Stetter cyclication

The regioselective attack of nonactivated C-H-bonds by an excited carbonyl group is demonstrated with the transannular cyclization of bicyclic diketones 76, which can easily be prepared from cyclic ketones 75 according to Stetter et al. [61]. Upon irradiation, the selectively excited benzoyl... 

The first documented synthetic macrocycle was synthesized by Baeyer via the condensation of pyrrole and acetone in the presence of mineral acid (Baeyer, 1886). Other examples, from a historical point of view, are listed in a review by Newkome and coworkers (Newkome et al., 1977). The aliphatic macrocycles were synthesized later as exemplified by Willstatter s synthesis of eight-membered rings (Willstatter and Veraguth, 1905) and Ruzicka s studies of the chemistry of muscone and civetone (Ruzicka, 1926). The synthesis of thiacycloalkanes using the reaction of sodium sulfide with an alkyl dihalide was also investigated early in the twentieth century (Braun and Tcherniac, 1907). A cyclam (cyclic amine) was first synthesized by Alphen (1937). The preparation of the peraza-crowns was first developed by Stetter (1953a,... 

A few typical examples will show the wide application of high dilution in the preparation of the cyclic bis-amides. Stetter prepared many bisamide... 

The nitrosation method is not recommended for a-aminoketones, but it works well for 2-amino-l,3-dicarbonyl compounds, as found by Wolff (1902) for the preparation of 3-diazopentane-2,4-dione (2.31). Cyclic diazo-a, a -diketones, such as 2-diazocyclohexane-l,3-dione (2.32, R=H) and its 5,5-dimethyl derivative (diazo-dimedone, 2.32 R=CH3), can be synthesized without major difficulties (Eistert et al., 1959 Stetter and Kiehs, 1965). The parent compound, diazomalonodialdehyde (2.33) was prepared only in 1973 by Arnold and Sanliova. The smooth formation of diazo-a,a -diketones and the decreased tendency for proton addition at the central C-atom can be explained by the resonance structures 2.31 a-c. 

Acetophenone and N-phenylglutarimide in abs. dioxane added with stirring at 80° to a suspension of NaH in abs. dioxane, and refluxed 10 min. until Hg-evolution subsides 5,6-dioxo-7-phenylheptanoic anilide. Y 75%. - Similarly with N-methyldiacetamide in ether after 3 hrs. reflex benzoylacetone. Y 81%. F. e. with cyclic diacylamines s. H. Stetter and W. Steinbeck, B. 103, 1088 (1970). 

In 2006, Matsumoto and Tomioka developed a chiral symmetric N-heterocyclic earbene generated from a dihydroimidazolium salt and strong base (potassium hydride or /r-butyllithium) and applied these catalysts to asymmetric intramolecular Stetter reactions with up 80% ee. It is remarkable to note that high temperature (reflux in toluene) is crucial for the formation of cyclic products with relatively high enantioseleetivity. Racemization of the product was almost sufficiently suppressed by adjusting the ratio of base to dihydroimidazolium salt to 1 2. 

Unfettered by the bounds of common Michael acceptors with electron-withdrawing groups, the Glorius group have impressively demonstrated the Stetter reaction of aldehydes with tethered unactivated 1,1-disubstituted alkenes. The cyclization reaction generally proceeds smoothly to afford cyclic ketones with quaternary stereocenters in excellent yields with high enantioselectivity. Based on detailed DFT calculations, they proposed a concerted mechanism for this reaction the proton migration and C—C bond formation between the Breslow enolate and the alkene occur simultaneously (Scheme 7.23). 

Later, p-acetoxy-substituted cyclic enones 87 with various ring sizes were also examined for intramolecular Stetter cyclization. Under the optimized Stetter conditions (1.0 equiv. of thiazolium salt 88 and 1.2 equiv. of EtsN in EtOH under reflux), bicyclic enedione 89 could be synthesized effectively (Scheme 4.27), but the yields mainly depended on the size of the ring in the substrate 87." Increasing the substrate ring size led to improved yields of 89. Cycloheptenone and cyclooctenone derivatives 87c,d afforded the desired enediones 89c,d in 80% yields. To reduce the conjugated C-C double bond, McMurry s procedure" using TiCls as a reductant was employed to give diketones 90 in excellent yields. 

Rabinovich L, Lev O, Tsirlina GA (1999) Electrochemical characterization of Pd modified ceramic vertical bar carbon electrodes partially flooded versus wetted channel hydrophobic gas electrodes. J Llectroanal Chem 466(l) 45-59 Rog G, Kielski A, Kozlowska-Rog A, Bucko M (1998) Composite (CaFj-AljOj) solid electrolytes-preparation, properties and application to the solid oxide galvanic cells. Ceram Int 24 91-98 Roh S-W, Stetter JR (2003) Amperometric sensing of NOx with cyclic voltammetry. J Electrochem Soc 150(11) H266-H272... 

Ritzau, M., Keller, M Wessels, P., Stetter, K.O., and Zeeck, A. (1993) New cyclic polysulfides from hyperthermophilic Archaea of the genus Thermococcus. Liebigs Ann. Chem., 871-876. 

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