Cycloisomerization versus Hydration Reactions in Aqueous Media: A Au(III)-NHC Catalyst That Makes the Difference

Abstract

A novel water-soluble Au(III)-NHC complex has been synthesized and successfully applied in the intramolecular cyclization of γ-alkynoic acids into enol-lactones under biphasic toluene/water conditions, thus representing a rare example of an active and selective catalyst for this transformation in aqueous media. Remarkably, competing alkyne hydration processes were not observed, even during the desymmetrization reaction of challenging 1,6-diyne substrates. In addition, after phase separation, the water-soluble Au(III) catalyst could be recycled 10 times without loss of activity or selectivity.

Water-Soluble Gold(I) and Gold(III) Complexes with SulfonatedN-Heterocyclic Carbene Ligands: Synthesis, Characterization, and Application in the Catalytic Cycloisomerization of γ-Alkynoic Acids into Enol-Lactones

“…the catalytic cycloisomerization of γ-alkynoic acids (Figure 2). 12 It is worth mentioning that this catalytic transformation provides an easy and atom-economical entry to enol-lactones, an important class of functionalized heterocycles useful as synthetic intermediates. Although a large number of catalysts able to convert γ-alkynoic acids into enol-lactones are already known, 13,14 most of the reported procedures require water-free reaction conditions.…”

“…Hydrogen atoms, except those on the N(3) atoms, have been omitted for clarity. (14) C(3)-N(1) 1.409(13) 1.367 (12) Angles 5b 5c…”

Metal-Catalyzed Intra- and Intermolecular Addition of Carboxylic Acids to Alkynes in Aqueous Media: A Review

“…Since then, a number of gold-based catalysts capable of operating in pure water or in aqueous biphasic mixtures have been described, most involving functionalized N-heterocyclic carbenes (NHC) as auxiliary ligands. In this regard, the groups of Michelet, Cadierno and Conejero developed the zwitterionic Au(III)-NHC complex 10b which proved to be active in the cycloisomerization of a broad range of γ-alkynoic acids under biphasic toluene/water conditions (Scheme 6) [44]. Remarkably, the participation of a silver(I) co-catalyst, usually employed in catalytic gold chemistry to generate vacant coordination sites on the metal through chloride ligands abstraction, was not required.…”

The intermolecular hydro-oxycarbonylation of internal alkynes: current state of the art

“…the cycloisomerization of alkynoic acids. [58][59][60][61][62][63] However, we would like to stress that these intramolecular reactions are favoured from a thermodynamic point of view and do not represent a notable synthetic problem. 52,64 Another challenging aspect related with the use of internal alkynes concerns the control of the regio-and stereoselectivity of the addition process since, starting from non-symmetrically substituted substrates R ), up to four isomeric enol esters can be formed (obviously difficult to separate).…”