alder-ene reaction: aromaticity and activation-strain analysis

Alder-Ene Reaction: Aromaticity and Activation-StrainAnalysis

Israel Fernandez,[a]* and F. Matthias Bickelhaupt[b]*

We have computationally explored the trend in reactivity of the

Alder-ene reactions between propene and a series of seven

enophiles using density functional theory at M06-2X/def2-TZVPP.

The reaction barrier decreases along the enophiles in the order

H2C¼¼CH2 > HCBCH > H2C¼¼NH > H2C¼¼CH(COOCH3) > H2C¼¼O> H2C¼¼PH > H2C¼¼S. Thus, barriers drop in particular, if third-

period atoms become involved in the double bond of the enophile.

Activation-strain analyses show that this trend in reactivity

correlates with the activation strain associated with deforming

reactants from their equilibrium structure to the geometry they

adopt in the transition state. We discuss the origin of this trend and

its relationship with the extent of synchronicity between H transfer

from ene to enophile and the formation of the new CAC bond.VC 2011 Wiley Periodicals, Inc.

DOI: 10.1002/jcc.22877

Introduction

The Alder-ene reaction constitutes one of the simplest ways to

form CAC bonds. This process, which was systematically stud-

ied by Alder,[1] involves the addition of a multiple bond (eno-

phile) to an alkene (ene) via allylic transposition (Scheme 1). In

this sense, this transformation belongs to the so-called group-

transfer pericyclic reactions,[2] and therefore, usually requires

highly activated substrates and/or high temperatures. The

Alder-ene reaction is compatible with a great variety of func-

tional groups that can be appended to the ene and enophile

moieties. Thus, it is not surprising that this general reaction

has been widely used toward the synthesis of complex mole-

cules and natural products.[3]

As most of the group-transfer pericyclic reactions, the ene

reaction is believed to proceed in a concerted and synchronous

fashion via a transition state featuring a six-membered aromatic

transition state (Scheme 1).[4] Differently, when the reaction is

promoted by Lewis acids, the mechanism can be either con-

certed or stepwise involving cationic intermediates.[5] Despite the

aromatic character of these transition states, ene reactions are

associated with relatively high barriers. This situation is quite sim-

ilar to that found for double group-transfer reactions[6] and other

pericyclic reactions such [3 þ 2] cycloaddition processes.[7,8] In all

cases, it has been found that the gain in stability through aroma-

ticity of the transition structures cannot compensate the strongly

destabilizing effect of the strain associated with the structural

rearrangement of the reactants, which becomes the controlling

factor for the high activation barriers of these transformations.

Therefore, the ene reaction constitutes a paramount oppor-

tunity to study the origins of the barrier heights of this funda-

mental and useful transformation. We report the results of a

density functional theory (DFT) study of seven archetypal

examples of such a transformation based on the so-called

‘‘activation-strain model.’’[9] It will appear that similar to other

pericyclic reactions, the ene reaction is mainly controlled by

the activation strain associated with the structural rearrange-

ment of the reactants.

Theoretical Methods

Computational details

All the calculations reported in this article were obtained with the

GAUSSIAN 09 suite of programs.[10] All reactants, transition states,

and reaction products were optimized using Truhlar’s meta

hybrid exchange–correlation functional M06-2X[11] with the tri-

ple-f quality def2-TZVPP basis sets,[12] which are supposed to be

close to the DFT basis set limit. Reactants and products were

characterized by frequency calculations, and have positive defi-

nite Hessian matrices. Transition structures (TSs) show only one

negative eigenvalue in their diagonalized force constant matrices,

and their associated eigenvectors were confirmed to correspond

Scheme 1. Alder-ene reaction.

[a] I. Fernandez

Departamento de Quımica Organica, Facultad de Quımica, Universidad

Complutense, Madrid 28040, Spain

E-mail: [email protected]

[b] F. M. Bickelhaupt

Department of Theoretical Chemistry and Amsterdam Center for Multiscale

Modeling (ACMM), VU University, De Boelelaan 1083, Amsterdam 1081 HV,

The Netherlands

E-mail: [email protected]

Contract/grant sponsor: Spanish MICINN and CAM; contract/grant

number: CTQ2010-20714-C02-01, Consolider-Ingenio 2010; contract/

grant number: CSD2007-00006, and S2009/PPQ-1634; Contract/grant

sponsors: Ramon y Cajal contract to I.F; The Netherlands Organization

for Scientific Research; contract/grant number: NWO/CW; contract/

grant number: NWO/NCF.

VC 2011 Wiley Periodicals, Inc.

Journal of Computational Chemistry 2012, 33, 509–516 509

WWW.C-CHEM.ORG FULL PAPER

to the motion along the reaction coordinate under consideration

using the intrinsic reaction coordinate (IRC) method.[13]

Activation-strain analyses of reaction profiles

The relatively recent introduction of the so-called ‘‘activation-

strain model’’ has allowed us to gain more insight into the

physical factors which control how the activation barriers arise

in different fundamental processes. This model is the same as

the ‘‘distortion/interaction model,’’ independently developed by

Houk and coworkers.[7,8] The activation-strain model is a frag-

ment approach to understanding chemical reactions, in which

the height of reaction barriers is described and understood in

terms of the original reactants.[9,14] The activation-strain model

is a systematic extension of the fragment approach from equi-

librium structures to transition states as well as ‘‘nonstationary’’

points, for example, points along a reaction coordinate. Thus,

the potential energy surface DE(f) is decomposed, along the

reaction coordinate n, into the strain DEstrain(f) associated with

deforming the individual reactants plus the actual interaction

DEint(f) between the deformed reactants:

DEðfÞ ¼ DEstrainðfÞ þ DEintðfÞ:

Here, the reaction coordinate is defined as the projection of the

IRC on the forming CAC distance between the carbon atom of

propene and the carbon atom of the enophile. This reaction coor-

dinate f undergoes a well-defined change in the course of the

reaction from1 to the equilibrium HAC distance in the product.

The strain DEstrain(f) is determined by the rigidity of the

reactants and on the extent to which groups must reorganize

in a particular reaction mechanism, whereas the interaction

DEint(f) between the reactants depends on their electronic

structure and on how they are mutually oriented, as they

approach each other. It is the interplay between DEstrain(f) andDEint(f) that determines if and at which point along f a barrier

arises. The activation energy of a reaction DE‡ ¼ DE(fTS) con-sists of the activation strain DE‡strain ¼ DEstrain(f

TS) plus the TS

interaction DE‡int ¼ DEint(fTS), (see Fig. 1):

DE‡ ¼ DEstrain‡ þ DEint

‡:

Molecular orbital theory and energy decomposition analysis

The interaction DEint(f) between the strained reactants is fur-

ther analyzed in the conceptual framework provided by the

Kohn–Sham molecular orbital (KS-MO) model.[15] To this end, it

is further decomposed into three physically meaningful terms:

DEintðfÞ ¼ DVelstat þ DEPauli þ DEoi

The term DVelstat corresponds to the classical electrostatic

interaction between the unperturbed charge distributions of

the deformed reactants and is usually attractive. The Pauli

repulsion DEPauli comprises the destabilizing interactions

between occupied orbitals and is responsible for any steric

repulsion. The orbital interaction DEoi accounts for charge

transfer (interaction between occupied orbitals on one moiety

with unoccupied orbitals on the other, including HOMO–LUMO

interactions) and polarization (empty-occupied orbital mixing

on one fragment due to the presence of another fragment).

As the KS-MO method of DFT in principle yields exact energies,

and in practice, with the available density functionals for

exchange and correlation, rather accurate, we have the special sit-

uation that a seemingly one-particle model (an MO method) in

principle fully accounts for the bonding energy.[15] Through this

energy decomposition analyses (EDA), it has previously been pos-

sible, for example, to compare the strength of conjugation, hyper-

conjugation, and aromaticity in p-conjugated systems[16,17] and

to analyze the nature of a chemical bond in terms of electrostatic

attraction versus r-, p- and d-orbital (covalent) bonding.[18,19]

Figure 1. Illustration of the activation-strain model for an Alder-ene reac-

tion. [Color figure can be viewed in the online issue, which is available at

wileyonlinelibrary.com.]

Table 1. Activation and reaction energies (DEz, DER in kcal mol21) and

NICS values in the TS (in ppm) of the considered ene reactions[a].

Reaction X Y DE‡ DER NICS(3,þ1)

1 CH2 CH2 þ33.2 �22.5 �25.0

2 CH CH þ32.1 �33.4 �22.2

3 CH2 NH þ29.3 �18.7 �23.4

4 CH2 CH(CO2Me) þ28.2 �21.0 �23.7

5 CH2 O þ24.6 �16.4 �23.0

6 CH2 PH þ21.0 �23.3 �22.7

7 CH2 S þ14.7 �25.7 �22.6

[a] Computed at M06–2X/def2-TZVPP. Energies include zero-point vibra-

tional effects.

FULL PAPER WWW.C-CHEM.ORG

510 Journal of Computational Chemistry 2012, 33, 509–516 WWW.CHEMISTRYVIEWS.COM

The EDA calculations were performed with the Amsterdam

density functional (ADF) program developed by Baerends and

coworkers[20,21] with the dispersion-corrected DFT-D3 method

developed by Grimme et al.[22] in combination with the

BLYP[23] functional: BLYP-D3. The MOs were expanded in a

large uncontracted set of Slater-type orbitals (STOs) containing

diffuse functions, TZ2P. This basis is of triple-f quality and has

been augmented by two sets of polarization functions, that is,

p and d functions for the hydrogen atom and d and f func-

tions for the other atoms. An auxiliary set of s, p, d, f, and g

STOs was used to fit the molecular density and to represent

the Coulomb and exchange potentials accurately in each SCF

cycle. Relativistic effects were accounted for by using the zer-

oth-order approximation.[24]

Nuclear independent chemical shifts

The aromatic character of the transition states has been con-

firmed by the computation of the nuclear independent chemi-

cal shift (NICS) values[25] computed at the [3,þ1] ring critical

point of the electron density[26] (see below). These calculations

have been carried out with the Gaussian 09 suite of programs

using the gauge invariant atomic orbital (GIAO) method,[27] at

the M06-2X level using the triple zeta plus polarization basis

sets, def2-TZVPP, with the optimized M06-2X/def2-TZVPP geo-

metries. This scheme is denoted as GIAO-M06-2X/def2-TZVPP//

M06-2X/def2-TZVPP.

The diatropic currents associated with the aromatic charac-

ter of the transition states have been studied with the help of

the anisotropy of the induced current density (ACID) method,

developed by Herges and coworkers.[28]

Results and Discussion

Structures and aromaticity

Table 1 lists the activation barriers and reaction energies of

the considered ene reactions computed at the M06-2X/def2-

TZVPP level. Structures of the corresponding TSs are depicted

in Figure 2. We used the same ene-fragment (propene) varying

the respective enophile partner to study the effect of different

heteroatoms and substituents in the process. The computed

activation barriers concur quite well with previous calculations

and the available experimental data[4a] which validates the use

of the M06-2X/def2-TZVPP method. The enophiles ethene

(entry 1 in Table 1) and ethyne (entry 2) have very similar reac-

tion barriers DE‡ of 33 and 32 kcal mol�1, respectively. Pro-

ceeding from the parent reaction involving ethene (entry 1 in

Table 1), the energy barrier DE‡ decreases by some 5 kcal

mol�1 when the double bond is activated by an electron with-

drawing group such as CO2Me (entry 4), in line with experi-

mental observations.[2] Similarly, the presence of a heteroatom

in the enophile (entries 3, 5, 6, and 7) makes the transforma-

tion much easier compared to the parent process, especially in

the case of the third-period elements sulfur and phosphorous

(see entries 6 and 7, Table 1).

Considering the computed bond lengths in the transition

states of each reaction (Fig. 2), there appears to be a correla-

tion between the barrier heights and the geometries of the

TS, in particular, the breaking CAH and forming CAC bond

distances. In general, it can be observed that shorter forming

CAC and shorter breaking CAH bond distances are associated

with lower reaction barriers. Thus, the more asynchronous the

reaction is in terms of CAH breaking and CAC formation, the

lower is the barrier. In other words, the transformation seems

to be easier, when the new CAC bond is already developed,

whereas the formation of the new CAH bond is lagging

behind.[29] We will come back to this, later on, in the section

on activation-strain analyses of our model reactions.

The saddle points depicted in Figure 2 clearly indicate that

all transformations proceed through highly planar six-mem-

bered cyclic transition states, regardless the synchronicity of

the process. Moreover, the distances of the CAY and the form-

ing CAC bonds are intermediate between those of double and

single bonds. Both geometrical features are in line with the

Figure 2. Alder-ene transition-state geometries (in A), computed at M06-2X/def2-TZVPP.



expected aromatic character of these transition states, which is

confirmed by the high negative NICS values (see Table 1) com-

puted at the (3,þ1) ring critical point of the electron density[25]

in the TS. Earlier analyses have shown that aromatic transition

states do indeed receive stabilization from cyclic conjugation.[6]

But at the same time, these saddle points can be high in

energy due to the activation strain required to bring the reac-

tants into the geometry in which the six electrons can enter in

such aromatic conjugation.[6] This is why these transition states

tend to localize these bonds again toward either the reactants

or the product. In fact, this is not different from the behavior

found in benzene in which the six p electrons favor a geometry

with localized double bonds but in that case, are hindered to

do so by the scaffold of the r electrons.[17c–e]

Similar to other in-plane aromatic transition states,[6,8,28,30]

the six [r2 þ p2 þ p2] electrons involved in the concerted proc-

esses lie approximately in the molecular plane giving rise to a

ring current. This, in turn, promotes a significant diamagnetic

shielding at the ring critical point of the electron density lead-

ing to the observed highly negative NICS values. The delocali-

zation of the six electrons within the molecular plane can be

viewed with the help of the ACID method.[29] The in-plane

magnetic aromaticity for the parent TS1 is clearly represented

by the presence of a pronounced diamagnetic current along

the toroid shown in Figure 3a. Moreover, the variation of the

NICS along the z-axis perpendicular to the molecular plane has

been also studied to further confirm the in-plane aromatic

character of TS1. As expected for this kind of saddle points,[30]

a typical bell-shaped plot with a maximum NICS value at z ¼ 0

A, that is, in the [3,þ1] ring critical point, was found (Fig. 3b).

Activation-strain analyses of reactivity

In this section, we address the main purpose of our study: to

understand what causes the relatively high barrier of the par-

ent Alder-ene reaction of propene þ ethylene (and also acety-

lene; entries 1 and 2 in Table 1) and which factors are respon-

sible for the lowering of the barrier along reactions 1–7. To

this end, we have carried out activation-strain analyses for all

model reactions. The results of these analyses for the TS are

collected in Table 2. Full activation-strain diagrams, that is, the

reaction profile DE(f) together with its decomposition into the

strain energy DEstrain(f), and the instantaneous interaction

energy DEint(f) between the deformed reactants are shown for

the parent reaction 1 and reactions 3–7 in Figure 4.

The activation-strain analyses of the transition states show

that the barrier in all our Alder-ene reactions stems from the

activation strain DE‡strain (see Table 2). Interestingly, as it can

be seen in the activation-strain diagrams in Figure 4, the reac-

tion profile is initially going up in energy because of a destabi-

lizing interaction DEint(f) between the reactants. Only in the

proximity of the TS (i.e., at forming CAC distances in the range

Table 2. Activation-strain analyses (in kcal mol21) of Alder–ene reactions[a].

Reaction Enophile DE‡

DE‡strain[b]

DE‡intTotal Propene Enophile

1 CH2¼¼CH2 þ33.2 45.5 32.6 12.9 �12.3

2 CH[tbond]CH þ32.1 43.4 26.3 17.1 �10.7

3 CH2¼¼NH þ29.3 36.0 29.3 6.7 �7.0

4 CH2¼¼CH(CO2Me) þ28.2 39.0 24.1 14.9 �11.5

5 CH2¼¼O þ24.6 35.0 24.3 10.7 �11.5

6 CH2¼¼PH þ21.0 32.8 22.4 10.4 �12.0

7 CH2¼¼S þ14.7 24.7 15.2 9.5 �11.1

[a] Computed at the M06–2X/def2-TZVPP. [b] DEstrain‡(total) ¼ DEstrain

‡(propene) þ DEstrain‡(enophile); see also ‘‘Theoretical Methods’’ section.

Figure 3. a) ACID plot of saddle point TS1 (isosurface value of 0.05 a.u.). b) Computed NICS values along the z axis perpendicular to the molecular plane

of TS1. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]



from 2.6 to 2.0 A), the interaction curve becomes stabilizing,

and the sole remaining reason for the high activation barrier

in the TS is the aforementioned activation strain. This behavior

is quite similar to that found for the related pericyclic double

group-transfer and cycloaddition reactions.[6,8] It has been

traced to steric (Pauli) repulsion DEPauli between closed-shell

occupied orbitals on each of the reactants. This repulsion ini-

tially prevails but eventually, as the reactants further approach

and deform, the stabilizing donor–acceptor orbital interactions

DEoi and classical electrostatic attraction DVelstat dominate the

interaction DEint that therefore becomes stabilizing at the TS.

This behavior is illustrated for the parent reaction between

propene and ethene in Figure 5 which shows the EDA (com-

puted with ADF at BLYP-D3/TZ2P) of the interaction curve

DEint(f) into the various energy terms along the reaction coor-

dinate f. Note that the dispersion term DEdisp hardly changes

along the reaction and has essentially no influence on the

interaction curve.

Figure 4. Activation-strain analysis of ene reactions 1 and 3–7 (subgraphs a–f ) along the reaction coordinate projected onto the forming CAC bond dis-

tance, computed at M06-2X/def2-TVZPP.

Figure 5. Decomposition of the interaction energy for the reaction

between propene and ethene along the reaction coordinate projected

onto the CAC bond length, computed at the DFT-D3/TZ2P.



As mentioned above, the situation that we find here for

Alder-ene reactions is similar to that for other pericyclic reac-

tions.[6,8] It contrasts however with SN2 and E2 reactions

between a base/nucleophile B� and a substrate CH3CH2L fea-

turing a leaving group L.[9a,h] In SN2 and E2 reactions, the net

interaction DEint(f) is stabilizing along the entire reaction coor-

dinate f. This is the result of a more potent donor–acceptor

interaction between the HOMO of the nucleophile or base and

the relatively low-energy LUMO of the substrate.

Both the activation-strain diagrams and the numerical data in

Table 2 show that the trend of a lowering in activation barrier

DE‡ from 33 to 15 kcal mol�1 along reactions 1–7 originates

from the activation strain DE‡strain that drops by a similar but

slightly larger amount, from 46 to 25 kcal mol–1. The transition-

state interaction DE‡int is relatively constant (it varies between

�12 and �7 kcal mol�1), and the small variations are also less

systematic. The fact that our Alder-ene reactions are controlled

by activation strain is further illustrated by the good correlation

between barrier height DE‡ and activation-strain energies

DE‡strain. Figure 6 shows that there is a clear linear relationship

between both parameters with a good correlation coefficient of

0.996 and standard deviation of 0.7 kcal mol�1. Note that this is

excluding reaction 3, with imine CH2¼¼NH as enophile, which

conforms to the trend qualitatively but deviates somewhat

from the ‘‘linear’’ correlation (white data point in Fig. 5). Includ-

ing reaction 3 yields a somewhat smaller but still acceptable lin-

ear correlation coefficient of 0.960 and a standard deviation of

2 kcal mol�1.

Thus, the activation strain DE‡strain controls the height and

the trend in Alder-ene reactions. This result is consistent with

earlier findings that barriers of pericyclic reactions are con-

trolled by the activation strain.[6–8] The main contributor to

the activation strain of the Alder-ene reactions is the strain

DE‡strain(ene) stemming from the ene, in our case, this is pro-

pene (see Table 2). On the other hand, the strain in the eno-

phile is significantly smaller. The reason is that in the course of

the reaction, the ene reactant must break one of its CAH

bonds, which is quite costly in terms of energy, because CAH

bonds are quite strong. In the enophile, on the other hand,

no bond is broken in the course of the geometrical rearrange-

ment associated with the Alder-ene reaction (the formal disap-

pearance of the p bond only occurs ‘‘after’’ the transition-state

interaction DE‡int with the ene has been switched on).

Strikingly, the DE‡strain(ene) term not only is the larger of the

two contributors of strain but also varies more pronouncedly

than the smaller DE‡strain(enophile) term, although it is the

enophile that is varied in our model reactions, not the ene. In

fact, DE‡strain(ene) determines the trend in total strain and thus

in barrier heights. The trend in reaction barriers is the result of

a complex and subtle interplay of factors which are not fully

resolved here. However, we can distinguish a few more clear-

cut cases in which some factors work jointly and pronouncedly

into the same direction. This is the case if we go from reaction

1, that is, the parent reaction of propene þ H2C¼¼CH2, to reac-

tions 5–7 involving the enophiles H2C¼¼O, H2C¼¼PH, and

H2C¼¼S. Along this series, the reaction barrier drops signifi-

cantly, and this trend is dominated by the systematic reduc-

tion of the enophile activation strain DE‡strain(enophile) (see Ta-

ble 2). This behavior can be ascribed to variations in the

frontier orbitals of the enophile, in particular the LUMO(eno-

phile). The shape of this acceptor orbital determines how the

enophile attacks and deforms the ene. Figure 7 provides a

schematic illustration of the LUMO(enophile) that is the CAY

antibonding p* orbital.The dominant frontier-orbital interaction that occurs as the

ene, and enophile approach toward each other is the one

between the HOMO(ene) and the LUMO(enophile), also shown

in Figure 7. The HOMO(ene) arises as the antibonding combi-

nation of the p-bonding orbital in the [H2C¼¼CH] moiety of

propene and a CAH bonding orbital of the dissociating CAH

bond on the methyl group. This HOMO(ene) overlaps via its

terminal 2pp lobe as well as via the aforementioned terminal

CAH bonding lobe with the LUMO(ene).

In the case of ethene as the enophile, the overlap leading

to the formation of the new CAC bond and that leading to

weakening of the CAH bond (and eventually H transfer) are

Figure 6. Linear relationship between activation energy DE= and activa-

tion strain DE=strain of Alder-ene reactions. [Color figure can be viewed in

the online issue, which is available at wileyonlinelibrary.com.]

Figure 7. Schematic representation of HOMO(ene)–LUMO(enophile) inter-

action in Alder-ene reaction of propene þ CH2¼¼CH2 (left) and propene þCH2¼¼Y (right, see text). [Color figure can be viewed in the online issue,

which is available at wileyonlinelibrary.com.]



both well developed (see Fig. 7, left). This drives the Alder-ene

transformation via a relatively synchronous CAC bond forma-

tion and CAH bond breaking (see Fig. 2: compare TS1 with,

e.g., TS7) and thus via a relatively high activation strain (from

the ene reactant) and barrier (see Table 2). However, if the

enophile H2C¼¼Y becomes more polar, for example, if we go

from H2C¼¼CH2 to H2C¼¼O, the p* LUMO(enophile) achieves a

larger amplitude on C and a smaller one on Y¼¼O (see Fig. 7,

right). This yields a larger CAC and worse HAY overlap and

drives the Alder-ene transformation in a more asynchronous

fashion with CAC bond formation running somewhat more

ahead CAH bond breaking lagging a bit more behind (see Fig.

2, compare TS5 with TS1). The latter directly translates into a

reduction of the activation strain (from the ene) and thus a

lower barrier.

The electronegativity difference across the enophile CAY

bond and its effect on extent of polarization of the LUMO(eno-

phile) from Y to C above is not the only mechanism that

affects reactivity. The shift toward a more asynchronous,

lower-barrier Alder-ene process is reinforced by making the

LUMO(enophile) amplitude on Y more diffuse. This is why bar-

riers drop in particular, if third-period atoms (with more diffuse

3p instead of 2p lobes on Y ¼ P, S) are involved in the double

bond of the enophile. Thus, reactions 6 and 7 are most asyn-

chronous and have both the lowest strain and the lowest bar-

riers (see Fig. 2 and Table 2).

Conclusions

The parent Alder-ene reaction between propene and ethene

proceeds via a six-membered cyclic aromatic TS. The associ-

ated barrier is nevertheless relatively high (33 kcal/mol) due to

the activation strain associated with deforming the reactants

such that they adopt a cyclic geometry that is suitable for aro-

matic conjugation. This follows from our density functional cal-

culations and activation-strain analyses carried out at M06-2X/

def2-TZVPP.

The Alder-ene barrier decreases along the enophiles in the

order H2C¼¼CH2 > HCBCH > H2C¼¼NH > H2C¼¼CH(COOCH3) >

H2C¼¼O > H2C¼¼PH > H2CH2¼¼S. Thus, barriers drop in particu-

lar, if third-period atoms become involved in the double bond

of the enophile. Our activation-strain analyses reveal that this

trend in reactivity correlates with the activation strain.

In particular, along the reactions of propene with H2C¼¼CH2,

H2C¼¼O, H2C¼¼PH and CH2¼¼S, there is a clear-cut relationship

between barrier height and the activation strain stemming

from the ene (here, propene). This trend is related to the eno-

phile LUMO becoming less suitably shaped for overlapping

with the CAH bond of the hydrogen that is transferred from

ene to enophile. Consequently, along this series, ene CAH

bond breaking begins to lag behind forming the new ene–

enophile CAC bond in the TS, yielding a lower activation

strain in the ene reactant and thus a lower overall reaction

barrier.

Keywords: activation strain model � aromaticity � density func-

tional calculations � Alder-ene reaction � reactivity

How to cite this article: I. Fernandez, F. M. Bickelhaupt,, J.

Comput. Chem. 2012, 33, 509–516. DOI: 10.1002/jcc.22877

Additional Supporting Information may be found in the

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Received: 26 October 2011Accepted October 28, 2011Published online on 6 December 2011



alder-ene reaction: aromaticity and activation-strain analysis

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