Tactics prostaglandin synthesis

In the first Corey prostaglandin synthesis we saw the use of an acyl anion equivalent . Now we will see another application of the equivalency concept , use of a real reactant that, after some functional group manipulations, can be used to accomplish a transformation that could not be accomplished otherwise. Let s look at the tactics that were ultimately used by the Corey group. Sodium cyclopentadienide was alkylated with chloromethyl methyl ether to provide 37. Chloromethyl methyl ether is extremely reactive and thus, this reaction could be accomplished at a low temperature, below the temperature at which 37 isomerizes to cyclopentadienes 38 and 39. Cyclopentadiene 37 was then reacted with an excess of 2-chloroacrylonitrile, an extremely reactive dienophile. Under the influence of Lewis acid promotion (copper tetrafluoroborate) this diene-dienophile pair underwent cycloaddition, to give 40 at temperatures where diene isomerization did not occur. Although 40 was obtained as a mixture of endo and exo diasteromers, it is notable that the dienophile approached 37 from the sterically least... 

The synthesis of prostaglandins via the "Corey Lactone" was adopted by chemical industry and used to prepare kilogram quantities of materials. The synthesis met most of the stated goals, but there was room for tactical improvements. Some problems to be addressed were (1) How was the key hydroxy acid to be resolved (2) Could asymmetry be introduced into the Diels-Alder reaction such that resolution would be unnecessary (3) Could the need for stoichiometric use of n-BusSnH be avoided (4) Could the C,5 stereochemistry problem be solved Research directed toward solving these tactical problems led the the development of generally useful chemistry. 

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