Progress in Organocatalytic Dearomatization Reactions Catalyzed by N‐Heterocyclic Carbenes

ChemCatChem, Journal Year: 2022, Volume and Issue: 14(16)

Published: April 1, 2022

Abstract Dearomative reactions allow for concise assembly of structurally complex, highly functionalized three‐dimensional molecules by breaking the plane two‐dimensional aromatic starting materials. With growing interest in N‐heterocyclic carbene (NHC) organocatalysis as a powerful strategy synthesizing diversiform molecules, mainly polarity‐reversal (umpolung) approaches, NHC‐catalyzed dearomatization have recently been successfully used construction skeletons natural products and drugs. By generating various key intermediates (i. e., Breslow intermediates, acyl azolium homoenolate enolate dienolate intermediates), NHCs can readily destroy aromaticity electrophilic or nucleophilic interactions with compounds. In this overview, progress dearomative is summarized; are grouped according to reaction modes categories representative mechanisms provided. This review aims serve comprehensive reference work emerging field organocatalytic dearomatization.

Language: Английский

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Formation of Breslow Intermediates from N‐Heterocyclic Carbenes and Aldehydes Involves Autocatalysis by the Breslow Intermediate, and a Hemiacetal

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(23)

Published: March 3, 2022

Under aprotic conditions, the stoichiometric reaction of N-heterocyclic carbenes (NHCs) such as imidazolidin-2-ylidenes with aldehydes affords Breslow Intermediates (BIs), involving a formal 1,2-C-to-O proton shift. We herein report kinetic studies (NMR), complemented by DFT calculations, on mechanism this kinetically disfavored H-translocation. Variable time normalization analysis (VTNA) revealed that orders reactants vary for different NHC-to-aldehyde ratios, indicating and ratio-dependent mechanistic regimes. propose high H-shift takes place in primary, zwitterionic NHC-aldehyde adduct. With excess aldehyde, zwitterion is equilibrium hemiacetal, which occurs. In both regimes, critical auto-catalyzed BI. Kinetic isotope effects observed R-CDO are line our proposal. Furthermore, we detected an H-bonded complex BI NHC (NMR).

Language: Английский

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The triplet state of deprotonated mesoionic carbene Breslow intermediates is thermally accessible: Distal difunctionalization of aldehydes

Chem Catalysis, Journal Year: 2022, Volume and Issue: 2(12), P. 3517 - 3527

Published: Oct. 26, 2022

N-Heterocyclic carbene (NHC)-catalyzed transformations through electron-pair-transfer processes have witnessed remarkable developments in the past decades, especially umpolung of aldehydes via Breslow intermediates (BIs). The role BIs single-electron transfer (SET) pathways has long been established biosynthesis, and last decade, it was extended to NHC organocatalysis. Here, we report that deprotonated mesoionic (BI - s) an astonishing small singlet/triplet (S/T) gap only 4.0 kcal/mol, resulting a thermally accessible triplet state. This low-lying excited state allows for series distal difunctionalizations aryl biradical processes. At formyl side, oxidative esterification reaction takes place concomitantly with reduction side. three types chemical transformation are demonstrated: hydro(deutero)defunctionalization, hydrogenation, reductive alkylation. • MIC-Breslow is Catalytic difunctionalization Redox-neutral reactions simultaneous Over N-heterocyclic (NHC)-based organocatalysis, which involves (BIs), developed as important approach organic synthesis. Among them, NHC-catalyzed electron-pair radical BI − s, respectively. In this article, disclose accessible. Taking advantage property, describe mesoionic-carbene-catalyzed pathways. These feature redox neutrality reduction. Yan co-workers (BIs)

Language: Английский

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How To Enhance the Efficiency of Breslow Intermediates for SET Catalysis

The Journal of Organic Chemistry, Journal Year: 2023, Volume and Issue: 88(4), P. 2535 - 2542

Published: Jan. 31, 2023

Oxidative carbene organocatalysis, which proceeds via single electron transfer (SET) pathways, has been limited by the moderately reducing properties of deprotonated Breslow intermediates BI-s derived from thiazol-2-ylidene 1 and 1,2,4-triazolylidene 2. Using computational methods, we assess redox potentials based on ten different types known stable carbenes report our findings concerning key parameters influencing steps catalytic cycle. From calculated values first oxidation potential to 10, it appears that, apart diamidocarbene 7, all others are more than We observed that while power significantly decreases with increasing solvent polarity, oxidant can increase at a greater rate, thus facilitating reaction. The cation, associated base, also plays an important role when nonpolar is used; large weakly coordinating cations such as Cs+ beneficial. radical-radical coupling step probably most challenging due both electronic steric constraints. Based results, predict mesoionic 3 abnormal NHC 4 promising candidates for oxidative organocatalysis.

Language: Английский

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Theoretical study of an N-heterocyclic carbene-catalyzed annulation reaction between an enal and a β-silyl enone: Mechanism and origin of stereoselectivity

Molecular Catalysis, Journal Year: 2023, Volume and Issue: 551, P. 113621 - 113621

Published: Oct. 27, 2023

Language: Английский

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