LongLarf

Goldilocks and the sensitivity screen: This work introduces a standardized, systematic, and user‐friendly tool to gain valuable information on the sensitivity of a reaction, with the aim of enhancing reproducibility and supporting troubleshooting.

Abstract

A systematic, user‐friendly assessment tool that delivers a clear overview of the sensitivity of reactions to key parameters is highly desirable. Herein, the development of such a method is described. The intuitive, standardized presentation of the results in a radar diagram enables the sensitivity of a protocol to be rapidly assessed. This method was applied to five different visible‐light‐mediated photochemical reactions, and the results were correlated to the underlying mechanism. Ultimately, we believe that this assessment will help to increase the uptake of new synthetic methods and their reproducibility.

Most photoredox catalysts in current use are precious metal complexes or synthetically elaborate organic dyes, the cost of which can impede their application for large-scale industrial processes. We found that a combination of triphenylphosphine and sodium iodide under 456-nanometer irradiation by blue light–emitting diodes can catalyze the alkylation of silyl enol ethers by decarboxylative coupling with redox-active esters in the absence of transition metals. Deaminative alkylation using Katritzky’s N-alkylpyridinium salts and trifluoromethylation using Togni’s reagent are also demonstrated. Moreover, the phosphine/iodide-based photoredox system catalyzes Minisci-type alkylation of N-heterocycles and can operate in tandem with chiral phosphoric acids to achieve high enantioselectivity in this reaction.

Abstract

Unprecedented direct access to terminal enones via α‐methylenation of aryl ketones to form C=C bond is achieved under visible‐light conditions using methanol as one carbon source substrate and solvent as well. The reaction involves Cu@g‐C₃N₄‐catalysed in situ oxidation of methanol into formaldehyde followed by dehydrative cross aldol type reaction. Various aryl ketones react efficiently with MeOH, producing α,β‐unsaturated carbonyl compounds only in 4–8 h at room temperature in excellent yield (84–97%). Operational simplicity, wide substrate scope, ambient reaction conditions, visible‐light photocatalysis and novel application of MeOH as methylene donor substrate are the salient features making the envisaged protocol mild, efficient and green alternative to the existing methods for synthesis of such fine chemicals.

Photo mediator: An organic photocatalyst combined with suitable base allow the employment of readily available versatile nitroalkenes for alkenylation of ethers. Good Z/E selectivity was obtained via an efficient proton coupled electron transfer process.

Abstract

C−H alkenylation of cyclic ethers (THF, 1,4‐dioxane) using the readily available nitroalkenes as the alkenylating reagents has been developed. It allows the rapid access to the α‐alkenyl ethers with high E‐selectivity. The previous inaccessible α‐dienyl ethers are successfully obtained. Acyclic ether can also participate in this alkenylation process. The mechanism study reveals that alkenylation proceeded through a proton coupled electron transfer (PCET) process with a de‐nitration.

The tacticity of vinyl polymers has a profound effect on their physical properties. Despite the well-developed stereoselective methods for the polymerization of propylene and other nonpolar α-olefins, stereoselective polymerization of polar vinyl monomers has proven more challenging. We have designed chiral counterions that systematically bias the reactivity and chain-end stereochemical environment during cationic polymerization. This approach overrides conventional chain-end stereochemical bias to achieve catalyst-controlled stereoselective polymerization. We demonstrate that this method is general to vinyl ether substrates, providing access to a range of isotactic poly(vinyl ether)s with high degrees of isotacticity. The obtained materials display the tensile properties of commercial polyolefins but adhere more strongly to polar substrates by an order of magnitude, indicating their promise for next-generation engineering applications.

Model DyKAH: The first Brønsted acid catalyzed dynamic kinetic asymmetric hydroamination (DyKAH) of racemic allenes and asymmetric hydroamination of dienes with both high E/Z selectivity and enantioselectivity is presented. The transformation proceeds through a new catalytic asymmetric model involving a reactive π‐allylic carbocationic intermediate. This method affords expedient access to diverse enantioenriched, bioactive aza‐heterocycles.

Abstract

The first highly efficient and practical chiral Brønsted acid catalyzed dynamic kinetic asymmetric hydroamination (DyKAH) of racemic allenes and asymmetric hydroamination of unactivated dienes with both high E/Z selectivity and enantioselectivity are described herein. The transformation proceeds through a new catalytic asymmetric model involving a highly reactive π‐allylic carbocationic intermediate, generated from racemic allenes or dienes through a proton transfer mediated by an activating/directing thiourea group. This method affords expedient access to structurally diverse enantioenriched, potentially bioactive alkenyl‐containing aza‐heterocycles and bicyclic aza‐heterocycles.

Going full circle: An iridium (III) PONOP pincer complex is versatile for both electro‐reduction of CO₂ to formate and formate electro‐oxidation to CO₂. The Faradaic efficiency for CO₂ reduction to formate was 97 % and the turnover frequency was 67 s⁻¹, and formate electro‐oxidation was also efficient with turnover frequency of 4.8 s⁻¹ at 0.06 M formate. The hydride species is critical for the bifunctional reactivity.

Abstract

An iridium (III) complex based on a PONOP pincer ligand (PONOP=2,6‐bis(di‐tert‐butylphosphinito)pyridine) is a versatile catalyst for both electro‐reduction of CO₂ to formate and formate electro‐oxidation to CO₂. The electro‐reduction of CO₂ in acetonitrile is very efficient and selective, and the Faradaic efficiency for formate was 97 % and the turnover frequency (TOF) was as high as 67 s⁻¹. In addition, the complex is an effective electrocatalyst for formate electro‐oxidation with apparent TOF of 4.8 s⁻¹ (0.06 M formate), and CO₂ was the sole product. The catalyst was stable for 35 h of electrolysis. It can serve as a single catalyst for the roundtrip conversion between CO₂ and formate with potential for electrochemical energy storage. Electrochemical and NMR spectroscopic studies suggested that the hydride species is critical for the bifunctional reactivity.

Publication date: 14 June 2019

Source: Tetrahedron, Volume 75, Issue 24

Author(s): Trevor V. Nykaza, Junyu Yang, Alexander T. Radosevich

Graphical abstract

Pyrimidopteridine N ‐oxide‐based heterocycles exhibit excellent excited state reduction potentials paired with a suitable ground state reduction potential allowing for catalyst turnover with mild oxidants. The structural similarity between pyrimidopteridines and recently uncovered flavine N ‐oxides may draw an important link between organic photoredox catalysis and chemical biology.

Abstract

Herein we report the photo‐ and electrochemical characterization of pyrimidopteridine N‐oxide‐based heterocycles. The potential of their application as organic photoredox catalysts is showcased in the photomediated contra‐thermodynamic E→Z isomerization of cinnamic acid derivatives and oxidative cyclization of 2‐phenyl benzoic acid to benzocoumarin using molecular oxygen as a mild oxidant. Furthermore, unprecedented intermolecular non‐covalent n–π‐hole interactions in solid state are discussed based on crystallographic and theoretical data.

With a light touch: In situ generation of Cl₂ from highly diluted HCl and HNO₃ and its light‐mediated cleavage leads to efficient oxochlorination of aryl cyclopropanes. This method tolerates a wide range of functional groups and can be scaled up easily. The products are valuable synthetic intermediates that are difficult to obtain otherwise, and which might also find application in biochemistry, for example, as precursors to antibody–drug conjugates.

Abstract

We report the visible‐light‐mediated synthesis of β‐chloro ketones from aryl cyclopropanes, oxygen, hydrochloric acid, and nitric acid. The operationally simple and catalyst‐free method uses cheap standard laboratory reagents and displays broad functional‐group tolerance. Moreover, scale up of the reaction and late‐stage functionalization of bioactive compounds is possible, providing the opportunity to utilize the cyclopropane ring as a masked β‐chloro ketone in a reaction sequence. We propose a light‐driven radical chain reaction initiated by the reaction of diluted hydrochloric and nitric acid to produce small quantities of molecular chlorine. The mechanistic hypothesis is supported by ¹⁸O labelling and UV/Vis experiments, cyclovoltammetry, and several control reactions.

Double agent: P K‐edge XANES and TDDFT calculations were used to quantify how nontrigonal structural deformations affect the electronic structure and reactivity of a series of P(NNN) compounds. The results suggest that biphilic P^III reactivity reported previously with and without a transition‐metal host stems from a common low‐lying phosphorus‐based acceptor orbital that becomes energetically accessible in response to nontrigonal P^III distortions.

Abstract

Constraining σ³‐P compounds in nontrigonal, entatic geometries has proven to be an effective strategy for promoting biphilic oxidative addition reactions more typical of transition metals. Although qualitative descriptions of the impact of structure and symmetry on σ³‐P complexes have been proposed, electronic structure variations responsible for biphilic reactivity have yet to be elucidated experimentally. Reported here are P K‐edge XANES data and complementary TDDFT calculations for a series of structurally modified P(N)₃ complexes that both validate and quantify electronic structure variations proposed to give rise to biphilic reactions at phosphorus. These data are presented alongside experimentally referenced electronic structure calculations that reveal nontrigonal structures predicted to further enhance biphilic reactivity in σ³‐P ligands and catalysts.

New Stevens rearrangement: Zinc‐halide‐catalyzed ring‐opening of epoxides with α‐amino acid‐derived tertiary allylic, propargylic, and benzylic amines followed by [2,3]‐ and [1,2]‐Stevens rearrangements of the resulting quaternary ammonium ylide intermediates has been established as a convenient method to access polysubstituted morpholin‐2‐ones through tandem formation of C−N, C−O, and C−C bonds (see scheme).

Abstract

A new strategy has been established for the synthesis of polysubstituted morpholin‐2‐ones through Stevens rearrangements of tertiary amines via in situ activation with epoxides. A range of α‐amino acid‐derived tertiary allylic, propargylic, and benzylic amines reacted with epoxides in the presence of zinc halide catalysts to afford structurally diverse allyl‐, allenyl‐, and benzyl‐substituted morpholin‐2‐ones, respectively, in moderate‐to‐good yields with high regioselectivity. The process involves [2,3]‐ and [1,2]‐Stevens rearrangements of quaternary ammonium ylide intermediates and constitutes a very convenient method to prepare polysubstituted morpholin‐2‐ones through tandem formation of C−N, C−O, and C−C bonds. Moreover, replacing epoxides with aziridines permitted the synthesis of polysubstituted piperazin‐2‐ones.

The coupling of two or more molecules of dinitrogen (N₂) occurs naturally under the radiative conditions present in the ionosphere and may be achieved synthetically under ultrahigh pressure or plasma conditions. However, the comparatively low N–N single-bond enthalpy generally renders the catenation of the strongly triple-bonded N₂ diatomic unfavorable and the decomposition of nitrogen chains a common reaction motif. Here, we report the surprising organoboron-mediated catenation of two N₂ molecules under near-ambient conditions to form a complex in which a [N₄]^2– chain bridges two boron centers. The reaction entails reductive coupling of two hypovalent-boron-bound N₂ units in a single step. Both this complex and a derivative protonated at both ends of the chain were characterized crystallographically.

Synlett
DOI: 10.1055/s-0037-1612413

We describe the synthesis of ionic-liquid-supported 1,3-dimethylimidazolidin-2-one, together with the halogenation of alcohols in a reaction system in which this reagent is combined with oxalyl chloride. A new method was established that does not require additives such as bases, and which permits the ready isolation and purification of the product. Good conversions were obtained, and good reusability of the reagent was observed.
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© Georg Thieme Verlag Stuttgart · New York

Article in Thieme eJournals:
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Abstract

An original two‐step organocatalytic synthesis of optically active glutarimides from 2‐oxocyclobutane carboxamides is described featuring an isothiourea‐catalyzed two‐atom ring‐expansive rearrangement.

Three in a row: A short synthetic route to chiral and structurally elaborate cyclobutanes with three contiguous stereocenters from the terpene verbenone is presented. In the key step, a highly efficient directing‐group‐assisted C(sp³)−H arylation was used to install a wide range of aryl and heteroaryl substituents with excellent stereocontrol. Removal of the 8‐aminoquinoline directing group from these compounds was demonstrated using an ozonolysis‐based cleavage method.

Abstract

This work demonstrates how a series of complex, chiral cyclobutane derivatives can be accessed in four steps from the terpene verbenone through the application of a directed C−H functionalization approach. The developed synthetic route involved an 8‐aminoquinoline‐directed C(sp³)−H arylation as the key step, and this reaction could be carried out with a wide range of aryl and heteroaryl iodides to furnish a variety of cyclobutane products with three contiguous stereocenters. Moreover, it was shown that the 8‐aminoquinoline auxiliary could be effectively removed from the cyclobutane derivatives using an ozonolysis‐based cleavage method.

Boron on a Staudinger trip: HN₃ reacts with the strong Lewis acid B(C₆F₅)₃ to give a highly labile HN₃⋅B(C₆F₅)₃ adduct, which readily decomposes above −20 °C to the aminoborane H(C₆F₅)NB(C₆F₅)₂ and N₂. This Staudinger‐like reaction, which involves a C₆F₅ group migration from boron to the attached nitrogen atom, was transferred to a variety of organic azides, enabling the synthesis of C₆F₅‐substituted aminoboranes and amines of the type H(R)N(C₆F₅).

Abstract

The reaction of HN₃ with the strong Lewis acid B(C₆F₅)₃ led to the formation of a very labile HN₃⋅B(C₆F₅)₃ adduct, which decomposed to an aminoborane, H(C₆F₅)NB(C₆F₅)₂, above −20 °C with release of molecular nitrogen and simultaneous migration of a C₆F₅ group from boron to the nitrogen atom. The intermediary formation of azide–borane adducts with B(C₆F₅)₃ was also demonstrated for a series of organic azides, RN₃ (R=Me₃Si, Ph, 3,5‐(CF₃)₂C₆H₃), which also underwent Staudinger‐like decomposition along with C₆F₅ group migration. In accord with experiment, computations revealed rather small barriers towards nitrogen release for these highly labile azide adducts for all organic substituents except R=Me₃Si (m.p. 120 °C, T _dec=189 °C). Hydrolysis of the aminoboranes provided C₆F₅‐substituted amines, HN(R)(C₆F₅), in good yields.

Under control: Reactions that involve the addition of carbon‐centered radicals to basic heteroarenes, followed by formal hydrogen atom loss, have become widely known as Minisci‐type reactions. Whilst the original protocols for radical generation remain in active use today, they have been joined in recent years by a new array of radical generation strategies that allow use of a wider variety of radical precursors that often operate under milder conditions.

Abstract

Reactions that involve the addition of carbon‐centered radicals to basic heteroarenes, followed by formal hydrogen atom loss, have become widely known as Minisci‐type reactions. First developed into a useful synthetic tool in the late 1960s by Minisci, this reaction type has been in constant use over the last half century by chemists seeking to functionalize heterocycles in a rapid and direct manner, avoiding the need for de novo heterocycle synthesis. Whilst the originally developed protocols for radical generation remain in active use today, they have been joined in recent years by a new array of radical generation strategies that allow use of a wider variety of radical precursors that often operate under milder and more benign conditions. The recent surge of interest in new transformations based on free radical reactivity has meant that numerous choices are now available to a synthetic chemist looking to utilize a Minisci‐type reaction. Radical‐generation methods based on photoredox catalysis and electrochemistry have joined approaches which utilize thermal cleavage or the in situ generation of reactive radical precursors. This review will cover the remarkably large body of literature that has appeared on this topic over the last decade in an attempt to provide guidance to the synthetic chemist, as well as a perspective on both the challenges that have been overcome and those that still remain. As well as the logical classification of advances based on the nature of the radical precursor, with which most advances have been concerned, recent advances in control of various selectivity aspects associated with Minisci‐type reactions will also be discussed.