Superiority of Very Weakly Basic Amines as Catalysts for Alpha-Proton Abstraction via Iminium Ion Formation

Article abstract of DOI:10.1021/ja00543a027

Catalysis of the conversions of beta-ketol 6 and beta-acetoxy ketone 7 to enone 3 via amine-carbonyl condensation has been studied by using eight nontertiary amines having a pK_a range from 10.61 to 1.22, including the very weakly basic 3,3,4,4-tetrafluoropyrrolidine (pK_a = 4.05) and 1,1,1,3,3,3-hexafluoroisopropylamine (pK_a = 1.22).Kinetic terms reflecting rate-determining alpha-proton abstraction via iminium ion formation were identified.Primary kinetic isotope effects were observed when appropriately deuterated 6 and 7 were used.Intermediate eniminium and enimmonium ions 17 were detected.Unlike general-base catalysis, catalysis via iminium ion formation becomes more effective as the base strength of the catalyst decreases.With 1 M hexafluoroisopropylamine as catalyst, formation of 3 from 7 occurs > 10⁴ times via the iminium ion pathway for every time it occurs via direct general-base-catalyzed alpha-proton abstraction.