Natural product synthesis large ring formations

Elegant applications of this method to the syntheses of large ring (12,14, and 18) compounds and natural products have been reported by Corey and Wat 129>. The last step of the humulene synthesis by Corey and Hamanaka is the following coupling reaction of ally lie dibromide via jr-allylnickel complex formation 13°). 

Carothers, Hill and co-workers also began developing procedures for the synthesis of cyclic ring compounds. In his paper "Studies on Polymerization and Ring Formation" Carothers noted that bifunctional reactants produced cyclic products when 5- or 6-membered rings were possible. It was known from tiie work of Ruzicka on natural musk that some large chains were stable and that failure to obtain macromolecular cyclic compounds was due to the lowered possibility of ends of long chains to find one another. 

D.i.d. Diquinanes. The successful execution of AHRs for the formation of 6,6- and 6,5-ring systems from prochiral substrates clearly suggested an extension of the method to the formation of 5,5-systems, which form the backbone of a large number of natural products. The use of prochiral cyclopentadienyl systems, however, involves the generation of a rr-allylpalladium species, which must then be trapped with a suitable nucleophile. " The greater reactivity of the 1,3-diene substrate toward the silver salts used in the reactions and the propensity for undesirable side reactions such as Diels-Alder cycloadditions must also be borne in mind. The former problem, in fact, figures prominently in the first example of an AHR-based diquinane synthesis to be published (Scheme... 

The meta- or 1,3-photoaddition of olefins to arenes [(26) + (27) - (28)] is potentially a very useful synthetic reaction since it proceeds from readily available starting materials with the formation of three rings and up to six stereocentres. However, since its discovery in 1966 it has not been used to any extent for the synthesis of natural products, perhaps because a large number of isomeric products might result from the reaction of unsymmetrical arenes. However, as... 

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