Structure of a minor reaction product formed via base promoted hydrolysis of Thiele's ester

Base promoted hydrolysis of dimethyl 3a α ,4 α ,7 α ,7a α -tetrahydro-4,7-methano-l H -indene-2,5-dicarboxylate (i


Introduction
Carbonation of sodium cyclopentadienide leads to the formation of 3aα,4α,7α,7aα-tetrahydro-4,7-methano-lH-indene-2,6-dicarboxylic acid 1 [i.e., "Thiele's acid", 1, 60%] along with several isomeric C 12 H 12 O 4 minor products. 2Recently, our attention has turned to Thiele's acid as a potentially useful intermediate in the synthesis of unusual polycarbocyclic systems. 2,3n connection with ongoing research projects, it was necessary for us to prepare isomerically pure Thiele's acid in quantity.To this end, the crude mixture of carboxylic acids obtained via carbonation of sodium cyclopentadienide was esterified by using MeOH-H 2 SO 4 .Pure Thiele's ester, 2 (Scheme 1), mp 85 °C, 1 could be isolated in good yield via fractional recrystallization of the mixture of esterification products from 10% EtOAc-hexane mixed solvent.

Scheme 1
Subsequently, purified Thiele's ester was subjected to base promoted hydrolysis by using KOH-MeOH followed by aqueous acidic workup.As expected, Thiele's acid was obtained as the major reaction product.Pure Thiele's acid was obtained in an overall yield of 47% via application of the reaction sequence shown in Scheme 1.In addition, this material was accompanied by a second, minor product, 3, which was obtained in 10% yield.Inspection of the 1 H and 13 C NMR spectra of 3 suggested that base promoted hydrolysis of 2 might have been accompanied by Michael addition of MeO -to one of the two nonequivalent α,β-unsaturated ester moieties in 2.
Apropos of the present study, we recently elucidated the structure of a minor reaction product, 3c (Scheme 2), formed during acid promoted esterification of Thiele's acid. 4The similarity between 1 H and 13 C NMR spectra of 3 and 3c suggested that these two compounds are structurally very similar.However, on the basis of NMR spectral analysis alone, a clear choice could not be made between structures 3a and 3b for the minor product, 3, formed via reaction of 2 with KOH-MeOH.Accordingly, we turned to single crystal X-ray crystallographic analysis to provide unequivocal resolution to this question.

Results and Discussion
X-Ray crystal structure of the minor reaction product formed via base promoted hydrolysis of 2. A thermal ellipsoid plot of the minor reaction product, 3, is shown in Figure 1; the corresponding packing diagram, which shows intermolecular interactions, is presented in Figure 2. Therein, it can be seen that the minor reaction product possesses structure 3a rather than 3b.Crystal and refinement data for 3a are presented in Table 1.
As with most carboxylic acids, the molecules form strongly hydrogen bonded dimers, [see Figure 3; therein, O(5)-H(14     Mechanistic rationalization.Thiele's ester contains two α,β-unsaturated ester moieties, either or both of which might undergo Michael addition by methoxide ion.One of these moieties contains a norbornene C=C double bond, whereas the C=C double bond in the remaining α,βunsaturated ester moiety resides in a cyclopentene ring.In our hands, Michael addition of MeO - occurred exclusively at the β-position in the norbornene C=C double bond to afford 3a.It is likely that relief of additional steric strain present in the norbornene C=C vis-à-vis that associated with the cyclopentene C=C provides a driving force for nucleophilic attack at the former position.The fact that attack by MeO -occurs preferentially via the exo face of the norbornene C=C bond is consistent with earlier observations 5 with regard to the course of conjugate addition of nucleophiles to methyl 2-norborna-2,5-dienecarboxylate.Furthermore, the additional strain present in the norbornene C=C is expected to destabilize the ground state resonance form, 2a (Scheme 3), relative to the higher energy, charge-separated canonical form, 2b (Scheme 3), thereby minimizing norbornene C=C double bond character in the resonance hybrid.This effect is expected to render the carbon atom βto the C=O group in the norbornene α,β-unsaturated ester moiety more highly electrophilic (due to increased δ + charge at the β-carbon atom in the resonance hybrid) than would be the case in the less highly strained α,β-unsaturated ester system situated within the cyclopentene ring in Thiele's ester.As a consequence, the norbornene C=C is rendered more highly reactive toward nucleophilic attack by MeO -, a conclusion that is consistent with our experimental observations.

Scheme 3
Finally, the somewhat increased importance of the resonance contribution of the chargeseparated canonical form in the norbornene α,β-unsaturated ester moiety, i.e., 2b, is expected to reduce the C=O double bond character in the associated ester group, thereby rendering this CO 2 Me group more resistant to base promoted hydrolysis than the corresponding ester group in the cyclopentene α,β-unsaturated ester moiety.The conclusion that the cyclopentene CO 2 Me group in Thiele's ester thus is expected to be the more highly susceptible of the two ester functionalities toward base promoted ester hydrolysis is consistent with the experimentally observed preferential formation of 3a.

Experimental Section
General Procedures.Melting points are uncorrected.High-resolution mass spectral data reported herein were obtained at the Mass Spectrometry facility at the Department of Chemistry and Biochemistry, University of Texas at Austin, by using a ZAB-E double sector highresolution mass spectrometer (Micromass, Manchester, England) that was operated in the chemical ionization mode.

Figure 3 .
Figure 3. Thermal ellipsoid plot of the hydrogen bonded dimer of 3a.

Table 1 .
Crystal data and structure refinement for 3a