Single-Atom Ligation of Four Different Alcohols at One Silicon Center: Methodology Development and Proof of Concept

Abstract

Click chemistry continues to impact the chemistry and biology community. Currently, the CuAAC chemistry could only ligate one azide and one alkyne fragment and the state of art SuFEx and PFEx chemistry could only ligate two or three amine and alcohol fragments. Herein, we realized the single-atom ligation of four different alcohol fragments at one silicon center using triphenylchlorosilane as the ligation hub in an iterative, controllable, and programmable fashion. To fulfill the mission, we have established a new silicon-phenyl exchange reaction with alcohols and a broad spectrum of alcohols could be ligated using various types of phenylchlorosilanes as the ligation hubs to generate mixed-dialkoxysilanes, trialkoxysilanes, and tetraalkoxysilanes. Ultimately, four different biologically relevant alcohols, i.e. borneol, menthol, diacetone-d-glacatose, and metronidazole, were successfully ligated to one Si(IV) center as mixed-tetraalkoxysilane, highlighting the application potential for functional molecule engineering and discovery.