Organic Letters
Letter
a
under oxidative NHC catalysis to release a series of highly
functionalized cyclopentenones in an excellent diastereo- and
enanantioselective manner. The mechanism of cyclopentenone
formation is thoroughly different from that of Jørgensen’s
Table 1. Optimization of Reaction Conditions
7
report, and to the best of our knowledge, such an annulation
9
mode has not been disclosed in the realm of NHC catalysis.
Therefore, this work provides a new choice of direct and
asymmetric construction of cyclcopentenone rings. Herein, we
report the results (Scheme 1).
Scheme 1. Catalytic Asymmetric Construction of
time
(h)
yield
b
ee
(%)
c
entry catalyst
base
solvent
(%)
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
A
B
C
D
E
F
A
A
A
A
A
A
A
A
A
−
A
A
K CO3
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
toluene
1
1
1
1
1
1
1
1
1
1
1
1
1
6
6
6
6
6
62
17
93
82
−
−
−
−
−
−
89
87
86
90
92
91
93
−
2
K CO3
2
K CO3
trace
trace
trace
trace
trace
trace
53
2
K CO3
2
K CO3
2
K CO3
2
NaHCO3
Et N
3
Cs CO
2
3
0
1
2
3
4
5
6
7
8
tBuOK
51
DBU
38
15
38
68
70
14
61
57
K CO3
2
K CO3
2
CH Cl2
2
d
d
d
,e
K CO3
2
THF
THF
THF
THF
THF
−
f
K CO3
2
,f
K CO3
2
e
e
,
f
f
−
K CO3
2
92
93
,
a
Reaction conditions: 1a (0.2 mmol), 2a (0.24 mmol), base (0.02
mmol), solvent (1 mL), catalyst (0.02 mmol), G (0.2 mmol), under
b
c
argon protection, rt. Isolated yields based on 1a. Determined via
d
HPLC analysis on a chiral stationary phase. Base (0.04 mmol) was
added. Catalyst A (0.04 mmol) was used. G (0.26 mmol) was
First, we selected trans-4-bromocinnamaldehyde 1a, dike-
tone 2a, and NHC A to optimize the reaction conditions. To
our delight, cyclopentenone 3a was isolated as a single
diastereoisomer in 62% yield with excellent 93% ee using
K CO as the base, THF as the solvent, and G as the oxidant
e
f
added.
Having identified the optimal conditions, we then evaluated
the substrate scope to demonstrate the generality and
limitation of this transformation (Scheme 2). Using benzyl
diketone 2a as the nucleophile, a series of differently
substituted aromatic enals were examined. We found that the
reaction could tolerate enals with 4-ClC H , Ph, and electron-
2
3
(
Table 1, entry 1). It is noteworthy that possible byproduct
lactone 3a′, whose formation has been well documented in
10
literature reports via α,β-unsaturated acyl azoliums, was not
observed. Then we tested a series of amino indanol-derived
catalysts, such as B−D, but in these cases, only a minimal
amount of 3a was formed (Table 1, entries 2−4, respectively).
Catalysts E and F showed similar results (Table 1, entries 5
and 6, respectively). Using catalyst A, we further tested a series
6
4
donating 4-MeC H substituents, delivering the corresponding
6
4
products with excellent 90−93% ee in moderate to good yields
(Scheme 2, 3b−3d, respectively). Then we turned our
attention to unsymmetrical diketones such as benzyl/phenyl
diketone 2b. The variation of the R group from electron-
withdrawing 4-BrC H to Ph, heterocyclic furan, or electron-
t
of bases such as NaHCO , Et N, Cs CO , BuOK, and DBU,
3
3
2
3
1
but only inferior results were observed (Table 1, entries 7−11,
respectively). We then evaluated different solvents (i.e.,
toluene and CH Cl ) while using K CO as the base, but
6
4
donating 4-MeC H all proved successful, and the cyclo-
2
2
2
3
6
4
lower yields were detected (Table 1, entries 12 and 13,
respectively). Gratifyingly, increasing the amount of both
triazolium A and K CO to 20 mol % could enhance the yields
without affecting the enantioselectivity (Table 1, entry 14).
Then the yield of 3a was increased to 70% upon addition of
slightly more oxidant (Table 1, entry 15). We also tested the
reaction without an NHC catalyst and isolated a 14% yield of
pentenones could be obtained with ≤98% ee (Scheme 2, 3e−
1 n
3h). When R was methyl or heptyl groups, the reaction also
proceeded well to release the corresponding products with
90% ee (Scheme 2, 3i and 3j). Then using trans-4-
bromocinnamaldehyde 1a as a substrate, we evaluated a series
of differently substituted benzyl/phenyl diketones and found
that the substituents installed in the phenyl group had little
impact on the reactions (Scheme 2, 3k−3n). It is noteworthy
that the reaction of the 2-MeOC H -substituted enal with the
2
3
3
a, indicating that background reaction also occurs (Table 1,
entry 16). The reactions without K CO or with 10 mol %
2
3
6
4
K CO also occurred but delivered 3a in lower yields (entries
diketone could also provide the annulation product in 65%
yield with excellent 99% ee (Scheme 2, 3o). Furthermore, the
2
3
1
7 and 18).
3
404
Org. Lett. 2021, 23, 3403−3408