Study Of Asymmetric Synthesis Based On Pyrazolones

One-pot synthesis is an efficient, simple and practical method in synthetic chemistry. Catalystic asymmetric synthesis is the most effective way to obtain enantiomerically pure compouds. The compounds which contain pyrazolones heterocycle structure possess potential biological activity. Thus, synthesize these pyrazolones compounds of containing chiral center high selectively has certain significance in theory and practice. As a resault using’one-pot’-process to synthesize asymmetrical pyrazolones compounds has become a hot topic and difficult point in chemical sciences research.Based on rationally designed and screened of optimal conditions:0.2equiv. quinidine thiourea as catalyst, and ether as solvent, after unsaturated pyrazolone1.0equiv. react with1.2equiv.1,3-dicarbonyl compounds, completely finished under-10℃. Then,1.0equiv. α,β-unsaturated aldehyde was added, via a sequential Michael/Michael/Aldol reaction to afford optically active (up to99:1dr, up to95%ee) highly substituted spirocyclo hexanepyrazolones which have up to six consecutive stereogenic carbon centers including two quaternary stereocenters and four tertiary stereocenters. In the end we determined the molecular absolute configuration by X-ray diffraction. In conclusion, we have first one-pot synthesis of these compounds.In addition, when enhanced the positive electricity of one carbonyl in1,3-dicarbonyl compounds under the same conditions, unsaturated pyrazolones react with1,3-dicarbonyl compounds catalysed by quinidine thiourea via a sequential Michael/Aldol reaction highly diastereoselective synthesized (up to99:1dr) tetrahydropyrano[2,3-c]pyrazoles compounds which possess one quaternary stereocenters and two tertiary stereocenters.