Enantioselective Hydrodifluoroalkylation of Alkenes with Conformationally Tuned Peptidyl Hydrogen Atom Transfer Catalysts

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: March 20, 2025

We report the enantioselective hydrodifluoroalkylation of alkenes proceeding via an asymmetric hydrogen atom transfer (HAT) event catalyzed by thiol-containing tetrapeptides. Photocatalytic generation a difluoroacetyl radical followed carbon–carbon bond formation results in prochiral carbon-centered that engages with chiral catalyst. A trialkylamine reductant is proposed to turn over catalyst this net-reductive transformation. Notably, incorporating (S)-β-methyl-substituted cysteine as N-terminal residue improved selectivity relative native (Cys) residue, and X-ray crystallographic analysis supports conformational underpinning effect. range enantioenriched γ-substituted amides were synthesized up 96:4 enantiomeric ratio, demonstrating broad functional group tolerance method. Models accounting for induction are supporting DFT calculations.

Language: Английский

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Regiodivergent Hydroamidation of Alkenes via Cobalt-Hydride Catalysis

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: April 10, 2025

Regiodivergent hydroamin(d)ation of alkenes presents a valuable strategy for the synthesis diverse amines or amides from common set starting materials, yet achieving controlled regioselectivity remains significant challenge. In this work, we present cobalt-catalyzed regiodivergent hydroamidation alkenes, enabling enantioselective ipso- and migratory heterocyclic alkenes. The ability to finely tune various reaction parameters allows seamless switch in regioselectivity. Notably, selectivity are governed by choice cobalt catalyst anions. Mechanistic studies reveal neutral Co-H species mediating ipso-hydroamidation cationic intermediate promoting hydroamidation. This protocol exhibits broad substrate scope, high functional group tolerance, provides an efficient pathway synthetizing structurally amides.

Language: Английский

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A General Enantioselective α-Alkyl Amino Acid Derivatives Synthesis Enabled by Cobalt-Catalyzed Reductive Addition

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 12, 2024

Enantioenriched unnatural amino acids represent a prevalent motif in organic chemistry, with profound applications biochemistry, medicinal and materials science. Herein, we report cobalt-catalyzed aza-Barbier reaction of dehydroglycines unactivated alkyl halides to afford α-amino esters high enantioselectivity. This catalytic reductive alkylative addition protocol circumvents the use moisture-, air-sensitive organometallic reagents, stoichiometric chiral auxiliaries, enabling conversion variety primary, secondary, even tertiary α-alkyl-amino under mild conditions, thus leading broad functional group tolerance. The expedient access biologically active motifs demonstrates practicality this by reducing number synthetic steps enhancing efficiency.

Language: Английский

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Nickel‐Catalyzed α‐selective Hydroalkylation of Vinylarenes

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(47)

Published: Aug. 12, 2024

C(sp

Language: Английский

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Nickel‐Catalyzed α‐selective Hydroalkylation of Vinylarenes

Angewandte Chemie, Journal Year: 2024, Volume and Issue: 136(47)

Published: Aug. 12, 2024

Abstract C( sp 3 ) centers adjacent to (hetero) aryl groups are widely present in physiologically active molecules. Metal‐hydride‐catalyzed hydroalkylation of alkenes represents an efficient means forging )−C( bonds, boasting advantages as a wide source substrates, mild reaction conditions, and facile selectivity manipulation. Nevertheless, the vinylarenes encounters constraints terms substrate scope, necessitating employment activated alkyl halides or containing chelating groups, remains challenge. In this context, we report general nickel‐hydride‐catalyzed protocol for vinylarenes. Remarkably, system enables α‐selective both heteroaryl under extra ligand‐free condition, demonstrating excellent coupling efficiency selectivity. Furthermore, through incorporation chiral bisoxazoline ligands, have achieved regio‐ enantioselective vinylpyrroles, thereby facilitating synthesis α‐branched alkylated pyrrole derivatives.

Language: Английский

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Cobalt-Catalyzed Regio- and Enantioselective Hydroalkylation of 1,1-Disubstituted Styrenes

Synlett, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 2, 2024

Abstract The metal hydride catalyzed alkene hydroalkylation enables efficient alkyl–alkyl coupling, yielding structurally diverse chiral organic compounds. However, the control of stereochemical selectivity in still heavily relies on assistance substrate Lewis basic functional groups or polar heteroatom groups. We have recently developed a cobalt catalytic system and established paradigm enantioselective assisted by C–H···π noncovalent interactions. This approach asymmetric 1,1-disubstituted styrenes, thereby circumventing limitations imposed 1 Introduction 2 Reaction Development 3 Synthetic Applications 4 Mechanistic Investigation 5 Conclusion Future Outlook

Language: Английский

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Cobalt-Catalyzed Stereoselective Synthesis of Chiral Gem-Difluorocyclopropanes with Vicinal Stereocenters

Organic Chemistry Frontiers, Journal Year: 2024, Volume and Issue: 11(23), P. 6617 - 6626

Published: Jan. 1, 2024

We present a cobalt-catalyzed regio-, diastereo-, and enantioselective hydroalkylation of gem -difluorocyclopropenes, accessing chiral -difluorocyclopropanes with vicinal stereocenters.

Language: Английский

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Cobalt‐Catalyzed Hydroarylation of 2,3‐Dihydrofuran to Access α‐Arylated Tetrahydrofurans

ChemCatChem, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 11, 2024

Abstract The α ‐arylated tetrahydrofurans, commonly found in biologically active molecules, exhibit diverse biological activities and pharmacological effects. functionalization of 2,3‐dihydrofuran offers a potential route for the synthesis substituted tetrahydrofurans. Nevertheless, development earth‐abundant metal‐catalyzed regioselective hydrofunctionalization tetrahydrofurans remains to be pursued. Herein, we report cobalt‐catalyzed hydroarylation 2,3‐dihydrofuran, which serves as first example cobalt hydride‐catalyzed alkene hydroarylation. This reaction provides an efficient method with high efficiency, exclusive ‐arylation selectivity, remarkable functional group compatibility.

Language: Английский

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