Prostaglandin conjugate addition approach

The BINAL-H reduction works well with alkenic - and alkynic ketones affording alcohols with satisfactory optical purities (Scheme It is noteworthy that (S)-BINAL-H [(S)-(28)] reduces 1-halo-l-octen-3-one and 2-cyclopentene-l,4-dione to give the corresponding carbinols, which are important chiral building blocks for the synthesis of prostaglandins by the conjugate addition approach. ... 

For the cyclopentenone conjugate addition approach to prostaglandins to be useful, good syntheses of the chiral lower chain and cydopen-tenones must be available. Some peparations of the former have already... 

Since several excellent recent reviews of prostaglandin chemistry are available (14.15.16), we will limit the chemical discussion to the development at Lederle and elsewhere of the synthesis of prostaglandin analogs by the convergent conjugate-addition approach and by the derivatization of I-PGA2, available 0-8412-0536-l/80/47-118-301 16.40/0 1980 American Chemical Society... 

Conjugate addition of the complete allylic alcohol fragment is possible with the mixed cuprate reagents 33 prepared by asymmetric reduction (chapter 26) of acetylenic ketones 29 to give the alcohols 30, protection as a silyl ether 31 and hydroboration-iodination. Lithiation and reaction with hexynyl copper (I) gives the mixed cuprate 33 from which the less stable anion is transferred selectively to an enone.3 This approach has been widely used in the synthesis of prostaglandins. 

The Roussel-Uclaf group has published full details of the synthesis of dihydro-10,11 -PGA2, and Trost and his co-workers have described an interesting chiral synthesis of the PG analogue (92). The application of conjugate addition of zirconium alkenyls to cyclopentenones leading to prostaglandin intermediates has been reported, and Kondo et a/. have extended their approach to... 

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