Group-assisted purification (GAP) chemistry for the synthesis of Velcade via asymmetric borylation of N-phosphinylimines

• Jian-bo Xie,
• Jian Luo,
• Timothy R. Winn,
• David B. Cordes and
• Guigen Li

Beilstein J. Org. Chem. 2014, 10, 746–751, doi:10.3762/bjoc.10.69

• . Keywords: asymmetric borylation; GAP chemistry; organophosphorous; N-phosphinylimine; Velcade; Introduction The synthesis of chiral α-aminoboronic acids and their derivatives has attracted much attention in the organic and medicinal chemistry communities because of their importance for drug discovery and

• , MgSO4 or CaSO4 was chosen as the dehydration reagent together with molecular sieves for imine formation. Under these conditions, complete conversion can be reached after 5 days to give the chiral N-phosphinylimine, which can be directly used for the following asymmetric borylation reaction without

• hemiaminals 7 or as a mixture of imine and hemiaminal after purification by column chromatography. The hemiaminals were slowly transferred to the corresponding N-phosphinylimine as revealed by NMR analysis. The aliphatic imines are found to be unstable even in the presence of a trace amount of moisture, and