Cyclohexanes intramolecular Heck reactions

A twofold intramolecular Heck reaction has been employed as a key step for the synthesis of the skeleton of the natural product (—)-chimonanthine 58 (Scheme 19). The synthetically most challenging structural features of this bispyrro-loindoline alkaloid are its two adjacent quaternary centers. They were both built up by intramolecular double-bond carbopalladations, which stereoselectively produced the pentacycle 57 from the f72-symmetrical bis[A-(2-iodophenyl)-cyclohexane-1,2-dicarboxamide 55 via the intermediate 56. The key intermediate 57 was thus obtained as a single enantiomer in 90% yield. 

Intramolecular Heck reactions have frequently been used for the synthesis of cyclopen-tanoid structures. In nearly all cases reported so far, the ring closure occurs as a 5-exo process (for an exception, see Table 4, entry 6), for which 2-halo-l,6-heptadienes and related compounds are the appropriate starting materials. In some cases, however, these substrates cyclize by a 6-endo mode to give cyclohexane derivatives (see Sect. IV.2.2.1.B.V). 

B.M. Trost and co-workers conducted studies toward the total synthesis of saponaceolide B, an antitumor agent active against 60 human cancer cell lines. " One of the challenging structural features of this compound was the cis 2,4-disubstituted 1-methylene-3,3-dimethylcyclohexane ring. The key steps to construct this highly substituted cyclohexane ring were a diastereoselective Barbier reaction to install a vinyl bromide moiety followed by an intramolecular Heck cyclization reaction. 

In 1961 Heck proposed what is now generally considered to be the correct monometallic mechanism for [HCo(CO)4]-catalyzed hydroformylation [10]. He also proposed, but did not favor, a bimetallic pathway involving an intermolecular hydride transfer between [HCo(CO)4] and [Co(acyl)(CO)4] to eliminate aldehyde product (Scheme 2). Most proposals concerning polymetallic cooperativity in hydroformylation have, therefore, centered on the use of inter- or intramolecular hydride transfers to accelerate the elimination of aldehyde product. Bergman, Halpem, Norton, and Marko have all performed elegant stoichiometric mechanistic studies demonstrating that intermolecular hydride transfers can indeed take place between metal-hydride and metal-acyl species to eliminate aldehyde products [11-14]. The monometallic [HCo(CO)4] pathway involving reaction of the acyl intermediate with H2, however, has been repeatedly shown to be the dominant catalytic mechanism for 1-aUcenes and cyclohexane [15, 16]. 

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