Annulation

About: Annulation is a research topic. Over the lifetime, 10152 publications have been published within this topic receiving 189701 citations.

A Formal [3 + 3] Cycloaddition Reaction. Improved Reactivity Using α,β-Unsaturated Iminium Salts and Evidence for Reversibility of 6π-Electron Electrocyclic Ring Closure of 1-Oxatrienes

Abstract: A detailed account regarding a formal [3 + 3] cycloaddition method using 4-hydroxy-2-pyrones and 1,3-diketones is described here. This formal cycloaddition reaction or annulation reaction is synthetically useful for constructing 2H-pyranyl heterocycles. The usage of α,β-unsaturated iminium salts is significant in controlling competing reaction pathways to give exclusively 2H-pyrans. Most significantly, experimental evidence is provided to support the mechanism of this reaction that involves a sequential Knoevenagel condensation and a reversible 6π-electron electrocyclic ring-closure of 1-oxatrienes.

DFT perspective toward [3 + 2] annulation reaction of enals with α-ketoamides through NHC and Brønsted acid cooperative catalysis: mechanism, stereoselectivity, and role of NHC

Abstract: A systematic theoretical study has been carried out to understand the possible mechanisms and stereoselectivity of the N-heterocyclic carbene (NHC)-catalyzed [3 + 2] annulation reaction of enals with α-ketoamides using density functional theory (DFT) calculations. The calculated results reveal that the favorable pathway comprises of seven steps, i.e., addition of the catalyst, formation of the Breslow intermediate, formation of the enolate intermediate, the C–C bond formation step, the proton transfer process, the ring-closure process and the regeneration of the catalyst. For the proton transfer process, apart from the direct proton transfer mechanism, the base TMEDA and the in situ generated Bronsted acid TMEDA·H+ mediated proton transfer mechanisms are also investigated; the free energy for the crucial proton transfer steps is found to be significantly lowered by explicit inclusion of the Bronsted acid TMEDA·H+. The computational results show that the C–C bond formation step is the stereoselectivity-determining step, in which two chirality centers assigned to the coupling carbon atoms are formed, and the RR-configured diastereomer is the predominant product, which is in good agreement with the experimental observations. Global reaction index (GRI) analysis has been performed to confirm that NHC mainly plays a role of a Lewis base catalyst. In addition, the distortion/interaction, NCI, and NBO analyses show that the strong interaction and electron delocalization of the reaction active site determine the stereoselectivity, with the RR-configured product being generated preferentially. The mechanistic insights obtained in the present study should be valuable for the rational design of an effective organocatalyst for this kind of reaction with high stereoselectivity.

Enantio- and Diastereodivergent Synthesis of Spirocycles through Dual-Metal-Catalyzed [3+2] Annulation of 2-Vinyloxiranes with Nucleophilic Dipoles.

Abstract: The development of efficient and straightforward methods for obtaining all optically active isomers of structurally rigid spirocycles from readily available starting materials is of great value in drug discovery and chiral ligand development. However, the stereodivergent synthesis of spirocycles bearing multiple stereocenters remains an unsolved challenge owing to steric hindrance and ring strain. Herein, we report an enantio- and diastereodivergent synthesis of rigid spirocycles through dual-metal-catalyzed [3+2] annulation of oxy π-allyl metallic dipoles with less commonly employed nucleophilic dipoles (imino esters). A series of spiro compounds bearing a pyrroline and an olefin were easily synthesized in an enantio- and diastereodivergent manner (up to 19:1 dr, >99 % ee), which showed great promise as a new type of N-olefin ligand. Preliminary mechanistic studies were also carried out to understand the process of this bimetallic catalysis.

Tandem and concurrent cycloaddition/annulation reactions of chromium alkynyl carbene complexes

Abstract: La reaction de Diels-Alder des complexes α,β-acetyleniques de carbene-Cr, a lieu avec un certain nombre de dienes. Ces complexes alcynyl peuvent servir de synthons pour les esters propiolates substitues. Les cycloadditions et annelations peuvent etre realisees en tandem ou concurremment

Synthesis of Conformationally Restricted 2,3-Diarylbenzo[b]furan by the Pd-Catalyzed Annulation of o-Alkynylphenols: Exploring a Combinatorial Approach

Abstract: The palladium/bpy-catalyzed annulation of o-alkynylphenol with various aryl halides to generate diversified 2,3-diarylbenzo[b]furan is herein described. This method provides an efficient synthetic pathway for the combinatorial synthesis of conformationally restricted 2,3-diarylbenzo[b]furan for drug discovery.