Control of Activation Mode To Achieve Diastereodivergence in Asymmetric Syntheses of Chiral Spiropiperidinone Derivatives

An efficient organocatalytic
cascade reaction has been developed involving a Michael–hemiaminalization
relay for the asymmetric synthesis of spiropiperidinone derivatives
bearing adjacent quaternary and tertiary chiral centers via LUMO or
HOMO activation. Importantly, this methodology demonstrates that applying
distinct activation modes to different substrates in the same reaction
can diverge diastereoselectivity. To our knowledge, this is also one
of the few published cases of primary amine catalytic [3 + 3] cycloaddition
reactions involving α-branched β-ketoamides.