Mononuclear or Dinuclear? Mechanistic Study of the Zinc‐Catalyzed Oxidative Coupling of Aldehydes and Acetylenes

Abstract

Although zinc catalysis is widely used in organic synthesis, very few studies on the dinuclear zinc mechanism have been reported. Here, a dinuclear zinc pathway is proposed for the Zn(OTf) -catalyzed oxidative coupling of aldehydes with terminal alkynes. DFT calculations revealed that the deprotonation of the terminal alkyne would preferentially lead to the formation of a dinuclear zinc intermediate. The nucleophilic addition of this intermediate to an aldehyde, followed by an Oppenauer-type oxidation was investigated theoretically according to the mono- and dinuclear pathways. The formation of a dinuclear zinc intermediate from a mononuclear alkynyl zinc complex was exergonic, favoring the dinuclear zinc pathway. The subsequent protonation and regeneration of the active dinuclear catalyst were also evaluated by DFT calculations. The oxidizabilities of various aldehydes and ketones were evaluated to determine the best oxidant for this step. Trifluoroacetaldehyde was predicted to be a better oxidant for this reaction because its calculated energy barrier for the Oppenauer-type oxidation step was much lower than that of the other carbonyl complexes.

Zn-Catalyzed Multicomponent KA2 Coupling: One-Pot Assembly of Propargylamines Bearing Tetrasubstituted Carbon Centers

“…It is important to mention that although the addition of zinc acetylides to electrophiles is usually considered to involve mononuclear zinc species, recent advancements regarding the elucidation of a dinuclear mode of action of zinc catalysts should also be taken into consideration. 66,70…”

“…Step V represents a possible catalyst deactivation pathway, with the interaction of amine substrates and in situ produced water with zinc, giving coordination complexes that might be either off-cycle species, or able to participate in the next cycle, depending on their exact nature. It is important to mention that although the addition of zinc acetylides to electrophiles is usually considered to involve mononuclear zinc species, recent advancements regarding the elucidation of a dinuclear mode of action of zinc catalysts should also be taken into consideration. , …”

Theoretical Study of the Addition of Cu–Carbenes to Acetylenes to Form Chiral Allenes

“…Because of the acidity of the terminal hydrogen atom of terminal alkynes, the C–H bond can be deprotonated to generate the corresponding acetylide, which usually acts as a nucleophile to react with possible electrophiles (type a). − The π bonds of alkynes are electron-rich, so unsaturated C–C triple bonds can be attacked by electrophiles to give the corresponding vinyl cation­(type b). , The C–C triple bond can act as a ligand and coordinate to transition metal centers with moderate π-backbonding, which weakens the CC bond and enables subsequent nucleophilic attack to generate vinyl metal intermediates (type c). Moreover, coordination to a transition metal also increases the acidity of the terminal hydrogen atom of the terminal alkyne group, so subsequent deprotonation can also occur to give a metal–acetylide species (type d). − In the past few decades, a series of new synthetic methodologies have enhanced alkyne chemistry and made alkynes one of the most versatile building blocks. − Among these methodologies, transition-metal-catalyzed coupling reactions, such as Glaser–Hay reactions, , Sonogashira reactions, , Glaser–Eglinton reactions, , Cadiot–Chodkiewicz reactions, and Castro–Stephens reactions, , have received extensive attention as simple and convenient methods to construct internal C–C triple and double bonds.…”

Mechanistic Investigation of Cu-Catalyzed Asymmetric Alkynylation of Cyclic N-Sulfonyl Ketimines with Terminal Alkynes

“…Acetylides can coordinate to a transition metal to yield active metal acetylides, which would react with electrophiles to generate the desired cross-coupling products (Scheme ). An alternative way for alkyne C–H functionalization is the addition of a nucleophile to a C–C triple bond to generate an active vinyl cation intermediate, where the alkyne acts as a π-electron donor . A subsequent deprotonation process could regenerate the C–C triple bond to yield an internal alkyne product.…”