The ability to access diverse targets from a common intermediate is a very attractive prospect in organic synthesis. We sought to prepare both �-substituted-a-amino esters and substituted tetrahydroisoquinolines from a common aziridinium intermediate via a regio- and stereoselective ring opening by either an external or internal nucleophile, providing an elegant one-pot approach to a library of compounds with potential biological activity.Activation of enantiopure �-amino-a-hydroxy esters with XtalFluor-E� resulted in formation of the corresponding aziridinium ion. In situ opening by a range of external nucleophiles was achieved upon treatment with either NEt3�3HF or TMS-X (X = N3-, AcO-, NC-). After deprotection, this methodology provides an efficient route to a wide range of �-substituted-a-amino acids with high regioselectivity (99:1) and complete diastereocontrol (>99:1 dr).An elegant, one-pot strategy for the synthesis of the tetrahydroisoquinoline core was also developed: treatment of �-amino-a-hydroxy esters with Tf2O promoted rearrangement to the requisite tetrahydroisoquinoline in >99:1 dr and up to 75% yield. The substrate scope of this methodology, including alternative N- and �-substitution patterns, will also be discussed.

Aziridinium intermediates in the regio- and stereoselective synthesis of �-substituted-a-amino acids and tetrahydroisoquinolines

248th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.