Diastereoselective Homocoupling of Benzylic C(sp3)–H Bonds Enabled by Halogen Transfer DOI
Xirong Liu, Xin An, Xue Zhao

et al.

Organic Letters, Journal Year: 2024, Volume and Issue: 26(43), P. 9257 - 9262

Published: Oct. 18, 2024

A transition-metal- and harsh-oxidant-free strategy for diastereoselective homocoupling of benzylic α-boryl carbanions has been developed. Central to this methodology is the ability halogen transfer reagent seamlessly integrate halogenation substitution within a compatible process. Additionally, also applicable diarylmethanes alkylheteroarenes. Substrates bearing oxidatively sensitive functional groups were well-tolerated. Preliminary studies suggest that hydrogen bond between two boryl contributes high diastereoselectivities.

Language: Английский

Direct Benzylic C–H Etherification Enabled by Base‐Promoted Halogen Transfer DOI

Kendelyn I. Bone,

Thomas R. Puleo,

Michael D. Delost

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 21, 2024

We disclose a benzylic C-H oxidative coupling reaction with alcohols that proceeds through synergistic deprotonation, halogenation and substitution sequence. The combination of tert-butoxide bases 2-halothiophene halogen oxidants enables the first general protocol for generating using benzyl halides deprotonative pathway. In contrast to existing radical-based methods functionalization, this process is guided by acidity trends. This gives rise new synthetic capabilities, including ability functionalize diverse methyl(hetero)arenes, tolerance oxidizable nucleophilic functional groups, precision site-selectivity polyalkylarenes use double etherification controllably oxidize methylarenes benzaldehydes.

Language: Английский

Citations

5
Annulation-induced hidden reactivity of N-(2-ethynylaryl)-1,2,3-triazoles to cinnolines under microwave irradiation DOI Creative Commons

Yangang Wu,

Chaewon Yi,

L.‐G. LIN

et al.

Green Synthesis and Catalysis, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

0
Direct Benzylic C–H Etherification Enabled by Base-Promoted Halogen Transfer DOI Creative Commons

Kendelyn I. Bone,

Thomas R. Puleo,

Michael D. Delost

et al.

Published: March 29, 2024

We disclose a benzylic C–H oxidative coupling reaction with alcohols that proceeds through synergistic deprotonation, halogenation and substitution sequence. The combination of tert-butoxide bases 2-halothiophene halogen oxidants enables the first general protocol for generating using benzyl halides deprotonative pathway. In contrast to existing radical-based pathways functionalization, this process is guided by acidity trends. This gives rise new synthetic capabilities, including ability functionalize diverse methyl(hetero)arenes, tolerance oxidizable nucleophilic functional groups, precision regioselectivity polyalkylarenes use double etherification controllably oxidize methylarenes benzaldehydes.

Language: Английский

Citations

1
6‐Hydroxy Picolinohydrazides Promoted Cu(I)‐Catalyzed Hydroxylation Reaction in Water: Machine‐Learning Accelerated Ligands Design and Reaction Optimization DOI
Lanting Xu, Jiazhou Zhu, Xiaodong Shen

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(52)

Published: Aug. 27, 2024

Hydroxylated (hetero)arenes are privileged motifs in natural products, materials, small-molecule pharmaceuticals and serve as versatile intermediates synthetic organic chemistry. Herein, we report an efficient Cu(I)/6-hydroxy picolinohydrazide-catalyzed hydroxylation reaction of (hetero)aryl halides (Br, Cl) water. By establishing machine learning (ML) models, the design ligands optimization conditions were effectively accelerated. The N-(1,3-dimethyl-9H- carbazol-9-yl)-6-hydroxypicolinamide (L32, 6-HPA-DMCA) demonstrated high efficiency for bromides, promoting reactions with a minimal catalyst loading 0.01 mol % (100 ppm) at 80 °C to reach 10000 TON; substrates containing sensitive functional groups, needs be increased 3.0 under near-room temperature conditions. N-(2,7-Di-tert-butyl-9H-carbazol-9-yl)-6-hydroxypicolinamide (L42, 6-HPA-DTBCA) displayed superior activity chloride substrates, enabling 100 2-3 loading. These represent state art both lowest copper-catalyzed reactions. Furthermore, this method features sustainable environmentally friendly solvent system, accommodates wide range shows potential developing robust scalable synthesis processes key pharmaceutical intermediates.

Language: Английский

Citations

1
Aryne Aminohalogenation Using Protic Amines Enabled by Halogen Transfer DOI
Joshua Gavin,

Lars Anderson,

Courtney C. Roberts

et al.

Organic Letters, Journal Year: 2024, Volume and Issue: 26(36), P. 7530 - 7534

Published: Aug. 28, 2024

Methods for aryne difunctionalization have been the focus of recent research, but one limitation is use nucleophiles with proton sources. Herein, we demonstrate halogen transfer reagents to enable protic amines in aminohalogenation difunctionalizations up 86% yield. This method uses and arynes a variety N-heterocyclic scaffolds. Through derivatizations, synthetic utility these products demonstrated.

Language: Английский

Citations

1
Transition Metal–Free Synthesis of Vinyl Nitriles from Aldehydes with Acetonitrile at Room Temperature DOI
Qing Li, Wenjing Liu,

Yuyao Xie

et al.

ChemistrySelect, Journal Year: 2024, Volume and Issue: 9(36)

Published: Sept. 19, 2024

Abstract A simple and mild protocol for the direct synthesis of vinyl nitriles is described. By employing potassium trimethylsilanolate as base benzyl chloride efficient promoter, a series E‐configured are selectively obtained from readily available aldehydes acetonitrile at room temperature without aid transition metal catalyst. Mechanistical investigations reveal that this transformation may go through Knoevenagel condensation process.

Language: Английский

Citations

1
Base-Promoted Direct C–H Hydroxylation of N-Heteroarenes DOI
Paul Richardson

Synfacts, Journal Year: 2024, Volume and Issue: 20(07), P. 0682 - 0682

Published: June 14, 2024

Key words halogen transfer - hydroxylation pyridines 1,3-azoles electron-deficient arenes

Language: Английский

Citations

0
Direct Benzylic C–H Etherification Enabled by Base‐Promoted Halogen Transfer DOI

Kendelyn I. Bone,

Thomas R. Puleo,

Michael D. Delost

et al.

Angewandte Chemie, Journal Year: 2024, Volume and Issue: 136(39)

Published: June 28, 2024

Abstract We disclose a benzylic C−H oxidative coupling reaction with alcohols that proceeds through synergistic deprotonation, halogenation and substitution sequence. The combination of tert ‐butoxide bases 2‐halothiophene halogen oxidants enables the first general protocol for generating using benzyl halides deprotonative pathway. In contrast to existing radical‐based methods functionalization, this process is guided by acidity trends. This gives rise new synthetic capabilities, including ability functionalize diverse methyl(hetero)arenes, tolerance oxidizable nucleophilic functional groups, precision site‐selectivity polyalkylarenes use double etherification controllably oxidize methylarenes benzaldehydes.

Language: Английский

Citations

0
6‐Hydroxy Picolinohydrazides Promoted Cu(I)‐Catalyzed Hydroxylation Reaction in Water: Machine‐Learning Accelerated Ligands Design and Reaction Optimization DOI
Lanting Xu, Jiazhou Zhu, Xiaodong Shen

et al.

Angewandte Chemie, Journal Year: 2024, Volume and Issue: 136(52)

Published: Aug. 27, 2024

Abstract Hydroxylated (hetero)arenes are privileged motifs in natural products, materials, small‐molecule pharmaceuticals and serve as versatile intermediates synthetic organic chemistry. Herein, we report an efficient Cu(I)/6‐hydroxy picolinohydrazide‐catalyzed hydroxylation reaction of (hetero)aryl halides (Br, Cl) water. By establishing machine learning (ML) models, the design ligands optimization conditions were effectively accelerated. The N ‐(1,3‐dimethyl‐9 H ‐ carbazol‐9‐yl)‐6‐hydroxypicolinamide ( L32 , 6‐HPA‐DMCA) demonstrated high efficiency for bromides, promoting reactions with a minimal catalyst loading 0.01 mol % (100 ppm) at 80 °C to reach 10000 TON; substrates containing sensitive functional groups, needs be increased 3.0 under near‐room temperature conditions. ‐(2,7‐Di‐ tert ‐butyl‐9 ‐carbazol‐9‐yl)‐6‐hydroxypicolinamide L42 6‐HPA‐DTBCA) displayed superior activity chloride substrates, enabling 100 2–3 loading. These represent state art both lowest copper‐catalyzed reactions. Furthermore, this method features sustainable environmentally friendly solvent system, accommodates wide range shows potential developing robust scalable synthesis processes key pharmaceutical intermediates.

Language: Английский

Citations

0
Diastereoselective Homocoupling of Benzylic C(sp3)–H Bonds Enabled by Halogen Transfer DOI
Xirong Liu, Xin An, Xue Zhao

et al.

Organic Letters, Journal Year: 2024, Volume and Issue: 26(43), P. 9257 - 9262

Published: Oct. 18, 2024

A transition-metal- and harsh-oxidant-free strategy for diastereoselective homocoupling of benzylic α-boryl carbanions has been developed. Central to this methodology is the ability halogen transfer reagent seamlessly integrate halogenation substitution within a compatible process. Additionally, also applicable diarylmethanes alkylheteroarenes. Substrates bearing oxidatively sensitive functional groups were well-tolerated. Preliminary studies suggest that hydrogen bond between two boryl contributes high diastereoselectivities.

Language: Английский

Citations

0