Handbook of Functionalized Organometallics Applications in S

354
8 Polyfunctional 1,1-Organodimetallic for Organic Synthesis
O Nysted reagent (1.0 mmol)
R R'
(1.0 mmol)
O
β-TiCl 3 (2.0 mmol)
BF 3•OEt 2 (0.1 mmol)
THF
H3C n-C10H21 O
96% 86%
O
H 3 C Ph
O
CH 2
R R'
n-C 8 H 17
O
99%
76% 68% 38%
Scheme 8.10 Methylenation of ketones with Nysted reagent (2) and b-TiCl 3.
As shown in Scheme 8.11, methylenation of polyketone was performed by
bis(iodozincio)methane (4) and b-TiCl 3. In this substrate, Wittig reagent, Tebbe
reagent, and Zn-CH 2X 2-TiCl 4 did not give any satisfactory result. Acombination of
4 and b-TiCl 3 gave fully methylenated product without racemization (Scheme 8.11)
[25]. The difference between Zn-CH 2X 2-TiCl 4 and 4-b-TiCl 3 is the existence of excess
amount of Lewis acid. The latter system excludes an existence of Ti (IV) salt.
O
n
CH 2(ZnI) 2 (4), β-TiCl 3
THF / CH2Cl2 n
RT, 3 h CH2 Scheme 8.11 Methylenation of optically active polyketones
with bis(iodozincio)methane (4) and b-TiCl 3.
Areagent consisting of 4-b-SiCl 3-TMEDAwas also examined for the methylenation
of esters as shown in Scheme 8.12 [26]. In these cases, TMEDAis indispensable.
It may enhance the nucleophilicity of 4 and prevents the decomposition
of products. The product, vinyl ether, is easily decomposed by existing Lewis acid
in the reaction mixture without an amine such as TMEDA.
As described above, without an addition of titanium salt, for example, treatment
of 2-dodecanone with bis(iodozincio)methane (4) at room temperature resulted in
the sluggish reaction (run 1, Table 8.3). Even at higher temperature, the methylenation
product was not obtained in good yield (run2). On the contrary, an addition
of small amount of tetrahydrothiophene (THT) to the reaction mixture improved
the yield of methylenated product dramatically (run 3). It seems to be a good substitute
for b-TiCl 3. In practice, however, its strong odor makes the experimental
procedure in large scale uncomfortable. It should be noted that an ionic liquid,
1-butyl-3-methylimidazolium
78%
O