Iodine-Catalyzed C-N Cleavage of Tertiary Amines: Synthesis of Methylene-Bridged Bis-1,3-dicarbonyl Compounds

Article abstract of DOI:10.1055/s-0034-1378208

A novel and efficient iodine-catalyzed C-N cleavage of tertiary amines via an sp³ C-H bond oxidative coupling reaction is described. A wide range of methylene-bridged bis-1,3-dicarbonyl compounds were synthesized in up to 92% yield by using an

Full text of DOI:10.1055/s-0034-1378208

PAPER
▌2445
paper
Iodine-Catalyzed C–N Cleavage of Tertiary Amines: Synthesis of Methylene-
Bridged Bis-1,3-dicarbonyl Compounds
Iodine-Catalyzed C–N Cleavage of Tertiary Amines
Lin Lu, Shengmei Guo,* Qiheng Xiong, Shengyi Liu, Xiang Li, Hu Cai*
Department of Chemistry, Nanchang University, Nanchang, Jiangxi 330031, P. R. of China
Fax +86(791)88109568; E-mail: smguo@ncu.edu.cn; E-mail: caihu@ncu.edu.cn
Received: 04.03.2014; Accepted after revision: 30.04.2014
tions. For example, the groups of Itoh and Prabhu have in-
Abstract: A novel and efficient iodine-catalyzed C–N cleavage of
dependently successfully developed a molecular iodine
catalyzed cross-dehydrogenative coupling reaction be-
tween N-phenyltetrahydroisoquinoline and a series of nu-
tertiary amines via an sp3 C–H bond oxidative coupling reaction is
described. A wide range of methylene-bridged bis-1,3-dicarbonyl
compounds were synthesized in up to 92% yield by using an envi-
ronmentally benign catalytic system in combination with 1,3-dicar- cleophiles (e.g., carbonyl derivatives, phenols, indoles,
amides, nitroalkanes),17g,18 while Yan and Wang have re-
bonyl compounds.
ported the intramolecular oxidative decarboxylative ami-
nation of primary α-amino acids for the synthesis of
quinazolines.19 However, little attention has been paid to
the use of iodine as a catalyst to realize the C–N bond
cleavage of amines.12 Herein, we present an iodine-cata-
lyzed oxidative coupling reaction via C–N bond cleavage
of tertiary amines.
Key words: iodine, oxidative coupling, C–N cleavage, tertiary
amines, methylene-bridged bis-1,3-dicarbonyl compounds
The cleavage of C–N bonds has attracted much attention
from organic chemists due to the wide existence of nitro-
containing compounds in natural products and numerous
organisms.1 However, since C–N bonds are usually inert,
harsh conditions are generally required for their cleav-
age.2,3 During the past decades, much effort has been de-
voted to the design of efficient protocols to solve this
problem,3 including (1) conversion of nitro groups into
better leaving groups, such as diazonium salts,1b,4 ammo-
nium salts and azaheterocycles,5 to facilitate the C–N
bond cleavage, and (2) use of transition metals to directly
catalyze the C–N bond cleavage.6 Recently, oxidative
coupling reactions have been developed to construct C–C
and C–N bonds via C–N cleavage based on sp3 C–H bond
activation of secondary or tertiary amine derivatives. For
example, iron,7 copper,8 gold,9 ruthenium10 and palladi-
um11 have been employed as catalysts or photocatalysts in
the construction of 1,3-dicarbonyl compounds and alkyl
aryl ketones, and in the C3-selective formylation of in-
doles using N-methylaniline or N,N-dimethylaniline as
the formylating reagent under oxidation conditions,10,12
thus avoiding many side reactions which occur when
formaldehyde and dihalomethanes are used as a methy-
lene source.13 Besides C–C bond formation, new C–N
bond formation via C–N bond cleavage of tertiary amines
has also been reported by the groups of Huang,14 Wang15
and Xu.16 However, in the above transformations, expen-
sive and toxic transition-metal catalysts are essential.
Thus, new catalytic systems capable of performing the C–
N bond cleavage both in an environmentally friendly
manner and with high efficiency are highly desirable.
Initially, the reaction was conducted with N,N,N′,N′-te-
tramethylethylenediamine (TMEDA) as substrate and
ethyl 3-oxo-3-phenylpropanoate as the reaction partner,
without the addition of catalyst, at 100 °C in the presence
of di-tert-butyl peroxide (DTBP) as oxidant for 12 hours;
however, as shown in Table 1, the desired methylene-
bridged bis-1,3-dicarbonyl compound was not obtained
(entry 1). When potassium iodide or sodium iodide was
used as the catalyst, the desired product was isolated in
61% and 34% yield, respectively (Table 1, entries 2 and
3). The reaction with iodine as catalyst gave the best re-
sult, affording the product in 86% yield (Table 1, entry 4).
Then, a series of other oxidants was screened; it was
found that air, tert-butyl hydroperoxide (TBHP), oxygen
and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ)
were less efficient for this transformation, providing low-
er yields of product (Table 1, entries 5–8). Other oxidants,
such as m-chloroperoxybenzoic acid, benzoyl peroxide
(BPO) and 1,4-benzoquinone (BQ), were barely able to
promote the reaction (Table 1, entries 9–11). Further
screening of the solvent indicated its key role in the reac-
tion outcome. Tetrahydrofuran, N,N-dimethylformamide,
dimethyl sulfoxide, benzene, toluene, xylene and 1,2-di-
chloroethane gave the corresponding product in moderate
yield (Table 1, entries 12–18), and were thus less produc-
tive than the use of acetonitrile as solvent. The reaction
temperature was also explored; when the temperature was
raised to 120 °C, the product was obtained in 63% yield,
while lowering the temperature to 60 °C resulted in 33%
yield of product (Table 1, entries 19 and 20). When the re-
action time was prolonged to 16 hours, the yield was 82%,
while this reaction gave the desired product in 72% yield
when the time was shortened to 8 hours (Table 1, entries
21 and 22). The use of other tertiary amines, such as N,N-
dimethylaniline (Table 1, entry 23), was investigated
Iodine is an inexpensive, environmentally benign reagent
with a low toxicity.17 In the past decade, iodine sources
have proved useful as catalysts in oxidative coupling reac-
SYNTHESIS 2014, 46, 2445–2450
Advanced online publication: 24.06.2014
0
0
3
9
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7
8
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1
1
4
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2
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DOI: 10.1055/s-0034-1378208; Art ID: ss-2014-f0153-op
© Georg Thieme Verlag Stuttgart · New York

2446
L. Lu et al.
PAPER
which resulted in lower yields of the methylene-bridged donating groups on the phenyl ring, the corresponding
bis-1,3-dicarbonyl compound.
methylene-bridged compounds were obtained in excellent
yields. For example, when a 4-methoxy, 4-ethoxy or 4-
morpholino group was present on the phenyl ring, the cor-
responding products 2d–f were obtained in up to 92%
yield (Table 2, entries 4–6). Moreover, meta-substituted
substrates also gave the corresponding products, 2g and
2h, in 86% and 82% yield, respectively (Table 2, entries 7
and 8). However, for the reactions of substrates with an
electron-withdrawing substituent on the phenyl ring, there
was a clear decrease in the yield of product (2i–k; Table
2, entries 9–11). 1,3-Diketones such as 1,3-diphenylpro-
pane-1,3-dione and 1-phenylbutane-1,3-dione could be
transformed into the corresponding products 2l and 2m in
moderate yields under the optimized conditions (Table 2,
entries 12 and 13). Methyl 3-(2-naphthyl)-3-oxopropano-
ate and a β-keto amide also participated in the reaction,
and gave the desired products 2n and 2o in 68% and 71%
yield, respectively (Table 2, entries 14 and 15).
Table 1 Optimization of the Reaction Conditions
O
O
O
O
[I] (20 mol%),
O
O
[O] (4 equiv)
Ph
Ph
OEt
OEt
Me
N
N
Me
+
MeMe
0.6 mmol
MeCN,
100 °C, 12 h
Ph
OEt
0.5 mmol
Entry
[I]
Oxidant
Solvent
Yielda (%)
1
2
–
DTBP
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
THF
trace
61
KI
DTBP
3
NaI
I2
I2
I2
I2
I2
I2
I2
I2
I2
I2
I2
I2
I2
I2
I2
I2
I2
I2
I2
I2
DTBP
34
4
DTBP
86
5
air (1 atm)
64
6
TBHP (70% aq)
O2 (1 atm)
DDQ
20
Table 2 Reaction Scope
7
52
O
O
I2 (20 mol%)
8
23
O
O
DTBP (4 equiv)
Ar
Ar
R
R
Me
Me
N
N
+
MeCN
100 °C, 12 h
9
MCPBA
BPO
trace
trace
trace
47
Ar
R
MeMe
1
10
11
12
13
14
15
16
17
18
19b
20c
21d
22e
23f
O
O
2
BQ
Entry
Ar
R
Product Yielda (%)
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
1
2
Ph
Ph
OEt
2a
2b
2c
2d
2e
2f
86
78
67
88
91
92
86
82
69
73
51
46
41
68
71
DMF
45
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OMe
Ph
DMSO
benzene
toluene
xylene
DCE
48
3
4-Tol
41
4
4-MeOC6H4
4-EtOC6H4
morpholino
3-MeOC6H4
3,4-OCH2O-
4-FC6H4
4-ClC6H4
4-BrC6H4
Ph
40
5
37
6
42
7
2g
2h
2i
MeCN
MeCN
MeCN
MeCN
MeCN
63
8
33
9
82
10
11
12
13
14
15
2j
72
2k
2l
23
a Isolated yield.
b Reaction temperature: 120 °C.
c Reaction temperature: 60 °C.
d Reaction time: 16 h.
Ph
Me
2m
2n
2o
2-Naph
OMe
morpholino
e Reaction time: 8 h.
f N,N-Dimethylaniline was used as the methylene source.
Ph
a Isolated yield.
With the optimized conditions in hand, we then explored
the scope of the reaction; the results are summarized in
Table 2. Firstly, when methyl 3-oxo-3-phenylpropanoate
was used as the substrate, the yield of the corresponding
product 2b was slightly lower than that of the ethyl ester
2a (Table 2, entries 1 and 2). For substrates with electron-
To obtain more information about the reaction mecha-
nism, (diacetoxyiodo)benzene [PhI(OAc)2] instead of io-
dine was used as a catalyst under the optimized reaction
conditions; the corresponding product 2a was isolated in
Synthesis 2014, 46, 2445–2450
© Georg Thieme Verlag Stuttgart · New York

PAPER
Iodine-Catalyzed C–N Cleavage of Tertiary Amines
2447
O
O
PhI(OAc)2
(20 mol%),
DTBP
O
O
Ph
Ph
OEt
OEt
eq. 1
+
Me
N
N
Me
Ph
OEt
MeCN,
100 °C, 12 h
MeMe
0.6 mmol
0.5 mmol
O
O
51% yield
I2 (20 mol%),
DTBP(4 equiv)
TEMPO
O
O
O
O
(200 mol%)
Ph
Ph
OEt
OEt
eq. 2
Me
N
N
Me
+
Ph
OEt
MeCN,
100 °C, 12 h
MeMe
0.6 mmol
0.5 mmol
O
O
56% yield
O
O
O
O
I2 (120 mol%)
Ph
Ph
OEt
OEt
Me
N
N
Me
eq. 3
+
Ph
OEt
MeCN,
100 °C, 12 h
MeMe
0.6 mmol
0.5 mmol
O
O
72% yield
Scheme 1 Probe of the reaction mechanism
51% yield (Scheme 1, eq 1), which indicates that the cat-
alyst might go through a hypervalent iodine process. Next,
a radical inhibitor (TEMPO) was added to the reaction
mixture under the optimized conditions; in this case, the
yield of product decreased dramatically (to 56%; Scheme
1, eq 2), suggesting a process with a radical intermediate.
Taking into account that iodine may undergo homolysis
and heterolysis reactions, which could generate I•, I+ and
I–, we then increased the amount of iodine to 1.2 equiva-
lents under nitrogen atmosphere without DTBP as oxi-
dant, and found that the reaction took place smoothly,
giving the product in 72% yield (Scheme 1, eq 3). This
suggests that the reaction goes through a radical process
and a hypervalent iodine process.
I2
t-BuOOt-Bu
O
O
•
Me
N
N
Me
t-BuOH
Ph
OEt
MeMe
IO–
B
Me
+N CH2
Me
Me
N
N
Me
t-BuOOt-Bu
Me
N
Me
Me
C
•
I–
t-BuO
A
O
O
Ph
OEt
Me
N
Me
Me
N
IO–
O
O
D
Based on our studies and previous literature,8a,b,12,19 we
propose a possible mechanism for this reaction (Scheme
2). First, thermal homolysis of di-tert-butyl peroxide
would generate the tert-butoxy radical A (t-BuO•). Then,
occurrence of a single-electron transfer procedure be-
tween TMEDA and the tert-butoxy radical would result in
formation of the TMEDA radical B. On the other hand, io-
dine would be oxidized by di-tert-butyl peroxide to afford
hypervalent iodine, which could then oxidize radical B to
produce iminium ion C and iodine. Attack of the β-keto
ester at the iminium ion would give intermediate D, which
could then undergo a nucleophilic substitution reaction to
afford the desired product 2a.
SN2
Ph
Ph
OEt
OEt
O
O
2a
Scheme 2 Proposed reaction mechanism
tion proceeds via a radical process. Further study is cur-
rently underway in our laboratory.
1H and 13C NMR spectra were determined for solutions in CDCl3
with TMS as internal standard on BRUKER DRX 600 spectrome-
ters or agilent 400 spectrometers. ESI-HRMS data were measured
on a Bruker Compass DataAnalysis 4.0 mass instrument (ESI).
In conclusion, we have described a general and efficient
iodine-catalyzed C–N cleavage of tertiary amines under
mild conditions. This protocol provides a practical and
green method for the synthesis of bis-1,3-dicarbonyl com-
pounds in moderate to excellent yields using DTBP as an
oxidant. Studies of the mechanism showed that the reac-
Methylene-Bridged Bis-1,3-dicarbonyl Compounds 2a–o;
General Procedure
A 1,3-dicarbonyl compound 1 (0.5 mmol), I2 (25.4 mg, 20 mol%),
TMEDA (1.2 equiv), DTBP (4 equiv) and MeCN (2 mL) were add-
ed to a 25-mL flame-dried Schlenk tube under air. The Schlenk tube
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 2445–2450

2448
L. Lu et al.
PAPER
was sealed with a rubber septum and stirred for 12 h at 100 °C. The
reaction progress was monitored by TLC. After completion of the
reaction, the mixture was allowed to cool to r.t., the solvent was re-
moved under reduced pressure and the residue was purified by col-
umn chromatography on silica gel (EtOAc–hexane, 1:40, 1:20) to
afford the desired product.
HRMS (ESI): m/z [M+ + 23] calcd for C29H34N2NaO8: 561.2207;
found: 561.2210.
Dimethyl 2,4-Bis(3-methoxybenzoyl)pentanedioate (2g)
White solid; yield: 92 mg (86%); two diastereomers (1.3:1).
1H NMR (400 MHz, CDCl3): δ = 7.66–7.61 (m, 2 H), 7.57 (s, 2 H),
7.42–7.36 (m, 2 H), 7.16–7.11 (m, 2 H), 4.63 (t, J = 7.2 Hz, 1 H),
4.54 (t, J = 7.2 Hz, 1 H), 3.88 (d, J = 8.8 Hz, 6 H), 3.75 (s, 3 H), 3.64
(s, 3 H), 2.77–2.53 (m, 2 H).
13C NMR (101 MHz, CDCl3): δ = 195.08, 194.64, 170.31, 169.93,
160.14, 160.11, 137.19, 136.71, 130.00, 121.70, 121.58, 120.96,
120.85, 55.65, 52.80, 52.78, 51.61, 51.34, 28.65, 28.08.
Diethyl 2,4-Dibenzoylpentanedioate (2a)
White solid; yield: 85 mg (86%); two diastereomers (1.2:1).
1H NMR (601 MHz, CDCl3): δ = 8.06–8.05 (m, 4 H), 7.62–7.61 (m,
2 H), 7.52–7.46 (m, 4 H), 4.64 (t, J = 7.2 Hz, 1 H), 4.55 (t, J = 7.2
Hz, 1 H), 4.24–4.21 (m, 2 H), 4.11–4.09 (m, 2 H), 2.78–2.52 (m, 2
H), 1.22 (t, J = 7.2 Hz, 3 H), 1.11 (t, J = 7.2 Hz, 3 H).
13C NMR (151 MHz, CDCl3): δ = 195.29, 194.92, 169.80, 169.44,
135.95, 135.46, 133.93, 133.92, 129.01, 128.92, 61.77, 61.75,
51.65, 51.39, 28.30, 27.75, 14.10, 13.97.
HRMS (ESI): m/z [M+ + 23] calcd for C23H24NaO8: 451.1363;
found: 451.1382.
Dimethyl 2,4-Bis(1,3-benzodioxol-5-ylcarbonyl)pentanedioate
(2h)
White solid; yield: 93 mg (82%); two diastereomers (1.5:1).
Dimethyl 2,4-Dibenzoylpentanedioate (2b)
White solid; yield: 72 mg (78%); two diastereomers (1.8:1).
1H NMR (400 MHz, CDCl3): δ = 7.72–7.66 (m, 2 H), 7.50 (dd, J1 =
7.6 Hz, J2 = 1.2 Hz, 2 H), 6.87 (dd, J1 = 9.6 Hz, J2 = 8.4 Hz, 2 H),
6.07 (d, J = 6.0 Hz, 4 H), 4.54 (t, J = 7.2 Hz, 1 H), 4.45 (t, J = 7.6
Hz, 1 H), 3.75 (s, 4 H), 3.65 (s, 2 H), 2.72–2.50 (m, 2 H).
13C NMR (101 MHz, CDCl3): δ = 193.32, 192.83, 170.41, 170.01,
152.68, 152.66, 148.59, 148.53, 130.69, 130.22, 125.92, 125.74,
108.63, 108.59, 108.27, 102.20, 102.17, 52.76, 51.24, 50.99, 28.89,
28.26.
1H NMR (601 MHz, CDCl3): δ = 8.05 (dd, J1 = 7.2 Hz, J2 = 1.2 Hz,
4 H), 7.63–7.58 (m, 2 H), 7.52–7.47 (m, 4 H), 4.67 (t, J = 7.2 Hz, 1
H), 4.58 (t, J = 7.2 Hz, 1 H), 3.75 (s, 4 H), 3.64 (s, 2 H), 2.77–2.55
(m, 2 H).
13C NMR (151 MHz, CDCl3): δ = 195.22, 194.82, 170.33, 169.93,
135.89, 135.42, 134.05, 134.03, 129.08, 129.01, 128.98, 128.87,
52.78, 51.41, 51.16, 28.47, 27.93.
HRMS (ESI): m/z [M+ + 23] calcd for C23H20NaO10: 479.0949;
found: 479.0969.
Dimethyl 2,4-Bis(4-methylbenzoyl)pentanedioate (2c)
White solid; yield: 66 mg (67%); two diastereomers (1.2:1).
1H NMR (400 MHz, CDCl3): δ = 7.94 (d, J = 8.0 Hz, 4 H), 7.27 (d,
J = 8.0 Hz, 4 H), 4.64–4.52 (m, 2 H), 3.74 (s, 5 H), 3.63 (s, 1 H),
2.74–2.52 (m, 2 H), 2.42 (d, J = 8.8 Hz, 6 H).
13C NMR (101 MHz, CDCl3): δ = 194.82, 170.44, 145.03, 132.99,
129.68, 129.21, 52.72, 51.36, 28.59, 21.85.
Dimethyl 2,4-Bis(4-fluorobenzoyl)pentanedioate (2i)
White solid; yield: 70 mg (69%); two diastereomers (2.1:1).
1H NMR (400 MHz, CDCl3): δ = 8.14–8.08 (m, 4 H), 7.20–7.14 (m,
4 H), 4.63 (t, J = 8.0 Hz, 1 H), 4.53 (t, J = 8.0 Hz, 1 H), 3.76 (s, 4
H), 3.65 (s, 2 H), 2.75–2.50 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 193.70, 193.22, 170.25, 169.74,
167.67, 165.12, 131.98, 131.88, 116.35, 116.14, 52.90, 51.31,
51.08, 28.45, 27.77.
Dimethyl 2,4-Bis(4-methoxybenzoyl)pentanedioate (2d)
White solid; yield: 94 mg (88%); two diastereomers (1.4:1).
1H NMR (400 MHz, CDCl3): δ = 8.06 (d, J = 8.8 Hz, 4 H), 6.99–
6.93 (m, 4 H), 4.60 (t, J = 7.2 Hz, 1 H), 4.52 (t, J = 7.6 Hz, 1 H),
3.89 (d, J = 7.6 Hz, 6 H), 3.75 (s, 3 H), 3.64 (s, 3 H), 2.75–2.51 (m,
2 H).
13C NMR (101 MHz, CDCl3): δ = 193.79, 193.34, 170.63, 170.17,
164.29, 131.57, 131.47, 128.92, 128.41, 114.20, 55.70, 55.68,
52.71, 51.25, 50.96, 28.86, 28.20.
Dimethyl 2,4-Bis(4-chlorobenzoyl)pentanedioate (2j)
White solid; yield: 80 mg (73%); two diastereomers (5.4:1).
1H NMR (400 MHz, CDCl3): δ = 8.01 (d, J = 8.4 Hz, 4 H), 7.47 (t,
J = 8.8 Hz, 4 H), 4.60 (t, J = 7.2 Hz, 2 H), 3.75 (s, 6 H), 2.73–2.50
(m, 2 H).
13C NMR (101 MHz, CDCl3): δ = 194.03, 170.09, 140.78, 133.72,
130.50, 129.40, 73.08, 52.98, 51.29, 28.30.
Dimethyl 2,4-Bis(4-ethoxybenzoyl)pentanedioate (2e)
White solid; yield: 104 mg (91%); two diastereomers (1.1:1).
Dimethyl 2,4-Bis(4-bromobenzoyl)pentanedioate (2k)
White solid; yield: 67 mg (51%); two diastereomers (2.5:1).
1H NMR (400 MHz, CDCl3): δ = 8.04 (d, J = 8.8 Hz, 4 H), 6.93 (dd,
J1 = 15.2 Hz, J2 = 8.8 Hz, 4 H), 4.60 (t, J = 7.2 Hz, 1 H), 4.51 (t,
J = 7.2 Hz, 1 H), 4.11 (dq, J1 = 14.2 Hz, J2 = 7.2 Hz, 4 H), 3.75 (s,
3 H), 3.64 (s, 3 H), 2.75–2.51 (m, 2 H), 1.45 (m, 6 H).
13C NMR (101 MHz, CDCl3): δ = 193.77, 193.32, 170.63, 170.19,
163.72, 131.55, 131.45, 128.70, 128.20, 114.60, 114.59, 64.01,
63.98, 52.68, 51.20, 50.92, 28.88, 28.21, 14.78, 14.77.
1H NMR (601 MHz, CDCl3): δ = 7.92–7.90 (m, 4 H), 7.66–7.62 (m,
4 H), 4.59 (t, J = 7.2 Hz, 1 H), 4.50 (t, J = 7.2 Hz, 1 H), 3.75 (s, 4
H), 3.64 (s, 2 H), 2.72–2.51 (m, 2 H).
13C NMR (151 MHz, CDCl3): δ = 194.23, 193.82, 170.05, 169.61,
134.60, 134.17, 132.41, 130.55, 130.45, 129.59, 129.53, 52.92,
51.24, 51.08, 28.24, 27.64.
HRMS (ESI): m/z [M+ + 23] calcd for C25H28NaO8: 479.1676;
found: 479.1687.
2,4-Dibenzoyl-1,5-diphenylpentane-1,5-dione (2l)
White solid; yield: 53 mg (46%).
Dimethyl 2,4-Bis(4-morpholinobenzoyl)pentanedioate (2f)
White solid; yield: 124 mg (92%); two diastereomers (1.2:1).
1H NMR (400 MHz, CDCl3): δ = 8.00 (d, J = 9.2 Hz, 4 H), 6.87 (dd,
J1 = 12.8 Hz, J2 = 8.8 Hz, 4 H), 4.58 (t, J = 7.2 Hz, 1 H), 4.50 (t,
J = 7.2 Hz, 1 H), 3.85 (d, J = 3.6 Hz, 8 H), 3.74 (s, 3 H), 3.63 (s, 3
H), 3.35–3.32 (m, 8 H), 2.74–2.50 (m, 2 H).
1H NMR (400 MHz, CDCl3): δ = 8.15 (d, J = 7.6 Hz, 7 H), 7.58 (t,
J = 6.8 Hz, 4 H), 7.48 (t, J = 7.6 Hz, 9 H), 5.75 (t, J = 6.8 Hz, 2 H),
2.76 (t, J = 6.8 Hz, 2 H).
13C NMR (101 MHz, CDCl3): δ = 196.72, 135.54, 134.03, 129.17,
128.95, 54.11, 29.06.
13C NMR (101 MHz, CDCl3): δ = 193.27, 192.82, 170.82, 170.34,
154.68, 154.66, 131.28, 131.20, 126.28, 125.75, 113.30, 66.56,
52.53, 51.09, 50.69, 47.30, 29.01, 28.33.
3,5-Dibenzoylheptane-2,6-dione (2m)
White solid; yield: 35 mg (41%); two diastereomers (1:1).
Synthesis 2014, 46, 2445–2450
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Iodine-Catalyzed C–N Cleavage of Tertiary Amines
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1H NMR (601 MHz, CDCl3): δ = 8.07 (dd, J1 = 7.2 Hz, J2 = 1.2 Hz,
2 H), 8.03 (dd, J1 = 7.2 Hz, J2 = 0.6 Hz, 2 H), 7.64–7.61 (m, 2 H),
7.58–7.48 (m, 4 H), 4.71 (t, J = 6.6 Hz, 1 H), 4.64 (t, J = 6.6 Hz, 1
H), 2.61–2.46 (m, 2 H), 2.19 (s, 3 H), 2.15 (s, 3 H).
13C NMR (151 MHz, CDCl3): δ = 204.07, 203.53, 196.79, 196.57,
136.15, 135.84, 134.22, 129.20, 129.15, 129.08, 128.99, 59.57,
59.40, 29.56, 29.25, 27.59, 27.23.
A.; Mahon, M. F.; Abu Naser, M.; Vélez, A.; Whittlesey, M.
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Lobkovsky, E. B. J. Am. Chem. Soc. 1996, 118, 5132.
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Fouquet, E. Tetrahedron 2011, 67, 2815. (b) Taylor, J. G.;
Moro, A. V.; Correia, C. R. D. Eur. J. Org. Chem. 2011,
1403.
Dimethyl 2,4-Di(2-naphthoyl)pentanedioate (2n)
(5) (a) Hoerter, J. M.; Otte, K. M.; Gellman, S. H.; Cui, Q.;
Stahl, S. S. J. Am. Chem. Soc. 2008, 130, 647. (b) Liu, C.-R.;
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Lett. 2011, 13, 6308.
White solid; yield: 80 mg (68%); two diastereomers (1.1:1).
1H NMR (400 MHz, CDCl3): δ = 8.63 (d, J = 12.0 Hz, 2 H), 8.12 (d,
J = 20.0 Hz, 1 H), 8.05–8.02 (m, 2 H), 7.94–7.92 (d, J = 8.0 Hz, 2
H), 7.89–7.82 (m, 3 H), 7.65–7.49 (m, 4 H), 4.85 (t, J = 8.0 Hz, 1
H), 4.79 (t, J = 8.0 Hz, 1 H), 3.78 (s, 3 H), 3.64 (s, 3 H), 2.93–2.69
(m, 2 H).
13C NMR (101 MHz, CDCl3): δ = 195.22, 194.74, 170.36, 170.06,
136.04, 135.97, 133.21, 132.78, 132.65, 132.56, 131.43, 131.25,
130.08, 130.04, 129.15, 129.08, 128.91, 128.85, 127.89, 127.79,
127.10, 126.98, 124.20, 124.11, 52.87, 52.81, 51.46, 51.33, 28.83,
28.24.
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(b) Zhao, X.; Liu, D.; Guo, H.; Liu, Y.; Zhang, W. J. Am.
Chem. Soc. 2011, 133, 19354. (c) Li, B.-J.; Wang, H.-Y.;
Zhu, Q.-L.; Shi, Z.-J. Angew. Chem. Int. Ed. 2012, 51, 3948.
(d) Li, M.-B.; Wang, Y.; Tian, S.-K. Angew. Chem. Int. Ed.
2012, 51, 2968. (e) Krackl, S.; Someya, C. I.; Enthaler, S.
Chem. Eur. J. 2012, 18, 15267. (f) Wang, Y.; Chi, Y.;
Zhang, W.-X.; Xi, Z. J. Am. Chem. Soc. 2012, 134, 2926.
(g) Huang, H.; Ji, X.; Wu, W.; Huang, L.; Jiang, H. J. Org.
Chem. 2013, 78, 3774. (h) Liang, D.; He, Y.; Liu, L.; Zhu,
Q. Org. Lett. 2013, 15, 3476. (i) Li, Y.; Guo, F.; Zha, Z.;
Wan, Z. Chem. Asian J. 2013, 8, 534. (j) Szostak, M.; Spain,
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49, 9039. (l) Hao, Q.; Miao, T.; Zhang, X. Org. Biomol.
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2,4-Dibenzoyl-1,5-dimorpholinopentane-1,5-dione (2o)
White solid; yield: 85 mg (71%); two diastereomers (3:1).
1H NMR (601 MHz, CDCl3): δ = 8.15 (d, J = 1.2 Hz, 1 H), 8.12–
8.08 (m, 3 H), 7.63 (t, J = 7.2 Hz, 1 H), 7.58 (t, J = 7.2 Hz, 1 H),
7.54 (t, J = 7.8 Hz, 1 H), 7.49 (t, J = 7.8 Hz, 3 H), 4.90–4.84 (m, 2
H), 3.74–3.56 (m, 16 H), 2.75–2.25 (m, 2 H).
13C NMR (151 MHz, CDCl3): δ = 196.32, 196.25, 168.70, 168.65,
135.61, 135.41, 134.01, 129.21, 129.16, 128.68, 66.87, 66.76,
66.67, 49.56, 49.52, 46.49, 46.36, 42.67, 42.55, 29.06, 28.94.
HRMS (ESI): m/z [M+ + 23] calcd for C27H30N2NaO6: 501.1996;
found: 501.2001.
(8) (a) Zhang, L.; Peng, C.; Zhao, D.; Wang, Y.; Fu, H.-J.; Shen,
Q.; Li, J.-X. Chem. Commun. 2012, 48, 5928. (b) Chen, J.;
Liu, B.; Liu, D.; Liu, S.; Cheng, J. Adv. Synth. Catal. 2012,
354, 2438. (c) Zhao, D.; Wang, Y.; Zhu, M.-X.; Shen, Q.;
Zhang, L.; Du, Y.; Li, J.-X. RSC Adv. 2013, 3, 10272.
(9) Balamurugan, R.; Manojveer, S. Chem. Commun. 2011, 47,
11143.
Acknowledgment
We acknowledge financial support from the National Key Basic Re-
search Program of MOST of China (2012CBA01204) and the Na-
tional Natural Science Foundation of China (21302084).
(10) Wu, W.; Su, W. J. Am. Chem. Soc. 2011, 133, 11924.
(11) (a) Liu, Y.; Yao, B.; Deng, C.-L.; Tang, R.-Y.; Zhang, X.-
G.; Li, J.-H. Org. Lett. 2011, 13, 2184. (b) Tang, R.-Y.; Guo,
X.-K.; Xiang, J.-N.; Li, J.-H. J. Org. Chem. 2013, 78, 11163.
(12) Li, L.-T.; Huang, J.; Li, H.-Y.; Wen, L.-J.; Wang, P.; Wang,
B. Chem. Commun. 2012, 48, 5187.
Supporting Information for this article is available online
at
http://www.thieme-connect.com/products/ejournals/journal/
10.1055/s-00000084.SunpfgIpi
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