Copper-catalyzed multicomponent reaction of ß-trifluoromethyl ß-diazo esters enabling the synthesis of ß-trifluoromethyl N,N-diacyl-ß-amino esters.

An efficient multicomponent reaction of newly designed ß-trifluoromethyl ß-diazo esters, acetonitrile, and carboxylic acids via an interrupted esterification process under copper-catalyzed conditions has been developed, which affords various unsymmetrical ß-trifluoromethyl N,N-diacyl-ß-amino esters in good to excellent yields. The reaction features mild conditions, a wide scope of ß-amino esters and carboxylic acids, and also applicability to large-scale synthesis, thus providing an efficient way for the synthesis of ß-trifluoromethyl ß-diacylamino esters. Furthermore, this reaction represents the first example of a Mumm rearrangement of ß-trifluoromethyl ß-diazo esters.

A Cu-promoted reaction of ß-keto trifluoromethyl amines enabling stereoselective synthesis of trifluoromethylated aziridines.

An efficient Cu(I) complex-promoted intramolecular cyclization reaction of ß-keto trifluoromethyl amines has been developed, providing access to a series of unprotected trifluoromethylated aziridines with good chemical yields and excellent stereoselectivity (trans : cis > 99 : 1). The reaction can be carried out under mild conditions and tolerates a wide range of substrates with diverse functional groups, representing a straightforward method for the preparation of trifluoromethylated aziridines from readily available starting materials.

Assembly of trifluoromethylated fused tricyclic pyrazoles via cyclization of ß-amino cyclic ketones.

Fused polycyclic pyrazoles are an important class of heterocyclic compounds; thus, the development of efficient methods for their preparation becomes highly urgent. Herein, we reported an efficient method for the synthesis of trifluoromethylated fused tricyclic pyrazoles via intramolecular cyclization of cyclic ketone-derived amines. Mechanistic studies provide evidence for the in situ generation of trifluoromethylated ß-diazo ketones as intermediates via diazotization with the use of tert-butyl nitrite. The synthetic utility of this method is highlighted by scale-up synthesis and the derivatization of the obtained fused tricyclic pyrazole products.