Organic Letters
Letter
a
in good yields. Nitrones substituted at the ortho-, meta-, and
para-position with methyl group proceed smoothly, showing
that no obvious steric effect was observed (3ab−3ad). Both
electron-rich and electron-deficient aryl substituents of the
nitrones can be tolerated, giving the corresponding imides in
yields of 62−88% (3ae−3ak). Naphthyl-substituted nitrones
underwent the present reaction, and the rearrangement
products 3al and 3am were isolated in 78% and 74% yields,
respectively. This chemistry can be extended to heteroaromatic
substituted nitrones (3an and 3ao), thus highlighting the
generality of the current methodology. Moreover, changing the
methyl group on N atom to a benzyl group also proved the
compatibility, while no reaction proceeded using N-phenyl
nitrone (3ap and 3aq).
Table 1. Screening of Reaction Conditions
b
entry
catalyst
solvent
yield (%)
1
2
3
4
5
6
7
8
9
10
AgSbF6
AgOTf
AgBF4
AgOAc
AgNTf2
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
THF
DME
toluene
DCE
40
71
65
39
66
n.r.
66
75
67
64
87
87
86
69
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
The reaction scope with respect to cyclopropenones 2 was
then examined (Scheme 3). Gratifyingly, substrates carrying
c
ab
11
DME
DME
DME
DME
Scheme 3. Scope of Cyclopropenones
cd
,
12
13
14
e
cf
,
a
Conditions: 1a (0.2 mmol), 2a (0.3 mmol), [Ag] (10 mol %) in 1.0
b
c
mL of solvent at 80 °C under Ar for 8 h. Isolated yields. 100 °C, 30
d
e
f
min. 5 mol % of AgOTf was used. 120 °C. Under air condition. n.r.
= no reaction.
experiments indicated that silver salt was crucial for this
transformation (entry 6). Different solvents were next tested;
the reaction proceeded well in most of solvents, but DME was
the best among all (entries 7−10). Furthermore, increasing the
temperature to 100 °C and reducing the reaction time to 30
min showed a positive effect, improving the yield to 87%
(entry 11).10 Satisfyingly, reduction of the catalyst loading to
5% had no impact on the overall yield (entry 12).
With the optimized reaction conditions in hand, we
examined the scope of nitrones for this reaction. As
exemplified in Scheme 2, a wide range of nitrones can be
engaged in this transformation, affording the desired products
a
Conditions: 1a (0.2 mmol), 2a (0.3 mmol), AgOTf (5 mol %) in 1.0
b
c
mL of solvent at 100 °C under Ar for 30 min. Isolated yields. Ratio
of 3ha to 3ha′.
methyl, fluoro, chloro, bromo, and methoxyl were all
compatible, giving good to excellent yields (3ba−3fa). The
employment of cyclopropenone with thienyl moiety generated
the product 3ia in moderate yield. However, when dialkyl-
substituted cyclopropenone 1g was exposed under the optimal
reaction conditions, no product was detected.11 Interestingly,
nonsymmetrical cyclopropenone 1h can be successfully reacted
with nitrone, showing that the C(O)−C(Ph) bond was
preferentially cleaved.
ab
Scheme 2. Scope of Nitrones
To further confirm the synthetic practicality and utility of
this novel methodology, gram-scale synthesis of 3aa was
performed under the established reaction conditions (Scheme
4a). When 5.0 mmol scale of cyclopropenone 1a was involved,
the corresponding imide 3aa was isolated in 76% yield with
only 1.5 mol % loading of catalyst, which can be further
transformed into (E)-N-methyl-2,3-diphenylacrylamide 4
under hydrolysis condition (Scheme 4b). Moreover, imide
3ah and 3ea could work well under Suzuki reaction conditions,
and the coupling products 5 and 6 were obtained in
satisfactory yields (Scheme 4c and d).
To gain more insights into the reaction mechanism, several
experiments were designed and carried out (Scheme 5).12
First, intermolecular competition experiments between 2d and
2g showed that electron-rich aryl nitrone was preferred. Next,
when [D]-2a (80% deuterium) was tested in the reaction
conditions, 55% deuterium incorporation at the position of
a
Conditions: 1a (0.2 mmol), 2a (0.3 mmol), AgOTf (5 mol %) in 1.0
b
mL of solvent at 100 °C under Ar for 30 min. Isolated yields.
B
Org. Lett. XXXX, XXX, XXX−XXX
Xu, Jing-Lei
