Palladium(II)‐Catalyzed Domino Reaction of 2‐(1‐Alkynyl)‐2‐alken‐1‐ones with Nucleophiles: Scope, Mechanism and Synthetic Application in the Synthesis of 3,4‐Fused Bicyclic Tetrasubstituted Furans

Abstract

Described herein is the development of a palladium(II)-catalyzed two-or three-component reaction of 2-(1-alkynyl)-2-alken-1-ones with nucleophiles and allylic chlorides. Various types of nucleophiles such as O-, N-, C-based nucleophiles and olefin-tethered O-, N-, C-based nucleophiles were investigated. The scope, mechanism and application of this Pd(II)-catalyzed domino reaction were studied. In these transformations, the palladium catalyst exhibits a dual role, serving simultaneously as a Lewis acid and a transition metal. Two possible reaction pathways (cross-coupling reaction vs. Heck reaction) from the same intermediate furanylpalladium species were observed. The reaction pathway is dependent on the property of the nucleophile and the length of the tethered chain as well. When olefin-tethered Obased nucleophiles were used, only the cross-coupling reaction pathway was observed, in contrast, both reaction pathways were observed when olefintethered C-based nucleophiles were employed. The product ratio is dependent on the length of the tethered chain. Furthermore, ring-closing metathesis (RCM) of corresponding furans with C=C bonds provides an easy method for the preparation of functionalized oxygen-heterocycles -3,4-fused bicyclic furans. It is also noteworthy that allylic chloride can be as an oxidant besides its well known function as an alkylating reagent.

Paracyclophane‐based Silver Phosphates as Catalysts for Enantioselective Cycloisomerization/Addition Reactions: Synthesis of Bicyclic Furans

“…Also, p ‐toluenesulfonamide can serve as a suitable N ‐nucleophile giving the expected product 4 d in nearly quantitative yield (entry 10). The good reactivity observed here with silver hexafluorophosphate should be considered against the lack of reactivity reported previously with palladium(II) catalysts . Thus, in this case, the silver catalyst expands the scope of N ‐nucleophiles in this domino reaction.…”

Indium‐Catalysed Transfer Hydrogenation for the Reductive Cyclisation of 2‐Alkynyl Enones towards Trisubstituted Furans

“…Among the numerous synthetic approaches towards furans, the cyclisation of 2‐alkynyl‐substituted 1,3‐conjugated enones 1 with alcohols was first reported by Larock [3] in 2004 (Scheme 1) utilising catalytic amounts of gold(III) and various nucleophiles for the synthesis of trisubstituted furans. Further developments by Zhang, Liu, and several other groups (Scheme 1) utilising transition metal catalysts, such as gold, [4a–n] palladium, [4o–r] rhodium, [4s] copper, [4t,u] and silver, [4v–x] were reported over the last two decades. In these transition‐metal‐catalysed cyclisation reactions of alkynyl enones of type 1 , a large number of different types of nucleophiles were reported for the synthesis of highly substituted and functionalised furans and annulated bicyclic systems.…”

Yne–Enones Enable Diversity-Oriented Catalytic Cascade Reactions: A Rapid Assembly of Complexity

“…As shown in Scheme , the detailed scope, mechanism, and application of the Pd­(II)-catalyzed cascade reaction were studied . Reagent-based divergent reactions of yne–enones with allyl nucleophiles and an allyl chloride were further developed.…”

“…As shown in Scheme 2, the detailed scope, mechanism, and application of the Pd(II)-catalyzed cascade reaction were studied. 13 Reagent-based divergent reactions of yne−enones with allyl nucleophiles and an allyl chloride were further developed. Notably, allyl-substituted alcohols enabled the process to cross-couple reaction products 3, while the Heck reaction was achieved with dimethyl 2-allylmalonate 4.…”