Insights into Alkene Activation by Gold: Nucleophile Activation with Base as a Trigger for Generation of Lewis Acidic Gold

Previously, the generation of alkyl
gold intermediates (B) from
nucleophilic addition to inactivated alkenes was limited by the use
of trigold oxo complexes (A) with arylphosphine ligands, [(Ar3PAu)3O]­BF4, in the presence of amine
base. In this mechanism study, we have found that the basicity of
the gold complex is key to favoring alkyl gold complex formation.
Kinetic and substrate studies have shown that the strongly Brønsted
basic IPrAuOH also mediates alkyl gold complex formation. The observation
of an intermediate gold amide complex suggests these processes are
initiated by deprotonation of the nucleophile. Trigold oxo reactions
in the absence of base reveal that the byproduct from the reaction
of substrate with A is digold hydroxide complex, [(LAu)2OH]­BF4 (C). This complex is catalytically active for urea
hydroamination at room temperature to form pyrrolidine D; however,
it does not catalyze the hydroalkoxylation of the alcohol substrate.
Importantly, catalysis to D occurs faster than can be accounted for
by alkyl gold protodeauration, and the alkyl gold does not react significantly
on the catalyzed time scales observed. Preformed gold triethylamine
complexes are not reactive toward alkenyl alcohols; however, when
alkenyl urea was treated with gold triethylamine complex [Ph3PAu­(NEt3)]­SbF6, a similar case was observed,
in which alkyl gold formation triggered the initiation of a pathway
to form D. These results show that Brønsted basic conditions
highly favor the formation of alkyl gold intermediates by a process
that incorporates both nucleophile and π-activation. Additional
experiments support the conclusion that the alkyl gold intermediates
are not productive structures en route to pyrrolidine D. Work by Nolan
et al. suggests that C is not simply a Brønsted Acid, but rather
a source of cationic gold and gold hydroxide (L-Au-OH). Alkene gold
activation modes that do not involve protodeauration of discrete alkyl
gold intermediates must be considered more carefully in future studies.