Palladium mono-<i>N</i>-protected amino acid complexes: experimental validation of the ligand cooperation model in C–H activation

Fernández-Moyano, Sara; Salamanca, Vanesa; Albéniz, Ana C.

doi:10.1039/d3sc02076b

“…The byproduct [Pd(C 6 F 5 ) 2 (py) 2 ] formed by group reorganization between two different palladium complexes was also observed in a 30 % yield. This reorganization is not uncommon for pentafluorophenyl derivatives, [11] and it occurs by transmetalation between palladium centers. [18] In toluene, only 10 % of the coupling product was observed after heating for 30 min.…”

Section: Resultsmentioning

confidence: 99%

“…This is shown in Scheme 1 for bipy-6-OH, [7,8a] and MPAAs. [11] We decided to apply this tool to other potential cooperating ligands of similar structure which have been little used in CÀ H functionalization reactions but could be interesting in this field. Taking into account the features that have made MPAAs and bipy-6-OH successful cooperating ligands in CÀ H activation, the cooperating ability of the related 6-hydroxypicolinic acid and pyridyl-amide type ligands is assessed in this work.…”

Section: Introductionmentioning

confidence: 99%

Assessing the Cooperating Ability of 6‐Hydroxypicolinic Acid and Pyridyl‐Amide Ligands in Palladium‐Mediated C−H Activation

Pinilla,

Albéniz

2024

Eur J Inorg Chem

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The behavior of 6‐hydroxypicolinic acid (pic‐6‐OH) and pyridyl‐amides as cooperating ligands in the C‐H activation of arenes has been studied experimentally. When deprotonated, both compounds are chelating ligands and bear either a pyridone moiety or and an N‐acyl substituent that can assist the C‐H cleavage in the same way as the successful bipyridone ligands and MPAAs do. In addition, they are easily available, commercially or via straightforward syntheses. Palladium complexes of formula (NBu4)[Pd(κ2‐O, N‐pic‐6‐O)(C6F5)py] (2) and [Pd(κ2‐N, N‐ py‐CH2N(COCF3)(C6F5)py] (6) have been synthesized and their decomposition in the presence of an arene gives the C6F5‐arene coupling product, showing that the ligands enable the C‐H activation of the arene (arene = pyridine, toluene, ethyl benzoate). The amount of C6F5‐arene products observed leads to the following trend in cooperating ability: pic‐6‐OH > pyridyl‐amide. DFT calculations on the pyridine activation are consistent with the experimental findings. The C‐H activation does not occur for the isomeric complex (NBu4)[Pd(κ2‐O, N‐pic‐4‐O)(C6F5)py] (4) with the pyridone oxygen far from the metal, showing the involvement of this moiety in the C‐H cleavage. The performance of these ligands in the direct arylation of arenes has been evaluated.

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“…N ‐Acetyl) of the MPAA ligand was likely serving as the internal base in the CMD C−H cleavage step to deprotonate the C−H bond, while the MPAA carboxylate serves to anchor the bidentate ligand to the metal (Figure 1). [41] Albéniz has also recently disclosed detailed organometallic, kinetic, and computational studies supporting the bifunctional MPAA C−H cleavage model with a monometallic Pd catalyst [42] . The participation of the amidate group, which is both significantly more basic and less sterically hindered than acetate, results in a C−H cleavage activation barrier that is significantly lower in energy (4 kcal/mol) than acetate CMD with Pd(OAc) 2 .…”

Section: The ‘Reactivity’ Challenge: Key Enabling Elements For Challe...mentioning

confidence: 99%

Palladium (II)‐Catalyzed C−H Activation with Bifunctional Ligands: From Curiosity to Industrialization

Wu,

Lam,

Strassfeld

et al. 2024

Angew Chem Int Ed

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In 2001, our curiosity to understand the stereochemistry of C–H metalation with Pd prompted our first studies in Pd(II)‐catalyzed asymmetric C–H activation. We identified four central challenges: 1. poor reactivity of simple Pd salts with native substrates; 2. few strategies to control site selectivity for remote C–H bonds; 3. the lack of chiral catalysts to achieve enantioselectivity via asymmetric C–H metalation, and 4. low practicality due to limited coupling partner scope and the use of specialized oxidants. These challenges necessitated new strategies in catalyst and reaction development. For reactivity, we developed approaches to enhance substrate‐catalyst affinity together with novel bifunctional ligands which participate in and accelerate the C–H cleavage step. For site‐selectivity, we introduced the concept of systematically modulating the distance and geometry between a directing template, catalyst, and substrate to selectively access remote C–H bonds. For enantioselectivity, we devised predictable stereomodels for catalyst‐controlled enantioselective C–H activation based on the participation of bifunctional ligands. Finally, for practicality, we have developed varied catalytic manifolds for Pd(II) to accommodate diverse coupling partners while employing practical oxidants such as simple peroxides. These advances have culminated in numerous C–H activation reactions of broadly useful native substrates with diverse coupling partners under mild conditions.

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“…[41] Albéniz has also recently disclosed detailed organometallic, kinetic, and computational studies supporting the bifunctional MPAA CÀ H cleavage model with a monometallic Pd catalyst. [42] The participation of the amidate group, which is both significantly more basic and less sterically hindered than acetate, results in a CÀ H cleavage activation barrier that is significantly lower in energy (4 kcal/mol) than acetate CMD with Pd(OAc) 2 . These mechanistic observations indicate that the MPAA ligands are actively involved in the CÀ H cleavage transition state itself and enabling ligandaccelerated catalysis.…”

Section: Development Of Bifunctional Ligands For the Cà H Activation ...mentioning

confidence: 99%

Palladium (II)‐Catalyzed C−H Activation with Bifunctional Ligands: From Curiosity to Industrialization

Wu,

Lam,

Strassfeld

et al. 2024

Angewandte Chemie

0

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In 2001, our curiosity to understand the stereochemistry of C–H metalation with Pd prompted our first studies in Pd(II)‐catalyzed asymmetric C–H activation. We identified four central challenges: 1. poor reactivity of simple Pd salts with native substrates; 2. few strategies to control site selectivity for remote C–H bonds; 3. the lack of chiral catalysts to achieve enantioselectivity via asymmetric C–H metalation, and 4. low practicality due to limited coupling partner scope and the use of specialized oxidants. These challenges necessitated new strategies in catalyst and reaction development. For reactivity, we developed approaches to enhance substrate‐catalyst affinity together with novel bifunctional ligands which participate in and accelerate the C–H cleavage step. For site‐selectivity, we introduced the concept of systematically modulating the distance and geometry between a directing template, catalyst, and substrate to selectively access remote C–H bonds. For enantioselectivity, we devised predictable stereomodels for catalyst‐controlled enantioselective C–H activation based on the participation of bifunctional ligands. Finally, for practicality, we have developed varied catalytic manifolds for Pd(II) to accommodate diverse coupling partners while employing practical oxidants such as simple peroxides. These advances have culminated in numerous C–H activation reactions of broadly useful native substrates with diverse coupling partners under mild conditions.

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Palladium mono-N-protected amino acid complexes: experimental validation of the ligand cooperation model in C–H activation

Abstract: Mechanistic proposals for the C-H activation reaction enabled by mono-N-protected amino acid ligands (MPAAs) have been supported by DFT calculations. The direct experimental observation of the ligand-assisted C-H activation has...

Cited by 3 publications

References 52 publications

Assessing the Cooperating Ability of 6‐Hydroxypicolinic Acid and Pyridyl‐Amide Ligands in Palladium‐Mediated C−H Activation

Assessing the Cooperating Ability of 6‐Hydroxypicolinic Acid and Pyridyl‐Amide Ligands in Palladium‐Mediated C−H Activation

Palladium (II)‐Catalyzed C−H Activation with Bifunctional Ligands: From Curiosity to Industrialization

Palladium (II)‐Catalyzed C−H Activation with Bifunctional Ligands: From Curiosity to Industrialization

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