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

Click chemistry continues to impact the chemistry and biology community, with the most well-known being the CuAAC click chemistry. Topologically, the CuAAC click chemistry only ligated two fragments in a two-dimensional manner. While the SuFEx and PFEx chemistry could ligate fragments three-dimensionally, maximally three fragments (amine/alcohol) could be clicked together for now. Herein, we report the three-dimensional single-atom ligation of four different fragments (alcohols) at one silicon center using triphenylchlorosilane as the ligation hub in an iterative, controllable, and programmable fashion. To fulfill the mission, we established a new silicon-phenyl exchange reaction with alcohols. A broad spectrum of alcohols could be ligated using various types of phenylchlorosilanes as ligation hubs, affording a library of mixed-dialkoxysilanes, trialkoxysilanes, and tetraalkoxysilanes. Notably, fully heteroleptic tetraalkoxysilanes were barely known in literature and extremely difficult to access in a selective fashion from a retrosynthetic viewpoint. Our protocol thus provided a robust solution to materials of such nature. To highlight the application potential, four different biologically relevant alcohols, representing four different functions, were successfully ligated to one Si(IV) center as fully heteroleptic tetraalkoxysilane. More importantly, the four alcohols could be released and recovered via silicon-alkoxy exchange of the stable yet cleavable Si-O bonds.