Featured Publications
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.
Enantiomer stability of atropisomeric 1,5-disubstituted 1,2,3-triazoles
The synthesis and characterisation of axially chiral atropisomeric 1,5-disubstituted 1,2,3-triazoles is reported. Molecules designed to display restricted rotation about 1,2,3-triazole N-1-aryl or 1,2,3-triazole C-5-aryl bonds were investigated by physical and computational techniques. The barrier to 1,2,3-triazole N-1-aryl rotation was found to be higher than that for 1,2,3-triazole C-5-aryl rotation, confirming axial chirality stemming from restricted rotation about an N-1-aryl bond in a 1,5-disubstituted 1,2,3-triazole to be the most suitable for the development of an axial chirality triazole-based platform..
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%.
Publications
21) Synthesis of atropisomeric phosphino-triazoles and their corresponding gold(I) complexes. Zhao Y.; Meloni F.; Male L.; Le Duff C. S.; Brittain, W. D. G*; Buckley B. R.*; Fossey J. S.*, Organic Chemistry Frontiers, 2023, 10, 3460-3466.
20) HFO-1234yf as a CF3 building block: synthesis of trifluoromethyl quinoline and chromene derivatives from trifluoromethyl-ynones. Marsh, T. G. F.; Santambrogio, A.; Murray, B. J.; Boulton, L. T.; Aquilar, J. A.; Yufit, D. S.; Sandford, G.; Brittain, W. D. G*, European Journal of Organic Chemistry, 2023, 26, e202300058.
19) One-pot ester and thioester formation mediated by pentafluoropyridine (PFP). Beardmore, L. N. D.; Cobb, S. L.; Brittain, W. D. G.*, Organic and Biomolecular Chemistry, 2022, 20, 8059.
18) Aminoacyl chain translocation catalysed by a type II thioesterase domain in an unusual non-ribosomal peptide synthetase. Wang, S.; Brittain, W. D. G.; Zhang, Q.; Lu, Z.; Tong, M. H.; Wu, K.; Kyeremeh, K.; Jenner, M.*; Yu, Y.*; Cobb, S. L.*; Deng, H.*, Nature Communications, 2022, 13, 62.
17) Enantiomer stability of atropisomeric 1,5-disubstituted 1,2,3-triazoles. Meloni, F.; Brittain, W. D. G.; Male, L.; Le Duff, C. S.; Buckley, B. R.*; Leach, A. G.*; Fossey, J. S.*, Tetrahedron Chem, 2022, 1, 100004
16) Perfluoroaryl and Perfluoroheteroaryl Reagents as Emerging New Tools for Peptide Synthesis, Modification and Bioconjugation. Brittain, W. D. G.*; Coxon, C. R.*, Chemistry a European Journal, 2022, e202103305.
15) Carboxylic Acid Deoxyfluorination and One-Pot Amide Bond Formation Using Pentafluoropyridine (PFP). Brittain, W. D. G.*; Cobb, S. L., Organic Letters, 2021, 23 (15), 5793-5798.
14) Synthesis of complex unnatural fluorine-containing amino acids. Brittain, W. D. G.*; Lloyd, C. M.; Cobb S. L., Journal of Fluorine Chemistry, 2020, 239, 109630
13) Remote Regioselective Electrophilic Aromatic Substitution Reactions. Brittain, W. D. G.*; Cobb S.L.*, The Journal of Organic Chemistry, 2020, 85, 6862-6871
12) N-Terminal Speciation in Native Chemical Ligation. Maguire O. R.; Hudson A. S.; Brittain W. D. G.; Cobb S. L.; O’Donoghue A. C.*, Chemical Communications, 2020, 56, 6114-6117
11) Coetaneous catalytic kinetic resolution of alkynes and azides through asymmetric triazole formation. Brittain W. D. G.; Dalling, A. G.; Sun, Z.; Duff, C. S. L.; Male, L.; Buckley, B. R.; Fossey, J. S.*, Scientific Reports, 2019, 9, 15086
10) Tetrafluoropyridyl (TFP): A General Phenol Protecting Group Readily Cleaved Under Mild Conditions. Brittain W. D. G.*; Cobb S. L.*, Organic and Biomolecular Chemistry, 2019, 17, 2110-2115.(Cover Article).
9) Synthesis of pentafluorosulfanyl (SF5) containing aromatic amino acids. Grigolato, L.; Brittain, W. D. G.; Hudson, A.S.; Czyzewska, M. M.; Cobb, S. L.*, Journal of Fluorine Chemistry, 2018, 212, 166-170
8) A Direct Route for the Preparation of Fmoc/OtBu Protected Iodotyrosine. Steer, A. M.; Bolt, H. L.; Brittain, W. D. G.; Cobb, S. L.*, Tetrahedron Letters, 2018, 59, 2644-2646.
7) Negishi Cross-Couplings in the Synthesis of Amino Acids. Brittain, W. D. G.*; Cobb, S. L.*, Organic and Biomolecular Chemistry, 2018, 16, 10-20.
6) Rapid Determination of Enantiomeric Excess via NMR Spectroscopy: A Research Informed Experiment. Fossey, J. S.*; Anslyn E. V.; Brittain, W. D. G.; Bull, S. D.; Chapin, B. M.; Duff, C. S. L.; James, T. D.; Lees, G.; Lim, S.; Lloyd, J. A. C.; Manville, C. V.; Payne, D. T.; Roper, K., Journal of Chemical Education, 2016, 94 (1), 79-84, (Cover Article).
5) The Bull-James Assembly as a Chiral Auxiliary and Shift Reagent in the Kinetic Resolution of Alkyne Amines by the CuAAC Reaction. Brittain, W. D. G.; Chapin, B .M.; Zhai, W.; Lynch, V. M.; Buckley, B. R.; Anslyn, E.V.; Fossey, J. S.* Organic and Biomolecular Chemistry, 2016, 14 (46), 10778-10782. (Cover Article).
4) Asymmetric Copper-Catalyzed Azide–Alkyne Cycloadditions. Brittain, W. D. G.*; Buckley, B. R.; Fossey, J. S. ACS Catalysis, 2016, 6, 3629-3636.
3) Kinetic Resolution of Alkyne-Substituted Quaternary Oxindoles via Copper Catalysed Azide-Alkyne Cycloadditions. Brittain, W. D. G.; Buckley, B. R.; Fossey, J. S.* Chemical Communications, 2015, 51, 17217-17220. (Cover Article).
2) Recent advances in the use of chiral metal complexes with achiral ligands for application in asymmetric catalysis. Cao, Z.-Y.; Brittain, W. D. G.; Fossey, J. S.; Zhou, F.* Catalysis Science & Technology, 2015, 5, 3441. (Cover Article).
1) The CASE 2014 symposium: Catalysis and sensing for our environment, Xiamen 7th-9th November 2014. Fossey, J. S.; Brittain, W. D. G. Organic Chemistry Frontiers, 2015, 2, 101-105. (Invited)
Preprints
3) Enantiomer stability of atropisomeric 1,5-disubstituted 1,2,3-triazoles. Meloni, F.; Brittain, W. D. G.; Male, L.; Duff, C. S. L.; Buckley, B. R.*; Leach, A. G.*; Fossey, J. S.,* ChemRxiv, 2021.
2) Remote Regioselective Electrophilic Aromatic Substitutions Using a Tetrafluoropyridyl (TFP) Phenol Protecting Group. Brittain, W. D. G.*; Cobb, S. L.,* ChemRxiv, 2019.
1) Simultaneous Kinetic Resolution: Coetaneous catalytic kinetic resolution of alkynes and azides through asymmetric triazole formation. Brittain, W. D. G.; Dalling, A. G.; Sun, Z.; Duff, C. S. L.; Male, L.; Buckley, B. R.;* Fossey, J. S.,* ChemRxiv, 2017