2
Tetrahedron Letters
b
Reaction performed under air.
continuation of our efforts in the development of reactions in
c
1
9, 20
Yield of 2a based on NHPI was determined by HPLC/UV using caffeine as an
water,
we considered whether it was possible to perform the
internal standard.
Reaction performed at 50 °C for 9 h.
d
radical dioxygenation of styrene with NHPI under micellar
conditions in water. Herein, we disclose the radical
dioxygenation of styrene derivatives in an aqueous solution
including Triton X-100-based micelles.
When the concentration of Triton X-100 was increased from 2
wt% to 5 wt% or decreased to 1 wt% (Table 1, entries 10 and
1
1), the yields decreased to 51% and 73%, respectively,
Following Xia and co-workers conditions which were
published in 2015, we initiated our studies with styrene 1a as a
model substrate for the synthesis of 2-(2-hydroxy-2-
phenylethoxy)-2,3-dihydro-1H-isoindoline-1,3-dione 2a using
commercially available NHPI, catalytic PTSA, and excess TBHP
under air in an aqueous solution of TPGS-750-M (2 wt%) at
room temperature (Table 1, entries 1 and 2). The reaction without
surfactant was carried out in parallel as a control. Disappointedly,
unsatisfactory yields were obtained (5% without surfactant and
suggesting the dependence of the reaction on the concentration of
Triton X-100. Surprisingly, the absence of the PTSA catalyst did
not have a significant impact on the reaction and produced 2a in
2
0
8
8% yield (Table 1, entry 12). On another hand, decreasing 1a or
TBHP to 2 equivalents led to a significant decrease in yield (55%
and 51%, respectively, Table 1, entries 13 and 14).
In an effort to accelerate the reaction, the temperature was
raised to 50 °C (Table 1, entry 15), resulting in an exacerbation
of side reactions and producing 2a in only 62% yield. Several
other catalyst/oxidant combinations also have been reported in
9
% in the TPGS-750-M solution), which prompted us to run
subsequent reactions under O with different types of surfactants
2
2
0, 24-28
(
Table 1, entries 3-9). To our delight, the reaction proceeded well
the alkene 1,2-dioxygenation with NHPI.
Herein, we tested
in the aqueous solution of Triton X-100 (2 wt%) and produced 2a
several used combinations TBAI/TBHP, CuBr /DTBP, CuCl,
2
in 87% yield. Other surfactants did not produce better yields
Cu(OAc) /TBHP, FeCl and PhI(OAc) . However, except for
2
3
2
(58% TPGS-750-M, 73% Brij 30, 83% TPGS-1000, 14% SPGS-
TBAI/TBHP which led to trace amounts of 2a, most did not give
5
50-M, 57% Tween-80, 15% SDS). Interestingly, when the
the desired product.
structures of these surfactants were compared (ESI, Fig. S1), it
was noticeable that all the surfactants bearing one terminal
hydroxyl group (Brij 30, TPGS-1000, Triton X-100) were
favorable to the reaction except for Tween 80. In contrast with
most of the reactions reported so far, surfactants bearing terminal
ether groups such as TPGS-750-M or SPGS-550-M, appeared
less efficient. Lipshutz and co-workers proposed that the size of
To examine the scope of the established method, various
styrene derivatives were investigated as substrates to react with
NHPI under the optimized conditions (Table 1, entry 12). As
shown in Scheme 2, the electronic properties and positions of the
substituents on styrene have a large influence on the reactivity.
The dioxygenation reaction of 2-vinylnaphthalene proceeded in
excellent yield (93% 2b). The presence of a chlorine atom on the
styrene moiety was well tolerated, producing moderate yields for
the ortho-position (64% 2c) and para-position (59% 2e).
However, a significant improvement in yield occured when the
chlorine atom was present at the meta-position (89% 2d).
Substrates with fluorine or bromine atom on the styrene moiety
were also well tolerated (72% 2f, 74% 2g).Disappointingly, the
introduction of electron-donating groups, such as a methoxy
group, at the ortho- or para-position of the aromatic ring
produced less satisfactory results (52% 2h, 26% 2i). The
efficiency of the dioxygenation reaction was affected by the
steric hindrance of a substituent at the β-position of the double
bond. The methyl group significantly lowered the reactivity (49%
3
-10
the micelle may have an impact on the reaction. According to
Lipshutz and co-workers, with a diameter of about 50 nm,
micelles formed by TPGS-750-M are suitable for micellar
5
, 9
chemistry. In contrast, TPGS-1000 and Triton X-100 lead to
micelles with a small diameter of 15 nm and 10 nm, respectively,
while micelles resulting from Brij-30 have a diameter of 110 nm
5
, 9, 21, 22
(ESI, Table S1).
In this work, the good yields obtained
with TPGS-1000, Triton X-100 and Brij-30 indicate that micelle
diameter does not significantly influence the reaction. The
common point of these three nonionic surfactants is the presence
of a hydroxyl group at the terminus of the PEG moiety. Further
work will be necessary to explain the role of this hydroxyl group
in this reaction under micellar conditions Triton X-100 and
.
2
3
2
j compared to 88% 2a). With a phenyl group at the β-position,
TPGS-1000 are both stable and biodegradable surfactants, but
since triton X-100 is much cheaper than TPGS-1000, it was
preferred for the following reactions in water.
the reaction proceeded sluggishly and compound 2k was
obtained in only 25% yield. Finally, starting from indene,
compound 2l was obtained in 9% yield after purification. The
configuration of compound 2j, 2k and 2l were deduced by
comparing the coupling constant of the α proton with the
a
Table 1. Optimization of the Reaction Conditions.
1
9, 20, 29, 30
corresponding diols reported in the literature.
Indeed,
syn-diols show a coupling constant of about 4-5 Hz versus 7-8
Hz for anti-diols. In contrast, the presence of either a methyl or a
phenyl group at the α-position of styrene did not alter the
dioxygenation reaction, leading to 2m (81%), 2n (51%), and 2o
1
a
TBHP
(equiv.)
PTSA
(mol%)
Surfactant
(% w/w in H O)
Yield
(%)
(78%).
Entry
c
(equiv.)
2
b
1
2
3
3
3
3
4
4
4
10
10
10
-
5
9
Remarkably, this in water dioxygenation reaction could be
b
TPGS-750-M (2)
TPGS-750-M (2) 58
Brij 30 (2)
performed on the gram scale with mechanical stirring. Treatment
of 1a (2.1 mL, 18.3 mmol) with NHPI (1.0 g, 6.1 mmol) and
TBHP (2.3 mL, 24.4 mmol) in a 2 wt% Triton X-100 aqueous
solution (100 mL) afforded product 2a in excellent yield (92%,
Scheme 3).
4
5
6
7
8
9
1
1
1
1
3
3
3
3
3
3
3
3
3
2
4
4
4
4
4
4
4
4
4
4
10
10
10
10
10
10
10
10
-
73
83
87
14
57
15
51
73
88
TPGS-1000 (2)
Triton X-100 (2)
SPGS-550-M (2)
Tween 80 (2)
SDS (2)
Triton X-100 (5)
Triton X-100 (1)
Triton X-100 (2)
Triton X-100 (2)
Triton X-100 (2)
Triton X-100 (2)
0
1
2
3
4
5
-
-
-
55
51
62
1
3
3
2
4
d
1
a
Reactions were carried out in a vial on a bioshaker (1800 rpm) using NHPI
0.122 mmol, 1 equiv.), styrene (1a), PTSA, TBHP, and the surfactant in water (2
mL) under an O balloon at r.t. for 19 h, unless otherwise noted.
Scheme 3. Gram-scale synthesis of 2a
(
2
Tang, Shuang-Qi
