Ph3P-mediated tandem synthesis of functionalized cyclopentadienes from primary alkylamines and acetylenic esters

Article abstract of DOI:10.1055/s-0030-1258027

Dialkyl 4-[alkyl(alkoxycarbonyl)amino]-3-alkoxy-1,3-cyclopentadiene-1,2- dicarboxylates are obtained in good yields via a tandem reaction between triphenylphosphine, primary alkylamines, and acetylenic esters in dichloromethane in the absence of catalyst. Georg Thieme Verlag Stuttgart - New York.

Full text of DOI:10.1055/s-0030-1258027

LETTER
2293
Ph3P-Mediated Tandem Synthesis of Functionalized Cyclopentadienes from
Primary Alkylamines and Acetylenic Esters
S
ynthesi
s
s
of Funct
s
ionalized
aCyclopentadienesYavari,* Mohammad J. Bayat
Chemistry Department, Tarbiat Modares University, PO Box 14115-175, Tehran, Iran
Fax +98(21)88006544; E-mail: yavarisa@modares.ac.ir
Received 14 June 2010
which the structural prerequisite is absent in the initial
substrate is triggered by the first reaction.
Abstract: Dialkyl 4-[alkyl(alkoxycarbonyl)amino]-3-alkoxy-1,3-
cyclopentadiene-1,2-dicarboxylates are obtained in good yields via
a tandem reaction between triphenylphosphine, primary alky-
lamines, and acetylenic esters in dichloromethane in the absence of
catalyst.
As part of our current studies on the development of new
multicompnenent reactions to synthesize novel functional
carbocycles and heterocycles,6–9 we report herein a facile
one-pot synthesis of dialkyl 3-alkoxy 4-[alkyl(alkoxycar-
bonyl)amino]-1,3-cyclopentadiene-1,2-dicarboxylates 4
via the reaction between triphenylphosphine, dialkyl acet-
ylenedicarboxylates 1 and 3, and primary alkylamines 2 in
CH2Cl2 at room temperature in good yields10 (Table 1).
Key words: primary alkylamine, acetylenic ester, 1,3-cyclopenta-
diene, tandem reaction
Tandem reactions that require in situ generation of reac-
tive species are a special type of organic reaction in which
the products are formed by sequential reactions1–5 and can
lead to skeletal changes rather than merely functional-
group transformations when the subsequent reaction for
The structures of compounds 4 were assigned on the basis
of spectroscopic data. The 1H NMR and 13C NMR spectra
of the crude products clearly indicated the formation of di-
Table 1 Reaction of Ph3P, Acetylenic Esters, and Primary Alkylamines
R3
N
CO2R1
CO2R2
O
CH2Cl2, r.t
CO2R1
CO2R1
+
R3NH2
Ph P
3
+
+
– Ph3PO
24 h
R2O
CO2R1
R2O
CO2R2
1a,b
2a–f
3a,b
4a–m
Acetylenedicarboxylate 1
Amine 2
Acetylenedicarboxylate 3
Product 4
Yield (%)
R1
R3
R2
1a
1a
1a
1a
1a
1a
1b
1b
1b
1b
1b
1b
1a
Me
Me
Me
Me
Me
Me
Et
2a
2b
2c
2d
2e
2f
C6H5CH2
3a
3a
3a
3a
3a
3a
3b
3a
3a
3a
3a
3a
3b
Me
Me
Me
Me
Me
Me
Et
4a
4b
4c
4d
4e
4f
71
78
80
65
62
67
59
75
77
73
63
69
67
4-MeC6H4CH2
4-MeOC6H4CH2
2-ClC6H4CH2
1-C10H7CH2
n-Bu
2a
2a
2c
2d
2e
2f
C6H5CH2
4g
4h
4i
Et
C6H5CH2
Me
Me
Me
Me
Me
Et
Et
4-MeOC6H4CH2
2-ClC6H4CH2
1-C10H7CH2
n-Bu
Et
4j
Et
4k
4l
Et
Me
2a
C6H5CH2
4m
SYNLETT 2010, No. 15, pp 2293–2295
x
x
.x
x
.2
0
1
0
Advanced online publication: 09.08.2010
DOI: 10.1055/s-0030-1258027; Art ID: D14710ST
© Georg Thieme Verlag Stuttgart · New York

2294
I. Yavari, M. J. Bayat
LETTER
alkyl 3-alkoxy 4-[alkyl(alkoxycarbonyl)amino]-1,3- tained. This result supports the proposed mechanism
cyclopentadiene-1,2-dicarboxylates 4 with no other prod- shown in Scheme 1.
uct other being identified in the reaction mixture.
In conclusion, we have reported the synthesis of highly
The 1H NMR spectrum of 4a exhibited six sharp singlets functionalized cyclopenta-1,3-dienes via a tandem reac-
readily recognized as arising from methylene (d = 3.52 tion between Ph3P, primary alkylamines, and dialkyl acet-
and 5.50 ppm) and methoxy (d = 3.58, 3.76, 3.84, and ylenedicarboxylates in CH2Cl2. This tandem protocol may
3.89 ppm) protons along with characteristic resonances be considered as a practical route for the synthesis of func-
for the phenyl group. The 13C NMR spectrum of 4a tionalized 1,3-cyclopentadine ring systems.
showed 17 distinct resonances in agreement with the pro-
posed structure. The H NMR and 13C NMR spectra of
4b–m are similar to those for 4a, except for the alkyl and
ester groups, which showed characteristic signals in ap-
1
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
propriate regions of the spectra. The mass spectra of com-
pounds 4 displayed molecular ion peaks at appropriate
m/z values.
References and Notes
(1) Mukaiyama, T. Challenges in Synthetic Organic Chemistry;
Clarendon Press: Oxford, 1990.
(2) Ho, T.-L. Tandem Organic Reactions; John Wiley and Sons:
New York, 1992.
(3) Ho, T.-L. Tactics of Organic Synthesis; John Wiley and
Sons: New York, 1994.
(4) Serratosa, F.; Xicart, J. Organic Chemistry in Action: The
Design of Organic Synthesis; Elsevier: New York, 1996.
(5) Smith, W. A.; Bochkov, A. F.; Caple, R. Organic Synthesis:
The Science behind the Art; RSC: Cambridge / UK, 1998.
(6) Yavari, I.; Khalili, G.; Mirzaei, A. Tetrahedron Lett. 2010,
51, 1190.
(7) Yavari, I.; Mirzaei, A.; Moradi, L.; Khalili, G. Tetrahedron
Lett. 2010, 51, 396.
(8) Yavari, I.; Souri, S.; Sirouspour, M.; Bayat, M. J. Synlett
2009, 1921.
Although the mechanistic details of the reaction have not
been elucidated, a plausible rationalization may be ad-
vanced to explain the product formation. Presumably, the
zwitterionic intermediate 5, generated from Ph3P and
acetylenic ester 1, is trapped by the enaminoester 6, gen-
erated in situ from the corresponding alkylamine 2 and
acetylenic ester 3,11 to produce intermediates 7 and 8
(Table 1). Nucleophilic attack of the conjugate base 7 on
intermediate 8 leads to an adduct 9, which undergoes in-
tramolecular Wittig reaction to afford imino-cyclopentene
derivative 10. Intermediate 10 undergoes a [1,5]-H shift to
generate 11, which is converted to 4 via the bicyclic tetra-
hedral intermediate 12.
(9) Yavari, I.; Piltan, M.; Moradi, L. Tetrahedron 2009, 65,
2067.
+
2
3
(10) Compounds 4a–g – General Procedure
To a stirred solution of amine 2 (2 mmol) and the acetylenic
ester (4 mmol) in CH2Cl2 (10 mL), was added Ph3P (0.53 g,
2 mmol) at 0 °C, and the mixture was allowed to reach r.t.
After completion of the reaction (6–12 h; TLC monitoring,
EtOAc–hexane = 1:4), the solvent was evaporated, and the
residue was purified by column chromatography (silica gel
(230–400 mesh; Merck), hexane–EtOAc = 5:1): pure
product.
CO2R2
R3HN
CHCO2R2
CO2R
CO2R
CHCO2R2
+
CHCO2R1
CO2R1
6
Ph P
+ 2
3
3 Ph3P
Ph3P
R2O2C
NR
5
7
8
R2O2C
R2O2C
R3N
Dimethyl 4-[Benzyl(methoxycarbonyl)amino]-3-
methoxy-1,3-cyclopentadiene-1,2-dicarboxylate (4a)
Yellow oil; yield 0.53 g (71%). IR (KBr): nmax = 1732, 1707,
1625, 1560, 1506, 1451, 1409, 1282, 1248, 1151, 1090, 742,
687 cm–1. 1H NMR (500.1 MHz, CDCl3): d = 3.52 (2 H, s,
CH2), 3.58, 3.76, 3.84, 3.89 (12 H, s, 4 MeO), 5.50 (2 H, s,
CH), 6.97 (2 H, d, 3J = 7.8 Hz, CH), 7.25–7.32 (3 H, m, CH)
ppm. 13C NMR (125.7 MHz, CDCl3): d = 29.3 (CH2), 48.8,
51.8, 52.0, 52.2 (4 MeO), 63.0 (CH2N), 113.6 (C), 120.1 (C),
121.0 (C), 125.9 (2 CH), 127.4 (CH), 128.7 (2 CH), 136.7
(C), 143.9 (C), 161.0 (COO), 164.9 (COO), 169.5 (COO)
ppm. MS: m/z (%) = 376 (7) [M+ + 1], 375 (22) [M+], 361
(4), 344 (10), 311 (11), 284 (5), 91 (75), 77 (21), 59 (11).
Anal. Calcd for C19H21NO7 (375.37): C, 60.80; H, 5.64; N,
3.73. Found: C, 61.1; H, 5.7; N, 3.7.
CO2R1
CO2R1
CO2R1
Wittig reaction
R3N
[1,5]-H shift
– POPh3
CO2R1
R2O
O
R2O
PPh3
9
10
R2O2C
O
OR2
CO2R1
CO2R1
CO2R1
CO2R1
R3HN
R3HN
4
R2O
R2O
11
12
Scheme 1 A proposed mechanism of the reaction
Compounds 4h–m – General Procedure
According to this mechanism, the formation of a single
product when two different alkynes are used (Table 1,
compounds 4h–m), is presumably controlled by the se-
quence in which the reaction is carried out. When the eth-
yl and methyl substituents of the acetylenedicarboxylates
are reversed, two different products 4h and 4m were ob-
To a stirred solution of amine 2 (2 mmol) and the first
acetylenic ester (2 mmol) in CH2Cl2 (10 mL), was
simultaneously added Ph3P (0.52 g, 2 mmol) and the second
acetylenic ester (2 mmol) at 0 °C. The mixture was then
allowed to reach r.t. After completion of the reaction (6–12
h; TLC monitoring, EtOAc–hexane = 1:4), the solvent was
evaporated, and the residue was purified by column
Synlett 2010, No. 15, 2293–2295 © Thieme Stuttgart · New York

LETTER
chromatography [silica gel (230–400 mesh; Merck),
Synthesis of Functionalized Cyclopentadienes
2295
Dimethyl 4-[Benzyl(ethoxycarbonyl)amino]-3-ethoxy-
1,3-cyclopentadiene-1,2-dicarboxylate (4m)
hexane–EtOAc = 5:1]: pure product.
Diethyl 4-[Benzyl(methoxycarbonyl)amino]-3-methoxy-
1,3-cyclopentadiene-1,2-dicarboxylate (4h)
Pale yellow oil; yield 0.54 g (67%). IR (KBr): nmax = 1738,
1714, 1630, 1590, 1513, 1458, 1421, 1291, 1247, 1155,
1099, 745, 690 cm–1. 1H NMR (500.1 MHz, CDCl3): d = 1.19
(3 H, t, 3J = 7.1 Hz, Me), 1.30 (3 H, t, 3J = 7.1 Hz, Me), 3.49
(2 H, s, CH2), 3.76, 3.87 (6 H, s, 2 MeO), 4.02 (2 H, q,
3J = 7.1 Hz, CH2O), 4.04 (2 H, q, 3J = 7.1 Hz, CH2O), 5.50
(2 H, s, CH2N), 6.94 (2 H, d, 3J = 7.3 Hz, CH), 7.23 (1 H, t,
Pale yellow oil; yield 0.60 g (75%). IR (KBr): nmax = 1735,
1704, 1629, 1596, 1503, 1452, 1416, 1280, 1247, 1150,
1094, 744, 693 cm–1. 1H NMR (500.1 MHz, CDCl3): d = 1.26
(3 H, t, 3J = 7.1 Hz, Me), 1.38 (3 H, t, 3J = 7.1 Hz, Me), 3.52
(2 H, s, CH2), 3.58, 3.85 (6 H, s, 2 MeO), 4.22 (2 H, q,
3J = 7.1 Hz, CH2O), 4.36 (2 H, q, 3J = 7.1 Hz, CH2O), 5.50
(2 H, s, CH2N), 6.98 (2 H, d, 3J = 7.3 Hz, CH), 7.25 (1 H, t,
3J = 7.2 Hz, CH), 7.28 (2 H, t, 3J = 7.2 Hz, CH) ppm. 13
C
NMR (125.7 MHz, CDCl3): d = 14.0 (Me), 15.3 (Me), 29.6
(CH2), 48.8, 51.9 (2 MeO), 52.0, 61.3 (2 OCH2), 71.5
(CH2N), 114.5 (C), 121.1 (C), 121.8 (C), 125.9 (2 CH),
127.4 (CH), 128.7 (2 CH), 135.8 (C), 144.7 (C), 161.5
(COO), 163.4 (COO), 168.5 (COO) ppm. MS: m/z
(%) = 404 (8) [M+ + 1], 403 (17) [M+], 389 (4), 372 (6), 325
(11), 91 (70), 77 (22), 73 (12), 59 (9). Anal. Calcd for
C21H25NO7 (403.42): C, 62.52; H, 6.25; N, 3.47. Found: C,
62.7; H, 6.4; N, 3.6.
3J = 7.2 Hz, CH), 7.31 (2 H, t, 3J = 7.2 Hz, CH) ppm. 13
C
NMR (125.7 MHz, CDCl3): d = 13.9 (Me), 14.1 (Me), 28.9
(CH2), 48.7, 52.2 (2 MeO), 60.8, 60.9 (2 OCH2), 63.0
(CH2N), 114.0 (C), 120.1 (C), 120.8 (C), 125.9 (2 CH),
127.4 (CH), 128.6 (2 CH), 136.8 (C), 143.7 (C), 160.6
(COO), 164.5 (COO), 169.6 (COO) ppm. MS: m/z
(%) = 404 (12) [M+ + 1], 403 (28) [M+], 389 (4), 372 (6), 325
(13), 312 (5), 91 (75), 77 (25), 73 (16), 59 (12). Anal. Calcd
for C21H25NO7 (403.42): C, 62.52; H, 6.25; N, 3.47. Found:
C, 62.4; H, 6.3; N, 3.5.
(11) Yavari, I.; Shaabani, A.; Soleimani, H.; Nourmohammadian,
F.; Bijanzadeh, H. R. Magn. Reson. Chem. 1996, 34, 1003.
Synlett 2010, No. 15, 2293–2295 © Thieme Stuttgart · New York

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