One-Pot Synthesis of 1-Aryl-3-trifluoromethylpyrazoles Using Nitrile Imines and Mercaptoacetaldehyde As a Surrogate of Acetylene.

A synthetically useful approach for one-pot preparation of 1-aryl-3-trifluoromethylpyrazoles using in situ generated nitrile imines and mercaptoacetaldehyde applied as 1 equiv of acetylene is presented. This protocol comprises (3 + 3)-annulation of the mentioned reagents to form 5,6-dihydro-5-hydroxy-4H-1,3,4-thiadiazine, followed by cascade dehydration/ring contraction reactions with p-TsCl. In addition, representative nonfluorinated analogues functionalized with Ph, Ac, and CO2Et groups at the C(3)-position of the pyrazole ring were also prepared by the devised method.

Trifluoromethylated 4,5-Dihydro-1,2,4-triazin-6(1H)-ones via (3+3)-Annulation of Nitrile Imines with α-Amino Esters.

The synthesis of two series of monocyclic and bicyclic trifluoromethylated 4,5-dihydro-1,2,4-triazin-6(1H)-one derivatives based on (3+3)-annulation of methyl esters derived from natural α-amino acids with in situ generated trifluoroacetonitrile imines has been described. The devised protocol is characterized by a wide scope, easily accessible substrates, remarkable functional group tolerance, and high chemical yield. In reactions with chiral starting materials, no racemization at the stereogenic centers was observed and the respective enantiomerically pure products were obtained. Selected functional group interconversions carried out under catalytic hydrogenation and mild PTC oxidation conditions were also demonstrated.