Cascade reactions alkene derivatives

Finally, a novel three-component radical cascade reaction involving isonitriles has just been published [6]. In this paper, aromatic disulfides, alkynes, and isonitriles have been reported to react under photolytic conditions to afford -arylthio-substituted acrylamides 49 or acrylonitriles 50 in fair yields as mixtures of the E and Z geometric isomers (Scheme 21). The procedure entails addition of a sulfanyl radical to the alkyne followed by attack of the resulting vinyl radical on the isonitrile. A fast reaction, for example, scavenging by a nitro-derivative (route a) or f-fragmentation (route b), is necessary in order to trap the final imidoyl radical, since addition of vinyl radicals to isonitriles seems to be a reversible process. The reaction provides very easy access to potentially useful poly-functionalized alkenes through a very selective tandem addition sequence. 

Later, the same group succeeded in achieving a cascade Michael/nitro-Mannich/ acetalization reaction by the combination of covalent enamine catalysis and noncovalent bifunctional base/Br0nsted acid catalysis [32]. The fuUy substituted piperidines with diverse substitution patterns were prepared efficiently starting from simple aliphatic aldehydes, Ts-protected imines, and trani -P-nitro alkenes (Scheme 9.36). This finding effectively incorporated prolinol silyl ether-catalyzed Michael addition of aldehyde 65 to nitroalkene 75 and valine-derived bifunctional thiourea-mediated nitro-Mannich reaction of y-nitro aldehyde 106 to imine 105 in the cascade process, providing a complementary contribution to the well-known single catalyst-promoted triple cascade reactions and two catalyst-promoted reaction cascades. 

Using the catalyst system described above in combination with a rhodium phosphine catalyst Lebel reported the de novo synthesis of alkenes from alcohols [100]. They developed a one-pot process, avoiding the isolation and purification of the potentially instable aldehyde intermediate. They combined the oxidation of alcohols developed by Sigman [89] with their rhodium-catalyzed methylenation of carbonyl derivatives. The cascade process is compatible with primary and secondary aliphatic as well as benzyUc alcohols in good yields. They even added another reaction catalyzed by a NHC complex, the metathesis reaction, which has not been addressed in this review as there are many good reviews, which exclusively and in great depth describe all aspects of the reaction. 

When the carbopalladation of the bicyclopropylidene is performed in the presence of methyl acrylate, the reaction takes a different course (Scheme 8.34) [79]. The 1,3-diene intermediate 75 reacts in situ with the dienophile to give the spiro[2.5]octane derivative 76. An extension of this cascade Heck-Diels-Alder reaction involving l,3-dicyclopropyl-l,2-propadiene as the alkene partner, an alkenyl or aryl halide and a dienophile has been reported [80]. 

Generation of 3-indolylacyl radicals from the selenoesters 149, using either /j-Bu3SnH or tris(trimethylsilyl)silane (TTMSS) followed by reaction with various alkenes, offers a route to 3-acylindoles 150. On the other hand, the use of n-Bu Sn2 under irradiation gave cyclopent[6]indole derivatives such as 151 via a cascade involving initial addition of the acyl radical to the alkene, and a subsequent oxidative cyclization at the indole C-2 <02JOC6268>. 

Ru-catalysed enyne metathesis offers a short approach to chiral derivatives of 3-vinyl-5,6-dihydro-2//-pyrans. Some epimerisation can occur at the pyranyl C atom at elevated temperatures (Scheme 3) <02T5627>. The bispropargyloxynorbomene derivative 6 undergoes a cascade of metathesis reactions in the presence of alkenes and Grubbs catalyst incorporating an enyne-RCM that leads to fused cyclic dienes. A dienophile can be added to the reaction mixture, resulting in Diels-Alder reactions and the formation of functionalised polycyclic products <02TL1561>. 

Norbornene derivatives bearing two alkynes undergo cascade enyne metathesis reactions when treated with a first generation ruthenium carbene and ethylene, giving heterocyclic dienes [28]. The ROM of the norbornene moiety initiates the cascade enyne RCM reactions (Scheme 14). When ethylene is replaced by a monosubstituted alkene, a single enyne RCM takes place, after the initial ROM of norbornene. 

D.i.b. Insertion of Another Alkenyl Unit In certain cases, however, the 3-exo-trig process may be retarded and an additional alkene moiety participates in the cascade carbopalladation. A pioneering example of this kind has been demonstrated by Overman and co-workers in their total synthesis of scopadulcic acid A, starting from an iodoaUcenyl-substituted methylenecycloheptene derivative (Scheme 24). The first intramolecular carbopalladation occurs across the disubstituted double bond of the exomethylene group, and the trisubstituted endocyclic double bond acts as the terminator to give a tricyclic system, which was further elaborated to the natural product (Scheme 24). It is remarkable that all three quaternary carbon centers can be created by intramolecular Heck reactions. 

Figure 11.17. Examples of unsaturated fatty acids. Large numbers of such alkenes both as ( )- and (Z)-isomers exist. The intermediate in the oxidation of arachidonic acid to (only one shown member of the) prostaglandins is part of a cascade of reactions to an entire family of compounds that vary in oxidation state. Leukotrienes (three conjugated double bonds and no five-membered ring) and thromboxanes with six-membered oxygen-containing rings (oxa-cyclohexane, pyran, oxane) are also derived from C20 polyalkenes.

Imino-Diels-Alder reaction [49] containing the coupling of imine and electron-rich alkene gradually became a powerful tool for the synthesis of quinazohne derivatives [50], In Povarov imino-Diels-Alder reaction, aniline and ethyl glyoxalate were chosen as substrates. And two molecules of a-iminoesters, which were obtained from the condensation of aniline and ethyl glyoxalate, were hypothesized to form the direct additive product. Cascade imino-Diels-Alder reaction conducted by Chenetal. [51] (Scheme 13.11) was extended from the Povarov imino-Diels-Alder reaction. In this research, researchers chose the same substrates as in the Povarov imino-Diels-Alder reaction, adopted various kinds of Lewis acids as catalysts, and finally produced quinazoline derivatives. Iron powder was determined as the optimized catalyst with highest yields. 

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