Efficient Synthesis of (P-Chirogenic) <i>o</i>‑Boronated Phosphines from <i>sec</i>-Phosphine Boranes

An efficient synthesis of boronated phosphines with an <i>o</i>-phenylene-bridge prepared from <i>sec</i>-phosphine boranes and using benzyne chemistry is reported. Successive reactions of <i>sec</i>-phosphine boranes with <i>n</i>-BuLi and 1,2-dibromobenzene, and then with boron reagents, afford the <i>o</i>-boronato­phenyl­phosphine derivatives in 71% yields. The use of P-chirogenic <i>sec</i>-phosphine boranes leads to the free boronated phosphines with retention of configuration at the P-center after decomplexation. The reaction of P-chirogenic <i>o</i>-boronato­phenyl­phosphine with KHF₂ affords the corresponding trifluoroborated phosphine with ee >98%

<i>o</i>‑Boronato- and <i>o</i>‑Trifluoroborato–Phosphonium Salts Supported by l‑α-Amino Acid Side Chain

The synthesis of <i>o</i>-boronato- and <i>o</i>-trifluoroborato–phosphonium salts supported by the l-amino acid side chain is described. The synthesis of these new class of amino acid derivatives was achieved by stereoselective quaternization of <i>o</i>-(pinacolato)­boronatophenylphosphine with β- or γ-iodo amino acid derivatives which are prepared from l-serine or l-aspartic acid, respectively. The quaternization of the phosphine was performed using either iodo amino ester or carboxylic acid derivatives. In addition, free carboxylic acid and amine derivatives were obtained by saponification or HCl acidolysis of <i>o</i>-boronato–phosphonium amino esters, respectively. The usefulness of these compounds in peptide coupling was demonstrated by coupling an <i>o</i>-boronato–phosphonium amino ester with an aspartic acid moiety. When the <i>o</i>-boronato–phosphonium amino acid or dipeptide derivatives were mixed with fluoride, the corresponding <i>o</i>-trifluoroborated products were cleanly and rapidly obtained in high isolated yields. The hydrolysis of these compounds at room temperature using a phosphate buffer pH 7/CD₃CN mixture has shown only traces of free fluoride F^– after several days. Finally, a preliminary radiolabeling essay has proven the facile [¹⁸F]-fluoride incorporation and high stability of the radiolabeled product in aqueous conditions. Indeed, this new class of boron–phosphonium amino acid derivatives shows promising properties for their applications in synthesis and labeling of peptides