Alkyne Metathesis in Synthesis Syntheses of -Ferrugine and

Alkyne Metathesis in Synthesis Syntheses of (+)-Ferrugine and Anatoxin-a 

Although much emphasis has been placed on the importance of alkene metathesis in organic synthesis, alkyne metathesis is also significant. Metathesis reactions of alkynes with alkenes and metathesis reactions of alkynes with alkynes have both been carried out efficiently. 

An enantiospecific synthesis of the potent anti-Alzheimer s agent (-i-)-ferruginine 1 and two enantiospecific syntheses of the potent anti-Alzheimer s agent anatoxin-a 2 were submitted essentially simultaneously earlier this year. In each case, the starting material used was the inexpensive pyroglutamic acid 3, and in each case the synthesis depended on Ru-catalyzed alkyne-alkene metathesis. 

The first report, received on Februai-y 25, by Varinder Aggarwal of Bristol University (Organic Lett. 2004, 6, 1469) is representative of all three. Ohira homologation of the aldehyde 6 gave the enyne 

A detailed study showed that the alkyne-alkene metathesis was proceeding cleanly, but that the product 10 was then decomposed by the Ru catalyst. Use of the less reactive first generation Grubbs catalyst 9 gave clean conversion of 8 to 10. 

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