A process-scale stereoselective synthesis of natural (-)-(S,S)-7-hydroxy-calamenal1 in a 96% enantiomeric purity is described. The key step is the enantioselective hydrogenation of easily accessible 2-(4-methoxyphenyl)-3-methyl-2-butenoic acid to (+)-(S)-2-(4-methoxyphenyl)-3-methylbutanoic acid. Enantiomeric excesses up to 86% were achieved with a ruthenium complex of (-)-(R)-TetraMe-BITIOP, a chiral biheteroaromatic diphosphine which was projected by us a few years ago.2 Substantial increase in optical purity up to 96% was achieved by crystallization of intermediate 4-i-propyl-7-methoxy-3,4-dihydro-2H-naphthalene-1-one by seeding the n-hexane solution of the latter with crystals of the enantiopure compound. Computational conformational analysis carried out on (-)-(S)-1-i-propyl-6-methoxy-4-methyl-1,2-dihydronaphthalene explains the high diastereoselection levels attained in the catalytic hydrogenation of the double bond to give (-)-(S,S)-1-isopropyl-6-methoxy-4-methyl-1,2,3,4-dihydro-naphthalene.
|Titolo:||Process-scale total synthesis of natural (-)-(S,S)-7-hydroxy-calamenal in high enantiomeric purity through a catalytic enantioselective hydrogenation process|
SANNICOLO', FRANCESCO (Ultimo)
|Settore Scientifico Disciplinare:||Settore CHIM/06 - Chimica Organica|
|Data di pubblicazione:||2005|
|Tipologia:||Book Part (author)|
|Appare nelle tipologie:||03 - Contributo in volume|