An efficient self-assembled methanoproline–thiourea organocatalyst for the synthesis of optically active 6-isopropyl-3,4-dihydro-pyrimidines via an asymmetric Biginelli reaction was developed, which is superior to the individual precatalyst. A wide range of optically active 6-isopropyl-3,4-dihydropyrimidines with remarkable pharmacological interest was obtained in high yields with excellent enantioselectivities (up to 99% ee). A plausible transition state has been proposed to explain the origin of the activation and the asymmetric induction.