ACTIVATION AND REGIOSELECTIVE ORTHO-FUNCTIONALIZATION OF THE A-RING OF BETA-ESTRADIOL PROMOTED BY CP-ASTERISK-IR - AN EFFICIENT ORGANOMETALLIC PROCEDURE FOR THE SYNTHESIS OF 2-METHOXYESTRADIOL

5,6,7,8-Tetrahydro-2-naphthol (3) and beta-estradiol (1) gave eta(6)-a rene complexes using [CpIr-(solvent)(3)][BF4](2) (4) prepared in situ ; subsequent O-deprotonation with NEt3 produced the corresponding comp lexes [CpIr(oxo-eta(5)-dienyl)][BF4] (5 and 6a,b). In the case of the complexed hormone, the CpIr moiety coordinates the A-ring either a ( metal down, 6a) or beta (metal up, 6b) relative to the methyl group at C(13). The X-ray molecular structure of the cl-isomer 6a was determin ed. These (oxo-eta 5-dienyl)iridium derivatives 5 and 6a react with Na OMe in methanol at -40 degrees C to give respectively the novel iridiu m cyclohexadienone complexes [CpIr(methoxy-eta(4)-dienone)] (7a and 8 a) in 95 and 91% yields, respectively, with nucleophilic attack occurr ing exclusively at the ortho-position relative to the C=O function. Th e novel iridium cyclohexadienone compound of the complexed steroid 8a can be oxidized easily by iodine to produce 2-methoxyestradiol (2) in 60% overall yield from beta-estradiol. This efficient organometallic p rocedure is preferable to the classical organic procedure, which requi res five steps and affords 2 in less than 5% yield.