Synthesis of β-cyclodextrin-based per-6-phosphoramidates

An convenient methodology is reported to obtain beta-cyclodextrin (CD) derivatives perfunctionalized with phosphoramidates by reacting a per-6-azido-beta-CD substrate with various phosphites. This Staudinger-like ligation reaction can be successfully profited to prepare a range of novel per -6 -substituted beta-CD derivatives in moderate to excellent yields. The methodology worked well with phosphites containing less sterically hindered primary alkyl groups but showed limited scope for phosphites containing secondary alkyl groups. Some compatible functionality, such as alkene functionality, can be effectively embedded in the alkyl groups to obtain functionalized beta-CD-phosphoramidates for future chemical derivatization. The benefits of this methodology include the metal -free coupling to easily accessible per-6-azides of beta-CD that complement the popularly used copper(I)catalyzed Huisgen azide-alkyne cycloaddition.