Racemization of phenanthrene 3,4-oxide. Absolute stereochemistry of cis- and trans-phenanthrene 3,4-dihydrodiols

Abstract

trans-3,4-Dihydroxy-1,2,3,4-tetrahydrophenanthrene (11) and cis-3,4-dihydroxy-1,2,3,4-tetrahydrophenanthrene (12) have been prepared in optically pure form via: (i) chromatographic separation of the trans-3-bromo-4-menthyloxyacetoxy-1,2,3,4-tetrahydrophenanthrene diastereoisomers (7a), (7b), (ii) conversion of (7a) into the optically pure (+)-tetrahydro-3,4-epoxide (8), (iii)acid-catalysed hydrolysis of (+)-(8) by attack at C-4 to yield (+)-trans-(11) and (–)-cis-(12). Several lines of evidence, including spectral methods and chemical transformation to compounds of known absolute stereochemistry, have been used to assign absolute stereochemistry to all chiral compounds described in the present study. The availability of optically pure diols (11) and (12) has allowed the absolute stereochemistry of the trans- and cis-3,4-dihydrodiol metabolites of phenanthrene (4) and (2) to be determined as (–)-(3R,4R) and (+)-(3S,4R) respectively. Phenantherene 3,4-oxide, an initial mammalian metabolite of phenanthrene prepared from optically pure precursors, was optically active but racemized spontaneously at ambient temperature.