SOLVENT DEPENDENCE OF ENANTIOSELECTIVITY FOR A BASE-CATALYZED 1,3-HYDRON TRANSFER-REACTION - A KINETIC ISOTOPE EFFECT AND NMR SPECTROSCOPIC STUDY

The base-catalyzed rearrangement of 1-methylindene (1) to 3-methylindene (2) has been studied. The reaction proceeds with substrate enantioselectivity (kinetic resolution) when chiral tertiary amines are used as catalysts. When dihydroquinidine (DHQD) (3) is used to accomplish the 1,3-hydron shift, the enantioselectivity shows a change of sense when the solvent is changed from o-dichlorobenzene (o-DCB) (k(+)/k(-) = 3.70) to dimethyl sulfoxide (DMSO) (k(+)/k(-) = 0.579). The enantiomer-dependent primary deuterium kinetic isotope effects (KIEs) have been determined to (k(H)/k(D))(+) = 5.30 and (k(H)/k(D))(-) = 5.86 in o-DCB and (k(H)/k(D))(+) = 7.76 and (k(H)/k(D))(-) = 8.26 in DMSO, respectively. The enantioselectivity was found to decrease slightly with increasing concentration of the catalyst. Using (p-chlorobenzoyl)dihydroquinidine (p-CIBzDHQD) (4) as catalyst in o-DCB yields the same sense of the enantioselectivity (k(+)/k(-) = 0.502) as dihydroquinidine (3) in DMSO. The conformational properties of the alkaloid DHQD (3) in the solvents acetone, chloroform, DMSO, dioxane, o-DCB, and tetrahydrofuran and of p-ClBzDHQD (4) in o-DCB and chloroform were investigated by means of H-1 NMR spectroscopy. The observed solvent dependence of the enantioselectivity is rationalized in terms of the conformational composition of the cinchona alkaloid catalyst.