Chemistry Reference
In-Depth Information
increasing the concentration. In the cases of the lower Sc loading level (2 and 5 mol %),
the yields leveled off at much lower concentrations, 0.5 and 1.0 M, respectively. These
results indicated that Sc(DS)
3
might be saturated by aq. HCHO. Based on the experi-
ments, it can be said that, in spite of the extreme solubility of HCHO in water,
the popu-
lation of HCHO in the hydrophobic environment increases in the presence of Sc(DS)
3
due to Lewis acid-Lewis base interaction between Sc(DS)
3
and HCHO
, and therefore,
the reaction of HCHO with silicon enolate
2
can proceed smoothly even in water.
Furthermore, the hydroxymethylation of various silyl enol ethers proceeded smoothly
(Scheme 1.12). Consequently, these experiments suggest that Lewis acid-surfactant com-
bined catalyst (LASC) reaction system can be applied to hydrophilic substrates as well
as hydrophobic substrates.
OSiMe
3
O
Sc(DS)
3
(5 mol %)
H
2
O, 1.0 M, 20°C, 6 h
R
1
aq. HCHO
+
R
3
R
3
HO
(5.0 equiv)
R
1
R
2
R
2
7 examples
69-94% yield
Scheme 1.12.
Lewis acid-catalyzed asymmetric reactions in water using hydrophilic substrates are
recognized as highly challenging [18], considering the importance of
Lewis acid- Lewis
base interactions
, since Lewis acids lose their acidity upon coordination from chiral
ligands. Additionally, chiral ligands compete with substrates and water molecules for
coordination with Lewis acids. Therefore, the development of chiral Lewis acid-cata-
lyzed hydroxymethylation using aq. HCHO with water as the sole solvent would make
a great impact in the fi eld.
The investigation of asymmetric variants of hydroxymethylations using aq. HCHO
revealed that the addition of a chiral ligand and a small amount of a surfactant sup-
pressed the competitive hydrolysis of silicon enolates. Eventually, catalytic asymmetric
hydroxymethylation reactions are successfully carried out in the presence of a catalytic
amount of Sc(DS)
3
, chiral ligand
L - 3
[19] , or
L - 4
[20] in the presence of additives to
afford the desired products in high yields with high selectivities. It is noteworthy that
thioketene silyl acetals, which are known to be much less stable than silyl enol ethers
(ketone-derived silicon enolates) in water, reacted smoothly under the conditions to
afford the desired hydroxymethylated adducts in good yields with high enantioselectivi-
ties (Scheme 1.13 ).
This method could be applied to the synthesis of an artifi cial odorant (S) - (+) -
3
(Scheme 1.14 ) [12] . Hydroxymethylation of
1
was performed using Sc(DS)
3
•
L - 3
as a
catalyst. After the reaction, the reaction mixture was centrifuged (3000 rpm, 20 min) to
separate the colloidal white dispersion into three phases. The upper, middle, and bottom
phases are water, surfactant, and organic layers, respectively. After the separation of
organic phase, followed by hydrogenation with polymer incarcerated palladium (PI-Pd)
[13] in benzotrifl uoride (BTF), the compound (S)-(+)-
3
was obtained in 56% yield with
91% ee over two steps. It should be noted that the synthesis has been accomplished using
a catalytic asymmetric reaction in water and a hydrogenation with an immobilized cata-
lyst, which are suitable for green sustainable chemistry [3,14].
