Cyclic-Protected Hexafluoroacetone as an Air-Stable Liquid Reagent for Trifluoromethylations

• Published in: European journal of organic chemistry Vol. 2016; no. 23; pp. 4099 - 4104
• Main Authors: Negishi, Kazuyuki, Aikawa, Kohsuke, Mikami, Koichi
• Format: Journal Article
• Language: English
• Published: WEINHEIM Blackwell Publishing Ltd 01.08.2016; Wiley; Wiley Subscription Services, Inc
• Subjects: Chemistry; Chemistry, Organic; Cuprates; Fluorinated compounds; Fluorine; Physical Sciences; Reagent design; Science & Technology; Synthetic methods; NUCLEOPHILIC TRIFLUOROMETHYLATION; DIRECT CUPRATION; Fluorine; Reagent design; CARBONYL-COMPOUNDS; TERMINAL ALKYNES; OXIDATIVE TRIFLUOROMETHYLATION; COPPER REAGENT; Cuprates; EFFICIENT PRECURSOR; ARYL BORONIC ACIDS; FLUOROFORM-DERIVED CUCF3; CATALYZED TRIFLUOROMETHYLATION; Synthetic methods; Fluorinated compounds
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201600711

An air‐stable liquid trifluoromethylating reagent is readily synthesized from gaseous hexafluoroacetone and 2‐methylproline on a gram scale. The reaction of the trifluoromethylating reagent with tert‐butoxy cuprate K[Cu(OtBu)2] leads to the CuCF3 in high yield. This species is directly formed from the tetrahedral cuprate intermediate through intramolecular migration of the trifluoromethyl group to copper. The CuCF3 reagent prepared in situ by our method can be used for the trifluoromethylation of aryl iodides, arylboronic acids, and terminal alkynes in good to excellent yields, even on a gram scale. Furthermore, the CuC2F5 reagent can be prepared in the same way, and this can be used in the pentafluoroethylation of arylboronic acids or aryl bromides in good to excellent yields. An air‐stable liquid trifluoromethylating reagent is readily synthesized from gaseous hexafluoroacetone and 2‐methylproline on a gram scale. The reaction of the trifluoromethylating reagent with tert‐butoxy cuprate K[Cu(OtBu)2] leads to the CuCF3 reagent, which can then be used for the trifluoromethylation of aryl iodides, arylboronic acids, and terminal alkynes in good to excellent yields.