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Although the palladium-catalyzed Suzuki-Miyaura cross-coupling of aryl esters has received significant attention, there is a lack of methods that utilize cheap and readily accessible Pd-phosphane catalysts, and can be routinely carried out with high cross-coupling selectivity. Herein, we report the first general method for the cross-coupling of pentafluorophenyl esters (pentafluorophenyl = pfp) by selective C–O acyl cleavage. The reaction proceeds efficiently using Pd(0)/phosphane catalyst systems. The unique characteristics of pentafluorophenyl esters are reflected in the fully selective cross-coupling vs. phenolic esters. Of broad synthetic interest, this report establishes pentafluorophenyl esters as new, highly reactive, bench-stable, economical, ester-based, electrophilic acylative reagents via acyl-metal intermediates. Mechanistic studies strongly support a unified reactivity scale of acyl electrophiles by C(O)–X (X = N, O) activation. The reactivity of pfp esters can be correlated with barriers to isomerization around the C(acyl)–O bond.
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This content will become publicly available on July 2, 2026
Direct electrochemical synthesis of pentafluorophenyl esters via oxyl-radical-promoted nucleophilic aromatic substitution
An electrochemical coupling between carboxylic acids and penta uorophenol (PFP–OH) to access synthetically versatile penta uorophenyl (PFP) esters has been developed. Novel reactivity of PFP–OH was turned on by modulating its oxidation state, leveraging both its native O-nucleophilicity and its latent, oxidation-induced C-electrophilicity to promote a unique cascade of nucleophilic aromatic and acyl substitutions. Its esteri cation with acids was thus achieved for the rst time without exogenous dehydrating agents. The acidity of PFP–OH and the oxidizability of its conjugate base enabled its mild and selective activation via deprotonation–oxidation, readily affording PFP esters that are useful in many applications (peptide synthesis, chemical biology, etc.) and that contain redox-sensitive functional groups. Finally, we verified in a unified forum that an amino-acid-derived PFP ester can be converted into a range of acyl-substitution products while retaining key stereochemical information, and we demonstrated that PFP esters have excellent stability to hydrolysis, comparing favorably even to N-hydroxysuccinimidyl (NHS) esters.
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- Award ID(s):
- 2339405
- PAR ID:
- 10645868
- Publisher / Repository:
- Royal Society of Chemistry
- Date Published:
- Journal Name:
- Organic & Biomolecular Chemistry
- Volume:
- 23
- Issue:
- 26
- ISSN:
- 1477-0520
- Page Range / eLocation ID:
- 6373 to 6385
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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