Chemistry Defense: Jiaqi Zhu- "Transition Metal-Catalyzed Diastereo-, Enantio-, and Z/E- Selective Allylation and Alkylation of Azatrienes for the Preparation of Chiral Amine Derivatives"

Presenter: Jiaqi Zhu

Transition Metal-Catalyzed Diastereo-, Enantio-, and Z/E- Selective Allylation and Alkylation of Azatrienes for the Preparation of Chiral Amine Derivatives

The stereoselective synthesis and derivatization of chiral allylic amines have attracted extensive attention in synthetic chemistry, not only because this motif is prevalent in pharmacologically active compounds but also due to its importance as a structural element in chiral ligands and functional molecules. Chiral allylic amines bearing two contiguous stereogenic centers represent particularly valuable but challenging building blocks, as their preparation requires precise control over multiple stereochemical elements.

To address these challenges, this dissertation describes the development of transition-metal hydride-catalyzed reductive coupling reactions of azatrienes that enable the highly stereoselective construction of chiral allylic amine derivatives. Using copper hydride catalysis, enantio- and diastereoselective syntheses of chiral allylic amino alcohols were achieved with broad functional group tolerance and high levels of efficiency and selectivity. In parallel, cobalt- and nickel-hydride catalytic systems were investigated for the synthesis of chiral allylic amines via reductive coupling with carbonyl and alkyl electrophiles, representing rare examples of catalytic allylation reactions that simultaneously establish two stereogenic centers in a single enantioselective step.

In addition, density functional theory (DFT) calculations were performed to gain mechanistic insight into the copper-catalyzed processes. The computed energy profiles suggest that azatriene hydrocupration is followed by a stereocontrolled C-C bond-forming step, providing a mechanistic explanation for the experimentally observed regio- and stereochemical outcomes.

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