Transition-Metal-Catalyzed Asymmetric Allylic Dearomatization Reactions

Accounts of Chemical Research, Год журнала: 2014, Номер 47(8), С. 2558 - 2573

Опубликована: Июнь 18, 2014

ConspectusDearomatization reactions serve as powerful methods for the synthesis of highly functionalized, three-dimensional structures starting with simple planar aromatic compounds. Among processes this type, catalytic asymmetric dearomatization (CADA) are attractive owing to large number compounds that readily available and fact they enable direct access enantiopure polycycles spirocycles, which frequently key structural motifs in biologically active natural products pharmaceuticals. However, a consequence their high stabilities, arenes only difficultly participate take place levels enantioselectivity.Transition-metal-catalyzed allylic substitution have been demonstrated be enantioselective formation C–C C–X (X = O, N, S, etc.) bonds. scope these has explored mainly using soft carbon nucleophiles, some hard nucleophiles such enolates preformed organometallic reagents, heteroatom nucleophiles. Readily accessible rarely used directly reactions.In Account, we present results studies conducted aimed at development transition-metal-catalyzed reactions. By utilizing general process, devised indoles, pyrroles, phenols, naphthols, pyridines, pyrazines, produce various functionalized bearing all-carbon quaternary stereogenic centers straightforward manner. In mechanistic investigations found five-membered spiroindolenines intermediates, undergo stereospecific migration form corresponding tetrahydro-1H-carbazoles upon treatment amount TsOH. It is worth noting no notable loss enantiomeric excess spiroindolenine derivatives takes during rearrangement process intervention "three-center–two-electron"-type transition state, proposal gained support from DFT calculations. Equally intriguing, tuning electronic nature tethers, pyrroles or indoles unprecedented Ir Ru catalyzed intramolecular alkylation promoted dearomatization/migration The operation novel reaction pathway provides additional information leading greater understanding functionalizations indoles. combined effort provide not efficient enantioenriched fused spiro but also strategies field catalysis.

Язык: Английский

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Catalytic Enantioselective Construction of Quaternary Stereocenters: Assembly of Key Building Blocks for the Synthesis of Biologically Active Molecules

Accounts of Chemical Research, Год журнала: 2015, Номер 48(3), С. 740 - 751

Опубликована: Фев. 25, 2015

The ever-present demand for drugs with better efficacy and fewer side effects continually motivates scientists to explore the vast chemical space. Traditionally, medicinal chemists have focused much attention on achiral or so-called "flat" molecules. More recently, has shifted toward molecules stereogenic centers since their three-dimensional structures represent a larger fraction of space number superior properties compared flat aromatic compounds. Quaternary stereocenters, in particular, add greatly three-dimensionality novelty molecule. Nevertheless, synthetic challenges building quaternary stereocenters largely prevented implementation drug discovery. lack effective broadly general methods enantioselective formation simple molecular scaffolds prompted us investigate new chemistry develop innovative tools solutions. In this Account, we describe three approaches constructing stereocenters: nucleophilic substitution 3-halooxindoles, conjugate addition boronic acids cyclic enones, allylic alkylation enolates. first approach, malonic ester nucleophiles attack electrophilic mediated by copper(II)-bisoxazoline catalyst. A variety oxindoles containing benzylic stereocenter can be accessed through method. However, it is only applicable specialized 3,3-disubstituted oxindole system. To access more context, turned our carbon α,β-unsaturated carbonyl acceptors. We discovered that presence catalytic palladium-pyridinooxazoline complex, arylboronic smoothly β-substituted enones furnish ketones β-benzylic high yields enantioselectivities. reaction compatible wide range acids, β-substituents, ring sizes. Aside from challenging motif not adjacent an group. Such but are difficult form asymmetric catalysis. address greater challenge, motivated reward, entered field palladium-catalyzed prochiral enolate about decade ago. On basis Tsuji's work, which solved issue positional selectivity unsymmetrical ketones, phosphinooxazoline ligand effectively rendered enantioselective. Extensive investigations then revealed exhibits broad scope accepts substrate classes, each its unique advantage applications. diverse array compounds bearing α-quaternary obtained excellent enantioselectivities, possibilities yet explored. As alternative palladium catalysis, also studied iridium-catalyzed alkylations generate vicinal tertiary single transformation. Overall, these provide small molecule blocks stereocenter, applied various scaffolds, tolerate functional groups. envision reported Account will increasingly useful discovery design.

Язык: Английский

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Iridium-Catalyzed Asymmetric Allylic Substitution Reactions

Chemical Reviews, Год журнала: 2018, Номер 119(3), С. 1855 - 1969

Опубликована: Дек. 24, 2018

In this review, we summarize the origin and advancements of iridium-catalyzed asymmetric allylic substitution reactions during past two decades. Since first report in 1997, Ir-catalyzed have attracted intense attention due to their exceptionally high regio- enantioselectivities. been significantly developed recent years many respects, including ligand development, mechanistic understanding, substrate scope, application synthesis complex functional molecules. an explicit outline ligands, mechanism, scope nucleophiles, applications is presented.

Язык: Английский

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Enantioselective construction of remote quaternary stereocentres

Nature, Год журнала: 2014, Номер 508(7496), С. 340 - 344

Опубликована: Апрель 8, 2014

Язык: Английский

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Acyclic Quaternary Carbon Stereocenters via Enantioselective Transition Metal Catalysis

Chemical Reviews, Год журнала: 2017, Номер 117(19), С. 12564 - 12580

Опубликована: Сен. 14, 2017

Whereas numerous asymmetric methods for formation of quaternary carbon stereocenters in cyclic systems have been documented, the construction acyclic with control absolute stereochemistry remains a formidable challenge. This Review summarizes enantioselective from achiral or chiral racemic reactants via transition metal catalysis.

Язык: Английский

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Stereodivergent α-Allylation of Linear Aldehydes with Dual Iridium and Amine Catalysis

Journal of the American Chemical Society, Год журнала: 2014, Номер 136(8), С. 3020 - 3023

Опубликована: Фев. 9, 2014

We describe the fully stereodivergent, dual catalytic α-allylation of linear aldehydes. The reaction proceeds via direct iridium-catalyzed substitution racemic allylic alcohols with enamines generated in situ. use an Ir(P,olefin) complex and a diarylsilyl prolinol ether as catalysts presence dimethylhydrogen phosphate promoter proved to be crucial for achieving high enantio- diastereoselectivity (>99% ee, up >20:1 dr). utility method is demonstrated concise enantioselective synthesis antidepressant (-)-paroxetine.

Язык: Английский

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An Ir/Zn Dual Catalysis for Enantio- and Diastereodivergent α-Allylation of α-Hydroxyketones

Journal of the American Chemical Society, Год журнала: 2016, Номер 138(35), С. 11093 - 11096

Опубликована: Авг. 22, 2016

An Ir/Zn dual catalysis has been developed for the enantio- and diastereodivergent α-allylation of unprotected α-hydroxyketones under mild conditions, in absence any additional base. The cooperative action a chiral iridium complex derived from phosphoramidites Zn-ProPhenol is most likely responsible its high reactivity, excellent enantioselectivity (up to >99% ee), good diastereoselectivity >20:1 dr). All four product stereoisomers could be prepared same set starting materials identical conditions by simple selection appropriate catalyst combinations.

Язык: Английский

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Stereodivergent Allylic Substitutions with Aryl Acetic Acid Esters by Synergistic Iridium and Lewis Base Catalysis

Journal of the American Chemical Society, Год журнала: 2016, Номер 139(1), С. 87 - 90

Опубликована: Дек. 17, 2016

The preparation of all possible stereoisomers a given chiral molecule bearing multiple stereocenters by simple and unified method is significant challenge in asymmetric catalysis. We report stereodivergent allylic substitutions with aryl acetic acid esters catalyzed synergistically metallacyclic iridium complex benzotetramisole. Through permutations the enantiomers two catalysts, four products adjacent are accessible high diastereoselectivity enantioselectivity. resulting activated ester can be converted readily to enantioenriched amides, unactivated esters, carboxylic acids one-pot manner.

Язык: Английский

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Chiral Monophosphorus Ligands for Asymmetric Catalytic Reactions

ACS Catalysis, Год журнала: 2016, Номер 6(8), С. 4814 - 4858

Опубликована: Июнь 9, 2016

Chiral monophosphorus ligands are playing an important role for the recent advances in asymmetric catalysis. This review summarizes latest progress various catalytic reactions with employment of chiral including allylic substitution, dearomative arylation, Heck reaction, cross-coupling, C–H bond functionalization, coupling π systems, addition, hydrogenation, and organocatalytic reactions. The new reactivity, selectivity, reaction mechanism enabled by these discussed.

Язык: Английский

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Iridium-Catalyzed Diastereo-, Enantio-, and Regioselective Allylic Alkylation with Prochiral Enolates

ACS Catalysis, Год журнала: 2016, Номер 6(9), С. 6207 - 6213

Опубликована: Авг. 17, 2016

ADVERTISEMENT RETURN TO ISSUEPREVViewpointNEXTIridium-Catalyzed Diastereo-, Enantio-, and Regioselective Allylic Alkylation with Prochiral EnolatesJ. Caleb Hethcox, Samantha E. Shockley, Brian M. Stoltz*View Author Information The Warren Katharine Schlinger Laboratory for Chemistry Chemical Engineering, Division of California Institute Technology, Pasadena, 91125, United States*E-mail: [email protected]Cite this: ACS Catal. 2016, 6, 9, 6207–6213Publication Date (Web):August 17, 2016Publication History Received6 July 2016Published online17 August inissue 2 September 2016https://pubs.acs.org/doi/10.1021/acscatal.6b01886https://doi.org/10.1021/acscatal.6b01886editorialACS PublicationsCopyright © 2016 American Society. This publication is available under these Terms Use. Request reuse permissions free to access through this site. Learn MoreArticle Views6013Altmetric-Citations166LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum full text article downloads since November 2008 (both PDF HTML) across all institutions individuals. These metrics regularly updated reflect usage leading up last few days.Citations number other articles citing article, calculated by Crossref daily. Find more information about citation counts.The Altmetric Attention Score a quantitative measure attention that research has received online. Clicking on donut icon will load page at altmetric.com additional details score social media presence given article. how calculated. Share Add toView InAdd Full Text ReferenceAdd Description ExportRISCitationCitation abstractCitation referencesMore Options onFacebookTwitterWechatLinked InRedditEmail (1 MB) Get e-AlertscloseSUBJECTS:Alcohols,Enolates,Post-translational modification,Selectivity,Substitution reactions e-Alerts

Язык: Английский

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