Diastereoselective and enantioselective desymmetrization of α-substituted cyclohexadienones via intramolecular stetter reaction

Article abstract of DOI:10.1021/jo3022555

Highly diastereoselective and enantioselective desymmetrization of α-substituted cyclohexadienones via NHC-catalyzed intramolecular Stetter reaction was realized. Amino-indanol derived triazolium salt bearing a C ₆F₅ group was found to be the optimal catalyst precursor in the intramolecular Stetter reaction furnishing tricyclic products bearing multi-stereocenters in up to 96% yield and >99% ee.

Full text of DOI:10.1021/jo3022555

Note
pubs.acs.org/joc
Diastereoselective and Enantioselective Desymmetrization of
α‑Substituted Cyclohexadienones via Intramolecular Stetter Reaction
Min-Qiang Jia, Chuan Liu, and Shu-Li You*
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345
Lingling Lu, Shanghai 200032, PR China
S
* Supporting Information
ABSTRACT: Highly diastereoselective and enantioselective
desymmetrization of α-substituted cyclohexadienones via
NHC-catalyzed intramolecular Stetter reaction was realized.
Amino-indanol derived triazolium salt bearing a C6F5 group
was found to be the optimal catalyst precursor in the
intramolecular Stetter reaction furnishing tricyclic products
bearing multi-stereocenters in up to 96% yield and >99% ee.
N-Heterocyclic carbenes (NHCs) as organocatalysts have
witnessed rapid development since the first isolation of stable
carbene in 1991.1 Reversing the reactivity (umpolung) of
aldehyde functionality opens a new area for organic chemists.2
The Stetter reaction is a powerful tool that takes advantage of
umpolung reactivity of aldehyde, in which aldehyde adds to a
Michael acceptor to construct a bisfunctionalized backbone.3
When an α-substituent is introduced in the Michael acceptor,
an additional stereocenter will be generated.4 To our
knowledge, NHC-catalyzed diastereoselective Stetter reactions
from enantioselective protonation have been rarely explored.5−8
Rovis et al. reported the first highly diastereoselective and
enantioselective Stetter reaction in 2005 by introducing an α-
substituent.5 In 2006 Rovis et al. reported another highly
diastereoselective and enantioselective Stetter type desymmet-
rization of cyclohexadienones to afford the bicyclic com-
pounds.6,7 The same group also reported the intermolecular
Stetter reaction in good to excellent yields, enantioselectivity
and diastereoselectivity in 2009 with glyoxamide as substrate.8
On the basis of these elegant works and our interest in NHC-
catalyzed desymmetrization of cyclohexadienones, we recently
reported the enantioselective desymmetrization of cyclo-
hexadienones via D-camphor-derived triazolium salts catalyzed
intramolecular Stetter reaction to construct novel tricyclic
structures.9,10 However, α-methyl substituted cyclohexadienone
aldehyde reacted poorly under the standard conditions. After
extensive efforts toward catalyst screening, amino-indanol
derived NHC was found to be highly efficient for this type of
substrate (Scheme 1). Herein, we report our detailed results on
this subject.
Scheme 1. Diastereoselective and Enantioselective
Desymmetrization of Cyclohexadienones
Figure 1. Several readily available chiral NHC precursors.
To begin our study, dimethyl substituted cyclohexadienone
1a was used as a model substrate under NHC catalysis to
optimize the reaction conditions. Several readily available chiral
NHC precursors (Figure 1) were examined in the desymmet-
rization of cyclohexadienone 1a via an intramolecular Stetter
reaction. The results are summarized in Table 1. With 10 mol
% of triazolium salt E bearing a C6F5 group and 10 mol % of
DIEA in o-xylene, the desired intramolecular Stetter reaction
Received: October 16, 2012
Published: November 9, 2012
© 2012 American Chemical Society
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Note
a
a
Table 1. Screening of the Chiral NHC Catalysts
Table 2. Optimization of the Reaction Conditions
b
entry
catalyst
yield (%)
ee (%)
1
2
A
B
C
D
E
F
G
H
I
NR
NR
NR
trace
9
concentration
(mol/L)
yield
(%)
ee
b
entry
base
solvent
(%)
3
c
4
1
DIEA
o-xylene
toluene
CH2Cl2
CHCl3
THF
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.2
0.05
0.025
0.1
72
82
71
86
55
59
54
55
70
92
88
95
80
85
>99
>99
95
5
−99
2
DIEA
6
NR
NR
NR
NR
72
3
DIEA
7
4
DIEA
91
8
5
DIEA
99
9
6
DIEA
dioxane
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
99
10
J
>99
7
DBU
>99
>99
>99
>99
>99
>99
>99
>99
a
8
Et3N
Reaction conditions: 1a (0.1 mmol), 10 mol % of catalyst, 10 mol %
of DIEA in o-xylene (1.0 mL) at room temperature. Determined by
HPLC.
b
9
Cs2CO3
KHMDS
KHMDS
KHMDS
KHMDS
KHMDS
10
11
12
13
proceeded sluggishly affording the desymmetrization product
2a with 99% ee but in only 9% yield (entry 5, Table 1).10
However, other camphor-derived triazolium salts A−D11 were
found almost ineffective in this intramolecular Stetter reaction
(entries 1−4, Table 1). Then, amino-indanol derived triazolium
salts F−J12 were screened under otherwise identical conditions.
To our great delight, with 10 mol % amino-indanol derived
triazolium salt J bearing a C6F5 group, the desired intra-
molecular Stetter reaction proceeded smoothly affording
desymmetrization product 2a in 72% yield with >99% ee
(entry 10, Table 1). However, other substituted amino-indanol
derived triazolium salts F−I failed to catalyze the reaction.
Other reaction parameters were further examined with 10
mol % of triazolium salt J as the optimal catalyst precursor. The
results are summarized in Table 2. Various solvents were first
examined in the model reaction. All tested solvents such as
toluene, CH2Cl2, CHCl3, and dioxane were well tolerated,
affording the desired product with excellent ee, although
reaction activity varied slightly (entries 1−6, Table 2). Reaction
in o-xylene and toluene gave the highest ees. Compared with o-
xylene, reaction in toluene was much faster, and the reaction
proceeded to completion in 15 h (82% yield, 99% ee, entry 2,
Table 2). With toluene as the optimal solvent, several bases
such as DBU, Et3N, Cs2CO3, and KHMDS were further
examined (entries 7−10, Table 2). All bases screened gave
excellent ees, and the reaction with KHMDS (0.5 M in
toluene) led to an elevated yield and excellent enantioselectivity
(92% yield, >99% ee, entry 10, Table 2). The substrate
concentration of reaction was further optimized (entries 11−
13, Table 2). When the substrate concentration was 0.05 mol/
L, slightly higher yield (95%) was obtained. The catalyst
loading could be reduced to 5 mol % (85% yield, >99% ee,
entry 14, Table 2).
d
14
a
Reaction conditions: 1 (0.1 mmol), 10 mol % of J, 10 mol % of
KHMDS (0.5 M in toluene) in solvent (1.0 mL) at room temperature.
KHMDS = potassium bis(trimethylsilyl)amide. Determined by
HPLC. Reaction time: 72 h. With 5 mol % of J and 5 mol % of
b
c
d
KHMDS.
Table 3. NHC-Catalyzed Desymmetrization of
Cyclohexadienones via Intramolecular Stetter Reaction
a
b
entry
R1
R2
product
yield (%)
ee (%)
1
2
Ph
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Et
2a
2b
2c
2d
2e
2f
95
90
85
80
86
86
91
90
96
92
96
70
>99
99
4-Me-C6H4
3-Me-C6H4
2-Me-C6H4
4-F-C6H4
4-Cl-C6H4
2-thienyl
Me
c
3
98
cd
,
4
5
6
7
98/87
98
99
2g
2h
2i
99
e
8
87
9
n-Pr
>99
98
10
11
cyclopropyl
Ph
2j
2k
2l
99
f
12
Ph
i-Pr
>99
a
Reaction conditions: 1 (0.2 mmol), 10 mol % of J, 10 mol % of
KHMDS (0.5 M in toluene) in toluene (4.0 mL) at room temperature,
unless noted otherwise. Determined by HPLC. Reaction time: 40 h.
dr: 5/1. dr: 10/1. Reaction time: 60 h. Concentration: 0.02 mol/L.
Intermolecular benzoin product 2l′ was observed.
To investigate the generality of the reaction, various
substrates were tested under the optimized conditions [10
mol % of J, 10 mol % of KHMDS (0.5 M in toluene), 0.05 M of
substrate in toluene, rt, 15 h]. The results are summarized in
Table 3. For substrates bearing a tolyl group (R1), the position
of methyl substituent had almost no influence on the
b
c
d
e
f
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Note
enantioselectivity, and products 2b−d were obtained in
excellent yields and ee (80−90% yields, 98−99% ee, entries
2−4, Table 3). It should be noted that substrate 1d bearing a 2-
Me-C6H4 group resulted in a product with 5/1 dr originated
from an observed atropisomer. Electron-withdrawing groups
such as F or Cl were tolerated in this reaction, and only one
derived triazolium salt J bearing a C6F5 group was found to be
the optimal catalyst precursor for the intramolecular Stetter
reaction (up to 96% yield, >99% ee). Highly enantioenriched
functionalized tricyclic structures containing a quaternary
stereogenic center and three contiguous stereocenters could
be formed efficiently in one step under mild reaction
conditions.
1
diastereomer was observed in both cases by H NMR analysis.
When 4-F-C6H4 group was introduced, the corresponding
product 2e was obtained in 86% yield and 98% ee (entry 5,
Table 3). The substrate bearing 4-Cl-C6H4 group also led to the
desired product 2f in good yield with excellent ee (86% yield,
99% ee, entry 6, Table 3). Moreover, heteroaryl group was also
well tolerated. The reaction of 2-thienyl bearing substrate
provided the desired tricyclic product 2g in 91% yield with 99%
ee (entry 7, Table 3). Various alkyl substituents such as methyl,
n-propyl, cyclopropyl were also demonstrated as suitable
substrates (entries 8−10, Table 3). When methyl group was
EXPERIMENTAL SECTION
■
General Methods. Unless stated otherwise, all reactions were
carried out in flame-dried glassware under a dry argon atmosphere. All
solvents were purified and dried according to standard methods prior
to use. 1H and 13C NMR spectra were recorded on a 300 or 400 MHz
spectrometer and internally referenced to tetramethylsilane signal or
residual protic solvent signals. Data for 1H NMR are recorded as
follows: chemical shift (δ, ppm), multiplicity (s = singlet, d = doublet, t
= triplet, q = quartet, dd = doublet of doublets, m = multiplet or
unresolved, coupling constant(s) in Hz, integration). Data for 13C
NMR are reported in terms of chemical shift (δ, ppm). Substrates 1a−
l10 were synthesized according to reported procedure.
2-(3-Iodo-7,9-dimethyl-2,8-dioxo-4-phenyl-1-azaspiro[4.5]-
deca-3,6,9-trien-1-yl)acetaldehyde (1a). White solid, 920 mg, 47%
overall yield in four steps starting from 5-iodo-2-methoxy-1,3-
dimethylbenzene (4.5 mmol scale): mp 214−216 °C; 1H NMR
(300 MHz, CDCl3) δ 9.57 (s, 1H), 7.41−7.34 (m, 3H), 7.27−7.22 (m,
2H), 6.33 (s, 2H), 4.13 (s, 2H), 1.86 (s, 6H); 13C NMR (75 MHz,
CDCl3) δ 195.4, 185.0, 167.5, 160.4, 140.2, 137.7, 132.0, 130.0, 128.5,
127.5, 96.0, 70.6, 50.5, 16.0; IR (thin film) νmax (cm−1) = 2920, 2838,
1729, 1692, 1668, 1638, 1388, 1037, 913, 756, 699; MS (ESI-TOF)
434 ([M + H]+); HRMS (MALDI-TOF) mass calcd. for C19H17INO3
([M + H]+) 434.0248, found 434.0255.
2-(3-Iodo-7,9-dimethyl-2,8-dioxo-4-(p-tolyl)-1-azaspiro[4.5]-
deca-3,6,9-trien-1-yl)acetaldehyde (1b). White solid, 244 mg,
21% overall yield in four steps starting from 5-iodo-2-methoxy-1,3-
dimethylbenzene (2.6 mmol scale): mp 204−206 °C; H NMR (400
MHz, CDCl3) δ 9.56 (s, 1H), 7.16 (d, J = 3.9 Hz, 4H), 6.34 (s, 2H),
4.12 (s, 2H), 2.35 (s, 3H), 1.86 (s, 6H); 13C NMR (100 MHz, CDCl3)
δ 195.5, 185.1, 167.5, 160.3, 140.1, 139.9, 137.9, 129.2, 128.9, 127.3,
95.4, 70.5, 50.4, 21.3, 16.0; IR (thin film) νmax (cm−1) = 2925, 2833,
1732, 1692, 1640, 1384, 1346, 823, 760; MS (ESI-TOF) 448 ([M +
H]+); HRMS (ESI-TOF) mass calcd. for C20H19INO3 ([M + H]+)
448.0404, found 448.0395.
2-(3-Iodo-7,9-dimethyl-2,8-dioxo-4-(m-tolyl)-1-azaspiro-
[4.5]deca-3,6,9-trien-1-yl)acetaldehyde (1c). White solid, 661 mg,
48% overall yield in four steps starting from 5-iodo-2-methoxy-1,3-
1
introduced, a dr value of 10/1 was observed by H NMR
analysis (90% yield, 87% ee, entry 8, Table 3). n-Propyl,
cyclopropyl substituted substrates led to the products with
excellent yields and ee (92−96% yields, 98 to >99% ee, entry
9−10, Table 3). Other substrates bearing Et or i-Pr at the α-
position of the ketone were also investigated. The reaction of
substrate 1k bearing an ethyl group ran smoothly affording
product in high yield with excellent ee (96% yield, 99% ee,
entry 11, Table 3). When i-Pr bearing substrate 1l was used, the
reaction proceeded with excellent ee albeit slightly lower yield
because of intermolecular benzoin reaction. The intermolecular
benzoin condensation could be suppressed by running the
reaction with a lower substrate concentration (70% yield, >99%
ee, entry 12, Table 3). The absolute configuration of the
product was determined by a single crystal X-ray analysis of
enantiopure 2a as (6aR,7R,10aS).13
A postulated model of transition state is depicted in Figure 2.
The exceptional enantioselectivity is rationalized by avoiding
the steric collision with amino-indanol backbone in the favored
transition state.
In summary, highly diastereoselective and enantioselective
desymmetrization of cyclohexadienones via NHC-catalyzed
intramolecular Stetter reaction was realized. Amino-indanol
1
1
dimethylbenzene (3.1 mmol scale): mp 203−205 °C; H NMR (400
MHz, CDCl3) δ 9.57 (s, 1H), 7.26−7.19 (m, 2H), 7.07−7.00 (m, 2H),
6.34 (s, 2H), 4.14 (s, 2H), 2.34 (s, 3H), 1.86 (s, 6H); 13C NMR (100
MHz, CDCl3) δ 195.4, 185.0, 167.5, 160.6, 140.0, 138.1, 137.7, 131.9,
130.6, 128.3, 128.1, 124.5, 95.7, 70.6, 50.4, 21.3, 15.9; IR (thin film)
νmax (cm−1) = 2921, 1733, 1691, 1643, 1602, 1383, 1218, 1161, 805,
757, 706; MS (ESI-TOF) 448 ([M + H]+); HRMS (ESI-TOF) mass
calcd. for C20H19INO3 ([M + H]+) 448.0404, found 448.0394.
2-(3-Iodo-7,9-dimethyl-2,8-dioxo-4-(o-tolyl)-1-azaspiro[4.5]-
deca-3,6,9-trien-1-yl)acetaldehyde (1d). White solid, 837 mg,
41% overall yield in four steps starting from 5-iodo-2-methoxy-1,3-
1
dimethylbenzene (4.6 mmol scale): mp 177−179 °C; H NMR (400
MHz, CDCl3) δ 9.60 (s, 1H), 7.32−7.18 (m, 2H), 7.17−7.09 (m, 1H),
6.82 (d, J = 7.2 Hz, 1H), 6.45 (q, J = 1.6 Hz, 1H), 6.37 (q, J = 1.6 Hz,
1H), 4.20 (s, 2H), 2.23 (s, 3H), 1.88 (d, J = 1.6 Hz, 3H), 1.75 (d, J =
1.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 195.4, 184.7, 167.2,
161.8, 140.4, 139.5, 137.3, 137.2, 135.4, 130.7, 130.5, 129.5, 127.8,
125.1, 104.9, 97.9, 72.2, 50.9, 19.8, 15.86, 15.84; IR (thin film) νmax
(cm−1) = 2925, 1734, 1701, 1671, 1642, 1378, 1339, 1299, 1017, 841,
801, 754; MS (ESI-TOF) 448 ([M + H]+); HRMS (ESI-TOF) mass
calcd. for C20H19INO3 ([M + H]+) 448.0404, found 448.0402.
2-(4-(4-Fluorophenyl)-3-iodo-7,9-dimethyl-2,8-dioxo-1-
azaspiro[4.5]deca-3,6,9-trien-1-yl)acetaldehyde (1e). White
solid, 356 mg, 33% overall yield in four steps starting from 5-iodo-2-
Figure 2. Postulated model of transition states.
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Note
methoxy-1,3-dimethylbenzene (2.4 mmol scale): mp 173−175 °C; 1H
NMR (400 MHz, CDCl3) δ 9.57 (s, 1H), 7.32−7.22 (m, 2H), 7.12−
6.97 (m, 2H), 6.34 (s, 2H), 4.14 (s, 2H), 1.87 (s, 6H); 13C NMR (100
MHz, CDCl3) δ 195.2, 184.9, 167.3, 163.3 (d, J = 249.9 Hz), 159.3,
140.2, 137.6, 129.6 (d, J = 8.5 Hz), 127.9 (d, J = 3.4 Hz), 115.9 (d, J =
21.7 Hz), 96.5, 70.6, 50.5, 16.0; IR (thin film) νmax (cm−1) = 2936,
2831, 1733, 1693, 1641, 1601, 1503, 1383, 1233, 1158, 840, 802, 760,
690; MS (ESI-TOF) 452 ([M + H]+); HRMS (ESI-TOF) mass calcd.
for C19H16FINO3 ([M + H]+) 452.0153, found 452.0152.
2-(4-(4-Chlorophenyl)-3-iodo-7,9-dimethyl-2,8-dioxo-1-
azaspiro[4.5]deca-3,6,9-trien-1-yl)acetaldehyde (1f). White
solid, 260 mg, 23% overall yield in four steps starting from 5-iodo-2-
methoxy-1,3-dimethylbenzene (2.4 mmol scale): mp 184−186 °C; 1H
NMR (300 MHz, CDCl3) δ 9.57 (s, 1H), 7.36 (d, J = 8.1 Hz, 2H),
7.24 (d, J = 8.1 Hz, 2H), 6.37 (s, 2H), 4.16 (s, 2H), 1.86 (s, 6H). 13C
NMR (75 MHz, CDCl3) δ 195.3, 184.7, 167.0, 159.0, 140.1, 137.3,
135.8, 130.2, 128.8, 96.6, 70.3, 50.3, 15.9. IR (thin film) νmax (cm−1) =
2926, 1683, 1602, 1392, 1215, 1155, 743, 692; MS (ESI-TOF) 468
([M + H]+); HRMS (ESI-TOF) mass calcd. for C19H16ClINO3 ([M +
H]+) 467.9858, found 467.9858.
2-(3-Iodo-7,9-dimethyl-2,8-dioxo-4-(thiophen-2-yl)-1-
azaspiro[4.5]deca-3,6,9-trien-1-yl)acetaldehyde (1g). Pale yel-
low solid, 130 mg, 13% overall yield in four steps starting from 5-iodo-
2-methoxy-1,3-dimethylbenzene (2.3 mmol scale): mp 201−203 °C;
1H NMR (400 MHz, CDCl3) δ 9.54 (s, 1H), 7.75 (dd, J = 4.0, 1.2 Hz,
1H), 7.53 (dd, J = 4.8, 0.8 Hz, 1H), 7.12 (dd, J = 4.8, 3.6 Hz, 1H), 6.34
(s, 2H), 4.10 (s, 2H), 1.94 (s, 6H); 13C NMR (100 MHz, CDCl3) δ
195.4, 185.3, 167.7, 151.4, 140.3, 138.8, 132.5, 130.1, 129.7, 127.5,
91.3, 69.5, 49.9, 16.10, 16.08; IR (thin film) νmax (cm−1) = 2924, 1734,
1688, 1634, 1599, 1387, 1345, 796, 729; MS (ESI-TOF) 440 ([M +
H]+); HRMS (ESI-TOF) mass calcd. for C17H15INO3S ([M + H]+)
439.9812, found 439.9801.
2-(3-Iodo-4,7,9-trimethyl-2,8-dioxo-1-azaspiro[4.5]deca-
3,6,9-trien-1-yl)acetaldehyde (1h). White solid, 530 mg, 37%
overall yield in four steps starting from 5-iodo-2-methoxy-1,3-
dimethylbenzene (3.9 mmol scale): mp 173−175 °C; 1H NMR
(300 MHz, CDCl3) δ 9.54 (s, 1H), 6.21 (s, 2H), 4.10 (s, 2H), 1.94 (s,
6H), 1.89 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 195.6, 185.1, 167.4,
159.1, 140.1, 138.2, 93.9, 70.3, 50.5, 16.0, 15.5; IR (thin film) νmax
(cm−1) = 2888, 1741, 1686, 1637, 1490, 1391, 1159, 748, 691; MS
(ESI-TOF) 372 ([M + H]+); HRMS (ESI-TOF) mass calcd. for
C14H14INO3 ([M + H]+) 372.0091, found 372.0081.
2-(3-Iodo-7,9-dimethyl-2,8-dioxo-4-propyl-1-azaspiro[4.5]-
deca-3,6,9-trien-1-yl)acetaldehyde (1i). White solid, 250 mg, 28%
overall yield in four steps starting from 5-iodo-2-methoxy-1,3-
dimethylbenzene (2.2 mmol scale): mp 177−179 °C; 1H NMR
(300 MHz, CDCl3) δ 9.46 (s, 1H), 6.13 (s, 2H), 4.02 (s, 2H), 2.12−
1.98 (m, 2H), 1.86 (s, 6H), 1.50−1.35 (m, 2H), 0.87 (t, J = 7.2 Hz,
3H); 13C NMR (75 MHz, CDCl3) δ 195.7, 185.1, 167.4, 162.1, 139.8,
138.1, 94.2, 70.5, 50.4, 31.4, 21.6, 15.9, 14.1; IR (thin film) νmax (cm−1)
= 2926, 1734, 1692, 1642, 1383, 804, 758, 690; MS (ESI-TOF) 400
([M + H]+); HRMS (ESI-TOF) mass calcd. for C16H19INO3 ([M +
H]+) 400.0404, found 400.0398.
Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 195.3, 184.1, 167.5, 160.8,
145.6, 136.0, 132.1, 129.9, 128.4, 127.5, 95.8, 70.7, 50.5, 22.3, 12.2; IR
(thin film) νmax (cm−1) = 2970, 2856, 1729, 1702, 1668, 1639, 1458,
1375, 834, 752, 703; MS (ESI-TOF) 462 ([M + H]+); HRMS (ESI-
TOF) mass calcd. for C21H21INO3 ([M + H]+) 462.0561, found
462.0553.
2-(3-Iodo-7,9-diisopropyl-2,8-dioxo-4-phenyl-1-azaspiro-
[4.5]deca-3,6,9-trien-1-yl)acetaldehyde (1l). White solid, 630 mg,
39% overall yield in four steps starting from 5-iodo-1,3-diisopropyl-2-
1
methoxybenzene (3.3 mmol scale): mp 179−181 °C; H NMR (400
MHz, CDCl3) δ 9.56 (s, 1H), 7.42−7.30 (m, 3H), 7.22−7.17 (m, 2H),
6.24 (s, 2H), 4.11 (s, 2H), 2.91 (q, J = 6.8 Hz, 2H), 1.00 (t, J = 6.4 Hz,
6H), 0.91 (t, J = 6.4 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 195.3,
183.1, 167.5, 160.9, 150.1, 134.4, 132.0, 129.8, 128.3, 127.5, 95.6, 70.5,
50.4, 26.6, 21.6, 21.3; IR (thin film) νmax (cm−1) = 2970, 2838, 1739,
1701, 1664, 1640, 1464, 1394, 1374, 1248, 828, 702; MS (ESI-TOF)
490 ([M + H]+); HRMS (ESI-TOF) mass calcd. for C23H25INO3 ([M
+ H]+) 490.0874, found 490.0864.
General Procedure for Intramolecular Stetter Reaction. A
flame-dried Schlenk tube was cooled to room temperature and filled
with argon. To this flask were added triazolium salt J (9.4 mg, 0.02
mmol, 10 mol %), toluene (4.0 mL), KHMDS (0.5 M in toluene)
(40.0 μL, 0.02 mmol, 10 mol %). The reaction mixture was stirred at
25 °C for 30 min. The aldehyde substrate (0.2 mmol) was then added.
The reaction mixture was stirred at room temperature for 15 h unless
noted otherwise. All the volatiles were removed under reduced
pressure, and the resultant residue was purified by column
chromatography on silica gel (eluent:ethyl acetate/petroleum ether
= 1/4) to afford the product.
(6aR,7R,10aS)-2-Iodo-7,9-dimethyl-1-phenyl-6a,7-
dihydropyrrolo[2,1-i]indole-3,6,8(5H)-trione (2a). White solid,
82.0 mg, 95% yield, >99% ee [Daicel Chiralpak IC, n-hexane/2-
propanol = 60/40, v = 0.8 mL·min−1, λ = 254 nm, t (minor) = 26.7
20
min, t (major) = 34.4 min]: [α]D = −37.5 (c = 0.2, CHCl3); mp
1
215−217 °C; H NMR (300 MHz, CDCl3) δ 7.56−7.35 (m, 3H),
7.28−7.20 (m, 2H), 6.49 (s, 1H), 4.49 (AB, JAB = 19.2 Hz, 1H), 3.64
(AB, JBA = 19.2 Hz, 1H), 3.08 (q, J = 7.8 Hz, 1H), 2.52 (s, 1H), 1.91
(s, 3H), 0.41 (d, J = 8.1 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ
209.4, 196.6, 169.4, 165.1, 140.5, 137.5, 133.4, 130.2, 129.0, 127.8,
98.4, 73.7, 57.6, 49.8, 37.9, 17.7, 16.7; IR (thin film) νmax (cm−1) =
2925, 2853, 1768, 1703, 1680, 1362, 1007, 846, 797, 752, 693; MS
(ESI-TOF) 434 ([M + H]+); HRMS (MALDI-TOF) calcd. for
C19H17INO3 ([M + H]+) 434.0248, found 434.0256.
(6aR,7R,10aS)-2-Iodo-7,9-dimethyl-1-(p-tolyl)-6a,7-
dihydropyrrolo[2,1-i]indole-3,6,8(5H)-trione (2b). White solid,
80.3 mg, 90% yield, 99% ee [Daicel Chiralpak IC, n-hexane/2-
propanol = 60/40, v = 0.8 mL·min−1, λ = 254 nm, t (minor) = 25.1
20
min, t (major) = 33.5 min]: [α]D = −18.1 (c = 0.2, CHCl3); mp
1
>240 °C; H NMR (300 MHz, CDCl3) δ 7.25 (d, J = 8.1 Hz, 2H),
7.14 (d, J = 8.1 Hz, 2H), 6.49 (s, 1H), 4.48 (AB, JAB = 18.9 Hz, 1H),
3.62 (AB, JBA = 18.9 Hz, 1H), 3.07 (q, J = 7.8 Hz, 1H), 2.53 (s, 1H),
2.39 (s, 3H), 1.90 (s, 3H), 0.44 (d, J = 8.1 Hz, 3H); 13C NMR (75
MHz, CDCl3) δ 209.6, 196.7, 169.5, 165.2, 140.4, 137.6, 130.3, 129.6,
127.7, 97.8, 73.6, 57.6, 49.8, 37.9, 21.3, 17.8, 16.6; IR (thin film) νmax
(cm−1) = 2926, 1765, 1700, 1679, 1371, 824, 747, 703; MS (ESI-
TOF) 448 ([M + H]+); HRMS (ESI-TOF) mass calcd. for
C20H19INO3 ([M + H]+) 448.0404, found 448.0391.
2-(4-Cyclopropyl-3-iodo-7,9-dimethyl-2,8-dioxo-1-azaspiro-
[4.5]deca-3,6,9-trien-1-yl)acetaldehyde (1j). White solid, 305 mg,
28% overall yield in four steps starting from 5-iodo-2-methoxy-1,3-
1
dimethylbenzene (2.7 mmol scale): mp 181−183 °C; H NMR (300
MHz, CDCl3) δ 9.52 (s, 1H), 6.25 (s, 2H), 4.05 (s, 2H), 1.94 (s, 6H),
1.42−1.21 (m, 3H), 1.02−0.86 (m, 2H); 13C NMR (75 MHz, CDCl3)
δ 195.7, 185.4, 167.7, 161.1, 139.8, 138.6, 87.1, 70.8, 50.1, 16.0, 11.9,
7.8; IR (thin film) νmax (cm−1) = 2831, 2719, 1734, 1689, 1637, 1600,
1406, 1387, 830, 756, 682; MS (ESI-TOF) 398 ([M + H]+); HRMS
(ESI-TOF) mass calcd. for C16H17INO3 ([M + H]+) 398.0248, found
398.0240.
(6aR,7R,10aS)-2-Iodo-7,9-dimethyl-1-(m-tolyl)-6a,7-
dihydropyrrolo[2,1-i]indole-3,6,8(5H)-trione (2c). White solid,
76.2 mg, 85% yield, 98% ee [Daicel Chiralpak IC, n-hexane/2-
propanol = 60/40, v = 0.8 mL·min−1, λ = 254 nm, t (minor) = 23.3
20
min, t (major) = 31.0 min]: [α]D = −54.9 (c = 0.2, CHCl3); mp
1
234−235 °C; H NMR (400 MHz, CDCl3) δ 7.44−7.17 (m, 2H),
7.05−7.02 (m, 2H), 6.50−6.45 (m, 1H), 4.48 (dd, J = 19.2, 1.2 Hz,
1H), 3.63 (d, J = 19.2 Hz, 1H), 3.07 (qd, J = 8.0, 1.2 Hz, 1H), 2.52 (d,
J = 1.2 Hz, 1H), 2.37 (s, 3H), 1.90 (d, J = 1.6 Hz, 3H), 0.43 (d, J = 8.0
Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 209.5, 196.6, 169.5, 165.2,
140.4, 138.7, 137.6, 133.2, 130.8, 128.8, 128.4, 124.9, 97.9, 73.6, 57.5,
49.8, 37.9, 21.4, 17.6, 16.6; IR (thin film) νmax (cm−1) = 2957, 2919,
1761, 1716, 1663, 1348, 798, 758, 696; MS (ESI-TOF) 448 ([M +
2-(7,9-Diethyl-3-iodo-2,8-dioxo-4-phenyl-1-azaspiro[4.5]-
deca-3,6,9-trien-1-yl)acetaldehyde (1k). White solid, 700 mg, 41%
overall yield in four steps starting from 1,3-diethyl-5-iodo-2-
1
methoxybenzene (3.7 mmol scale): mp 203−205 °C; H NMR (400
MHz, CDCl3) δ 9.57 (s, 1H), 7.45−7.30 (m, 3H), 7.22 (d, J = 7.2 Hz,
2H), 6.27 (s, 2H), 4.13 (s, 2H), 2.41−2.13 (m, 4H), 0.96 (t, J = 7.2
10999
dx.doi.org/10.1021/jo3022555 | J. Org. Chem. 2012, 77, 10996−11001

The Journal of Organic Chemistry
Note
H]+); HRMS (ESI-TOF) mass calcd. for C20H19INO3 ([M + H]+)
448.0404, found 448.0404.
Hz, 3H), 1.44 (d, J = 8.0 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ
209.6, 196.9, 169.6, 163.5, 140.2, 138.8, 96.8, 72.6, 57.1, 49.7, 37.7,
19.3, 18.2, 16.7; IR (thin film) νmax (cm−1) = 2924, 1760, 1701, 1668,
1429, 1380, 1354, 1037, 750, 705; MS (ESI-TOF) 372 ([M + H]+);
HRMS (ESI-TOF) mass calcd. for C14H15INO3 ([M + H]+) 372.0091,
found 372.0088.
(6aR,7R,10aS)-2-Iodo-7,9-dimethyl-1-(o-tolyl)-6a,7-
dihydropyrrolo[2,1-i]indole-3,6,8(5H)-trione (2d). White solid,
71.2 mg, 80% yield, 98% ee (major diastereomer)/87% ee (minor
diastereomer) [Daicel Chiralpak IC, n-hexane/2-propanol = 60/40, v
= 0.8 mL·min−1, λ = 254 nm, major diastereomer t (minor) = 22.1
min, t (major) = 29.9 min; minor diastereomer t (minor) = 28.0 min, t
(major) = 33.1 min]: [α]D20 = −51.2 (c = 0.2, CHCl3); mp >240 °C;
1H NMR (400 MHz, CDCl3) δ 7.40−7.29 (m, 2H), 7.25−7.20 (m,
(6aR,7R,10aS)-2-Iodo-7,9-dimethyl-1-propyl-6a,7-
dihydropyrrolo[2,1-i]indole-3,6,8(5H)-trione (2i). White solid,
79.0 mg, 96% yield, >99% ee [Daicel Chiralpak IC, n-hexane/2-
propanol = 60/40, v = 0.8 mL·min−1, λ = 254 nm, t (minor) = 19.2
20
min, t (major) = 22.3 min]: [α]D = −171.0 (c = 0.2, CHCl3); mp
1H), 6.94 (d, J = 7.6 Hz, 1H), 6.42 (s, 1H), 4.48 (AB, JAB = 19.2 Hz,
1H), 3.64 (AB, JBA = 19.2 Hz, 1H), 3.10 (q, J = 8.0 Hz, 1H), 2.60 (s,
1H), 2.34 (s, 3H), 1.85 (s, 3H), 0.51 (d, J = 8.0 Hz, 3H); 13C NMR
(100 MHz, CDCl3) δ 209.2, 196.6, 168.8, 165.1, 139.9, 138.0, 135.7,
132.4, 131.1, 129.8, 126.9, 125.8, 100.8, 74.4, 56.6, 49.6, 38.1, 20.3,
16.9, 16.6; IR (thin film) νmax (cm−1) = 2925, 1759, 1678, 1453, 1373,
852, 758, 734; MS (ESI-TOF) 448 ([M + H]+); HRMS (ESI-TOF)
mass calcd. for C20H19INO3 ([M + H]+) 448.0404, found 448.0378.
(6aR,7R,10aS)-1-(4-Fluorophenyl)-2-iodo-7,9-dimethyl-6a,7-
dihydropyrrolo[2,1-i]indole-3,6,8(5H)-trione (2e). White solid,
77.4 mg, 86% yield, 98% ee [Daicel Chiralpak IC, n-hexane/2-
propanol = 60/40, v = 0.8 mL·min−1, λ = 254 nm, t (minor) = 21.3
109−111 °C; 1H NMR (300 MHz, CDCl3) δ 6.16 (s, 1H), 4.42 (AB,
JAB = 19.2 Hz, 1H), 3.56 (AB, JBA = 19.2 Hz, 1H), 3.25 (q, J = 7.8 Hz,
1H), 2.48 (s, 1H), 2.46−2.38 (m, 1H), 2.37−2.23 (m, 1H), 1.86 (s,
3H), 1.75−1.52 (m, 2H), 1.43 (d, J = 7.8 Hz, 3H), 1.00 (t, J = 7.5 Hz,
3H); 13C NMR (75 MHz, CDCl3) δ 209.8, 196.9, 169.8, 167.1, 140.1,
138.7, 96.2, 72.8, 57.1, 49.6, 37.7, 33.0, 21.3, 19.0, 16.7, 14.2; IR (thin
film) νmax (cm−1) = 2923, 1765, 1671, 1602, 1461, 803, 751; MS (ESI-
TOF) 400 ([M + H]+); HRMS (ESI-TOF) mass calcd. for
C16H19INO3 ([M + H]+) 400.0404, found 400.0392.
(6aR,7R,10aS)-1-Cyclopropyl-2-iodo-7,9-dimethyl-6a,7-
dihydropyrrolo[2,1-i]indole-3,6,8(5H)-trione (2j). White solid,
73.3 mg, 92% yield, 98% ee [Daicel Chiralpak IC, n-hexane/2-
propanol = 60/40, v = 0.8 mL·min−1, λ = 254 nm, t (minor) = 30.5
20
min, t (major) = 26.6 min]: [α]D = −43.2 (c = 0.2, CHCl3); mp
1
235−237 °C; H NMR (300 MHz, CDCl3) δ 7.35−7.22 (m, 2H),
20
min, t (major) = 33.5 min]: [α]D = −190.4 (c = 0.2, CHCl3); mp
7.17 (t, J = 8.4 Hz, 2H), 6.48 (s, 1H), 4.49 (AB, JAB = 19.2 Hz, 1H),
3.64 (AB, JBA = 19.2 Hz, 1H), 3.10 (q, J = 7.8 Hz, 1H), 2.53 (s, 1H),
1.91 (d, J = 0.9 Hz, 3H), 0.48 (d, J = 8.1 Hz, 3H); 13C NMR (75 MHz,
CDCl3) δ 209.2, 196.4, 169.2, 164.0, 163.6 (d, J = 250.7 Hz), 140.7,
137.2, 130.0 (d, J = 1.6 Hz), 129.3 (d, J = 3.5 Hz), 116.3 (d, J = 21.8
Hz), 99.0, 73.6, 57.6, 49.8, 37.8, 17.9, 16.7; IR (thin film) νmax (cm−1)
= 2918, 1757, 1702, 1677, 1504, 1370, 1228, 846, 798, 748, 697; MS
(ESI-TOF) 452 ([M + H]+); HRMS (ESI-TOF) mass calcd. for
C19H16FINO3 ([M + H]+) 452.0153, found 452.0143.
1
164−166 °C; H NMR (400 MHz, CDCl3) δ 6.25−6.20 (m, 1H),
4.43 (dd, J = 18.8, 0.8 Hz, 1H), 3.56 (d, J = 18.8 Hz, 1H), 3.26 (qd, J =
8.0, 1.2 Hz, 1H), 2.56 (d, J = 1.2 Hz, 1H), 1.87 (d, J = 1.2 Hz, 3H),
1.74−1.66 (m, 1H), 1.58−1.51 (m, 1H), 1.49 (d, J = 8.0 Hz, 3H),
1.43−1.35 (m, 1H), 1.18−1.08 (m, 1H), 1.07−0.99 (m, 1H); 13C
NMR (100 MHz, CDCl3) δ 209.8, 197.2, 170.3, 165.6, 140.7, 139.3,
86.8, 74.0, 58.0, 49.9, 37.6, 19.0, 16.8, 12.4, 9.0, 8.2; IR (thin film) νmax
(cm−1) = 2929, 1767, 1693, 1666, 1593, 1348, 840, 753, 691; MS
(ESI-TOF) 398 ([M + H]+); HRMS (ESI-TOF) mass calcd. for
C16H17INO3 ([M + H]+) 398.0248, found 398.0236.
(6aR,7R,10aS)-1-(4-Chlorophenyl)-2-iodo-7,9-dimethyl-6a,7-
dihydropyrrolo[2,1-i]indole-3,6,8(5H)-trione (2f). White solid,
80.4 mg, 86% yield, 99% ee [Daicel Chiralpak IC, n-hexane/2-
propanol = 60/40, v = 0.8 mL·min−1, λ = 254 nm, t (minor) = 21.2
(6aR,7R,10aS)-7,9-Diethyl-2-iodo-1-phenyl-6a,7-
dihydropyrrolo[2,1-i]indole-3,6,8(5H)-trione (2k). White solid,
89.6 mg, 96% yield, 99% ee [Daicel Chiralpak IC, n-hexane/2-
propanol = 60/40, v = 0.8 mL·min−1, λ = 254 nm, t (major) = 17.8
20
min, t (major) = 25.4 min]: [α]D = −41.9 (c = 0.2, CHCl3); mp
1
>240 °C; H NMR (400 MHz, CDCl3) δ 7.45 (d, J = 8.8 Hz, 2H),
20
min, t (minor) = 19.8 min]: [α]D = −37.2 (c = 0.2, CHCl3); mp
7.22 (d, J = 8.8 Hz, 2H), 6.48 (t, J = 1.4 Hz,1H), 4.74 (AB, JAB = 19.0
Hz, 1H), 3.63 (AB, JBA = 19.0 Hz, 1H), 3.10 (qd, J = 8.0, 1.2 Hz, 1H),
2.56 (s, 1H), 1.90 (d, J = 1.2 Hz, 3H), 0.50 (d, J = 8.0 Hz, 3H); 13C
NMR (100 MHz, CDCl3) δ 209.1, 196.3, 169.0, 163.7, 140.7, 137.1,
136.3, 131.7, 129.29, 129.21, 99.2, 73.5, 57.6, 49.7, 37.8, 18.0, 16.7; IR
(thin film) νmax (cm−1) = 2927, 1767, 1699, 1681, 1484, 1368, 1146,
1008, 835, 747, 708; MS (ESI-TOF) 468 ([M + H]+); HRMS (ESI-
TOF) mass calcd. for C19H16ClINO3 ([M + H]+) 467.9858, found
467.9848.
1
180−182 °C; H NMR (400 MHz, CDCl3) δ 7.51−7.39 (m, 3H),
7.30−7.24 (m, 2H), 6.41 (s, 1H), 4.49 (AB, JAB = 19.2 Hz, 1H), 3.61
(AB, JBA = 19.2 Hz, 1H), 2.79 (dd, J = 10.0, 6.8 Hz, 1H), 2.68 (s, 1H),
2.41−2.32 (m, 1H), 2.30−2.20 (m, 1H), 1.07 (t, J = 7.6 Hz, 3H),
1.03−0.94 (m, 1H), 0.62 (t, J = 7.2 Hz, 3H), 0.27−0.12 (m, 1H); 13C
NMR (100 MHz, CDCl3) δ 210.0, 195.8, 169.3, 165.1, 145.4, 135.5,
133.4, 130.1, 128.7, 127.7, 98.5, 73.8, 54.2, 49.8, 45.9, 23.8, 23.0, 12.3,
11.9; IR (thin film) νmax (cm−1) = 2962, 1765, 1707, 1669, 1366, 1219,
784, 758, 704; MS (ESI-TOF) 462 ([M + H]+); HRMS (ESI-TOF)
mass calcd. for C21H21INO3 ([M + H]+) 462.0561, found 462.0552.
(6aR,7R,10aS)-2-iodo-7,9-diisopropyl-1-phenyl-6a,7-
dihydropyrrolo[2,1-i]indole-3,6,8(5H)-trione (2l). White solid,
68.0 mg, 70% yield, >99% ee [Daicel Chiralpak IC, n-hexane/2-
propanol = 80/20, v = 0.8 mL·min−1, λ = 254 nm, t (major) = 22.8
(6aR,7R,10aS)-2-Iodo-7,9-dimethyl-1-(thiophen-2-yl)-6a,7-
dihydropyrrolo[2,1-i]indole-3,6,8(5H)-trione (2g). White solid,
70.5 mg, 91% yield, 99% ee [Daicel Chiralpak IC, n-hexane/2-
propanol = 60/40, v = 0.8 mL·min−1, λ = 254 nm, t (minor) = 25.9
20
min, t (major) = 32.9 min]: [α]D = +62.2 (c = 0.2, CHCl3); mp
1
216−218 °C; H NMR (400 MHz, CDCl3) δ 7.55−7.50 (m, 2H),
20
min, t (minor) = 26.2 min]: [α]D = −28.5 (c = 0.2, CHCl3); mp
7.18 (dd, J = 4.8, 4.0 Hz, 1H), 6.47 (s, 1H), 4.52 (AB, JAB = 18.8 Hz,
1H), 3.64 (AB, JBA = 18.8 Hz, 1H), 3.14 (q, J = 8.0 Hz, 1H), 2.62 (s,
1H), 1.95 (d, J = 0.8 Hz, 3H), 0.65 (d, J = 8.0 Hz, 3H); 13C NMR
(100 MHz, CDCl3) δ 209.4, 196.6, 169.5, 157.7, 142.9, 136.9, 132.8,
130.2, 129.4, 127.7, 97.1, 73.2, 58.3, 49.8, 37.4, 17.6, 16.8; IR (thin
film) νmax (cm−1) = 2924, 1766, 1680, 1598, 1378, 748, 706; MS (ESI-
TOF) 440 ([M + H]+); HRMS (ESI-TOF) mass calcd. for
C17H15INO3S ([M + H]+) 439.9812, found 439.9817.
1
185−187 °C; H NMR (400 MHz, CDCl3) δ 7.52−7.39 (m, 3H),
7.34−7.32 (m, 2H), 6.33−6.30 (m, 1H), 4.47 (dd, J = 19.2, 1.0 Hz,
1H), 3.53 (d, J = 19.2 Hz, 1H), 3.04−2.92 (m, 1H), 2.84 (s, 1H), 2.51
(d, J = 8.4 Hz, 1H), 1.11 (d, J = 7.2 Hz, 3H), 1.05 (d, J = 7.2 Hz, 3H),
0.63 − 0.36 (m, 7H); 13C NMR (100 MHz, CDCl3) δ 210.2, 195.7,
169.3, 164.9, 149.8, 133.6, 133.3, 130.1, 128.5, 127.9, 99.0, 74.1, 54.1,
53.2, 49.6, 29.6, 27.0, 26.8, 21.5, 21.3, 21.0, 20.6; IR (thin film) νmax
(cm−1) = 2924, 1764, 1702, 1669, 1464, 1373, 1344, 806, 764, 703;
MS (ESI-TOF) 490 ([M + H]+); HRMS (ESI-TOF) mass calcd. For
C23H25INO3 ([M + H]+) 490.0874, found 490.0864.
(6aR,7R,10aS)-2-Iodo-1,7,9-trimethyl-6a,7-dihydropyrrolo-
[2,1-i]indole-3,6,8(5H)-trione (2h). White solid, 66.5 mg, 90% yield,
87% ee (major diastereomer) [Daicel Chiralpak IC, n-hexane/2-
propanol = 60/40, v = 0.8 mL·min−1, λ = 254 nm, t (minor) = 28.1
Benzoin Product 2l′. Pale yellow solid, 16.2 mg, 17% yield, 0% ee
[Daicel Chiralpak IC, n-hexane/2-propanol = 60/40, v = 0.8
mL·min−1, λ = 254 nm, t (major) = 15.1 min, t (minor) = 20.8
min]: mp 226−228 °C; 1H NMR (400 MHz, CDCl3) δ 7.40−7.28 (m,
6H), 7.25−7.28 (m, 4H), 6.35−6.10 (m, 4H), 4.69 (AB, JAB = 18.8 Hz,
20
min, t (major) = 30.4 min]: [α]D = −207.0 (c = 0.2, CHCl3); mp
1
169−171 °C; H NMR (400 MHz, CDCl3) δ 6.22−6.10 (m, 1H),
4.43 (dd, J = 19.2, 1.0 Hz, 1H), 3.56 (d, J = 19.2 Hz, 1H), 3.27 (qd, J =
8.0, 1.2 Hz, 1H), 2.55 (d, J = 1.2 Hz, 1H), 2.16 (s, 3H), 1.87 (d, J = 1.6
11000
dx.doi.org/10.1021/jo3022555 | J. Org. Chem. 2012, 77, 10996−11001

The Journal of Organic Chemistry
Note
(4) NHC-catalyzed diastereoselective and enantioselective proto-
nation: (a) Reynolds, N. T.; Rovis, T. J. Am. Chem. Soc. 2005, 127,
16406. (b) Wang, X.-N.; Lv, H.; Huang, X.-L.; Ye, S. Org. Biomol.
́
Chem. 2009, 7, 346. (c) Concellon, C.; Duguet, N.; Smith, A. D. Adv.
Synth. Catal. 2009, 351, 3001. (d) Kena Diba, A.; Noll, C.; Richter, M.;
Gieseler, M. T.; Kalesse, M. Angew. Chem., Int. Ed. 2010, 49, 8367.
(e) Jousseaume, T.; Wurz, N. E.; Glorius, F. Angew. Chem., Int. Ed.
2011, 50, 1410. (f) Kravina, A. G.; Mahatthananchai, J.; Bode, J. W.
Angew. Chem., Int. Ed. 2012, 51, 9433.
(5) Read de Alaniz, J.; Rovis, T. J. Am. Chem. Soc. 2005, 127, 6284.
(6) Liu, Q.; Rovis, T. J. Am. Chem. Soc. 2006, 128, 2552.
(7) For a secondary amine catalyzed desymmetrization of cyclo-
hexadienones reaction: Leon, R.; Jawalekar, A.; Redert, T.; Gaunt, M.
J. Chem. Sci. 2011, 2, 1487.
1H), 4.31 (t, J = 5.6 Hz, 1H), 4.17 (AB, JBA = 18.8 Hz, 1H), 3.66−3.50
(m, 2H), 3.05−2.80 (m, 4H), 1.10 (d, J = 6.8 Hz, 3H), 1.06−1.01 (m,
6H), 0.97 (d, J = 7.2 Hz, 3H), 0.92−0.87 (m, 12H); 13C NMR (100
MHz, CDCl3) δ 206.2, 183.3, 183.2, 171.1, 167.4, 162.5, 161.1, 150.8,
150.2, 149.9, 149.2, 134.9, 134.5, 134.4, 132.2, 132.1, 129.79, 129.75,
128.3, 127.7, 127.6, 95.7, 94.8, 72.5, 70.8, 48.0, 47.0, 29.7, 26.9, 26.8,
26.7, 26.5, 21.8, 21.68, 21.65, 21.63, 21.5, 21.3, 20.9, 14.1; IR (thin
film) νmax (cm−1) = 2963, 2921, 1733, 1696, 1667, 1643, 1463, 1390,
843, 755, 697; MS (ESI-TOF) 979 ([M + H]+); HRMS (ESI-TOF)
mass calcd. for C46H49I2N2O6 ([M + H]+) 979.1674, found 979.1657.
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ASSOCIATED CONTENT
■
S
* Supporting Information
1H NMR, 13C NMR of all the new compounds, HPLC spectra
of 2a−2l′ and crystal data (CIF) for 2a. This material is
available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*Fax: (+86) 21-54925087. E-mail: slyou@sioc.ac.cn.
■
(13) See the Supporting Information for details.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank National Basic Research Program of China (973
Program 2009CB825300) and National Natural Science
Foundation of China (20972177, 21025209, 21121062) for
generous financial support.
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