Recent Computational Studies on Mechanisms of Hypervalent Iodine(III)-Promoted Dearomatization of Phenols

2020 ◽  
Vol 24 (18) ◽  
pp. 2106-2117
Author(s):  
Hanliang Zheng ◽  
Xiao-Song Xue
Keyword(s):  
Hypervalent Iodine ◽  
Computational Studies ◽  
Mechanistic Studies

Hypervalent iodine-promoted dearomatization of phenols has received intense attention. This mini-review summarizes recent computational mechanistic studies of phenolic dearomatizations promoted by hypervalent iodine(III) reagents or catalysts. The first part of this review describes mechanisms of racemic dearomatization of phenols, paying special attention to the associative and dissociative pathways. The second part focuses on mechanisms and selectivities of diastereo- or enantio-selective dearomatization of phenols.

TEMPO-mediated homocoupling of aryl Grignard reagents: mechanistic studies

2015 ◽  
Vol 13 (9) ◽  
pp. 2762-2767 ◽  
Author(s):  
Sandip Murarka ◽  
Juri Möbus ◽  
Gerhard Erker ◽  
Christian Mück-Lichtenfeld ◽  
Armido Studer
Keyword(s):  
Grignard Reagents ◽  
Computational Studies ◽  
Mechanistic Studies

The mechanism of TEMPO mediated oxidative homo-coupling of aryl Grignard reagents to biphenyls is investigated in detail by experimental and computational studies.

scholarly journals Mechanistic studies on the CAN-mediated intramolecular cyclization of δ-aryl-β-dicarbonyl compounds

2013 ◽  
Vol 9 ◽  
pp. 1472-1479 ◽  
Author(s):  
Brian M Casey ◽  
Dhandapani V Sadasivam ◽  
Robert A Flowers II
Keyword(s):  
Intramolecular Cyclization ◽  
Computational Studies ◽  
Mechanistic Studies ◽  
Dicarbonyl Compounds ◽  
Radical Intermediates ◽  
Aromatic Substrates ◽  
Site Selectivity ◽  
Intramolecular Cyclizations ◽  
Cyclohexadienyl Radical ◽  
The Stability

The synthesis of 2-tetralones through the cyclization of δ-aryl-β-dicarbonyl substrates by using CAN is described. Appropriately functionalized aromatic substrates undergo intramolecular cyclizations generating 2-tetralone derivatives in moderate to good yields. DFT computational studies indicate that successful formation of 2-tetralones from δ-aryl-β-dicarbonyl radicals is dependent on the stability of the subsequent cyclohexadienyl radical intermediates. Furthermore, DFT computational studies were used to rationalize the observed site selectivity in the 2-tetralone products.

scholarly journals Predicting the Right Mechanism for Hypervalent Iodine Reagents by Applying Two Types of Hypervalent Twist Models:Apical Twist and Equatorial Twist

2021 ◽  
Author(s):  
Tian-Yu Sun ◽  
Kai Chen ◽  
Qihui Lin ◽  
Ting-Ting You ◽  
Peng-gang Yin
Keyword(s):  
Reductive Elimination ◽  
Reaction Pattern ◽  
Hypervalent Iodine ◽  
Mechanistic Studies ◽  
General Reaction ◽  
The Right

Since the hypervalent twist followed by reductive elimination is a general reaction pattern for hypervalent iodine reagents, mechanistic studies about the hypervalent twist step could provide significant guidance for experiments....

scholarly journals Mechanism of Iodine(III)-Promoted Oxidative Dearomatizing Hydroxylation of Phenols: Evidence for Radical-Chain Pathway

2020 ◽  
Author(s):  
Karol Kraszewski ◽  
Ireneusz Tomczyk ◽  
Aneta Drabinska ◽  
Krzysztof Bienkowski ◽  
Renata Solarska ◽  
...  
Keyword(s):  
High Resolution Mass Spectrometry ◽  
Hypervalent Iodine ◽  
Synthetic Approach ◽  
Chain Mechanism ◽  
Mechanistic Studies ◽  
Radical Chain ◽  
Oxidative Dearomatization ◽  
Radical Chain Mechanism ◽  
Rate Determining Step ◽  
Mechanism Of The Reaction

In the recent years, the dearomatization of phenols with the addition of nucleophiles to the aromatic ring, induced by hypervalent iodine(III) reagents and catalysts, has emerged as a highly useful synthetic approach. However, experimental mechanistic studies of this important process have been extremely scarce. As a result, the mechanism of the reaction remained elusive and as of today there exist as many as three distinct mechanistic proposals. In this report, we describe systematic investigations of the dearomatizing hydroxylation of phenols using an array of experimental techniques. Kinetics, EPR spectroscopy, and reactions with radical probes demonstrate that all the previously suggested mechanisms are incorrect, and that the transformation in fact proceeds via a radical-chain mechanism, with the aryloxyl radical being the key chain-carrying intermediate. Moreover, UV and NMR spectroscopy, high-resolution mass spectrometry, and cyclic voltammetry show that before reacting with the aryloxyl radical, water molecule becomes activated by the interaction with the iodine(III) center, causing this formally nucleophilic substrate to act as an electrophile. The C–O bond formation is identified as the rate-determining step of the reaction. This step generates the dearomatized product and an iodanyl(II) species, which is the second chain-carrying radical. The radical-chain mechanism emerging from our investigations allows to rationalize all other existing observations regarding the iodine(III)-promoted oxidative dearomatization of phenols.<br>

scholarly journals Mechanism of Iodine(III)-Promoted Oxidative Dearomatizing Hydroxylation of Phenols: Evidence for Radical-Chain Pathway

2020 ◽  
Author(s):  
Karol Kraszewski ◽  
Ireneusz Tomczyk ◽  
Aneta Drabinska ◽  
Krzysztof Bienkowski ◽  
Renata Solarska ◽  
...  
Keyword(s):  
High Resolution Mass Spectrometry ◽  
Hypervalent Iodine ◽  
Synthetic Approach ◽  
Chain Mechanism ◽  
Mechanistic Studies ◽  
Radical Chain ◽  
Oxidative Dearomatization ◽  
Radical Chain Mechanism ◽  
Rate Determining Step ◽  
Mechanism Of The Reaction

In the recent years, the dearomatization of phenols with the addition of nucleophiles to the aromatic ring, induced by hypervalent iodine(III) reagents and catalysts, has emerged as a highly useful synthetic approach. However, experimental mechanistic studies of this important process have been extremely scarce. As a result, the mechanism of the reaction remained elusive and as of today there exist as many as three distinct mechanistic proposals. In this report, we describe systematic investigations of the dearomatizing hydroxylation of phenols using an array of experimental techniques. Kinetics, EPR spectroscopy, and reactions with radical probes demonstrate that all the previously suggested mechanisms are incorrect, and that the transformation in fact proceeds via a radical-chain mechanism, with the aryloxyl radical being the key chain-carrying intermediate. Moreover, UV and NMR spectroscopy, high-resolution mass spectrometry, and cyclic voltammetry show that before reacting with the aryloxyl radical, water molecule becomes activated by the interaction with the iodine(III) center, causing this formally nucleophilic substrate to act as an electrophile. The C–O bond formation is identified as the rate-determining step of the reaction. This step generates the dearomatized product and an iodanyl(II) species, which is the second chain-carrying radical. The radical-chain mechanism emerging from our investigations allows to rationalize all other existing observations regarding the iodine(III)-promoted oxidative dearomatization of phenols.<br>

scholarly journals Teaching an old carbocation new tricks: Intermolecular C–H insertion reactions of vinyl cations

Science ◽  
2018 ◽  
Vol 361 (6400) ◽  
pp. 381-387 ◽  
Author(s):  
Stasik Popov ◽  
Brian Shao ◽  
Alex L. Bagdasarian ◽  
Tyler R. Benton ◽  
Luyi Zou ◽  
...  
Keyword(s):  
Theoretical Studies ◽  
Computational Studies ◽  
Mechanistic Studies ◽  
Insertion Reactions ◽  
Bond Forming ◽  
The Past ◽  
Carbon Carbon Bond ◽  
Transition Structures ◽  
The Subject ◽  
Experimental And Theoretical Studies

Vinyl carbocations have been the subject of extensive experimental and theoretical studies over the past five decades. Despite this long history in chemistry, the utility of vinyl cations in chemical synthesis has been limited, with most reactivity studies focusing on solvolysis reactions or intramolecular processes. Here we report synthetic and mechanistic studies of vinyl cations generated through silylium–weakly coordinating anion catalysis. We find that these reactive intermediates undergo mild intermolecular carbon-carbon bond–forming reactions, including carbon-hydrogen (C–H) insertion into unactivated sp3 C–H bonds and reductive Friedel-Crafts reactions with arenes. Moreover, we conducted computational studies of these alkane C–H functionalization reactions and discovered that they proceed through nonclassical, ambimodal transition structures. This reaction manifold provides a framework for the catalytic functionalization of hydrocarbons using simple ketone derivatives.

Designing Rh(I)-Half-Sandwich Catalysts for Alkyne [2+2+2] Cycloadditions

Synlett ◽  
2020 ◽  
Author(s):  
Laura Orian ◽  
F. Matthias Bickelhaupt
Keyword(s):  
Rational Design ◽  
Computational Studies ◽  
Synthetic Route ◽  
Mechanistic Studies ◽  
Mild Conditions ◽  
Aromatic Ligand ◽  
Polycyclic Aromatic ◽  
Metal Catalyzed ◽  
Cyclopentadienyl Anion ◽  
Half Sandwich

AbstractMetal-mediated [2+2+2] cycloadditions of unsaturated molecules to cyclic and polycyclic organic compounds are a versatile synthetic route affording good yields and selectivity under mild conditions. In the last two decades, in silico investigations have unveiled important details about the mechanism and the energetics of the whole catalytic cycle. Particularly, a number of computational studies address the topic of half-sandwich catalysts which, due to their structural fluxionality, have been widely employed, since the 1980s. In these organometallic species, the metal is coordinated to an aromatic ring, typically the ubiquitous cyclopentadienyl anion, C5H5 –(Cp) or to the Cp moiety of a larger polycyclic aromatic ligand (Cp′). During the catalytic process, the metal continuously ‘slips’ on the ring, changing its hapticity. This phenomenon of metal slippage and its implications for the catalyst’s performance are discussed in this work, referring to the most important computational mechanistic studies reported in literature for Rh(I) half-metallocenes, with the purpose of providing hints for a rational design of this class of compounds.1 Introduction2 Mechanism of Metal-Catalyzed Acetylene [2+2+2] Cycloaddition to Benzene and the Problem of the Indenyl Effect2.1 Acetylene-Acetonitrile [2+2+2] Co-cycloaddition to 2-Methylpyridine: Evidence of the Indenyl Effect2.2 Heteroaromatic Catalysts and the Evidence of a Reverse Indenyl Effect2.3 Booth’s Mechanistic Hypothesis and the Evidence of the Indenyl Effect3 Structure–Reactivity Correlation: The Slippage-Span Model4 Conclusions and Perspectives

scholarly journals Visible-Light, Iodine-Promoted Formation of N-Sulfonyl Imines and N-Alkylsulfonamides from Aldehydes and Hypervalent Iodine Reagents

Molecules ◽  
2018 ◽  
Vol 23 (8) ◽  
pp. 1838 ◽  
Author(s):  
Megan Hopkins ◽  
Zachary Brandeburg ◽  
Andrew Hanson ◽  
Angus Lamar
Keyword(s):  
Drug Discovery ◽  
Visible Light ◽  
Initial Step ◽  
Hypervalent Iodine ◽  
Mechanistic Studies ◽  
Synthetic Methodology ◽  
Reaction Conditions ◽  
Drug Discovery And Development ◽  
Radical Initiator ◽  
Reaction Proceeds

Alternative synthetic methodology for the direct installation of sulfonamide functionality is a highly desirable goal within the domain of drug discovery and development. The formation of synthetically valuable N-sulfonyl imines from a range of aldehydes, sulfonamides, and PhI(OAc)2 under practical and mild reaction conditions has been developed. According to mechanistic studies described within, the reaction proceeds through an initial step involving a radical initiator (generated either by visible-light or heat) to activate the reacting substrates. The reaction provides a synthetically useful and operationally simple, relatively mild alternative to the traditional formation of N-sulfonyl imines that utilizes stable, widely available reagents.

scholarly journals Natural Apocarotenoids and Their Synthetic Glycopeptide Conjugates Inhibit SARS-CoV-2 Replication

2021 ◽  
Vol 14 (11) ◽  
pp. 1111
Author(s):  
Ilona Bereczki ◽  
Henrietta Papp ◽  
Anett Kuczmog ◽  
Mónika Madai ◽  
Veronika Nagy ◽  
...  
Keyword(s):  
Cathepsin L ◽  
Antiviral Effect ◽  
Food Additive ◽  
New Drugs ◽  
Computational Studies ◽  
Mechanistic Studies ◽  
Cell Viability Assay ◽  
Viability Assay ◽  
Main Protease ◽  
A Cell

The protracted global COVID-19 pandemic urges the development of new drugs against the causative agent SARS-CoV-2. The clinically used glycopeptide antibiotic, teicoplanin, emerged as a potential antiviral, and its efficacy was improved with lipophilic modifications. This prompted us to prepare new lipophilic apocarotenoid conjugates of teicoplanin, its pseudoaglycone and the related ristocetin aglycone. Their antiviral effect was tested against SARS-CoV-2 in Vero E6 cells, using a cell viability assay and quantitative PCR of the viral RNA, confirming their micromolar inhibitory activity against viral replication. Interestingly, two of the parent apocarotenoids, bixin and β-apo-8’carotenoic acid, exerted remarkable anti-SARS-CoV-2 activity. Mechanistic studies involved cathepsin L and B, as well as the main protease 3CLPro, and the results were rationalized by computational studies. Glycopeptide conjugates show dual inhibitory action, while apocarotenoids have mostly cathepsin B and L affinity. Since teicoplanin is a marketed antibiotic and the natural bixin is an approved, cheap and widely used red colorant food additive, these readily available compounds and their conjugates as potential antivirals are worthy of further exploration.

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