Base‐Promoted Tandem Reaction towards Conjugated Dienone or Chromone Derivatives with a Cyano Group: Insertion of Alkynes into C–C σ‐Bonds of 3‐Oxopropanenitriles

Abstract

Base‐promoted insertion reactions of alkynes into the C–C σ‐bonds of α‐cyano ketones were established to construct highly functionalized conjugated olefins or chromone derivatives via transition metal‐free tandem reactions. These reactions are initialized through the nucleophilic attack of α‐cyano ketones to alkynones followed by intramolecular nucleophilic addition/ring‐opening to furnish the cyano‐containing alkenes. In the cases of alkynones bearing an ortho‐halide‐substituted aryl ring, a further C–O bond coupling reaction occurs to afford chromone derivatives in good to high yields. Various alkynones bearing alkyl or aryl substituents were compatible in the reaction. This reaction has the potential to become a general synthetic protocol for the preparation of cyano‐substituted olefins and chromones due to the abundance of easily accessible starting materials possessing diverse substituent groups.magnified image

Base-Promoted Ring Expansion Reactions for the Construction of Cycloheptanones through C—C Bond Cleavage

“…On the basis of the aforementioned observations and previous reports, [7][8][9][10][11] a possible reaction mechanism was proposed as outlined in Scheme 4. Initially, the intermediate A could be generated from the ynone 1a attacked by acenaphthenone 2 in the presence of Cs 2 CO 3 .…”

“…Particularly, beside the highly reactive arynes [5] or cyclohexynes, [6] the reports involving insertions of unsaturated bonds into C-C σ-bonds are rare. Recently, Li's group have disclosed the insertion of alkynes into C-C σ-bonds of indene-1,3-diones, [7] indolin-2-ones, [8] 3-oxopropanenitriles, [9] ethanones, [10] and dicarbonyl compounds [11] under transition-metal-free conditions, which offer efficient routes towards benzoannulated seven-membered ring compounds, seven-membered ring benzolactams, conjugated dienones, hydroxydienones, xanthones and medium-sized ring compounds, respectively (Scheme 1b). To our best knowledge, cycloheptanone is a privileged seven-membered-ring struc-tural scaffold for drug discovery owing to its significant biological activities, which widely occurs in natural products such as purpurogallin, sinularia A, pavidolide B as shown in Figure 1.…”

Heteroarene‐tethered Functionalized Alkyne Metamorphosis

“…Nucleophilic addition of diketone to ynone followed by intramolecular nucleophilic addition and rearrangement, enolization, dehydration and intramolecular nucleophilic substitution (S N Ar) resulted the xanthone derivative 66 [22] . Base mediated insertion of alkyne into 3‐oxopropane nitrile was also reported by the same group yielding functionalized chromone 67 in 72 % yield [23] . The same ynone 65 when subjected to ethyl 2‐oxocyclohexane‐1‐carboxylate and Cs 2 CO 3 in DMAc at 80 °C, it resulted in the formation of the corresponding cyclooctachromene derivative 68 in 75 % yield by alkyne insertion into C−C σ‐bond (Scheme 13).…”

“…[22] Base mediated insertiono fa lkyne into 3-oxopropane nitrile was also reported by the same group yielding functionalized chromone 67 in 72 %y ield. [23] The same ynone 65 when subjected to ethyl 2-oxocyclohexane-1-carboxylate and Cs 2 CO 3 in DMAc at 80 8C, it resulted in the formation of the corresponding cyclo-octachromene derivative 68 in 75 %y ield by alkyne insertion into CÀC s-bond (Scheme13). [24] Synthesis of 7-or 8-membered ring fused pyranoindolones 71 from indolyl ynone 69 in atom economic fashion was reportedb yL ia nd co-workers in 2018 by using chronological Cs 2 CO 3 endorsed CÀC s-bond cleavage of cyclic ketoesters followed by ZnI 2 -mediated selective CÀH/OÀHc oupling reaction (Scheme 14).…”

Regioselectivity-Switchable Catalytic Annulations of Alkynyl α-Diketones and α-Cyanoketones

“…3a has a unique dihydrocyclopentafuranol skeleton, and 5a is a fully substituted furan compound. This observation is also in sharp contrast to the literature report using common ynones under similar conditions, which produces cyanoalkenes and chromones . Similar product distributions but lower yields were found when NaO t Bu, K 2 CO 3 , and K 3 PO 4 were employed (Table , entries 2–4).…”