Polyfused ring systems

A stereocontrolled synthesis of polyfused ring systems utilizing the chloroacetoxylation approach is shown in Scheme 8-26 [95]. Sequential ally lie substitution of the chloroacetates afforded key intermediate 75. Subsequent palladium-catalyzed tandem metalloene/Heck insertion reactions gave polyfused ring systems 76 and 77. 

In reactions which do not proceed via a /weyo-n-allyl complex, almost complete stereoselectivity in favor of the product with retenlion of configuration is observed, but regioselectivity may cause problems. The electron-withdrawing properties of the alkyl substituenl in the allylic aceiatc 22 is responsible for the exclusive formation of the distal product 2354 rather than its steric demand, since the nucleophile approaches the ir-allyl complex trans to the substituent. After further derivatization, the products 23 can be converted to polyfused ring systems by an intramolecular tandem palladium ene-Heck insertion reaction. 

Unique synthetic opportunities, particularly in alkaloid chemistry, are opened up on applying this protocol to diazo imides bearing a tethered heterocyclic ring. Thus, isomunchnone dipole, which is derived from these compounds, undergoes intramolecular cycloaddition across the heterocyclic CT-bond to produce bridged polyfused systems. Some examples of reactions with 2-furyl- and 1-indolyl-substituted substrates are shown in Schemes... 

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