Asymmetric Petasis reaction for the synthesis of chiral α- and β-butadienyl amines

The Petasis reaction using (1S,2R)-1-amino-2-indanol as the substrate and an activator to construct alpha- and beta-butadienyl amines in optically pure forms was realized, which are otherwise difficult to prepare. The reactions feature a metal-free nature, broad substrate scope, complete regioselectivities (gamma-selectivity of pinacol homoallenyl- and isoprenylboronates), and high to excellent chirality induction (up to >20 : 1 dr). The favored nucleophilic addition across the Si-face of the imine intermediate was explained using DFT calculations of the six-membered chair-like transition state.

Automated summary

The Petasis reaction successfully synthesized alpha- and beta-butadienyl amines using (1S,2R)-1-amino-2-indanol as the substrate, demonstrating metal-free nature, broad substrate scope, complete regioselectivities, and high to excellent chirality induction. The favored nucleophilic addition across the Si-face of the imine intermediate was explained using DFT calculations of the six-membered chair-like transition state.