Stetter reaction of enals

Scheme 7.26 NHC-catalyzed asymmetric intermolecular Stetter reaction of enals with modified chalcones reported by Chi.

Later in 2011, the Rovis group achieved excellent enantioselectivity and reactivity in the Stetter reaction of enals with nitroalkenes (up to 98% yield and 98% ee). Enals are reasoned to be a suitable alternative to heteroaromatic aldehydes due to their electronic similarity to aryl aldehydes but sterically less demanding and lacking a proximal Lewis base. The reaction rate and efficiency are profoundly impacted by the presence of catechol. Yield was improved... 

In 2011, Chi and coworkers disclosed the Stetter reaction of enals with 1,1-diactitvated Michael acceptors, providing the corresponding triketones 46 in good yields and with high enantioselectivities (Scheme 20.22). 

Very recently, Chi and co-workers [58] reported the Stetter reaction of enals with 1,1-diactitvated Michael acceptors, providing the corresponding producst in good yields with high enantioselectivities (Scheme 7.38). (B.y-Unsaturated-a-ketoesters were also successfully employed as acceptors for the intermolecular Stetter reaction. A variety of aldehydes worked well under the optimized conditions and afforded die corresponding products in up to 92% yield with up to 91% ee (Scheme 7.39) [59]. 

The Chi group reported in 2011 the enantioselective Stetter reaction between enals and modified chalcones proceeding through a Michael-type addition of NHC-bound enal acyl anions to the Michael acceptors. The Stetter reaction with p-alkyl enals afforded the Michael addition products with good enantioselectivity and yields (14 examples, up to 93% yield, 94% ee). While P-aryl enals were tested in this reaction, up to moderate yield was achieved. This was because the enolate pathway (giving Diels-Alder products)" dominated, which was difficult to suppress under these reaction conditions (Scheme 7.26). 

In 2009, Rovis and co-workers [54] developed the chiral NHC catalyzed intermolecular Stetter reaction of heteroarylaldehydes with nitroalkenes. In the presence of 10 mol% of chiral fluorine-modified triazolium salt 44, the desired products were obtained in very good yields with high enantioselectivities (Scheme 7.34). Recently, they successfiilly expanded the reactions to enals. It was foimd that protic solvents are required for the reactivity. In addition to cinnamic aldehyde derivative, (3-alkyl enals also worked well to give the adduct in good yields with good enantioselectivities (Scheme 7.35) [55]. 

Enals (92) react with modified chalcones (e.g. 93) in an enantioselective Stetter reaction, giving highly functionalized products (94) in ees up to 97%, using chiral NHC catalysis. A Michael-type addition of NHC-bound enal acyl anion to the chalcone is proposed. ... 

Figure 7.25 N-Heterocyclic carbenes catalyze reactions between ary aldehydes and enals. Depending on the nature of the catalysts, " "" 1,4-diones (Stetter products), y-lactones or even a 2+1 adduct (a hemiacetal) can be formed...

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