C−H Alkenylation of Pyrroles by Electronically Matching Ligand Control

Kim, Hyun Tae; Lee, Woohyeong; Kim, Eunmin; Joo, Jung Min

doi:10.1002/asia.201800558

Cited by 17 publications

(15 citation statements)

References 71 publications

(22 reference statements)

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“…Therefore, to functionalize this position, it is desirable to find a catalytic system that is suited for the standard CMD. Similar to the C5 alkenylation of pyrazole, the Pd/MPAA system was optimal for the C5 alkenylation of these pyrroles (Scheme A) . Alternatively, Laha and co-workers found that the more electron-rich C4 position can be alkenylated by a Pd(OAc) 2 /Cu(OAc) 2 system (Scheme B) .…”

Section: Regiodivergent Alkenylation Of Five-membered Heteroarenes Wi...mentioning

confidence: 99%

“…In this study, C–H alkenylation reactions of N -alkyl pyrroles were also performed to afford a 2:1 mixture of C2- and C3-regioisomers, illustrating the challenge of controlling the selectivity without substrate manipulation (Scheme A) . To develop ligand-controlled regiodivergent alkenylation of pyrroles, we first applied the electrophilic Pd catalytic system that was successful for the C4 alkenylation of pyrazole to alkenylation at the electron-rich C2 position of N -alkyl pyrroles (Scheme B) . For highly electron-rich pyrroles, the addition of acid was not required.…”

Section: Regiodivergent Alkenylation Of Five-membered Heteroarenes Wi...mentioning

confidence: 99%

“…45 To develop ligand-controlled regiodivergent alkenylation of pyrroles, we first applied the electrophilic Pd catalytic system that was successful for the C4 alkenylation of pyrazole to alkenylation at the electron-rich C2 position of N-alkyl pyrroles (Scheme 7B). 47 For highly electron-rich pyrroles, the addition of acid was not required. Furthermore, the combination of Pd(OAc) 2 and DAF in 1,4-dioxane allowed C2 alkenylation using oxygen as the terminal oxidant.…”

Section: Pyrrolementioning

confidence: 99%

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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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Section: Regiodivergent Alkenylation Of Five-membered Heteroarenes Wi...mentioning

confidence: 99%

Section: Regiodivergent Alkenylation Of Five-membered Heteroarenes Wi...mentioning

confidence: 99%

Section: Pyrrolementioning

confidence: 99%

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

Jeong

Joo

2021

Acc. Chem. Res.

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“…On the other hand, C5‐alkenylation of N ‐alkylpyrroles having electron‐withdrawing groups at the C2 position was achieved using Pd(OAc) 2 and a mono‐protected amino acid ligand, Ac−Val−OH. This convention dependent on the electronic effects of heterocycles and catalyst can quickly give a wide scope of alkenyl pyrroles from promptly accessible N‐alkylpyrroles and alkenes [38] . This experimental work is conceptualized in view of electronic coordinating among heterocycles and catalytic frameworks ought to be helpful for advancing the effective C−H functionalization of heterocycles with fluctuating electronic properties.…”

Section: C−h Functionalization Of Pyrrolesmentioning

confidence: 99%

Recent Advances in Functionalization of Pyrroles and their Translational Potential

Hunjan

Panday

Gupta

et al. 2021

The Chemical Record

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Among the known aromatic nitrogen heterocycles, pyrrole represents a privileged aromatic heterocycle ranging its occurrence in the key component of “pigments of life” to biologically active natural products to active pharmaceuticals. Pyrrole being an electron‐rich heteroaromatic compound, its predominant functionalization is legendary to aromatic electrophilic substitution reactions. Although a few excellent reviews on the functionalization of pyrroles including the reports by Baltazzi in 1963, Casiraghi and Rassu in 1995, and Banwell in 2006 are available, they are fragmentary and over fifteen years old, and do not cover the modern aspects of catalysis. A review covering a comprehensive package of direct functionalization on pyrroles via catalytic and non‐catalytic methods including their translational potential is described. Subsequent to statutory yet concise introduction, the classical functionalization on pyrroles using Lewis acids largely following an ionic mechanism is discussed. The subsequent discussion follows the various metal‐catalyzed C−H functionalization on pyrroles, which are otherwise difficult to implement by Lewis acids. A major emphasize is given on the radical based pyrrole functionalization under metal‐free oxidative conditions, which is otherwise poorly highlighted in the literature. Towards the end, the current development of pyrrole functionalization under photocatalyzed and electrochemical conditions is appended. Only a selected examples of substrates and important mechanisms are discussed for different methods highlighting their scopes and limitations. The aromatic nucleophillic substitution on pyrroles (being an electron‐rich heterocycle) happened to be the subject of recent investigations, which has also been covered accentuating their underlying conceptual development. Despite great achievements over the past several years in these areas, many challenges and problems are yet to be solved, which are all discussed in summary and outlook.

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“…Figure 1a shows that, in general, the more electron donor the ligand is, the more stable the complex becomes, but at expenses of decreasing the metal Lewis acidity/catalytic activity. This dichotomy has been often overcome with different chemical manifolds; such as oxidizing the ligand [5] or the metal to a high‐valence state, [6,7] and using non‐coordinating counteranions or other donor‐acceptor ligands, with anchimeric assistance or redox properties [8–18] . However, these approaches eventually increase the synthetic complexity and price of the final metal catalyst.…”

Section: Introductionmentioning

confidence: 99%

MOF‐Stabilized Perfluorinated Palladium Cages Catalyze the Additive‐Free Aerobic Oxidation of Aliphatic Alcohols to Acids

Greco

Tiburcio

Fernández

et al. 2022

Chemistry A European J

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Extremely high electrophilic metal complexes, composed by a metal cation and very electron poor σ‐donor ancillary ligands, are expected to be privileged catalysts for oxidation reactions in organic chemistry. However, their low lifetime prevents any use in catalysis. Here we show the synthesis of fluorinated pyridine‐Pd2+ coordinate cages within the channels of an anionic tridimensional metal‐organic framework (MOF), and their use as efficient metal catalysts for the aerobic oxidation of aliphatic alcohols to carboxylic acids without any additive. Mechanistic studies strongly support that the MOF‐stabilized coordination cage with perfluorinated ligands unleashes the full electrophilic potential of Pd2+ to dehydrogenate primary alcohols, without any base, and also to activate O2 for the radical oxidation to the aldehyde intermediate. This study opens the door to design catalytic perfluorinated complexes for challenging organic transformations, where an extremely high electrophilic metal site is required.

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C−H Alkenylation of Pyrroles by Electronically Matching Ligand Control

Cited by 17 publications

References 71 publications

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

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

Recent Advances in Functionalization of Pyrroles and their Translational Potential

MOF‐Stabilized Perfluorinated Palladium Cages Catalyze the Additive‐Free Aerobic Oxidation of Aliphatic Alcohols to Acids

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