Synthesis of tertiary amides from anionically activated aromatic trifluoromethyl groups.
In this paper, a novel synthesis of tertiary amides from anionically activated aromatic trifluoromethyl groups is presented. Anionically activated trifluoromethyl groups react with secondary amines under aqueous conditions to afford tertiary amides. The mechanism involves initial elimination of hydrogen fluoride by an E1cB mechanism to afford an electrophilic quinone methide- or azafulvene-type intermediate that reacts with secondary amines under aqueous conditions to afford the tertiary amide in good yield (up to 99%).
O'Mahony
Gavin
G
AstraZeneca R&D Mölndal, Pepparedsleden 1, 43183 Mölndal, Sweden. gavin.omahony@astrazeneca.com
Pitts
Andrew K
AK
D000577:Amides / Q000737:chemistry*; D006858:Hydrofluoric Acid / Q000737:chemistry; D014867:Water / Q000737:chemistry
D000577:Amides; D014867:Water; D006858:Hydrofluoric Acid