Michael reactions using supported fluorides

The base-catalysed addition of thiols to Jt-electron-deficient alkenes is an important aspect of synthetic organic chemistry. Particular use of Triton-B, in place of inorganic bases, has been made in the reaction of both aryl and alkyl thiols with 1-acyloxy-l-cyanoethene, which behaves as a formyl anion equivalent in the reaction [1], Tetra-n-butylammonium and benzyltriethylammonium fluoride also catalyse the Michael-type addition of thiols to a,P-unsaturated carbonyl compounds [2], The reaction is usually conducted under homogeneous conditions in telrahydrofuran, 1,2-dimethoxyethane, acetone, or acetonitrile, to produce the thioethers in almost quantitative yields (Table 4.22). Use has also been made of polymer-supported qua-... 

Nitroalkanes282 288 as well as alkyl sulfones283 288 can serve as useful and general alkyli-dene transfer reagents for highly activated Michael acceptors such as alkylidenemalonic esters (equation 131), Alumina-supported potassium fluoride is an effective reagent for the reaction of nitroalkanes282. The alkylidene transfer from sulfones may be promoted by Ni(acac)2289. 

A series of nitrocyclohexanol derivatives has been synthesized by using MW irradiation starting from nitromethane and unsaturated ketones in the presence of alumina-supported potassium fluoride under solvent-free conditions (Scheme 8.34). The reaction involves a double and diastereoselective Michael addition followed by ring closure [102]. 

Ohtani et al. used polystyrene-supported ammonium fluoride as a phase transfer catalyst (triphase catalysis) for several base-catalyzed reactions, such as cyanoethylation, Knoevenage reaction, Claisen condensation and Michael addition. The catalytic activity of the polystyrene-supported ammonium fluid was comparable to that of tetrabutylammonium fluoride (TBAF). The ionic loading and the ammonium structure of the fluoride polymers hardly affected the catalytic efficiency. The reaction was fast in a non-polar solvent (e.g., octane or toluene) from which the rate-determining step of the base-catalyzed reaction is very similar to that of the nucleophilic substitution reactions. 

The use of neutral alumina can lead to multiple addition reactions, but basic alumina gives clean reactions [146]. There are many examples of the use of potassium fluoride supported on alumina being used as a catalyst for Michael additions [125, 147]. 

Alkylation of j8-diketones using polymers as supports for the intermediate enolate anion has also been reported (Gelbard and Colonna, 1977). Reaction of several cyclohexyl j3-diketones with Amberlite IRA-9(K) formed a resin-linked j8-diketonate that could be readily alkylated. Similarly, it was shown that alkylation of phenoxide anions can be readily effected when the anions are supported via an ionic bond with the resin (Gelbard and Colonna, 1977). Alkylations of /3-diketones were also shown to occur if a fluoride-substituted, strongly basic resin (Amberlyst A26, A27, or Dowex MSA-1) is used (Miller et at., 1978). In this case, the presence of the fluoride ion was necessary before reaction would proceed. Considering the report on the use of Amberlite IRA-900— a very similar resin— the necessity for a fluoride ion is puzzling. In the same publication, the 0-alkylation of phenols, the sulfenylation of /3-diketones, and the Michael addition of a thiol to an ot,/8-unsaturated ketone were also investigated. 

Polymer-supported podands appear to be more commonly used in solid-liquid systems. A variety of chemical transformations including nucleophilic substitutions at saturated carbon atoms [214,215], esterifications [214], sodium bo-rohydride reduction [214], fluoride-catalyzed Michael addition [214], phenacyl ester synthesis, Darzen s reaction, Wittig alkenylation, and dichlorocarbene reactions can be carried out under these conditions [214],... 

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