An alternative method for the preparation of resin-bound secondary amines

Difficulties encountered in the synthesis of resin-bound secondary amines attached via an acid-labile linker encouraged us to employ an alternative approach. A one-pot, scalable procedure for the synthesis of Fmoc-protected, amine/linker constructs is reported. These compounds can be efficiently coupled to a solid support and be used in the synthesis of carboxamides and sulfonamides. The advantages of the method are the elimination of problems associated with variability of alkoxybenzaldehyde resins, minimization of difficulties encountered in solid-phase reductive aminations, and a means for quantifying the resin loading of the secondary amine.