Asymmetric Aza-Michael Addition from unsaturated diazoketones.

Abstract

Pyrrolidine, indolizidine and pyrrolizidine lkaloids are widely studied due to its medicinal properties, for example, antifungal, antibacterial, antiviral, antitumor activity and others. In view of this, methodologies enabling access to these compounds in a few steps and efficiently are big draws for organic chemistry. In this project we propose the study of asymmetric aza-Michael reactions from ±,²-unsaturated diazoketones, aiming the formation of chiral ²-amino diazoketones. The diazoketones will be prepared from Horner-Wadsworth-Emmons (HWE) olefination reactions between diazophosphonates and aldehydes. In sequence, methodological studies will be conducted for the asymmetric aza-Michael reaction employing chiral amines and asymmetric catalysts. Adducts will be then subjected to intramolecular N-H insertion reactions. Hydroxylated alkaloids from the prepared pyrrolidinones will be submited to biological studies. Another part of the project will be dedicated to the synthesis of pyrrolizidine and indolizidine skeletons from diazoketones.