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Synlett 2009(6): 886-904  
DOI: 10.1055/s-0028-1088211
ACCOUNT
© Georg Thieme Verlag Stuttgart ˙ New York

Utilization of N,N,N′,N′-Tetramethylfluoroformamidinium Hexafluoro­phosphate (TFFH) in Peptide and Organic Synthesis

Ayman El-Faham*a,b, Sherine N. Khattab*a
a Faculty of Science, Chemistry Department, Alexandria University, P.O. Box 426, Ibrahemia, 21321 Alexandria, Egypt
e-Mail: Aymanel_faham@hotmail.com; e-Mail: ShKh2@Link.net;
b College of Science, King Saud University, P.O. Box 2455, Riyadh, Saudi Arabia
Further Information

Publication History

Received 20 August 2008
Publication Date:
16 March 2009 (online)

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Abstract

N,N,N′,N′-Tetramethylfluoroformamidinium hexafluoro­phosphate (TFFH) has been shown to be an excellent peptide-coupling reagent. It is an easily handled, crystalline compound, it has a long shelf life, and it reacts rapidly with carboxylic acids to give the corresponding acid fluorides or mixed anhydrides depending on the reaction conditions. TFFH has been shown to be useful as a peptide-coupling reagent and for the preparation of various carboxylic acid derivatives. Both aspects will be surveyed in this Account.

1 Introduction

2 Formation of Carboxylic Acid Halides

3 General Method for the Synthesis of Fluoroformamidinium Salts

4 Solution and Solid-Phase Peptide Coupling Using TFFH

5 Synthesis of Small Phosphotyrosine-Containing Peptides and Peptide Mimetics Incorporating α-Methylated Amino Acids

6 Synthesis of Lysine Analogues

7 Synthesis of Proline Conformation in Tripeptide Fragments of Bovine Pancreatic Ribonuclease A Containing the Nonnatural Proline Analogue 5,5-Dimethylproline

8 Synthesis of Different Types of Dipeptide Building Units Containing N- or C-Terminal Arginine for the Assembly of Backbone Cyclic Peptides

9 Synthesis of Peptidyl Methylcoumarin Esters as Substrates and Active-Site Titrants for Prohormone Processing

10 Synthesis of Boc-(N-All)Xaa-(N-All)Xaa-OMe

11 Synthesis of Alamethicin F30 and Analogues Using TFFH

11.1 C-Terminal Alamethicin F30-Fullerene C60 and C70 Conjugates

11.2 N-Terminal Alamethicin F30-Fullerene C60 Conjugate

12 Miscellaneous Examples

12.1 Synthesis of Isothiocyanates and Hydrazides

12.2 Conversion of Carboxylic Acids into Anilides and Azides

12.3 Acylation of Alcohols, Thiols, and Dithiocarbamates

12.4 Conversion of Carboxylic Acids into Alcohols and Hydroxamic Acids Using TFFH/PTF

12.5 Preparation of 2-Aminobenzimidazole, 2-Aminobenz­oxazole, and 2-Aminobenzothiazole Derivatives

12.6 Formation of Interchain Carboxylic Anhydrides on Self-Assembled Monolayers

12.7 Synthesis of the A1B(A)C Fragment of Everninomicin 13,384-1

12.8 Synthesis of Chiral Polyionic Dendrimers with Complementary Charges

13 Conclusion

Key words

TFFH - amino acid fluorides - solution-phase peptide synthesis - solid-phase peptide synthesis - carboxylic acid derivatives - heterocycles