Regioselective Olefination of 3‐Substituted Five‐Membered Heteroarenes

Chen, Hao; Farizyan, Mirxan; Gemmeren, Manuel van

doi:10.1002/ejoc.202000659

Cited by 21 publications

(15 citation statements)

References 87 publications

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“…Heteroarenes and electron-rich or fluoro-substituted arenes can be utilized for palladium-catalyzed nondirected C-H functionalization, with the electronically and sterically differentiated C-H sites, and in certain cases even catalyst structure, governing the reactivity and site selectivity. [18][19][20][21] However, achieving the reactivity with unbiased arenes, even with benzene, is more difficult and frequently requires the use of excess arene, while the presence of several electronically and sterically similar C-H sites can lead to mixtures of regioisomeric C-H functionalization products.…”

Section: C-h Activation and The Cmd Mechanismmentioning

confidence: 99%

Introduction to Spatial Anion Control for Direct C–H Arylation

Čorić¹,

Dhankhar²

2022

Synlett

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C–H activation of functionally rich molecules without the need for directing groups promises shorter organic syntheses and late-stage diversification of molecules for drug discovery. We highlight recent examples of palladium-catalyzed nondirected functionalization of C–H bonds in arenes as limiting substrates with a focus on the development of the concept of spatial anion control for direct C–H arylation.1 C–H Activation and the CMD Mechanism2 Nondirected C–H Functionalizations of Arenes as Limiting Substrates3 Nondirected C–H Arylation4 Spatial Anion Control for Direct C–H Arylation5 Coordination Chemistry with Spatial Anion Control6 Conclusion

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Section: C-h Activation and The Cmd Mechanismmentioning

confidence: 99%

Introduction to Spatial Anion Control for Direct C–H Arylation

Čorić¹,

Dhankhar²

2022

Synlett

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“…Regiodivergency has been demonstrated with C3-substituted thiophenes for both the C2 and C5 positions. 55 Because of the electron-donating C3 substituent, the C2 position is more electron-rich and sterically hindered than the C5 position, resulting in many recent reports on ligand-controlled regioselective alkenylation (Scheme 10). Carrow and Fernańdez-Ibańẽz (Scheme 10A,B, respectively) independently showed that the electrophilic Pd(II) species derived from Scheme 7.…”

Section: Thiophenementioning

confidence: 99%

Transition-Metal-Catalyzed Divergent C–H Functionalization of Five-Membered Heteroarenes

Jeong

Joo

2021

Acc. Chem. Res.

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Metrics & MoreArticle Recommendations CONSPECTUS: Conversion of common reactants to diverse products is a key objective of organic syntheses. Recent developments in transition-metal-catalyzed C−H functionalization have increased the interest in such conversions. Both the position of functionalization and the type of the substituent can be varied, allowing systematic diversification of common structural cores. Because five-membered heteroarenes (pyrazole, imidazole, thiazole, pyrrole, and thiophene) are ubiquitous in pharmaceuticals and organic functional materials, the selective C−H functionalization of these heterocyclic cores facilitates both the optimization of their physicochemical properties and streamlining of their preparation. In addition, the parent forms of these heterocycles are more readily available and inexpensive than any other derivatives of their families. Hence, their nondirected C−H functionalization is highly desirable. Although various regioselective reactions have been developed, many of them target the most reactive site; hence, except for some extensively studied arylation reactions, regiodivergent functionalization of two or more sites has been limited. This Account summarizes our work on the regiodivergent, nondirected C−H functionalization of five-membered heteroarenes with alkenes and alkynes. These unsaturated hydrocarbons are readily available, and all the composing atoms can be incorporated into products with high atom efficiency. Furthermore, the installed alkenyl groups can be transformed to other useful functional groups.To achieve comparable selectivity to that observed in the traditional reactions of these heteroarenes with highly electrophilic reagents and strong bases, a transition metal catalytic system was carefully devised with a more streamlined synthesis. A judicious choice of metals, ligands, acid and base additives, and solvents orchestrates divergent transformations using electronic and steric effects of the heteroarenes. Although C−H cleavage is a rate-and site-selectivity-determining step in most cases, the subsequent steps involving the formation of C−C bonds are often more critical than the other steps. For the C−H cleavage step, modulating the electronic properties of catalysts to make them electrophilic allows preferential alkenylation at the nucleophilic position. In addition, the presence of an internal base that can be exploited for concerted metalation−deprotonation of the acidic C−H bond offers alternative regioselectivity. Furthermore, we developed our own ligand system based on a conformationally rigid pyrazolonaphthyridine scaffold that enables aerobic C−H alkenylation reactions with steric control. We showed that the electronic and steric effects of heteroarenes can be further extended to chemodivergent reactions with norbornene derivatives. Depending on whether the palladacycle is formed, heteroarenes selectively undergo 1:2 annulation with norbornene derivatives and threecomponent reactions with other azoles through the Pd−norbornene adducts or Catell...

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“…Beispielsweise werden 3-substituierte Thiophene (15), Furane (16) und Pyrrole (17) in der sterisch bevorzugten-aber weniger elektronenreichen C5-Position olefiniert, was eine zu Literaturmethoden komplementäre Produktpalette liefert. 13,14) Mit dem Wechselspiel zwischen elektronischer und sterischer Kontrolle haben wir kürzlich zwei komplementäre Katalysatorsysteme zur Alkinylierung von Thiophenen zu entwickelt. Damit lassen sich selektiv entweder die sterisch bevorzugte C5-Position (18) oder die elektronenreichste C2-Position (19) alkinylieren.…”

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Spot on: C‐H‐Aktivierung

Gemmeren¹

2021

Nachr Chem

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Regioselective Olefination of 3‐Substituted Five‐Membered Heteroarenes

Cited by 21 publications

References 87 publications

Introduction to Spatial Anion Control for Direct C–H Arylation

Introduction to Spatial Anion Control for Direct C–H Arylation

Transition-Metal-Catalyzed Divergent C–H Functionalization of Five-Membered Heteroarenes

Spot on: C‐H‐Aktivierung

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