Organocatalytic, Asymmetric Synthesis of Aza-Quaternary Center of Izidine Alkaloids: Synthesis of (−)-Tricyclic Skeleton of Cylindricine

Abstract

We report a highly efficient, enantioselective, organocatalytic method for the synthesis of izidinone alkaloids containing a bridgehead aza-quaternary center using ketone-derived N,O-hemiaminal with a tethered acetal. Alkyl-, aryl-, and alkenyl-substituted substrates cyclize to the respective products with excellent enantioselectivities. Five- and seven-membered ring formation has also been established. Furthermore, synthesis of the tricyclic skeleton of cylindricine alkaloids has been achieved in high yield.

Quaternary Ammonium Salts: Insights into Synthesis and New Directions in Antibacterial Applications

“…For example, Prakash et al used nitrogen-containing aromatics and alkynes to synthesize heterocyclic QASs with high efficiency under the catalytic oxidation of cobalt . Srinivas et al used an alkaloid as a catalyst to synthesize heterocyclic QASs containing a cylindrical tricyclic skeleton . It can be seen that the synthesis method of heterocyclic QASs is extremely common.…”

“…65 Srinivas et al used an alkaloid as a catalyst to synthesize heterocyclic QASs containing a cylindrical tricyclic skeleton. 66 It can be seen that the synthesis method of heterocyclic QASs is extremely common. Thus, how can it be applied to the field of antibacterials?…”

Sequential One-Pot Vilsmeier–Haack and Organocatalyzed Mannich Cyclizations to Functionalized Benzoindolizidines and Benzoquinolizidines

“…Although organocatalyzed Mannich reactions have been extensively studied, using such a reaction in a one-pot sequential process presents significant challenges. First, the amide activation for the Vilsmeier–Haack cyclization needs to be performed chemoselectively in the presence of a ketone or an aldehyde 7 .…”

Aminocatalytic Privileged Diversity‐Oriented Synthesis (ApDOS): An Efficient Strategy to Populate Relevant Chemical Spaces

“…The reaction proceeds via the in situ generation of an N ‐acyl iminium ion and an aldehyde motif from the N , O ‐hemiaminal and the acetal group, respectively. Notably, this method is applicable to the assembly of five‐, six‐, and seven‐membered rings (Scheme ) …”