3-Trifluoromethyl Pyrrole Synthesis Based on ß-CF3-1,3-Enynamides.

A new metal-free method for the rapid, productive, and scalable preparation of 3-trifluoromethyl pyrroles has been developed. It is based on the electrophilic nature of the double bond of ß-CF3-1,3-enynamides due to the electron-withdrawing characteristics of the trifluoromethyl groups and the strong nucleophilic nature of alkyl primary amines. Evidence for the highly regioselective 1,4-hydroamination was observed after the isolation and characterization of the allenamide intermediate.

Versatile Fluorine-Containing Building Blocks: ß-CF3-1,3-enynes.

The development of diversity-oriented synthesis based on fluorine-containing building blocks has been one of the hot research fields in fluorine chemistry. ß-CF3-1,3-enynes, as one type of fluorine-containing building blocks, have attracted more attention in the last few years due to their distinct reactivity. Numerous value-added trifluoromethylated or non-fluorinated compounds which have biologically relevant structural motifs, such as O-, N-, and S-heterocycles, carboncycles, fused polycycles, and multifunctionalized allenes were synthesized from these fluorine-containing building blocks. This review summarizes the most significant developments in the area of synthesis of organofluorine compounds based on ß-CF3-1,3-enynes, providing a detailed overview of the current state of the art.

Synthesis of Trifluoromethylated 4H-Pyran and 4H-Thiopyran via Divergent Reaction of ß-CF3-1,3-Enynes with ß-Ketothioamides.

A chemodivergent tandem intermolecular hydrocarbonation and intramolecular oxy- or thioheterocyclization sequence of ß-CF3-1,3-enyne with ß-ketothioamides (KTAs) leading to ring-trifluoromethylated 4H-pyran or 4H-thiopyran, respectively, by the combined use of AgNO3 as a catalyst and Et3N as a base was developed. A remarkable substituent effect was observed. The substituent on either the keto moiety or the nitrogen atom of ß-ketothioamides has a great impact on the chemoselectivity. Enynes possessing electron-withdrawing aryl groups on the alkyne moiety are generally good candidates for the present transformation.

Synthesis of Trifluoromethylated Pyrazolidines, Pyrazolines and Pyrazoles via Divergent Reaction of ß-CF3-1,3-Enynes with Hydrazines.

Three types of trifluoromethylated pyrazolidines, pyrazolines, and pyrazoles can be synthesized via divergent reaction of ß-CF3-1, 3-enyne with hydrazines. The reaction with simple hydrazine monohydrate or sulfonyl hydrazines as nucleophiles produces 1,3,4-trisubstituted pyrazolines, whereas the reaction with acetyl hydrazine as nucleophiles affords 1,4,5-trisubstituted pyrazolidines. Using phenylhydrazine or tert-butylhydrazine as a reaction partner, the products are easily oxidized to form 1,4,5-trisubstituted pyrazoles.