Accessing the Cloke-Wilson Rearrangement via Conjugate Addition of Phosphoranes to Michael Acceptors: A Route to Cyclopropanes and 5-Membered Ring Heterocycles Investigated by Density Functional and Ab Initio Theory

Conjugate addition of unstabilized Wittig-type phosphonium ylides to 1,1-diacceptor- and 1-acceptor-substituted alkenes is investigated by density functional theory and high-level ab initio (DLPNO–CCSD(T)) calculations. The results indicate that the initial conjugate addition step should be facile with barriers predicted to be between 0 and 21 kcal mol–1. Potential intramolecular follow-up reactions include the formation of acceptor-substituted cyclopropanes as well as the formation of dihydrofuran derivatives via intramolecular SN2-type transition state structures. The barriers calculated for these potentially valuable cyclization reactions are substantial with Gibbs free energies of activation between 19 and 40 kcal mol–1. Competing reaction channels include Wittig olefination (for ketones and aldehydes), as well as Claisen condensation reactions. The reaction offers an alternative entry point to the nucleophile-catalyzed Cloke-Wilson rearrangement.


■ INTRODUCTION
Schollkopf and Wittig's discovery of the olefination of ketones via reaction with triphenylphosphonium ylides 1,2 opened the path to the discovery of an array of related reactions, involving organophosphorus 3,4 as well as organotitanium compounds. 5,6he parent Wittig reaction involves concerted (yet asynchronous) 7 formation of an oxaphosphetane ring, followed by cycloreversion to yield triphenylphosphine oxide and an alkene.Betaines are unlikely to be involved under normal reaction conditions. 8However, computational work suggests that in very polar solvents, betaines can be formed as well, and that entropy plays an important role in the reaction outcome. 9It works well for ketones and aldehydes but not for esters, lactones, amides, and lactams.The Wittig reaction has been investigated in a number of computational studies, 9−13 and its stereochemical outcome (E-vs Z-olefin formation) is now well understood.Depending on the nature of the ylide involved (stabilized or nonstabilized), formation of the oxaphosphetane intermediate either goes through a very early puckered transition state structure leading to the Z-alkene (unstabilized ylides), 8,11,14,15 or through a tighter transition state governed by dipolar interactions, resulting in E-alkenes (stabilized ylides).There appears to be a correlation between the degree of bond formation in the transition state structure and the stereochemical outcome. 16 the case of α,β-unsaturated carbonyl compounds, in addition to the typical Wittig reaction, a conjugate addition can take place, which results in the formation of zwitterions. 17These zwitterions can undergo synthetically useful follow-up reactions.−21 It is noted, however, that this reaction has been neglected for a long time now and that there are only very few reports of its use in the literature and, so far, no computational study of it.
Upon heating, vinylcyclopropane rearranges into cyclopentene in a process that, depending on the substitution, can either be described as a concerted 1,3-sigmatropic carbon shift, or as occurring via biradical intermediates. 20Similarly, acyl cyclopropanes or imines derived thereof can be rearranged into dihydrofurans or dihydropyrroles in a process that is now known The Journal of Organic Chemistry as the Cloke-Wilson rearrangement, after the researchers who first described it 23,24 (Scheme 1).
While the uncatalyzed Cloke-Wilson rearrangement suffers from rather harsh reaction conditions required (180 °C for Cloke's synthesis of dihydropyrroles and about 400 °C for Wilson's rearrangement of cyclopropanecarbaldehyde), it can be catalyzed by transition metal complexes such as Ni(COD) 2 , 25 photoredox catalysis, 26 organocatalysis, 27 electrophiles, 28 acids, 29 and nucleophiles. 30−33 The reaction mechanism involves formation of zwitterionic species, as shown in Scheme 2.
This contribution looks at conjugate addition to the βposition of Michael acceptors (1), employing density functional theory as well as ab initio theory.Acceptor substituents investigated are ketone, nitrile, ester, amide, thioester, phosphonate ester, and nitro functionalities.The primarily formed products could be zwitterions (3) (formed via conjugate addition) or oxaphosphinines (3′) (formed via a formal 4π + 2π cycloaddition), which could be followed up by cyclopropane (4) or dihydrofuran (5) formation via intramolecular S N 2 (or S N i) reactions.Schemes 3 and 4 illustrate the structures involved.
It is noted that the structures of all stationary points calculated, if not already shown in a figure in this article, are found in the Supporting Information (Figures S1−S17).

■ RESULTS AND DISCUSSION
Due to the size of the molecules investigated, geometry optimizations and frequency calculations (which would be required for calculation of enthalpies, entropies, and Gibbs free energies) at the DLPNO−CCSD(T) level of theory would not have been feasible.To calculate Gibbs free energies based on the results of the coupled cluster single point energy calculations, a hybrid approach was used.The Gibbs free energies listed were calculated by adding the "Thermal correction to Gibbs free energy", as obtained in the DFT frequency calculations performed using Gaussian, to the DLPNO−CCSD(T) electronic energies of the stationary points optimized.The values refer to standard conditions (T = 298 K).The reference points of the calculations are the sums of the electronic energies of carbonyl compounds 1 and phosphoranes 2. In one case, the reaction of the extremely electrophilic 1,1-dinitroethene (system q), a transition state structure could not be localized using DFT, and the reaction presumably proceeds barrierless.The results of the calculations are shown in Table 1 (Gibbs free energies), Table S1 (see the Supporting Information, selected calculated geometric parameters), and Table S2 (see the Supporting Information, DLPNO−CCSD(T) electronic energies and Gibbs free energies calculated purely by DFT).
The initial step, addition of the phosphoranes to the Michael acceptors, reduces the number of translational degrees of freedom available to the system and is, therefore, entropically unfavorable.This is reflected in the fact that both the Gibbs free energies of activation for addition of the phosphoranes to the Michael acceptors and the Gibbs free energies of formation of the zwitterions 3 are consistently less favorable by ca.10−15 kcal The Journal of Organic Chemistry mol −1 than the corresponding electronic energies of activation and reaction.In this work, the focus is on the conjugate addition of the phosphorane.Conventional Wittig olefination, however, still needs to be considered, particularly for the ketones studied (systems a and b).
Ketones.For methylene acetylacetone (a), the Gibbs free energy of activation for oxaphosphetane (10a) formation is calculated (DLPNO−CCSD(T)/def2-TZVP(CPCM-(C),THF)//M06-2X/cc-pVDZ(THF)) as ΔG ⧧ = 21.5 kcal mol −1 .Formation of 10a is calculated to be exergonic by ΔG = −3.3kcal mol −1 .The final cycloreversion step, with the formation of dienone 11a and triphenylphosphine oxide, is calculated to be exergonic (relative to the starting materials 1a and 2) by ΔG = −44.7 kcal mol −1 , and it is impeded by a Gibbs free energy of activation of ΔG ⧧ = 23.0 kcal mol −1 (relative to 10a).The barrier for the formation of zwitterion 3a is calculated to be smaller than the barrier for Wittig olefination (ΔG ⧧ = 16.1 kcal mol −1 ).While zwitterion 3a is calculated to be significantly lower in energy than oxaphosphetane 10a, the products of the Wittig reaction, diene 11a and triphenylphosphine oxide, are the global minimum on the potential energy hypersurface (PES).Hence, under thermodynamic reaction control, the reaction of 1a with the parent triphenylphosphonium methylide should preferentially yield the Wittig-type product 11a, but the kinetic preference is for the reaction channel leading to zwitterion 3a and further to cyclopropane 4a.On the conjugate addition side of the PES, dihydrofuran 5a is calculated to be lower in energy than cyclopropane 4a, in agreement with experimental results that demonstrate the feasibility of the Cloke-Wilson rearrangement of diacyl cyclopropanes.The results of the reactions of 1a are shown in Figure 1.
In the case of methylvinylketone as electrophile (system b), the findings differ from system a in that both the thermodynamic and kinetic preferences are for Wittig olefination, see Figure S1 (Supporting Information).On the conjugate addition side, the cyclopropane is now more favored, both thermodynamically and kinetically.
Esters.If the ketone moieties are replaced by ester groups, as in dimethylmethylenemalonate 1c, then the selectivity of the The Journal of Organic Chemistry reaction is changed, now preferentially yielding the cyclopropane product 4c, both kinetically and thermodynamically.Figure 2 shows the results.
Figure 2 shows that the formation of zwitterion 3c should be a fast process for 1c.However, the follow-up cyclization of 3c to cyclopropane 4c, while thermodynamically favorable, is predicted to be impeded by a significant barrier of ΔG ⧧ = 27.8 kcal mol −1 .This places the reaction lifetime for the formation of 4c in the range of ca. 3 h, even at elevated temperatures (T = 400 K). 34Under these circumstances, side reactions such as the Claisen condensation might become competitive.If the ethylidene phosphorane 2B or the isopropylidene phosphorane 2C is reacted with 1c, the barriers of both the conjugate addition and the Wittig reaction go down with increasing degree of alkylation of the phosphorane, but the conjugate addition should still be the favored reaction pathway (Figures S2 and S3, see Supporting Information).Remarkably, the barriers for formation of both cyclopropane 4e and dihydrofuran 5e from zwitterion 3e (see Figure S3, Supporting Information) are calculated to be somewhat smaller than the corresponding barriers in system 3c, which lacks the methyl groups.Cyclopropane 4c is calculated to be lower in energy than dihydrofuran 5c, and likewise, 4d and 4e are lower in energy than 5d and 5e, respectively, indicating that for the esters, the equilibrium of Cloke-Wilson rearrangement should lie on the side of the cyclopropanes.
Figure 3 shows the optimized structures on the hypersurface of the reaction of dimethylmethylenemalonate 1c and the parent Wittig ylide 2A (system c), and Figure 4 shows the corresponding stationary points in the reaction of 1c and isopropylidene phosphorane 2C (system e).The transition state geometries for the initial conjugate addition step feature a long C−C distance of R C−C = 2.58 Å (system c) or even 3.12 Å (system e).Hence, while the steric effect of the additional methyl groups does come into play at the TS geometry, it is a very early transition state structure anyway, and the increased nucleophilicity of the ethylidene or isopropylidene phosphorane is important.The follow-up reactions involved in the decay of the zwitterions 3 are intramolecular S N 2 (i.e., S N i) reactions, as is clearly seen from the transition state structures, see Figures 1  and 2, bottom.
Going to the sterically more demanding isopropylidene phosphorane, the C−C and C−P distances in the reaction coordinates of all three transition state structures investigated The Journal of Organic Chemistry become significantly longer, see Figure 4.The barriers, however, are not increased, but�surprisingly�are lower (ΔG ⧧ for formation of 4c: 27.8 kcal mol −1 , ΔG ⧧ for formation of 5c: 36.9 kcal mol −1 ; ΔG ⧧ for formation of 4e: 23.3 kcal mol −1 , ΔG ⧧ for formation of 5e: 31.3 kcal mol −1 ), see also Figure S3.
The reactivity predicted for methyl acrylate 1f parallels the reactivity calculated for 1c, in that the barriers in the conjugate addition pathway are smaller than the barriers for Wittig olefination.Overall, the conjugate addition pathway is less exergonic here than that for 1c and has a higher barrier.This resembles the situation found for 1a vs 1b.Introducing a cyano group as second activating substituent, as in 1n, has the effect of reducing the barrier for conjugate addition again, see Figure S12.System f was the only system for which an oxaphospholene isomer (3f') to a zwitterion (3f) could be localized by DFT, see Figure S4, SI.Cyclic structure 3f' is calculated to be slightly higher in free energy than 3f, while being slightly more favorable in electronic energy.This finding makes sense in that among the carbonyl-based zwitterions 3, 3f is the one in which the negative charge is least stabilized and the cyclic structure offering less rotational degrees of freedom is entropically disfavored.
The presence of an additional benzene ring, as in systems g-l, slightly increases the free energy of activation for initial zwitterion formation and makes the reaction less exergonic.Again, the isopropylidene phosphoranes (systems h, j, and l) are predicted to react faster than the methylidene phosphoranes (systems g, i, and k).Among the three aromatic Michael acceptors studied, the p-nitro-substituted system k,l is predicted to be the most reactive, in agreement with the expectation that the position α to the benzene ring should be more electrophilic if a p-nitro functionality is present (see Figures S5−S10).Again, barriers for the conjugate addition reactions are predicted to be smaller for the sterically more demanding isopropylidene phosphorane 2C.
Other Functionalities: Amide, Cyano, Nitro, Imine, Thioester.Amides.The methylenemalonic diamide (system m) is predicted to be rather unreactive (see Figure S11), in agreement with the fact that amide groups are less electronwithdrawing than ester, nitrile, or nitro functionalities.Conjugate addition should preferentially yield cyclopropane 4m.
Phosphonates.The mixed ester/phosphonate ester system s (see Figure S17) is predicted to preferentially result in cyclopropanation, as both the formation of the dihydrofuran 5s and formation of the cyclic phosphorane 7s are calculated to be less favorable.
Nitriles.In the case of the nitriles 1o and 1p, it is again the doubly activated methylenemalodinitrile 1o that should show a far larger reactivity compared to acrylonitrile 1p.In the former, formation of cyclopropane 4o and triphenylphosphine is calculated to be significantly endothermic (yet exergonic, due to the entropically favorable release of triphenylphosphine) relative to zwitterion 3o, whereas the situation is different for zwitterion 3p, where formation of cyanocyclopropane 4p is calculated to be both exothermic and exergonic, see Figures S13  and S14 and Tables S1 and S2.
Nitroalkenes.1,1-Dinitroethylene 1q is an extremely electrophilic Michael acceptor that is predicted to react with parent The Journal of Organic Chemistry phosphorane 2A in a barrierless and strongly exergonic (ΔG = −34.1 kcal mol −1 ) reaction.Follow-up reactions, to either 1,1dinitrocyclopropane 4q or the cyclic nitrone 6q, are significantly endergonic from 4q and unlikely to be practicable, see Figure S15.The situation is different for nitroethene 1r, where the formation of nitrocyclopropane 4r should be the kinetic reaction outcome, whereas the cyclic nitrone 6r should be the product under thermodynamic reaction control, see Figure S16.It is noted, though, that the differences between the two reaction channels in terms of both free energies of activation and free energies are very small for system r.
Imines.Of interest is the cyano-substituted N-phenylimine (system t), where the formation of a dihydropyrrole (5t) is calculated to be the thermodynamically most favorable reaction outcome (Figure 5), while both an alternative aza-Wittig reaction and formation of cyclopropane 4t are predicted to be less exergonic.Hence, this system holds promise as a potential access to dihydropyrrole derivatives, akin to Cloke's original imine rearrangement. 21,22hioesters.In the case of the thioester system u, the higher reactivity of the C�S bond compared to a C�O bond results in the thia-Wittig reaction being predicted to have a fairly small barrier.The TS for the concerted 2 + 2 cycloaddition− cycloreversion sequence (the thiaphosphetane 10u is not predicted to be a minimum structure) is predicted to be higher in Gibbs free energy by 15.8 kcal mol −1 .A betaine structure 10u' is identified as a stationary point in at least one rotameric form but likely does not play a role in the chemistry, as its formation from the precursors is predicted to be slower than the concerted cycloaddition-cycloreversion reaction.Formation of zwitterion 3u is predicted to be facile and exergonic but slower than the thia-Wittig reaction.Among the two follow-up cyclization reactions, the formation of dihydrothiophene 5u is predicted to be favored, both thermodynamically and kinetically.This is likely due to the increased nucleophilicity of the thiocarbonyl sulfur atom, as compared to a carbonyl oxygen in other systems.Figure 6 shows the electronic energies of a range of calculated stationary points.
The results presented so far indicate that conjugate addition of (unstabilized) phosphoranes to acceptor-substituted alkenes in most cases will be a facile process, yielding zwitterionic species 3 in reactions that in most cases are significantly exergonic.Exceptions are alkenes activated by only one electron-withdrawing group such as acrylonitrile 1p.Follow-up reactions involve ring closure to cyclopropanes and to 5-ring heterocycles such as dihydrofurans or dihydropyrroles.The barriers calculated for the follow-up reactions, however, in most cases are significant, and the reactions will be slow.This implies that intermolecular reactions, which were not investigated here, might become competitive.In addition, at least for unsaturated ketones, and certainly also aldehydes, conventional Wittig olefination is predicted to compete efficiently with the conjugate addition.Does this imply that the reaction is confined to remain a laboratory curiosity?This does not necessarily have to be the case.It is important to realize that a barrier of 30 kcal mol −1 for the formation of a secondary product from a zwitterion 3 at a temperature T = 125 °C translates into a reaction duration of slightly more than an hour. 34It is also noted that the reaction provides an additional entry point to the nucleophile-catalyzed Cloke-Wilson rearrangement of cyclopropyl ketones to dihydrofurans. 32The latter is important if the cyclopropane precursor required for this reaction is not easily accessible.Using the phosphorane to access the zwitterion, it should also in principle be possible to access a different regioisomer of the The Journal of Organic Chemistry dihydrofuran product, as shown exemplarily in Scheme 6. Starting from the cyclopropane, the nucleophile will invariably attack the sterically less encumbered carbon atom of the cyclopropane moiety, whereas the other regioisomer of the zwitterion necessarily is formed by conjugate addition of the phosphorane.Very likely, however, this approach at regiocontrol should fail for systems in which the cyclopropane is the product formed under kinetic reaction control (i.e., most of the systems studied here except for the thiocarbonyl system u).
One result from this work requires commenting on.Comparing the reaction of dimethylmethylenemalonate 1c with the parent phosphorane 2A and the isopropylidene phosphorane 2C, we find that the barrier for formation of zwitterion 3c (from 1c and 2A, ΔG ⧧ = 14.4 kcal mol −1 relative to the free reactants) is larger than the barrier of formation of zwitterion 3e (from 1c and 2C, ΔG ⧧ = 9.9 kcal mol −1 relative to the free reactants).While this is likely due to a very early transition state structure in which steric effects do not strongly come into play, the prediction that the barrier for both the S N i reactions yielding the cyclopropane 4 and the dihydrofuran 5 is smaller for system e (ΔG ⧧ for the formation of 4e: 23.3 kcal mol −1 , ΔG ⧧ for the formation of 5e: 31.3 kcal mol −1 ) than for the less sterically demanding system c (ΔG ⧧ for the formation of 4c: 27.8 kcal mol −1 , ΔG ⧧ for the formation of 5c: 36.9 kcal mol −1 ) is remarkable.After all, it is generally thought (and taught) that S N 2 and S N i reactions work best for reactions on primary substrates (here: a primary phosphonium cation as in 3c), worse for secondary substrates (as in 3d), and not at all on tertiary substrates, as in 3e.The fact that the formation of 4e or 5e are sterically highly demanding reactions is revealed by the significantly increased interatomic distances along the reaction coordinate in the TS, see Table S1 and Figures 3 and 4. In the TS leading to the formation of 5e in particular, the C−P bond is stretched considerably, indicating that this intramolecular S N 2type reaction, while concerted, is not synchronous, with a carbocation-like geometry first being created on the reacting tertiary center, followed by bond formation with the incoming carbonyl oxygen atom.In the literature, precedent exists in the intramolecular reductive ring opening reaction of epoxide alcohols employing PhSiH 3 as reductant, where an intramolecular S N 2 reaction was also reported to occur preferentially on a tertiary carbon center rather than a secondary carbon center. 35he Gibbs free energy of activation for the initial conjugate addition step is a function of the electrophilicity of the acceptorsubstituted alkene.Based on the M06-2X/cc-pVDZ optimized geometries of the starting materials alkenes 1, the energies of the HOMO and LUMO were evaluated for each.The framework of conceptual density functional theory (CDFT) defines a number of parameters (electronic chemical potential μ, hardness η,  The Journal of Organic Chemistry electrophilicity index ω, 36−38 nucleophilicity index N 7,39 ).The values calculated (see Table S3) confirm that the alkenes do indeed react as electrophiles, whereas the phosphoranes function as nucleophiles.1,1-Dinitroethene 1q in fact is calculated to be a weaker nucleophile (negative N) than tetracyanoethene used as reference molecule in the definition of N. 39 Plotting the calculated Gibbs free energy of activation for the conjugate addition steps (reaction with ylide 2A) versus the electrophilicity index ω (in eV) of the alkene (see Table S3), obtained from the highest occupied molecular orbital (HOMO) and least unoccupied molecular orbital (LUMO) energies, a somewhat noisy linear plot is obtained,  7 does not come as a surprise for several reasons.First, the electrophilicity parameter ω is a global parameter (derived from HOMO and LUMO energies) and therefore does not reflect the fact that attack of the phosphorane occurs locally at the β-carbon.Second, the effects of steric destabilization and stabilization via π-complex formation are ignored.Third, the Gibbs free energies of activation contain the entropy term, which does not contribute to ω at all.

■ CONCLUSIONS
Reaction of unstabilized Wittig ylides with α,β-unsaturated carbonyl compounds and other acceptor-substituted alkenes is predicted to result in the formation of zwitterions by conjugate addition to the β-carbon atom of the alkene.The exceptions to this rule α,β-unsubstituted ketones (and presumably also α,β-unsubstituted aldehydes, which were not investigated here), which preferentially react via conventional Wittig olefination, and thioester derivatives, where a thia-Wittig reaction is predicted to be prevalent.In the case of the most electrondeficient alkenes, the zwitterions formed are the lowest energy points along the reaction coordinate.In most other systems, the formation of cyclopropanes is predicted to be the most favorable reaction and also the kinetically most preferred outcome.Synthetically interesting other products, such as dihydrofurans or dihydrothiophenes, in most cases, are calculated to be disfavored, both kinetically and thermodynamically.A potential exception to this rule are α,β-unsaturated Schiff bases, where the formation of dihydropyrroles was calculated to be the thermodynamically most favorable outcome, in system t.The reaction may offer an alternative entry point to the nucleophilecatalyzed Cloke-Wilson rearrangement that could result in a different regiochemical outcome compared to the conventional reactions starting from a cyclopropane.
■ EXPERIMENTAL SECTION AND COMPUTATIONAL METHODS All geometry optimizations and frequency calculations were performed employing the Gaussian09 suite of programmes. 40−44 For all transition state structures along the reaction coordinates, for at least one system, an IRC calculation was performed to verify the nature of the reaction end points.The influence of solvation by THF was accounted for by using a polarizable continuum model (scrf = pcm,solvent = tetrahydrofuran). 45,46Single point energy calculations were performed at the DLPNO−CCSD(T)/def2-TZVP(CPCM(C),THF)//M06-2X/cc-pVDZ(THF) level of theory, employing the Domain Based Local Pair Natural Orbital method 47−49 in combination with the CPCM (continuum solvation model with the conductor-like polarizable continuum model) method for approximation of the influence of solvation 50 and Ahlrich's def2-TZVP basis set. 51,52The older (T) rather than the more recent (T1) triple version was employed.These single point energy calculations were performed employing ORCA version 4.2.1. 53,54The CPCM model was used in combination with the COSMO epsilon function. 55

■ ASSOCIATED CONTENT Data Availability Statement
The data underlying this study are available in the published article and its Supporting Information.

* sı Supporting Information
The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.joc.4c00757.Calculated energies of stationary points optimized (Tables S1−S3  The Journal of Organic Chemistry

Scheme 3 .
Scheme 3. General Reaction Scheme for the Addition of Phosphoranes to Acceptor-Substituted Alkenes

Figure 3 .
Figure 3. Stationary points in system c, as optimized at the M06-2X/cc-pVDZ(THF) level of theory.Top left: transition state structure for the formation of 3c.Top right: zwitterion 3c.Bottom left: transition state structure for the formation of cyclopropane 4c + PPh 3 .Bottom right: transition state structure for the formation of dihydrofuran 5c + PPh 3 .Selected bond atomic distances in Å, angles in °.Dark gray large circles: phosphorus; light gray medium size circles: oxygen; white medium size circles: carbon, light gray small circles: hydrogen.

Figure 4 .
Figure 4. Stationary points in the system e, as optimized at the M06-2X/cc-pVDZ(THF) level of theory.Top left: transition state structure for the formation of 3e.Top right: zwitterion 3e.Bottom left: transition state structure for the formation of cyclopropane 4e + PPh 3 .Bottom right: transition state structure for the formation of dihydrofuran 5e + PPh 3 .Selected bond atomic distances in Å and angles in °.Dark gray large circles: phosphorus; light gray medium size circles: oxygen; white medium size circles: carbon, light gray small circles: hydrogen.

Figure 7 .
The values for nitriles 1n, 1o, 1p as well as the value for thioester 1u are outliers (cyano-functionalized alkenes are thus predicted to show a particularly pronounced reactivity toward phosphoranes), whereas the carbonyl-(and nitro-, phosphonyl-and imino-) substituted alkenes are reasonably linear with ω.Ignoring the outliers, the slope obtained is ‡ G d d = −6.3kcal mol −1 eV , with the outliers included ‡ G d d = −4.1 kcal mol −1 eV −1 .The scatter seen in Figure

Figure 7 .
Figure 7. Plot of the Gibbs free energy of activation for the addition of parent Wittig ylide 2A to acceptor-substituted alkenes 1 vs CDFT electrophilicity index parameter.