Chemistry Reference
In-Depth Information
Table 9.11
Thiourea catalysed Michael reaction
S
R
1
R
2
H
H
EtO
2
C
2
Et
(10 mol%)
NO
2
+
CH
2
(CO
2
Et)
2
Ph
NO
2
toluene, rt
Ph
R
1
R
2
Run
yield (%)
ee (%)
1
3,5-(CF
3
)
2
C
6
H
3
86
93
NMe
2
57
a
2
3,5-(CF
3
)
2
C
6
H
3
—
c-C
6
H
11
catalyst
b
3
14
35
a
Copresence of Et
3
N.
b
(
R
,
R
)-1-acetamindo-2-dimethylaminocyclohexane.
9.4.1.2 With Amine Function
Amore simple thiourea catalyst with amino functionality catalyses the asymmetricMichael
addition of 1,3-dicarbonyl compound to nitroolefin [29,30]. In the reaction of malonate to
nitrostyrene (Table 9.11) the adduct is satisfactorily obtained when N-[3,5-bis(trifluor-
omethyl)phenyl]-N
0
-(2-dimethylaminocyclohexyl)thiourea is used as a catalyst (run 1),
whereas the reaction proceeds slowlywhen the 2-amino group is lacking (run2). In addition,
chiral amine without a thiourea moiety gives a poor yield and enantioselectivity of the
product (run 3). These facts clearly show that both thiourea and amino functionalities are
necessary for rate acceleration and asymmetric induction, suggesting that the catalyst
simultaneously activates substrate and nucleophile as a bifunctional catalyst.
Furthermore, this catalyst promotes asymmetric Mannich reactions [31] and Michael
addition of active methylene compounds to
-unsaturated imides [32].
Yo o n et al. [33] found that thiourea catalyst with an amine function promotes the
stereoselective addition of a range of nitroalkanes to aromatic N-butoxycarbonyl (N-Boc)
imines. In the Mannich reaction of nitroethane (Table 9.12) high enantioselectivity, but low
yield, is observed when urea is used (run 1), whereas thiourea affords the adduct in
a
,
b
95%
yield with 92% ee (run 2). It should be noted that addition of powdered molecular sieves is
necessary for reproducible results.
The acyl-Mannich reaction [34], acyl-Pictet-Spengler reaction [35,36] and cyanosilyla-
tion [37] catalysed with bifunctional thiourea catalysts have also been developed by fine
tuning of the side chain.
>
9.4.1.3 With Alcohol Function
The alcohol group also works as an alternative functionality in thiourea catalysts. Catalytic
enantioselective Friedel-Crafts alkylation of indoles with nitroalkanes using alcohol-
