Highly Enantioselective Biginelli Reaction Promoted By Chiral Bifunctional Primary Amine-Thiourea Catalysts

3,4-Dihydropyrimidin-2(H)-ones have received great attention in organic synthetic chemistry due to their biological importance. In this dissertation, the application of the bifunctional thiourea organocatalysts in asymmetric synthesis as well as the synthetic methods of optically active 3,4-dihydropyrimidin-2(H)-ones and their derivatives were reviewed. In order to find new ways to synthesize optically active Dihydropyrimidin-2(H)-ones, we synthesized a series of simple bifunctional thiourea organocatalysts. Using CH2Cl2 and brine as solvent, we synthesized optically active 3,4-dihydropyrimidin-2(H)-ones and their derivates under different conditions. At the same time, we synthesized a series of racemic 3, 4-dihydropyrimidin-2(H)-ones and their derivates using a convenient and green method. Their structures were confirmed by 1H NMR,13C NMR, ESI-MS, FTIR and elemental analysis. Some of the target compounds were recrystallized and their structures were determined by X-ray diffraction analysis.The first part of optically active 3,4-dihydropyrimidin-2(H)-ones and their derivates have been achieved in high yields and high enantioselectivity via Biginelli reaction. The reaction was proceeded by using chiral bifunctional primary amine-thiourea as catalyst and 2,4,6-trichlorobenzoic acid as combined catalyst in CH2Cl2 in the same time 10 mol% BuNH2TFA was added. Aldehyde, urea/thiourea and ethyl acetoacetate were converted to dihydropyrimidin-2(H)-ones and their derivates, giving ratios of enantiomers higher than 99%. This procedure provides a rapid access to biologically important 3,4-dihydropyrimidin-2(H)-ones and their derivates. The structure was confirmed by X-ray diffraction analysis and the absolute configuration S was known by comparison of the optical rotation with the literature. Using a matched catalyst, we can achieved products with the absolute configuration R.The second part of optically active 3,4-dihydropyrimidin-2(H)-ones and their derivates have been achieved in water with shorte reaction time. The reaction was using the salt of chiral bifunctional primary amine-thiourea and trifluoromethanesulfonic acid as a chiral phase-transfer catalyst and 10 mol% BuNH2-TFA was added in saturated brine. Aldehyde, urea/thiourea and ethyl acetoacetate were converted to dihydropyrimidin-2(H)-ones and their derivates via Biginelli Reaction. Compared to the former work, this procedure provides a rapid access to optically active dihydropyrimidin-2(H)-ones and their derivates as well as greener system by using brine as solvent. The absolute configuration S was known by comparison of the optical rotation with the literature and by using a matched catalyst, we can obtain products with the opposite absolute configuration.The third part of racemic 3,4-dihydropyrimidin-2(H)-ones and their derivates have been obtained using a simple and fast way. Aldehydes, urea or thiourea,β-ketoester and 20mol% conc. hydrochloric acid were converted to biologically important dihydropyrimidin-2(H)-ones and their derivates quickly. The simplicity of the catalytic procedure and its environmentally benign make this catalytic reaction a potential, environmentally acceptable method for the synthesis of dihydropyrimidinones and applicability of the techniques for larger volume system as well.