Catalytic Asymmetric Syntheses of Quinolizidines by Dirhodium-Catalyzed Dearomatization of Isoquinolinium/Pyridinium Methylides–The Role of Catalyst and Carbene Source

Convenient
access to highly enantioenriched substituted quinolizidines
has been achieved by chiral dirhodium­(II) carboxylate-catalyzed dearomatizing
formal [3 + 3]-cycloaddition of isoquinolinium/pyridinium methylides
and enol diazoacetates. Coordination of Lewis basic methylides to
dirhodium­(II) prompts the rearrangement of the enol-carbene that is
bound to dirhodium to produce a donor–acceptor cyclopropene.
The donor–acceptor cyclopropene is in equilibrium with the
dirhodium-bound enol-carbene and undergoes both enantioselective [3
+ 3]-cycloaddition from the dirhodium-bound enol-carbene and diastereoselective
[3 + 2]-cycloaddition by uncatalyzed reaction of the cyclopropene
with isoquinolinium or pyridinium methylides. Increasing the mol %
of catalyst loading suppresses the [3 + 2]-cycloaddition pathway.