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

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.