Asymmetric catalysis towards stereoselective sustainable synthesis

With the aim of working at molecular level to achieve sustainability, the green chemistry goals are playing a pivotal role in modern synthetic chemistry.  Recently, the use of small organic molecules as catalysts, known as organocatalysis, has emerged as a greener alternative approach to the classical transition-metal catalysis. In this talk, three different aminocatalysed transformations for the asymmetric construction of C-C bonds will be presented, including a proline-catalysed desymmetrisation of 4-susbtituted cyclohexanones, an asymmetric Michael addition for the construction of fluorinated compounds as well as a Michael-Michael-aldol cascade for the stereoselective assembly of spirocompounds. Despite its impressive growth, asymmetric aminocatalysis still suffers from some general drawbacks, such as the relatively low catalytic efficiencies. As a result, most protocols require high loadings of catalyst, typically 10-20 mol%, to achieve satisfactory reactivity. To circumvent this issue, I developed the distribution of catalytic species as a new indicator to evaluate and in situ optimize the performance of catalytic reaction. The indicator graphically correlates the percentage of the different catalytic species present during the reaction course with their associated turnover frequency (TOF). Applied to the asymmetric conjugate addition of diverse C-nucleophiles to enals, it enables to reduce efficiently the catalyst loading to as little as 0.1 mol%. Further, the development of synthetic methodologies employing renewable feedstocks for the construction of new C-C bonds will be also presented. The implementation of a microfluidic photoreactor has enabled the design of new light-driven reactions of 2-methylbenzophenone derivatives in flow conditions through diverse reaction pathways, including Michael additions, [4+2] cycloadditions as well as asymmetric allylic benzylations.

 

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Seminario organizzato nell'ambito del ciclo di seminari per la selezione dei candidati al reclutamento per il Dipartimento di eccellenza