Process-scale total synthesis of nature-identical (-)-(S,S)-7-hydroxycalamental in high enantiomeric purity through catalytic enantioselective hydrogenation

A process-scale stereoselective synthesis of nature-identical (-)-(S,S)-7-hydroxycalamenal [(-)-(5S,8S)-5,6,7,8-tetrahydro-3-hydroxy-5-methyl-8-(1-methylethyl)naphthalene-2-carbaldehyde; (-)-I] in 96% enantiomeric excess (ee) with the aid of chiral Ru complexes has been developed. The key step was the enantioselective hydrogenation of easily accessible 2-(4-methoxyphenyl)-3-methylbut-2-enoic acid (II) to (+)-III in a 86% ee (Scheme 5 and Table 1). A substantial increase in optical purity (96% ee) was achieved by induced crystn. of the intermediate (+)-3,4-dihydro-4-(1-methylethyl)-7-methoxy-2H-naphthalen-1-one [(+)-IV]. Computational conformation anal. carried out on the analog (-)-V rationalized the high diastereoselectivity achieved in the catalytic hydrogenation of the C=C bond.