Design and Evaluation of Ambiphilic Aryl Thiol–Iminium-Based Molecules for Organocatalyzed Thioacyl Aminolysis

Progress toward the
design and synthesis of ambiphilic
aryl thiol–iminium-based
small molecules for organocatalyzed thioacyl aminolysis is reported.
Here we describe the synthesis of a novel tetrahydroisoquinoline-derived
scaffold, bearing both thiol and iminium functionalities, capable
of promoting the transthioesterification and subsequent amine capture
reactions necessary to achieve organocatalyzed thioacyl aminolysis.
Model studies demonstrate the ability of this designed organocatalyst
to deliver critical intermediates capable of undergoing these individual
reactions necessary for the proposed process. Future design improvements
and directions toward cysteine-independent organocatalyzed native
chemical ligation are discussed.