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.