Construction of Spirofused Tricyclic Frameworks by NHC-Catalyzed Intramolecular Stetter Reaction of a Benzaldehyde Tether with a Cyclic Enone

Abstract

Various benzaldehyde tethers with a cyclic enone were prepared from commercially available 2-hydroxybenzaldehydes via a three-step sequence involving triflate formation, Sonogashira cross-coupling, and regioselective hydrogenation. These substrates were then exposed to an N-heterocyclic carbene, whereupon intramolecular Stetter reaction proceeded smoothly to give various spirofused tricyclic 1,4-diketones in 30−87% yields. Furaldehyde and nicotinaldehyde derivatives also participated in the reaction under the Stetter conditions.

Electrogenerated NHCs in Organic Synthesis: Ionic Liquids vs Organic Solvents Effects

“…Recently, Hsu and Cheng developed an interesting intramolecular Stetter reaction to generate spirocyclic 1,4‐diketones (Table 2, entry 8) [40] . The authors showed the necessity of a protic solvent in this particular reaction.…”

Recent Advances in Stetter Reaction and Related Chemistry: An update

“…Next, these compounds through an NHC‐catalyzed intramolecular Stetter reaction afforded diverse spirofused tricyclic 1,4‐diketone derivatives in low to good yields. In addition, nicotinaldehydes and furaldehydes yielded good results via Stetter conditions [46] . This reactions were performed in the presence of thiazolium salt 128 (as catalyst) and TEA (as base) under reflux in ethanol.…”

“…In addition, nicotinaldehydes and furaldehydes yielded good results via Stetter conditions. [46] This reactions were performed in the presence of thiazolium salt 128 (as catalyst) and TEA (as base) under reflux in ethanol. The substrate scope of this reaction was examined by using other enone-aldehydes under the secured optimal reaction conditions.…”

N‐Heterocyclic Carbene‐Catalyzed Enantioselective Intramolecular Annulations to Construct Benzo‐Fused Pyranones with Quaternary Stereocenter

“…Subsequent base screening ( Table 1, entries 10-16) revealed, that different organic bases, even extremely strong ones such as BEMP or P 2 -Et could give the products with high yields and without erosion of stereoselectivity, remaining at < 99%. Additional screening of the reaction solvents did not show further improvements in the reaction outcomes ( Table 1, entries [16][17][18][19][20]. Finally, identification of diisopropylethylamine and toluene as the best-suited reaction conditions were indicated in terms of enantioselectivity for the developed annulation.…”

“…[13,14] In recent years N-heterocyclic carbene catalysis has emerged as an attractive and ideal strategy to synthesize complex heterocyclic molecules via umpolung reactivity. [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] Among various asymmetric catalytic strategies for the stereoselective construction and selective functionalization of the six-membered motifs, the Stetter reaction proved to be one of the universal and fundamental tool of the N-heterocyclic carbene (NHC) catalysis [30][31][32][33][34][35][36] After Ciganek initial contribution on intramolecular NHC-catalyzed synthesis of chromanones, during next years many highly enantioselective approaches have been developed (Scheme 1, eq a). [30,[37][38][39][40] In the later stage, Rovis and coworkers disclosed a highly enantioselective and diastereoselective Stetter reaction of salicylaldehyde-derived bearing a tethered α,β-disubstituted Michael acceptors (eq b).…”