Synthesis of Axially ChiralN‐Arylindoles via Atroposelective Cyclization of Ynamides Catalyzed by Chiral Brønsted Acids

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(20)

Published: March 5, 2022

In recent years, asymmetric catalysis of ynamides has attracted much attention, but these reactions mostly constructed central chirality, except for a few examples on the synthesis axially chiral compounds which exclusively relied noble-metal catalysis. Herein, facile access to N-heterocycles enabled by Brønsted acid-catalyzed 5-endo-dig cyclization is disclosed, represents first metal-free protocol construction from ynamides. This method allows practical and atom-economical valuable N-arylindoles in excellent yields with generally enantioselectivities. Moreover, organocatalysts ligands based such N-arylindole skeletons are demonstrated be applicable

Language: Английский

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Lewis Acid Catalyzed Cycloaddition of Bicyclobutanes with Ynamides for the Synthesis of Polysubstituted 2‐Amino‐bicyclo[2.1.1]hexenes

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(32)

Published: May 24, 2024

Abstract Synthesis of bicyclic scaffolds has gained significant attention in drug discovery due to their potential mimic benzene bioisosteres. Here, we present a mild and scalable Sc(OTf) 3 ‐catalyzed [3+2] cycloaddition bicyclo[1.1.0]butanes (BCBs) with ynamides, yielding diverse array polysubstituted 2‐amino‐bicyclo[2.1.1]hexenes good excellent yields. These products offer valuable starting materials for the construction novel functionalized bicyclo[1.1.0]butanes. Preliminary mechanistic studies indicate that reaction involves nucleophilic addition ynamides bicyclo[1.1.0]butanes, followed by an intramolecular cyclization situ generated enolate keteniminium ion. We expect these findings will encourage utilization complex bioisosteres foster further investigation into BCB‐based chemistry.

Language: Английский

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Brønsted Acid Catalyzed Dearomatization by Intramolecular Hydroalkoxylation/Claisen Rearrangement: Diastereo‐ and Enantioselective Synthesis of Spirolactams

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(52), P. 27164 - 27170

Published: Oct. 21, 2021

Described herein is a novel Brønsted acid catalyzed intramolecular hydroalkoxylation/Claisen rearrangement, allowing the practical and atom-economic synthesis of range valuable spirolactams from readily available ynamides in generally good to excellent yields with diastereoselectivities broad substrate scope. Importantly, an unexpected dearomatization nonactivated arenes heteroaromatic compounds involved this tandem sequence. Moreover, asymmetric version cyclization was also achieved by efficient kinetic resolution chiral phosphoric catalysis. In addition, [3,3]-rearrangement shown be kinetically preferred over related [1,3]-rearrangement theoretical calculations.

Language: Английский

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Copper‐Catalyzed Asymmetric Diyne Cyclization via [1,2]‐Stevens‐Type Rearrangement for the Synthesis of Chiral Chromeno[3,4‐c]pyrroles

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 61(7)

Published: Dec. 14, 2021

Here, we report a copper-catalyzed asymmetric cascade cyclization/[1,2]-Stevens-type rearrangement via non-diazo approach, leading to the practical and atom-economic assembly of various valuable chiral chromeno[3,4-c]pyrroles bearing quaternary carbon stereocenter in generally moderate good yields with wide substrate scope excellent enantioselectivities (up 99 % ee). Importantly, this protocol not only represents first example catalytic [1,2]-Stevens-type based on alkynes but also constitutes formal carbene insertion into Si-O bond.

Language: Английский

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General Synthesis of N-Trifluoromethyl Compounds with N-Trifluoromethyl Hydroxylamine Reagents

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(4), P. 1962 - 1970

Published: Jan. 19, 2022

N-CF3 compounds constitute valuable targets in medicinal chemistry. Extensive studies have been reported for the preparation of through fluorination and trifluoromethylation N-containing compounds. The development new synthetic methods from abundant easily available substrates is highly desirable but still challenging. Herein, we report design synthesis novel N-Cbz- N-Boc-N-trifluoromethyl hydroxylamine reagents by silver-mediated oxidative trifluoromethylation. These successfully applied to direct incorporation a NCF3 moiety into commonly used unsaturated under photoredox catalysis. This protocol enables efficient regioselective C-H trifluoromethylamination various (hetero)arenes, including complex bioactive molecules. Furthermore, variety alkenes, dienes, isonitriles undergo tandem trifluoromethylamination/functionalization delivering structurally diverse N-trifluoromethyl aliphatic heteroaromatic amines. Notably, previously unknown cyclic oxazolidinones oxazolones were conveniently prepared with reagents. diversification resulting α-trifluoromethylamino ketones afforded largely underexplored N-alkenyl- N-alkynyl-N-CF3

Language: Английский

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Enantioselective Copper‐Catalyzed Formal [2+1] and [4+1] Annulations of Diynes with Ketones via Carbonyl Ylides

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(43)

Published: Aug. 17, 2022

Carbonyl ylides have proven to be powerful synthons for the efficient construction of various valuable O-heterocycles, and formation carbonyl by reaction metal carbenes with carbonyls has attracted increasing attention over past decades. However, a catalyst-controlled highly enantioselective from is extremely challenging. Herein, we report novel copper-catalyzed asymmetric formal [2+1] [4+1] annulations diynes ketones via ylides. Importantly, this protocol not only represents first example successful epoxidation ylides, but also constitutes vinyl cations compounds. This method leads divergent, practical atom-economical synthesis range chiral oxiranes dihydrofurans in moderate excellent yields generally enantioselectivities diastereoselectivities remote-stereocontrol strategy.

Language: Английский

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Catalyst‐Dependent Stereospecific [3,3]‐Sigmatropic Rearrangement of Sulfoxide‐Ynamides: Divergent Synthesis of Chiral Medium‐Sized N,S‐Heterocycles

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(28)

Published: April 27, 2022

Medium-sized N,S-heterocycles have received tremendous interest due to their biological activities and potential medical applications. However, asymmetric synthesis of these compounds are extremely rare. Described herein is a catalyst-dependent [3,3]-sigmatropic rearrangement sulfoxide-ynamides, enabling divergent atom-economic series valuable medium-sized in moderate good yields with broad substrate scope. Importantly, excellent enantioselectivities been achieved via an unprecedented chirality-transfer. Moreover, theoretical calculations employed elucidate the origins stereospecific [3,3]-rearrangement.

Language: Английский

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Construction of Axially Chiral Arylpyrroles via Atroposelective Diyne Cyclization

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(23)

Published: March 30, 2023

Axially chiral biaryls widely exist in natural products and pharmaceuticals are used as ligands catalysts asymmetric synthesis. Compared to the well-established axially 6-membered biaryl skeletons, examples of 5-membered have been quite scarce, mono-substituted 3-arylpyrrole atropisomers not reported. Here, we disclose a copper-catalyzed atroposelective diyne cyclization for construction range arylpyrrole good excellent yields with generally enantioselectivities via oxidation X-H insertion vinyl cations. Importantly, this protocol only represents first synthesis atropisomers, but also constitutes example atropisomer Theoretical calculations further support mechanism cation-involved elucidate origin enantioselectivity.

Language: Английский

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Copper‐Catalyzed Enantioselective Doyle–Kirmse Reaction of Azide‐Ynamides via α‐Imino Copper Carbenes

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(10)

Published: Jan. 14, 2023

[2,3]-Sigmatropic rearrangement reaction involving sulfonium ylide (Doyle-Kirmse reaction) generated from metal carbenes represents one of the powerful methods for construction C(sp3 )-S and C-C bonds. Although significant advances have been achieved, asymmetric versions via generation ylides rarely reported to date, they so far limited diazo compounds as carbene precursors. Here, we describe a copper-catalyzed enantioselective Doyle-Kirmse azide-ynamide cyclization, leading practical divergent assembly an array chiral [1,4]thiazino[3,2-b]indoles bearing quaternary carbon stereocenter in generally moderate excellent yields enantioselectivities. Importantly, this protocol unique catalytic non-diazo approach unprecedented [2,3]-sigmatropic α-imino carbenes.

Language: Английский

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Regioselective Difunctionalization and Annulation of Ynamide

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(30)

Published: April 8, 2023

Abstract The use of ynamides in organic synthesis has gained significant attention due to their ability provide access complex molecular structures through transformations such as 1,2‐difunctionalization and annulation reactions. These reactions enable the formation highly functionalized N‐bearing olefins unusual heterocycles. In this minireview, we present a systematic overview regioselective difunctionalization ynamides. We discuss multi‐component reactions, radical‐triggered functionalizations across carbon–carbon multiple bonds bifunctional reagents ynamides, highlighting potential expanding substrate scope. Furthermore, insights into mechanistic breakthroughs that have been achieved recent years development these Finally, emphasize promising future prospects versatile building blocks for architectures.

Language: Английский

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