Stable monopyrrole atropisomers

Malonic ester derivatives of ethyl and methyl 3,5-dimethyl-4-(1'-iodoneopentyl)1H-pyrrole-2-carboxylate exhibit restricted rotation about the pyrrole C(4)-C(1') bond due to the bulky V-tert-butyl and malonic ester groups and the ortho effect at C(4) of the sterically crowded 3,5-dimethylpyrrole. The malonates belong to a rare class of atropisomers with restricted rotation about an sp(3)-sp(2) C-C bond, and they undergo diastereomeric separation by TLC and crystallization: the diastereomers are stable in solution at room temperature. A crystal of one of the diastereomers, suitable for X-ray crystallography, gave the relative configuration of the chiral axis and stereogenic center at C(1'). Dynamic NMR studies of the purified diastereomers provide kinetic and thermodynamic parameters associated with the atropisomerism: DeltaG(double dagger) = 132-134 kJ/mol (similar to32 kcal/mol) at 383 K in C2D2Cl4 solvent.