitrilimines with allenoates. Monatsh Chem Chem Mon 149:2183–2193. https://doi.org/10.1007/s00706-018-2311-y
Soleymani M (2019) A density functional theory study on the [3+ 2] cycloaddition of N-(p-methylphenacyl) benzothiazolium ylide and 1-nitro-2-(p-methoxyphenyl) ethene: the formation of two diastereomeric adducts via two different mechanisms. Theor Chem Acc 138:87. https://doi.org/10.1007/s00214-019-2477-3
Soleymani M (2020) Regio-, diastereo-and enantioselectivity in the synthesis of CF3-containing spiro [pyrrolidin-3, 2′ oxindole] through the organocatalytic [3+ 2] cycloaddition reaction: A molecular electron density theory study. J Fluorine Chem. https://doi.org/10.1016/j.jfluchem.2020.109566
Soleymani M, Chegeni ZK (2019) A molecular electron density theory study on the [3+ 2] cycloaddition reaction of 5, 5-dimethyl-1-pyrroline N-oxide with 2-cyclopentenone. J Mol Graphics Modell 92:256–266. https://doi.org/10.1016/j.jmgm.2019.08.007
Soleymani M, Jahanparvar S (2020) A computational study on the [3+ 2] cycloaddition of para-quinone methides with nitrile imines: a two-stage one-step mechanism. Monatsh Chem Chem Mon 151:51–61. https://doi.org/10.1007/s00706-019-02531-2
Sykes P (1986) A guidebook to mechanism in organic chemistry. Pearson Education, India
Vieira E, Vogel P (1982) Copper (I)-and Copper (II)-catalyzed Diels-Alder additions of α-substituted acrylonitrile to furan. The synthesis of 7-Oxa-bicyclo [2.2. 1] hept-5-en-2-one. Helv Chim Acta 65:1700–1706. https://doi.org/10.1002/hlca.19820650604
Vieira E, Vogel P (1983) The preparation of optically pure 7-Oxabicyclo [2.2. 1] hept-2-ene derivatives. The CD spectrum of (+)-(1R)-7-Oxabicyclo [2.2. 1] hept-5-en-2-one. Helv Chim Acta 66:1865–1871. https://doi.org/10.1002/hlca.19830660627
Vogel P, Cossy J, Plumet J, Arjona O (1999) Derivatives of 7-oxabicyclo [2.2. 1] heptane in nature and as useful synthetic intermediates. Tetrahedron 55:13521–13642. https://doi.org/10.1016/S0040-4020(99)00845-5
Wiberg KB (1968) Application of the pople-santry-segal CNDO method to the cyclopropylcarbinyl and cyclobutyl cation and to bicyclobutane. Tetrahedron 24:1083–1096. https://doi.org/10.1016/0040-4020(68)88057-3
Woodward RB, Hoffmann R (1965) Stereochemistry of electrocyclic reactions. J Am Chem Soc 87:395–397. https://doi.org/10.1021/ja01080a054
Yang W, Mortier WJ (1986) The use of global and local molecular parameters for the analysis of the gas-phase basicity of amines. J Am Chem Soc 108:5708–5711. https://doi.org/10.1021/ja00279a008
Zhao Y, Truhlar DG (2006) Comparative DFT study of van der Waals complexes: rare-gas dimers, alkaline-earth dimers, zinc dimer, and zinc-rare-gas dimers. J Phys Chem A 110:5121–5129. https://doi.org/10.1021/jp060231d
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
On behalf of all authors, the corresponding author states that there is no conflict of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Soleymani, M., Dashti Khavidaki, H. Regio- and stereochemistry in the intramolecular [4 + 2] and intermolecular [3 + 2] cycloaddition reactions in the synthesis of epoxypyrrolo[3,4-g]indazoles: a density functional theory study. Chem. Pap. 75, 951–965 (2021). https://doi.org/10.1007/s11696-020-01359-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11696-020-01359-z