Modular Hemisyntheses of Boronato- and Trifluoroborato-Substituted L-NHBoc Amino Acid and Peptide Derivatives

• Published in: European journal of organic chemistry 2013-12, Vol.2013 (35), p.7960-7972
• Main Authors: Audi, Hassib, Rémond, Emmanuelle, Eymin, Marie-Joëlle, Tessier, Arnaud, Malacea-Kabbara, Raluca, Jugé, Sylvain
• Format: Article
• Language: English
• Subjects: Amino acids; Boron; Chemical Sciences; Iridium; Phase-transfer catalysis; Trifluoroborates; Wittig reactions
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201301084

Modular hemisyntheses of boronato‐ and trifluoroborato‐substituted amino acid and peptide derivatives by using Wittig and C–H iridium‐catalyzed borylation as key reactions, are described. Amino ester precursors bearing an aromatic moiety on a lateral chain were prepared by reaction of a new L‐NHBoc‐amino acid Wittig reagent with the corresponding aromatic aldehydes. After esterification and hydrogenation, the borylation of amino esters was achieved with yields up to 82 % by using the catalysed reaction of bis(pinacolato) diborane reagent (B2Pin2) in the presence of an iridium complex. Interestingly, this iridium‐catalyzed borylation was also performed with a dipeptide in 78 % yield. Finally, reaction of the boronato amino acids with KHF2 or NaI in the presence of chloramine led to the corresponding trifluoroborato or iodo derivatives in good to excellent yields. A study of the hydrolysis of the trifluoroborates in buffer solution by using 19F NMR monitoring, showed an excellent stability for the 3‐methylthien‐2‐yl amino acid derivative. Consequently, this hemisynthesis offers an efficient route for the modular preparation of boron amino acid derivatives that are useful for the synthesis of modified peptides and the fluoride labelling of peptides. Modular hemisyntheses of new boron‐containing L‐amino acid derivatives by using Wittig and C–H Ir‐catalyzed borylation as key reactions, are reported. Reaction of the boronato amino acids with KHF2 or NaI in the presence of chloramine led to the iodo or trifluoroborato derivatives. An investigation of trifluoroborates hydrolysis in buffer solution (19F NMR) shows an excellent stability for the 3‐methylthienyl amino acid derivative.