Pd-Catalyzed C–H Annulation of Five-Membered Heteroaryl Halides with Norbornene Derivatives

Padhi, Birakishore; Kang, Geunhee; Kim, Eunmin; Ha, Jeongmin; Kim, Hyun Tae; Lim, Jeewoo; Joo, Jung Min

doi:10.1021/acscatal.9b05177

Cited by 17 publications

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“…T.LimJ.JooJ. M. Padhi, B. Kang, G. Kim, E. Ha, J. Kim, H. T. Lim, J. Joo, J. M. ACS Catal.20201017921798 Divergent Strategies for the π-Extension of Heteroaryl Halides Using Norbornadiene as an Acetylene SynthonJeongS.KimE.KimM.HwangY.…”

Section: Key Referencesmentioning

confidence: 99%

“…T.LimJ.JooJ. M. Padhi, B. Kang, G. Kim, E. Ha, J. Kim, H. T. Lim, J. Joo, J. M. ACS Catal.20201017921798 …”

Section: Key Referencesmentioning

confidence: 99%

“…Based on the reactivity pattern of iodothiophenes and pyrazoles under the Catellani reaction conditions, we began the optimization of the 1:2 coupling reaction with norbornadiene (NBD) (Scheme ). The 1:2 coupling reaction can generate a ladder-like structure with high exo - and trans -selectivity in the addition step to the bridged bicyclic ring, thus selectively preparing heteroarene-embedded rigid, nonplanar polycyclic compounds. In addition, NBD is a more attractive substrate than NBE because one of the alkene groups of NBD can be further elaborated by addition and polymerization.…”

Section: Chemodivergent Reactions Of Five-membered Heteroarenes With ...mentioning

confidence: 99%

“…Similarly, the halide position is important in the 1:2 coupling reactions of pyrazoles with NBD with a trend opposite to that of the Catellani reaction (Scheme ). 4-Iodopyrazole was transformed to the annulation product, whereas the 5-regioisomer was not tolerated.…”

Section: Chemodivergent Reactions Of Five-membered Heteroarenes With ...mentioning

confidence: 99%

“…74 We observed a similar dependence on the character of the C−H bond adjacent to the halide group at the pyrazole heterocycle (Scheme 16). 2 When the Lautens protocol was applied to iodopyrazoles, only 5-iodopyrazole gave the corresponding Catellani product. This result is attributed to the facile formation of the palladacycle from 5-iodopyrazole; in contrast, the steric effect of the nitrogen substituent in 4-iodopyrazole hampers the formation of the palladacycle and the subsequent oxidative addition with iodobutane.…”

Section: The Catellani Reactionmentioning

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: Key Referencesmentioning

confidence: 99%

“…T.LimJ.JooJ. M. Padhi, B. Kang, G. Kim, E. Ha, J. Kim, H. T. Lim, J. Joo, J. M. ACS Catal.20201017921798 …”

Section: Key Referencesmentioning

confidence: 99%

Section: Chemodivergent Reactions Of Five-membered Heteroarenes With ...mentioning

confidence: 99%

Section: Chemodivergent Reactions Of Five-membered Heteroarenes With ...mentioning

confidence: 99%

Section: The Catellani Reactionmentioning

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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Palladium‐Catalyzed Heck/Insertion/Decarboxylation Domino Sequence: Synthesis of Dihydrocyclohepta[de]naphthalenes

Chen

Zhuang

et al. 2021

Adv Synth Catal

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A Pd-catalyzed cascade cyclization for the construction of fused dihydrocyclohepta [de] naphthalene skeletons was developed. The skeleton was assembled from 3-iodo-4H-chromen-4-one, norbornene and 8-bromo-1-naphthoic acid. Unlike the classic Catellani reaction, which involves the removal of norbornene, in the present system, norbornene acts as a building block for the construction of rigid nonplanar molecular architectures rather than as an ortho-directing transient mediator. This synthesis involves the formation of three CÀ C bonds via a one-pot process, and it is compatible of a series of substituents.

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Pd‐Catalyzed Cyclization of Alkynyl Norbornene Derivatives for the Synthesis of Benzofused Heteroarenes

et al. 2021

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Modular approaches, which allow a systematic variation of heteroaromatic cores and substituents, are crucial for the development of heteroaromatic drug candidates and organic functional materials. A new strategy involving the cyclization of heteroarenes tethered with alkynes through a norbornene bridge was developed. The precursors were readily prepared by a three‐component coupling process of heteroaryl halides, norbornadiene, and terminal alkynes. The Pd catalytic system derived from Pd(OAc)2 and 2‐(pyrazol‐1‐yl)pyridine transformed a variety of five‐membered heteroarenes to the corresponding benzofused products, including (di)benzothiophene, indazole, carbazole, indole, and benzofuran, with aryl and alkyl substituents at the C4(C7) position. During the cyclization process, the norbornene ring underwent a retro‐Diels‐Alder reaction, serving as an acetylene synthon. This approach was used to synthesize naphthalene derivatives from electron‐rich arenes, demonstrating its versatility in the annulation of (hetero)aromatic rings.

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Pd-Catalyzed C–H Annulation of Five-Membered Heteroaryl Halides with Norbornene Derivatives

Cited by 17 publications

References 62 publications

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

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

Palladium‐Catalyzed Heck/Insertion/Decarboxylation Domino Sequence: Synthesis of Dihydrocyclohepta[de]naphthalenes

Pd‐Catalyzed Cyclization of Alkynyl Norbornene Derivatives for the Synthesis of Benzofused Heteroarenes

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