Gold catalysis in organic synthesis: efficient intramolecular cyclization of γ-acetylenic carboxylic acids to 5-exo-alkylidene-butyrolactones

Abstract

We have found that functionalized acetylenic acids may be cyclized under extremely mild conditions, at room temperature in the presence of AuCl catalyst and without the use of additives. The corresponding 5-exo-alkylidene-butyrolactones were isolated in high yields, and this process constitutes an easy and efficient route to highly valuable building blocks of natural products having biological interest.

Gold-Catalyzed Tandem Cyclizations of 1,6-Diynes Triggered by Internal N- and O-Nucleophiles

“…The bispropargylic carboxylic acid 11 was obtained by monosaponification of diethylmalonate derivative 10 in basic methanolic medium in 80% yield. 12 Treatment of carboxylic acid 11 with oxalylchloride provided the acyl chloride, which was subsequently transformed into the secondary ethylamide 12 in 80% yield. Bis-alkylation of the monoamide malonate 13 provided diyne 14 in 83% yield (Scheme 4).…”

“…Nevertheless, a potential requirement of a silver salt additive for the cyclization of 22 can be excluded, since the reaction proceeded with catalyst A in the absence of any silver additive (Table 4, entries 2 and 3). Since hardly soluble AgCl is formed by exchanging the Reactions were run at [12] or [14] = 500 mM in refluxing DCM for [12] and rt for [14] with 2.5-5.0 mol % catalyst loading. The reaction mixture was used directly for column chromatography.…”

“…The acid 11 was obtained as a colorless solid (60. (12). A solution of the acid 11 (150 mg, 0.675 mmol) in DCM (1.8 mL) and DMF (1 μL) was cooled to 0 °C, and oxalylchloride (107 mg, 0.844 mmol, 71.4 μL, 1.25 equiv) was added dropwise.…”

Cycloisomerization of π‐Coupled Heteroatom Nucleophiles by Gold Catalysis: En Route to Regiochemically Defined Heterocycles

“…A highly efficient and regioselective synthesis of functionalized γ‐lactones 103 by 5‐ exo ‐ dig cycloisomerization of γ‐acetylenic acids 104 is developed by Michelet et al . using AuCl as a catalyst [198,199] . In this paper, the authors have widened their studies by achieving this regioselective cyclization under biphasic conditions (toluene/water) using novel water soluble Au(I)‐ and Au(III)‐NHC complexes with sulphonated side chains (Scheme 23, eq 1) [200,201] …”

Gold-Catalyzed Hydroamination/Cycloisomerization Reaction of 1,6-Enynes

“…To the best of our knowledge, Kozmin's group 3a has described a unique example of intramolecular addition of an amino group to an alkene followed by trapping by an alkyne moiety. In pursuit of the investigation on atom-economical metal-catalyzed cycloisomerization reactions, we have envisaged to develop mild conditions for the Au-catalyzed intermolecular addition of amines to carbon−carbon double bond concomitant with a cyclization process. We wish therefore to present in this paper our preliminary results of the hydroamination/cycloisomerization reactions of 1,6-enynes leading to cyclic functionalized amines.…”