Polyfused systems

Scheme 8-26 Synthesis of polyfused. systems via stereoselective Pd-catalyzed reactions.

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... 

There is another type of multiple thermal Diels Alder reaction in which the initial monoadduct is involved, either directly or after one transformation, in a second cycloaddition that affords the final polycyclic compounds. These methodologies have been used especially in the synthesis of polycyclic cage compounds. Paquette was the first to report the conversion of 9,10-dihydroful-valene into polyfused cyclopentanoid systems [124],... 

The 2-cyanoacrylamide derivative 552, a building block for the synthesis of polyfused heterocyclic systems containing the 1,3-dithiole moiety, was obtained in the reaction of either ethyl cyanoacetate or cyanoacetamide with CS2 and ammonia and further reacted with tetrabromo-l,4-benzoquinone to give the corresponding 1,3-dithiole 553 (Scheme 77) <1995PS95>. 

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. 

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