Development of novel organocatalytic strategies for the asymmetric synthesis of chiral hydrazides

Chirality is a fundamental property of molecules that describes their asymmetry, resulting in two non-superimposable mirror images known as enantiomers. This phenomenon plays a crucial role in various fields, particularly in chemistry and pharmacology, where the spatial arrangement of atoms can significantly influence a compound's biological activity and therapeutic efficacy. The study of chirality encompasses the development of asymmetric synthesis methods, enabling the selective production of one enantiomer over another. In this regard, we pursuit the asymmetric synthesis of N-N atropisomers, initially discovered in the 1930s, that have recently gained attention due to their potential in drug development and biological activity. Our research contributes to this emerging field through an extensive computational study of the distinct rotational barriers associated with N-N atropisomeric hydrazides, which provides critical insights into their stability and reactivity. We also focused on the synthesis of enantio- and diastereo-enriched tetrasubstituted hydrazides, expanding the toolkit for creating chiral frameworks essential in pharmaceuticals. Moreover, we explored the synthesis of chiral enantiopure allylic hydrazides, which are of significant interest in medicinal chemistry. The asymmetric variant of the Tsuji-Trost reaction remains the most developed approach for generating these precious scaffolds; on the other side, advancements in electrophilic amination have been limited. To address this gap, we presented a novel method for synthesizing enantioenriched allylic hydrazides by employing azodicarboxylate as the electrophilic nitrogen source and allylic boronates as the donor, facilitated by a catalytic amount of chiral diol. Additionally, as side project conducted abroad, in the Nottingham University in the Silvi lab, photoredox catalysis has been employed as a sustainable and efficient approach to derivatize readily available feedstock like olefines in valuable compounds as 1,3 diols.