Enantiodivergent dearomative skeletal ring expansion of indoles through carbon atom insertion

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Март 8, 2024

Abstract Heterocycle skeletal editing has recently experienced a renaissance in chemical synthesis by offering simple retrosynthetic disconnection between complex structural scaffolds and starting materials. However, asymmetric dearomatization of heteroarenes through single atom “cut paste” remains unknown to date. Herein, we report the first enantiodivergent dearomative indoles via single-carbon-atom insertion using trifluoromethyl N -triftosylhydrazones as carbene precursors. This strategy provides straightforward methodology access both enantiomers 3,4-dihydroquinolines containing trifluoromethylated quaternary stereocenter switching chirality catalyst. The synthetic utility nature this were demonstrated scope evaluation, product derivatization, short drug analogues. Mechanistic studies disclose that selectivity induction are under catalyst control during initial cyclopropanation step.

Язык: Английский

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Copper‐Catalyzed Tunable Oxygenative Rearrangement of Tetrahydrocarbazoles

Chemistry - A European Journal, Год журнала: 2024, Номер 30(44)

Опубликована: Июнь 3, 2024

Herein, we report a general copper-catalyzed method for the tunable oxygenative rearrangement of tetrahydrocarbazoles to cyclopentyl-bearing spiroindolin-2-ones and spiroindolin-3-ones. The demonstrates excellent chemoselectivity, regioselectivity, product control simply by using H

Язык: Английский

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Diastereoselective Dearomatizing Cyclizations of 5‐Arylpentan‐2‐ones by Samarium Diiodide – A Computational Analysis

Chemistry - A European Journal, Год журнала: 2024, Номер 30(30)

Опубликована: Март 21, 2024

This study analyzes the samarium diiodide-promoted cyclizations of 5-arylpentan-2-ones to dearomatized bicyclic products utilizing density functional theory. The reaction involves a single electron transfer carbonyl group, which occurs synchronously with rate determining cyclization event, and second subsequent proton-coupled transfer. These redox reactions are accurately computed employing small core pseudo potentials explicitly involving all f-electrons samarium. Comparison energies possible final rules out thermodynamic control observed regio- diastereoselectivities. Kinetic via appropriate transition states is correctly predicted, but obtain reasonable energy levels influence co-solvent hexamethylphosphortriamide has be estimated by using correction term. steric effect bulky ligands decisive for stereoselectivity. Carbonyl groups in para-position aryl group change regioselectivity lead spiro compounds. computations suggest again kinetic this deviating outcome. However, standard mechanism modified involvement complex activated two SmI

Язык: Английский

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Enantioselective Relay Coupling of Perfluoroalkyl and Vinylogous Ketyl Radicals

Angewandte Chemie, Год журнала: 2024, Номер 136(35)

Опубликована: Июнь 12, 2024

Abstract β‐Chiral carboxylic acids and their derivatives are highly valuable structural motifs in the fields of asymmetric synthesis medicinal chemistry. However, introduction a sterically demanding sidechain to β‐carbon, such as an all‐carbon quaternary center, remains significant challenge classical polar processes. Recently, N ‐heterocyclic carbene (NHC) mediated coupling reactions involving persistent ketyl radicals have emerged promising strategy assemble crowded carbon‐carbon bonds. Nevertheless, achieving enantioselectivity these challenging. In this work, we report our recent progress controlling for relay perfluoroalkyl vinylogous radicals. We developed chiral bifunctional NHC‐squaramide catalyst that achieves high facial selectivity critical bond‐forming event congested tertiary carbon radical radical. Chiral carboxylates bearing center at β‐position can be prepared good yield excellent enantiomeric excess. Results from density functional theory (DFT) calculations nuclear Overhauser effect (NOE) experiments indicate , N’ ‐diaryl squaramide motif adopts unusual syn ‐ conformation, enabling hydrogen bonding interactions with enolate oxygen, thereby rigidifying overall conformation transition state.

Язык: Английский

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Samarium and Ytterbium Reagents for Carbonyl Conversions

Elsevier eBooks, Год журнала: 2024, Номер unknown

Опубликована: Янв. 1, 2024

Язык: Английский

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Schlenk line protocols for using SmI2 and the impact of THF solvent

Results in Chemistry, Год журнала: 2024, Номер 10, С. 101697 - 101697

Опубликована: Авг. 1, 2024

Samarium diiodide (SmI2) is a single electron reductant and versatile synthetic tool that can be used to create carbon- carbon bonds or other transformations. SmI2 typically with an Argon atmosphere glovebox anhydrous solvents from solvent purification system; however, not all labs have access these equipment. A more accessible air-free option Schlenk line glassware. Here in reports optimized method for the synthesis use of on line. During optimization system, it was found largest impact success THF solvent. Anhydrous achieved though distillation, but after storage over two weeks enough moisture/air accumulated significantly concentration formed solution. The molecular sieves further indicates water accumulation compared oxygen has most significant factor synthesizing SmI2. These observations overtime are important account when carrying out reactions air-sensitive

Язык: Английский

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Nickel-Catalyzed Radical Hydroalkylative Dearomatization of Indoles with Alkyl Bromides

Synlett, Год журнала: 2024, Номер unknown

Опубликована: Авг. 7, 2024

Abstract Dearomatization of indole derivatives offers a straightforward approach to accessing the indoline framework. However, highly efficient dearomatization indoles bearing electron-deficient groups remains underdeveloped. Herein, nickel-catalyzed intermolecular hydroalkylative reaction with simple alkyl bromides through single-electron-transfer process is reported. A wide variety various functional were compatible this protocol and reacted primary, secondary, or tertiary afford series indolines in good yields (up 82%) excellent diastereoselectivity >20:1). Notably, nickel-mediated hydrogen-atom-transfer was observed when terminal employed as radical precursors, which resulted branched products.

Язык: Английский

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Copper‐Catalyzed Oxygenative Skeletal Rearrangement of Tetrahydro‐β‐carbolines Using H₂O and O₂ as Oxygen Sources

Angewandte Chemie, Год журнала: 2023, Номер 135(51)

Опубликована: Ноя. 11, 2023

Abstract Herein, we report an unprecedented skeletal rearrangement reaction of tetrahydro‐ β ‐carbolines enabled by copper‐catalyzed single‐electron oxidative oxygenation, in which H 2 O and act as oxygen sources to generate a unique 2‐hydroxyl‐3‐peroxide indoline intermediate. The synthetic reactivity species was demonstrated multi‐step bond cleavage formation cascade. Using readily available copper catalyst under open‐air conditions, highly important yet synthetically difficult spiro[pyrrolidone‐(3,1‐benzoxazine)] products were obtained single operation. utility this methodology is the efficient synthesis natural donaxanine chimonamidine, well 3‐hydroxyl‐pyrroloindoline scaffold, just one or two steps.

Язык: Английский

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