Ammonium-Binding Bifunctional Aza-Crown Ether Catalysts for Substrate-Selective Hydroxyl Functionalization

Herein, we describe a new bifunctional macrocyclic catalyst that employs multiple weak noncovalent interactions to enable substrate-selective O-silylation of ammonium alcohols over more reactive aliphatic alcohols with up to >20:1 substrate selectivity. Our catalytic strategy merges (i) the use of crown ethers as ammonium-binding receptors and (ii) the exploitation of N-methyl imidazole as a catalytic motif. Our collective mechanistic studies reveal the importance of receptor size, conformational preorganization, and the number of hydrogen-bonding acceptor units needed to achieve high selectivity within the macrocyclic binding pocket.