a computational examination of diels–alder reactions with 1,3-cyclopentadienes bearing anionic and...

4
Pergamon Tetrahedron Letters 41 (2000) 995–998 TETRAHEDRON LETTERS A computational examination of Diels–Alder reactions with 1,3- cyclopentadienes bearing anionic and cationic substituents at C-5 James D. Xidos, Raymond A. Poirier and D. Jean Burnell * Department of Chemistry, Memorial University of Newfoundland, St. John’s, Newfoundland A1B 3X7, Canada Received 1 November 1999; accepted 30 November 1999 Abstract Ab initio calculations predict that deprotonation and protonation of 5-heterosubstituted 1,3-cyclopentadienes would significantly modify their facial selectivities in Diels–Alder additions. Anionic substituents enhance syn- addition, and cationic substituents promote anti-addition, relative to the neutral dienes. Stereoelectronic and steric effects together determine the facial selectivity of ionic dienes. © 2000 Elsevier Science Ltd. All rights reserved. Keywords: Diels–Alder reactions; cyclopentadienes; electronic effects; steric and strain effects. An important synthetic consideration in Diels–Alder chemistry is facial selectivity (e.g. Fig. 1). This is often a very selective process that is predictable in a straightforward way by estimation of the steric hindrance on either side of a plane-nonsymmetric diene or dienophile. Some heteroatom-substituted dienes, such as 13 and 6, undergo Diels–Alder reactions to give predominantly syn-addition products. 1,2 This seems inconsistent with steric control. A number of stereoelectronic phenomena have been proposed to control these reactions, 1,3 but we showed computationally that steric factors are still dominant in determining the facial selectivity with 16, as well as many other 5-substituted 1,3-cyclopentadienes. 4 However, it would be important, on both the fundamental and synthetic levels, if stereoelectronic factors could be provoked to take over control of facial selectivity with this type of diene. This idea has been explored computationally by a comparison of the reactions of 1, 2, 4, and 5, for which facial selectivities with the neutral dienes have been studied computationally, 4 and to some extent experimentally, 1,2 with the reactions of their deprotonated (anionic) and protonated (cationic) analogues. The transition states (TS) for the syn- and anti-additions of ethylene to 1, 2, 4, and 5 in their neutral, deprotonated and protonated forms were located with MUNGAUSS 5 at the HF/6-31++G(d)//HF/6- 31++G(d) level. 6–8 The data in Table 1 show that ionization of the substituent should have a profound effect on the facial selectivity. Isodesmic relationships provide reliable estimates of energies at the HF level, so the hypothetical reaction in Fig. 2 was employed to provide the isodesmic energy differences (ΔE iso ) shown in Table 1. A negative value of ΔE iso indicates stabilization of the transition state by the * Corresponding author. Tel: (709) 737-8535; fax: (709) 737-3702; e-mail: [email protected] (D. J. Burnell) 0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved. PII: S0040-4039(99)02225-X tetl 16153

Upload: james-d-xidos

Post on 02-Jul-2016

216 views

Category:

Documents


1 download

TRANSCRIPT

Page 1: A computational examination of Diels–Alder reactions with 1,3-cyclopentadienes bearing anionic and cationic substituents at C-5

Pergamon Tetrahedron Letters 41 (2000) 995–998

TETRAHEDRONLETTERS

A computational examination of Diels–Alder reactions with 1,3-cyclopentadienes bearing anionic and cationic substituents at C-5

James D. Xidos, Raymond A. Poirier and D. Jean Burnell�

Department of Chemistry, Memorial University of Newfoundland, St. John’s, Newfoundland A1B 3X7, Canada

Received 1 November 1999; accepted 30 November 1999

Abstract

Ab initio calculations predict that deprotonation and protonation of 5-heterosubstituted 1,3-cyclopentadieneswould significantly modify their facial selectivities in Diels–Alder additions. Anionic substituents enhancesyn-addition, and cationic substituents promoteanti-addition, relative to the neutral dienes. Stereoelectronic and stericeffects together determine the facial selectivity of ionic dienes. © 2000 Elsevier Science Ltd. All rights reserved.

Keywords:Diels–Alder reactions; cyclopentadienes; electronic effects; steric and strain effects.

An important synthetic consideration in Diels–Alder chemistry is facial selectivity (e.g. Fig. 1). Thisis often a very selective process that is predictable in a straightforward way by estimation of the sterichindrance on either side of a plane-nonsymmetric diene or dienophile. Some heteroatom-substituteddienes, such as1–3 and6, undergo Diels–Alder reactions to give predominantlysyn-addition products.1,2

This seems inconsistent with steric control. A number of stereoelectronic phenomena have been proposedto control these reactions,1,3 but we showed computationally that steric factors are still dominant indetermining the facial selectivity with1–6, as well as many other 5-substituted 1,3-cyclopentadienes.4

However, it would be important, on both the fundamental and synthetic levels, if stereoelectronic factorscould be provoked to take over control of facial selectivity with this type of diene. This idea has beenexplored computationally by a comparison of the reactions of1, 2, 4, and5, for which facial selectivitieswith the neutral dienes have been studied computationally,4 and to some extent experimentally,1,2 withthe reactions of their deprotonated (anionic) and protonated (cationic) analogues.

The transition states (TS) for thesyn- andanti-additions of ethylene to1, 2, 4, and5 in their neutral,deprotonated and protonated forms were located with MUNGAUSS5 at the HF/6-31++G(d)//HF/6-31++G(d) level.6–8 The data in Table 1 show that ionization of the substituent should have a profoundeffect on the facial selectivity. Isodesmic relationships provide reliable estimates of energies at the HFlevel, so the hypothetical reaction in Fig. 2 was employed to provide the isodesmic energy differences(�Eiso) shown in Table 1. A negative value of�Eiso indicates stabilization of the transition state by the

� Corresponding author. Tel: (709) 737-8535; fax: (709) 737-3702; e-mail: [email protected] (D. J. Burnell)

0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.PI I: S0040-4039(99)02225-X

tetl 16153

Page 2: A computational examination of Diels–Alder reactions with 1,3-cyclopentadienes bearing anionic and cationic substituents at C-5

996

Fig. 1. Diels–Alder facial selectivity with 5-substituted 1,3-cyclopentadienes

ionic center, and a positive�Eiso indicates destabilization by ionization. With the deprotonated dienes, thetransition states forsyn-addition are stabilized relative to those of the neutral dienes, and foranti-additionthe transition states are destabilized.syn-Addition to a protonated diene is energetically similar to that ofaddition to the neutral diene, but the energy foranti-addition is very much lowered in the reactions of theprotonated dienes. Thus, deprotonation enhancessyn-addition and protonation enhancesanti-addition,and changes in facial selectivity are the result of lowering�Eact for eithersyn- or anti-addition. This issynthetically very important because it implies that nonstoichiometric methods of ionization could bewell suited to bring about changes, even reversals, in facial selectivity.

Table 1Activation energies, predicted facial selectivities, and isodesmic energies for additions of ethylene to

5-substituted-1,3-cyclopentadienes

While changes inanti-addition energies suggest that a stereoelectronic factor has indeed emergedas an important contributor to facial selectivity, what is the relative importance of steric hindrance indetermining facial selectivity with ionic dienes? This question was approached in the same way as hadbeen done with the neutral dienes, for which facial selectivity correlated extremely well with a computed

Page 3: A computational examination of Diels–Alder reactions with 1,3-cyclopentadienes bearing anionic and cationic substituents at C-5

997

Fig. 2. Isodesmic ‘reaction’ for assessing the relative stabilities of thesyn-andanti-Diels–Alder transition states with ionized(X�) versus neutral (X0) C-5 substituents

Table 2Computed steric factors and estimates of diene deformation as both angular change and diene

deformation energy for additions of ethylene to 5-substituted 1,3-cyclopentadienes

Fig. 3. (a) Plot of diene deformation energy versus activation energy; (b) plot of computed steric factor4b versus activationenergy.syn-Transition states are circles: anionic=shaded, neutral=unfilled, cationic=black;anti-transition states, in (a), aresquares

steric factor (�C–X).4b In the study with neutral dienes, it had been shown that there is a correlationbetween�Eact and the amount of angular change about C-5 of the diene on going from the ground state

Page 4: A computational examination of Diels–Alder reactions with 1,3-cyclopentadienes bearing anionic and cationic substituents at C-5

998

to the transition state. In turn, the energy needed to deform the diene (�Ediene) into the transition stategeometries forsyn- andanti-addition clearly paralleled the facial selectivity, whereas neither dienophiledeformation energy nor the ‘interaction energy’, i.e., the remainder after subtracting both diene anddienophile deformation energies from�Eact, correlated significantly with facial selectivity.4b In Table2, the extent of angular change about C-5 (��) is presented for both thesyn- and theanti-transitionstates. It is not obvious that there is a correlation between�� and the facial selectivity, presumablybecause stereoelectronic effects can stabilize deformation. The diene deformation energies (�Ediene) arefairly similar for all theanti-transition states. However, for thesyn-transition states, a plot of�Ediene

versus�Eact (Fig. 3a) reveals a good correlation for each similarly-ionized set. Thus, forsyn-transitionstates, the activation energy is determined by a stereoelectronic factor that is fairly constant for aparticular charge, and a diene deformation energy that is variable. Furthermore, a plot of steric factors,computed as described previously,4b versus the activation energy (Fig. 3b) is obviously similar to thatshown in Fig. 3a, which is consistent with a variable steric component in the activation energy. (Plotsof dienophile deformation energies and interaction energies reveal no significant correlations with theactivation energy.)

In conclusion, deprotonation of the heteroatom substituent enhances additionsyn to the heteroatom,and protonation of the heteroatom enhances additionanti to the heteroatom. The facial selectivity can beascribed to a stereoelectronic factor, which is approximately constant for a given charge, and to a variabledegree of steric hindrance, which is reflected mainly in the energy required to deform the diene into itstransition state geometry.

Acknowledgements

Financial support from the Natural Sciences and Engineering Research Council of Canada is gratefullyacknowledged.

References

1. (a) Winstein, S.; Shatavsky, M.; Norton, C.; Woodward, R. B.J. Am. Chem. Soc.1955, 77, 4183. (b) Mironov, V. A.; Dolgaya,M. E.; Lukyanov, V. T.; Yankovskii, S. A.Zh. Organich. Khim.1976, 12, 1436. (c) Wellman, M. A.; Burry, L. C.; Letourneau,J. E.; Bridson, J. N.; Miller, D. O.; Burnell, D. J.J. Org. Chem.1997, 62, 939.

2. (a) Macaulay, J. B.; Fallis, A. G.J. Am. Chem. Soc.1990, 112, 1136. (b) McClinton, M. A.; Sik, V.J. Chem. Soc., PerkinTrans. 11992, 1891. (c) Ishida, M.; Kakita, S.; Inagaki, S.Chem. Lett.1995, 469.

3. (a) Anh, N. T.Tetrahedron1973, 29, 3227. (b) Inagaki, S.; Fujimoto, H.; Fukui, K.J. Am. Chem. Soc.1976, 98, 4054. (c)Kahn, S. D.; Hehre, W. J.J. Am. Chem. Soc.1987, 109, 663. (d) Fallis, A. G.; Lu, Y.-F. InAdvances in Cycloaddition; Curran,D. P., Ed.; JAI Press: Greenwich, CT, 1993; Vol. 3, pp. 1–66. (e) Cieplak, A. S.Chem. Rev.1999, 99, 1265.

4. (a) Poirier, R. A.; Pye, C. C.; Xidos, J. D.; Burnell, D. J.J. Org. Chem.1995, 60, 2328. (b) Xidos, J. D.; Poirier, R. A.; Pye,C. C.; Burnell, D. J.J. Org. Chem.1998, 63, 105.

5. (a) Poirier, R. A.; Wang, Y.; Pye, C. C.; Xidos, J. D. MUNGAUSS V1.1; Department of Chemistry, Memorial Universityof Newfoundland, St. John’s, Newfoundland, Canada. (b) Colonna, F.; Jolly, L.-H.; Poirier, R. A. Angyan, J. G.; Jansen, G.Comput. Phys. Commun.1994, 81, 293.

6. Clark, T.; Chandrasekhar, J.; Spitznagel, G. W.; Schleyer, P. v. R.J. Comp. Chem.1983, 4, 294.7. Analytical force constants were evaluated to ensure that ground state molecules had no imaginary frequencies and that

transition states were first-order saddle-points.8. A transition state for theanti-addition of protonated2 could not be found at the HF/6-31++G(d)//HF/6-31++G(d) level;

dissociation of the C–O bond is predicted instead. However, an hypotheticalanti-transition state was approximated by fixingthe C–O bond to a length consistent with that seen in otheranti-transition states.