Activation and regioselective ortho-functionalization of the A-ring of beta-estradiol promoted by ''Cp*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)-arene complexes using [Cp*Ir-(solvent)(3)][BF4](2) (4) prepared in situ; subsequent O-deprotonation with NEt3 produced the corresponding complexes [Cp*Ir(oxo-eta(5)-dienyl)][BF4] (5 and 6a,b). In the case of the complexed hormone, the Cp*Ir 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 determined. These (oxo-eta 5-dienyl)iridium derivatives 5 and 6a react with NaOMe in methanol at -40 degrees C to give respectively the novel iridium cyclohexadienone complexes [Cp*Ir(methoxy-eta(4)-dienone)] (7a and 8a) in 95 and 91% yields, respectively, with nucleophilic attack occurring exclusively at the ortho-position relative to the C=O function. The 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 procedure is preferable to the classical organic procedure, which requires five steps and affords 2 in less than 5% yield.