Stetter adducts

In 1955, cyclophane derivatives of type (261) (with n = 3 or 4) were described (Stetter Roos, 1955). After recrystallization from benzene or dioxan, these species crystallized as the 1 1 adducts of these solvents. Once such adducts are formed, it is difficult to remove the solvent and it was concluded that the solvent molecules are housed inside the cavities of the respective guests. In accord with this, the smaller ring system (261 ... 

Electrophilic alkenes have been appended to imidazolium-type ILs for use in the Diels-Alder cycloaddition, 1,4-addition, Heck and Stetter reactions.Electrophilic alkenes containing Wang-type linkers were alkylated to imidazole followed by ion exchange and esterification giving the desired TSIL. Diels-Alder cycloaddition was carried out with 2,3-dimethylbutadiene and cyclopentadiene to give corresponding adducts. After washing with ether, transesterification resulted in cyclohexene derivatives. Scheme 29. 

Nucleophilic additions were studied using the same TSIL with pyrrolidine and thiophenol as models. As with the Diels-Alder reaction above, the reaction gave the required adducts which were then transesterified to give the final products. Heck coupling catalyzed by a transition metal and the Stetter reaction, Scheme 30, to prepare 1,4-dicarbonyl compounds were also studied by the same group using similar TSILs. 

The thiazolium salts may be converted into ylides by deprotonation. These ylides are comparable to the cyanide adducts in their ability to catalyze the Stetter Reaction effectively. 

First attempts of an asymmetric Stetter reaction were made 1989 in our research group with the investigation of chiral thiazolium salts such as 136 as precatalysts. The reaction of n-bu Lanai (133) with chalcone (134) in a two-phase system gave the 1,4-diketone 135 with an enanan-tiomeric excess of 39%, but a low yield of only 4% (Scheme 37) (Tiebes 1990 Enders 1993 Enders et al. 1993b). The catalytic activity of thiazolium as well as triazolium salts in the Stetter reaction persisted at a rather low level. Triazolium salts have been shown to possess a catalytic activity in the non-enantioselective Stetter reaction (Stetter and Kuhlmann 1991), but in some cases stable adducts with Michael acceptors have been observed (Enders et al. 1996a), which might be a possible reason for their failure in catalysis. 

The synthesis we are going to describe is particularly ingenious. A Stetter reaction (chapter 14) with the Diels-Alder adduct 44 (it doesn t matter that this is racemic and a mixture of exo/endo isomers) and the enone 45 provides the 1,4-diketone in 85% yield and hence, by retro-Diels-Alder, the achiral enedione 47 in 81% yield.7... 

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...

Very recently, Rovis et al. have examined the intermolecular Stetter reaction of glyoxamide with alkylidenemalonates [304] and alkylideneketoamides [305]. hi the presence of a suitable base, phenylalanine-derived triazolium salt 180 catalyzes the reactions in CCl at low temperature to afford the corresponding adducts in good yields, good diastereoselectivities, and excellent enantioselectivities (Scheme 2.110). 

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]. 

R. Hilgenfeld and W. Saenger, Angew. Chem., 94, 788 (1982). An X-ray structure analysis of the adduct of 1,6,19,24-tetraaza-[6.0.6.0]paracyclophane with benzene (the Stetter complex) showed that the benzene molecules are not accommodated in the cavity... 

A plausible reaction mechanism is illustrated in Scheme 5.50. Initially, Knoevenagel condensation between an aryl aldehyde and malononitrile, under basic conditions, gives Michael acceptor 69, which reacts with intermediate 156 via intermolecular Stetter reaction, leading to adduct 70. Then, upon effect of the base, an intramolecular cyclization occurs to give friran 68. 

The ThDP-dependent enzyme from Serratia marcescens (PigD), is an interesting carboligase since it has the ability to catalyze umpolung, Stetter type 1,4-additions to a,p-unsaturated ketones using pyruvate as donor substrate (Table 10.7) [51]. Aliphatic, aromatic as wdl as heterocydic a,p-unsaturated ketones selectively furnish the 1,4-adducts in the presence of pyruvate with PigD catalysis. Pyruvate is the preferred donor substrate, but 2-oxobutanoate can also be employed depending on the acceptor [51]. 

---