Carboxylic Acid Deoxyfluorination and One-Pot Amide Bond Formation Using Pentafluoropyridine (PFP)

This work describes the application of pentafluoropyridine (PFP), a cheap commercially available reagent, in the deoxyfluorination of carboxylic acids to acyl fluorides. The acyl fluorides can be formed from a range of acids under mild conditions. We also demonstrate that PFP can be utilized in a one-pot amide bond formation via in situ generation of acyl fluorides. This one-pot deoxyfluorination amide bond-forming reaction gives ready access to amides in yields of ≤94%

Kinetic resolution of alkyne-substituted quaternary oxindoles via copper catalysed azide-alkyne cycloadditions

Kinetic resolution of alkyne-substituted quaternary oxindoles via copper catalysed azide-alkyne cycloaddition

Asymmetric copper catalyzed azide-alkyne cycloadditions

Since its discovery independently by Sharpless and Meldal in 2002, the copper-catalyzed azide–alkyne cycloaddition (CuAAC) has become a ubiquitous molecular linking platform. Easy access to substituted 1,4-triazoles can be exploited to engender asymmetry to a myriad of potentially useful targets in high yields. Utilizing the CuAAC to form chiral triazolic products in a single step is an attractive and powerful approach for the synthetic chemist. The area of asymmetric CuAAC is still in its infancy compared to more established asymmetric metal-mediated transformations; however, this leads to exciting challenges that need to be overcome to usher in the next era in the story of the triazole and click chemistry in general. This review details the steps taken into asymmetric CuAAC and the exciting results achieved thus far. [Note that diagrams accompany this abstract in the published version and can be found at http://dx.doi.org/10.1021/acscatal.6b00996.

Perfluoroaryl and Perfluoroheteroaryl Reagents as Emerging New Tools for Peptide Synthesis, Modification and Bioconjugation

Perfluoroaromatic and perfluoroheteroaromatic reagents have emerged in recent years as powerful reagents for peptide and protein modification. Dominated by their regio- and chemoselective nucleophilic aromatic substitution chemistry under mild conditions, they have been used in peptide synthesis, tagging, cyclisation, stapling and protein bioconjugation. Peptides and proteins are becoming increasingly valuable as medicines, diagnostic agents and as tools for biomedical sciences. Much of this has been underpinned by the emergence of new methods for the manipulation and augmentation of native biomolecules. Perfluoroaromatic reagents are perhaps one of the most diverse and exciting tools with which to modify peptides and proteins, due principally to their nucleophilic substitution chemistry, high electron deficiency and the ability for their reactivity to be tuned towards specific nucleophiles. As discussed in this minireview, in recent years, perfluoroaromatic reagents have found applications as protecting groups or activating groups in peptide synthesis and as orthogonal handles for peptide modification. Furthermore, they have applications in chemoselective ‘tagging’, stapling and bioconjugation of peptides and proteins, as well as tuning of ‘drug-like’ properties. This review will also explore possible future applications of these reagents in biological chemistry

Tetrafluoropyridyl (TFP): a general phenol protecting group readily cleaved under mild conditions

Phenols are extremely valuable building blocks in the areas of pharmaceuticals, natural products, materials and catalysts. In order to carry out modifications on phenols, the phenolic oxygen is routinely protected to prevent unwanted side reactions. Presently many of the protecting groups available can require harsh conditions, specialist equipment, expensive or air/moisture-sensitive reagents to install and remove. Here we introduce the use of the tetrafluoropyridyl (TFP) group as a general protecting group for phenols. TFP can be installed in one step with no sensitivity to water or air, and it is stable under a range of commonly employed reaction conditions including acid and base. The TFP protecting group is readily cleaved under mild conditions with quantitative conversion to the parent phenol, observed in many cases in less than 1 hour

The CASE 2014 symposium: Catalysis and sensing for our environment, Xiamen 7th–9th November 2014

The CASE 2014 symposium: catalysis and sensing for our environment, Xiamen 7th–9th November 2014</p

Asymmetric Copper-Catalyzed Azide–Alkyne Cycloadditions

This paper was accepted for publication in the journal ACS Catalysis and the definitive published version is available at http://dx.doi.org/10.1021/acscatal.6b00996.Since its discovery independently by Sharpless and Meldal in 2002, the copper-catalyzed azide–alkyne cycloaddition (CuAAC) has become a ubiquitous molecular linking platform. Easy access to substituted 1,4-triazoles can be exploited to engender asymmetry to a myriad of potentially useful targets in high yields. Utilizing the CuAAC to form chiral triazolic products in a single step is an attractive and powerful approach for the synthetic chemist. The area of asymmetric CuAAC is still in its infancy compared to more established asymmetric metal-mediated transformations; however, this leads to exciting challenges that need to be overcome to usher in the next era in the story of the triazole and click chemistry in general. This review details the steps taken into asymmetric CuAAC and the exciting results achieved thus far. [Note that diagrams accompany this abstract in the published version and can be found at http://dx.doi.org/10.1021/acscatal.6b00996.

Synthesis of Complex Unnatural Fluorine-Containing Amino Acids

The area of fluorinated amino acid synthesis has seen rapid growth over the past decade. As reports of singly fluorinated natural amino acid derivatives have grown, researchers have turned their attention to develop methodology to access complex proteinogenic examples. A variety of reaction conditions have been employed in this area, exploiting new advances in the wider synthetic community such as photocatalysis and palladium cross-coupling. In addition, novel fluorinated functional groups have also been incorporated into amino acids, with SFX and perfluoro moieties now appearing with more frequency in the literature. This review focuses on synthetic methodology for accessing complex non-proteinogenic amino acids, along with amino acids containing multiple fluorine atoms such as CF3, SF5 and perfluoroaromatic groups

Kinetic resolution of alkyne-substituted quaternary oxindoles via copper catalysed azide–alkyne cycloadditions

This is an Open Access article licensed under a Creative Commons Attribution 3.0 Unported Licence

One-pot ester and thioester formation mediated by pentafluoropyridine (PFP)

Acyl fluorides are valuable synthetic intermediates, but in some cases they can be challenging to handle and difficult to isolate given their susceptibility to degradation. In addition, many reagents utilised to prepare acyl fluorides are incompatible with in situ generation strategies and require the acyl fluoride to be isolated before any further reaction can take place. The combination of these factors has meant that acyl fluorides are currently under investigated in nucleophilic substitution processes, and often only a limited substrate scope is tolerated where they have been used. Herein, we report that pentafluoropyridine can be utilised to generate acyl fluorides in situ under mild conditions, and that they can subsequently be used to generate a range of esters and thioesters. This methodology offers a simple one-pot synthesis of esters and thioesters directly from parent carboxylic acids