Origin of Regioselectivity in Palladium-Catalyzed Cross-Coupling Reactions of Polyhalogenated Heterocycles

Legault, Claude Y.; Garcia, Yeimy; Merlic, Craig A.; Houk, K. N.

doi:10.1021/ja075785o

Cited by 272 publications

(178 citation statements)

References 23 publications

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“…For dihalobenzenes, the reaction preferentially occurs at the carbon-halogen bond bearing the less electron-rich carbon [16]. For dihaloheteroarenes, detailed studies have been conducted [17], and the site-selectivity has been found to be determined by factors, such as the strengths of the carbon-halogen bonds and the coefficients of the heterocycle π* (LUMO) [18,19].…”

Section: Open Accessmentioning

confidence: 99%

Catalyst-Controlled Site-Selectivity Switching in Pd-Catalyzed Cross-Coupling of Dihaloarenes

Manabe

Yamaguchi

2014

Catalysts

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Pd-catalyzed, site-selective mono-cross-coupling of substrates with two identical halo groups is a useful method for synthesizing substituted monohalogenated arenes. Such arenes constitute an important class of compounds, which are commonly identified as drug components and synthetic intermediates. Traditionally, these site-selective reactions have been realized in a "substrate-controlled" manner, which is based on the steric and electronic differences between the two carbon-halogen bonds of the substrate. Recently, an alternative strategy, "catalyst-controlled" site-selective cross-coupling, has emerged. In this strategy, the preferred reaction site of a dihaloarene can be switched, merely by changing the catalyst used. This type of selective reaction further expands the utility of Pd-catalyzed cross-coupling. In this review, we summarize the reported examples of catalyst-controlled site-selectivity switching in Pd-catalyzed cross-coupling of dihaloarenes.

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Section: Open Accessmentioning

confidence: 99%

Catalyst-Controlled Site-Selectivity Switching in Pd-Catalyzed Cross-Coupling of Dihaloarenes

Manabe

Yamaguchi

2014

Catalysts

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“…[9] They showed, for instance, how the activation barrier of S N 2 reactions originates from steric congestion around the carbon atom that is nucleophilically attacked, and how electronic factors modulate the barrier height. [9,10] Not much later, Houk et al [11] were the first to successfully apply the activation strain model (or distortion/interaction model) to pericyclic reactions, in particular to [3+2] cycloaddition reactions. The latter, curiously, are concerted and occur through highly synchronous and in-plane aromatic transition states, very similar to the situation for DGT reactions.…”

Section: Introductionmentioning

confidence: 99%

Double Group Transfer Reactions: Role of Activation Strain and Aromaticity in Reaction Barriers

Fernández

Bickelhaupt

Cossío

2009

Chemistry A European J

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Double group transfer (DGT) reactions, such as the bimolecular automerization of ethane plus ethene, are known to have high reaction barriers despite the fact that their cyclic transition states have a pronounced in-plane aromatic character, as indicated by NMR spectroscopic parameters. To arrive at a way of understanding this somewhat paradoxical and incompletely understood phenomenon of high-energy aromatic transition states, we have explored six archetypal DGT reactions using density functional theory (DFT) at the OLYP/TZ2P level. The main trends in reactivity are rationalized using the activation strain model of chemical reactivity. In this model, the shape of the reaction profile DeltaE(zeta) and the height of the overall reaction barrier DeltaE( not equal)=DeltaE(zeta=zeta(TS)) is interpreted in terms of the strain energy DeltaE(strain)(zeta) associated with deforming the reactants along the reaction coordinate zeta plus the interaction energy DeltaE(int)(zeta) between these deformed reactants: DeltaE(zeta)=DeltaE(strain)(zeta)+DeltaE(int)(zeta). We also use an alternative fragmentation and a valence bond model for analyzing the character of the transition states.

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“…the interactions between the catalyst and the organo-halide and the BDEs) are usually at play. [65][66][67] To better understand the regioselectivity in the OA of (2b), we performed some detailed calculations. We used the aldimine (2b), with the Ms-group, instead of Ts-or Ns to reduce the conformational complexity.…”

Section: -61mentioning

confidence: 99%

A catalytic route to dibenzodiazepines involving Buchwald–Hartwig coupling: reaction scope and mechanistic consideration

et al. 2015

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We report a new synthetic method for the synthesis of a family of dibenzodiazepines (DBDAs), employing Pd-catalyzed C-N coupling of o-bromoaldimine, with o-bromoaniline as the key step. Eleven DBDAs were prepared, containing electron-withdrawing groups (CN, F, NO 2 ) and electron-donating groups (OMe). The reaction conditions were optimized (catalyst, phosphine, base and solvent) and best results were obtained with Pd(OAc) 2 , SPhos, Cs 2 CO 3 in THF. Due to the ambiguity of the mechanism at hand, various mechanistic studies were performed, that included DFT calculations. The oxidative addition process was studied in detail by DFT, and these studies supported the observed reaction regioselectivity. The adducts formed between the aldimine and the Pd(0) catalyst were calculated to be more stable than the ones formed with the amine, and the barrier for the oxidative addition at the C-Br bond of the aldimine was calculated to be lower than the one at the C-Br bond of the aryl amine. The formation of DBDA over the dibenzoaminopiperidine has been explained in the final cyclization step.

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Origin of Regioselectivity in Palladium-Catalyzed Cross-Coupling Reactions of Polyhalogenated Heterocycles

Cited by 272 publications

References 23 publications

Catalyst-Controlled Site-Selectivity Switching in Pd-Catalyzed Cross-Coupling of Dihaloarenes

Catalyst-Controlled Site-Selectivity Switching in Pd-Catalyzed Cross-Coupling of Dihaloarenes

Double Group Transfer Reactions: Role of Activation Strain and Aromaticity in Reaction Barriers

A catalytic route to dibenzodiazepines involving Buchwald–Hartwig coupling: reaction scope and mechanistic consideration

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