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

• Abstract A new approach to the anticancer drug Velcade was developed by performing asymmetric borylation of an imine anchored with a chiral N-phosphinyl auxiliary. Throughout the 7-step synthesis, especially in the imine’s synthesis and in the asymmetric borylation reactions, operations and work-up were

• hexane; the chiral N-phosphinyl auxiliary can be easily recovered after deprotection is finished. Several other N-phosphinylimines were also investigated for the asymmetric borylation reaction. The absolute configuration of the borylation product was confirmed by single crystal X-ray diffraction analysis

• in these two cases. Conclusion We have successfully demonstrated that N-phosphinylimines can undergo electrophilic borylation reactions, and that this reaction can be applied in the synthesis of the anticancer drug Velcade. The N-phosphinyl auxiliary displayed good to excellent asymmetric induction

Synthesis of chiral N-phosphinyl α-imino esters and their application in asymmetric synthesis of α-amino esters by reduction

• Yiwen Xiong,
• Haibo Mei,
• Lingmin Wu,
• Jianlin Han,
• Yi Pan and
• Guigen Li

Beilstein J. Org. Chem. 2014, 10, 653–659, doi:10.3762/bjoc.10.57

• chromatography and recrystallization. The chiral phosphinyl auxiliary could be easily cleaved under acidic conditions. Keywords: α-amino ester; α-imino ester; group-assisted purification; phosphinyl auxiliary; reduction; Introduction α-Imino esters play a very important role in the field of imine chemistry [1

• configuration The phosphinyl auxiliary could be easily cleaved by treating with concentrated hydrochloric acid in methanol. After stirring of 4a with acid overnight, the conversion was complete and the corresponding amino ester hydrochloride was obtained. Then, the obtained free amino ester was directly