Handbook of Functionalized Organometallics Applications in S

350
O
8 Polyfunctional 1,1-Organodimetallic for Organic Synthesis
(1.0)
Zn (9.0 ), Metal halide (1.0 )
CH2X2 (3.0 )
CH2
CH2I2, Me3Al
CH2I2, AlCl3
CH2I2, VCl4
CH2I2, TICl4
CH2Br2, TICl4
Scheme 8.3 Methylenation of 4-dodecanone with Zn-CH 2X 2-Lewis acid.
62%
42%
70%
83%
89%
In other words, the aging period for the preparation of dizinc reagent should be
much longer, when pure zinc without lead was used for this purpose.
Actually, this method was claimed not to be reproducible and was modified by
Lombardo in 1982 [12]. Lombardo applied Takai and Oshima's procedure to the
methylenation of gibberellin derivative with Zn (pure, without lead)±CH 2Br 2-
TiCl 4, and only decomposition of the substrate was observed. He showed an
improved procedure. According to Lombardo's report, the aging period for the
preparation of the reagent should be three days (Scheme 8.4). This method is
effective for methylenation of ketones. Methylenation of the ester group with this
system did not proceed efficiently, except for a few examples [13].
Zn (440 mmol) + CH 2Br 2 (144 mmol) + TiCl 4 (103 mmol)
MeO 2C
O H
(100 mmol) O
OH
O
3 days, 5 ºC
THF (250 ml)
MeO 2C
H 2C H
Scheme 8.4 Methylenation of gibberellin derivative by Lombardo's method.
3
[ active species]
Lombardo's method had been applied to various types natural product synthesis.
In Scheme 8.5, some examples are shown [14±16].
The problem about the aging period for preparation of reactive species 3,
argued by Lombardo, should not be attributed only to the formation of gem-dizinc
species. As titanium(IV) chloride is also reduced with zinc powder, [17] the titanium
salt that works as a mediator would be the low-valent one. The reduction
process of titanium(IV) may also sometimes cause the problem of reproducibility
of methylenation reaction. In 1998, Matsubara and coworkers reported a general
3
O
OH
O
90%