Enantio‐ and Diastereoselective Synthesis of Chiral Tetrasubstituted α‐Amino Allenoates Bearing a Vicinal All‐Carbon Quaternary Stereocenter with Dual‐Copper‐Catalysis

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(31)

Published: June 1, 2023

The skeletons of chiral tetrasubstituted allenes bearing a vicinal all-carbon quaternary stereocenter are importance but still challenging to synthesize. Herein, we report enantio- and diastereoselective γ-additions 1-alkynyl ketimines with dual-copper-catalysis under mild conditions, affording α-amino allenoates in high yields (up 99 % yield) excellent enantioselectivities ee) diastereoselectivities >20 : 1 dr). Importantly, the stereodivergent synthesis products was realized by asymmetric γ-addition reaction Grignard reagent promoted epimerization. Moreover, dual-copper-catalyzed reactions were smoothly applied gram-scale adopted introduce allenyl moieties into bioactive molecules. Mechanistic experiments density functional theory (DFT) calculations demonstrated that catalyzed double copper catalysts.

Language: Английский

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Direct Catalytic Asymmetric and Regiodivergent N1‐ and C3‐Allenylic Alkylation of Indoles

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(21)

Published: March 21, 2023

Herein we report a Pd-catalyzed asymmetric allenylic alkylation strategy for the direct functionalization of 1H-indoles by employing P-chiral BIBOP-type ligands. The regioselectivity (N1/C3) this process can be switched efficiently. Using Cs2 CO3 at elevated temperatures in MeCN, N1-alkylated indoles bearing axial chirality with stereocenter non-adjacent (β) to nitrogen are produced good yields high enantioselectivity and complete N1-regioselectivity regardless electronic properties substitution patterns diverse indoles. K2 room temperature CH2 Cl2 , chiral C3-alkylated also obtained. Notably, introduce new class tri-substituted electrophiles that proceeded through different pathways from di-substituted electrophiles.

Language: Английский

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Challenging Task of Ni-Catalyzed Highly Regio-/Enantioselective Semihydrogenation of Racemic Tetrasubstituted Allenes via a Kinetic Resolution Process

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(11), P. 7419 - 7430

Published: March 6, 2024

The first earth-abundant transition metal Ni-catalyzed highly regio- and enantioselective semihydrogenation of racemic tetrasubstituted allenes via a kinetic resolution process as challenging task was well established. This protocol furnishes expedient access to diversity structurally important enantioenriched chiral allylic molecules with high regio-, enantio-, Z/E-selectivity. Remarkably, this proceeded one carbon–carbon double bond allenes, which regioselective complementary the Rh-catalyzed asymmetric version. Deuterium labeling experiments density functional theory (DFT) calculations were carried out reveal reasonable reaction mechanism explain regio-/stereoselectivity.

Language: Английский

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Recent advances in organocatalytic atroposelective reactions

Beilstein Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: 21, P. 55 - 121

Published: Jan. 9, 2025

Axial chirality is present in a variety of naturally occurring compounds, and becoming increasingly relevant also medicine. Many axially chiral compounds are important as catalysts asymmetric catalysis or have chiroptical properties. This review overviews recent progress the synthesis via organocatalysis. Atroposelective organocatalytic reactions discussed according to dominant catalyst activation mode. For covalent organocatalysis, typical enamine iminium modes presented, followed by N -heterocyclic carbene-catalyzed reactions. The bulk devoted non-covalent activation, where Brønsted acids feature most prolific catalytic structure. last part article discusses hydrogen-bond-donating other motifs such phase-transfer catalysts.

Language: Английский

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Recent advances in the metal-catalyzed asymmetric synthesis of chiral allenes

Organic Chemistry Frontiers, Journal Year: 2022, Volume and Issue: 9(18), P. 5053 - 5073

Published: Jan. 1, 2022

Recent advances in the metal-catalyzed asymmetric synthesis of chiral allenes are summarized. This review is categorized based on starting material, including alkynes, racemic allenes, and conjugated dienes.

Language: Английский

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Enantioselective Synthesis of Dihydropyrazoles by Palladium/Xu‐Phos‐Catalyzed Alleneamination of β,γ‐Unsaturated Hydrazones with Propargylic Acetates

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(20)

Published: March 10, 2023

The palladium-catalyzed asymmetric carboamination reaction is one of the most significant transformations in organic chemistry. Herein, we report first alleneamination β,γ-unsaturated hydrazones with propargylic acetates. This protocol enables efficient installation various multisubstituted allene groups onto dihydropyrazoles good yields excellent enantioselectivities. chiral sulfinamide phosphine ligand Xu-5 exhibits highly stereoselective control this protocol. salient features include readily available starting materials, a broad substrate scope, an easy scale-up, mild conditions and versatile transformations.

Language: Английский

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Construction of Acyclic All‐Carbon Quaternary Stereocenters and 1,3‐Nonadjacent Stereoelements via Organo/Metal Dual Catalyzed Asymmetric Allenylic Substitution of Aldehydes

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(20)

Published: March 13, 2023

A method for the asymmetric construction of functionalized acyclic all-carbon quaternary stereocenters and 1,3-nonadjacent stereoelements has been developed via organo/metal dual catalyzed allenylic substitution branched linear aldehydes, by developing an unknown secondary-secondary diamine as enabling organocatalyst. Although it is believed that diamines are difficult to be used organocatalysts in catalysis, this study demonstrates such can successfully combined with a metal catalyst catalysis. Our enables two important classes motifs which were previously access, axially chiral allene-containing bearing allenyl axial chirality central chirality, good yields high enantio- diastereoselectivity.

Language: Английский

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Novel Stereo‐Induction Pattern in Pudovik Addition/Phospha‐Brook Rearrangement Towards Chiral Trisubstituted Allenes

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(22)

Published: March 23, 2024

Abstract Despite the significance of chiral allene skeletons in catalysis, organic synthesis and medicinal chemistry et al., there is a scarcity reports on axially allenyl phosphorus compounds. Here, we disclosed an efficient straightforward cascade reaction between ethynyl ketones phosphine oxides, resulting broad array trisubstituted allenes incorporating moiety high yields with excellent stereoselectivities facilitated by peptide‐mimic phosphonium salt (PPS) Additionally, comprehensive series mechanistic experiments have been conducted to elucidate that this proceeds via asymmetric Pudovik addition followed subsequent phospha ‐Brook rearrangement occurs concomitantly kinetic resolution, representing stereospecific protonation process facilitating central‐to‐axial chirality transfer manner. We anticipate our research will pave way for promising exploration novel stereo‐induction pattern addition/ reaction.

Language: Английский

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Construction of axially chiral compounds via catalytic asymmetric radical reaction

Green Synthesis and Catalysis, Journal Year: 2022, Volume and Issue: 3(3), P. 212 - 218

Published: June 22, 2022

Language: Английский

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Catalyst-Controlled Divergent Reactions of 2,3-Disubstituted Indoles with Propargylic Alcohols: Synthesis of 3H-Benzo[b]azepines and Axially Chiral Tetrasubstituted Allenes

Organic Letters, Journal Year: 2022, Volume and Issue: 24(35), P. 6472 - 6476

Published: Aug. 30, 2022

Catalyst-controlled divergent reactions of 2,3-disubstituted indoles with propargylic alcohols were developed for the first time. In presence TsOH or B(C6F5)3 as catalyst, reacted smoothly 3-alkynyl-3-hydroxyisoindolinones to afford 3H-benzo[b]azepines by selective C2(sp2)-C3(sp2) ring expansion indoles. contrast, decreasing catalyst strength (e.g., chiral phosphoric acid) interrupted cascade reactions, affording axially tetrasubstituted allenes bearing an adjacent quaternary carbon stereocenter. Control experiments provided insights into reaction mechanism.

Language: Английский

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