Conjugated systems Heck reactions

Multiple-component difunctionalization reactions of a,/ -unsaturated carbonyl systems have been achieved by catalytic conjugate addition/aldol sequences. As Scheme 8.13 illustrates, an efficient method reported by Montgomery [46] allows regioselective addition of an aryl iodide to the /i-position of an unsaturated ester under nickel catalysis and subsequent trapping with an aldehyde to give / -hydroxyesters (e.g. 33). Significantly, premature termination of the sequence by the /Miydride elimination process that is usually observed in Pd-catalyzed Heck reactions does not occur here. 

Drawn from these examples it is apparent that controlling the chemose-lectivity in inter-intermolecular Heck-Diels-Alder reactions of two different alkenes can be tedious if the alkenes show comparable reactivities. Nevertheless, the stepwise approach was realized in several other cases. In a synthesis of a derivative of cephalostatin 1 containing a central benzene instead of the pyrazine ring, Winterfeldt et al. linked two steroidal systems by a Heck coupling and subsequently performed high pressure Diels-Alder reactions of the conjugated diene with electron-deficient alkynes [34], Another example, reported by Hayashi et al., involves a selective Heck reaction of a bromoglu-cal with ethylene or acrylic acid derivatives followed by cycloadditions with maleic anhydride or N-phenylmaleimide [35]. 

Although Heck reactions with tetrasubstituted alkenes are known, their examples are rare (Scheme 3-3) [50-52]. One trendsetting observation was that tetrasubstituted alkenes with a conjugated carbonyl group have a sufficiently increased reactivity. The application of such coupling reactions gave a rapid entry to systems with quaternary carbon centers. 

Equations 12.45103 and 12.46104 show two examples of intramolecular Heck olefination. In the first case, under Jeffrey s ligandless conditions, the Pd catalyst also acts to isomerize a C=C bond to give a final product that has the C=N bond in conjugation with the aromatic ring. The second example demonstrates how the Heck reaction can cause alkynes as well as alkenes to undergo 1,2-insertion. The transformation is also a nice application of tandem Pd-catalyzed reactions to create a rather complex ring system. 

Many solid-phase syntheses that involve the extension of ir-conjugated systems are known in the literature. Heck, Stille, Suzuki, Homer-Emmons, Wittig, and other metal-induced coupling reactions were all demonstrated to work on solid supports, some at relatively high yields [154—156]. Table 7.2 summarizes some of these reactions with respect to conditions and yields many other examples may be found in the literature. 

Beccaria, L., Deagostino, A., Prandi, C. et al. (2006) Heck reaction on l-alkoxy-l,3-dienes in ionic liquids a superior medium for the regioselective arylation of the conjugated dienic system. Synlett, 2989 92. 

Palladium-catalysed conjugate addition of 2-hydroxyarylmercury chlorides with a -unsaturated ketones, in a two-phase system, leads to a new synthesis of 2-chromanals and 2-chromenes. As the usual Heck reaction can tolerate a wide range of functional groups in the aromatic ring, this process could be fairly versatile. 

The consecutive reaction of vinyl halides and alkenes with activated methylene systems [42] in the presence of a palladium catalyst and phase-transfer catalyst results from the addition of the methylene carbanion with the initially formed Heck product (Scheme 6.31) an intramolecular version of the reaction leads to the formation of bicycloalk-l-enes (Scheme 6.31) [42], The analogous combined coupling reaction of iodoarenes and activated methylene compounds with non-conjugated dienes under similar conditions forms the monoalkene (Scheme 6.31) [43]. 

Following our first report on the palladium-catalyzed reaction of vinyl triflates with olefins (Heck-type reaction), oxidative insertion of palladium(O) into the carbon-oxygen bond of easily available vinyl triflates has proved to be a general method for the generation of o-vinyl palladium intermediates which can react directly with a variety of olefinic systems, carbon monoxide and alcohols or amines,or 1-alkynes, to give conjugated... 

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