Synthesis of Atropisomers by Transition-Metal-Catalyzed Asymmetric C–H Functionalization Reactions

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(35), P. 14025 - 14040

Published: Aug. 25, 2021

Transition-metal-catalyzed enantioselective C-H functionalization has become a powerful strategy for the formation of C-C or C-X bonds, enabling highly asymmetric synthesis wide range enantioenriched compounds. Atropisomers are widely found in natural products and pharmaceutically relevant molecules, have also applications as privileged frameworks chiral ligands catalysts. Thus, research into routes atropisomers garnered great interest recent years. In this regard, transition-metal-catalyzed emerged an atom-economic efficient toward their synthesis. Perspective, approaches by reactions summarized. The main focus here is on catalysis via Pd, Rh, Ir complexes, which been most frequently utilized catalysts among reported reactions. Finally, we discuss limitations available protocols give outlook possible future avenues research.

Language: Английский

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Cobalt-Catalyzed Enantioselective C–H Arylation of Indoles

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(2), P. 798 - 806

Published: Jan. 10, 2022

Atropoisomeric (hetero)biaryls are scaffolds with increasing importance in the pharmaceutical and agrochemical industries. Although it is most obvious disconnection to construct such compounds, direct enantioselective C–H arylation through concomitant induction of chiral information remains extremely challenging uncommon. Herein, unprecedented earth-abundant 3d-metal-catalyzed atroposelective reported, furnishing rare atropoisomeric C2-arylated indoles. Kinetic studies DFT computation revealed an uncommon mechanism for this asymmetric transformation, oxidative addition being rate- enantio-determining step. Excellent stereoselectivities were reached (up 96% ee), while using unusual N-heterocyclic carbene ligand bearing essential remote substituent. Attractive dispersion interactions along positive C–H---π exerted by identified as key factors guarantee excellent enantioselection.

Language: Английский

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Traditional and sustainable approaches for the construction of C–C bonds by harnessing C–H arylation

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Feb. 28, 2022

Abstract Biaryl scaffolds are found in natural products and drug molecules exhibit a wide range of biological activities. In past decade, the transition metal-catalyzed C–H arylation reaction came out as an effective tool for construction biaryl motifs. However, traditional reactions have limitations like harsh conditions, narrow substrate scope, use additives etc. therefore encouraged synthetic chemists to look alternate greener approaches. This review aims draw general overview on bond formation C–C bonds with aid different methodologies, majorly highlighting sustainable

Language: Английский

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Catalytic Asymmetric Construction of Axially and Centrally Chiral Heterobiaryls by Minisci Reaction

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(13), P. 6040 - 6049

Published: March 24, 2022

Axially chiral biaryls and heterobiaryls constitute the most represented subclass of atropisomers with prevalence in natural products, bioactive compounds, privileged ligand/catalysts, optically pure materials. Despite many ionic protocols for their construction, radical-based variants represent another highly desirable intriguing strategy but are far less developed. Moreover, efficient synthesis axially heterobiaryl molecules, especially ones having multiple heteroatoms other types elements, through radical routes remains extremely limited. We herein disclose first catalytic asymmetric, metal-free construction centrally by Minisci reaction 5-arylpyrimidines α-amino acid-derived redox-active esters. This is enabled use 4CzIPN as an organic photoredox catalyst conjunction a phosphoric acid catalyst. The achieved variety interesting featuring union α-branched amine generally excellent regio-, diastereo-, enantioselectivity (up to 82% yield; >19:1 dr; >99% ee). finding also builds up new platform development desymmetrization methods via radical-involved atroposelective functionalization at heteroarene prochiral heterobiaryls.

Language: Английский

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Enantioselective Access to Triaryl-2-pyrones with Monoaxial or Contiguous C–C Diaxes via Oxidative NHC Catalysis

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(4), P. 2565 - 2575

Published: Feb. 6, 2023

We present herein an unprecedented stereoselective synthesis of triaryl-2-pyrones with monoaxial or contiguous diaxes from readily available starting materials. This N-heterocyclic carbene catalysis method adopts atroposelective annulation 2-aryketones ynals under oxidative conditions. The includes the construction one two axes in a single operation, achieves step economy, and affords axially chiral moderate to good yields, high excellent enantioselectivities. DFT calculations relative energies stereoisomers rotational barriers were performed.

Language: Английский

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Binaphthyl Scaffold: A Class of Versatile Structure in Asymmetric C–H Functionalization

ACS Catalysis, Journal Year: 2022, Volume and Issue: 12(15), P. 9359 - 9396

Published: July 18, 2022

Over the past decades, transition metal-catalyzed enantioselective C–H functionalization has emerged as a straightforward and powerful tool for rapid access to chiral molecules. The enormous advances achieved in this emerging area largely rely on development of ligands that can enable both high levels enantiocontrol efficiency. Chiral bearing binaphthyl scaffolds have been proven be versatile asymmetric due their availability, unique stereochemical features, ease fine-tuning steric electronic properties. In Review, we summarized advance applications basis scaffold functionalization.

Language: Английский

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Sulfoxide-Directed or 3d-Metal Catalyzed C–H Activation and Hypervalent Iodines as Tools for Atroposelective Synthesis

Accounts of Chemical Research, Journal Year: 2023, Volume and Issue: 56(3), P. 189 - 202

Published: Jan. 27, 2023

ConspectusThe expanding applications of atropisomeric compounds combined with the growing diversity such chiral molecules translate into an urgent need for innovative synthetic strategies allowing their rapid, efficient, and sustainable synthesis. Recently, C-H activation approach has provided new opportunities synthesizing axially compounds. The two complementary approaches implementation methodology toward synthesis imply either ortho-functionalization preexisting prochiral or atropo-unstable biaryl substrates direct arylation sterically encumbered aromatics. first required preinstallation a directing group on precursor, which drastically limits thus generated products. To tackle this important limitation, we have envisioned using sulfoxide as both auxiliary. Indeed, in addition to efficiently coordinating Pd-catalyst induction, moiety can be easily removed, via sulfoxide/lithium exchange, after step, guaranteeing almost unlimited postdiversification efficiency generality concept could illustrated by developing atropo-diastereoselective oxidative Heck reaction, acetoxylation, iodination, well arylation. Besides, utility was demonstrated designing expedient steganone precursor. This unique transformation also allowed us build up unprecedented triaryl scaffolds perfectly controlled axes, original skeletons ligand design. While considering atroposelective arylations, clear antagonism between harsh reaction conditions frequently coupling hindered atropo-stability product, resulted scarcity transformations. solve fundamental challenge, focused application low-valent cobalt catalyst, prompted catalyze indoles at C2 position under extremely mild (room temperature). Accordingly, C2-arylation achieved carbene delivering uncommon atropoisomerically pure excellent yields enantioselectivities. Detailed experimental theoretical mechanistic studies shed light mechanism transformation, providing strong evidence regarding origin enantioselectivity. Finally, steric hindrance guarantee molecule couple partners is limitation not only development but C-N Despite long history incredible advances Ullmann-Goldberg Buchwald-Hartwig couplings, versions transformations remained until recently. Our idea challenging issue consisted hypervalent iodines highly reactive partners, desired N-arylations occur room temperature. hypothesis validated reporting Cu-catalyzed N-arylation, λ3-iodanes partners. Subsequently, enantioselective version N-arylation successfully established Cu-complex bearing BOX ligand. In conclusion, report herein tailored-made solutions provide construct molecules, including biaryls molecules.

Language: Английский

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Enantioselective Synthesis of Indole-Fused Polycycles Bearing Four Consecutive Stereocenters via Rhodium Catalysis

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 3, 2025

Indole-fused polycycles are common in natural products and bioactive molecules, yet their concise efficient synthesis remains challenging, especially for compounds with multiple stereocenters. Herein, we report the application of a chiral CpxRhIII catalyst enantioselective C–H activation/[4+2] annulation indoles bicyclic alkenes. This catalytic system exhibits high enantioselectivity broad functional group tolerance operates under benign conditions. The scope this methodology encompasses variety substrates, delivering novel polycyclic four consecutive stereocenters bridged ring good to excellent yields remarkable enantioselectivities (≤1:99 er). approach facilitates structurally diverse molecules that retain integrity while introducing chirality. More importantly, 3ab significantly inhibited proliferation CESS Kasumin-1 cells IC50 values 0.76 0.28 μM, respectively. In addition, has been demonstrated as an effective agent promoting apoptosis cells.

Language: Английский

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Rhodium(III)-Catalyzed Enantioselective C–H Activation/Annulation of Ferrocenecarboxamides with Internal Alkynes

ACS Catalysis, Journal Year: 2022, Volume and Issue: 12(5), P. 3083 - 3093

Published: Feb. 21, 2022

Efficient synthesis of planar chiral ferrocene-fused heterocyclic molecules is challenging in asymmetric synthesis. Herein, we report an enantioselective C–H activation/annulation ferrocenecarboxamides with internal alkynes promoted by CpRh(III) catalysis. Trisubstituted Cp-derived Rh complexes are found to be enabling catalysts, which lead a broad substrate scope good functional group compatibility. Planar pyridone products obtained high yields (up 90%) excellent enantioselectivity 99% ee). Combined experimental and computational studies support the proposed reaction mechanism.

Language: Английский

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Access to axially chiral aryl 1,3-dienes by transient group directed asymmetric C–H alkenylations

Organic Chemistry Frontiers, Journal Year: 2022, Volume and Issue: 9(8), P. 2109 - 2115

Published: Jan. 1, 2022

An enantioselective olefinic C–H alkenylation using transient group was disclosed to afford axially chiral aryl 1,3-dienes in up 99% yields and >99% ee. The derived carboxylic acid efficient ligand asymmetric alkylation.

Language: Английский

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