Prostaglandin synthesis Corey method

Because the Corey synthesis has been extensively used in prostaglandin research, improvements on the various steps in the procedure have been made. These variations include improved procedures for the preparation of norbomenone (24), alternative methods for the resolution of acid (26), stereoselective preparations of (26), improved procedures for the deiodination of iodolactone (27), alternative methods for the synthesis of Corey aldehyde (29) or its equivalent, and improved procedures for the stereoselective reduction of enone (30) (108—168). For example, a catalytic enantioselective Diels-Alder reaction has been used in a highly efficient synthesis of key intermediate (24) in 92% ee (169). 

Dehydrahon of jS-hydroxyketones and jS-hydroxyesters with carbodiimides is used to introduce double bonds into organic molecules. For example, Corey and coworkers used this method in the synthesis of prostaglandins." For example. The shown /3-hydroxyketone... 

Dehydration of /3-hydroxy ketones [1, 235, before references]. Schmidt and Moos-miiller29 reported that the reaction of carbodiimides with primary and secondary alcohols is catalyzed by cupric chloride. Corey et al,30 in a synthesis of prostaglandins, found that the reaction of (8-hydroxy ketones with DCC catalyzed by cupric chloride is a useful method for dehydration to the a S-unsaturated ketone under mild, nonacidic, nonbasic conditions. Presumably the hydroxyl group reacts to form a carbamidate derivative which undergoes cycloelimination. 

Auxiliary-controlled diastereoselective and enantioselective Diels-Alder reactions (Corey) and diastereoselective three-component reactions (Noyori), examples of which were tested for the first time in the total synthesis of prostaglandins, enriched the arsenal of methods in modem preparative organic chemistry. 

Corey and coworkers , in a synthesis of prostaglandins, prepared diene 34 by alkylation of the lithiodithiane 32 with 2-bromomethyl-l,3-butadiene (equation 41). A synthesis of jasmone (35), in an overall yield of 50%, has been reported by Ellison and Woessner in which the bisdithianylethane 33 was sequentially alkylated, followed by hydrolysis and cyclization (equation 42). A similar route for preparation of 4-hydroxy-2-cyclopenten-l-ones has been reported . This method appears to provide a general route to 1,4-diketones via 1,3-dithianes. 

The need for hydroxy protecting groups in the prostaglandin field, which combine the features of stability under a wide variety of conditions and facile selective removal, has prompted Corey to examine the use of the t-butyl-dimethylsilyl group for the protection of alcohols. Indeed this protecting group was found to offer many advantages over other methods, and a paper outlines its particular use in total PG synthesis. ... 

Corey has reported a fairly efficient method for effecting inversion of configuration at C-11, thus making possible the synthesis of 11-epi-prostaglandins. 

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