Metal-free Csp3-N bond cleavage of amides using tert-butyl hydroperoxide as oxidant

Article abstract of DOI:10.1055/s-0034-1379879

A mild and efficient protocol for the metal-free C-N bond-cleavage of amides has been developed. The methodology employs iodine as a catalyst to cleave the C(Me)-N bond of dimethylformamide or dimethylacetamide, providing novel access to methylene-bridged bis-1,3-dicarbonyl compounds instead of enol carbamates in the presence of tert-butyl hydroperoxide.

Full text of DOI:10.1055/s-0034-1379879

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© Georg Thieme Verlag Stuttgart · New York
2015, 26, 543–546
letter
543
S. Guo et al.
Letter
Synlett
Metal-Free Csp3–N Bond Cleavage of Amides Using tert-Butyl
Hydroperoxide as Oxidant
Shengmei Guo
O
O
O
I2 (5 mol%)
TBHP (0.6 equiv)
Zheng Zhu
Lin Lu
O
O
Ar
Ar
R
R
+ DMAc
100 °C, 24 h, N2
Ar
R
Wenbiao Zhang
Jiuhan Gong
Hu Cai*
O
College of Chemistry, Nanchang University, Nanchang, Jiangxi
330031, P. R. of China
caihu@ncu.edu.cn
Received: 30.10.2014
Accepted after revision: 24.11.2014
Published online: 08.01.2015
The synthesis of methylene-bridged compounds has re-
ceived increasing attention in recent years. Among the pre-
vious reports, tertiary amines served as a carbon source
through metal-catalyzed cross-dehydrogenative coupling
(CDC) reaction. Common solvents were rarely utilized as a
carbon source except for a recent example, in which nitro-
methane severed as a carbon source under the catalysis of
AuCl3 or Cu(OTf)2.10 Very recently, we developed a metal-
free methylenation of β-keto esters and diketone with
N,N,N,N-tetramethylethane-1,2-diamine (TMEDA) severing
as the carbon source.11 Therefore, in a continuation of our
efforts in this field, β-keto esters were chosen as the reac-
tion partner to accept the C–N bond-cleavage fragment of
DMF or DMA. This reaction system has been reported to
proceed in the present of a copper catalyst.12
Initially, ethyl 3-oxo-3-phenylpropanoate and DMF
were chosen as the model substrates to optimize the reac-
tion conditions. As summarized in Table 1, the reaction
gave a trace amount of the desired product without catalyst
using K2S2O8 as the oxidant at 100 °C for 24 h under a nitro-
gen atmosphere (Table 1, entry 1). In the presence of KI (20
mol%), the reaction provided 2a in encouraging yield (13%
yield; entry 2). Further screening of a range of iodine spe-
cies revealed I2 to be superior, forming 2a in 18% yield (en-
tries 3 and 4).
When hypervalent iodine reagents such as ICl and
PhI(OAc)2 were used as catalysts, no product was detected,
which indicates that the reaction does not proceed through
a hypervalent iodine mediated process (Table 1, entries 5
and 6). When DMA was employed as the reaction partner,
the reaction proceeded more efficiently than with DMF,
providing 2a in 29% yield (entry 7). Therefore, various oxi-
dants were screened to improve the yield with DMA as the
carbon source. When using an aqueous solution of TBHP,
the reaction resulted in an enhanced yield (45% yield; entry
8). Use of the oxidant BQ or TEMPO gave the desired prod-
uct in 41 or 30% yields, respectively (entries 9 and 10).
However, other oxidants such as DTBP, Oxone, DDQ, BPO,
and CAN or more environmentally friendly oxidants such as
air and O2, were found to be ineffective in the catalysis of
DOI: 10.1055/s-0034-1379879; Art ID: st-2014-w0902-l
Abstract A mild and efficient protocol for the metal-free C–N bond-
cleavage of amides has been developed. The methodology employs io-
dine as a catalyst to cleave the C(Me)–N bond of dimethylformamide or
dimethylacetamide, providing novel access to methylene-bridged bis-
1,3-dicarbonyl compounds instead of enol carbamates in the presence
of tert-butyl hydroperoxide.
Key words metal-free, C–N bond cleavage, amides, dicarbonyl com-
pounds, oxidation
Amides such as dimethylformamide (DMF) and dimethyl-
acetamide (DMA) are not only commonly utilized solvents
in organic chemistry, they are also significant reagents in
organic synthesis industry.1 For instance, DMF provides a
CHO group for aryl compounds through the cleavage of the
C–N bond in the Vilsmeier–Haack reaction.2 DMF can also
serve as an amino source in C–H amination of benzoxaz-
oles, pyrazinones, and others.3 Amides can also be em-
ployed as a CN source in cyanation reactions.4 Recently, ex-
tensive efforts have been directed toward the cleavage of
Csp3–N bonds of DMF or DMA. In 2012, Xu developed an
iron-catalyzed benzylic vinylation between 2-methyl
azaarenes and DMA or DMF.5 At the same time, Wang re-
ported an iron-catalyzed sp3 C–H functionalization of 2-
methyl quinolones by using DMF as carbon source in the
presence of tert-butyl hydroperoxide (TBHP).6 More recent-
ly, Xue and Xiao disclosed an α-methylation of ketones with
DMF using Rh salt as catalyst.7 Miura developed a copper-
catalyzed methylenation of benzylpyridines by using DMA
as the carbon source.8 Meanwhile, Lei developed a methy-
lenation of 1-aryl-pyridinemethanes/arylketones and DMF
under oxidative conditions.9 Among the reactions men-
tioned above, transition-metal catalysts were generally
necessary. Herein, we report on the metal-free Csp3–N
bond-cleavage of DMA and DMF by utilization of I2 as the
catalyst.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 543–546

544
S. Guo et al.
Letter
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Table 1 Screening the Reaction Conditionsa
The decrease in the loadings of both oxidant and catalyst
may avoid the oxidation of the β-keto esters, which might
account for the elevation in the yield.13
O
O
O
O
O
O
[I] (X mol%)
[O] (X equiv)
With the optimized reaction conditions in hand, we
next investigated the scope and limitations of this transfor-
mation. As summarized in Table 2, 1b gave the desired
product 2b in an isolated yield of 47% under the optimal
conditions (entry 2). The nature of the substitutes on the
benzene ring was examined, and the results showed that
the electronic effect was not significant; electron-with-
drawing groups such as NO2 resulted in formation of the
corresponding product with 41% yield, and groups such as
4-bromo, 4-chloro, and 4-fluoro on the benzene ring also
giving moderate yields (entries 3–6). Substrates bearing an
electron-donating group on the phenyl ring such as 4-Me
and 4-MeO were also transformed into the corresponding
product 2g and 2h in moderate yield under the same condi-
tions (entries 7 and 8). Application of substrate 1i, with 3-
MeO group on the benzene, also proceeded, giving the de-
sired product in 43% yield (entry 9). 2-Nathyl and 4-mor-
pholino substituted substrates gave 2g and 2h in 53 and
50% yields, respectively (entries 10 and 11). β-Keto amides
such as 1l could also undergo this reaction, affording the
Ph
OEt
OEt
+ DMF–DMA
OEt
Ph
100 °C, 24 h, N2 Ph
1a
2a
Entry
Catalyst
Solvent
DMF
Oxidant
Yield (%)b
1
2
–
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
TBHP
BQ
trace
13
KI
DMF
DMF
DMF
DMF
DMF
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
3
NIS
15
4
I2
18
5
ICl
–
6
PhI(OAc)2
–
7
I2
I2
I2
I2
I2
I2
I2
I2
I2
I2
I2
I2
I2
I2
I2
I2
I2
29
8
45
9
41
10
11
12
13
14
15
16
17
18c
19d
20e
21f
22g
23h
TEMPO
DTBP
Oxone
DDQ
30
trace
trace
trace
trace
–
Table 2 Reaction Scopea
CAN
O
O
BPO
I2 (5 mol%)
TBHP (0.6 equiv)
O
O
O2
trace
trace
39
Ar
Ar
R
R
+ DMA
Ar
R
air
100 °C, 24 h, N2
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
O
O
27
Entry
Ar
1
R
Yield (%)b dr
1.1:1
55
40
1
2
Ph
Ph
1a
1b
1c
1d
1e
1f
OEt
61 (2a)
47 (2b)
41 (2c)
51 (2d)
59 (2e)
50 (2f)
51 (2g)
57 (2h)
43 (2i)
53 (2j)
50 (2k)
30 (2l)
0 (2m)
0 (2n)
61
OMe
OEt
6:5
24
3
4-O2NC6H4
4-BrC6H4
1.1:1
1.3:1
1.3:1
4:3
a Reaction conditions: 1a (0.5 mmol), cat. (20 mol%), oxidant (1.2 equiv),
4
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OMe
morpholino
Ph
DMF–DMA (2.0 mL), 100 °C, 24 h, N2 atmosphere; BPO = benzoyl peroxide.
b Isolated yield.
c 120 °C.
5
4-ClC6H4
6
4-FC6H4
d 80 °C.
e TBHP (0.6 equiv).
f TBHP (2.0 equiv).
g I2 (5 mol%).
h I2 (1 mol%).
7
4-MeC6H4
4-MeOC6H4
3-MeOC6H4
2-naphthyl
1g
1h
1i
1:1
8
1.1:1
5:4
9
10
11
12
13
14
1j
1.3:1
1:1
4-morpholinophenyl
1k
1l
this transformation (entries 10–17). Evaluation of the effect
of temperature and the loading of TBHP suggested that per-
forming the reaction at 100 °C and with 0.6 equiv. of oxi-
dant was effective (entries 18–21). A decrease in the cata-
lyst loading from 20 to 5 mol% improved the yield of 2a to
61%, whereas a further decrease in catalyst loading to 1
mol% did not benefit the transformation (entries 21–22).
Ph
Ph
Me
6:5
1m
1n
OEt
a Reaction conditions: 1a (0.5 mmol), I2 (5 mol%), DMA (2 mL), TBHP (70%
aq; 45.0 μL), 100 °C, 24 h, N2 atmosphere.
b Isolated yield.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 543–546

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S. Guo et al.
Letter
Synlett
I2
TBHP
I–
I
O
O
O
O
TBHP
N
N
N
H
H
B
O
O
A
R1
OR2
O
O
O
O
O
R1
R1
OR2
OR2
Micheal addition
R1
OR2
C
O
Scheme 1 Proposed mechanism for C–N cleavage of DMA for the synthesis of bridged bis-1,3-dicarbonyl compounds
desired product 2l in 30% yield (entry 12). Unfortunately,
the diketone and alkyl β-keto ester did not undergo the re-
action (entries 13 and 14).
References and Notes
(1) (a) Brahma, S.; Ray, J. K. Tetrahedron 2008, 64, 2883. (b) Muzart,
J. Tetrahedron 2009, 65, 8313. (c) Ding, S. Angew. Chem. Int. Ed.
2012, 51, 9226.
The exact mechanism for the C–N cleavage of amides is
still not clear; however, a proposed mechanism is illustrat-
ed in Scheme 1. Firstly, iodine radical is generated through a
hemolytic reaction. Secondly, a radical relay occurs be-
tween the iodine radical and DMA to produce radical A,
which undergoes oxidation mediated by TBHP to afford
imine ions B. The latter undergoes hydrolysis to generate
formaldehyde, which is followed by an aldol reaction with
β-keto esters to form intermediate C. Finally, nucleophilic
attack of the β-keto esters on intermediate C affords to the
target products.5,9
In summary, a metal-free C–N cleavage of DMF and
DMA has been demonstrated.14 Methylene-bridged com-
pounds were obtained with moderate yields by using β-
keto esters as the fragment acceptor under the oxidative
conditions. Screening of the substrate scope showed that
the electronic effect of substituents onto the benzene ring
was weak. Further extension of the substrate scope and
study of the mechanism of this type of C–N cleavage are un-
der investigation in this lab.
(2) (a) Vilsmeier, A.; Haack, A. Ber. Dtsch. Chem. Ges. 1927, 60, 119.
(b) Cheung, G. K.; Downie, I. M.; Earle, M. J.; Heaney, H.;
Matough, M. F. S.; Shuhaibar, K. F.; Thomas, D. Synlett 1992, 77.
(c) Lanke, V.; Prabhu, K. P. Org. Lett. 2013, 15, 6262. (d) Naik, P.
N.; Khan, A.; Kusurkar, R. S. Tetrahedron 2013, 69, 10733.
(e) Pedras, M. S. C.; Yaya, E. E. Org. Biomol. Chem. 2013, 11, 1149.
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hedron Lett. 2014, 55, 2233. (b) Wang, J.; Hou, J.-T.; Wen, J.;
Zhang, J.; Yu, X.-Q. Chem. Commun. 2011, 47, 3652. (c) Li, Y.; Xie,
Y.; Zhang, R.; Jin, K.; Wang, X.; Duan, C. J. Org. Chem. 2011, 76,
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Int. Ed. 2009, 48, 9127. (e) Sharma, A.; Mehta, V. P.; Eychen, E. V.
Tetrahedron 2008, 64, 2605. (f) Agarwal, A.; Chauhan, P. M. S.
Synth. Commun. 2004, 34, 2925. (g) Gao, L.; Tang, H.; Wang, Z.
Chem. Commun. 2014, 50, 4085. (h) Zhang, X.; Wang, L. Green
Chem. 2012, 14, 2141.
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(b) Zhang, G.; Ren, X.; Chen, J.; Hu, M.; Cheng, J. Org. Lett. 2011,
13, 5004. (c) Kim, J.; Chang, S. J. Am. Chem. Soc. 2010, 132,
10272. (d) Ushijima, S.; Togo, H. Synlett 2010, 1067.
(e) Ushijima, S.; Togo, H. Synlett 2010, 1562. (f) Ishii, G.;
Moriyama, K.; Togo, H. Tetrahedron Lett. 2011, 52, 2404.
(5) Lou, S.-J.; Xu, D.-Q.; Shen, D.-F.; Wang, Y.-F.; Liu, Y.-K.; Xu, Z.-Y.
Chem. Commun. 2012, 48, 11993.
Acknowledgment
(6) Li, Y.; Guo, F.; Zha, Z.; Wang, Z. Chem. Asian J. 2013, 8, 534.
(7) Li, Y.; Xue, D.; Lu, W.; Wang, C.; Liu, Z.-T.; Xiao, J. Org. Lett. 2014,
16, 66.
(8) Itoh, M.; Hirano, K.; Satoh, T.; Miura, M. Org. Lett. 2014, 16,
2050.
This work was supported by the National Key Basic Research Program
of MOST of China (2012CBA01204), National Natural Science Founda-
tion of China (21302084).
(9) Liu, J.; Hong, Y.; Zhang, X.; Liu, C.; Liu, R.; Zhang, G.; Lei, A. Chem.
Commun. 2014, 50, 7636.
Supporting Information
(10) (a) Balamurugan, R.; Manojveer, S. Chem. Commun. 2011, 47,
11143. (b) Li, H.; He, Z.; Guo, X.; Li, W.; Zhao, X.; Li, Z. Org. Lett.
2009, 11, 4176. (c) Liu, W.; Liu, J. D.; Nishihara, O. Y.; Guo, X.; Li,
Z. Org. Lett. 2011, 13, 6272. (d) Yoo, W.-J.; Tanoue, A.; Kobayashi,
S. Chem. Asian J. 2012, 7, 2764. (e) Xu, X.; Ge, Z.; Cheng, D.; Li, X.
ARKIVOC 2012, (viii), 107. (f) Zhao, D.; Wang, Y.; Zhu, M.-X.;
Shen, Q.; Zhang, L.; Du, Y.; Li, J.-X. RSC Advances 2013, 3, 10272.
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0034-1379879.
S
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p
p
ortioInfgrmoaitn
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p
p
ortiInfogrmoaitn
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(g) Li, Y.; Ma, L.; Li, Z. Chin. J. Org. Chem. 2013, 33, 704. (h) He, Z.;
Liu, W.; Li, Z. Chem. Asian J. 2011, 6, 1340. (i) Zheng, G.; Ma, X.;
Liu, B.; Dong, Y.; Wang, M. Adv. Synth. Catal. 2014, 356, 743.
(11) Lu, L.; Guo, S.; Xiong, Q.; Liu, S.; Li, X.; Cai, H. Synthesis 2014, 46,
2445.
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.
(12) Kumar, S. G.; Maheswari, U. C.; Kumar, A. R.; Kantam, L. M.;
Reddy, R. K. Angew. Chem. Int. Ed. 2011, 50, 11748.
(13) Huang, L.; Cheng, K.; Yao, B.; Xie, Y.; Zhang, Y. J. Org. Chem.
2011, 76, 5732.
Dimethyl 2,4-bis(4-methylbenzoyl)pentanedioate (2g): Yield:
51%; 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), 4.52–4.64 (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-methoxybenzoyl)pentanedioate (2h):
Yield: 57%; two diastereomers (1.1:1). 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(3-methoxybenzoyl)pentanedioate (2i):
Yield: 43%; two diastereomers (5:4). 1H NMR (400 MHz, CDCl3):
δ = 7.66–7.61 (m, 2 H), 7.57 (s, 2 H), 7.39 (dt, J = 16.8, 8.0 Hz,
2 H), 7.19–7.09 (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.
(14) Preparation of 2a; Typical Procedure: A mixture of ethyl 3-
oxo-3-phenylpropanoate (0.5 mmol), iodine (6.4 mg, 0.025
mmol), DMA (2.0 mL), and 70% TBHP (32.0 μL) was stirred at
100 °C for 24 h under an N2 atmosphere. The reaction was mon-
itored by TLC. Upon completion, the reaction mixture was
poured into H2O (20 mL) and extracted with EtOAc (3 × 15 mL).
The organic phase was concentrated and the resulting crude
product was purified by column chromatography on silica gel
(petroleum ether–EtOAc, 10:1) to provide the desired com-
pound. The identity of the product and the diastereomer ratio
were determined by 1H NMR analysis.
Diethyl 2,4-dibenzoylpentanedioate (2a): Yield: 61%; two
diastereomers (1.1:1). 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.
Dimethyl 2,4-dibenzoylpentanedioate (2b): Yield: 47%; two
diastereomers (6:5). 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.
Diethyl 2,4-bis(4-nitrobenzoyl)pentanedioate (2c): Yield:
41%; two diastereomers (1.1:1). 1H NMR (400 MHz, CDCl3): δ =
8.34–8.37 (m, 4 H), 8.20–8.25 (m, 4 H), 4.66 (t, J = 8.0 Hz, 1 H),
4.55 (t, J = 8.0 Hz, 1 H), 4.21–4.25 (m, 2 H), 4.11–4.14 (m, 2 H),
2.54–2.79 (m, 2 H), 1.21 (t, J = 8.0 Hz, 3 H), 1.11 (m, 3 H).
Dimethyl 2,4-bis(4-bromobenzoyl)pentanedioate (2d): Yield:
51%; two diastereomers (1.3:1). 1H NMR (601 MHz, CDCl3): δ =
7.94–7.88 (m, 4 H), 7.67–7.60 (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.
Dimethyl 2,4-di(2-naphthoyl)pentanedioate (2j): Yield: 53%;
two diastereomers (1.3:1). H NMR (400 MHz, CDCl3): δ = 8.63
1
(d, J = 12.0, 2 H), 8.12 (d, J = 20.0 Hz, 2 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.
Dimethyl 2,4-bis(4-morpholinobenzoyl)pentanedioate (2k):
Yield: 50%; two diastereomers (1:1). 1H NMR (400 MHz, CDCl3):
δ = 8.00 (d, J = 9.2 Hz, 4 H), 6.87 (dd, J = 12.8, 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). 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.
2,4-Dibenzoyl-1,5-dimorpholinopentane-1,5-dione
(2l):
Yield: 30%; two diastereomers (6:5). 1H NMR (601 MHz, CDCl3):
δ = 8.15 (d, J = 7.8 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
Dimethyl 2,4-bis(4-chlorobenzoyl)pentanedioate (2e): Yield:
59%; two diastereomers (1.3:1). 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-fluorobenzoyl)pentanedioate (2f): Yield:
50%; two diastereomers (4:3). 1H NMR (400 MHz, CDCl3): δ =
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 543–546

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