A Simple and Efficient Synthesis of Optically Active (+)-4-Demethoxydaunomycinone

Diels-Alder reaction of 2-chloro-1,3-butadiene with anthracene-1,4,9,10-tetrone was found to occur exclusively at the external (C2,3) double bond, giving the adduct in an excellent yield. The adduct was elaborated to 5,12-dihydroxy-1,2,3,4-tetrahydro-2,6,11-naphthacenetrione. The conventional cyanohydrin formation of this sample followed by acid hydrolysis gave (±)-2,5,12-trihydroxy-6,11-dioxo-1,2,3,4-tetrahydro-2-naphthacenecarboxylic acid. The racemic acid was found to be cleanly resolved by forming a salt with (−)-N-methylephedrine, furnishing optically pure (R)-carboxylic acid. Successive treatments of the (R)-carboxylic acid with N,N′-carbonyldiimidazole and methylmagnesium bromide in the presence of trimethylsilyl triflate readily produced optically pure (R)-(−)-7-deoxy-4-demethoxydaunomycinone, the key synthetic intermediate of (+)-4-demethoxydaunomycinone.