Chiral N-Heterocyclic Carbene-Catalyzed Annulations of Enals and Ynals with Stable Enols: A Highly Enantioselective Coates–Claisen Rearrangement

Abstract

A combination of a chiral N-heterocyclic carbene catalyst and α,β-unsaturated aldehyde leads to a catalytically generated α,β-unsaturated acyl azolium, which participates in a highly enantioselective annulation to give dihydropyranone products. This full account of our investigations into the scope and mechanism of this reaction reveals the critical role of both the type and substitution pattern of the chiral triazolium precatalyst in inducing and controlling the stereochemistry. In an effort to explain why stable enols such as naphthol, kojic acid, and dicarbonyl are uniquely efficient, we have postulated that this annulation occurs via a Coates-Claisen rearrangement that invokes the formation of a hemiacetal prior to a sigmatropic rearrangement. Detailed kinetic investigations of the catalytic annulation are consistent with this mechanistic postulate.

Imidazolium Salt‐Catalyzed Friedel–Crafts‐Type Conjugate Addition of Indoles: Analysis of Indole/Imidazolium Complex by High Level ab Initio Calculations

“…It is also notable that the reaction under neat conditions proceeded smoothly in a higher yield (Table 1, entry 7). [14] As examples of NHC catalysis requiring no base are scarce, [15] we examined Friedel-Crafts-type conjugate additions catalyzed by azolium salts ( Table 2). The choice of azolium salts was critical.…”

N‐Heterocyclic Carbene‐Catalyzed Enantioselective Annulation of Indolin‐3‐ones with Bromoenals

“…1,3‐Dicarbonyl compounds were recognized as the most common Michael donors to conduct 1,4‐addition reactions followed by Claisen rearrangements and intramolecular acylations, which delivered dihydropyranones. Bode and co‐workers have recently reported NHC‐catalyzed annulations of α,β‐unsaturated acylazoliums with stable enols such as naphthol5c and kojic acid 5a. In addition, the NHC‐catalyzed rearrangement of α,β‐unsaturated enol esters to form dihydropyranones was demonstrated by Lupton and co‐workers 10.…”

N‐Heterocyclic Carbene Catalysis as a Tool for Gaining Access to the 3,4‐Dihydropyran‐2‐one Skeleton

“…The mechanism is depicted in Scheme . The possibility of starting from enals and stoichiometric amounts of oxidant was also explored 37b…”