Theoretical Evaluation of Global and Local Electrophilicity Patterns to

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Theoretical Evaluation of Global and Local Electrophilicity Patterns to Characterize Hetero-Diels-Alder Cycloaddition of Three-Membered 2H-Azirine Ring System Pratibha Sharma,* Ashok Kumar, and Vinita Sahu School of Chemical Sciences, DeVi Ahilya UniVersity, Takshashila Campus, Indore, MP 452 001, India ReceiVed: September 12, 2009; ReVised Manuscript ReceiVed: October 22, 2009

Present communication elicits an interesting interaction between 2H-azirine and a number of electron rich and electron deficient dienes. A series of substituted 2H-azirine 1-10, and three dienes namely cyclopentadiene D-1, furfural D-2, and dinitrofuran D-3 were chosen to investigate and critically review the reactivity and selectivity of Diels-Alder cycloaddition strategy. The global and local electrophilicity patterns have been evaluated to interpret the electrophilic/nucleophilic behavior of dienes D-1 to D-3 and dienophiles 1-10, in polar Diels-Alder cycloaddition, using the DFT method at the B3LYP/6-31G* level of theory. Regional nucleophilicity have been evaluated using local nucleophilicity descriptor Nk (Pe´rez, P.; Domingo, L. R.; Duque-Norena, M.; Chamorro, E. J. Mol. Struct. THEOCHEM 2009, 895, 86-91), and regional electrophilicity at the active sites of the interactive species involved in Diels-Alder processes have been described on a quantitative basis using local electrophilicity index ωk. 1. Introduction The hetero-Diels-Alder (DA) reaction is one of the most useful synthetic strategies and is often an important icon to provide a range of biologically active heterocyclic systems. In particular, 2H-azirine,1,2 a strained three-membered nitrogen heterocycle, is a highly reactive and imperative starting material for the synthesis of amino acids and alkaloids. The inherent ring strain and electron rich CdN bond vis-a`-vis the presence of a lone pair on the nitrogen atom accounts for its distinct reactivity. The aza DA cycloaddition of 2H-azirines3,4 has received much more recent interest for providing a number of useful chemical compounds. Buoyed from these findings, we wish to exploit the ring strain of 2H-azirine upon its interaction with a number of electron rich and electron deficient dienes. The DA reactions are primarily controlled by the type of substituent present on diene and dienophlie. By varying the nature of substituent on diene/dienophile, the reactivity of cycloaddition reactions can be altered significantly. Therefore, the electronic features of diene/dienophile play a central role in determining the cycloaddition reactivity. A number of global and local reactivity descriptors, namely, global electrophilicity,5 global hardness, global softness, local hardness, local softness, Fukui function,6 nucleophilicity index17,18 (N) etc., based on density functional theory (DFT) has received great importance in order to determine the fate of the DA reaction. The study of changes in the global and local reactivity profiles of a reacting system is quite important to understand the reactivity of the total chemical process. In this context, for a long time, Domingo’s group has been involved in the study of the DA reaction using these parameters to establish the polar character of cycloaddition.7 The results of these studies indicate a direct relationship between the decrease of cycloaddition activation barrier and charge transfer (CT) through a nonsynchronous bond-formation process.8 A great deal of work concerning the evaluation of global quantities based on DFT has been reported.9 Moreover, a significant amount of work * To whom correspondence should be addressed. Telephone: +91-7312460208. Fax: +91-731-2470372. E-mail: [email protected].

exploring the local and global electrophilicity index to assign the regioselectivity10 of the DA interaction between unsymmetrical diene and dienophiles has also been documented successfully. Thus, keeping this in view and in pursuance of our research program devoted to the study of heterocycles11 and DFT, we have made an effort to interpret the cycloaddition of 2H-azirine with various dienes D-1 to D-3. In this context, regioselectivity of DA cycloaddition has also been determined on the basis of local descriptors. Also, an attempt has been made to establish a correlation between various electronic parameters and mechanistic aspects of DA cycloaddition strategy. 2. Theoretical Background In a view to unravel mechanistic details of DA cycloaddition, we have undertaken the theoretical approach considering global and local electrophilicity parameter. The global electrophilicity index ω5 (ω ) µ2/2η) measures the stabilization energy in the process of getting an additional electronic charge ∆Nmax from the environment. Here, µ ) (I + A)/2 and η ) (A - I) are the electronic chemical potential µ12,14b and chemical hardness η13 of the ground state of atoms and molecules, respectively. These are approximated in terms of the vertical ionization potential (I) and electron affinity (A) using Koopman’s theorem.14 Associated with this, there is an additional and useful relationship that accounts for the maximum electronic charge ∆Nmax5 (∆Nmax ) -µ/η) that the electrophile may accept from the environment. The global softness S15,14b and local softness s (r)16,14b can be expressed as: S ) (1/2)η, s(r) ) Sf(r), respectively. It is also possible to define local philicity quantity ωk9a,7h ) ωfk+ by considering the electrophilic Fukui function fk+ to characterize most electrophilic sites in regioselective reactions. The above equation predicts the most electrophilic site in a molecule. Also, the partition for ∆Nmax in terms of the electrophilic/ nucleophilic Fukui function can be stated as follows: ∆Nmax (K) ) ∆Nmax fk+ /∆Nmaxfk-. The polar character of the interaction is described according to the proposed model by the difference in the absolute electrophilicity power ∆ω.28a Further, the empirical nucleophilicity index, N, based on the HOMO energies obtained within the Kohn-Sham scheme,17 defined as:18a

10.1021/jp9088222  2010 American Chemical Society Published on Web 11/18/2009

Hetero-Diels-Alder Cycloaddition of 2H-Azirine Ring

N ) EHOMO(Nu) - EHOMO(TCE)

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(1)

SCHEME 1: DA Cycloaddition between 2H-Azirines 1-10 and Dienes D-1 to D-3

Here, in the nucleophilicity scale, tetracyanoethylene (TCE) is taken as the reference because it presents lowest HOMO energy. This choice allows us to provide nucleophilicity scale with positive values.18a Similarly, the local nucleophilicity index18b Nk, can be expressed as:

Nk ) Nfk

(2)

According to eq 2, maximum nucleophilicity power in a molecule will be developed at the site where nucleophilic Fukui function fk- displays its maximum value. Thus, the role of these variable quantities has been rigorously examined in the present studies with a view to gain a deep insight into the mechanistic details of DA cycloaddition strategy. 3. Computational Details DFT calculations were carried out using the B3LYP/6-31G* theory19–22 in the Gaussian 0323 suite of programs. All the dienes and dienophiles under investigation were optimized using Berny analytical gradient optimization method.24 The global electrophilicity parameters were evaluated using equations given in the Theoretical section. The electronic chemical potential µ and chemical hardness η values were approximated in terms of EH (I) and EL (A), respectively, for one-electron energies of frontier molecular orbital, HOMO and LUMO, using µ ) (I + A)/2 and η ) (A - I) at the ground state (GS) of the molecules. The global maximum charge transfer toward the electrophile was evaluated using ∆Nmax ) -µ/η. Regional Fukui functions for electrophilic (fk-) and nucleophilic (fk+) attacks were obtained from a single point calculation at the optimized structures of the GS of molecules by a method described elsewhere.25 Fukui functions were calculated using both Mulliken population analysis (MPA)26 and natural population analysis (NPA)27 schemes, and only MPA results are reported in all the cases. With the nucleophilic Fukui function at hand, the regional (site) electrophilicity power is readily obtained.

ing groups are strong electrophiles, and the dienophile 6-10 with electron donating substituents are less electrophilic than 1-4. The order of electrophilicity is as per the substitution pattern in the phenyl ring attached to azirine. Similarly, dienes D-1, D-2, and D-3 can also be classified. The electrophilicity ω of cyclopentadiene D-1 is 0.83 eV, it is located at the limit between the moderate and marginal electrophile (nucleophile) in electrophilicity scale, and it therefore probably acts as a nucleophile in polar DA reaction with strong electrophile. Similarly, D-2 can be considered as a moderate electrophile as its electrophilicity ω (1.74 eV) lies between the limits of moderate to strong electrophile,28c although D-3 is a strong electrophiles as ω ) 3.93 eV. On the basis of global electrophilicity index ω, Table 1, a comparative view of electrophilicity of different dienophiles 1-10 and dienes D-1 to D-3 can be presented as follows: 1 (3,4-Dintro) > 2 (4-NO2) > 3 (3-NO2) > 4 (3-Cl) > 5 (1-H) > 6 (3-OH) > 7 (3-OCH3) > 8 (3,4-Dimethyl) > 9 (4-CH3) > 10 (4-NH2) Cyclopentadiene (D-1, ω ) 0.83 eV) < Furfural (D-2, ω ) 1.74 eV) < Dinitro furan (D-3, ω ) 3.93 eV) It is revealed from this order that D-1 is the most electron rich diene, whereas D-3 is the least one. In order to have interaction between cyclopentadiene D-1 and dienophile 1-10, the electrophilicity of D-1 (ω ) 0.83 eV) is much lower than dienophiles 1-10 (ω ) 4.09-2.07 eV), irrespective of the nature of substituent present on dienophile. Thus, it can be inferred that cyclopentadiene D-1 is less electrophilic than

4. Results and Discussion Reactivity of Dienes and Dienophiles. The concepts of global and local electrophilicity parameters have been employed rigorously to interpret the reactivity patterns.9,10 To have a better understanding of the impact of global electrophilicity parameters on DA mechanism, we have initialized our study with three dienes, namely, cyclopentadiene D-1, furfural D-2, dinitrofuran D-3, and a series of dienophiles 1-10 (Scheme 1). Optimized geometries of different dienes and dienophiles are depicted in Figures 1 and 2, respectively. 2H-azirines 1-10, the dienophiles, are chosen to explore their dienophilic behavior owing to their reactivity and strained behavior. Different functional groups, namely, -NO2, -OH, -OCH3, -NH2 etc., present on the phenyl ring of dienophile 1-10 have significant impact on electrophilicity of dienophiles due to their electron withdrawing and electron donating nature. According to the electrophilicity scale proposed by Domingo et al.28 the dienophiles 1-10 are characterized as strong electrophiles, as ω ranges between 4.09-2.07 eV. The dienophiles 1-4 substituted by electron withdrawing groups have higher electrophilicity values, ranging between 4.09-2.73 eV, whereas dienophile 6-10 have lower electrophilicity values (2.45-2.07 eV). Thus, the dienophiles with electron withdraw-

Figure 1. Optimized geometries (B3LYP/6-311G*) with atom numbering and frontier molecular orbital of dienes D-1 to D-3.

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Figure 2. Optimized geometries (B3LYP/6-311G*) with atom numbering and frontier molecular orbital of dienophiles 1-10.

Sharma et al.



TABLE 1: Calculated Global Electronic Parameters (eV) for Dienes D-1, D-2, D-3 and Dienophiles 1-10 diene/ dienophiles D-1 D-2 D-3 1 2 3 4 5 6 7 8 9 10

R

I

A

µ

η

S

ω

N

∆Nmax

3,4-dinitro 4-NO2 3-NO2 3-Cl 1-H 3-OH 3-OCH3 3,4-dimethyl 4-CH3 4-NH2

-5.76 -6.79 -8.32 -7.58 -7.29 -7.18 -6.92 -6.69 -6.40 -6.30 -6.50 -6.57 -5.81

-0.27 -1.66 -3.72 -3.69 -3.32 -3.04 -2.69 -2.46 -2.43 -2.37 -2.32 -2.19 -2.06

-3.01 -4.23 -6.02 -5.64 -5.31 -5.11 -4.81 -4.58 -4.41 -4.34 -4.41 -4.38 -3.94

5.49 5.13 4.61 3.89 3.97 4.13 4.22 4.24 3.97 3.92 4.18 4.38 3.74

0.09 0.10 0.11 0.13 0.13 0.12 0.12 0.12 0.13 0.13 0.12 0.11 0.13

0.83 1.74 3.93 4.09 3.55 3.16 2.73 2.47 2.45 2.39 2.33 2.19 2.07

3.36 2.33 0.80 1.54 1.83 1.94 2.20 2.43 2.72 2.82 2.62 2.55 3.31

0.55 0.82 1.31 1.45 1.34 1.24 1.14 1.08 1.11 1.11 1.06 1.00 1.05

dienophile 1-10 and will acts as a nucleophile in DA cycloaddition with dienophile 1-10. Moreover, chemical potential µ, which gives the direction of charge transfer (CT) between diene and dienophile, is highest for cyclopentadiene (-3.01 eV) as compared to dienophile 1-10 (-5.64 to -3.94 eV), and is accountable for charge transfer from electron rich diene D-1 to electron deficient dienophiles 1-10 to assist polar cycloaddition. Dienophile 1 is the most electron deficient, having two electron deficient -NO2 groups, whereas dienophile 10 is the least electron deficient, which is evidenced by the highest value of ∆ω (3.26 eV) for interaction between D-1 and dienophile 1 with the most polar nature, whereas it is minimum for the D-1-dienophile 10 interaction (∆ω )1.24 eV) with the least polar nature. Likewise, the nucleophilicity descriptor N, very recently introduced by Domingo’s group, is highest for D-1 (3.36 eV). It presents its most nucleophilic nature among dienes and dienophiles. Furthermore, the ∆Nmax that represents the maximum propensity of the system to acquire additional electronic charge from the environment is maximum for dienophile 1 (∆Nmax ) 1.45 eV) and minimum for dienophile 9 (∆Nmax ) 1.00 eV). It gives an estimate about the relative electrophilicity and nucleophilicity of a particular species toward DA cycloaddition. These parameters clearly indicate that during the interaction of D-1 with dienophiles 1-10, the D-1 will act as a nucleophile and favorably interact with dienophile 1 in a polar transition state with minimum activation energy barrier. Furfural D-2 is comparatively electron deficient diene compared to cyclopentadiene D-1 (D-1; ω ) 0.83 eV, D-2; ω ) 1.74 eV) and falls into the category of moderate-strong electrophile in electrophilicity scale. But, dienophiles 1-10 are comparatively electron deficient, with ω in the range of 2.07-4.09 eV, than diene D-2. Subsequently, the dienophiles 1-10 would behave as electrophiles in DA reaction with D-2. A similar trend can be a prelude for the remaining electrophilicity parameters, namely, ω, µ, η, ∆ω, etc., as for the diene D-1. Lastly, interesting results can be followed by analyzing the interaction between diene D-3 (dinitrofuran) and dienophiles 1-10. Diene D-3 exhibit maximum electrophilicity, ω ) 3.93 eV, compared to D-1, D-2, and dienophiles 2-10, with the exception of dienophile 1, which is most electron deficient. As we move from electron deficient dienophile 1 to comparatively electron rich dienophiles 2-10, electrophilicity decreases and approaches a minimum of 2.07 eV. The dienophiles 2-10 exhibit lower electrophilicity than D-3, which allows the reversal in flow of electron flux from electron rich dienophiles 2-10 to D-3. Subsequently, in the DA reaction D-3 will act as an electrophile, and dienophiles 2-10 as nucleophile. In a polar cycloaddition, the most polar interaction with maximum ∆ω

(1.87 eV) will occur between D-3 and dienophile 10. The results, in terms of electrophilicity index ω, µ, η, ∆Nmax, etc., are consistent with the above findings. Above results clearly indicate that diene D-1 and D-2 would primarily behave as nucleophiles in cycloaddition with dienophile 1-10, whereas diene D-3, being an electron deficient

Figure 3. A comparative overview of global electrophilicity parameters (eV) for dienophiles 1-10.

Figure 4. Plot of electrophilicity index vs electronegativity for dienophiles 1-10.

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TABLE 2: Local Properties (eV) for Dienes*

* k defines the site in the molecule where the property is being evaluated.

TABLE 3: Local Properties (eV) for Dienophiles 1-10a fk+

Sk+

∆Nmax (k)

ωk

dienophile

R

N-11

C-10

N-11

C-10

N-11

C-10

N-11

C-10

1 2 3 4 5 6 7 8 9 10

3,4-dinitro 4-NO2 3-NO2 3-Cl 1-H 3-OH 3-OCH3 3,4-dimethyl 4-CH3 4-NH2

0.098 0.096 0.106 0.111 0.117 0.116 0.116 0.117 0.112 0.119

0.059 0.053 0.058 0.057 0.058 0.058 0.057 0.056 0.034 0.054

0.013 0.012 0.013 0.013 0.014 0.015 0.015 0.014 0.013 0.016

0.008 0.007 0.007 0.007 0.007 0.007 0.007 0.007 0.004 0.007

0.40 0.34 0.34 0.30 0.29 0.28 0.28 0.27 0.25 0.25

0.24 0.19 0.18 0.16 0.14 0.14 0.14 0.13 0.07 0.11

0.14 0.13 0.13 0.13 0.13 0.13 0.13 0.12 0.11 0.13

0.09 0.07 0.07 0.07 0.06 0.06 0.06 0.06 0.03 0.06

a

k defines the site in the molecule where the property is being evaluated.

diene, will acts as an electrophile in DA cycloaddition. A complete overview of various global electrophilicity parameters for dienophiles 1-10 is depicted in Figure 3. Moreover, multiple linear regression analysis has also been performed to correlate the electron affinity (A) with electrophilicity index (ω) of dienophiles 1-10, and results (Figure 4) are interpreted in terms of statistical parameters, namely, standard deviation (SD ) 0.044), regression coefficient (r ) 0.99, r2 ) 0.98), etc., which were found to be quite promising. On this basis it is clear that electron affinity A and electrophilicity index ω are in excellent correlation with each other. Thus, the global electrophilicity parameters are quite successful in explaining the experimental outcomes of the DA reaction. Although the reaction temperature may affect the quantitative data to some extent, the overall trend of observation remains unaffected. Hence, the importance of these findings can be usefully exploited in designing synthetic strategies. In this context, Domingo’s group has been actively engaged and has successfully explained the chemical reactivity and selectivity of DA reaction using these indices.7

population at atomic termini and can afford regioselective cycloadducts. The analysis (Table 2) of local nucleophilicity descriptor Nk at interacting terminal atomic centers (C-1, C-4) of dienes preludes that the local nucleophilicity descriptor Nk is similar at C-1 and C-4 for symmetrical dienes, namely, cyclopentadiene D-1 (C-1 and C-4 ) 0.36 eV) and dinitrofuran D-3 (C-1 and C-4 ) 0.05 eV). Subsequently, there will be no regioselectivity in these cases. However, diene D-2, which is an unsymmetrical diene, exhibits higher nucleophilicity at C-1 rather than C-4

5. Regioselective Studies The interaction between an unsymmetrical diene with unsymmetrical dienophile can provide two isomeric cycloadduct; headto-head or head-to-tail, depending on the relative position of substituent. The selective formation of one cycloadduct over the other is termed as regioselectivity. Recent studies devoted to regioselective18,29 DA reactions using DFT have shown that the combined analysis of local electrophilicity ωk and local nucleophilicity Nk at electrophile and nucleophile allows the prediction of regioselectivity. In the present study only one diene, D-2 (furfural), is unsymmetrical with different orbital

Figure 5. Plot of local electrophilicity index ωk at N-11 and C-10 for a series of dienophiles 1-10.



SCHEME 2: An Overview to Predict Regioselective DA Cycloadduct

termini (C-1 ) 0.27, C-4 ) 0.13 eV). Therefore, site C-1 is most susceptible toward electrophilic attack to allow regioselectivity. The C-1 site of D-2 possesses approximately 50% higher nucleophilic probability than C-4 toward electrophilic attack. Moreover, the close inspection of local electrophilicity ωk at dienophile 1-10 interacting sites are also important to project regioselectivity. Comprehensive analysis of site selectivity for nucleophilic attack on dienophile 1-10 reveals that in all the dienophiles, the local electrophilicity ωk is higher at the N-11 position than the C-10 (Table 3), and there is no measurable effect of nature of substituent on phenyl moiety of dienophile on site selectivity, that is, on N-11/C-10. It may be seen that the entire series of dienophiles 1-10 shows higher electrophilicity at N-11 than C-10. Hence, this site (N-11) is most reactive toward the nucleophilic site (C-1) with larger Nk value on furfural to afford regioselective adducts (Figure 5). Another remarkable result follows from the maximum charge transfer described by the ∆Nmax (k) quantity, which presents the maximum propensity of the system to acquire additional electronic charge from the environment. The ∆Nmax (k) value follows exactly the same pattern as local descriptor ωk to assess the site selectivity in the DA cycloaddition. For instance, all the dienophiles 1-10 exhibit maximum ωk at N-11 rather than C-10 and also exhibit a higher ∆Nmax (k) value at N-11 to facilitate the preferable attack of nucleophilic site of diene in a regioselective manner. On the other hand, for symmetrical dienes D-1 and D-3, the descriptor ∆Nmax (k) concentrates equally (50%) at both sites, C-1 and C-4, to allocate non-regioselective cycloadditions. So, the most favorable interaction would be between C-1 sites of diene D-2 with maximum Nk and N-11 site of dienophiles 1-10 with maximum ωk. Thus, on this basis it can be concluded that interaction between D-2 with dienophiles 1-10 would provide R-1 as a preferred regioisomer (Scheme 2). Consequently, the local electrophilicity parameters are very useful in identifying electrophilic/nucleophilic sites within a static reactivity picture to understand the regioselectivity pattern. 6. Concluding Remarks In summary, in a new approach, considering 2H-azirine as dienophiles, the global electrophilicity pattern have been successfully evaluated for a series of substituted 2H-azirines 1-10 and dienes D-1 to D-3 to rationalize the polarity of cycloaddition reaction. The electrophilicity hierarchy, namely, electrophilicity index, chemical potential, chemical hardness, softness, ∆Nmax, etc., was found in good agreement with substitution pattern on dienes and dienophiles. The analysis of global reactivity indices

provided an explanation for the participation of dienes D-1 and D-2 as nucleophile toward powerful electrophiles 1-10, whereas D-3 exhibited an opposite trend of reactivity due to its electron deficient nature. Moreover, the local reactivity descriptors were found to be very powerful in predicting the regioselectivity of DA cycloaddition. The multiple regression analysis also provided a better estimate to establish a correlation between different global electronic parameters, which is quite significant in unraveling the chemical reactivity pattern. Thus, these studies can become a powerful tool for the prediction of reactivity and selectivity of DA cycloaddition and may be quite useful for simulation of molecular electronics to predict the reaction outcomes. Similar studies on hetero-DA reactions are underway. Acknowledgment. V.S. is thankful to the Council of Scientific and Industrial Research (CSIR), India for providing a senior research fellowship (SRF). We are grateful to the reviewers for constructive criticism and helpful suggestions to improve the standard of the manuscript and also to Professor Sandor Kunsagi-Mate, University of Pecs, Hungary for helpful suggestions. References and Notes (1) (a) Padwa, A.; Smolanoff, J.; Tremper, A. J. Org. Chem. 1976, 41, 543. (b) Verstappen, M. M. H.; Ariaans, G. J. A.; Zwanenburg, B. J. Am. Chem. Soc. 1996, 118, 8491. (c) Katritzky, A. R.; Wang, M.; Wilkerson, C. R.; Yang, H. J. Org. Chem. 2003, 68, 9105. (d) Palacios, F.; Ochoa de Retana, A. M.; Gil, J. I.; Ezpeleta, J. M. J. Org. Chem. 2000, 65, 3213. (2) (a) Palacios, F.; Ochoa de Retana, A. M.; Martıńez de Marigorta, E.; de los Santos, J. M. Org. Prep. Proced. Int. 2002, 34, 219. (b) Gilchrist, T. L. Aldrichim. Acta 2001, 34, 51. (c) Davis, F. A.; Liu, H.; Liang, C.; Reddy, V.; Zhang, Y.; Fang, T.; Titus, D. D. J. Org. Chem. 1999, 64, 8929. (3) (a) Anderson, D. J.; Hassner, A. Synthesis 1975, 483. (b) Anderson, D. J.; Hassner, A. J. Org. Chem. 1974, 39, 2031. (c) Anderson, D. J.; Hassner, A. J. Org. Chem. 1974, 39, 3070. (d) Timeń, A. S.; Somfai, P. J. Org. Chem. 2003, 68, 9958. (e) Davis, F. A.; Deng, J. Org. Lett. 2007, 9, 1707. (4) (a) Ray, C. A.; Risberg, E.; Somfai, P. Tetrahedron Lett. 2001, 42, 9289. (b) Anderson, D. J.; Hassner, A.; Tang, D. Y. J. Org. Chem. 1974, 39, 3076. (5) Parr, R. G.; Szentpaly, L.v.; Liu, S. J. Am. Chem. Soc. 1999, 121, 1922. (6) (a) Parr, R. G.; Yang, W. J. Am. Chem. Soc. 1984, 106, 4049. (b) Fukui, K. Science 1987, 218, 747. (7) (a) Domingo, L. R.; Jones, R. A.; Picher, M. T.; Sepulveda-arques, J. Tetrahedron 1995, 51, 8739–8748. (b) Domingo, L. R.; Picher, M. T.; Andres, J.; Moliner, V.; Safont, V. S. Tetrahedron 1996, 52, 10693–10704. (c) Domingo, L. R.; Picher, M. T.; Andres, J.; Safont, V. S. J. Org. Chem. 1997, 62, 1775–1778. (d) Domingo, L. R.; Picher, M. T.; Zaragoza, R. J. J. Org. Chem. 1998, 63, 9183–9189. (e) Domingo, L. R.; Picher, M. T.; Aurell, M. J. J. Phys. Chem. A 1999, 103, 11425–11430. (f) Domingo, L. R. Eur. J. Org. Chem. 2004, 4788–4793. (g) Domingo, L. R.; Chamorro, E.; Pe´rez, P. J. Phys. Chem. A 2008, 112, 4046–4053. (h) Domingo, L. R.; Aurell, M. J.; Contreras, R.; Pe´rez, P. J. Phys. Chem. A 2002, 106, 6871.

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