Synthesis of highly strained bicyclic[3.n.1]alkenes by a metal-catalyzed Conia-ene reaction

Abstract

A high yielding metal-catalysed Conia-ene reaction of 2-acetylenic ketones for the synthesis of bicyclo[3.n.1]alkenes has been developed. This simple and efficient 6-endo-dig-cyclization protocol enables the synthesis of a wide variety of bicyclic systems, present in many natural products.

Carbonyl-assisted reverse regioselective cascade annulation of 2-acetylenic ketones triggered by Ru-catalyzed C–H activation

“…As part of our program aimed at the desymmetrization of C 2 -symmetric molecules, 11 we became interested in executing a less expensive ruthenium-catalyzed annulation of acetylenic 1,3-diketones with N -methoxybenzamides. We envisioned that the ketone functionality would initially form an intermolecular chelation with the five-membered ruthenacycle of benzamide and subsequently undergo insertion with the alkyne ( Scheme 1c ).…”

Organocatalytic Reductive Propargylation: Scope and Applications

“…Because there are numerous synthetic applications starting from the 2-(3-aryl/alkylprop-2-yn-1-yl)­cyclohexane-1,3-diones 5ab–aq (see Scheme ). − The reported 2-(3-aryl/alkylprop-2-yn-1-yl)­cyclohexane-1,3-diones 5ab–aq were obtained in good-to-excellent yields through a coupling reaction of simple cyclohexane-1,3-dione 1a with a variety of 3-aryl/alkylpropiolaldehydes ( 2b–q ) containing halogen atoms, electron-withdrawing, electron-donating, neutral, and heteroatom-substituted aryl moieties as well as achiral alkyl groups (Table ). Organocatalytic three-component reductive coupling of 1a with 2b and 3 in DCM at 25 °C for 60 min followed by precipitation in cold 10% ethyl acetate in hexanes and quick filtration gave the analytically pure coupling product 2-(3-phenylprop-2-yn-1-yl)­cyclohexane-1,3-dione 5ab in 85% yield without further column purification (Table ).…”

“…One such reaction is the chemoselective propargylation of cyclic 1,3-diones at the C-2 position. Owing to its numerous potential applications in the synthesis of drugs and natural products, chemoselective C -propargylation drew the attention of many research groups …”

“…In the previous methods, the C-2 selective propargylation was performed using the base in the solvent with or without the phase transfer catalyst but it suffered from the competition with O -propargylation. It is evident from the literature that many researchers succeeded in double propargylation at the C-2 position of cyclic 1,3-diones . However, when it comes to monopropargylation at the C-2 position, it has always ended up in low yields and sometimes even failed in introducing the functionally rich propargyl groups.…”

Cobalt‐Catalysed C–C Bond Formation and [2+2+2] Annulation of 1,3‐Dicarbonyls to Terminal Alkynes

“…Intramolecular addition of activated carbonyl compounds, enolates or enols to an unsaturated enophile, leading to cyclization, with 100 % atom economy, is popularly known as Conia‐Ene reaction The classic transformation involves thermal cyclization,[1a], however chemists have developed catalytic, especially transition metal catalyzed cyclization procedures, which were well documented in the literature. [1b], [1c], …”