Short Peptide-Derived Bifunctional Brønsted Base Catalysts in Asymmetric Michael Reactions

Abstract

Peptide catalysis has proven to be an effective tool for the synthesis of enantiomerically enriched compounds with synthetic applications or that are precursors of molecules with biological and pharmacological interest. Their ability to interact through H-bonds with the substrates and form complex H-bond networks is extremely helpful for reaction stereocontrol. Likewise, asymmetric Brønsted base (BB) catalysis is also a well stablished activation protocol for a great variety of transformations, and especially interesting and effective are bifunctional BB catalysts bearing H-bond donors, which can activate the nucleophile and the electrophile at the same time. In this context, and in spite of the big progress in the realm of asymmetric catalysis, there are still many new and challenging reactions that have not been resolved and/or require improvement. So, the main goal of this Thesis has been to design and synthesize a new family of catalysts that combine a short peptide, a typical privileged H-bond donating scaffold used in organocatalysis (squaramide/ ureidoaminal) and a BB, and to investigate them in some challenging transformations involving the generation of quaternary carbon stereocenters. Figure