10.1021/om961079c.s001
J. Le Bras
J.
Le Bras
M. N. Rager
M. N.
Rager
Y. Besace
Y.
Besace
H. Amouri
H.
Amouri
J. Vaissermann
J.
Vaissermann
Activation and Regioselective Ortho-Functionalization of
the A-Ring of β-Estradiol Promoted by “Cp*Ir”: An
Efficient Organometallic Procedure for the Synthesis of
2-Methoxyestradiol
American Chemical Society
1997
BF
NEt 3
nucleophilic attack
methyl group
arene complexes
organometallic procedure
Efficient Organometallic Procedure
estradiol
dienyl
η 6
Cp
novel iridium cyclohexadienone compound
6 b
novel iridium cyclohexadienone complexes
complexed hormone
1997-04-15 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Activation_and_Regioselective_Ortho-Functionalization_of_the_A-Ring_of_-Estradiol_Promoted_by_Cp_Ir_An_Efficient_Organometallic_Procedure_for_the_Synthesis_of_2-Methoxyestradiol/3779313
5,6,7,8-Tetrahydro-2-naphthol (<b>3</b>) and β-estradiol
(<b>1</b>) gave η<sup>6</sup>-arene complexes using
[Cp*Ir(solvent)<sub>3</sub>][BF<sub>4</sub>]<sub>2</sub>
(<b>4</b>) prepared <i>in situ</i>; subsequent O-deprotonation
with NEt<sub>3</sub> produced the
corresponding complexes
[Cp*Ir(oxo-η<sup>5</sup>-dienyl)][BF<sub>4</sub>]
(<b>5</b> and <b>6a,b</b>). In the case of
the
complexed hormone, the Cp*Ir moiety coordinates the A-ring either α
(metal down, <b>6a</b>) or
β (metal up, <b>6b</b>) relative to the methyl group at C(13).
The X-ray molecular structure of
the α-isomer <b>6a</b> was determined. These
(oxo-η<sup>5</sup>-dienyl)iridium derivatives <b>5</b> and
<b>6a</b> react
with NaOMe in methanol at −40 °C to give respectively the novel
iridium cyclohexadienone
complexes [Cp*Ir(methoxy-η<sup>4</sup>-dienone)] (<b>7a
</b>and<b> 8a</b>) in 95 and 91% yields, respectively,
with
nucleophilic attack occurring exclusively at the ortho-position
relative to the CO function.
The novel iridium cyclohexadienone compound of the complexed
steroid <b>8a</b> can be oxidized
easily by iodine to produce 2-methoxyestradiol (<b>2</b>) in 60%
overall yield from β-estradiol. This
efficient organometallic procedure is preferable to the classical
organic procedure, which
requires five steps and affords <b>2</b> in less than 5% yield.