Reigoselective Arylation of Thiazole Derivatives at 5-Position via Pd Catalysis under Ligand-Free Conditions

Liu, Xiang‐Wei; Shi, Jingyuan; Yan, Jia‐Xuan; Wei, Jiangbo; Peng, Kun; Dai, Liyi; Li, Chenguang; Wang, Bi‐Qin; Shi, Zhang‐Jie

doi:10.1021/ol4027073

Cited by 50 publications

(26 citation statements)

References 86 publications

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“…Gratifyingly, the direct arylation proceeded smoothly within 2–12 h in the presence of catalyst 1 to afford the products in synthetically useful yields. Molecules containing furan, thiazole, and benzothiophene rings resulted in biaryl products in moderate to good yields, similar to previously reported direct arylation methodologies (Table 2, Entries 1–12) 3c,14. Nevertheless, these reactions indicated the strength and practical merit of catalyst 1 in direct arylation.…”

Section: Resultssupporting

confidence: 85%

A Robust and Efficient Catalyst Possessing an Electron‐Deficient Ligand for the Palladium‐Catalyzed Direct Arylation of Heteroarenes

Jakab¹,

Dalicsek²,

Soós³

2014

Eur J Org Chem

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The exploration of the direct arylation capacity of a unique, thermally stable, and air‐stable Pd0–phosphine catalyst is reported. Besides decisively contributing to catalyst robustness, the electron‐deficient trifluoromethyl‐substituted triphenylphosphine ligands make the palladium center more electron‐deficient and accelerate the direct arylation step. The combination of only 0.5–2 mol‐% of the catalyst and a substoichiometric quantity of pivalic acid generates an efficient system to promote biaryl‐forming reactions of a broad range of electronically varied hetarenes and aryl bromides. The observed regioselective arylations suggest that a concerted metalation–deprotonation pathway is involved in the C–H activation step.

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Section: Resultssupporting

confidence: 85%

A Robust and Efficient Catalyst Possessing an Electron‐Deficient Ligand for the Palladium‐Catalyzed Direct Arylation of Heteroarenes

Jakab¹,

Dalicsek²,

Soós³

2014

Eur J Org Chem

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“…55,56 Importantly, the thiazole and oxazole motifs included in this study could conceivably be amenable to further functionalization at the C-5 position, which would extend the scope to mimic other amino acids and enable structure-activity relationships in an analogous fashion to small molecules. 57,58 Our study shifts the discourse on privileged scaffolds to macrocycles and suggests permeability as the focal point, which will likely contribute to the emergence of other molecules for early stages of discovery campaigns. The discovery of privileged motifs disclosed in this work should also find use in training sets for machine learning approaches.…”

Section: Discussionmentioning

confidence: 88%

Property-driven development of privileged macrocyclic scaffolds using heterocycles

Saunders

Yudin

2022

Preprint

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Passive membrane permeability is a fundamental challenge in the development of bioactive macrocycles. To achieve this objective, chemists have resorted to various strategies, the most common of which is deployment of N-methylated amino acids and/or D-amino acids. Here we investigate the effect of heterocyclic grafts on the passive membrane permeability of macrocycles and report the structural consequences of iterative amino acid replacement by azole rings. Through stepwise sub-stitution of amino acid residues for heterocycles, we show that lipophilicity and PAMPA permeability of a macrocycle can be vastly improved. Overall, changes in permeability do not scale linearly as more heterocycles are incorporated, underscor-ing the subtleties of conformation-property relationships in this class of molecule. NMR analysis and molecular dynamics simulations provide insights into the structural consequences of the added heterocycles and foreshadow the emergence of privileged macrocyclic scaffolds for drug discovery.

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“…As shown in Figure 11, small-molecule C H activation of the Tz unit reveals an interesting reactivity pattern: Pd-catalysts are highly regioselective toward the C H activation of the C-5 position due to a lower activation energy barrier compared to the C-2 position (23.7 vs. 26.3 kcal/mol). [195][196][197] On the other hand, the C-2 position of the Tz is more selective for Cu catalysts through the strong Cu-coordination at the N-3 site, which effectively increases the acidity of the C H bond at the C-2 position. 28,30,198 Therefore, in order to conform with the Pdcatalytic system used in the Oxi-DArP of P25, the 4,4 0dimethyl-2,2 0 -bithiazole monomer was used with C-5 sites available for the C H activation.…”

Section: Thiazole-c-5 Directed Pd-catalyzed Oxi-darpmentioning

confidence: 99%

Improving the efficiency and sustainability of catalysts for direct arylation polymerization (DArP)

Thompson

2021

Journal of Polymer Science

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In the past decade, direct arylation polymerization (DArP) has rapidly developed as a sustainable synthetic protocol for cost-effective, atom-economical preparation of conjugated polymers. By circumventing monomer functionalization with toxic transmetallating reagents such as organostannane and organoboron required for Stille-Migita and Suzuki-Miyaura polymerization methods, DArP proceeds through a metal-catalyzed C H activation pathway for the preparation of highperformance conjugated polymer materials. This review evaluates the development of several classes of efficient catalysts/catalytic systems from small-molecule studies to polymerizations, including the mechanisms involved in these transformations and how they inspire catalyst and monomer design for defect-free conjugated polymer synthesis. Recent advances in developing more sustainable first-row transition metal catalysts for DArP are also highlighted, and the fundamental understanding of these efficient and sustainable catalysts should motivate the pursuit for the next generation of catalytic design to enable more effective and environmentally friendly conjugated polymer synthesis.

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Reigoselective Arylation of Thiazole Derivatives at 5-Position via Pd Catalysis under Ligand-Free Conditions

Cited by 50 publications

References 86 publications

A Robust and Efficient Catalyst Possessing an Electron‐Deficient Ligand for the Palladium‐Catalyzed Direct Arylation of Heteroarenes

A Robust and Efficient Catalyst Possessing an Electron‐Deficient Ligand for the Palladium‐Catalyzed Direct Arylation of Heteroarenes

Property-driven development of privileged macrocyclic scaffolds using heterocycles

Improving the efficiency and sustainability of catalysts for direct arylation polymerization (DArP)

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