Hemiacetals as versatile substrates for organocatalytic asymmetric transformations

Abstract

Acetals and hemiacetals are interesting building blocks for organic synthesis due to their easy preparation from alcohols and carbonyl compounds (both ubiquitous motifs in commercial and natural products). However, the first impressive application of these functional groups in organic synthesis came out just recently: acetals as substrates for photo-induced formylation reactions, through the rapid development of phoredox catalysis. Up to date, acetals were massive employed just as protecting groups in organic synthesis. On the other hand, hemiacetals appears as an unstable and unexplored functionalities. Aknowloging that hemiacetals can play a major role on organic synthetic protocols, our research group has been, in the last 5 years, focusing our efforts on developing new strategies, in which hemiacetals can be employed as bifunctional structures (aldehyde and alcohol or enol), specially in Ugi-type Multicomponent Reactions. In this scenario, this project aims to go one step forward into this chemistry by employing organocatalytic Brønsted acid asymmetric strategies in a broad variety of Ugi-type reactions, instead of using the previous substrate control report until now. Moreover, it is also of our interesting to employ acetals as substrates for the synthesis of total synthesis' intermediates via the Petasis-Ferrier Rearrangement. Since the end of the last century, this rearrangement has gained a proeminent position as a versatile synthetic tool, being employed in a variety of total syntheses of natural products. Although the great advances made in this field, so far no enantioselective protocol is reported, therefore another goal of this project is to develop an enantioselective organocatalytic Lewis acid variant of the Petasis-Ferrier Rearrangement. (AU)