Piperazino-Functionalized Silica Gel as a Deblocking-Scavenging Agent for the 9-Fluorenylmethyloxycarbonyl Amino-Protecting Group

Article abstract of DOI:10.1021/jo00153a009

Bonding cyclic secondary amino residues to the surface of silica gel has given insoluble reagents capable of deblocking the 9-fluorenylmethyloxycarbonyl amino-protecting group and at the same time scavenging the dibenzofulvene (DBF) liberated in the deblocking process.A piperazino silica reagent 6 bearing approximately 1.1 mequiv of NH/g was easiest to prepare by reaction of trimethoxysilane 5 with chromatographic-grade silica.After use, spent reagent could be regenerated by treatment with excess piperidine.Piperidino silicas 14 and 15 were made similarly.For the amino-functionalized silica reagents and a variety of simple cyclic secondary amines (piperazine, piperidine, etc.) the existence of an equilibrium (eq 3) between DBF (2) and adduct 7 has been established with the position of equilibrium being dependent on the nature of the amine, solvent, etc.Both deblocking and attainment of equilibrium were faster in Me2SO than in chloroform or dichloromethane.With piperazines in Me2SO the equilibrium was shifted toward complete scavenging by precipitation of the adduct from the reaction medium.