Grignard reagents, nitrile oxide cycloadditions

The first synthesis of this compound to be completed was the result of studies by Smith and co-workers in 1982. The readily available flavor constituent cyclotene (368) (Scheme 2.28) was reduced and isomerized to 2-methyl-2-cyclopenten-l-one (369) in 64% yield. Addition of dimethyl cuprate followed by isomerization and Baeyer-Villiger oxidation gave the racemic 8-lactone 370 (86%). Addition of allyl Grignard reagent followed by formation of the methyl ketal provided a 71% yield of 371, which possesses the expected axial methoxy group. Conversion of the terminal olefin into the functionalized isoxazoline 373 was accomplished in 68% by the 1,3 dipolar cycloaddition of nitrile oxide 372. 

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