{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T02:42:36Z","timestamp":1775702556006,"version":"3.50.1"},"reference-count":74,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2019,11,16]],"date-time":"2019-11-16T00:00:00Z","timestamp":1573862400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Economy and Competitiveness of the Spanish Government","award":["CTQ2016-78669-P"],"award-info":[{"award-number":["CTQ2016-78669-P"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The reaction of diphenyl nitrilimine (NI) with methyl 1-methyl-allenoate yielding a spirobipyrazoline has been studied within molecular electron density theory (MEDT) at the MPWB1K\/6-311G(d) computational level in dichloromethane. This reaction is a domino process that comprises two consecutive 32CA reactions with the formation of a pyrazoline intermediate. Analysis of the relative Gibbs free energies indicates that both 32CA reactions are highly regioselective, the first one being also completely chemoselective, in agreement with the experimental outcomes. The geometries of the TSs indicate that they are associated to asynchronous bond formation processes in which the shorter distance involves the C1 carbon of diphenyl NI. Despite the zwitterionic structure of diphenyl NI, the appearance of a pseudoradical structure at the beginning of the reaction path, with a very low energy cost, suggests that the 32CA reaction between diphenyl NI, a strong nucleophile, and the allenoate, a moderate electrophile, should be mechanistically considered on the borderline between pmr-type and cb-type 32CA reactions, somewhat closer to the latter.<\/jats:p>","DOI":"10.3390\/molecules24224159","type":"journal-article","created":{"date-parts":[[2019,11,18]],"date-time":"2019-11-18T04:31:10Z","timestamp":1574051470000},"page":"4159","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["A Molecular Electron Density Theory Study of the Synthesis of Spirobipyrazolines through the Domino Reaction of Nitrilimines with Allenoates"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2023-0108","authenticated-orcid":false,"given":"Luis R.","family":"Domingo","sequence":"first","affiliation":[{"name":"Department of Organic Chemistry, University of Valencia, Dr Moliner 50, 46100 Burjassot, Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatemeh","family":"Ghodsi","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Sistan and Baluchestan, Zahedan 98135-674, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8894-2710","authenticated-orcid":false,"given":"Mar","family":"R\u00edos-Guti\u00e9rrez","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, University of Valencia, Dr Moliner 50, 46100 Burjassot, Valencia, Spain"},{"name":"Department of Chemistry and Chemical Biology, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4L8, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9007","DOI":"10.1016\/S0040-4020(99)00482-2","article-title":"Stereocontrolled Synthesis of Spirocyclics","volume":"55","author":"Sannigrahi","year":"1999","journal-title":"Tetrahedron"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1055\/s-0028-1083300","article-title":"Selected Synthetic Strategies to Spirocyclics","volume":"2","author":"Kotha","year":"2009","journal-title":"Synthesis"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"5506","DOI":"10.1021\/cr100352k","article-title":"Bicyclic Conformationally Restricted Diamines","volume":"111","author":"Grygorenko","year":"2011","journal-title":"Chem. Rev."},{"key":"ref_4","unstructured":"Scheuer, P.J. (1983). Marine Natural Products, Academic Press. Chapter 1."},{"key":"ref_5","first-page":"1937","article-title":"Synthesis of Some Isatin Based Novel Spiroheterocycles and their Biological Activity Studies","volume":"44B","author":"Mashelkar","year":"2005","journal-title":"Indian J. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/s10593-005-0148-x","article-title":"Spiropyrans: Synthesis, Properties, and Application (Review)","volume":"41","author":"Lukyanov","year":"2005","journal-title":"Chem. Heterocycl. Compd."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1007\/s00706-006-0475-3","article-title":"Synthesis and Antimycobacterial Activity of New 2-Hydroxy-N-(3-oxo-1-Thia-4-Azaspiro[4.4]non-4-yl)\/(3-Oxo-1-Thia-4-Azaspiro[4.5]dec-4-yl)-2,2-Diphenylacetamide Derivatives","volume":"137","author":"Ilhan","year":"2006","journal-title":"Monatsh. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1007\/s10593-006-0146-7","article-title":"Synthesis of some Thiadiazoles, Selenadiazoles and Spiroheterocyclic Compounds from Their 2,2-Dimethyl-Benzopyran Precursor","volume":"42","author":"Joshi","year":"2006","journal-title":"Chem. Heterocycl. Compd."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Habib-Zahmani, H., Viala, J., Hacini, S., and Rodriguez, J. (2007). Synthesis of Functionalized Spiroheterocycles by Sequential Multicomponent Reaction\/Metal-Catalyzed Carbocylizations from Simple \u03b2-Ketoesters and Amides. Synlett, 1037\u20131042.","DOI":"10.1055\/s-2007-973896"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1021\/ol9902881","article-title":"Design and Synthesis of the First Spiro Bis(isoxazoline) Derivatives as Asymmetric Ligands","volume":"1","author":"Arai","year":"1999","journal-title":"Org. Lett."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2907","DOI":"10.1021\/ja005920w","article-title":"A New Asymmetric Wacker-Type Cyclization and Tandem Cyclization Promoted by Pd(II)-Spiro Bis(isoxazoline) Catalyst","volume":"123","author":"Arai","year":"2001","journal-title":"J. Am. Chem. Soc."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2349","DOI":"10.1016\/j.tet.2012.01.029","article-title":"Thermal [3+2] Cycloaddition Reaction of Azomethine Imines with Allenoates for Dinitrogen-fused Heterocycles","volume":"68","author":"Na","year":"2012","journal-title":"Tetrahedron"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"8274","DOI":"10.1016\/j.tet.2016.10.064","article-title":"Thermal [3+2] Cycloaddition of N-Iminoquiazoline Ylides with Allenoates for Synthesis of Tetrahydropyrazoloquinazoline Derivatives","volume":"72","author":"Zhang","year":"2016","journal-title":"Tetrahedron"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5376","DOI":"10.1021\/acs.orglett.5b02724","article-title":"1,3-Dipolar Cycloadditions of 4-Acetoxy Allenoates: Access to 2,3-Dihydropyrazoles, 2,3-Dihydroisoxazoles, and Indolizines","volume":"17","author":"Li","year":"2015","journal-title":"Org. Lett."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"34481","DOI":"10.1039\/C5RA04374C","article-title":"Phosphine-Catalyzed [4+3] Cycloaddition reaction of Aromatic Azomethine Imines with Allenoates","volume":"5","author":"Li","year":"2015","journal-title":"RSC Adv."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1880","DOI":"10.1002\/adsc.201600223","article-title":"Phosphane-Catalyzed [3+3] Annulation of C,N-Cyclic Azomethine Imines with Ynones: A Practical Method for Tricyclic Dinitrogen-Fused Heterocycles","volume":"358","author":"Li","year":"2016","journal-title":"Adv. Synth. Catal."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5644","DOI":"10.1021\/acs.orglett.6b02885","article-title":"Phosphine-Catalyzed Enantioselective [4+3] Annulation of Allenoates with C,N-Cyclic Azomethine Imines: Synthesis of Quinazoline-Based Tricyclic Heterocycles","volume":"18","author":"Yuan","year":"2016","journal-title":"Org. Lett."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2316","DOI":"10.1002\/adsc.201601434","article-title":"Enantioselective Synthesis of Quinazoline-Based Heterocycles through Phosphine-Catalyzed Asymmetric [3+3] Annulation of Morita-Baylis-Hillman Carbonates with Azomethine Imines","volume":"359","author":"Zhou","year":"2017","journal-title":"Adv. Synth. Catal."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.ejmech.2013.01.059","article-title":"Cycloadditions and Condensations as Essential Tools in Spiropyrazoline Synthesis","volume":"63","author":"Dadiboyena","year":"2013","journal-title":"Eur. J. Med. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4145","DOI":"10.1016\/S0040-4039(00)97565-8","article-title":"Reaction of Diarylnitrilimines with 3-Arylidene-4-Isothiochromanones. A General Approach to the First Thiadiazaphenanthrene","volume":"31","author":"Kerbal","year":"1990","journal-title":"Tetrahedron Lett."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"7537","DOI":"10.1021\/jo0507587","article-title":"Electrolytic Partial Fluorination of Organic Compounds. 79. Anodic Fluorination of Spiropyrazoline-5,3\u2018-chroman-4-ones and Thiochromanone Analogues. A Route to Aroyl Fluoride Derivatives","volume":"70","author":"Dawood","year":"2005","journal-title":"J. Org. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Singh, V., Singh, V., and Batra, S. (2008). Straightforward Strategy for the Stereoselective Synthesis of Spiro-Fused (C-5)Isoxazolino- or (C-3)Pyrazolino-(C-3)quinolin-2-ones from Baylis\u2013Hillman Adducts by 1,3-Dipolar Cycloaddition and Reductive Cyclization. Eur. J. Org. Chem., 5446\u20135460.","DOI":"10.1002\/ejoc.200800746"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1016\/j.steroids.2009.02.001","article-title":"Stereoselective Synthesis of Spiro and Condensed Pyrazolines of Steroidal \u03b1,\u03b2-Unsaturated Ketones and Nitrilimines by 1,3-Dipolar Cycloaddition","volume":"74","author":"Mernyak","year":"2009","journal-title":"Steroids"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2536","DOI":"10.1016\/j.tetlet.2011.03.004","article-title":"One Pot Spiropyrazoline Synthesis via Intramolecular Cyclization\/Methylation","volume":"52","author":"Dadiboyena","year":"2011","journal-title":"Tetrahedron Lett."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1021\/om950770x","article-title":"1,3-Dipolar Cycloaddition to Tricarbonyl[(1\u22124-\u03b7)-2- Methoxy-5-Methylenecyclohexa-1,3-Diene]iron:\u2009 Rapid Construction of a Spiro[4.5]decane System","volume":"15","author":"Ong","year":"1996","journal-title":"Organometallics"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1055\/s-1998-2195","article-title":"Stereoselective Diazoalkane Cycloadditions to Chiral 5-Alkylidene-1, 3-Dioxan-4-Ones and 3-Benzylidene-\u03b2-lactones","volume":"11","author":"Bartels","year":"1998","journal-title":"Synthesis"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1080\/00304940209458078","article-title":"Synthesis of Spiro-1-Pyrazolines by the Reaction of z-3-Arylidene-1-Thioflavanones with Diazomethane","volume":"34","author":"Levai","year":"2002","journal-title":"Org. Prep. Proced. Int."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4764","DOI":"10.1021\/jo200582z","article-title":"Highly Selective Synthesis of Pyrazole and Spiropyrazoline Phosphonates via Base-Assisted Reaction of the Bestmann\u2013Ohira Reagent with Enones","volume":"76","author":"Verma","year":"2011","journal-title":"J. Org. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3812","DOI":"10.1016\/j.tet.2014.03.109","article-title":"Synthesis of Chiral Spiropyrazoline-\u03b2-Lactams and Spirocyclopropyl-\u03b2-Lactams from 6-Alkylidenepenicillanates","volume":"70","author":"Santos","year":"2014","journal-title":"Tetrahedron"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.tetasy.2017.01.009","article-title":"The Stereochemistry of the 1,3-Dipolar Cycloadditions of Diazomethane to Pseudoguaianolides","volume":"28","author":"TorresValencia","year":"2017","journal-title":"Tetrahedron Asymmetry"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.molstruc.2017.02.037","article-title":"The Cytotoxic Effect of Spiroflavanone Derivatives, their Binding Ability to Human Serum Albumin (HSA) and a DFT Study on the Mechanism of their Synthesis","volume":"1137","author":"Budzisz","year":"2017","journal-title":"J. Mol. Struct."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3758","DOI":"10.1021\/jo00961a024","article-title":"Diaziridines","volume":"38","author":"Nabeya","year":"1973","journal-title":"J. Org. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Makhova, N.N., Petukhova, V.Y., and Kuznetsov, V.V. (2008). Synthesis of Monocyclic Diaziridines and their Fused Derivatives. ARKIVOC, 128\u2013152.","DOI":"10.3998\/ark.5550190.0009.105"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5842","DOI":"10.1021\/ol202452b","article-title":"Gold(I)-Catalyzed Formation of 3-Pyrazolines through Cycloaddition of Diaziridine to Alkynes","volume":"13","author":"Capretto","year":"2011","journal-title":"Org. Lett."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Bird, C.W., and Cheesemen, G.W.H. (1973). Aromatic and Heteroaromatic Chemistry, RSC.","DOI":"10.1039\/9781847555694"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Li, J.J. (2009). Name Reactions: A Collection of Detailed Mechanisms and Synthetic Applications, Springer. [4th ed.].","DOI":"10.1007\/978-3-642-01053-8"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Li, J.J., and Corey, E.J. (2011). Name Reactions in Heterocyclic Chemistry II (Comprehensive Name Reactions), Wiley.","DOI":"10.1002\/9781118092828"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2673","DOI":"10.2174\/138527212804004553","article-title":"Synthesis of Spiro-heterocycles via 1,3-Dipolar Cycloadditions of Nitrilimines to Exoheterocyclic Enones. Site-, Regio- and Stereo-Selectivities Overview","volume":"16","author":"Shawali","year":"2012","journal-title":"Curr. Org. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.ejmech.2014.04.023","article-title":"Synthesis of Novel Spiropyrazoline Oxindoles and Evaluation of Cytotoxicity in Cancer Cell Lines","volume":"79","author":"Monteiro","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4714","DOI":"10.1021\/acs.orglett.7b01961","article-title":"Synthesis of Spirobidihydropyrazole through Double 1,3-Dipolar Cycloaddition of Nitrilimines with Allenoates","volume":"19","author":"Liu","year":"2017","journal-title":"Org. Lett."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Domingo, L.R. (2016). Molecular Electron Density Theory: A Modern View of Reactivity in Organic Chemistry. Molecules, 21.","DOI":"10.3390\/molecules21101319"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1016\/j.tet.2019.02.014","article-title":"The Carbenoid-Type Reactivity of Simplest Nitrile Imine from a Molecular Electron Density Theory Perspective","volume":"75","author":"Domingo","year":"2019","journal-title":"Tetrahedron"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"6908","DOI":"10.1021\/jp048147q","article-title":"Hybrid Meta Density Functional Theory Methods for Thermochemistry, Thermochemical Kinetics, and Noncovalent Interactions: The MPW1B95 and MPWB1K Models and Comparative Assessments for Hydrogen Bonding and van der Waals interactions","volume":"108","author":"Zhao","year":"2004","journal-title":"J. Phys. Chem. A"},{"key":"ref_44","unstructured":"Hehre, M.J., Radom, L., Schleyer, P.v.R., and Pople, J. (1986). Ab initio Molecular Orbital Theory, Wiley."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1002\/jcc.540030212","article-title":"Optimization of Equilibrium Geometries and Transition Structures","volume":"3","author":"Schlegel","year":"1982","journal-title":"J. Comput. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Yarkony, D.R. (1994). Modern Electronic Structure Theory, World Scientific Publishing.","DOI":"10.1142\/1957-part2"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4161","DOI":"10.1021\/j100717a029","article-title":"Formulation of the Reaction Coordinate","volume":"74","author":"Fukui","year":"1970","journal-title":"J. Phys. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5523","DOI":"10.1021\/j100377a021","article-title":"Reaction Path Following in Mass-Weighted Internal Coordinates","volume":"94","author":"Schlegel","year":"1990","journal-title":"J. Phys. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"5853","DOI":"10.1063\/1.461606","article-title":"Improved Algorithms for Reaction Path Following: Higher-order Implicit Algorithms","volume":"95","author":"Schlegel","year":"1991","journal-title":"J. Chem. Phys."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2027","DOI":"10.1021\/cr00031a013","article-title":"Molecular Interactions in Solution: And Overview of Methods Based on Continuous Distributions of the Solvent","volume":"94","author":"Tomasi","year":"1994","journal-title":"Chem. Rev."},{"key":"ref_51","unstructured":"Simkin, B.Y., and Sheikhet, I.I. (1995). Quantum Chemical and Statistical Theory of Solutions\u2013Computational Approach, Ellis Horwood."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/0009-2614(96)00349-1","article-title":"Ab Initio Study of Solvated Molecules: A New Implementation of the Polarizable Continuum Model","volume":"255","author":"Cossi","year":"1996","journal-title":"Chem. Phys. Lett."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3032","DOI":"10.1063\/1.474659","article-title":"A New Integral Equation Formalism for the Polarizable Continuum Model: Theoretical Background and Applications to Isotropic and Anisotropic Dielectrics","volume":"107","author":"Cances","year":"1997","journal-title":"J. Chem. Phys."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1002\/(SICI)1096-987X(199803)19:4<404::AID-JCC3>3.0.CO;2-W","article-title":"Geometry Optimization of Molecular Structures in Solution by the Polarizable Continuum Model","volume":"19","author":"Barone","year":"1998","journal-title":"J. Comput. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"32415","DOI":"10.1039\/C4RA04280H","article-title":"A New C-C Bond Formation Model Based on the Quantum Chemical Topology of Electron Density","volume":"4","author":"Domingo","year":"2014","journal-title":"RSC Adv."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1063\/1.449486","article-title":"Natural Population Analysis","volume":"83","author":"Reed","year":"1985","journal-title":"J. Chem. Phys."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1021\/cr00088a005","article-title":"Intermolecular Interactions from a Natural Bond Orbital, Donor-Acceptor Viewpoint","volume":"88","author":"Reed","year":"1988","journal-title":"Chem. Rev."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1021\/cr990029p","article-title":"Conceptual Density Functional Theory","volume":"103","author":"Geerlings","year":"2003","journal-title":"Chem. Rev."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Domingo, L.R., R\u00edos-Guti\u00e9rrez, M., and P\u00e9rez, P. (2016). Applications of the Conceptual Density Functional Indices to Organic Chemistry Reactivity. Molecules, 21.","DOI":"10.3390\/molecules21060748"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.1039\/C2RA22886F","article-title":"Understanding the Local Reactivity in Polar Organic Reactions through Electrophilic and Nucleophilic Parr Functions","volume":"3","author":"Domingo","year":"2013","journal-title":"RSC Adv."},{"key":"ref_61","unstructured":"Frisch, M.J., Trucks, G.W., Schlegel, H.B., Scuseria, G.E., Robb, M.A., Cheeseman, J.R., Scalmani, G., Barone, V., Petersson, G.A., and Nakatsuji, H. (2016). Gaussian 16, Gaussian, Inc."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"5397","DOI":"10.1063\/1.458517","article-title":"A Simple Measure of Electron Localization in Atomic and Molecular-Systems","volume":"92","author":"Becke","year":"1990","journal-title":"J. Chem. Phys."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/S0097-8485(99)00039-X","article-title":"Computational Tools for the Electron Localization Function Topological Analysis","volume":"23","author":"Noury","year":"1999","journal-title":"Comput. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"7277","DOI":"10.1021\/jp9711508","article-title":"Characterization of Elementary Chemical Processes by Catastrophe Theory","volume":"101","author":"Krokidis","year":"1997","journal-title":"J. Phys. Chem. A"},{"key":"ref_65","unstructured":"Dennington, T.A., and Keith, J.M. (2016). GaussView, Version 6.1, R., Millam, Semichem Inc."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"R\u00edos-Guti\u00e9rrez, M., and Domingo, L.R. (2019). Unravelling the Mysteries of the [3+2] Cycloaddition Reactions. Eur. J. Org. Chem., 267\u2013282.","DOI":"10.1002\/ejoc.201800916"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.molstruc.2017.12.052","article-title":"A Combined Experimental and Theoretical Study of the Thermal [3+2] Cycloaddition of Carbonyl Ylides with Activated Alkenes","volume":"1157","author":"Domingo","year":"2018","journal-title":"J. Mol. Struct."},{"key":"ref_68","unstructured":"Huisgen, R. (1961). 1,3-Dipolar Cycloadditions. Proc. Chem. Soc., 357\u2013396."},{"key":"ref_69","unstructured":"Parr, R.G., and Yang, W. (1989). Density Functional Theory of Atoms and Molecules, Oxford University Press."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1922","DOI":"10.1021\/ja983494x","article-title":"Electrophilicity Index","volume":"121","author":"Parr","year":"1999","journal-title":"J. Am. Chem. Soc."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"4615","DOI":"10.1021\/jo800572a","article-title":"Understanding the Reactivity of Captodative Ethylenes in Polar Cycloaddition Reactions. A Theoretical Study","volume":"73","author":"Domingo","year":"2008","journal-title":"J. Org. Chem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1039\/tf9353100875","article-title":"Some Applications of the Transition State Method to the Calculation of Reaction Velocities, Especially in Solution","volume":"31","author":"Evans","year":"1935","journal-title":"Trans. Faraday Soc."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.1016\/j.tet.2017.02.012","article-title":"How Does the Global Electron Density Transfer Diminish Activation Energies in Polar Cycloaddition Reactions? A Molecular Electron Density Theory study","volume":"73","author":"Domingo","year":"2017","journal-title":"Tetrahedron"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"8791","DOI":"10.1021\/jo801575g","article-title":"Understanding the Participation of Quadricyclane as Nucleophile in Polar [2\u03c3 + 2\u03c3 + 2\u03c0] Cycloadditions toward Electrophilic \u03c0 Molecules","volume":"73","author":"Domingo","year":"2008","journal-title":"J. Org. Chem."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/22\/4159\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:35:04Z","timestamp":1760189704000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/22\/4159"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,16]]},"references-count":74,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2019,11]]}},"alternative-id":["molecules24224159"],"URL":"https:\/\/doi.org\/10.3390\/molecules24224159","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,16]]}}}