Inter-intramolecular coupling cascade

The same type of inter-intramolecular coupling cascade with formation of a six-membered ring as in 136/137 can be performed under Jeffery conditions ([Pd(OAc)]2, K2CO3, Bii4NBr, DMF, 80 C) with norbornene (53) and haloalkenes such as jS-bromostyrene yielding 141 (45% isolated) (Scheme 3-37) [188d]. With 9 10-... 

This chapter contains a survey of free-radical-mediated multicomponent reactions (MCRs), which permit the coupling of three or more components. Even though they are not technically classified as MCRs, remarkable intramolecular radical cascade processes have been developed. Some examples, such as those shown in Scheme 6.3, use an isonitrile or acrylonitrile as the intermolecular component for each reaction [6]. These examples demonstrate the tremendous power of the combination of inter- and intramolecular radical cascade processes in organic synthesis. Readers are advised to be aware of remarkable intramolecular aspects of modem radical chemistry through excellent review articles published elsewhere [1, 7]. It should also be noted that there has also been remarkable progress in the area of living radical polymerizations, but this will not be covered here. 

Scheme 21 Access to tricyclic isoxazolidines by an inter-intramolecular cross-coupling-cydoaddition cascade [81]...

Scheme 3-37 Inter-intramolecular alkenyl-alkene coupling cascades involving C H activation on an alkene and arene, respectively [188d,e]. A = Pd(OAc), K2CO3, Bu NBr, DMF, 80 °C.

Scheme 8.49 Inter-intramolecular alkenyl-alkene and aryl-alkene coupling cascades involving C-H activation [1 1 5, 357d,e], A Pd(OAc)j, KjCOj, riBu NBr, DMF, 80°C, 24h. B Like A, but, 100°C for 7 and 21 days, respectively [115],...

Scheme 8.78 Synthesis of isoquinolines by an inter-intramolecular Heck-type coupling cascade [570].

Much effort has been devoted to the extension of this chemistry by the use of new starting materials and by combining the carbonylation step with new modes of trapping reactions of the intermediate acylmetal complex. The combination of metal-catalyzed C-C coupling reactions with carbonylation chemistry to develop regio- and stereoselective atom-economic cascade reactions has been a major subject of interest. This resulted in a number of new inter- and intramolecular methods for the synthesis of complex organic intermediates, mainly heterocycles. 

Early findings by Heck et al. [149a, 337] revealed that coupling reactions of haloalkenes 126 with aUcenes 125 in the presence of secondary amines gave allylamines (Scheme 8.30 132/133 Nu = NR2). On the basis of this observation, inter-intermolecular as well as intra-intramolecular cascade reactions (Scheme 8.34) [338], the latter ones leading to a variety of bicycles (Scheme 8.35) [339], were developed. 

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