DIASTEREOSELECTIVE SYNTHESIS OF 3-(2-((N,N-DIMETHYLAMINO)METHYL)FERROCENYL)-4-(4-METHOXYPHENYL)HEXAN-3-OLS, IN RACEMIC AND OPTICALLY-ACTIVE SERIES - X-RAY DETERMINATION OF THEIR RELATIVE CONFIGURATION

We describe herein the diastereoselective synthesis of 3-(2-((NN-dimethylamino)methyl)-ferrocenyl)-4-(4-methoxyphenyl)-hexan-3-ols. The relative configurations of these amino alcohols (pR*,3R*,4S*), 5(a+b), and (pR*,3S*,4R*), 6(a+b), were unambiguously determined by X-ray diffraction analysis. In the optically active series, the absolute configuration is related to that of the starting 1-((NN-dimethylamino)methyl)-2-lithioferrocene, 7. The orientation of nucleophilic addition of this lithiated reactant on the chiral ketone 4-(4-methoxyphenyl)hexan-3-one, 2 is under ketonic chiral center control, and independent of the planar chirality of the lithiated ferrocene entity. This reaction opens a route to the synthesis of ferrocene analogs of hexestrol and diethylstilbestrol. Compounds 5(a+b) and 6(a+b) crystallize in the monoclinic space group P2(1)/n with Z = 4 and P2(1)/a with Z = 8, respectively. The main structural feature of 5(a+b) is a strong intramolecular hydrogen bond between the hydroxyl and the amino groups (d(N-O) = 2.74 angstrom). Compound 6(a+b) exists in two conformations, one which is similar to compound 5(a+b) with a hydrogen bond(d(N-O) = 2.73 angstrom), and the other which does not have such a hydrogen bond.