Palladium catalyzed carbonylative generation of potent, pyridine-based acylating electrophiles for the functionalization of arenes to ketones

Liu, Yi; Kaiser, Angela; Arndtsen, Bruce A.

doi:10.1039/d0sc03129a

Cited by 8 publications

(4 citation statements)

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“…Other monodentate phosphine ligands were also ineffective. Instead, palladium black is formed in these systems, which may arise from the generation of a destabilized cationic palladium in the presence of CO. Bidentate ligands have been noted in other systems to be generating more stable and efficient palladium catalysts for aryl triflate carbonylations. − While no reaction is observed under our conditions with smaller bidentate phosphines, those with larger bite angles or phosphorus substituents do lead to low yield of product. Moving to the large DPE-Phos ligand results in a dramatic increase in reactivity to form 2a in 75% yield.…”

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confidence: 73%

Palladium Catalyzed Conversion of Aryl Triflates to Acyl-DMAP Salts: A Mild and Versatile Approach to Carbonylations

et al. 2022

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The use of metal catalysis to form potent acylating agents offers an important avenue to broaden the applicability of carbonylation reactions. However, the often disfavored reductive elimination of these reactive products presents a challenge, and has made these often high temperature, high pressure reactions and limited in their scope. Herein, we describe a mild and versatile palladium catalyzed carbonylative method to generate electrophilic acyl-DMAP (4-dimethylaminopyridine) salts by exploiting an alternative feature of these reactions: the counterion. In this, the weakly coordinating triflate anion is found to strongly destabilize Pd(II) toward irreversible reductive elimination of the reactive products, while ligand design can allow the rapid activation of aryl or vinyl triflates. Together, this provides a route to carry out palladium catalyzed carbonylations under exceptionally mild conditions, with low catalyst loading (0.5 mol % Pd), and with broadly available C(sp 2 )-triflate reagents. Coupling their formation with the addition of nucleophiles can be used to assemble a variety of products by carbonylation reactions, including those with palladium reactive functionalities.

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confidence: 73%

Palladium Catalyzed Conversion of Aryl Triflates to Acyl-DMAP Salts: A Mild and Versatile Approach to Carbonylations

et al. 2022

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“…Nonetheless, even acid chlorides, one of the most reactive carboxylic acid derivatives, could not be reduced (for 20 , E o = −1.53 V vs SCE) by the iridium photocatalyst Ir[dF(CF 3 )ppy] 2 (dtbbpy)PF 6 ( E o red = −1.37 V vs SCE). Therefore, the application of a more reactive acyl surrogate, N -acylpyridinium compounds, which can be formed in situ by reacting acid chlorides with pyridine derivatives, was envisioned to enable facile single-electron reductive fragmentation. Notably, a similar strategy was reported in parallel by the Wu group where alkyloxalyl chlorides were utilized instead of acid chlorides to generate N -alkoxyoxalyllutidinium intermediates and perform an alkoxycarbonylation reaction of alkenes (Scheme c) .…”

Section: Acylation Of Unactivated C(sp3)–h Bonds With α-Amino Acid Ch...mentioning

confidence: 99%

Direct C(sp³)–H Acylation by Mechanistically Controlled Ni/Ir Photoredox Catalysis

Lee

Hong

2023

Acc. Chem. Res.

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Metrics & MoreArticle RecommendationsCONSPECTUS: Synthetic chemists have consistently aimed to develop efficient methods for synthesizing ketones, which are essential building blocks in organic chemistry and play significant roles in bioactive molecules. Recent efforts have focused on using photoredox catalysis, which enables previously inaccessible activation modes, to synthesize ketones through the cross-coupling of an acyl electrophile and simple C(sp 3 )−H bonds. Over the past few years, we have worked on developing effective and versatile approaches for directly acylating activated hydrocarbons to forge ketones. Initially, thioesters were explored as the acyl source to achieve the direct acylation of ethers, but an unexpected thioesterification reaction was observed instead. To gain insights into this reactivity, we conducted the optimization of reaction conditions, substrate scope evaluation, and mechanistic studies. Drawing from our understanding of Ni/Ir photocatalysis obtained in this study, we subsequently developed a method for the direct acylation of simple hydrocarbons. The use of less-reactive amides as the acyl electrophiles was found to be critical for suppressing undesired pathways. This seemingly counterintuitive reactivity was carefully studied, revealing a substrate-assisted reaction mechanism in which the suppressed oxidative addition leads to early-stage nickel oxidation and C−H activation.To address the drawbacks of this method, which primarily arose from decarbonylative and transmetallative side pathways, we employed N-acyllutidiniums as the acyl electrophile. This prevented undesired decomposition pathways, enabling the use of α-chiral acyl substrates with the retention of their stereochemistry, particularly those derived from α-amino acids. The developed versatile methodology allowed us to access a diverse range of α-amino ketones and their homologues. Despite the elegant utility of Ni/photoredox catalysis in developing new synthetic methodologies, the precise behavior of nickel catalysts under redox conditions is incompletely understood. To gain insight into this behavior and develop new chemical reactions, we used a combination of experimental and computational methods. Our investigations revealed that devised adjustments to the reaction conditions in nickel/photoredox catalysis can result in significant differences in the reaction outcomes, providing chemists with opportunities to tailor reactions through carefully designed mechanistic strategies. We believe that continued efforts to study and apply nickel redox modulation will lead to the discovery of additional organic transformations.

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“…Under the same conditions, by using as starting material p -Br-benzoyl chloride 3c and p -Bu t -benzoyl chloride 3d , the α-regioisomer was preferentially formed with a β- 4 /α -4 regioselectivity of 40/60 for both (entries 9,10). Interestingly, with p -MeO-benzoyl chloride 3e , marked regioselectivity for α- 4e was observed with a β/α ratio of 30/70 (entry 11) . When N -methylpyrrole 2 was reacted with p -NO 2 -benzoyl chloride 3f in the presence of C (26 mol %) at 50 °C for 5 h (Table , entry 12), only the product α -4 was obtained in 99% yield.…”

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“…Interestingly, with p -MeO-benzoyl chloride 3e , marked regioselectivity for α- 4e was observed with a β/α ratio of 30/70 (entry 11). 12 When N -methylpyrrole 2 was reacted with p -NO 2 -benzoyl chloride 3f in the presence of C (26 mol %) at 50 °C for 5 h ( Table 1 , entry 12), only the product α -4 was obtained in 99% yield. Based on these results, we can conclude that when the FC benzoylation of 2 occurs inside the confined space of C , the regiochemistry of product 4 is driven by the confinement effects of the substrates.…”

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Insights into the Friedel–Crafts Benzoylation of N-Methylpyrrole inside the Confined Space of the Self-Assembled Resorcinarene Capsule

Iuliano,

Talotta,

De Rosa

et al. 2023

Org. Lett.

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Friedel–Crafts benzoylation of N-methylpyrrole 2 can run inside the confined space of the hexameric resorcinarene capsule C. The bridged water molecules at the corner of C act as H-bonding donor groups to polarize the C–Cl bond of benzoyl chlorides 3a–f. Confinement effects on the regiochemistry of the FC benzoylation of N-methylpyrrole are observed. The nature of the para-substituents of 3a–f and their ability to establish H-bonds with the water molecules of C work synergistically with the steric constrictions imposed by the capsule to drive the regiochemistry of products 4a–f. QM investigations indicate that inside the cavity of C, the FC benzoylation of 2 has a bimolecular concerted SN2 mechanism, appropriately, above-plane nucleophilic vinylic substitution (SNVπ)supported by H-bonding interactions between water molecules and both the leaving Cl atom and the carbonyl group.

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Palladium catalyzed carbonylative generation of potent, pyridine-based acylating electrophiles for the functionalization of arenes to ketones

Abstract: We describe here the design of a palladium catalyzed route to generate aryl ketones via the carbonylative coupling of (hetero)arenes and aryl- or vinyl-triflates. In this, the use of the...

Cited by 8 publications

References 95 publications

Palladium Catalyzed Conversion of Aryl Triflates to Acyl-DMAP Salts: A Mild and Versatile Approach to Carbonylations

Palladium Catalyzed Conversion of Aryl Triflates to Acyl-DMAP Salts: A Mild and Versatile Approach to Carbonylations

Direct C(sp³)–H Acylation by Mechanistically Controlled Ni/Ir Photoredox Catalysis

Insights into the Friedel–Crafts Benzoylation of N-Methylpyrrole inside the Confined Space of the Self-Assembled Resorcinarene Capsule

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Palladium catalyzed carbonylative generation of potent, pyridine-based acylating electrophiles for the functionalization of arenes to ketones

Abstract: We describe here the design of a palladium catalyzed route to generate aryl ketones via the carbonylative coupling of (hetero)arenes and aryl- or vinyl-triflates. In this, the use of the...

Cited by 8 publications

References 95 publications

Palladium Catalyzed Conversion of Aryl Triflates to Acyl-DMAP Salts: A Mild and Versatile Approach to Carbonylations

Palladium Catalyzed Conversion of Aryl Triflates to Acyl-DMAP Salts: A Mild and Versatile Approach to Carbonylations

Direct C(sp3)–H Acylation by Mechanistically Controlled Ni/Ir Photoredox Catalysis

Insights into the Friedel–Crafts Benzoylation of N-Methylpyrrole inside the Confined Space of the Self-Assembled Resorcinarene Capsule

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Direct C(sp³)–H Acylation by Mechanistically Controlled Ni/Ir Photoredox Catalysis