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-phosphinylauxiliary. 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-phosphinylauxiliary 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-phosphinylauxiliary displayed good to excellent asymmetric induction
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Graphical Abstract
Scheme 1:
Previous work for (R)-(1-amino-3-methylbutyl)boronic acid synthesis.
Beilstein J. Org. Chem.2014,10, 653–659, doi:10.3762/bjoc.10.57
chromatography and recrystallization. The chiral phosphinylauxiliary could be easily cleaved under acidic conditions.
Keywords: α-amino ester; α-imino ester; group-assisted purification; phosphinylauxiliary; reduction; Introduction
α-Imino esters play a very important role in the field of imine chemistry [1
configuration
The phosphinylauxiliary 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