Synthesis of Carborane-Modified Sugars and Nucleosides via Pd(II)-Catalyzed B-H Bond Activation.

Abstract

Carborane-modified sugars and nucleosides are promising boron-delivery agents for boron neutron capture therapy (BNCT). Accordingly, a series of carborane-based sugars and nucleosides have been successfully prepared. Nevertheless, current research on such compounds is mainly focused on carbon-site modification of carboranes, yet methods for directly forming B-sugars/nucleosides without a protecting group are scarce. Herein, we establish an unprecedented and highly efficient protocol for the stereoselective synthesis of carborane-modified sugars and nucleosides via Pd(II)-catalyzed selective B-H bond activation of carboranes and subsequent addition to unsaturated sugars and nucleosides. The transformation selectively occurs at the C2 site of the sugar ring, exclusively affording products with the carboranyl moiety in an equatorial conformation. Remarkably, this protocol avoids preprotection of hydroxyl groups on glycal and unsaturated nucleoside substrates and exhibits broad substrate compatibility as well as excellent synthetic scalability. Mechanistic control experiments further demonstrate that hydroxyl groups and nitrogenous bases can act as weak coordinating groups to interact with the Pd catalytic center, which are indispensable for facilitating this catalytic transformation.