Linker-Controlled Macrocyclizations Enabling Selective Formation of Cyclic Trimers via Si–O Bond Formations

Highly efficient Si-O bond-forming macrocyclization has recently emerged as a powerful platform for the selective construction of structurally precise macrocycles. Here, we demonstrate that modification of the diol linker structure completely alters the preferred reaction outcome. Whereas the previously reported Ar-O-Si-O-Ar system exclusively afforded cyclic tetramers, introduction of methylene spacers into the linker overturns this inherent selectivity to achieve the selective formation of cyclic trimers in high yields. A series of silyl ether macrocycles were synthesized with outstanding efficiencies even at high concentrations. These results show that the outcome of Si-O-based macrocyclization can be effectively tuned by rational linker design.