Heck reaction, intramolecular alternative

Several routes to the pyrrolo[l,2-f][l,2,3]triazole skeleton have been described. Intramolecular dipolar cycloaddition of azido-alkenes or alkynes seems to be the most convenient process, although the cyclization efficiency seems to be highly substrate dependent (Scheme 16) <2002JA2134, 2003T1477, 2005SL2187, 2005TL8639>. The formation of this bicyclic system by an intramolecular Heck reaction is an attractive alternative. The recent syntheses of sulfamides by intramolecular cyclization of alkenes or allenes offer a complementary route to the classical... 

In 2006, Fukuyama presented an approach to codeine and morphine based on a Tsuji-Trost coupling and intramolecular Heck reaction as key steps [49, 61]. The synthesis was carried out in the racemic manifold however, by devising an alternative stereoselective route to epoxide 41, access to either the natural or the enantiomeric form of morphine could be achieved. 

Indole is one of the most important heterocyclic scaffolds for drug discovery. Approaches for indole synthesis using hydroamination as a key step in their syntheses has been an ongoing area of investigation over the past several years [329, 330]. Early examples focused on one-pot intermolecular hydrohydrazination followed by the Lewis-acid-catalyzed Fischer indole synthesis [331, 332] (Scheme 15.102) or one-pot intermolecular hydroamination followed by cross-coupling to either form a C-N bond (via the Buchwald-Hartwig amination) [333] (Scheme 15.103) or a C-C bond (via a Heck reaction) [334, 335] (Scheme 15.104). Alternatively, o-alkynylanilines can be used directly as substrates for intramolecular hydroamination (Scheme 15.105) [198, 200, 336-340]. These approaches have been thoroughly reviewed [10]. 

Transition metal catalyzed insertion reactions offer a variety of alternate approaches for the preparation of six membered heterocyclic rings. Besides intramolecular Heck-couplings, annulation reactions involving the insertion of an acetylene derivative, in most cases accompanied by the incorporation of carbon monoxide constitute the majority of this chapter. Although some of these processes involve the formation of a carbon-heteroatom bond, they are discussed here, while the similar annulation reactions not involving CO insertion are mentioned in Chapter 4.4. 

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