Stable monopyrrole atropisomers

摘要

Malonic ester derivatives of ethyl and methyl 3,5-dimethyl-4-(1'-iodonepentyl)-1H-pyrrrole-2-carboxylate exhibit resitricted rotation about the pyrrole C(4)-C(1') bond due tothe bulky 1'-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 clas 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 rom 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=132-134kJ/mol(approx 32 kcal/mol) at 383K in C_2D_2Cl_4 solvent.