Reaction Steps
To a flame-dried 50 mL round-bottomed flask containing a solution of (3S)-2-methylidene-3-(2-hydroxy-4'-bromo-5'-methoxyphenyl)methyl-4,4-dimethylcyclohexan-1-one (61) (150.0 mg, 0.322 mmol) in 15 mL THF at -70° C. under nitrogen atmosphere was added methyllithium (0.60 mL of a 1.40M solution in ether, 0.840 mmol, 2.61 equiv), and the mixture was allowed to stir for 5 min before quenching with saturated aqueous NH4C1. Upon warming to room temperature, the reaction mixture was extracted with ethyl acetate, and the organic phase was washed with brine, dried over Na2SO4, and concentrated under diminished pressure gave a 3:1 (1R,3S: 1S,3S) mixture of the diastereomeric tertiary hydroxyls. Purification by flash column chromatography (silica gel, hexanes/ethyl acetate, gradient elution) afforded 28 mg (18%) of the less polar, minor 1S,3S isomer (63), along with 88 mg (57%) of the more polar, major 1R,3S isomer (62), as well as 30.2 mg (20%) recovered starting material. The diastereomeric alcohols were then independently converted to the corresponding free phenols in the usual manner, providing the trans, 1R,3S isomer (62) 1H NMR (400MHz, CDCl3) δ0.84 and 1.04 (2s, 2×3 H, geminal-CH3 's), 1.39 (s, 3H, 5-CH3), 2.43 (br dd, 1H, J-- 11.3, 2.9 Hz, 3-H), 2.72 and 2.85 (d of ABq, 2H, JAB =16.1 Hz, JA =3.1 Hz, JB =11.5 Hz, benzylic-CH2) 3.77 (s, 3H, OCH3), 4.57 and 5.16 (2s, 2×1H, methylidene-CH2), 6.63 (s, 1H, 6'-H), 6.93 ppm (s, 1H, 3'-H); and the cis, 1S,3S isomer (63) 1H NMR (400MHz, CDCl3) δ0.77 and 1.08 (2s, 2×3H, geminal-CH3 's), 1.36 (s, 3H, 5-CH3), 2.65 and 2.82 (d of ABq, 2H, JAB =16.0 Hz, JA =3.0 Hz, JB =11.8 Hz, benzylic-CH2), 2.97 (br dd, 1H, J=11.7, 2.5 Hz, 3-H), 3.79 (s, 3H, OCH3), 4.64 and 4.96 (2s, 2×1H, methylidene-CH2), 6.73 (s, 1H, 6'-H), 6.92 ppm (s, 1H, 3'-H). [Compound 63 is hereinafter also referred to as COMPOUND "J" or 120286, and Compound 62 is hereinafter also referred to as COMPOUND "P" or 120273] ##STR12##
