Application of pyrrolo-protected amino aldehydes in the stereoselective synthesis of anti-1,2-amino alcohols

Abstract

Herein, we demonstrate the applicability of the 2,5-dimethylpyrrolo unit as a complementary N-protecting group in the highly diastereoselective synthesis of more than 20 different anti-amino alcohols (63–90% yields with up to 20 : 1 dr). Cleavage of the pyrrolo-N-protecting group was accomplished, e.g. in the presence of NH₂OH under microwave conditions with yields exceeding 80%. The applicability of the protecting groups was further demonstrated by a short total synthesis of the sphinganine-like natural product clavaminol A. The introduction of the N-pyrrolo protecting group also offers the possibility to analyse product mixtures by NMR measurements due to the absence of conformational isomers, which are otherwise common for N-protecting groups.