Article
A Useful Classification of Organic Reactions Bases on the Flux of the Electron Density
Luis R. Domingo and Mar Ríos-Gutiérrez
Sci. Rad. 2023, 2, 1
A useful classification of polar organic reactions in Forward Electron
Density Flux (FEDF) and Reverse Electron Density Flux (REDF), based on the unambiguously
analysis of the direction of the flux of the global electron density transfer
(GEDT) at the transition state structures (TSs), has been recently proposed (RSC Adv. 2020, 10, 15394) within
the Molecular Electron Density Theory (MEDT). Further, non-polar reactions have been
classified as Null Electron Density Flux (NEDF) (Eur. J. Org. Chem. 2020, 5938). This classification allows
characterizing the nucleophilic/electrophilic species participating in polar
reactions. Analysis of the reactivity indices, i.e. the electronic chemical
potential m, and the electrophilicity w and nucleophilicity N indices
at the ground state of the reagents, permits to establish also this useful classification
of organic reaction.
This new classification updates the obsolete classifications of the organic reactions of Sustmann (Pure Appl.
Chem. 1974, 40, 569) and Houk (J. Am.
Chem.Soc. 1973, 95, 7287) based on the FMO analysis.
Changes in electron density along a polar reaction are not controlled by any molecular orbital interaction, but by the different electronic chemical potential, i.e. electronegativity, of the interacting molecules.
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Book Chapter
Application of Reactivity Indices in the Study of Polar Diels–Alder Reactions.
Conceptual Density Functional Theory: Towards a New Chemical Reactivity Theory,
Luis R. Domingo and Mar Ríos-Gutiérrez.
Ed. Shubin Liu. WILEY-VCH GmbH. 2022, Vol. 2, pp, 481-502.
Application of reactivity indices, including CDFT-based electrophilicity index w, the empirical nucleophilicity N index, and the Parr functions, in the study of polar organic Diels-Alder reactions are presented in this Chapter. To this end, their reactivity properties, e.g., regioselectivity and chemoselectivity, in experimental Diels-Alder reactions are thoroughly analyzed by using these reactivity indices.
Article
A Molecular Electron Density Theory Study of the Higher–Order Cycloaddition Reactions of Tropone with Electron-rich Ethylenes. The Role of the Lewis Acid Catalyst in the Mechanism and Pseudocyclic Selectivity
Luis R. Domingo and Patricia Pérez
New J.
Chem. 2021, 46, 294–308.
The higher–order cycloaddition reactions of
tropone with nucleophilic ethylenes, in the absence and presence of Lewis acid
(LA) catalysts, have been studied within Molecular Electron Density Theory
(MEDT) at the wB97X-D/6-311G(d,p) and B3LYP-D3BJ/6-311G(d,p) computational
levels. The strong electrophilic character of tropone, enhanced by the presence
of LAs, allows its participation in polar cycloaddition reactions of reverse
electron density flux (REDF) towards nucleophilic ethylenes. Analysis of the
Parr functions indicates that the C2 and the C4 position of tropone are the
most electrophilic centers. These polar higher–order cycloaddition reactions
take place via a non-concerted two-stage one-step or a two-step mechanism,
yielding only one cycloadduct via a total regio and pseudocyclic selectivity.
The present MEDT study allows establishing that these higher–order
cycloaddition reactions are kinetically controlled by
nucleophilic/electrophilic interactions taking place at the polar transition
state structures (TSs). LAs not only accelerate the reaction and make it
completely regioselective but also determine the pseudocyclic selectivity
yielding exclusively [4+2] or [8+2] cycloadducts, which depends on a series of
weak attractive/repulsive intramolecular electronic interactions present at the
corresponding diastereoisomeric TSs.
MEDT aims to
explain the chemical organic reactivity based on the changes in electron
density along an organic reaction. Outdated concepts such as ‘periselectivity’’
and the ‘‘secondary orbital interactions (SOI)”, based on molecular orbital
interactions, should be rejected today of any serious manuscript. Thus, the
recently proposed pseudocyclic selectivity concept (Molecules, 2018, 23, 1913)
to describe the formation of constitutional isomers should be used instead of
the “periselectivity” concept proposed by Houk since “pericyclic reactions” do
not exist.
Article
Unveiling the Intramolecular Ionic
Diels-Alder Reactions within the Molecular Electron Density Theory
Luis
R. Domingo, Mar Ríos-Gutiérrez, and María José Aurell
Chemistry 2021, 3, 834–853
Article
A comprehensive experimental and theoretical study on
the [{(η5-C5H5)2Zr[P(µ-PNEt2)2P(NEt2)2P]}2O
crystalline system
A.
Łapczuk-Krygier, K. Kazimierczuk, J. Pikies, M. Ríos-Gutiérrez
Molecules
2021, 26, 7282.
The structure of
tetraphosphetane zirconium complex C52H100N8OP10Zr2 1 was determined by single crystal X-Ray
diffraction analysis. The crystal belongs to the monoclinic system, space group
P21/c, with a=19.6452(14), b=17.8701(12), c=20.7963(14) Å, α=γ=90°,
β= 112.953(7)°, V= 6722.7(8) Å3, Z=4. The
electronic structure of the organometallic complex has been characterized
within the framework of Quantum Chemical Topology. The topology of the Electron
Localization Function (ELF) and the electron density according to the Quantum
Theory of Atoms in Molecules (QTAIM) show no covalent bonds involving the Zr
atom, but rather dative, coordinate interac-tions between the metal and the
ligands. This is the first reported case of a Zr complex stabilized by an oxide
anion, anionic cyclopentadienyl ligands and rare tetraphosphetane anions.
Article
The Participation of 3,3,3-Trichloro-1-nitroprop-1-ene
in 6 the [3 + 2] Cycloaddition Reaction with Selected Nitrile N-Oxides in the
Light of the Experimental and MEDT Quantum Chemical Study
K.
Zawadzinska, M. Ríos-Gutiérrez, K. Kula, P. Wolinski, B. Mirosław, T. Krawczyk,
R. Jasinski.
Molecules
2021, 26, 6774.
The regioselective
zw-type [3 + 2] cycloaddition (32CA) reactions of a series of arylsubstituted
nitrile N-oxides (NOs) with trichloronitropropene (TNP) have been both
experimentally and theoretically studied within the Molecular Electron Density
Theory (MEDT). Zwitterionic NOs behave as moderate nucleophiles while TNP acts
as a very strong electrophile in these polar 32CA reactions of forward electron
density flux, which present moderate activation Gibbs free energies of
22.8–25.6 kcal/mol and an exergonic character of 28.4 kcal/mol that makes them
irreversible and kinetically controlled. The most favorable reaction is that
involving the most nucleophilic MeO substituted NO. Despite Parr functions
correctly predicting the experimental regioselectivity with the most favorable
O-CCCl3 interaction, these reactions follow a two-stage one-step
mechanism in which formation of the O-C(CCl3) bond takes place once
the C-C(NO2) bond is already formed. The present MEDT concludes that
the reactivity differences in the series of NOs come from their different
nucleophilic activation and polar character of the reactions, rather than any
mechanistic feature.
Article
Unveiling the Regioselectivity in Electrophilic
Aromatic Substitution Reactions of Deactivated Benzenes through Molecular
Electron Density Theory
Luis R. Domingo, Mar Ríos-Gutiérrez, and María José Aurell
New J. Chem. 2021, 45, 13626–13638
The origin of the meta regioselectivity in electrophilic aromatic substitution (EAS) reactions of deactivated benzene derivatives is herein analysed through Molecular Electron Density Theory (MEDT). To this end, the EAS reaction of benzenesulfonic acid with nitronium NO2+ ion in H2SO4 solution has been studied at the wB97X-D/6-311G(d,p) level. This reaction takes place through a two-step polar mechanism involving the formation of an unstable cation intermediate. The activation Gibbs free energies associated with the three competitive regioisomeric reaction paths are found in the narrow range of 15.5 – 18.3 kcal·mol-1. By using the Eyring-Polanyi equation a relationship of 18.7 (ortho) : 81.0 (meta) : 0.3 (para) is obtained, in agreement with the experimental outcome. From this MEDT study it is possible to conclude that the presence of the SO3H group in benzenesulfonic acid only slightly polarises the aromatic electron density towards the substituted C1 position. However, while the -SO3H group markedly deaccelerated the EAS reaction with respect to that of benzene, it has a low incidence in the regioselectivity, which is the result of the slight polarization of the ring electron density towards the substituted C1 carbon and the weak repulsive steric interactions appearing along the ortho approach mode, but not of the stability of resonance structures as was proposed.
Regioselectivity results of a
slight polarization of the electron density and weak repulsive interactions
appearing along the ortho approach mode.
Understanding the Participation of
Fluorinated Azomethine Ylides in Carbenoid-type [3+2] Cycloaddition Reactions
with Alkynal Systems: A Molecular Electron Density Theory Study
Luis
R. Domingo, Karolina Kula, Mar Ríos-Gutiérrez and Radomir Jasiński
J. Org. Chem. 2021, 86, 12644-12653
The carbenoid-type
(cb-type) 32CA reaction of 1,1-difluoroated azomethyne ylide (DFAY) with
phenylpropynal has been studied within Molecular Electron Density Theory
(MEDT). Topological analysis of the Electron Localization Function (ELF)
permits to characterize this three-atom-component (TAC) as a carbenoid species
participating in cb-type 32CA reactions. The supernucleophilic character of
DFAY and the strong electrophilic character of the ynal cause this polar 32CA
reaction to have unappreciable activation energy, the reaction being totally
chemo- and regioselective. Formation of the corresponding oxazolidines is
strongly exothermic. ELF topological analysis of the bonding changes along this
32CA reaction establishes its non-concerted two-stage one-step mechanism, in
which the nucleophilic attack of the carbenoid carbon of DFAY on the
electrophilic carbonyl carbon of the ynal characterizes the cb-type reactivity
of this TAC. The presence of the two fluorines at one methylene of DFAY changes
its basic pseudodiradical electronic structure and reactivity to that of a
carbenoid TAC participating in cb-type 32CA reactions towards electrophilic species.
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Article
Unveiling
the Unexpected Reactivity of Electrophilic Diazoalkanes in [3+2] Cycloaddition
Reactions within Molecular Electron Density Theory
Chemistry
The [3+2] cycloaddition (32CA) reactions of strongly nucleophilic norbornadiene with simplest diazoalkane (DAA) and three DAAs of increased electrophilicity have been studied within the Molecular Electron Density Theory (MEDT). These pmr-type 32CA reactions follow an asynchronous one-step mechanism with activation enthalpies ranging from 17.7 to 27.9 kcal·mol-1 in acetonitrile. The presence of electron-withdrawing (EW) substituents in the DAA increases the activation enthalpies, in complete agreement with the experimental slowing-down of the reactions The present MEDT study allows establishing that the depopulation of the N-N-C core in this series of DAAs with the increase of the EW character of the substituents present at the carbon center is responsible for the experimentally found deceleration.
This MEDT study shows as sometimes the Conceptual DFT cannot predict chemical organic reactivity. Despite the nucleophilic and electrophilic character of the reagents, the global electron density transfer at the TSs indicates rather non-polar 32CA reactions.
Unexpected decrease of reaction rate with the substitution
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The Lithium Cation Catalyzed Benzene Diels-Alder reaction. Insights on the Molecular Mechanism within the Molecular Electron Density Theory
Luis R. Domingo and
Patricia Pérez
J. Org. Chem. 2020, 85, 13121−13132
The lithium
cation Li+ catalyzed Diels-Alder (DA) reactions of benzene towards a
series of acetylenes of improved nucleophilicity can be described within the context
of the Molecular Electron Density Theory (MEDT) at the wB97XD/6-311G(d,p) level. Conceptual DFT indices
characterize the crown ether solvated complex benzene-lithium Bz-Li-Cro as superelectrophile. Coordination
of lithium cation to benzene does not change substantially the ELF electronic
structure of benzene. The DA reaction of Bz-Li-Cro
with acetylene experiences a reduction of the energy of activation 6.9 kcal·mol-1,
which is not sufficient for the reaction takes place, thus demanding the
participation of strong nucleophilic acetylenes. DA reactions of complexes Bz-M-Cro (M = Li, Na, and K) are decelerated with the diminution of the ionization potential
of the alkali metal. The one-step mechanism of these lithium cation Li+
catalyzed DA reactions changes to a two-step one for the reaction with dimethyl
propynamine. The present MEDT study proves that the analysis of the
electrophilicity and nucleophilicity indices is a strong tool for experimental
organic chemists to understand, even to predict, the chemical organic
reactivity.
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Unveiling the High Reactivity of Benzyne in the Formal [3+2] Cycloaddition Reactions towards Thioamides through the Molecular Electron Density Theory
Lydia Rhyman, Mar Ríos-Gutiérrez, Luis R.
Domingo, Ponnadurai Ramasami
Tetrahedron 2020, 76, 131458
The domino reaction of benzyne with thioamide has been
studied within the Molecular Electron Density Theory (MEDT) at the MPWB1K/6-311G(d)
level. This domino reaction takes place through i) a formal [3+2] cycloaddition
(32CA) reaction affording an ammonium ylide, and ii) an extrusion of ethylene from this species yielding
a dihydrothyazole. Topological analysis
of the electron density of benzyne shows
its pseudodiradical structure, that
is, without any energy cost, changes to a carbenoid one, allowing its
participation as electrophile in polar reactions. As a consequence, the formal
32CA reaction does
not has activation enthalpy. Analysis
of the changes of electron density along the domino reaction indicates that while
the formal 32CA reaction takes place through a two-stage one-step mechanism, the
extrusion of ethylene takes place through an intramolecular E2
elimination mechanism. The present MEDT study reveals the chameleonic structure/reactivity
of benzyne, allowing its participation in both non-polar and polar reaction
with an unappreciable activation enthalpy.
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Unravelling the Strain-Promoted [3+2] Cycloaddition Reactions of Phenyl Azide with Cycloalkynes from the Molecular Electron Density Theory Perspective
Luis R Domingo, Nivedita
Acharjee
New J. Chem. 2020,
The strain-promoted [3+2] cycloaddition
(SP-32CA) reactions of phenyl azide with a series of five strained cycloalkynes
C5–C9 have been studied within molecular electron density theory
(MEDT) at the MPWB1K/6-311G(d,p) computational level. These zwitterionic type
SP-32CA reactions take place through a one-step
mechanism, with activation enthalpies in acetonitrile between 4.2 and 19.9 kcal·mol-1. An excellent linear
correlation between the decrease in activation enthalpies and the ring size of
this series of cycloalkynes can be established. The present study shows that
the highly strained cycloalkynes C5 and C6 experience a different
chemical reactivity than less strained cycloalkynes C7 – C9,
caused by the noticeable electrophilic character of the former ones. The
present MEDT study permits establishing that the loss of the cycloalkyne strain
along the reaction path together with easy depopulation of the CCºCC bonding region along these
SP-32CA reactions, and not “less
distortion of the 1,3-dipole in the transition state geometry“, as has been
suggested, is responsible for the kinetics and thermodynamics of these SP-32CA reactions.
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Unveiling the Lewis Acid Catalysed Diels–Alder
Reactions Through
the Molecular Electron Density Theory.
Luis R. Domingo, Mar Ríos-Gutiérrez, Patricia Pérez.
Molecules 2020, 25, 2535.
The
effects of metal-based Lewis acid (LA) catalysts on the reaction rate and
regioselectivity in polar Diels-Alder (P-DA) reactions has been analysed within
the molecular electron density theory (MEDT). A clear correlation between the
reduction of the activation energies and the increase of the polar character of
the reactions measured by analysis of the global electron density transfer at
the corresponding transition state structures (TS) is found, a behavior easily
predictable by analysis of the electrophilicity w and nucleophilicity N indices
of the reagents. The presence of a strong electron-releasing group in the diene
changes the mechanism of these P-DA reactions from a two-stage one-step to a
two-step one via formation of a zwitterionic intermediate. However, this change
in the reaction mechanism does not have any chemical relevance. This MEDT study
makes it possible to establish that the more favourable
nucleophilic/electrophilic interactions taking place at the TSs of LA catalysed
P-DA reactions are responsible for the high acceleration and complete
regioselectivity experimentally observed.
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A Molecular Electron Density Theory Study of the Reactivity of
Tetrazines in Aza-Diels-Alder Reactions.
Luis R. Domingo, Mar Ríos-Gutiérrez, Patricia Pérez.
RSC Adv. 2020, 10, 15394–15405.
The reactions of eight tetrazines of increased electrophilic
character with nucleophilic tetramethyl ethylene (TME) and with electrophilic
tetracyanoethylene (TCE) have been studied within the Molecular Electron
Density Theory. These reactions are domino processes comprising an aza-Diels-Alder
(ADA) reaction followed by an extrusion of molecular nitrogen, yielding a dihydropyridazine.
Analysis of the conceptual DFT (CDFT) indices showed the increase of the
electrophilicity and the decrease of the nucleophilicity of tetrazines with the
increase of the electron-withdrawing character of the substituent. A very good
correlation between the global electron density transfer at the transition
structures and the activation enthalpies for the ADA reactions involving TME was
found. However, tetrazines have no tendency to react with electrophilic
ethylenes such as TCE. Bonding Evolution Theory (BET) analysis of the ADA reaction
of dinitro tetrazine with TME showed that the activation energy is mainly
associated to the continuous depopulation of the C-C and C-N double bonds.
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Unveiling the Different Chemical Reactivity of Diphenyl Nitrilimine
and Phenyl Nitrile Oxide in [3+2] Cycloaddition Reactions with
(R)-Carvone through the Molecular Electron Density Theory.
M. Ríos-Gutierrez, L. R. Domingo, M. Esseffar, A. Oubella,
M. Y. Ait Itto
Molecules 2020, 25, 1085
The [3+2] cycloaddition (32CA) reactions of diphenyl
nitrilimine and phenyl nitrile oxide with (R)-carvone have been studied within
the Molecular Electron Density Theory (MEDT). Electron localisation function (ELF)
analysis of these three-atom-components (TACs) permits its characterisation as
carbenoid and zwitterionic TACs, thus having different reactivity. Analysis of
the conceptual DFT indices accounts for the very low polar character of these
32CA reactions, while analysis of the DFT energies accounts for the opposite chemoselectivity
experimentally observed. Topological analysis of the ELF along the single bond
formation makes it possible to characterise the mechanisms of these 32CA
reactions as cb- and zw-type. The present MEDT study supports the proposed
classification of 32CA reactions into pdr-, pmr-, cb- and zw-type, thus asserting
the MEDT as the theory able to explain chemical reactivity in Organic Chemistry.
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A Molecular Electron Density Theory Study of the Enhanced Reactivity of
Aza
Aromatic Compounds Participating in Diels-Alder Reactions.
Luis R. Domingo, Mar Ríos-Gutiérrez, Patricia Pérez
Org. Biomol. Chem. 2020,18, 292 –304
The enhanced reactivity of a series of four aza
aromatic compounds (AACs) participating in the Diels-Alder (DA) reactions with
ethylene has been studied within the Molecular Electron Density Theory (MEDT). The
analysis of the electronic structure of these AACs allows establishing that the
substitution of the CH unity by the isoelectronic N: unity linearly decreases
the ring electron density (RED) of these compounds and concomitantly decreases
their aromatic character and increases their electrophilic character. These
behaviours do not only decrease drastically the activation energies of these DA
reactions, but also increase the reaction energies when they are compared with
the very unfavourable DA reaction between benzene and ethylene. Very good
correlations between the NICS(0) values and the electrophilicity indices of
these AACs with the RED values are found. The present MEDT study makes it
possible to establish two empirical electron density unity (EDU) indices accounting
for the contribution of the ñC and
the ñN unities,
2.77 and 2.19 e, respectively, for the RED, which is mainly responsible for the
reactivity of these AACs. Comprehensive chemical concepts such as electron
density, aromaticity and electrophilicity make it possible to explain the
chemical reactivity of these AACs participating in DA reactions towards
ethylene.
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Are One-Step Aromatic Nucleophilic Substitutions of Non-Activated
Benzenes
Concerted Processes?.
Luis R. Domingo, Mar Ríos-Gutiérrez, Eduardo Chamorro and
Patricia Pérez.
Org. Biomol. Chem. 2019, 17, 8185 – 8193
The aromatic nucleophilic substitution (SNAr)
reactions of non-electrophilically activated benzenes have been studied within
the Molecular Electron Density Theory (MEDT) at the B3LYP/6-311+G(d)
computational level. These reactions, taking place through a one-step
mechanism, present a high activation Gibbs free energy, DG≠
= 31.0 kcal·mol-1, which decreases to 22.1 kcal·mol-1 in the intramolecular
process. A topological analysis of the electron localisation function along the
reaction paths permits establishing the non-concerted nature of these SNAr
reactions. A series of unstable structures, with similar electronic structures than
those of Meisenheimer intermediates, are characterised. The present MEDT study
makes it possible to establish that even these one-step SNAr reactions
involving only two single bonds are non-concerted processes.
On the Nature of Organic Electron Density Transfer Complexes
within the Molecular
Electron Density Theory
L. R. Domingo; M. Ríos-Gutiérrez
Org. Biomol. Chem. 2019, 17, 6478–6488
The structural features of a series of organic
molecular complexes formed between the strong electrophilic tetracyanoethylene
and twelve benzene derivatives of increased nucleophilic character, herein
named Electron Density Transfer Complexes (EDTCs), have been studied within the
Molecular Electron Density Theory. The favourable nucleophilic/electrophilic
interactions, which favour the global electron density transfer (GEDT) towards
the electrophile, are responsible for the formation of these species. Molecular
complexes presenting a GEDT above 0.05 e are classified as EDTCs. Analysis of
the Parr functions at the separated reagents as well as the topological
analysis of the electron density at the EDTCs allow understanding the subtle
changes in the electronic structure of this significant class of molecular
complexes, and consequently, their physical properties.
An MEDT Study of the Mechanism and Selectivities of the [3+2]
Cycloaddition Reaction of Tomentosin with Benzonitrile Oxide.
Abdellah Zeroual, Mar Ríos-Gutiérrez, Mohammed El Idrissi,
Habib El Alaoui El Abdallaoui, Luis R. Domingo
Int. J. Quantum Chem. 2019, e25980
The
[3+2] cycloaddition (32CA) reaction of tomentosin with benzonitrile oxide
yielding a spiro-isoxazoline has been studied within the Molecular Electron
Density Theory at the B3LYP/6-31(d,p) computational level. Given the
multifunctionality of tomentosin, this 32CA reaction can take place along
sixteen competitive reaction paths. The chemo-, regio- and stereoisomeric
reaction paths involving the two C-C double bonds of tomentosin have been studied.
DFT calculations account for the total chemo- and regioselectivity, in complete
agreement with the experimental outcomes, being suggestive of low diastereofacial
selectivity. Analysis of the Conceptual DFT indices accounts for the non-polar
character of this 32CA reaction. On the other hand, the topological analysis of
the ELF of the selected points of the IRC associated with the formation of the
C-C and C-O single bonds emphasizes the zw-type reactivity of the phenyl
nitrile oxide; the reaction taking place through a non-concerted two-stage one-step
mechanism initialized with the formation of the C-C single bond involving the -conjugated
carbon of tomentosin.
A Molecular Electron Density Theory Study of the Chemoselectivity,
Regioselectivity and Diastereofacial Selectivity in the Synthesis of
an Anti-Cancer Spiro-Isoxazoline
derived from α-Santonin.
L. R. Domingo, M. Ríos-Gutiérrez and N. Acharje
Molecules 2019, 24, 832
The
[3+2] cycloaddition (32CA) reaction of an α-santonin derivative having an
exocyclic C-C double bond with p-bromophenyl nitrile oxide yielding only one
spiro-isoxazoline has been studied within the Molecular Electron Density Theory
(MEDT) at the MPWB1K/6-311G(d,p) computational level. Analysis of the
conceptual DFT reactivity indices and the global electron density transfer
account for the non-polar character of this zwitterionic-type 32CA reaction,
which presents an activation enthalpy of 13.3 kcal·mol−1. This 32CA
reaction takes place with total ortho regio- and syn diastereofacial
selectivity involving the exocyclic C-C double bond, in complete agreement with
the experimental outcomes. While both, the more favourable C-C bond formation
involving the -conjugated carbon of α-santonin derivative than the C-O one is
responsible for the ortho regioselectivity, the favourable electronic
interactions taking place between the oxygen of the nitrile oxide and two axial
hydrogen atoms of the α-santonin derivative are responsible for the syn
diastereofacial selectivity.
The Carbenoid-Type Reactivity of Simplest Nitrile Imine from
a Molecular Electron Density Theory perspective.
M. Ríos-Gutiérrez and L. R. Domingo
Tetrahedron 2019, 75, 1961-1967
The [3+2] cycloaddition (32CA) reactions of the
simplest nitrile imine (NI) with ethylene and electrophilic dicyanoethylene (DCE)
have been studied within the Molecular Electron Density Theory (MEDT) with the
aim of characterising its reactivity. Topological analysis of the electron
localisation function (ELF) of NI shows that it has a carbenoid structure. The activation
energy of the 32CA reaction of the simplest nitrile imine with dicyanoethylene is
5.6 kcal·mol-1 lower than that involving ethylene, in agreement with the high
polar character of the former reaction. Bonding Evolution Theory accounts for
the cb-type reactivity of nitrile imine. Along the more favourable ortho
regioisomeric path associated with the 32CA reaction involving dicyanoethylene,
which takes place through a non-concerted two-stage one-step mechanism,
formation of the first C3-C4 single bond takes place at a C-C distance of 2.02 Å,
by donating the non-bonding electron density of the carbenoid center of nitrile
imine to the -conjugated C4 carbon of dicyanoethylene.
Unveiling the high reactivity of cyclohexynes in [3 + 2] cycloaddition
reactions through the molecular electron density theory.
L. R. Domingo, Mar Ríos-Gutiérrez and Patricia Pérez
Org. Biomol. Chem. 2019, 17, 498–508
The [3+2] cycloaddition (32CA) reactions of
cyclohexyne, a cyclic strained acetylene, with methyl azide and methoxycarbonyl
diazomethane have been studied within the Molecular Electron Density Theory
(MEDT) at the MPWB1K/6-311G(d) computational level. These 32CA reactions, which
take place through a one-step mechanism involving highly asynchronous
transition state structures, proceed with relatively low activation enthalpies
of 6.0 and 4.3 kcal·mol-1, respectively, both reactions being
strongly exothermic. The reactions are initiated by the creation of a pseudoradical
center at one of the two acetylenic carbons of cyclohexyne with a very low energy
cost, 1.0 kcal·mol-1,
which promotes the easy formation of the first C-N(C) single bond in the
adjacent acetylenic carbon. This scenario is completely different from that of
the 32CA reaction involving non-strained but-2-yne; thus, strain in cyclohexyne
triggers a high reactivity as a consequence of its unusual electronic structure
at the ground state. Finally, the experimental regioselectivity of the 32CA
reactions involving 3-alkoxy-cyclohexyne derivatives is correctly explained within
MEDT.
High reactivity of cyclohexyne
Unveiling the High
Reactivity of Cyclohexynes in [3+2] Cycloaddition Reactions through the
Molecular Electron Density Theory
Minireview
Coordination of BF3 LA to the oxygen of formaldehyde drastically accelerates both reactions given the high electrophilic character of the BF3:formaldehyde complex. As a consequence, these reactions present a very low activation enthalpy, less than 2.2 kcal·mol-1, thus becoming competitive. In dioxane, the P-AE reaction is slightly favoured because of the larger polar character of the corresponding transition state (TS) structure.
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Understanding the domino reactions between 1-diazopropan-2-one and 1,1-dinitroethylene. A molecular electron density theory study of the [3+2] cycloaddition reactions of diazoalkanes with electron-deficient ethylenes
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How does the Global Electron Density Transfer Diminish Activation Energies in Polar Cycloaddition Reactions? A Molecular Electron Density Theory Study
Article
ChemistrySelect 2016, 1, 6026 - 6039.
Electrophilic activation of CO2 in cycloaddition reactions towards a nucleophilic carbenoid intermediate: new defying insights from the Molecular Electron Density Theory.
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