Enantioselective N‐Heterocyclic Carbene Catalyzed Cyclopentene Synthesis via the β‐Azolium Ylide

Abstract

Herein we report the cycloisomerization of electron-poor 1,5-dienes via the β-azolium ylide to give enantioenriched cyclopentenes. The reaction is mediated by a chiral N-heterocyclic carbene (NHC) catalyst, exploits readily available substrates, has good generality (17 examples), and displays excellent enantioselectivity (mostly >94:6). Studies demonstrating the viability of a related dynamic kinetic resolution are reported, as are those with alternate tethers and derivatizations.

NHC-Catalyzed Formal [2+2] Annulations of Allenoates for the Synthesis of Substituted Oxetanes

“…An intriguing “β-Umpolung” reaction with carbene catalysis was reported by Fu in 2006, and this alternate mode of NHC nucleophilicity has since only been reported in relatively few studies by our lab and others . Notably, recent elegant studies uniquely aimed at specifically harnessing this unconventional mode of NHC nucleophilic catalysis have been disclosed by Lupton …”

Recent advances of N-heterocyclic carbenes in the applications of constructing carbo- and heterocyclic frameworks with potential biological activity

“…Additionally, the highly stereoselective reaction was accomplished through the β-azolium ylide, which was reported lesser than Breslow intermediate ( Scheme 42b ). 91 …”

Polarity Inversion Catalysis by the 1,4-Addition of N-Heterocyclic Carbenes

“…Although enantioselectivity was possible with the previous design, an alternative cycloisomerization was developed by the same group to access more highly enantioenriched materials (Scheme 11). [19] In this transformation, the cyclization sets a stereocentre that is retained in the product. As a consequence, this design was more robust, allowing a wide array of cyclopentanes (i.e.…”