Towards The Direct Synthesis Of Chiral Amines Via Asymmetric Rhodium Catalyzed Hydroaminomethylation Reactions

Identifier:  TDX:4279

Handle: https://hdl.handle.net/20.500.11797/TDX4279

Authors:  Langlois, Joris

Abstract:
Chiral amines, pivotal in natural substances, pharmaceuticals, and industrial compounds, constitute 40–45% of small-molecule drugs. They serve as versatile tools in chemical synthesis. This thesis delves into homogeneous asymmetric hydroaminomethylation of alkenes (1,1-diarylethenes, cyclopropylmethacrylamides) and intramolecular hydroaminomethylation of amine-containing styrene derivatives. Preliminary findings on heterogenized chiral catalysts for hydroaminomethylation are discussed. In asymmetric hydroformylation and hydroaminomethylation of 1,1-diarylethenes, sugar-based ligands L14 and L15 excel, achieving good conversions, moderate chemoselectivity, and up to 41% enantiomeric excess (ee). Chiral amines are obtained with 30-47% yield and ee values between 23 and 36%. Protected phenol 3.20 enhances chemoselectivity and enantioselectivity, reaching up to 46% ee. Chiral chromanols 3.8a-g are synthesized in yields of 45-90% via asymmetric hydroformylation, marking a milestone in the direct synthesis of Tolterodine and derivatives. Chapter IV focuses on the reactivity of 2-cyclopropylmethacrylamides in Rh-catalyzed hydroformylation and hydroaminomethylation.