Three-component synthesis, prostaglandins

Jasmone, 8.21, is a volatile component of the fragrant oil isolated from jasmine flowers and is thus important compound in the fragrance industry. In plants, it plays an important role in defense and development [55]. Methodologies developed for this molecule also have applications in the field of prostaglandin synthesis. Three syntheses have been chosen as examples. 

Scheme 5. Larock s palladium-promoted, three-component coupling strategy for prostaglandin synthesis.

A short synthesis of prostaglandin derivatives via a three component coupling reaction is reported, in which the enolates are trapped with nitroalkenes. The nitro group is removed via... 

Treating benzaldehyde with diethylzinc in the presence of 2 mol% (—)-DAIB gives (5)-alcohol in 98% ee (Scheme 2-43). When compound 112 is treated in the same manner, compound 113, a chiral building block in the three-component coupling prostaglandin synthesis, is also obtained with high ee (Scheme 2-43). 

Scheme 18.40 Synthesis of the allenic prostaglandin 123 by three-component coupling [121].

Suzuki, M. Morita, Y. Koyano, H. Koga, M. Noyori, R. Three-Component Coupling Synthesis of Prostaglandins. A Simplified, General Procedure, Tetrahedron 1990,46,4809. 

This method is particularly effective with cyclic substrates, and the combined effects of intramolecular and intermolecular asymmetric induction give up to 76 1 (kf/ks) differentiation between enantiomers of a cyclic allylic alcohol. This kinetic resolution provides a practical method to resolve 4-hydroxy-2-cyclopentenone, a readily available but sensitive compound. Hydrogenation of the racemic compound at 4 atm H2 proceeds with kf/ks =11, and, at 68% conversion, gives the slow-reacting R enantiomer in 98% ee. The alcoholic product is readily convertible to its crystalline, enantiomerically pure fert-butyldimethylsilyl ether, an important building block in the three-component coupling synthesis of prostaglandins (67). 

Scheme 12.3. Synthesis of prostaglandin Et using a three-component conjugate addition/enolate trapping on cyclopentenones, by Noyori and co-workers [10], TBS = t-butyldimethylsilyl, THF = tetrahydrofuran,...

The jasmonates are another class of disubstituted cyclopentanoid natural products very reminiscent of the prostaglandins. To efficiently assemble their main skeleton, Yamamoto and co-workers developed a clever three-component reaction methodology that was demonstrated by the total synthesis of both trans- and cis-methyl jasmonates 36 and 37 (Scheme 12.7) [25],... 

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