Reaction Steps
This set of diastereomeric alcohols was prepared from (2R)-1-methylidene-2-[2'-(tert-butyl)dimethylsilyloxy-4'-bromo-5'-methoxyphenyl]methyl-3,3-dimethylcyclohexane (48) (0.750 g, 1.66 mmol) in the manner previously described for the synthesis of alcohol 54, affording 741 mg (95%) of an inseparable 1:1 mixture of diastereomeric allylic alcohols. A portion (40 mg, 0.085 mmol) of this diastereomeric mixture was subjected to deprotection of the silylphenol in the usual manner, yielding mixture of free phenols, separable by flash column chromatography (silica gel, hexanes lethyl acetate, gradient elution), to give 14.0 mg (46%) of the less polar 1R,3R diastereomer (56), along with 13.0 mg (43%) of the more polar 1S,3R diastereomer (57) as white solids. Data for 56: 1H NMR (400MHz, CDCl3) δ0.93 and 1.12 (2s, 2×3H, geminal-CH3 's), 1.70 (m, 2H, 1-H), 1.94 (m, 3H, 6,3-H), 2.65 and 3.00 (d of ABq, 2H, JAB =14.0 Hz, JA =3.1 Hz, JB =14.0 Hz, benzylic-CH2) 3.84 (s, 3H, OCH3), 4.37 (br s, 1H, 5-H), 4.39 and 4.92 (2s, 2×1H, methylidene-CH2), 6.58 (s, 1H, 6'-H), 7.02 ppm (s, 1H, 3'-H). Data for 57: 1H NMR (400 MHz, CDCl3) δ1.00 and 1.02 (2s, 2×3H, geminal-CH3 's), 2.45 (dd, 1H, J=11.5, 3.2 Hz, 3-H), 2.70 and 2.88 (d of ABq, 2H, JAB =14.1 Hz, JA =13.1 Hz, JB =4.2 Hz, benzylic-CH2) 3.80 (s, 3H, OCH3), 4.40 (br dd, 1H, J13 11.5, 4.5 Hz, 5-H), 4.47 and 4.86 (2s, 2×1H, methylidene-CH2). 6.61 (s, 1H, 6'-H), 7.94 ppm (s, 1H, 3'-H). [Compound 56 is hereinafter also referred to as COMPOUND "R" or 120243]
