Application of a Dual Linker with a Reference Cleavage Site to Discover a New Reaction between Amines and N-Hydroxyphthalimide

摘要

Successful solid-phase organic synthesis requires careful optimization of reaction conditions for individual chemical transformations because there is no opportunity to purify polymer-supported intermediates.Typical optimization protocol involves analysis of numerous samples corresponding to different reaction conditions.The analytical technique of choice for assessing the composition of products cleaved from solid support is the LC/MS technique.To obtain meaningful data,all resin-bound components need to be released from the solid support.We have designed and used dual linkers with a reference cleavage site that provide complete cleavage of all resin-bound reaction components and allow their identification using LC/MS.The concept of dual linkers is not a new one and was recently reviewed.We have already reported the use of a dual linker for the identification of a side-product in the Mitsunobu transformation of polymer-supported alcohols to amines.Herein,we report the use of a dual linker with a reference cleavage site in the discovery of a new reaction between amines and N-hydroxyphthalimide (PhtNOH).