Chiral Aldehyde/Palladium Catalysis Enables Asymmetric Branched-Selective Ring-Opening Functionalization of Methylenecyclopropanes with Amino Acid Esters

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

Published: Jan. 10, 2025

Achieving catalytic asymmetric functionalization of methylenecyclopropanes (MCPs) by selective C–C bond cleavage is a notable challenge due to the intricate reaction partners involved. In this work, we report that chiral aldehyde/palladium combined catalysis enables MCPs with NH2-unprotected amino acid esters. This proceeds through regiospecific branched ring-opening mechanism, resulting in optically active α,α-disubstituted α-amino esters bearing nonconjugated terminal alkene units. Mechanism studies indicate pathways are irreversible and ultimate regioselectivity governed palladium catalysis. The products can be utilized construction dihydropyrazoles, α-methyl aspartic derivatives, analogues VPC01091 BMS-986104.

Language: Английский

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Enantio‐ and Regioselective Cascade Hydroboration of Methylenecyclopropanes for Facile Access to Chiral 1,3‐ and 1,4‐Bis(boronates)

Advanced Science, Journal Year: 2024, Volume and Issue: 11(21)

Published: March 13, 2024

Abstract Chiral 1, n‐bis(boronate) plays a crucial role in organic synthesis and medicinal chemistry. However, their catalytic asymmetric has long posed challenge terms of operability accessibility from readily available substrates. The recent discovery the C═C bond formation through β‐C elimination methylenecyclopropanes (MCP) provided an exciting opportunity to enhance molecular complexity. In this study, catalyzed cascade hydroboration MCP is developed. By employing different ligands, various homoallylic boronate intermediate are obtained ring opening process. Subsequently, with HBpin or B 2 pin resulted enantioenriched chiral 1,3‐ 1,4‐bis(boronates) high yields, accompanied by excellent chemo‐ enantioselectivities. selective transformation these two distinct C─B bonds also demonstrated application potential synthesis.

Language: Английский

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Enantioselective 1,4-Borylamination via Copper-Catalyzed Cascade Hydroborylation and Hydroamination of Arylidenecyclopropanes

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(47), P. 32283 - 32291

Published: Nov. 13, 2024

Compounds bearing both boryl and amino groups at distal positions are invaluable synthons for synthesizing pharmaceuticals, drug candidates, natural products, but their catalytic enantioselective synthesis remains rarely explored. We report the first 1,4-borylamination reaction through a copper-catalyzed cascade hydroborylation hydroamination of arylidenecyclopropanes. This combines four readily available components in highly chemo-, site-, fashion (>20:1 r.r. up to 99% ee), yielding diverse array synthetically valuable enantioenriched 4-amino alkylboronates. The versatile utility these products is highlighted by transformations wide applications pharmaceutical discovery. Preliminary mechanistic studies were conducted elucidate operative pathway, intermediates, origins its high chemo- site-selectivity.

Language: Английский

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Enantioselective 1,4-borylative amination

Trends in Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Enantioselective Pd- and Cu-Catalyzed Hydrofunctionalization of Methylenecyclopropanes via a Distal C–C Bond Cleavage

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

Published: Jan. 28, 2025

The enantioselective ring-opening reactions of methylenecyclopropanes (MCPs) involving C–C bond activation via oxidative addition transition metals have been rarely reported. Here, we disclose a Pd/Cu-catalyzed enantio- and regioselective coupling between cyclic imino esters MCPs to produce α-allylated 2H-pyrrole derivatives. In this reaction, azomethine ylide formed by chiral copper catalyst with ketimine ester would serve as nucleophile react activated palladium catalysis. This bimetallic system exhibited broad substrate scope high regio- enantioselectivities.

Language: Английский

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Ligand-Controlled Enantioselective Copper-Catalyzed Hydroboration and Ring-Opening Dihydroboration of Arylidenecyclobutanes

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

Published: March 25, 2025

Arylidenecyclobutanes are readily accessible and versatile reagents in synthetic chemistry due to the multifaceted reactivity exhibited by their alkene strained cyclobutane moieties. However, metal-catalyzed enantioselective functionalization of arylidenecyclobutanes, particularly controllable ring-retaining ring-opening reactions, is rarely explored. Considering utility enantioenriched organoboronate compounds, herein we report ligand-controlled copper-catalyzed hydroboration dihydroboration reactions arylidenecyclobutanes that afford chiral α-cyclobutyl benzylboronate 1,5-diboronate compounds with high enantioselectivity when (S)-DTBM-Segphos (S,S)-Ph-BPE employed, respectively. Mechanistic studies reveal process via β-C elimination significantly slower than arylidenecyclopropanes presence CuOAc (S,S)-Ph-BPE. The these two protocols further demonstrated through conducting various stereospecific site-selective transformations organoboron products, including concise synthesis bioactive molecules.

Language: Английский

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Enantioselective 1,4-Borylamination Enabled by Copper Catalysis

Synlett, Journal Year: 2025, Volume and Issue: unknown

Published: April 9, 2025

Abstract Compounds bearing both boryl and amino groups are highly valuable synthons in organic synthesis. However, while enantioselective 1,1- 1,2-borylamination reactions have been developed, processes enabling distal borylamination rarely investigated. Here, we present an 1,4-borylamination reaction, achieved through a copper-catalyzed cascade hydroborylation hydroamination of arylidenecyclopropanes. This four-component reaction provides direct access to enantioenriched 4-aminoalkylboronate products with high chemo-, site-, enantioselectivity. The versatility these was demonstrated their broad transformations extensive applications the synthesis various drug core structures. Additionally, preliminary mechanistic studies were conducted investigate pathway, intermediates, chemo- site-selectivity.

Language: Английский

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Modular Assembly of Axially Chiral QUINAP Derivatives via Nickel-Catalyzed Enantioselective C–P Cross-Coupling

ACS Catalysis, Journal Year: 2025, Volume and Issue: unknown, P. 8268 - 8273

Published: May 2, 2025

Language: Английский

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Modular Synthesis of Chiral 1,3-Diboronates with Differentiable Boryl Groups via Cu-Catalyzed Borylalkylation of Styrenes

ACS Catalysis, Journal Year: 2025, Volume and Issue: unknown, P. 8913 - 8924

Published: May 12, 2025

Language: Английский

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Pd-Catalyzed Hydrocyanation of Methylenecyclopropanes: A Highly Selective Ring-Opening Access to 2-Substituted Allylic Nitriles

Organic Letters, Journal Year: 2024, Volume and Issue: 26(44), P. 9431 - 9435

Published: Oct. 30, 2024

Transition-metal-catalyzed hydrofunctionalization of methylenecyclopropanes presents a useful but challenging transformation due to the complex selectivity and multiple reaction pathways. We describe herein an unprecedented highly efficient selective palladium-catalyzed hydrocyanation give various 2-substituted allylic nitriles. Mechanistic studies demonstrated that may undergo Markovnikov-type hydrometalation β-carbon elimination.

Language: Английский

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