THEO CHEM

Journal of Molecular Structure (Theochem) 3.58 (1996) 23-27

The role of hard Lewis acids in the tunning of the exo/endo stereoselectivity in Diels-Alder reactions:

ab initio calculations

Javier Gonzhleza, Tom&s L. Sordob, Josit A. Sordob,*

“Institute Universitario de Quimica Organometblica “Enrique Moles”, Universidad de Oviedo. 33071-Oviedo, Spain ‘Departamento de Quimica-Fisica y Analitica. Universidad de Oviedo. c/ Julirin Claveria 8. 33006Oviedo, Spain

Received 9 June 1995; accepted 20 June 1995

Abstract

Recent experimental studies (D.C. Bradock, J.M. Brown and P.J. Guiry, J. Chem. Sot., Chem. Commun., (1993) 1244) on the stereoselectivity of the Diels-Alder reaction of thionofumarate derivatives with cyclopentadiene show that the hard or soft character of the Lewis acid catalysts can play a very important role controlling the steric course of this type of cycloaddition. RHF/3-21G* ab initio calculations allow one to obtain a qualitatively correct description of the stereochemical outcome of that reaction both in the thermal and in the (hard) Lewis acid-catalysed cases.

Keywords: Ab initio calculations; Catalysed reactions; Diels-Alder reactions; Hard Lewis acid; Stereoselectivity

1. Introduction

One of the most interesting and intriguing topics in Diels-Alder chemistry is the endo vs. exo stereo-

selectivity of the reaction [I]. It has been shown that the Lewis acid catalysis causes an important

increase in the endo selectivity in the Diels-Alder reactions of CX, P-unsaturated carbonyl com-

pounds, as for example in the case of acrylates [2]. This effect has been attributed to the coordina- tion of the Lewis acid to the carbonyl group, thus

favouring the secondary orbital interactions between the diene and dienophile moieties in the transition state [3].

Recently, Braddock et al. [4] reported that the

* Corresponding author.

soft or hard character of the Lewis acid

influences to a great extent the diastereo- selectivity of the Diels-Alder reaction of dimethyl monothionofumarate with cyclopentadiene. Thus, strong and hard Lewis acids such as BC13 or

Et,BCl cause an increase in the endo-ester dia-

stereoisomer, as compared with the thermal reac- tion, whereas soft Lewis acids, such as Cu(OTQz,

give the endo-thionoester adduct as the major dia- stereoisomer.

We present here the results of an ab initio study

[5] of the Diels-Alder reaction of cyclopentadiene with monothionofumaric acid (1) (Scheme 1) as a model of dimethyl monothionofumarate. Both the thermal and the Lewis acid-catalysed reactions were studied, choosing in the latter case the proton as a model for a hard Lewis acid [6].

0166-1280/95/$09.50 0 1995 Elsevier Science B.V. All rights reserved SSDI 0166-1280(95)04358-6

24 J. Gonzdez et al./Journal qf Molecular Structure (Theochem) 358 (1995) 23-27

Scheme 1.

2. Computational aspects

Ab initio calculations were carried out using the GAUSSIAN 92 package of programs [5]. Structures were fully optimized (at the restricted Hartree- Fock level of theory) with the 3-21G* basis set [7], followed by vibrational frequency calculations which confirmed that the reactants and transition structures (located by means of Schlegel’s algo- rithm) [S] have zero and one imaginary frequency, respectively.

The basis set used in this study (3-21G*) was dictated by the sizes of the systems involved (see Scheme 1). Nevertheless, previous work on Diels- Alder cycloadditions involving a sulphur-contain- ing dienophile [9] have shown that such a basis set provides results in good consonance with those from higher levels of theory which cannot be

A

afforded in the present study. Indeed, as shown in Ref. [SC], the relative energies computed at the 3-21G* and 6-31G* levels compare fairly well (for example, the relative energies of the transition structures of the thermal and Lewis acid-catalysed reactions of 1,3-butadiene with sulphur dioxide are (thermal) 18.1 (endo), 19.7 (exe) and (Lewis acid- catalysed) 4.4 (endo), 7.2 (exo) kcalmol-’ when computed with the 3-21*G basis set and (thermal) 16.6 (endo), 18.4 (exo) and (Lewis acid-catalysed) 4.9 (endo), 8.9 (exo) kcalmol-’ when using the 6-31G* basis set [SC]. Therefore, as concluded in Ref. [SC]: “. . . for the kind of reactions dealt with in this paper (Diels-Alder cycloadditions involving a sulphur-containing dienophile), the relative acti- vation energies computed at the RHF/3-21G* level are satisfactory approximations to the much more expensive RHF/6-3 lG* relative activation ener- gies”. Finally, it should be mentioned that our pre- vious work [9] indicates that, for this type of system, although the correlation makes significant contribu- tions to the absolute values of the energies, the ordering according to the relative energies of the transition structures leading to the different stereo- isomers remains the same.

TSl TS2

Fig. 1. Transition structures corresponding to the thermal Diels-Alder reaction of monothionofumaric acid with cyclopentadiene. TSl (carbonyl group endo); TS2 (thionocarbonyl group endo).

J. Gonzdez et al.lJournal of Molecular Structure (Theochem) 358 11995) 23-27 25

TS3 TS4

TS5 TS6

Fig. 2. Transition structures corresponding to the Diels-Alder reaction of carbonyl- (TS3. TS4) and thionocarbonyl-protonated (TS5, TS6) monothionofumaric acid with cyclopentadiene.

3. Results and discussion

The geometries of the transition structures for the Diels-Alder reaction of cyclopentadiene with monothionofumaric acid and the structures of the monothionofumaric acid protonated at the car- bony1 oxygen or at the thiocarbonyl sulphur were

optimized at the RHF/3-2lG* theory level. The transition structures located (TSl to TS6) are shown in Figs. 1 and 2, and their free activation energies, asynchronicities (Ar) and charge transfer (from diene to dienophile) are given in Table 1.

The transition structures corresponding to the thermal Diels-Alder reaction of cyclopentadiene

26 J. Gonzcilez et al./Journal of Molecular Structure (Theochem) 358 (1995) 23-27

Table 1 HF/3-21G* free ac$vation energies, AC* (kcalmol-‘)a, asyn-

chronicities, / Ar 1 (A), and charge transfer, CT (from diene to

dienophile)

Transition

structure

AC+ JArI CT

TS1 35.2

TS2 34.8

TS3 10.3

TS4 11.7

TSS 12.7

TS6 11.3

a Calculated at 2$8 K and 1 atm.

0.133 0.200

0.116 0.200

0.710 0.369

0.792 0.339

0.767 0.272

0.638 0.276

with monothionofumaric acid (TSl and TS2) are similar to those found for the Diels-Alder reac- tions of butadiene and cyclopentadiene with typical electron-deficient dienophiles such as acrolein [ 1 O] or methyl vinyl ketone [l 11. The transition struc- tures located show a slight asynchronicity, pith forming bond lengths of 02.290 and 2.157 A in TSl and 2.280 and 2.164A in TS2. As expected on the basis of the frontier molecular orbitals of the diene and dienophile, this is a normal demand Diels-Alder reaction, with a charge transfer of 0.20 electrons from the diene to the dienophile.

According to the RHF/3-21G* calculations, the transition structure TS2, in which the thionocar- bony1 group is endo, is more stable than the TSl by 0.4 kcal mol-’ (see Table l), the diastereomeric ratio 2 : 3 (calculated at 298 K) being predicted to be 66 : 34, which compares well with the experimen- tal value (70 : 30) measured in the reaction of cyclo- pentadiene with dimethyl monothionofumarate [4].

The most puzzling experimental result in the study of this reaction is the fact that, when the cycloaddition of cyclopentadiene and dimethyl monothionofumarate is carried out in the presence of a hard Lewis acid, the diastereomeric ratio is reversed and strongly increased, the en&-ester isomer becoming the major product (endo-thiono- ester/en&-ester ratio 4: 96). In order to obtain some insight into this effect, we selected the proton as an extreme example of a hard Lewis acid [6]. Four transition structures (TS3-TM, see Fig. 2 and Table 1) were located for the Diels-Alder reac- tion of carbonyl- and thionocarbonyl-protonated monothionofumaric acid with cyclopentadiene.

The first interesting effect of the Lewis acid is the drastic decrease in the reaction barrier (see Table 1) as compared with the thermal reaction. On the other hand, the transition structures located show an important increase in the asynchronicity (see Table 1). In all cases, the longest forming bond is that between cyclopentadiene and the carbon atom of the dienophile with the protonated group adja- cent. In addition, there is an increase in the charge transfer from the diene to the dienophile (see Table 1). These effects of the Lewis acids on the barrier, asynchronicity and charge transfer of the transition structures for the Diels-Alder reactions appear to be general according to previous theoretical studies on different systems [9,12]. The lowering of the reaction barrier and the increase in the length of the forming bonds in the catalysed case as com- pared with the thermal case seem to reflect the fact that these transition structures appear earlier in the reaction coordinate 1131.

As can be seen from data in Table 1, the most stable transition structure is that in which the oxygen of the carbonyl group is protonated (TS3). This effect suggests the preference in the isolated dienophile for oxygen coordination to the proton. In order to verify this assumption, the structures of both the oxygen- and sulphur- protonated monothionofumaric acid were opti- mized. The sulphur-protonated monothionofuma- ric is less stable than the oxygen-protonated system by 5.1 kcalcal-‘. This result is in good agreement with the predictions based on the prin- ciple of hard and soft acids and bases [ 141.

From Table 1, we can see that the transition structure TS3 in which the endo-carbonyl group or protonated is now the most stable form by 1 .O and 1.4 kcal mol-’ as compared with those having the exo-carbonyl group protonated (TS4) and the endo-thiocarbonyl group coordinated to the proton (TS6), respectively. Thus, in sharp contrast with the results corresponding to the thermal reactions, the formation of the stereoisomer 3 is now favoured, the diastereoisomeric ratio 2 : 3 (calcu- lated at 298 K) being predicted to be 16 : 84, in rea- sonable agreement with the experimental value (4 : 96) [4]. This result is consistent with the general rule that Lewis acid coordination increases the endo selectivity in Diels-Alder cycloadditions [3,9].

J. Gonzdlez et al./Journal of’ Molecular Structure (Theochem) 358 (199s) 23-27 ?l

It is interesting that the increase in the charge transfer from the diene to dienophile in the Lewis acid-catalysed transition structures as compared with those for the thermal reaction is higher in the case of the carbonyl-protonated systems (TS3 and TS4) than in the corresponding thiocarbonyl- protonated systems. This trend seems to be related to the previously mentioned preference of the proton for oxygen coordination. This is a typical hard-hard acid-base interaction in which, accord- ing to the principle of hard and soft acids and bases [14], the charge transfer is favoured. As the role of the Lewis acid catalysts in the Diels-Alder reac- tions is to increase the charge transfer from diene to dienophile, it can be expected, when a hard Lewis acid is used, that in the transition structure having the Lewis acid coordinated to the hard moiety of the dienophile (here TS3 and TS4) the charge transfer will be favoured as compared with the case in which the hard Lewis acid coordinates to the soft moiety of the dienophile (TS5 and TS6), thus enhancing the catalytic effect.

computer time in the CRAY YMP of the Centro de Investigaciones Energeticas y Medioambientales (CIEMAT), and also to the Centro de Proceso de Datos de la Universidad de Oviedo.

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4. Conclusions PI

The important effects of Lewis acid complexation on the stereoselectivity of the Diels-Alder reaction of monothionofumaric dienophiles have been studied ab initio. The good agreement between the theoretical results and the experimental find- ings indicates that this level of theory is, at least qualitatively, adequate for the study of this type of reaction. This conclusion opens up the poss- ibility of tackling further theoretical studies in order to address other important questions [4] such as the puzzling different behaviour observed when BF,OEtz and BCls Lewis acids are used or the role played by the soft Lewis acids derived from transition metals (e.g. Cu(OTf);!.

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PI [91

Acknowledgements

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The authors are grateful to the Comision Inter- ministerial de Ciencia y Tecnologia (Spain) for

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