Highly Selective Monomethylation of Primary Amines Through Host-Guest Product Sequestration

This Communication reports the highly selective monomethylation of primary amines through host-guest product sequestration. Complete control of the outcome of the N-methylation reaction has been achieved by adding to the reaction medium stoichiometric amounts of a teraphosphonate phosphonate cavitand Tiiii, capable of selectively and quantitatively trapping the monomethylated ammonium salt formed. The synergistic combination of ion-dipole, H-bonding, and CH3-pi interactions provide the high association constants (K-ass > 10(9)) and the specific complexation mode necessary for the exclusive sequestration of the monomethylated intermediate reaction product.