Enantioselective Radical Addition Research Articles

Photoredox-catalyzed C(sp3)─H radical functionalization to enable asymmetric synthesis of α-chiral alkyl phosphine.

α-Chiral alkyl phosphines are privileged structural motifs with a wide application in organic and medical synthesis. It is highly desirable to develop stereoselective methods to prepare these enantioenriched molecules. The incorporation of C(sp3)─H functionalization and chiral phosphine chemistry is much less explored, probably because of the weak reactivity of C(sp3)─H bonds and/or the challenging site- and stereoselectivity issues. Herein, we disclose a synergistic catalysis system to enable an enantioselective radical addition process of α-substituted vinylphosphine oxides. An array of diverse α-chiral alkyl phosphors compounds is smoothly accessed by using the readily available chemicals as the inert C(sp3)─H bond reagent, such as sulfides, amines, alkenes, and toluene derivatives, exerting remarkable chemo-, site-, and enantioselectivity. On the basis of the mechanistic studies, both the C(sp3)─H bond activation and the stereochemistry-determining step are proposed to involve a single-electron transfer/proton transfer process.

Dual-Catalyzed Stereodivergent Electrooxidative Homocoupling of Benzoxazolyl Acetate.

The development of a reliable strategy for stereodivergent radical reactions that allows convenient access to all stereoisomers of homocoupling adducts with multiple stereogenic centers remains an unmet goal in organic synthesis. Herein, we describe a dual-catalyzed electrooxidative C(sp3)-H/C(sp3)-H homocoupling with complete absolute and relative stereocontrol for the synthesis of molecules with contiguous quaternary stereocenters in a general and predictable manner. The stereodivergent electrooxidative homocoupling reaction is achieved by synergistically utilizing two distinct chiral catalysts that convert identical racemic substrates into inherently distinctive reactive chiral intermediates, dictate enantioselective radical addition, and allow access to the full complement of stereoisomeric products via simple catalyst permutation. The successful execution of the dual-electrocatalytic strategy programmed via electrooxidative activation provides a significant conceptual advantage and will serve as a useful foundation for further research into cooperative stereocontrolled radical transformations and diversity-oriented synthesis.

Visible-light-driven asymmetric aldol reaction of ketones and glycinates via synergistic Lewis acid/photoredox catalysis.

Visible-light-driven direct asymmetric α-C(sp3)-H bond functionalization of glycinate provides a direct and efficient route for the synthesis of diverse optically enriched α-amino acid derivatives. However, asymmetric coupling between glycinate radical species and ketones faces significant challenges, including competitive pathways, mutable intermediates, as well as congested stereogenic centers. Herein, we disclose the first example for the asymmetric photocatalytic synthesis of a diverse array of β-diaryl-β-hydroxy-α-amino acetate derivatives from glycinates and heteroaryl ketones through the synergistic catalysis of achiral iridium photoredox catalyst and chiral lanthanide Lewis acid catalysts. The enantioselective radical addition pathway is supported by spectroscopic experiments, control experiments and DFT calculations.

Asymmetric [3 + 2] Photocycloaddition of β-Keto Esters and Vinyl Azides by Dual Photoredox/Nickel Catalysis.

Photocatalytic [3 + 2] cycloadditions and control of stereochemistry have remained a substantial challenge, particularly in the context of heterocycle synthesis; sporadic successful examples have involved enantioselective [3 + 2] photocycloaddition between redox-active direct group-containing cyclopropanes and alkenes for creation of cyclopentanes. Herein, we report a cooperative catalytic system comprising a chiral nickel Lewis acid catalyst and an organic photocatalyst fueled by visible-light irradiation that allows for the hitherto elusive asymmetric [3 + 2] photocycloaddition of β-keto esters with vinyl azides under redox-neutral conditions. This protocol enables highly enantioselective construction of polycyclic densely substituted 3,4-dihydro-2H-pyrrole heterocycles featuring two contiguous tetrasubstituted carbon stereocenters, including a useful chiral N,O-ketal motif that is not easily accessible with other catalytic methods. Mechanistic studies revealed that the overall reactivity relies on the seamless integration of dual roles of nickel catalysts by the catalytic formation of the substrate/Ni complex, assisting both photoredox event and enantioselective radical addition.

Enantioselective Radical Addition to Ketones through Lewis Acid-Enabled Photoredox Catalysis.

Photocatalysis opens up a new window for carbonyl chemistry. Despite a multitude of photochemical reactions of carbonyl compounds, visible light-induced catalytic asymmetric transformations remain elusive and pose a formidable challenge. Accordingly, the development of simple, efficient, and economic catalytic systems is the ideal pursuit for chemists. Herein, we report an enantioselective radical photoaddition to ketones through a Lewis acid-enabled photoredox catalysis wherein the in situ formed chiral N,N'-dioxide/Sc(III)-ketone complex serves as a temporary photocatalyst to trigger single-electron transfer oxidation of silanes for the generation of nucleophilic radical species, including primary, secondary, and tertiary alkyl radicals, giving various enantioenriched aza-heterocycle-based tertiary alcohols in good to excellent yields and enantioselectivities. The results of electron paramagnetic resonance (EPR) and high-resolution mass spectrum (HRMS) measurements provided favorable evidence for the stereocontrolled radical addition process involved in this reaction.

Visible-Light-Driven Enantioselective Radical Addition to Imines Enabled by the Excitation of a Chiral Phosphoric Acid–Imine Complex

Visible-Light-Driven Enantioselective Radical Addition to Imines Enabled by the Excitation of a Chiral Phosphoric Acid–Imine Complex

Access to axially chiral styrenes via a photoinduced asymmetric radical reaction involving a sulfur dioxide insertion

The wide applicability in various fields enables development of novel methods to access axially chiral styrenes to be of significance. Among the developed and potential synthetic strategies for this type of framework, the route based on an asymmetric radical process is more challenging and has not been achieved so far. Here we report a photo-promoted, three-component, asymmetric free radical reaction of potassium alkyltrifluoroborates, potassium metabisulfite, and 1-alkynylnaphthalen-2-ols, delivering axially chiral ( S , E )-1-(1-(alkylsulfonyl)-2-vinyl)naphthalen-2-ols with excellent enantioselectivity (93%–99% enantiomeric excess) and good yield (up to 97%). The transformation involves in situ generation of alkylsulfonyl radicals, tandem enantioselective radical addition, and a reduction process of radical species. • Photoinduced asymmetric catalytic radical approach to access axially chiral styrenes • A rare success in the field of asymmetric sulfur dioxide insertion • Broad substrate scope with excellent enantioselectivity and regioselectivity Development of new pathways for generation of axially chiral styrenes has gained great attention in recent years because of the wide applicability of axially chiral styrenes in chiral ligands, catalysts, and functional materials. Among the developed and potential synthetic strategies for synthesis of axially chiral styrenes, the synthetic route through an asymmetric radical process is more challenging and has not been achieved so far. Here we developed a photoinduced asymmetric catalytic radical approach to access sulfonyl-containing axially chiral styrenes with excellent enantioselectivity, regioselectivity, good yield, and broad substrate scope. Control experiments and DFT calculations were carried to understand the mechanism and the origin of the high enantioselectivity and Z/E selectivity of the reaction. Photoinduced three-component asymmetric free radical reaction of potassium alkyltrifluoroborates, potassium metabisulfite and 1-alkynylnaphthalen-2-ols, delivering axially chiral ( S , E )-1-(1-(alkylsulfonyl)-2-vinyl)naphthalen-2-ols with excellent enantioselectivity (93%–99% ee) and good yield (up to 97%). The transformation involves in situ generation of alkylsulfonyl radicals and a tandem enantioselective radical addition process.

Visible Light-mediated Enantioselective Radical Addition to α,β-Unsaturated Aldehydes

Key words radical conjugate addition - enals - photocatalysis - iminium ion catalysis

Enantioselective Radical Addition to Vinylpyridines by Photoredox Catalysis

Enantioselective Radical Addition to Vinylpyridines by Photoredox Catalysis

Enantioselective Radical Addition to Heteroarenes

Key words iridium catalysis - photocatalysis - Brønsted acids - Minisci-type reaction - heteroarenes

Enantioselective Radical Addition of CX4 to Olefins

Enantioselective Radical Addition of CX4 to Olefins

Rhodium‐Catalyzed Enantioselective Radical Addition of CX4 Reagents to Olefins

AbstractWe describe the synthetically useful enantioselective addition of Br−CX3 (X=Cl or Br) to terminal olefins to introduce a trihalomethyl group and generate optically active secondary bromides. Computational and experimental evidence supports an asymmetric atom‐transfer radical addition (ATRA) mechanism in which the stereodetermining step involves outer‐sphere bromine abstraction from a [(bisphosphine)RhIIBrCl] complex by a benzylic radical intermediate. This mechanism appears unprecedented in asymmetric catalysis.

Rhodium-Catalyzed Enantioselective Radical Addition of CX4 Reagents to Olefins.

We describe the synthetically useful enantioselective addition of Br-CX3 (X=Cl or Br) to terminal olefins to introduce a trihalomethyl group and generate optically active secondary bromides. Computational and experimental evidence supports an asymmetric atom-transfer radical addition (ATRA) mechanism in which the stereodetermining step involves outer-sphere bromine abstraction from a [(bisphosphine)RhII BrCl] complex by a benzylic radical intermediate. This mechanism appears unprecedented in asymmetric catalysis.

Combining the catalytic enantioselective reaction of visible-light-generated radicals with a by-product utilization system.

We report an unusual reaction design in which a chiral bis-cyclometalated rhodium(iii) complex enables the stereocontrolled chemistry of photo-generated carbon-centered radicals and at the same time catalyzes an enantioselective sulfonyl radical addition to an alkene. Specifically, employing inexpensive and readily available Hantzsch esters as the photoredox mediator, Rh-coordinated prochiral radicals generated by a selective photoinduced single electron reduction are trapped by allyl sulfones in a highly stereocontrolled fashion, providing radical allylation products with up to 97% ee. The hereby formed fragmented sulfonyl radicals are utilized via an enantioselective radical addition to form chiral sulfones, which minimizes waste generation.

ChemInform Abstract: Recent Synthetic Additions to the Visible Light Photoredox Catalysis Toolbox

AbstractReview: [93 refs.

Enantioselective Radical Addition to Ketimines: A Synthetic Route Towards α,α-Disubstituted α-Amino Acids

This article from Chemistry – A European Journal, published online on October 11, 2010 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors, the journal Editor in Chief, Neville Compton, and Wiley-VCH Verlag GmbH & Co. KGaA. The retraction has been agreed due to the wrong assignment of structure to prepared compounds 1c and 1d, which were used as catalysts in the title transformation. Accordingly, although the assigned structure, optical purity, and yield of products obtained through the title transformation are believed to be correct, conclusions derived from 1H NMR data obtained to determine the reaction mechanism are invalid.

Enantioselective radical addition to ketimines: a synthetic route towards α,α-disubstituted α-amino acids.

This article from Chemistry – A European Journal, published online on October 11, 2010 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors, the journal Editor in Chief, Neville Compton, and Wiley-VCH Verlag GmbH & Co. KGaA. The retraction has been agreed due to the wrong assignment of structure to prepared compounds 1c and 1d, which were used as catalysts in the title transformation. Accordingly, although the assigned structure, optical purity, and yield of products obtained through the title transformation are believed to be correct, conclusions derived from 1H NMR data obtained to determine the reaction mechanism are invalid.

Recent synthetic additions to the visible light photoredox catalysis toolbox.

The boom in visible light photoredox catalysis (VLPC) research has demonstrated that this novel synthetic approach is here to stay. VLPC enables reactive radical intermediates to be catalytically generated at ambient temperature, a feat not generally allowed through traditional pyrolysis- or radical initiator-based methodologies. VLPC has vastly extended the range of substrates and reaction schemes that have been traditionally the domain of radical reactions. In this review the photophysics background of VLPC will be briefly discussed, followed by a report on recent inroads of VLPC into decarboxylative couplings and radical C-H functionalization of aromatic compounds. The bulk of the review will be dedicated to advances in synergistic catalysis involving VLPC, namely the combination of photoredox catalysis with organocatalysis, including β-functionalization of carbonyl groups, functionalization of weak aliphatic C-H bonds, and anti-Markovnikov hydrofunctionalization of alkenes; dual catalysis with gold or with nickel, photoredox catalysis as an oxidation promoter in transition metal catalysis, and acid-catalyzed enantioselective radical addition to π systems.

Retraction of Highly Enantioselective Radical Addition to N-Benzoyl Hydrazones Using Chiral Ammonium Salts

ADVERTISEMENT RETURN TO ISSUEPREVAddition/CorrectionNEXTORIGINAL ARTICLEThis notice is a correctionRetraction of Highly Enantioselective Radical Addition to N-Benzoyl Hydrazones Using Chiral Ammonium SaltsDoo Ok Jang* and Sang Yoon KimCite this: J. Am. Chem. Soc. 2013, 135, 33, 12475Publication Date (Web):August 7, 2013Publication History Published online7 August 2013Published inissue 21 August 2013https://doi.org/10.1021/ja406816bCopyright © 2013 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views3128Altmetric-Citations1LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (114 KB) Get e-Alerts Get e-Alerts

ChemInform Abstract: Enantioselective Radical Addition to Ketimines: A Synthetic Route Towards α,α‐Disubstituted α‐Amino Acids.

AbstractThe title reaction provides a general route for the synthesis of α,α‐disubstituted α‐amino acids under metal‐free conditions.