Experimental and theoretical study of the influence of the solvent on asymmetric diels—alder reactions

Abstract

Rate, endo/exo and diastereofacial selectivities of the Diels–Alder reaction between cyclopentadiene and (—)‐menthyl acrylate were measured in a series of organic solvents and organic–aqueous mixtures. Regression analyses show that a model with the α empirical solvent parameter accounts for most of the changes in rates and diastereofacial selectivities, whereas in the case of the endo/exo selectivity, inclusion of the π* and δ parameters is needed. Theoretical calculations carried out on the model reaction between methyl acrylate and cyclopentadiene using dielectric continuum and supermolecule models do not clearly show the effect of the different solvation mechanisms on rate. However, they agree with the above‐mentioned influence of α and π* on the endo/exo and diastereofacial selectivities.

Rationalisation of Solvent Effects in the DielsAlder Reaction Between Cyclopentadiene and Methyl Acrylate in Room Temperature Ionic Liquids

“…The cycloaddition of cyclopentadiene to methyl acrylate (Scheme 1) is perhaps the most intensively studied Diels-Alder reaction, and has been conducted in organic solvents, [2,6,19,20] water [7,8] and in a series of room temperature ionic liquids. [11,13,14,16,18,21] As such, the reaction was chosen for the study described herein.…”

“…Cativiela and co-workers correlated the selectivity in the cycloaddition of cyclopentadiene to (À)-menthyl acrylate with the Kamlet-Taft parameters for organic solvents. [6] They concluded that all types of interaction (p* -non-specific, mainly coulombic, a -hydrogen bond donor acity -as well as b -hydrogen bond acceptor basity) contributed to the overall selectivity, although the relative contribution of a was about twice that of b.…”

“…[5] The Diels-Alder reaction has been extensively studied in organic solvents and in water and, in general, higher reaction rates and selectivities are obtained in polar solvents rather than non-polar solvents. [6] Often, the reaction rates and endo:exo product selectivities are higher in aqueous solution. [7] These effects have been attributed to enhanced hydrogen bonding between the solvent and the transition state, as well as to enforced hydrophobic interactions, essentially creating a hydrophobic pocket, which facilitates alignment of the substrates.…”

Diels_Alder reactions in water

“…The term "enforced" is used to stress the fact that the association of the nonpolar reagents is driven by the reaction and only enhanced by water. Other solvent effect studies by a large number of authors further demonstrated that reactivity is primarily determined by two solvent parameters: the hydrogen-bond donating capacity and the solvophobicity [14]. This pattern strongly suggests that in water, a hydrogen-bond donating solvent par excellence, the Diels-Alder reaction benefits not only from enforced hydrophobic interactions but also from hydrogen-bonding interactions.…”

“…Mechanistic investigations have been carried out on the reaction between cyclopentadiene and (1R,2S,5R)-menthyl acrylate, which has been shown to be dominated by the hydrogen-bond donor characteristics of the solvent together with its polarity [14].…”