New Reactions in Metal-based and Enzymatic Catalysis

Identifier:  TDX:4034

Handle: https://hdl.handle.net/20.500.11797/TDX4034

Authors:  Faraone, Adriana

Abstract:
The objective of this research thesis was to upgrade established strategies of asymmetric catalysis by disclosing novel catalytic functions, useful to develop mechanistically-divergent enantioselective processes. In the first project, visible light irradiation was used to divert the well-established reactivity of a chiral iridium(III)--allyl complex that functioned as a general electrophile in the ground state. Upon excitation it became instead a single electron transfer (SET) oxidant in the excited state. The photoexcitation of this chiral organoiridium complex enabled a mechanistically-novel enantioselective radical C-C cross coupling that was unattainable in the thermal domain. The method allowed us to couple racemic benzyl allylic alcohols and 4-alkyl-dihydropyridines (DHPs), which delivered α-amino radicals upon SET oxidation by the excited state of the iridium(III) complex. The reaction proceeded under 460 nm irradiation at room temperature and afforded the desired allylic products in high yields and enantiomeric excess. In the second project, we used the genetic modification of a well-established enzyme to turn it into a multifunctional biocatalyst, which could drive a mechanistically-novel biocascade reaction by catalyzing all the steps of the cascade sequence with high stereocontrol. Our new multifunctional biocatalysts belonged to the 4-oxalocrotonate tautomerase (4-OT) family of enzymes and they could perform both the enamine activation of linear aldehydes and the iminium ion activation of enals in a sequential way. This allowed us to implement the enzymatic versions of the two classic organocascade reactions reported by Enders for the synthesis of complex and highly enantioenriched cyclohexene carbaldehyde scaffolds. Our biocatalytic protocol matched, and sometimes surpassed, the organocatalytic approach in terms of efficiency and stereoselectivity.