Exocyclic enol ether cyclization

All these results seemed to indicate that this reaction was ideal for the con-stmction of the (—)-berkelic acid skeleton. However, a serious problem was still unresolved at this point how to constmct the additional pyran ring contained in the natural product. Nevertheless, our experience on cycloisomerization reactions led us to speculate on the possibility that a unique metal complex could promote the cycloisomerization of alkynol 15 to give the exo-cyclic enol ether 19 and also that the cycloisomerization of an alkynyl-substituted salicylaldehyde 23 would give 25. Thus, activation of the alkyne of 15 should promote a hydroalkoxylation reaction to give the exocyclic enol ether 19. On the other hand, activation of the alkyne in 23 should promote a cascade cyclization process to finally give the 8//-isochromen-8-one derivative 25. The formal [4-F 2]-cycloaddition reaction between intermediates 19 and 25 would result in the formation of the core structure of (—)-berkehc acid 24 in a very simple way (Scheme 7). 

An alternative method for the synthesis of spiroacetals involves cyclization of a pendant alcohol to an exocyclic enol ether. A recent example of an acid-catalyzed cyclization of an exocyclic enol ether has been reported by Goekjian et al. [79] in their synthesis of the cytotoxic marine metabolite bistramide A, 72 (Scheme 35). Lactone 137 and benzothiazole 138 were coupled in a modified Julia-Koscienski olefination [80] to give the requisite exocyclic enol ether 139 subsequent treatment with catalytic PTSA in dichloromethane afforded the spiroacetal 140 in good yield over two steps. 

By Cyclization of Alkenyl Silyl Enol Ethers. A simple method for the construction of bicyclo[4.3.0]nonanes and bicyclo[3.3.0]-octanes has been developed and this involves a palladium-catalyzed cycloalkenylation reaction as the pivotal step. The selective formation of products incorporating an exocyclic double-bond was observed in a number of cases (eq 117). ... 

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