Organocatalytic Enantioselective Nucleophilic Alkynylation of Allyl Fluorides Affording Chiral Skipped Ene-ynes.

Asymmetric methods for preparation of chiral alkynyl-containing compounds are in extremely high demand in many sectors of chemical research. In this work, we report the discovery of a general organocatalytic enantioselective alkynylation based on the idea of Si/F activation of the allylic C-F bond. This approach features reasonably broad substrate scope, functional group tolerance, and relatively neutral, mild, and operationally convenient reaction conditions; all of which bode well for the synthetic value of the discovered method. In particular, this method provides unique chiral skipped 1,4-ene-ynes having two kinds of versatile functional groups.

Regioselective 1,4-trifluoromethylation of α,ß-unsaturated ketones via a S-(trifluoromethyl)diphenylsulfonium salts/copper system.

Regioselective conjugate 1,4-trifluoromethylation of α,ß-unsaturated ketones by the use of shelf-stable electrophilic trifluoromethylating reagents, S-(trifluoromethyl)diphenylsulfonium salts and copper under mild conditions is described. A wide range of acyclic aryl-aryl-enones and aryl-alkyl-enones were converted into ß-trifluoromethylated ketones in low to moderate yields.

Organocatalytic asymmetric synthesis of trifluoromethyl-substituted diarylpyrrolines: enantioselective conjugate cyanation of ß-aryl-ß-trifluoromethyl-disubstituted enones.

Ether way: the cinchona-alkaloid-catalyzed title reaction was achieved in high yields with high to excellent ee values for the first time, and affords key intermediates for the biologically important 2 having a trifluoromethylated all-carbon quaternary chiral center. Ether-type catalysts (1) are more efficient in this transformation than the conventional hydroxy analogues.

Alkynyl Cinchona Catalysts affect Enantioselective Trifluoromethylation for Efavirenz under Metal-Free Conditions.

Efavirenz is manufactured worldwide, and its asymmetric synthesis requires a complex organometallic approach, while an organocatalytic approach is far less efficient. The first highly enantioselective approach is disclosed for the synthesis of Efavirenz under nonmetal organocatalysis with up to 93% ee for the Merck intermediate and 91% ee for the Lonsa intermediate using novel alkynyl cinchona catalysts.

Difluoromethylation of Terminal Alkynes by Fluoroform.

The difluoromethylation of terminal alkynes through the use of fluoroform as a source of difluorocarbene is described. The choice of solvents and bases was found to be crucial for the transformation. A series of terminal alkynes 1 were nicely converted into the corresponding difluoromethyl alkynes 2 using potassium tert-butoxide in n-decane in moderate to good yields. Functional groups such as methoxy, dimethylamino, and bromo as well as phenyl, heteroaryl, and sterically demanding naphthyl were well tolerated under the reaction conditions. One-step transformations of difluoromethyl alkynes 2 to difluoromethylated isoxazoles 3 and 1,2,3-triazoles 4 were also achieved.

Organocatalyzed Trifluoromethylation of Ketones and Sulfonyl Fluorides by Fluoroform under a Superbase System.

Fluoroform (HCF3, HFC-23) is a side product in the manufacture of polytetrafluoroethylene (Teflon). Despite its attractive properties, taming HCF3 for trifluoromethylation is quite problematic owing to its low acidity and the lability of the naked trifluoromethyl carbanion generated from HCF3. Herein we report the organic-superbase-catalyzed trifluoromethylation of ketones and arylsulfonyl fluorides by HCF3. The reactions were carried out by using a newly developed "superbase organocatalyst system" consisting of catalytic amounts of P4-tBu and N(SiMe3)3. A series of aryl and alkyl ketones were converted into the corresponding α-trifluoromethyl carbinols in good yields under the organocatalysis conditions in THF. The superbase organocatalytic system can also be applied to the trifluoromethylation of arylsulfonyl fluorides for biologically important aryl triflones in THF or DMF in good yields. Protonated P4-tBu, H[P4-tBu](+), is suggested to be crucial for the catalytic process. This new catalytic methodology using HCF3 is expected to expand the range of synthetic applications of trifluoromethylation.