Studies Of Reactions Based On 4-isothiocyanato And Diazo Pyrazolones

Pyrazolone is a ubiquitous motifs found in various pharmaceuticals and bioactive molecules.In recent years,new synthetic methods for constructing structurely novel pyrazolones have been explored incessantly.Pyrazolones are powerful synthons for the synthesis of pyrazolone and pyrazole derivatives.Recently,numerous related compounds have been constructed from different pyrazolone synthons via organo-and metal-catalysts.Among them,4-isothiocyanato pyrazolones and 4-diazo pyrazolones are powerful substrates which were less studied.Therefore,asymmetric tandem reactions and metal carbene reactions were developed based on these two synthons to construct structurally novel pyrazolone derivatives,which led to the following results.The strategy of constructing spiropyrazolones has been developed.With 4-isothiocyanato pyrazolones and alkynyl ketones as substrates,a wide range of optically active spiropyrazolones with various electronic properties were accessed via an asymmetric[3+2]annulation catalyzed by quinine squaramide.This reaction delivered the products in high yields with good to excellent enantioselectivities.The strategy of constructing spiro[pyrrole-pyrazolone]heterocycles and structurally novel spiro[thiopyranopyrrole-pyrazolone]has been developed.With 4-isothiocyanato pyrazolones and allenyl ketones as the starting materials,spiro[pyrrole-pyrazolone]heterocycles and structurally novel spiro[thiopyranopyrrole-pyrazolone]were synthesized in the presence of quinine squaramide via catalytic asymmetric sequential annulation/aldol reaction.This reaction furnished a series of products in good yields with high to excellent enantioselectivities.Notably,parallel resolution of racemic spiro[pyrrole-pyrazolones]was achieved by catalyst-controlled asymmetric intramolecular vinylogous aldol process.The strategy of constructing difunctional pyrazolones has been developed.With allyl or propargyl sulfides and 4-diazopyrazolones as substrates,4-allyl-4-thiopyrazolones and 4-allenyl-4-thiopyrazolones were synthesized via Rh-catalyzed[2,3]-sigmatropic rearrangement.This strategy provides various 4-allyl(allenyl)-4-arylthio pyrazolones in good to excellent yields.The strategy of constructing novel Z/E-spiro[thiacycloalkene-pyrazolones]was developed.With 4-diazopyrazolones and 2-vinylthiochromanes as subsrates,a series of Z/E-spiro[thiacycloalkene-pyrazolones]were synthesized via Rh-catalyzed ring-expansion reaction.The reaction represents a unique approach for the construction of Z/E-spiro[thiacycloalkene-pyrazolones]with good stereoselectivity controlled by reaction temperature.The stereoselectivity of ring enlargement was also discussed.Besides,Cu-catalyzed ring-expansion/rearrangement reaction was also developed to construct trans-pyrazole polyheterocycles with 4-diazopyrazolones and 2-vinylthiochromanes as subsrates and a series of cis-pyrazole polyheterocycles were obtained under the Sc(OTf)3 catalysis with Z-spiro[thiocyclononene-pyrazolone]as the substrates.Then,a plausible mechanism to rationalize the formation of pyrazole-polyheterocycles is depicted.