Chemistry Reference
In-Depth Information
NBoc
O
BocHN
10 mol%
2
TBS
O
H
O
Toluene
-20
o
C, 48h
73% yield, 58% ee
+
O
i
Pr
5
6
7
Scheme 16.3
Mannich reaction catalyzed by urea/salen carbohydrate organocatalyst
2.
5
with silyl ketene acetal
6
(Scheme 16.3) [12]. The corresponding
-amino acid
ester
7
was obtained in good yield, albeit with moderate enantioselectivity.
β
16.2.3
Nitro-Mannich Reactions
Aspiring to imitate enzymatic synergistic cooperation, chemists have succeeded
in developing many kinds of bifunctional catalysts for asymmetric synthesis [4e,
10c, 15, 16]. One site of the bifunctional catalyst could involve a Lewis acid moiety
or a hydrogen-bond donor that coordinates electrophilic substrates while another
site activates nucleophilic reagents. The catalyst positions the two reaction partners
in close proximity and with the correct relative geometry, thus facilitating the reac-
tion in a synergistic manner. The first (thio)urea-based bifunctional catalyst was
reported Takemoto and coworkers. They found that the tertiary amine and thiou-
rea were indispensable for the reaction efficiencies and selectivities [17a]. Subse-
quently, the design of bifunctional (thio)urea catalysts has received considerable
attention [17b
f].
In 2006, Ma's group developed a new class of chiral bifunctional amine-thiourea
catalysts based on the monosaccharide d-glucose, and the disaccharides maltose
and lactose [18]. Starting from commercially available
−
-d-glucopyranose, glycosyl
isothiocyanate
8
was readily prepared via acetylation, bromination, and nucle-
ophilic substitution [19]. Consequently, addition of (1
S
,2
S
)-
N
1
,
N
1
-dimethylcy-
clohexane-1,2-diamine
9
to isothiocyanate afforded the desired bifunctional
thiourea catalyst
10a,
with the glycosyl scaffold and the tertiary amine group, in 55%
yield (Scheme 16.4). Using the same procedure, other thiourea catalysts
10b
α
−
h
were also synthesized in moderate to good yields.
The catalytic asymmetric nitro-Mannich reaction is also a useful process for the
synthesis of versatile
-nitroamine derivatives [20, 21]. Ma's group employed the
tertiary amino-thioureas
10a
β
h
as bifunctional organocatalysts in asymmetric
nitro-Mannich reaction. Most of these thiourea compounds were proven to be
effective organocatalysts for the enantioselective nitro-Mannich reaction of benza-
limine with nitromethane (Table 16.3) [22]. Notably, both the carbohydrate struc-
ture and the configuration of the 1,2-diaminocyclohexane moiety influence the
enantioselectivity of this reaction. It was found that the combination of a
−
-d-
glucopyranose and a
(R,R)
-configured 1,2-diaminocyclohexane unit lead to a
matched combination of the two chiral subunits, giving a high ee. In addition, the
stereoselectivity was found to be partially dependent on the alkyl substituents of
β
Search WWH ::
Custom Search