Furanoterpene synthesis via intramolecular nitrile oxide cycloaddition reaction: a total synthesis of (+)-menthofuran

Article abstract of DOI:10.3987/COM-92-6231

A fused furan assembling strategy based on an intramolecular <3+2> dipolar cycloaddition reaction of nitrile oxide has been applied to a total synthesis of perfumy furanomonoterpene (+)-menthofuran (1).The key cycloaddition substrates (9) and (12) are easily prepared via straightforward routes starting from (+)-citronellal and these are treated with sodium hypochlorite and p-chlorophenyl isocyanate, respectively.The cycloaddition reactions generate 10 : 1 mixture of diastereoisomeric isoxazolines (2a) and (2b) in good to excellent yields.The isoxazolines (2a,b)thus obtained are converted to (+)-menthofuran (1) by sequential reductive hydrolysis and alkaline hydrolysis (or vice versa) followed by acid treatment of the resulting β,γ-dihydroxy ketone (14).