Two-Component Domino Reactions Initiated from Ketenes: Serendipitous Synthesis of Quinolizidinones Analogous to Chelated Lobeline’s Conformation

An original and efficient synthesis of quinolizidinones through a one-pot two-component cascade reaction of norlobelanine with in situ generated ketenes is reported. Functionalized fused azabicyclic scaffolds bearing multiple stereogenic centers were prepared with excellent diastereoselectivities. Mild optimized conditions involving a key “shuttle base” deprotonation strategy was applied to the synthesis, in a short sequence, of a constrained mimetic of the privileged H-bonded conformation of (−)-lobeline.