Tributylphosphine, excellent organocatalyst for conjugate additions of non-nucleophilic N-containing compounds

Article abstract of DOI:10.1016/j.tet.2007.05.088

Conjugate additions of non-nucleophilic N-containing compounds such as amides, thioamides, sulfonamides, and electron-poor anilines with different Michael acceptors can be promoted through the use of tributylphosphine. The range of useful pK_a's of nucleophiles has been established (pK_a<25) and new insights into the mechanism proposed.

Full text of DOI:10.1016/j.tet.2007.05.088

Tetrahedron 63 (2007) 8305–8310
Tributylphosphine, excellent organocatalyst for conjugate
additions of non-nucleophilic N-containing compounds
!
Carolina Gimbert, Marcial Moreno-Manas, Elisabet Perez and Adelina Vallribera
*
ꢀ
˜
Department of Chemistry, Universitat Autoꢁnoma de Barcelona, Cerdanyola, 08193-Barcelona, Spain
Received 23 April 2007; revised 18 May 2007; accepted 22 May 2007
Available online 26 May 2007
Abstract—Conjugate additions of non-nucleophilic N-containing compounds such as amides, thioamides, sulfonamides, and electron-poor
anilines with different Michael acceptors can be promoted through the use of tributylphosphine. The range of useful pKa’s of nucleophiles has
been established (pKa<25) and new insights into the mechanism proposed.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
under a CsF–Si(OEt)4 system;13 intramolecular Michael
addition of urea to unsaturated esters has been described in
the presence of NaOH;14conjugate addition of 4-nitroaniline
and carbamic acid methyl ester to a,b-unsaturated com-
pounds can be mediated by RuCl3 in poly(ethylene
glycol).15
Conjugate additions constitute a powerful method for the
formation of carbon–carbon1 and carbon–heteroatom bonds.
Carbon–nitrogen bonds are especially valuable since the re-
sulting functionality can be readily transformed. For in-
stance, the b-aminocarbonyl group is a common moiety in
biologically active natural products such as alkaloids. To
avoid typical disadvantages resulting from the presence of
basic or acid catalysis, a variety of methods have been
used for the reaction of amines with poor alkenes as, for ex-
ample, promotion through the use of stoichiometric
CeCl3$7H2O–NaI system supported in silica gel2 or Li-
ClO4.3 Other research groups have described that conjugate
addition of amines of poor alkenes can be catalysed using
Lewis acids such as Bi(OTf)3,4 Bi(NO)35 or ZrOCl2$8H2O.6
From the point of view of recovering the catalyst the use of
Cu–Al hydrotalcite7 is proposed. Recently a green approach
using b-cyclodextrin in water8 or ionic liquids9 has been de-
veloped. Microwave-promoted synthesis of N-aryl b-amino-
esters have been recently described.10 Moreover asymmetric
aza-Michael reactions can be promoted using a Mg(II),
Cu(II), Ni(II) or Ti(IV) catalyst containing different chiral
ligands.11 While aza-Michael-type addition reactions of
amines to a,b-unsaturated substrates are well known, we
found no general method for non-nucleophilic N-containing
compounds such as amides, thioamides, sulfonamides, urea,
and electron-poor anilines. Few isolated examples can be
found: amides react efficiently with enones under a catalytic
Recently the scientific community has begun to appreciate
the great potential of organocatalysis,16 which is defined as
the acceleration of chemical reactions with a substoichio-
metric amount of an organic compound, and phosphines
have been recognized as a useful nucleophilic organocata-
lyst.17 We have previously described that triphenylphos-
phine and tributylphosphine are excellent catalysts for the
reaction of b-dicarbonyl compounds and electron-poor ole-
fins.18 The mechanism involves the so-called nucleophilic
phosphine catalysis (NPC), initiated by the nucleophilic at-
tack of the phosphine to the b-position of an activated alkene
or alkyne. The generated a-carbanion then reacts as a nucleo-
phile or as a base. The reaction of the phosphonium ylide
as a base affords the conjugated base of the dicarbonyls
(Fig. 1) that triggers the propagation steps as indicated. As
an extension we now want to describe a study on the use
of tributylphosphine for the conjugate addition of a selection
of non-nucleophilic N-containing compounds. Moreover
some NMR experiments have been carried out to bring
insights into the proposed mechanism.
12
amount of Pd(PhCN)2Cl2 and with unsaturated esters
2. Results and discussion
We selected a series of non-nucleophilic N-containing
compounds that were chosen as to embrace a broad diversity
of pKa’s (range of pKa’s 14–27 in dimethyl sulfoxide,19
Fig. 2) and studied their conjugate additions to different
activated alkenes under the presence of a catalytic amount
Keywords: Phosphine; Conjugate addition; Organocatalyst; C–N bond;
Mechanism.
* Corresponding author. Tel.: +34 935813045; fax: +34 935811265; e-mail:
adelina.vallribera@uab.es
Deceased on 20th February 2006.
!
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.05.088

8306
C. Gimbert et al. / Tetrahedron 63 (2007) 8305–8310
Moreover, thioacetamide 1d reacted with 2b and 2c to af-
R3P
+
R3P
R3P
Z
Z
ford di-N-alkylated adducts, albeit the excess of electro-
phile mono-alkylated adducts 3db (4%) and 3dc (9%)
being also isolated although in very low yields. In addi-
tion, compounds 4bb and 4cc (Scheme 2) being identified
by GC–MS (4bb: MS (m/z) 140 (M+), 100, 54; 4cc: MS
(m/z) 243 (M+), 160, 143) as subproducts of the reactions
corresponding to entries 6 and 7 of Table 2, respectively.
Formation of compounds 4 can be explained through the
mechanism proposed in Scheme 2, which is based on
the resonance stabilization of the thioacetamide conjugated
base.
Initiation
steps
R3P
NuH
+
+
Nu
Nu
+
Z
Z
Z
Nu
Nu
Nu
+
Z
Propagation
steps
Z
Z
+
NuH
Nu
Figure 1. Mechanism of nucleophilic phosphine catalysis.
Less acidic 4-nitroaniline 1e reacted with 2b and 2c although
yields were slightly lower. Then reactions of acetamide 1f
with acrylonitrile and diethyl vinylphosphonate were also
studied. In the case of acrylonitrile the mono-adduct was
identified but could not be completely purified. In the con-
trary, mono and di-adducts were isolated and purified in
the reactions with 2d. Even diphenylamine reacted at
140 ꢀC to afford 29% of 3gd. However urea (pKa¼26.9)
was inert in the same reaction conditions using 2c and 2d
as Michael acceptors.
O
S
O
S
H
N
NH2
H3C
NH2
NH
O
S
O
N
H
O
O
1c
1d
1b
1a
pKa= 18.45
pKa= 17.5
pKa= 16.0
O
pKa= 14.1
H
N
O
Some general trends can be established from a perusal of all
the results. First, yields are excellent for nucleophiles with
a pKa<20 (DMSO). Additionally, larger quantities of
mono-adduct compounds are obtained from less active nu-
cleophiles. Furthermore it is obvious that conjugate addi-
tions are slower using less active nucleophiles and in these
cases the formation of dimers coming from the Michael ac-
ceptor becomes to be a competitive reaction. In fact the
phosphate-catalyzed dimerization of electron-deficient al-
kenes was first reported by Rauhut and Currier in 196322
and more recently has been used by Krische23 and co-
workers in cycloisomerizations and the group of Roush24
in the vinylogous intramolecular Morita–Baylis–Hillman
reaction.
NH2
NH2
O2N
NH2
H2N
1g
1e
1f
1h
pKa= 26.9
pKa= 20.9
pKa= 23.35
pKa= 24.95
Figure 2. pKa’s in dimethyl sulfoxide solution for nucleophiles 1.
of tributylphosphine (Scheme 1). We have previously
established that tributylphosphine is more active18b than tri-
phenylphosphine corresponds to the higher nucleophilicity
parameters N [Bu3P (15.49), Ph3P (14.33)].20 All conjugate
additions were carried out in acetonitrile, a relative polar
solvent. Recently, Liu and co-workers21 have found that
the solvent exerts profound effects on the basicity of phos-
phines and reported the basicity of a huge number of
phosphines in acetonitrile [Bu3PH+ (pKa¼16.2), Ph3PH+
(pKa¼6.5)], tributylphosphine being more basic than tri-
phenylphosphine.
In order to obtain new insights to the mechanism we con-
ducted some 31P NMR spectroscopy experiments. 31P
chemical shift for Bu3P in CD3OD is ꢁ32.5 whereas after
addition of butenone to the NMR tube the d changed to
30.5, typical chemical shift of a phosphonium salt. This
suggested the presence of the b-phosphonium ketone 5.
First reaction of Scheme 3 illustrates this process. An equiv-
alent of this phosphonium ketone was independently pre-
pared through an alternative route25 (reaction 2, Scheme
3) in order to compare chemical shifts. Compound 6 was
obtained from addition of tetrabutylammonium iodide to
butenone followed by reaction with tributylphosphine. 31P
chemical shift value for 6 was 32.7. The match on the
chemical shifts suggests that the initial attack of the phos-
phine on the olefin generates a phosphonium b-ylide being
quickly protonated in hydroxylic solvents. In the case of the
conjugate addition, since there is an anhydrous media this
b-ylide causes deprotonation of the nucleophile giving con-
jugated base, which triggers the propagation steps indicated
in Figure 3 as a cycle (pathway 1). However, we envisaged
another possibility consisting of direct attack of conjugate
base to phosphonium cation (pathway 2). Experiments
with the sodium salts of 1,3-diphenyl-1,3-propandione and
1,3-cyclohexandione with phosphonium salt 6 permitted
Z1
Z1
R
Z2
Bu3P
Z2
+
N
NH
R1
1
2
3
Z1 and Z2 = electron withdrawing groups
Scheme 1. Conjugate addition catalyzed by phosphines.
The results obtained are reported in Tables 1 and 2. All
reactions were carried out in the presence of a 10% mol
equiv of Bu3P unless stated otherwise. Uracil 1a reacted
at room temperature with an excess of butenone and less
active acrylonitrile to obtain di-N-alkylated compounds
3aaa (95% yield) and 3abb (89% yield), respectively. In
addition sulfonamide 1b was tested with acrylonitrile
and ethyl acrylate affording products 3bbb and 3bcc in
high yields at room temperature. Also Oppolzer’s sultam
reacted with ethyl acrylate and the N-alkylated compound
3cc was obtained at room temperature in a high 85% yield.

C. Gimbert et al. / Tetrahedron 63 (2007) 8305–8310
8307
Table 1. Preparation of products 3 (Scheme 1)
Entry
Nucleophile
Electrophile
Products
H3COC
O
N
H
O
N
N
N
COCH3
2a
COCH3
1
H
O
O
1a
3aaa
NC
O
CN
N
CN
2
3
1a
N
O
2b
3abb
H3C
SO2 N
H3C
SO2 NH2
CN
2b
2
1b
3bbb
H3C
SO2
N
COOEt
2c
COOEt
4
5
1b
2
3bcc
2c
NH
N
S
S
COOEt
O
O
O
O
1c
3cc
S
CN
S
S
N
6
2b
CN
NH2
1d
N
H
CN
3db
3dbb
S
S
COOEt
N
H
COOEt
7
8
9
1d
2c
2b
2c
2
N
3dc
O2N
3dcc
CN
N
O2N
NH2
2
1e
3ebb
COOEt
COOEt
O2N
O2N
NH
3ec
N
2
1e
3ecc
O
O
O
CN
CN
N
H
NH2
2
N
10
11
2b
1f
3fb
3fbb
O
O
P(O)(OEt)2
P(O)(OEt)2
P(O)(OEt)2
N
H
N
2
1f
2d
3fd
3fdd
P(O)(OEt)2
NH
N
12
2d
1g
3gd

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C. Gimbert et al. / Tetrahedron 63 (2007) 8305–8310
Table 2. Experimental conditions for the preparation of compounds 3 in
CH3CN (Scheme 1)
D
CD3OD
(1)
(2)
PBu3
CD3O
+
Bu3P
Entry
Product
Molar
ratio 2:1
Temp
(ꢀC)
Timea
(h)
Yield
(%) 3
O
O
5
Bu4N I
1
2
3
4
5
6
7
8
3aaa
3abb
3bbb
3bcc
3cc
3db/3dbb
3dc/3dcc
3ebb
3ec/3ecc
3fb/3fbb
3fd/3fdd
3gd
2.8
5.9
6.0
3.0
5.9
5.7
5.8
6.1
9.4
5.9
2.2
1.5
rt
rt
rt
rt
rt
rt
rt
rt
3.5
22
6
18
24
23
3
20
30.5
142
5
95
89
76
52
Bu3P
THF
I
I
PBu3
CF3CO2H
O
O
O
6
85
4b/50
9b/43
71
Scheme 3. Synthesis of phosphonium salts 5 and 6.
9c
10
11
12
reflux
rt
reflux
2b/56
7b/27
24b/51
29
the nucleophile that triggers the propagation steps, no direct
reaction with the phosphonium salt being observed.
140d
14
a
Not optimized.
Mono-adduct.
Bu3P (20%) was used.
Closed reactor.
4. Experimental
b
c
d
4.1. General procedure
A mixture of benzamide 1f (0.518 g, 4.30 mmol), diethyl vi-
nylphosphonate 2d (1.4 mL, 9.4 mmol), and Bu3P (104 mL,
0.417 mmol) in anhydrous CH3CN (1.5 mL) was stirred in
a Schlenk tube under nitrogen atmosphere and reflux tem-
perature. After 5 h the solvent was evaporated and the resi-
due was chromatographed through silica gel with ethyl
acetate/methanol (9.5:0.5) to afford 3fd and 3fdd. Both
products were further purified by chromatography with ethyl
acetate/diethyl ether (1:1) and diethyl ether/methanol
(9.5:0.5), respectively, to afford 0.292 g of pure 3fd in
24% yield and 0.977 g of pure 3fdd in 51% yield.
us to reject this mechanism due to the fact that no nucleo-
philic substitution of the tributylphosphine by the conjugate
bases of the b-diketones was observed.
3. Conclusion
In summary, we discovered a novel phosphine-catalyzed
aza-Michael type reaction of non-nucleophilic N-containing
compounds. The procedure is very simple and the scope is
huge not only from the point of view of nucleophiles (am-
ides, thioamides, sulfonamides, and electron-poor anilines)
but also electrophiles (butenone, acrylonitrile, ethylacrylate,
and diethylvinylphosphonate). The range of useful pKa’s of
nucleophiles has been established (pKa <25). The investiga-
tion of the mechanism permitted us to demonstrate that
a phosphonium b-ylide was formed, which deprotonates
4.1.1. N-[2-(Diethoxyphosphoryl)ethyl]benzamide (3fd).
1H NMR (250 MHz, CDCl3): d¼1.32 (t, J¼7.0 Hz, 6H),
2.07 (dt, J¼17.2, 6.3 Hz, 2H), 3.76 (dt, J¼22.4, 6.3 Hz,
2H), 4.06–4.19 (m, 4H), 7.29 (br s, 1H), 7.38–7.51 (m,
3H), 7.79–7.83 (m, 2H). 13C NMR (62.5 MHz, CDCl3):
d¼16.7 (d, J¼6.4 Hz), 25.6 (d, J¼139.2 Hz), 34.1 (d,
CN
NC
COOEt
EtOOC
S
S
4bb
4cc
Z
Bu3P
Z
Z
2
2
CH3-CN
Z
Z
S
4
SH
R3P
Z
S
S
S
N
H
H
R3P
N
H
Z
Z
Z
S
S
S
S
N
H
N
H
H
H
N
N
H
Z
N
H
Scheme 2. Possible mechanism for the formation of compounds 4.

C. Gimbert et al. / Tetrahedron 63 (2007) 8305–8310
8309
1H NMR (250 MHz, CDCl3): d¼2.45 (s, 3H), 2.74 (t,
J¼7.0 Hz, 4H), 3.44 (t, J¼7.0 Hz, 4H), 7.35 (d, J¼8.3 Hz,
2H), 7.70 (d, J¼8.3 Hz, 4H). 13C NMR (62.5 MHz,
CDCl3): d¼19.2, 21.8, 46.3, 117.8, 130.5, 134.9, 145.1. IR
(ATR): n¼2944, 2254, 1597, 1340, 1159, 1112, 712,
R3P
R3P
+
Z
698 cmꢁ1
.
Z
NuH
4.1.6. N,N-Bis[(2-ethoxycarbonyl)ethyl]-4-methylbenz-
enesulfonamide (3bcc).29 1H NMR (250 MHz, CDCl3):
d¼1.23 (t, J¼7.1 Hz, 6H), 2.41 (s, 3H), 2.61 (t, J¼7.3 Hz,
4H), 3.40 (t, J¼7.3 Hz, 4H), 4.11 (t, J¼7.3 Hz, 4H), 7.30
(d, J¼7.3 Hz, 4H), 7.68 (d, J¼7.3 Hz, 4H). 13C NMR
(62.5 MHz, CDCl3): d¼14.3, 21.7, 34.6, 45.2, 61.0, 127.4,
129.9, 136.1, 143.7, 171.4. IR (ATR): n¼2981, 1727,
R3P
Nu
R3P
Nu
Z
+
Pathway 2
Nu
3
1598, 1314, 1184, 1155, 690 cmꢁ1
.
Z
3
Pathway 2
Z
Z
4.1.7. (2R)-N-[2-(Ethoxycarbonyl)ethyl]bornano-10,2-
sultame (3cc). H NMR (250 MHz, CDCl3): d¼0.88 (s,
1
Pathway 1
Pathway 1
3H), 1.07 (s, 3H), 1.22 (t, J¼7.1 Hz, 3H), 1.23–1.43 (m,
2H), 1.65 (dd, J¼8.0, 12.7 Hz, 1H), 1.75–1.90 (m, 3H),
2.02–2.10 (m, 1H), 2.60 (ddd, J¼5.6, 7.4, 16.5 Hz, 1H),
2.76 (dt, J¼7.6, 16.5 Hz, 1H), 3.03 (dd, J¼4.5, 8 Hz, 1H),
3.10 (s, 2H), 3.14 (dt, J¼7.6, 13.7 Hz, 1H), 3.32 (ddd,
J¼5.6, 7.1, 13.7 Hz, 1H), 4.11 (q, J¼7.1 Hz, 1H). 13C
NMR (62.5 MHz, CDCl3): d¼16.8, 22.4, 22.6, 29.0, 34.0,
34.7, 36.9, 40.3, 45.9, 48.8, 50.9, 51.0, 61.4, 67.8, 167.5.
IR (ATR): n¼3622, 3554, 3447, 2955, 1730, 1374, 1303,
1151, 1120, 788, 682 cmꢁ1. Anal. Calcd for C15H25NO4S:
C, 57.12; H, 7.99; N, 4.44. Found: C, 57.45; H, 7.99; N,
4.30. [a]D ꢁ79.4 (c 1.00, CHCl3).
NuH
R3P
Nu
Z
Z
Figure 3. Possible competition between pathways 1 and 2.
J¼6.6 Hz), 62.2 (d, J¼6.1 Hz), 127.2, 128.8, 131.7, 134.4,
167.3. IR (ATR): n¼3295, 2981, 1640, 1538, 1924,
1221 cmꢁ1. HRMS (ESI): m/z calcd for C13H20NO4P
[M]+: 285.1130; found [M+H]+: 286.1203.
4.1.8. N,N-Bis(2-cyanoethyl)thioacetamide (3dbb). 1H
NMR (250 MHz, CDCl3): d¼2.75 (s, 3H), 2.76 (t,
J¼6.8 Hz, 2H), 3.02 (t, J¼6.2 Hz, 2H), 4.07 (t, J¼6.8 Hz,
2H), 4.22 (t, J¼6.2 Hz, 2H). 13C NMR (62.5 MHz,
CDCl3): d¼14.7, 17.3, 32.9, 49.1, 49.5, 116.5, 118.4,
202.9. IR (ATR): n¼2996, 2249, 1453, 1359, 1274, 1218,
1004 cmꢁ1. Anal. Calcd for C8H11N3S: C, 52.93; H, 6.12;
N, 23.18. Found: C, 56.80; H, 6.00; N, 22.95.
4.1.2. N,N-Bis[2-(diethoxyphosphoryl)ethyl]benzamide
1
(3fdd). H NMR (250 MHz, DMSO) T¼373 K: d¼1.28 (t,
J¼7.0 Hz, 12H), 2.05–2.19 (m, 4H), 3.56–3.67 (m, 4H),
4.04 (dq, J¼8.6, 7.0 Hz, 8H), 7.41–7.50 (m, 5H). 13C
NMR (62.5 MHz, DMSO) T¼373 K: d¼16.2 (d,
J¼5.4 Hz), 24.9 (d, J¼134.9 Hz), 41.6, 61.4 (d,
J¼6.4 Hz), 126.6, 128.4, 129.3, 137.1, 170.8. IR (ATR):
n¼2981, 2907, 1633, 1239, 1022, 956 cmꢁ1. HRMS (ESI):
m/z calcd for C19H33NO7P2 [M]+: 449.1732; found
[M+H]+: 450.1805.
4.1.9. N,N-Bis[2-(ethoxycarbonyl)ethyl]thioacetamide
(3dcc). 1H NMR (250 MHz, CDCl3): d¼1.24 (t, J¼7.1 Hz,
3H), 1.26 (t, J¼7.1 Hz, 3H), 2.65 (t, J¼7.6 Hz, 2H), 2.66
(s, 3H), 2.84 (t, J¼7.0 Hz, 2H), 3.92 (t, J¼7.6 Hz, 2H),
4.09–4.20 (m, 6H). 13C NMR (62.5 MHz, CDCl3):
d¼14.4, 31.2, 32.8, 33.1, 48.9, 49.2, 61.0, 61.5, 170.5,
172.0, 201.0. IR (ATR): n¼2980, 2937, 1724, 1501, 1454,
4.1.3. 1,3-Bis(3-oxobutyl)uracil (3aaa).26 1H NMR
(250 MHz, CDCl3): d¼2.12 (s, 3H), 2.13 (s, 3H), 2.71 (t,
J¼7.5 Hz, 2H), 2.89 (t, J¼5.8 Hz, 2H), 3.89 (t, J¼5.8 Hz,
2H), 4.12 (t, J¼7.5 Hz, 2H), 5.62 (d, J¼8.0 Hz, 1H), 7.36
(d, J¼8.0 Hz, 1H). 13C NMR (62.5 MHz, CDCl3): d¼30.1,
30.3, 36.6, 41.3, 41.9, 45.3, 101.2, 144.4, 151.5, 163.1,
206.7, 206.8. IR (ATR): n¼3093, 2964, 1701, 1648, 1455,
1419, 1375, 1181, 1014 cmꢁ1
.
Anal. Calcd for
C18H21NO4S: C, 52.34; H, 7.69; N, 5.09. Found: C, 52.27;
H, 7.91; N, 4.82.
1355, 1226, 1165, 804, 767 cmꢁ1
.
4.1.10. N,N-Bis(2-cyanoethyl)-4-nitroaniline (3ebb). Mp
159–161 ꢀC (lit. mp 163–164 ꢀC).29 1H NMR (250 MHz,
CDCl3): d¼2.85 (t, J¼6.9 Hz, 4H), 3.88 (t, J¼6.9 Hz, 4H),
7.01 (d, J¼9.5 Hz, 2H), 8.08 (q, J¼9.5 Hz, 2H). 13C NMR
(62.5 MHz, CDCl3): d¼15.7, 46.3, 112.3, 119.5, 126.4,
137.7, 152.2. IR (ATR): n¼2249, 1588, 1492, 1315, 1112,
4.1.4. 1,3-Bis(2-cyanoethyl)uracil (3abb).27 1H NMR
(250 MHz, CDCl3): d¼2.74 (t, J¼7.0 Hz, 2H), 2.81 (t,
J¼6.2 Hz, 2H), 3.99 (t, J¼6.2 Hz, 2H), 4.23 (t, J¼7.0 Hz,
2H), 5.79 (d, J¼7.9 Hz, 1H), 7.27 (d, J¼7.9 Hz, 1H). 13C
NMR (62.5 MHz, CDCl3): d¼16.4, 17.7, 36.8, 46.3, 102.5,
117.1, 117.4, 143.0, 151.1, 162.3. IR (ATR): n¼2976,
834, 751 cmꢁ1
.
2244, 1704, 1649, 1451, 1345, 1228, 802, 764 cmꢁ1
.
4.1.11. N-[2-(Ethoxycarbonyl)ethyl]-4-nitroaniline (3ec).
Mp 72–75 ꢀC .1H NMR (250 MHz, CDCl3): d¼1.26 (t,
J¼7.1 Hz, 3H), 2.63 (t, J¼6.1 Hz, 2H), 3.53 (t, J¼6.1 Hz,
2H), 4.16 (q, J¼7.1 Hz, 2H), 4.94 (br s, 1H), 6.54 (dd,
4.1.5. N,N-Bis[(2-cyanoethyl)]-4-methylbenzenesulfon-
amide (3bbb). Mp 102–104 ꢀC (lit. mp 100–102 ꢀC).28

8310
C. Gimbert et al. / Tetrahedron 63 (2007) 8305–8310
J¼7.0, 2.1 Hz, 2H), 8.08 (dd, J¼7.0, 2.1 Hz, 2H). 13C NMR
(62.5 MHz, CDCl3): d¼14.4, 33.8, 39.0, 61.3, 111.4, 126.7,
138.6, 153.1, 172.2. IR (ATR): n¼3367, 2921, 1705, 1612,
1596, 1311, 1113 cmꢁ1. Anal. Calcd for C11H14N2O4: C,
55.46; H, 5.92; N, 11.76. Found: C, 54.45; H, 5.96; N, 11.41.
References and notes
1. For reviews see: (a) Christoffers, J. Eur. J. Org. Chem. 1998,
1259; (b) Comelles, J.; Moreno-Man˜as, M.; Vallribera, A.
Arkivoc 2005, ix, 207; Available from the web page: http://
www.arkat-usa.org/ark/journal/2005/I09_Molina-Elguero/1302/
ME-1302R.pdf.
4.1.12. N,N-Bis[2-(ethoxycarbonyl)ethyl]-4-nitroaniline
1
(3ecc). H NMR (250 MHz, CDCl3): d¼1.24 (t, J¼7.1 Hz,
2. Bartoli, G.; Bosco, M.; Marcantoni, E.; Petrini, M.; Sambri, L.;
Torregiani, E. J. Org. Chem. 2001, 66, 9052.
6H), 2.61 (t, J¼7.2 Hz, 4H), 3.76 (t, J¼7.2 Hz, 4H), 4.13
(q, J¼7.1 Hz, 4H), 6.63 (dd, J¼7.4, 2.1 Hz, 2H), 8.10 (dd,
J¼7.4, 2.1 Hz, 2H). 13C NMR (62.5 MHz, CDCl3):
d¼14.4, 32.4, 47.1, 61.2, 110.9, 126.6, 137.9, 151.8,
171.5. IR (ATR): n¼2981, 1724, 1592, 1308, 1181,
1111 cmꢁ1. Anal. Calcd for C16H22N2O6: C, 56.80; H,
6.55; N, 8.28. Found: C, 56.80; H, 6.58; N, 8.18.
3. Azizi, N.; Saidi, M. R. Tetrahedron 2004, 60, 383.
4. (a) Varala, R.; Alam, M.-M.; Adapa, S. R. Synlett 2003, 720; (b)
Monfray, J.; Koskinen, A. M. P. Lett. Org. Chem. 2006, 3, 324.
5. Srivastava, N.; Banik, B. K. J. Org. Chem. 2003, 68, 2109.
6. (a) Hashemi, M. M.; Eftekhari-Sis, B.; Abdollahifar, A.;
Khalili, B. Tetrahedron 2006, 62, 672; (b) Firouzabadi, H.;
Iranpoor, N.; Jafarpour, M.; Ghaderi, A. J. Mol. Catal. A:
Chem. 2006, 252, 150.
7. Kantam, M. L.; Neelima, B.; Reddy, Ch. V. J. Mol. Catal. A:
Chem. 2005, 241, 147.
8. Surendra, K.; Krishnaveni, N. S.; Sridhar, R.; Rao, K.-R.
Tetrahedron Lett. 2006, 47, 2125.
9. (a) Yadav, J. S.; Reddy, B. V. S.; Basak, A. K.; Narsaiah, A. V.
Chem. Lett. 2003, 32, 988; (b) Xu, L.-W.; Li, J.-W.; Zhou,
S.-L.; Xia, C.-G. New J. Chem. 2004, 28, 183.
10. Amore, K. M.; Leadbeater, N. E.; Miller, T. A.; Schmink, J. R.
Tetrahedron Lett. 2006, 47, 8583.
11. Vicario, J. L.; Badia, D.; Carrillo, L.; Etxebarria, J.; Reyes, E.;
Ruiz, N. Org. Prep. Proced. Int. 2005, 37, 513.
12. Takasu, K.; Nishida, N.; Ihara, M. Synlett 2004, 1844.
13. Ahn, K. H.; Lee, S. J. Tetrahedron Lett. 1994, 12, 1875.
14. Xin, Z.; Pei, Z.; Geldem, T.; Jirousek, M. Tetrahedron Lett.
2000, 41, 1147.
4.1.13. N,N-Bis(2-cyanoethyl)benzamide (3fbb). Mp 101–
104 ꢀC (lit. mp 106–108 ꢀC).30 1H NMR (250 MHz,
DMSO): d¼2.87 (t, J¼6.7 Hz, 4H), 3.70 (t, J¼6.7 Hz,
4H), 7.45–7.54 (m, 5H). 13C NMR (62.5 MHz, DMSO):
d¼16.7, 119.1, 127.3, 129.2, 130.2, 136.4, 171.9. IR
(ATR): n¼2967, 2246, 1630, 1417, 1255, 1024, 701 cmꢁ1
.
4.1.14. Diethyl[2-(diphenylamino)ethyl]phosphonate
1
(3gd). H NMR (250 MHz, CDCl3): d¼1.32 (t, J¼7.1 Hz,
6H), 2.08–2.22 (m, 2H), 3.98–4.14 (m, 6H), 6.93–7.01 (m,
6H), 7.24–7.30 (m, 4H). 13C NMR (62.5 MHz, CDCl3):
d¼16.5 (d, J¼6.2 Hz), 23.9 (d, J¼134.1 Hz), 46.0, 61.7 (d,
J¼6.6 Hz), 121.0, 121.7, 129.4, 147.1. IR (ATR): n¼2979,
2904, 1858, 1493, 1242, 1023, 954 cmꢁ1. HRMS (ESI): m/z
calcd for C18H24NO3P [M]+: 333.1494; found [M+H]+:
334.1567.
15. Zhang, H.; Zhang, Y.; Liu, L.; Xu, H.; Wang, Y. Synthesis 2005,
13, 2129.
16. (a) Dalko, P. I.; Moisan, L. Angew. Chem., Int. Ed. 2004, 43,
5138; (b) Seayad, J.; List, B. Org. Biomol. Chem. 2005, 3, 719.
17. Methot, J. L.; Roush, W. R. Adv. Synth. Catal. 2004, 346, 1035.
4.1.15. Tributyl(3-oxobutyl)phosphonium iodide (6). A
mixture of butenone (0.84 mL, 0.01 mmol) and tetrabutyl-
ammonium iodide (5.2 g, 0.014 mmol) in distilled
CF3CO2H (10 mL) was stirred in a Schlenk tube under nitro-
gen atmosphere at room temperature. After 1 h a mixture of
30 mL of water and 30 mL of pentane is added to the reac-
tion mixture. The organic layer was then dried and evapo-
rated obtaining 0.815 g (41% yield) of 4-iodobutan-2-one.
No purification was required. Then a mixture of 4-iodobu-
tan-2-one (0.353 g, 0.0018 mmol) and tributylphosphine
(1.4 mL, 0.005 mmol) in 3.5 mL of anhydrous THF was
stirred in a Schlenk tube under nitrogen atmosphere at
room temperature for 20 h. Solvent was evaporated off and
water was added to the residue. Extraction with diethyl ether
(4ꢂ30 mL), the aqueous layer was evaporated and the
residue dried at 50 ꢀC to afford 0.437 g (61%) of compound
6. 31P NMR (101 MHz, CD3OD): d¼32.7. 1H NMR
(250 MHz, CD3OD): d¼1.04 (t, J¼7 Hz, 9H), 1.48–1.68
(m, 12H), 2.28 (s, 3H), 2.22–2.35 (m, 6H), 2.48 (dt, J¼
7.2, 13 Hz, 2H), 3.02 (dt, J¼7.2, 12.2 Hz, 2H). HRMS: m/z
calcd for [M]+: 273.2342; found: 273.2338.
ꢀ
18. (a) Lumbierres, M.; Marchi, C.; Moreno-Man˜as, M.; Sebastian,
R. M.; Vallribera, A.; Lago, E.; Molins, E. Eur. J. Org. Chem.
2001, 2321; (b) Gimbert, C.; Lumbierres, M.; Marchi, C.;
ꢀ
Moreno-Man˜as, M.; Sebastian, R. M.; Vallribera, A.
Tetrahedron 2005, 61, 8597.
19. Bordwell, F. G. Acc. Chem. Res. 1988, 21, 456.
20. Kempf, B.; Mayr, H. Chem.—Eur. J. 2005, 11, 917.
21. Li, J.-N.; Fu, Y.; Liu, L.; Guo, Q.-X. Tetrahedron 2006, 62,
11801.
22. Rauhut, M. M.; Currier, H. U.S. Patent, 3,074,999,1963; 0122,
1963(American CyanamidCo.);Chem. Abstr. 1963, 58, 11224a.
23. (a) Wang, L.-C.; Luis, A. L.; Agapiou, K.; Jang, H.-Y.; Krische,
M. J. J. Am. Chem. Soc. 2002, 124, 2402; (b) Luis, A. L.;
Krische, M. J. Synthesis 2004, 15, 2579.
24. Frank, S. A.; Mergott, D. J.; Roush, W. R. J. Am. Chem. Soc.
2002, 124, 2404.
25. Shi, M.; Chen, L.-H.; Li, C.-Q. J. Am. Chem. Soc. 2005, 127,
3790.
Acknowledgements
26. (a) Peshakova, L.; Kalcheva, V. Z. Chem. 1990, 30, 438; (b)
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Financial support from Ministry of Education and Science of
Spain (Project CTQ2005-04968-C02-01 and predoctoral
scholarship to E.P.) and Generalitat de Catalunya (Project
2005SGR00305 and predoctoral scholarship to C.G.) is
gratefully acknowledged.
30. Sorrel, T. N.; Garrity, M. L. Inorg. Chem. 1991, 30, 210.