Using Fluorine to ‘Freeze Out’ Catalyst Conformations

Significance

Sparr and Gilmour disclose a conformational analysis study of MacMillan’s organocatalyst 1 using their recent technique of introducing a sterically undemanding, yet highly electroni-cally influential fluorine atom into an organocatalyst. This concept relies on the strong hyperconjugative and electrostatic interactions of a C-F bond with neighboring substituents to effectively ‘fix’ their geometry in space. The authors synthesized two diastereomeric fluorinated MacMillan-type catalysts 2 and 3, which adopted stable conformations I and II upon iminium formation due to the fluorine-iminium ion gauche effect. These structures were studied as ‘equivalents’ of the expected transient conformations of the MacMillan iminium adduct 4.