Substrate-Regiocontrolled Synthesis of Enantioenriched Allylic Amines by Palladium-Catalysed Asymmetric Allylic Amination: Formal Synthesis of Fagomine

Article abstract of DOI:10.1002/adsc.201600583

Branched allyl amines or linear amines can be obtained from E-4-hydroxybuten-2-yl methyl carbonate using the palladium/1,2-diaminocyclohexane (DACH)-catalysed allylic amination by just starting from the unprotected or the protected derivative, respectively. Unhindered primary amines can be used as nucleophiles, thus enlarging the scope of the Pd/DACH catalytic system. Hydrogen bonding involving the free hydroxy group in the unprotected allylic carbonate is proposed to be responsible for the control of the regioselectivity to afford branched isomers, obtained in high ee. A short and enantioselective formal synthesis of the glycosidase inhibitor fagomine is described using this method. (Figure presented.).