Gold-catalyzed bis-cyclization of 1,2-diol- or acetonide-tethered alkynes. Synthesis of ?-lactam-bridged acetals: a combined experimental and theoretical study

Gold(I)-Catalyzed Activation of Alkynes for the Construction of Molecular Complexity

“…Recently, the selective conversion of acetonide-tethered alkynes into bridged acetals through an analogous process using Ph 3 PAuCl and AgOTf in the presence of water was reported. 86 …”

Gold(I)-catalyzed intermolecular dioxolane addition to alkynes: the role of water

“…Particularly, gold-catalyzed intramolecular hydroalkoxylation reactions have been often used in the synthesis of several heterocycles [6][7][8] and natural products [9], mainly starting with free alcoholic groups as O-suppliers; only a few cases have used an ether (linear or cyclic) as a nucleophile, and even less have studied the double addition of two consecutive O atoms belonging to the same molecule. Alcaide et al have reported some intramolecular bis-cyclizations of acetonides tethered to alkynes where the bridge between these functionalities contains a linear ether/amine [10], a 2-azetidinone ring [11], or a 2-azetidinone ring plus a double bond [12]. When the bridge is a 2-azetidinone ring [11], 1,2 diols and acetonide cycles were independently considered as nucleophiles, and both rendered the same tricyclic product, although under different experimental conditions.…”

“…Alcaide et al have reported some intramolecular bis-cyclizations of acetonides tethered to alkynes where the bridge between these functionalities contains a linear ether/amine [10], a 2-azetidinone ring [11], or a 2-azetidinone ring plus a double bond [12]. When the bridge is a 2-azetidinone ring [11], 1,2 diols and acetonide cycles were independently considered as nucleophiles, and both rendered the same tricyclic product, although under different experimental conditions. The reaction of the acetonide did not need the presence of an acid but it did require the participation of water.…”

“…Actually, the absence of an acid prevented the hydrolysis of the acetonide to the corresponding diol. Authors claim that, looking for a maximal total efficiency of the organic transformation, the use of 1,3-dioxolanes is preferred over that of free hydroxyl groups from a diol [11]. Theoretical mechanisms where proposed for the reactions starting with the diol and the acetonide and they were different [11].…”

“…Authors claim that, looking for a maximal total efficiency of the organic transformation, the use of 1,3-dioxolanes is preferred over that of free hydroxyl groups from a diol [11]. Theoretical mechanisms where proposed for the reactions starting with the diol and the acetonide and they were different [11]. As seen in Scheme 1, for the acetonide 1, external water allowed the hydrolysis of the intermediate 3 formed after metal coordination to the triple C-C bond and the first acetonide-O addition leading to the tricyclic product 6 after the second acetonide-O addition and proton transfer.…”