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. 2025 Sep 30:e00864.
doi: 10.1002/asia.202500864. Online ahead of print.

NHC/Urea Cocatalyzed Intramolecular Stetter Reaction to Construct Bicyclic and Tricyclic Spirocarbocycles

Day-Shin Hsu  1 , Wen-Hsin Lin  1 , Pui-Wai Un  1 , Li-Ying Wang  1
Affiliations

NHC/Urea Cocatalyzed Intramolecular Stetter Reaction to Construct Bicyclic and Tricyclic Spirocarbocycles

Day-Shin Hsu et al. Chem Asian J. .

Abstract

An NHC/urea-cocatalyzed intramolecular Stetter reaction is described. Various cyclic enone-aldehydes and enone-benzaldehydes were exposed to an N-heterocyclic carbene and urea in toluene in the presence of 4 Å molecular sieves, whereupon the intramolecular Stetter reaction proceeded smoothly at room temperature to give the corresponding bicyclic and tricyclic 1,4-diketones in 27%-96% yields. The ring size of the spiro compounds could be easily controlled by using different cyclic enones or by altering the length of the carbon tether. Both cyclic enone-benzaldehydes and cyclic enones tethered with a four-carbon side chain aldehyde gave the desired products, whereas substrates bearing a five-carbon side chain aldehyde resulted a complicated mixture of the products. The presence of a substituent in the cyclic enone moiety caused a decrease in the yields. An asymmetric intramolecular Stetter reaction was also attempted, and 94% ee was achieved when using an aromatic aldehyde as the substrate. The reaction of an aliphatic aldehyde led to poor yield and lower ee.

Keywords: Cyclization; N‐Heterocyclic carbene; Spirocarbocycles; Stetter reaction; Urea.

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