Enyne metathesis-oxidation sequence for the synthesis of 2-phosphono pyrroles: Proof of the "yne-then-ene" pathway

Article abstract of DOI:10.1002/chem.200600789

A new tandem reaction sequence has been developed for the synthesis of 2-phosphono pyrroles. The sequence consists of ring-closing enyne metathesis of a substituted aminophosphonate, containing a terminal alkyne and an internal alkene, in combination with

Full text of DOI:10.1002/chem.200600789

FULL PAPER
DOI: 10.1002/chem.200600789
Enyne Metathesis–Oxidation Sequence for the Synthesis of 2-Phosphono
Pyrroles: Proof of the “Yne-then-Ene” Pathway
Nicolai Dieltiens, Kristof Moonen, and Christian V. Stevens*[a]
Abstract: A new tandem reaction se-
quence has been developed for the syn-
thesis of 2-phosphono pyrroles. The se-
quence consists of ring-closing enyne
produced 3-pyrrolines using tetrachlor-
oquinone. By analyzing the formation
of the end and certain byproducts,
taking into account the difference in
reactivity of different substrates and
carefully studying spectroscopic data, it
was found that the reaction proceeds
by means of the “yne-then-ene” path-
way. During the initiation phase, a new
ruthenium carbene is formed which
continues the propagation cycle.
metathesis of
phosphonate, containing
a
substituted amino-
terminal
Keywords: amino phosphonates
·
a
metathesis · reaction mechanisms ·
ruthenium carbenes · ruthenium
alkyne and an internal alkene, in com-
bination with in situ oxidation of the
Introduction
With the discovery of new, well-defined catalysts, like the
first- (1)[1] and second-generation (2)[2] Grubbs catalysts,
olefin metathesis has become a very powerful synthetic tool
in organic synthesis.[3] Over the years, ring-closing metathe-
sis (RCM) has been applied to the synthesis of a wide varie-
ty of ring systems. The very related enyne metathesis, in-
volving reaction between an alkene and an alkyne, has re-
ceived much less attention.[4] Unlike olefin metathesis, all
carbon atoms from the starting material are retained in the
end product which contains a synthetically useful 1,3-diene
moiety. The intramolecular enyne metathesis is categorized
into three reaction patterns as illustrated in Scheme 1.[5] The
metathesis of 1,w-enynes 3 gives cyclic molecules 4 which
contain exo and endo enes (type a). The reaction of alkynyl-
cycloalkenes 5 with ethylene proceeds through the tandem
ring-opening, ring-closing metathesis to yield the rearranged
products 6 (type b). And finally, the tandem metathesis of
the dienynes 7 gives the bicyclic heterocycles 8 (type c). De-
spite its usefulness, however, little is known about the mech-
anism of the reaction. Although important mechanistic work
Scheme 1. The three reaction patterns of intramolecular enyne metathe-
sis.
has already been carried out by Mori,[6] Kozmin,[7] and Wal-
lace,[8] the question as to whether the reaction proceeds by
means of the “yne-then-ene” or the “ene-then-yne” mecha-
nism is still often raised. The yne-then-ene mechanism, a
Chauvin-type mechanism,[9] is commonly postulated for the
Ru-catalyzed enyne RCM reaction,[10] possibly as a legacy
from earlier work with catalysts based on GroupVI ele-
ments.[11] Recent kinetic studies, however, have brought up
evidence for the ene-then-yne pathway in cross-enyne meta-
thesis[12] and enyne metathesis with terminal olefins.[13]
[a] N. Dieltiens, K. Moonen,+ Prof. Dr. C. V. Stevens
Research GroupSynBioC, Department of Organic Chemistry
Faculty of Bioscience Engineering, Ghent University
Coupure links 653, 9000 Ghent (Belgium)
Fax : (+32)9-264-6243
Furthermore, enyne metathesis reactions of acyclic ole-
fins, other than terminal olefins, with terminal alkynes have
not been studied systematically.[6,14] A common goal in the
E-mail: chris.stevens@ugent.be
[+] K. Moonen is aspirant of the FWO (Fund for Scientific Research
Flanders).
Chem. Eur. J. 2007, 13, 203 – 214
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203

development of new reactions is to achieve multiple chemi-
cal transformations in a single synthetic operation.[15] Such
sequential reactions have been demonstrated for olefin
metathesis,[16] but have hardly been developed for enyne
metathesis. So far, only a one-pot combination of enyne
metathesis with a Diels–Alder reaction[14,17] or a cyclopropa-
nation[18] have been reported. In this paper, we wish to
report on the intramolecular
pyrrolobenzodiazepines, analogues of various amino acids,
anticancer antibiotics, and analogues of porphobilinogen.[24]
a,b-Unsaturated N-propargyl aldimines 9 were phospho-
nylated with complete regioselectivity[25] by using dimethyl
phosphite (DMP) and a-aminoalkenyl phosphonates 10
were obtained in high purity after a straightforward acid/
base extraction (Scheme 2).[26] Subsequent benzylation by
enyne metathesis involving the
reaction between a terminal
alkyne and an internal olefin
leading to 2-phosphono pyrro-
lines, followed by in situ oxida-
tion to the corresponding 2-
phosphono pyrroles.[19] The
synthesis of aromatic com-
pounds by RCM has only re-
cently appeared in the litera-
ture,[20] but it is emerging as an
important area and has very
recently been reviewed by Do-
nohoe and co-workers.[21] We
also offer evidence pointing to
the yne-then-ene pathway in
this particular case. The evi-
dence is threefold and is based
on 1) the formation of certain
end and byproducts, 2) the dif-
ference in reactivity of differ-
Scheme 2. a) 2 equiv DMP, MeOH, D, 2–3 h; b) 1.5 equiv BnBr, acetone, K2CO3, D, 16–20 h; c) 5 mol% 2, ben-
zene, D, 1 h; d) 5 mol% 2, 1 equiv TCQ, benzene, D, 1 h.
ent substrates, and 3) spectroscopic data. With this work, we
wish to contribute to a better mechanistic insight in enyne-
metathesis and further developthe usefulness of this reac-
tion.
using benzyl bromide in acetone with K2CO3 as a base and a
catalytic amount of NaI provided the substrates 11 for the
enyne metathesis.
To evaluate the effect of other substituents, N-tosyl
amines 16 were also synthesized in two straightforward
steps starting from monopropargylamine 14 (Scheme 3).
Results and Discussion
During our ongoing research into the synthesis of phospho-
nylated azaheterocycles,[22] interest grew in the use of ring-
closing enyne metathesis for the synthesis of functionalized
phosphono pyrroles. As we have demonstrated before, suita-
ble diallylamines can be converted to the corresponding 3-
pyrrolines by treatment with second-generation Grubbs cat-
alyst and in situ oxidation to the pyrrole nucleus by a one-
stepone-pot protocol with the addition of tetrachloroqui-
none (TCQ).[23] However, we also observed that the correct
choice of oxidizing agent is crucial, as DDQ (DDQ=2,3-di-
chloro-5,6-dicyano-1,4-benzoquinone) caused decomposition
of the metathesis catalyst, illustrating the delicate balance of
this one-pot reaction sequence. As enyne metathesis in-
volves different ruthenium-species intermediates, it was
hard to predict if TCQ would be able to oxidize the pyrro-
lines to the corresponding pyrroles while not affecting the
metathesis reaction. The compounds thus obtained, 3-(1H-
pyrrol-3-yl)alk-2-enes, are considered an important class of
chemical compounds because of their application in the syn-
thesis of a variety of molecules of biological interest, such as
Scheme 3. a) 0.95 equiv TosCl, 1.1 equiv pyridine, CH2Cl2, RT, 16 h;
b) 1.5 equiv electrophile, acetone, K2CO3, D, 16–20 h; c) 5 mol% 2, ben-
zene, D, 1 h.
Treatment of derivative 11a with 5% of catalyst 2 in re-
fluxing CH2Cl2 under a N2 atmosphere resulted in a very
slow (>12 h) conversion to 12a as an E/Z mixture. Adding
one equivalent of TCQ to the reaction mixture together
with the catalyst resulted in the formation of the corre-
sponding pyrrole 13a in about the same time. It was found,
however, that these transformations occur in less than 30
minutes when switching to refluxing benzene as a solvent
(Table 1). In the case of 11b, only catalytic deprotection of
the propargyl amine was observed.[27,28] The detailed mecha-
204
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Chem. Eur. J. 2007, 13, 203 – 214

Synthesis of 2-Phosphono Pyrroles
FULL PAPER
Table 1. Synthesis of 2-phosphono pyrrolines 12 and 2-phosphono pyr-
roles 13.
nism, two pathways are possible (Scheme 5). In the yne-
then-ene pathway enyne 11 reacts with the active catalyst
26, with the bulky alkylidene groupat the least-hindered
end of the alkyne, to form metallacyclobutene 18. Electrocy-
clic ring opening provides the diene 19. Subsequent [2+2]
cycloaddition and ring opening of the intermediate metalla-
cyclobutane yields diene 12 and regenerates the active cata-
lyst 26. Alternatively, the ene-then-yne pathway begins with
reaction of the alkene and provides the carbenoid 27 and
side-product 30. Carbenoid 27 undergoes an intramolecular
cycloaddition to provide bicyclic metallacyclobutene 28,
which collapses to carbenoid 29. Subsequent cross metathe-
sis with another molecule of 11 generates product 12 and
continues the catalytic cycle. Very often, both reaction path-
ways are reported as possible reaction routes. Recently,
Lloyd-Jones and co-workers[13] reported that when working
under “Moriꢁs conditions”[30] ethylene gas reacts with carbe-
noids of type 29 in a second catalytic cycle producing the
metathesis products and thus explaining the dramatic effect
of ethylene on both the yield and the reaction rate of Ru-
catalyzed enyne RCM reactions. As our experiments were
performed under an inert nitrogen atmosphere, the fact that
complete conversion is observed within 30 minutes tends to
rule out the possibility of the ene-then-yne pathway, as this
would contradict the low yields of enyne metathesis that
predate Moriꢁs observations. Looking at both reaction
mechanisms it is clear that although both pathways provide
the same end product, the intermediates are very different.
The most striking difference is that when x mol% of meta-
thesis catalyst is used in case of the yne-then-ene pathway,
x mol% of the produced pyrrolines 12 should have R=Ph
instead of R=R1. In case of the ene-then-yne pathway,
x mol% of 30 should be produced.
R1
R2
Yield 10 Yield 11 Yield 12 [%] Yield 13 [%]
[%]
[%]
(E/Z)
(E/Z)
a
b
c
d
e
f
2-furyl
CH3
Ph
propyl
Ph
isopropyl
H
Ph
CH3 92
H
H
H
69
82
54
68
65
60
64
46
68 (78:22)
0
88 (100:0)
78 (100:0)
86 (82:18)
75 (64:36)
78 (75:25)
0
85 (100:0)
48 (79:21)
82 (82:18)
95
70
65
[a]
–
[a] The pyrrole could not be obtained in sufficient purity.
nism for the deprotection of the propargyl amine 11b is un-
clear, but the ruthenium-hydride mechanism, which is typi-
cally used to explain the deprotection of allyl groups, may
also apply in this case (Scheme 4). The conversion of meta-
thesis intermediate 19b to 20b does not occur because of
the large steric hindrance between the phenyl group and the
phosphonate in intermediate 20b. As all steps are in equili-
brium, intermediate 19b can be converted back to com-
pound 11b, which can react with a RuH-species, formed by
decomposition of the metathesis catalyst, resulting in the
production of 25 upon workup.
Derivatives 16 were also cleanly converted to the pyrro-
lines but could, as we have described before, not be oxidized
to the pyrroles because of the electron-withdrawing substitu-
ent on nitrogen (Table 2).[29] Looking at the reaction mecha-
Table 2. Synthesis of N-tosyl pyrrolines 17.
R3
Yield 17 [%]
E/Z
g
h
i
CH2Cl
CH2Br
4-chloro-phenoxymethyl
Ph
86
76
73
89
100:0
100:0
63:37
100:0
This implies that, for example, derivative 12e should be
produced as a side product during the synthesis of deriva-
j
Scheme 4. Proposed mechanism for the catalytic deprotection of amine 11b.
Chem. Eur. J. 2007, 13, 203 – 214
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205

C. V. Stevens et al.
the signal of 1 (d=36.9 ppm)
slowly decreased and at the
same time a new signal ap-
peared at d=33.7 ppm. In
order to attribute this signal to
31, allylbromide was treated in
a separate experiment with 1,
resulting in the appearance of
the same signal. This proves
that it was indeed this rutheni-
um species that was formed
during enyne metathesis of
14h.
To obtain further proof of
the yne-then-ene hypothesis,
we looked for
a compound
that, depending on the reaction
pathway, would give a different
end product. Enediyne 32 was
Scheme 5. The yne-then-ene and ene-then-yne pathway.
synthesized for this purpose by
reacting two equivalents of 15
1
tives 12a, 12d, and 12 f. Indeed, it was found that in the H
and 31P NMR spectra of the crude reaction mixture of 12d,
about 5% of derivative 12e was present (Scheme 6). These
findings are supported by comparison with a pure sample of
12e and by LCMS analysis of the reaction mixture. Side
products of type 30 were never detected.
with one equivalent of (2Z)-1,4-dichloro-2-butene. Treat-
ment of 32 with catalyst 2 resulted in complete conversion
to 40 upon reflux in benzene. To the best of our knowledge,
this is the first example of enyne metathesis for the synthesis
of a conjugated triene from an enediyne. Although the
steric hindrance of the first stepin the yne-then-ene path-
way might be lower than the one in the ene-then-yne path-
way, the first metallocycle formed in this case is a strained
cyclobutene, while in the other case it is a less-strained cy-
clobutane. Accepting the yne-then-ene pathway cleanly
leads to the observed end product with concomitant produc-
tion of x mol% of 17j (Scheme 8). If, however, the ene-
then-yne pathway is active, the observed end product
cannot be obtained without accepting the yne-then-ene
pathway at a certain point and the side product produced
should be 16j (Scheme 9). Following this reaction with
1H NMR spectroscopy, a remarkable difference between cat-
alysts 1 and 2 was observed. At room temperature, no con-
version at all was observed when using catalyst 2. Elevating
the temperature to 358C resulted in the immediate produc-
Scheme 6. Formation of byproduct 12e during the synthesis of 12d.
Another striking difference between the two pathways is
that, in case of the yne-then-ene pathway, the Grubbs car-
bene is in situ converted to a new Ru species 26 which con-
tinues the catalytic cycle. This carbenoid is not formed in
the other pathway. To detect this compound, derivative 14h
was dissolved in C6D6 and treated with the first-generation
Grubbs catalyst 1 (Scheme 7). The reaction could easily be
monitored by using 31P NMR spectroscopy. The intensity of
1
tion of 40 and only trace amounts of 17j. H NMR spectro-
scopy revealed, however, that during the entire course of
the reaction undissociated catalyst was still present. This is
consistent with the fact that 2 shows very slow initiation, but
very fast propagation. Thus ruthenium species 36, continues
the catalytic cycle producing 40 without the formation of
17j. The reaction pattern of 1 is completely different on the
other hand. Spectral data showed that running the reaction
at 358C resulted in the production of 17j as the only reac-
tion product with the simultaneous complete consumption
of catalyst 1. This is consistent with the fact that 1 shows
very fast initiation but slower propagation and suggests that
ruthenium species 36 with a first-generation ligand (PCy3) is
a rather poor catalyst. Raising the temperature to 608C re-
sulted in the production of compound 40. The formation of
16j as a side product was never observed.
Scheme 7. Spectroscopic evidence for the formation of carbene 31.
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Synthesis of 2-Phosphono Pyrroles
FULL PAPER
switching of solvent to reflux-
ing toluene or chlorobenzene
did not result in any metathesis
activity. This shows that re-
moving the yne moiety has a
very dramatic effect in the re-
activity of these compounds.
Besides the aforementioned
mechanisms, the oxidative cyc-
lization mechanism[31] and the
possibility of
a noncarbene
complex acting as the catalytic
species[32] were also investigat-
ed. It was observed however
that treating the substrates
with [(p-cymene)RuCl2]2 or
[Cl2RuACHTRE(UGN PPh3)3] in refluxing tol-
uene did not result in the pro-
duction of the end products
obtained with catalysts 1 or 2.
This observation in combina-
tion with the other results
seems to rule out this possibili-
ty.
Scheme 8. Conversion of 32 to 40 following the yne-then-ene pathway.
Scheme 11 summarizes our
findings. In the initiation
phase, the substrate reacts with
the Grubbs carbene to yield,
after a sequence of cycloaddi-
tions and cycloreversions, the
byproduct and the new car-
bene. This new carbene can
then react further with another
molecule of substrate to pro-
duce the final product with re-
generation of the carbene,
after a sequence of cycloaddi-
tions and cycloreversions. In
the case of complete initiation
of the metathesis catalyst, x%
of catalyst gives rise to a mix-
ture of x% byproduct and
(100Àx)% of product upon completion of the reaction.
Scheme 9. The “ene-then-yne” pathway does not lead to 40.
Finally, evaluating 44[23b] as a substrate showed that no
metathesis occurred at all when a 2-methylallyl substituent
is introduced at nitrogen (Scheme 10). Initiation at either
double bond would result in a ruthenium species 45 or 46
with limited steric hindrance at the other double bound, es-
pecially compared to intermediates 19 in Scheme 4. Even
Conclusion
In summary, a new enyne-metathesis approach has been de-
scribed, leading either to phosphonylated pyrrolines or pyr-
roles. Combining this enyne metathesis with in situ oxida-
tion using tetrachloroquinone results in the exclusive forma-
tion of the 2-phosphono pyrroles. It was proven that, at least
in this case, enyne metathesis with terminal alkynes and
nonterminal alkenes follows the yne-then-ene pathway.
Proof of this reaction mechanism is based on the formation
of certain end and side products, spectroscopic data, and fi-
nally on the difference in reactivity of different substrates.
Scheme 10. Removal of the yne moiety blocks metathesis activity.
Chem. Eur. J. 2007, 13, 203 – 214
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207

C. V. Stevens et al.
Scheme 11. Complete catalytic cycle for the conversion of enynes to pyrrolines.
stir at room temperature for 24 h. After filtration of the solids and re-
moval of the volatiles, the obtained aldimines were directly used for the
synthesis of a-aminoalkenyl phosphonates 10.
This work contributes to a better mechanistic insight into
enyne metathesis.
Synthesis of a-aminoalkenyl phosphonates 10: Aldimine 9 (10 mmol) was
dissolved in MeOH (20 mL) in a round-bottomed flask. Then, dimethyl
phosphite (DMP, 20 mmol) was added and the mixture was refluxed for
3–4 h. After removing the solvent under vacuum, the resulting oil was
dissolved in diethyl ether (20 mL) and added to a separating funnel con-
taining aq HCl (1m, 20 mL). Both phases were vigorously mixed and the
organic phase was removed from the funnel. The aqueous phase was
washed twice with diethyl ether (10 mL), added to dichloromethane
(20 mL), and then neutralized by using aq NaOH (3m) until slightly alka-
line. Both phases were vigorously mixed and the organic phase was then
collected. The aqueous phase was extracted twice more with dichlorome-
thane (10 mL) and the combined organic phases were dried by using
MgSO4. The a-aminoalkenyl phosphonates 10 were obtained in pure
form after filtration and evaporation of the solvent.
Experimental Section
1
General remarks: High resolution H (300 MHz) and 13C NMR (75 MHz)
spectra were run on a Jeol JNM-EX 300 NMR spectrometer. Peak as-
signments were obtained with the aid of DEPT, 2D HSQC, and
2D COSY spectra. The compounds were diluted in deuterated solvents
and the solvent used is indicated for each compound. Multiplicities are
described by using the following abbreviations: s = singlet, d = doublet,
t = triplet, q = quartet, m = multiplet, br = broad. LRMS were re-
corded on an Agilent 1100 Series VS (ES, 4000 V) mass spectrometer. IR
spectra were obtained from a Perkin–Elmer Spectrum One IR spectrom-
eter. For liquid samples, the spectra were collected by preparing a thin
film of compound between two sodium chloride plates. The crystalline
compounds were mixed with potassium bromide and pressed until a
transparent potassium bromide plate was obtained. Melting points of
crystalline compounds were measured with a Büchi 540 apparatus and
are uncorrected. Elemental analysis was performed on a Perkin–Elmer
2400 Elemental Analyzer. Purification of reaction mixtures was per-
formed by flash chromatography using a glass column with silica gel
(Across, particle size: 0.035–0.070 mm, pore diameter: ca. 6 nm).
Dimethyl (2E)-3-(2-furyl)-1-(prop-2-ynylamino)prop-2-enylphosphonate
(10a): Yield: 69%; 1H NMR (300 MHz, CDCl3): d=1.88 (brs, 1H; NH),
2.26 (t, 4J
NCHAHB), 3.57 (brd, J
3.84 (m, 6H; 2”OCH3), 3.99 (dd, 2J
1H; CHP), 5.98 (ddd, 3J(H,H)=15.7 Hz, 3J
6.5 Hz, 1H; PCHCH), 6.29 (brs, 1H; CHfuryl), 6.38 (brs, 1H; CHfuryl),
6.55 (dd, 3J(H,H)=15.7 Hz, 4J
(H,P)=4.5 Hz, 1H; CH), 7.36 ppm (brs,
1H; OCHfuryl); 13C NMR (75 MHz, CDCl3): d=36.1 (d, J
NCH2), 53.6 (d, 2J(C,P)=7.5 Hz; OCH3), 53.7 (d, 2J
OCH3), 56.5 (d, 1J
(C,P)=156.9 Hz; CHP), 72.5 (CCH), 80.9 (CCH),
(H,H)=2.3 Hz, 1H; CHalkyne), 3.40 (brd, 2J=16.8 Hz, 1H;
ACHTREUNG
2
AHCTREUNG
A
ACHTREUNG
A
N
ACHTREUNG
A
ACHTREUNG
3
AHCTREUNG
Synthesis of aldimines 9: A suitable aldehyde was dissolved in dry
CH2Cl2 (freshly distilled from CaH2) and 1.1 equivalents of propargyla-
mine and 2 equivalents of MgSO4 were added. The mixture was left to
A
ACHTREUNG
AHCTREUNG
208
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Synthesis of 2-Phosphono Pyrroles
FULL PAPER
109.0 (d, 5J
10.4 Hz; CHCHP), 123.7 (d, 3J
151.9 ppm (d, 4J(C,P)=3.5 Hz; Cquat,furyl); 31P NMR (121 MHz, CDCl3):
C
3.78–3.85 (m, 7H; CHP+2”OCH3), 5.25–5.35 (m, 1H; CH), 5.78–
5.89 ppm (m, 1H; CH2CH); 13C NMR (75 MHz, CDCl3): d=13.6 (CH3),
AHCTREUNG
G
22.2 (CH3CH2), 34.6 (CH2CH), 35.7 (d, 3J
ACHTREUNG
(d, 2J
1J
9.2 Hz; CH), 138.3 ppm (d, 3J
AHCTREUNG
(C,P)=13.8 Hz; OCH3), 53.5 (d, 2J
ACHRTEUNG ACHTREUNG
(%): 270.7 [M+H]+ (52), 160.8 [MÀP(O)
C
A
ACHTREUNG
CDCl3): d=27.4 ppm; IR (film): n˜ =1245 (P=O), 2104 cmÀ1 (alkyne);
MS: m/z (%): 246.7 [M+H]+ (100); elemental analysis (%) calcd for
C11H20NO3P: C 53.87, H 8.22, N 5.71; found: C 53.69, H 8.19, N 5.71.
The aldehyde used for the synthesis of aldimine 9b was an E/Z mixture.
As a consequence, derivative 10b was also obtained as a mixture. The
two forms could be separated. Total yield: 82%.
Dimethyl
(10e): Yield: 70%; 1H NMR (300 MHz, CDCl3): d=1.89 (brs, 1H; NH),
2.27 (t, 4J(H,H)=2.0 Hz, 1H; CHalkyne), 3.40 (dd, 2J
(H,H)=17.2 Hz,
4J(H,H)=2.0 Hz, 1H; NCHAHB), 3.57 (dt, 2J(H,H)=17.2 Hz, 4J
(H,H)=
2.0 Hz, 1H; NCHAHB), 3.81 (d, 3J
(H,P)=10.7 Hz, 3H; OCH3), 3.82 (d,
3J(H,P)=10.7 Hz, 3H; OCH3), 4.03 (dd, 2J(H,P)=16.9 Hz, 3J
(H,H)=
8.8 Hz, 1H; CHP), 6.07 (ddd, 3J(H,H)=16.0 Hz, 3J
(H,H)=8.8 Hz,
3J(H,P)=6.1 Hz, 1H; PCHCH), 6.73 (dd, 3J(H,H)=16.0 Hz, 4J
(H,P)=
6.7 Hz, 1H; CHPh), 7.24–7.43 ppm (m, 5H; Ph); 13C NMR (75 MHz,
CDCl3): d=36.1 (d, 3J(C,P)=17.2 Hz; NCH2), 53.6 (d, 2J
(C,P)=7.5 Hz;
OCH3), 53.7 (d, 2J(C,P)=7.5 Hz; OCH3), 56.8 (d, 1J
(C,P)=156.0 Hz;
CHP), 72.5 (CCH), 81.0 (CCH), 122.6 (d, 2J (C,P)=9.2 Hz; CHCHP),
(2E)-3-phenyl-1-(prop-2-ynylamino)prop-2-enylphosphonate
Dimethyl
(10b): 1H NMR (300 MHz, CDCl3): d=1.67 (dd, 5J
3J(H,H)=6.9 Hz, 3H; CH3), 1.95 (brs, 1H; NH), 2.34 (t, 4J
2.3 Hz, 1H; CH), 3.51 (dd, 4J(H,H)=2.3 Hz, 2J
(H,H)=16.9 Hz, 1H;
NCHAHB), 3.59 (dt, 4J(H,H)=2.3 Hz, 2J
(H,H)=16.9 Hz, 1H; NCHAHB),
3.60 (d, 3J(H,P)=10.4 Hz, 3H; OCH3), 3.68 (d, 3J
(H,P)=10.4 Hz, 3H;
OCH3), 4.09 (d, 2J(H,H)=20.6 Hz, 1H; CHP), 6.00 (dq, 3J
(H,H)=
6.9 Hz, 4J
(H,P)=5.0 Hz, 1H; CHPh), 7.24–7.38 ppm (m, 5H; Ph);
13C NMR (75 MHz, CDCl3): d=15.0 (CH3), 35.9 (d, 3J
(C,P)=17.3 Hz;
NCH2), 53.3 (d, 2J(C,P)=6.9 Hz; OCH3), 53.4 (d, 2J
(C,P)=6.9 Hz;
(C,P)=155.8 Hz; CHP), 72.40 (CH), 81.3 (C), 127.1
(2E)-2-phenyl-1-(prop-2-ynylamino)but-2-enylphosphonate
(H,P)=5.5 Hz,
(H,H)=
A
ACHTREUNG
AHCTREUNG
A
N
ACHTREUNG
A
ACHTREUNG
AHCTREUNG
A
ACHTREUNG
A
N
ACHTREUNG
A
ACHTREUNG
A
ACHTREUNG
A
ACHTREUNG
A
N
ACHTREUNG
A
ACHTREUNG
ACHTREUNG
A
ACHTREUNG
AHCTREUNG
A
ACHTREUNG
A
ACHTREUNG
OCH3), 60.2 (d, 1J
ACHTREUNG
126.8 (2”CHarom), 128.2 (CHarom), 128.7 (2”CHarom), 135.8 (d, 3J
ACHTREUNG(C,P)=
(CHarom), 128.0 (d, 3J
(C,P)=10.4 Hz, CCH), 128.2 (2”CHarom), 129.4 (2”
13.8 Hz, CH), 136.2 ppm (Carom); 31P NMR (121 MHz, CDCl3): d=26.5;
IR (film): n˜ =1243 (P=O), 2106 cmÀ1 (alkyne); MS: m/z (%): 280.7
2
3
CHarom), 134.6 (d, J
(C,P)=4.6 Hz; CCH), 139.0 ppm (d, J
(C,P)=2.3 Hz;
Carom); 31P NMR (121 MHz, CDCl3): d=26.6 ppm; IR (film): n˜ =3293
[M+H]+ (50), 170.8 [MÀP(O)
(OMe)2+H]+ (100); elemental analysis
ACHTREUNG
(%) calcd for C14H18NO3P: C 60.21, H 6.50, N 5.02; found: C 60.38, H
6.53, N 5.22.
(NH), 1246 (P=O), 1055, 1030 cmÀ1; MS: m/z (%): 184.2 [MÀP(O)-
ACHTREUNG
(OMe)]+ (100), 294.2 [M+H]+ (23); elemental analysis (%) calcd for
C15H20NO3P: C 61.43, H 6.87, N 4.78; found: C 61.61, H 6.99, N 4.80.
Dimethyl (2Z)-2-phenyl-1-(prop-2-ynylamino)but-2-enylphosphonate
(10b): M.p. 81–828C; 1H NMR (300 MHz, CDCl3): d=1.89 (brs, 1H;
NH), 1.94 (dd, 5J(H,P)=4.5 Hz, 3J
(H,H)=7.0 Hz, 3H; CH3), 2.41 (t,
4J(H,H)=2.0 Hz, 1H; CH), 3.25 (dd, 4J(H,H)=2.0 Hz, 2J
(H,H)=
16.8 Hz, 1H; NCHAHB), 3.39 (dt, 4J(H,H)=2.0 Hz, 2J
(H,H)=16.8 Hz,
1H; NCHAHB), 3.72 (d, 3J(H,P)=8.8 Hz, 3H; OCH3), 3.75 (d, 3J
(H,P)=
9.1 Hz, 3H; OCH3), 4.60 (d, 2J
(H,P)=24.5 Hz, 1H; CHP), 6.02 (dq,
3J(H,H)=7.0 Hz, 4J
(H,P)=4.3 Hz, 1H; CHPh), 7.23–7.35 (m, 3H; 3”
CHarom), 7.57–7.60 ppm (m, 2H; 2”CHarom); 13C NMR (75 MHz, CDCl3):
d=14.5 (CH3), 36.3 (d, 3J(C,P)=19.6 Hz; NCH2), 53.4 (d, 2J
(C,P)=
6.9 Hz; OCH3), 53.7 (d, 2J(C,P)=6.9 Hz; OCH3), 54.4 (d, 1J
(C,P)=
156.9 Hz, 1H; CHP), 72.2 (CH), 81.3 (C), 127.2 (CHarom), 128.3 (2”
CHarom), 128.3 (2”CHarom), 131.7 (d, 3J
(C,P)=11.5 Hz; CCH), 135.4 (d,
2J(C,P)=3.5 Hz; CCH), 140.9 ppm (Carom); 31P NMR (121 MHz, CDCl3):
d=27.02; IR (KBr): n˜ =3239 (NH), 1235 (P=O), 1060, 1027 cmÀ1; MS:
(OMe)]+ (100), 294.2 [M+H]+ (65); elemental
Dimethyl
(10 f): Yield: 65%; 1H NMR (300 MHz, CDCl3): d=1.02 (d, 3J
6.9 Hz, 6H; CH3), 1.74 (brs, 1H; NH), 2.22 (t, 4J
(H,H)=2.2 Hz, 1H;
CHalkyne), 2.30–2.43 (m, 1H; CH), 3.34 (dd, 2J(H,H)=16.9 Hz, 4J
(H,H)=
2.2 Hz, 1H; NCHAHB), 3.52 (ddd, 2J(H,H)=16.9 Hz, 4J
(H,H)=2.2 Hz,
4J(H,P)=2.0 Hz, 1H; NCHAHB), 3.77 (dd, 2J(H,P)=19.3 Hz, 3J
(H,H)=
10.2 Hz, 1H; CHP), 3.79 (d, 3J
(H,P)=10.5 Hz, 3H; OCH3), 3.80 (d,
3J
(H,P)=10.5 Hz, 3H; OCH3), 5.22–5.32 (m, 1H; =CHCHP), 5.82 ppm
(ddd, 3J(H,H)=14.5 Hz, 3J(H,H)=6.6 Hz, 4J
(H,P)=4.3 Hz, 1H; =CH);
(2E)-4-methyl-1-(prop-2-ynylamino)pent-2-enylphosphonate
ACHTREUNG
AHCTREUNG
G
ACHTREUNG
A
ACHTREUNG
N
G
ACHTREUNG
A
ACHTREUNG
G
ACHTREUNG
N
A
ACHTREUNG
G
ACHTREUNG
AHCTREUNG
AHCTREUNG
AHCTREUNG
G
ACHTREUNG
G
A
ACHTREUNG
13C NMR (75 MHz, CDCl3): d=22.14 (2”CH3), 31.1 (CH), 35.6 (d,
G
ACHTREUNG
3J
2J
C
ACHTRE(UNG C,P)=8.1 Hz; OCH3), 53.5 (d,
R
ACHTREUNG
ACHTREUNG
G
AHCTREUNG
3J
ACHTREUNG
ACHTREUNG
(film): n˜ =2104 (C=C), 1243 (P=O), 1035 cmÀ1 (br, P O); MS: m/z (%):
À
246 [M+H]+ (62), 136 [M+HÀPO
(OMe)2]+ (100); elemental analysis
ACHTREUNG
m/z (%): 184.2 [MÀP(O)
ACHTREUNG
(%) calcd for C11H20NO3P: C 53.87, H 8.22, N 5.71; found: C 53.97, H
8.23, N 5.72.
analysis (%) calcd for C15H20NO3P: C 61.43, H 6.87, N 4.78; found: C
61.28, H 7.06, N 4.86.
Synthesis of N-benzyl a-aminoalkenyl phosphonates 11: a-Aminoalkenyl
phosphonate 10 (5 mmol), K2CO3 (20 mmol), NaI (0.5 mmol), and ace-
tone (10 mL) were added to a round-bottomed flask. Then, benzyl bro-
mide (10 mmol) was added and the mixture was refluxed for 24 h. The
course of the reaction was conveniently monitored by means of 31P NMR
spectroscopic analysis of samples taken directly from the reaction mix-
ture. After complete conversion of the starting material, the solids were
removed by filtration and the solvent was removed by evaporation under
reduced pressure. The corresponding N-benzyl a-aminoalkenyl phospho-
nate 11 can be obtained in pure form as a pale yellow oil after column
chromatography over silica gel by using a hexane/ethyl acetate mixture
as a mobile phase.
Dimethyl
(2E)-2-methyl-3-phenyl-1-(prop-2-ynylamino)prop-2-enyl-
phosphonate (10c): Yield: 92%; 1H NMR (300 MHz, CDCl3): d=1.98
(brs, 1H; NH), 2.01 (dd, 4J
A
G
4
2
2.48 (t, J
(H,H)=2.3 Hz, 1H; CH), 3.34 (dd, 4J
16.1 Hz, 1H; NCHAHB), 3.52 (dt, 4J
A
ACHTREUNG
3
3
1H; NCHAHB), 3.81 (d, J
A
ACHTRE(UNG H,P)=
10.5 Hz, 3H; OCH3), 3.96 (d, 2J
4J
(75 MHz, CDCl3): d=15.8 (CH3), 36.0 (d, J
(d, 2J(C,P)=6.9 Hz, 2”OCH3), 62.1 (d, 1J
(C,P)=153.4 Hz; CHP), 72.4
(CH), 81.0 (C), 126.9 (CHarom), 128.3 (2”CHarom), 129.1 (CHarom), 129.1
(CHarom), 131.0 (d, 3J(C,P)=12.7 Hz, CCH), 131.5 (d, 2J
(C,P)=6.9 Hz;
CCH), 137.2 ppm (d, 4J(C,P)=2.3 Hz; Carom); 31P NMR (121 MHz,
ACHTREUNG
ACHTREUNG
3
AHCTRE(UNG C,P)=19.6 Hz; NCH2), 53.6
H
ACHTREUNG
A
ACHTREUNG
AHCTREUNG
Dimethyl
phosphonate (11a): Yield: 54%; H NMR (300 MHz, CDCl3): d=2.25 (t,
4J(H,H)=2.2 Hz, 1H; CHalkyne), 3.43 (dd, 2J(H,H)=17.2 Hz, 4J
(H,H)=
2.2 Hz, 1H; NCHAHBC), 3.63 (brd, 2J(H,H)=17.2 Hz, 4J
(H,H)=2.2 Hz,
1H; NCHAHBC), 3.67 (d, 2J
(H,H)=13.8 Hz, 1H; NCHAHBPh), 3.74 (d,
3J(H,P)=10.8 Hz, 3H; OCH3), 3.86 (d, 3J
(H,P)=10.2 Hz, 3H; OCH3),
3.97 (dd, 2J(H,P)=22.4 Hz, 3J
(H,H)=9.5 Hz, 1H; CHP), 4.23 (d,
2J
(H,H)=13.8 Hz, 1H; NCHAHBPh), 6.20–6.40 (m, 3H; PCHCH+
CCHCHfuryl), 6.51 (dd, 3J(H,H)=15.7 Hz, 4J
(H,P)=3.0 Hz, 1H; CH),
7.06–7.39 ppm (m, 6H; Ph+OCHfuryl); 13C NMR (75 MHz, CDCl3): d=
40.7 (d, 3J(C,P)=8.1 Hz; NCH2C), 53.1 (d, 2J
(C,P)=6.9 Hz; OCH3), 53.8
(2E)-1-[benzyl(prop-2-ynyl)amino]-3-(2-furyl)prop-2-enyl-
1
CDCl3): d=26.67 ppm; IR (film): n˜ =3293 (NH), 1246 (P=O), 1053,
1030 cmÀ1; MS: m/z (%): 294.2 [M+H]+ (100); elemental analysis (%)
calcd for C15H20NO3P: C 61.43, H 6.87, N 4.78; found: C 61.37, H 6.65, N
4.89.
A
N
ACHTREUNG
A
ACHTREUNG
AHCTREUNG
Dimethyl (2E)-1-(prop-2-ynylamino)hex-2-enylphosphonate (10d): Yield:
A
ACHTREUNG
95%; 1H NMR (300 MHz, CDCl3): d=0.91 (t, 3H, 3J
R
A
ACHTREUNG
CH3), 1.44 (sextet, 3J
2.09 (dt, 3J
A
ACHTREUNG
H
E
A
ACHTREUNG
A
ACHTREUNG
A
N
A
ACHTREUNG
Chem. Eur. J. 2007, 13, 203 – 214
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
209

C. V. Stevens et al.
(d, 2J
1J(C,P)=161.5 Hz; CHP), 73.0 (CCH), 80.6 (CCH), 109.0 (d, 5J
2.3 Hz; CCHfuryl), 111.5 (CCHCHfuryl), 118.4 (CHCHP), 125.0 (d,
3J
(C,P)=15.0 Hz; CH), 127.4 (CHarom), 128.5 (2”CHarom), 129.1 (2”
A
G
CDCl3): d=26.98 ppm; IR (film): n˜ =1244 (P=O), 1034 cmÀ1; MS: m/z
(%): 336.7 [M+H]+ (100); chromatography (hexane/EtOAc 4:6): Rf =
0.27; elemental analysis (%) calcd for C18H26NO3P: C 64.46, H 7.81, N
4.18; found: C 64.27, H 7.79, N 4.29.
A
ACHTREUNG
ACHTREUNG
CHarom), 138.5 (Carom), 142.6 (OCH), 152.0 ppm (OC); 31P NMR
(121 MHz, CDCl3): d=25.9 ppm; IR (film): n˜ =1245 cmÀ1 (P=O); MS:
m/z (%): 360.8 [M+H]+ (100); chromatography (hexane/EtOAc 4:6):
Rf =0.28; elemental analysis (%) calcd for C19H22NO4P: C 63.50, H 6.17,
N 3.90; found: C 63.85, H 6.36, N 3.79.
Dimethyl
phosphonate (11e): 1H NMR (300 MHz, CDCl3): d: 2.26 (t, 4J
2.5 Hz, 1H; CHalkyne), 3.54 (dd, 2J(H,H)=17.1 Hz, 4J
(H,H)=2.5 Hz, 1H;
NCHAHBC), 3.65 (dd, 2J(H,H)=17.1 Hz, 4J
(H,H)=2.5 Hz, 1H;
NCHAHBC), 3.69 (d, 2J
(H,H)=13.5 Hz, 1H; NCHAHBPh), 3.73 (d,
3J(H,P)=10.5 Hz, 3H; OCH3), 3.87 (d, 3J
(H,P)=10.5 Hz, 3H; OCH3),
(H,P)=22.3 Hz, 3J
(H,H)=9.5 Hz, 1H; CHP), 4.22 (d,
(H,H)=13.5 Hz, 1H; NCHAHBPh), 6.42 (ddd, 3J
(H,H)=15.8 Hz,
(H,H)=9.5 Hz, 3J(H,P)=6.9 Hz, 1H; PCHCH), 6.66 (dd, 3J
(H,H)=
(H,P)=3.0 Hz, 1H; CHPh), 7.26–7.45 ppm (m, 10H; Ph);
13C NMR (75 MHz, CDCl3): d=40.7 (d, 4J
(C,P)=8.1 Hz; NCH2C), 53.1
(d, 2J(C,P)=6.9 Hz; OCH3), 53.9 (d, 2J
(C,P)=6.9 Hz; OCH3), 55.5 (d,
3J(C,P)=8.1 Hz; NCH2Ph), 61.0 (d, 1J
(C,P)=161.5 Hz, CHP), 73.1
(2E)-1-[benzyl(prop-2-ynyl)amino]-3-phenylprop-2-enyl-
ACHTREUNG
A
ACHTREUNG
A
ACHTREUNG
AHCTREUNG
For the synthesis of derivative 11b, the (2E)-form of 10b was used.
U
ACHTREUNG
3.99 (dd, 2J
G
ACHTREUNG
Dimethyl (2E)-1
nate (11b): Yield: 68%; 1H NMR (300 MHz, CDCl3): d=1.71 (dd, 3H,
5J(H,P)=1.9 Hz, 3J(H,H)=6.9 Hz; CH3), 2.48 (t, 4J
(H,H)=2.3 Hz, 1H;
CH), 3.43 (dd, 4J(H,H)=2.3 Hz, 2J
(H,H)=17.0 Hz, 1H; NCHAHB), 3.59
(d, 2J(H,H)=13.2 Hz, 1H; NCHAHBPh), 3.68 (dt, 4J
(H,H)=2.3 Hz,
2J(H,H)=17.0 Hz, 1H; NCHAHB), 3.71 (d, 3J
(H,P)=10.5 Hz, 3H;
OCH3), 3.79 (d, 3J(H,P)=10.5 Hz, 3H; OCH3), 4.05 (dd, 4J
(H,P)=
1.6 Hz, 2J(H,H)=13.2 Hz, 1H; NCHAHBPh), 4.10 (d, 2J
(H,P)=22.8 Hz,
1H; CHP), 6.44 (dq, 3J(H,H)=6.9 Hz, 4J
(H,P)=2.5 Hz, 1H; CHCH3),
7.05–7.38 ppm (m, 10H; Ph); 13C NMR (75 MHz, CDCl3): d=15.3 (CH3),
40.5 (d, 3J(C,P)=5.8 Hz; NCH2), 53.0 (d, 2J
(C,P)=6.9 Hz; OCH3), 53.6
(d, 2J(C,P)=6.9 Hz; OCH3), 55.7 (d, 3J
(C,P)=9.2 Hz; NCH2Ph), 62.4 (d,
1J
(C,P)=156.9 Hz; CHP), 72.6 (CH), 80.8 (C), 127.0 (CHarom), 127.2
(CHarom), 128.2 (2”CHarom), 128.2 (2”CHarom), 129.1 (2”CHarom), 129.2
(2”CHarom), 129.9 (d, 3J(C,P)=5.8 Hz, CCH), 133.7 (d, 2J
(C,P)=4.6 Hz,
CCH), 138.6 (Carom), 141.1 ppm (d, 3J(C,P)=10.4 Hz, CPh); 31P NMR
ACHTREUNG[benzyl(prop-2-ynyl)amino]-2-phenylbut-2-enylphospho-
2J
3J
G
ACHTREUNG
U
A
ACHTREUNG
A
N
ACHTREUNG
15.8 Hz, 4J
A
A
ACHTREUNG
AHCTREUNG
A
ACHTREUNG
C
ACHTREUNG
A
ACHTREUNG
G
ACHTREUNG
A
ACHTREUNG
(CCH), 80.8 (CCH), 119.9 (CHCHP), 126.8 (2”CHarom), 127.4 (CHarom),
A
ACHTREUNG
128.3 (CHarom), 128.5 (2”CHarom), 128.8 (2”CHarom), 129.1 (2”CHarom),
A
ACHTREUNG
136.3 (Carom), 137.2 (d, 3J
ACHTRE(UNG C,P)=15.0 Hz, CH), 138.5 ppm (Carom);
31P NMR (121 MHz, CDCl3): d=26.1 ppm; IR (film): n˜ =1246 cmÀ1 (P=
O); MS: m/z (%): 370.8 [M+H]+ (100); chromatography (hexane/EtOAc
4:6): Rf =0.42; elemental analysis (%) calcd for C21H24NO3P: C 68.28, H
6.55, N 3.79; found: C 68.42, H 6.56, N 3.78. Yield: 64%.
A
ACHTREUNG
A
ACHTREUNG
ACHTREUNG
A
N
Dimethyl
(2E)-1-[benzyl(prop-2-ynyl)amino]-4-methylpent-2-enyl-
1
T
phosphonate (11 f): Yield: 46%; H NMR (300 MHz, CDCl3): d=1.04 (d,
3
(121 MHz, CDCl3): d=26.38 ppm; IR (film): n˜ =1243 (P=O), 1058,
3J
4J
2J
C
ACHTRE(UNG H,H)=6.1 Hz, 3H; CH3), 2.22 (t,
1030 cmÀ1; MS: m/z (%): 384.2 [MÀP(O)
C
A
ACHTREUNG
R
3.71 (d, 3J
3J
(H,H)=9.6 Hz, 1H; CHP), 3.83 (d, J
(d, 2J
3J
G
ACHTREUNG
3
ACHTREUNG
Dimethyl (2E)-[benzyl(prop-2-ynyl)amino]-2-methyl-3-phenylprop-2-enyl
1
G
ACHTREUNG
phosphonate (11c): Yield: 65%; H NMR (300 MHz, CDCl3): d=2.11 (t,
4
4J
4J
A
G
A
ACHTREUNG
ACHTREUNG ACHTREUNG ACHTRENUG
(H,H)=2.1 Hz, 2J(H,H)=17.5 Hz, 1H; NCHAHB), 3.56 (dt, 4J
A
ACHTREUNG
3
2.1 Hz, J
ACHTREUNG(H,H)=17.5 Hz, 1H; NCHAHB), 3.78 (d, JACHTRENUG
OCH3), 3.84 (d, 3J
ACHTREUNG
A
ACHTREUNG
A
ACHTREUNG
AHCTREUNG
AHCTREUNG
ACHTREUNG
7.42 ppm (m, 10H; Ph); 13C NMR (75 MHz, CDCl3): d=17.6 (d,
A
3J
2J
3J
(C,P)=9.2 Hz; NCH2), 53.0 (d,
(C,P)=6.9 Hz; OCH3), 55.3 (d,
ACHTREUNG(C,P)=8.1 Hz; NCH2Ph), 67.1 (d, JACHTRE(GUN C,P)=154.6 Hz; CHP), 73.6 (CH),
AHCTREUNG
(121 MHz, CDCl3): d=26.86 ppm; IR (film): n˜ =2238 (alkyne), 1244 (P=
A
O), 1034 cmÀ1 (br, P O); MS: m/z (%): 336 [M+H]+ (100), 226
1
À
[M+HÀPO
(OMe)2]+ (27); chromatography (hexane/EtOAc 3:2): Rf =
79.2 (C), 127.0 (CHarom), 127.3 (CHarom), 128.3 (2”CHarom), 128.4
(CHarom), 128.4 (2”CHarom), 128.9 (CHarom), 129.1 (2”CHarom), 132.4 (d,
0.22; elemental analysis (%) calcd for C18H26NO3P: C 64.46, H 7.81, N
4.18; found: C 64.67, H 7.94, N 4.28.
3J(C,P)=11.5 Hz; CCH), 132.4 (d, 2J
ACHTREUNG HCATRE(UGN C,P)=3.5 Hz; CCH), 137.3 (Carom),
138.7 ppm (Carom); 31P NMR (121 MHz, CDCl3): d=26.7; IR (film): n˜ =
1600, 1248 (P=O), 1031 cmÀ1; MS: m/z (%): 384.2 [M+H]+ (100); chro-
matography (hexane/EtOAc 4:6): Rf =0.20; elemental analysis (%) calcd
for C22H26NO3P: C 68.92, H 6.83, N 3.65; found: C 68.76, H 7.03, N 3.45.
Synthesis of 2-phosphono 3-pyrrolines 12: Aminoalkenyl phosphonate 11
(0.39 mmol) and benzene (10 mL) were added to an oven-dried round-
bottomed flask. The solution was refluxed under a nitrogen atmosphere
and Grubbs second-generation catalyst
2 (0.02 mmol, 5 mol%) was
added to the boiling solution. The reaction mixture was then further re-
fluxed for 16 h. The course of the reaction was conveniently monitored
by means of 31P NMR spectroscopic analyses of samples taken directly
from the reaction mixture. The product was coated on silica gel by re-
moval of the solvent in vacuo and purified by flash chromatograhy. The
2-phosphono 3-pyrrolines 12 could also be obtained by an acid–base ex-
traction, but the yield was significantly lower in this fashion.
Dimethyl
(2E)-1-[benzyl(prop-2-ynyl)amino]hex-2-enylphosphonate
(11d): Yield: 60%; 1H NMR (300 MHz, CDCl3): d=0.93 (t, 3J
A
3
6.9 Hz, 3H; CH3), 1.46 (sextet, J
N
3J
2.1 Hz, 1H; CH), 3.35 (dd, 4J
NCHAHB), 3.56 (d, 2J
(H,H)=6.9 Hz, 3J
A
ACHTREUNG
A
ACHTREUNG
ACHTREUNG
ACHTREUNG ACHTREUNG ACHTRENUG
4J(H,H)=2.1 Hz, 2J(H,H)=17.6 Hz, 1H; NCHAHB), 3.72 (d, 3J
10.5 Hz, 3H; OCH3), 3.82 (dd, 3J
A
G
Dimethyl
phosphonate (12a): Yield: 68%; 1H NMR (300 MHz, CDCl3): d=3.43–
3.56 (m, 1H; NCHAHBC), 3.69 (d, 2J
(H,H)=13.0 Hz, 1H; NCHAHBPh),
3.77–3.87 (m, 7H; 2”OCH3 +NCHAHBC), 4.20–4.26 (m, 1H; CHP), 4.36
(d, 2J
(H,H)=13.0 Hz, 1H; NCHAHBPh), 5.81 (brs, 1H; NCHCH), 6.09
(d, 1H, 2J(H,H)=16.5 Hz; NCH2CCHCH), 6.23 (d, 3J
(H,H)=3.3 Hz,
1H; OCCH), 6.35–6.38 (m, 1H; OCHCH), 6.79 (d, 3J
(H,H)=16.5 Hz,
1H; NCH2CCH), 7.14–7.44 ppm (m, 6H; Ph+OCH); 13C NMR
1-benzyl-4-[(E)-2-(2-furyl)vinyl]-2,5-dihydro-1H-pyrrol-2-yl-
2
2
CHP), 3.84 (d, J
A
ACHTREUNG
1H; NCHAHBPh), 5.62 (ddd, 3J
A
N
ACHTREUNG
3J
A
A
ACHTREUNG
A
ACHTREUNG
A
ACHTREUNG
A
N
ACHTREUNG
A
ACHTREUNG
2
2
U
(75 MHz, CDCl3): d=53.2 (d, J
6.9 Hz; OCH3), 59.2 (d, 3J(C,P)=9.2 Hz, NCH2C), 60.3 (d, 3J
4.6 Hz, NCH2Ph), 69.0 (d, 1J
ACHRTEUNG(C,P)=8.1 Hz; OCH3), 53.9 (d, JACHTREUNG
(NCHCH), 127.3 (CHarom), 128.4 (2”CHarom), 129.1 (2”CHarom), 138.7
A
ACHTREUNG
(Carom), 139.8 ppm (d, 3J
A
ACHTREUNG
210
www.chemeurj.org
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Synthesis of 2-Phosphono Pyrroles
FULL PAPER
4
111.8 (OCHCH), 119.2 (d, J=4.6 Hz; NCH2CCHCH), 120.7 (d, J
A
Dimethyl
1-benzyl-4-[(E)-2-phenylvinyl]-2,5-dihydro-1H-pyrrol-2-yl-
phosphonate (12e): Yield: 86%; trans/cis 82:18; 1H NMR (300 MHz,
2
5.8 Hz; NCH2CCH), 122.6 (d, J
(C,P)=8.1 Hz; NCHCH), 128.4 (CHarom),
CDCl3): d=3.57 (d, 2J
2J(H,H)=13.5 Hz, 1H; NCHAHBPh), 3.76 (d, 3H, 3J
OCH3), 3.79 (d, 3J(H,P)=10.2 Hz, 3H; OCH3), 3.81 (d, 3J
10.5 Hz, 3H; OCH3), 3.85 (d, 3J
(H,P)=10.2 Hz, 3H; OCH3), 4.00 (dt,
2J(H,H)=12.9 Hz, 4J
(H,H)=7.0 Hz, 1H; NCHAHBC), 4.20–4.28 (m, 1H;
CHP), 4.37 (d, 2J
(H,H)=13.5 Hz, 1H; NCHAHBPh), 5.73 (brs, 1H;
CCH), 5.83 (brs, 1H; CCH), 6.20 (d, 3J
(H,H)=12.0 Hz, 1H; CHCHPh),
6.29 (d, 2J(H,H)=16.0 Hz, 1H; CHCHPh), 6.56 (d, 2J
(H,H)=12.0 Hz,
1H; CHCHPh), 6.88 (d, 2J
(H,H)=16.0 Hz, 1H; CHCHPh), 7.15–
7.44 ppm (m, 10H; 2”Ph); 13C NMR (75 MHz, CDCl3): d=53.2 (d,
ACHTREUNG
128.5 (2”CHarom), 128.7 (2”CHarom), 139.3 (Carom), 142.6 (OCH),
152.7 ppm (OC); 31P NMR (121 MHz, CDCl3): d=24.28 ppm; IR (film):
n˜ =1240 (P=O), 1056, 1033 cmÀ1; MS: m/z (%): 360.8 [M+H]+ (100);
chromatography (hexane/EtOAc 4:6): Rf =0.12; elemental analysis (%)
calcd for C19H22NO4P: C 63.50, H 6.17, N 3.90; found: C 63.31, H 6.07, N
3.91.
G
ACHTREUNG
E
ACHTREUNG
AHCTREUNG
N
ACHTREUNG
AHCTREUNG
AHCTREUNG
As described before, treatment of 11b with catalyst 2 resulted in catalytic
deprotection of the propargyl group after 72 h in refluxing benzene.
U
ACHTREUNG
AHCTREUNG
Dimethyl (2E)-1[benzylamino]-2-phenylbut-2-enylphosphonate (25):
Yield: 42%; 1H NMR (300 MHz, CDCl3): d=1.69 (dd, 5J
ACHTREUNG
2J
3J
3J
1J
4J
C
ACHTRE(UNG C,P)=8.1 Hz; OCH3), 59.4 (d,
3J
A
ACHTREUNG
ACHTREUNG
AHCTREUNG
ACHTREUNG
1
A
ACHTREUNG
ACHTREUNG
AHCTREUNG
ACHTREUNG
A
ACHTREUNG
AHCTREUNG
(2”CHarom), 127.0 (CHarom), 127.2 (CHarom), 127.3 (2”CHarom), 127.9 (2”
CHarom), 128.0 (CHarom), 128.3 (2”CHarom), 128.5 (2”CHarom), 128.7 (2”
A
ACHTREUNG
CHarom), 128.8 (2”CHarom), 128.9 (2”CHarom), 131.5 (d, 5J
ACHTREUNG
AHCTREUNG
CHPh), 132.1 (d, 5J
ACHTREUNG
ACHTREUNG
AHCTREUNG
AHCTREUNG
ACHTREUNG
AHCTREUNG
(121 MHz, CDCl3): d=26.38; IR (film): n˜ =1248 (P=O), 1057, 1031 cmÀ1
;
24.57, 24.36 ppm; IR (film): n˜ =1602, 1241 (P=O), 1057, 1032 cmÀ1; MS:
m/z (%): 370.8 [M+H]+ (100); chromatography (hexane/EtOAc 2:8):
Rf =0.35; elemental analysis (%) calcd for C21H24NO3P: C 68.28, H 6.55,
N 3.79; found: C 68.12, H 6.67, N 3.95.
MS: m/z (%): 346.3 [M+H]+ (100); chromatography (hexane/EtOAc
4:6): Rf =0.28; elemental analysis (%) calcd for C19H24NO3P: C 66.07, H
7.00, N 4.06; found: C 66.26, H 7.31, N 4.07.
Dimethyl
phosphonate (12 f): Yield: 75%; trans/cis 64:36; 1H NMR (300 MHz,
CDCl3): d=0.92 (d, 3J(H,H)=6.6 Hz, 3H; CH3), 0.94 (d, 3J
(H,H)=
6.6 Hz, 3H; CH3), 0.96 (d, 3J
(H,H)=6.9 Hz, 6H; CH3), 2.25–2.40 (m,
1H; CH), 2.48–2.61 (m, 1H; CH), 3.34–3.45 (m, 1H; CHAHB), 3.46–3.59
(m, 1H; CHAHB), 3.66 (d, 2J
(H,H)=13.5 Hz, 1H; CHAHBPh), 3.70 (d,
2J(H,H)=13.5 Hz, 1H; CHAHBPh), 3.80 (d, 3J
(H,P)=10.2 Hz, 6H;
OCH3), 3.83 (d, 3J(H,P)=10.2 Hz, 3H; OCH3), 3.84 (d, 3J
(H,P)=
10.2 Hz, 3H; OCH3), 3.83–3.89 (m, 1H; CHAHB), 3.90–3.98 (m, 1H;
CHAHB), 4.08–4.19 (m, 2”1H; CHP, trans+cis), 4.30 (d, 2J
(H,H)=
13.5 Hz, 1H; CHAHBPh), 4.34 (d, 2J
(H,H)=13.5 Hz, 1H; CHAHBPh),
5.25–5.32 (m, 1H; =CHCH), 5.42 (dd, 3J(H,H)=15.8 Hz, 3J
(H,H)=
6.9 Hz, 1H; =CHCH), 5.56–5.60 (m, 1H; =CHCHP), 5.61–5.65 (m, 1H;
=CHCHP), 5.78 (d, 3J(H,H)=11.8 Hz, 1H; =CH), 6.13 (d, 3J
(H,H)=
15.8 Hz, 1H; =CH), 7.23–7.41 ppm (m, 2”5H; CHarom trans+cis);
13C NMR (75 MHz, CDCl3): d=22.2 (CH3), 23.2 (CH3), 23.3 (CH3), 28.2
(CH), 31.3 (CH), 53.0 (d, 2J(C,P)=8.1 Hz; OCH3), 53.1 (d, 2J
(C,P)=
6.9 Hz; OCH3), 53.6 (d, 2J(C,P)=6.9 Hz; OCH3), 53.8 (d, 2J
(C,P)=
8.1 Hz; OCH3), 59.6 (d, 3J(C,P)=9.2 Hz; CH2), 60.2 (d, 3J
(C,P)=3.5 Hz;
(C,P)=3.5 Hz; CH2Ph), 62.2 (d, 3J
(C,P)=8.1 Hz;
(C,P)=174.2 Hz; CHP), 68.7 (d, 1J
(C,P)=175.4 Hz;
1-benzyl-4-(3-methyl-but-1-enyl)-2,5-dihydro-1H-pyrrol-2-yl-
Dimethyl 1-benzyl-3-methyl-4-[(E)-2-phenylvinyl]-2,5-dihydropyrrol-2-yl-
1
phosphonate (12c): Yield: 88%; H NMR (300 MHz, CDCl3): d=2.00 (d,
4J
3.67 (d, 2J
6H; 2”OCH3), 4.00 (dd, 2J
NCHAHBC), 4.05–4.14 (m, 1H; CHP), 4.32 (d, 2J
NCHAHBPh), 6.25 (dd, 3J(H,H)=16.2 Hz, 4J
(H,H)=1.5 Hz, 1H; CHPh),
6.95 (d, 3J
(H,H)=16.2 Hz, 1H; CHCHPh), 7.12–7.45 ppm (m, 10H; 2”
Ph); 13C NMR (75 MHz, CDCl3): d=12.4 (CH3), 53.4 (d, 3J
(C,P)=
8.1 Hz; NCH2C), 53.1 (d, 2J(C,P)=6.9 Hz; OCH3), 53.6 (d, 2J
(C,P)=
6.9 Hz; OCH3), 60.2 (d, 3J(C,P)=6.9 Hz; NCH2C), 60.9 (d, 3J
(C,P)=
5.8 Hz, NCH2Ph), 73.1 (d, 1J(C,P)=171.9 Hz; CHP), 120.5 (d, 4J
(C,P)=
4.6 Hz; CHCHPh), 126.4 (2”CHarom), 127.2 (CHarom), 127.7 (CHarom),
128.5 (2”CHarom), 128.7 (4”CHarom), 130.0 (d, 5J
(C,P)=3.5 Hz; CHPh),
130.9 (d, 2J(C,P)=6.9 Hz; CCH3), 134.0 (d, 3J
(C,P)=12.7 Hz; CCH),
ACHTREUNG ACHTRENUG
(H,P)=1.9 Hz, 3H; CH3), 3.56 (d, 2J
(H,H)=12.0 Hz, 1H; NCHAHBC),
(H,H)=13.2 Hz, 1H; NCHAHBPh), 3.82 (d, 3J
(H,P)=10.2 Hz,
(H,H)=12.0 Hz, 4J
(H,H)=5.8 Hz, 1H;
(H,H)=13.2 Hz, 1H;
A
ACHTREUNG
AHCTREUNG
A
ACHTREUNG
A
ACHTREUNG
AHCTREUNG
AHCTREUNG
A
ACHTREUNG
A
ACHTREUNG
A
ACHTREUNG
ACHTREUNG
AHCTREUNG
ACHTREUNG
A
ACHTREUNG
AHCTREUNG
A
ACHTREUNG
A
ACHTREUNG
A
ACHTREUNG
A
ACHTREUNG
AHCTREUNG
,
A
ACHTREUNG
137.4 (Carom), 139.5 ppm (NCH2Carom); 31P NMR (121 MHz, CDCl3): d=
24.8 ppm; IR (film): n˜ =1255 (P=O), 1056, 1030 cmÀ1; MS: m/z (%):
384.2 [M+H]+ (100); chromatography (hexane/EtOAc 2:8) Rf =0.26; ele-
mental analysis (%) calcd for C22H26NO3P: C 68.92, H 6.83, N 3.65;
found: C 68.75, H 6.85, N 3.70.
A
ACHTREUNG
A
ACHTREUNG
A
ACHTREUNG
CH2Ph), 60.3 (d, 3J
G
ACHTREUNG
CH2), 68.0 (d, 1J
A
ACHTREUNG
2
4
Dimethyl
1-benzyl-4-[(1E)-pent-1-enyl]-2,5-dihydro-1H-pyrrol-2-yl-
CHP), 119.4 (d, J
A
ACHTRE(UNG C,P)=4.6 Hz; =
1
CH), 121.1 (d, 4J
G
ACHTREUNG
phosphonate (12d): Yield: 78%; H NMR (300 MHz, CDCl3): d=0.87 (t,
3J
CH2CH3), 2.04 (q, 3J
NCHAHB), 3.66 (d, 2J
1H; NCHAHB), 3.80 (d, J
10.2 Hz, 3H; OCH3), 4.13–4.19 (m, 1H; CHP), 4.33 (d, 2J
13.2 Hz, 1H; NCHAHBPh), 5.46 (dt, 3J(H,H)=15.8 Hz, 3J
(H,H)=7.3 Hz,
1H; CHCH2), 5.56 (s, 1H; NCHCH), 6.16 (d, 3J
(H,H)=15.8 Hz, 1H;
CHCH), 7.23–7.45 ppm (m, 5H; Ph); 13C NMR (75 MHz, CDCl3): d=
13.8 (CH3), 22.4 (CH2CH3), 35.0 (CHCH2), 53.2 (d, 2J
(C,P)=8.1 Hz;
OCH3), 53.8 (d, 2J(C,P)=6.9 Hz; OCH3), 59.7 (d, 3J
(C,P)=8.1 Hz;
NCH2), 60.4 (d, 3J(C,P)=3.5 Hz; NCH2Ph), 68.8 (d, 1J
(C,P)=174.2 Hz;
CHP), 119.2 (d, 2J(C,P)=6.9 Hz; NCHCH), 124.1 (d, 4J
(C,P)=4.6 Hz;
CHCH), 127.1 (CHarom), 128.4 (2”CHarom), 128.7 (2”CHarom), 134.4 (d,
5J(C,P)=3.5 Hz, CHCH2), 139.5 (Carom), 141.6 ppm (d, 4J
(C,P)=12.7 Hz;
A
ACHTRE(UNG H,H)=7.3 Hz, 2H;
ACHTREUNG
A
ACHTREUNG
3.5 Hz; =CHCH), 141.6 (=CHCH), 141.6 ppm (d, 3J
ACHTREUNG
ACHTREUNG
3
3
Cq); 31P NMR (121 MHz, CDCl3): d=24.75, 24.77 ppm; IR (film): n˜ =
1645 (C=C), 1242 (P=O), 1032 cmÀ1; MS: m/z (%): 336 [M+H]+ (100),
A
ACHTRE(UNG H,P)=
AHCTREUNG
(OMe)2]+ (46); chromatography (hexane/EtOAc 1:4):
ACHTREUNG
Rf =0.35; elemental analysis (%) calcd for C18H26NO3P: C 64.46, H 7.81,
A
ACHTREUNG
226 [M+HÀPO
AHCTREUNG
N 4.18; found: C 64.47, H 7.82, N 4.20.
AHCTREUNG
Synthesis of 2-phosphono pyrroles 13: Aminoalkenyl phosphonate 11
(0.39 mmol), tetrachloroquinone (0.43 mmol), and benzene (10 mL) were
added to an oven-dried round-bottomed flask. The solution was refluxed
under a nitrogen atmosphere and Grubbs second-generation catalyst 2
(0.02 mmol, 5 mol%) was added to this boiling solution. The reaction
mixture was then further refluxed for 16 h. The course of the reaction
was conveniently monitored by means of 31P NMR spectroscopic analyses
of samples taken directly from the reaction mixture. The product was
coated on silica gel by removal of the solvent in vacuo and purified by
flash chromatography.
A
ACHTREUNG
A
ACHTREUNG
A
ACHTREUNG
A
ACHTREUNG
Cq); 31P NMR (121 MHz, CDCl3): d=24.80 ppm; IR (film): n˜ =1241 (P=
O), 1058, 1033 cmÀ1; MS: m/z (%): 336.7 [M+H]+ (100); chromatogra-
phy (hexane/EtOAc 0:1): Rf =0.4; elemental analysis (%) calcd for
C18H26NO3P: C 64.46, H 7.81, N 4.18; found: C 64.67, H 7.80, N 4.21.
Chem. Eur. J. 2007, 13, 203 – 214
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
211

C. V. Stevens et al.
Dimethyl
(13a): Yield: 78%; trans/cis 75:25; 1H NMR (300 MHz, CDCl3): d=3.61
(d, 3J(H,P)=5.5 Hz, 3H; OCH3), 3.62 (d, 3J
(H,P)=11.6 Hz, 6H; 2”
OCH3), 3.65 (d, 3J
(H,P)=5.8 Hz, 3H; OCH3), 5.31 (s, 2H; NCH2Ph),
5.35 (s, 2H; NCH2Ph), 6.08 (d, 3J
(H,H)=12.7 Hz, 1H; OCCH), 6.19 (d,
1H, 3J(H,H)=12.7 Hz; OCCHCH), 6.21 (d, 3J
(H,H)=3.3 Hz, 1H;
OCCH), 6.33 (d, 3J(H,H)=3.3 Hz, 1H; OCCH), 6.37 (dd, 3J
(H,H)=
3.3 Hz, 3J(H,H)=1.8 Hz, 1H; OCHCH), 6.60 (d, 3J
(H,H)=16.2 Hz, 1H;
OCCH), 6.84 (d, J
1.7 Hz, 4J(H,P)=5.5 Hz, 1H; NCH), 7.01 (dd, 4J
3J(H,P)=3.7 Hz, 1H; NCCH), 7.08 (dd, 4J(H,H)=1.8 Hz, 4J
3.6 Hz, 1H; NCH), 7.11 (dd, 4J(H,H)=1.8 Hz, 3J
(H,P)=3.6 Hz, 1H;
NCCH), 7.14–7.42 ppm (m, 6H; Ph+OCH); 13C NMR (75 MHz,
CDCl3): d=52.6 (2”NCH2), 52.9 (d, 2J
(C,P)=5.8 Hz; 4”OCH3), 107.0
(OCCH), 109.9 (OCCH), 111.4 (OCHCH), 111.5 (OCHCH), 113.7
(NCHCCHCH), 114.5 (NCHCCHCH), 119.2 (d, 2J
(C,P)=17.3 Hz; 2”
(C,P)=227.3 Hz; CP), 119.1 (d,
(C,P)=15.0 Hz; NCHC), 123.38 (d,
(C,P)=13.8 Hz; NCHC), 123.66 (d, 2J
(C,P)=17.3 Hz; NCCH), 125.99
(C,P)=
10.4 Hz; NCH), 127.89 (CHarom), 128.78 (2”CHarom), 128.69 (2”CHarom),
137.51 (d, 4J
(C,P)=3.5 Hz; Carom), 137.86 (Carom), 141.35 (OCH), 141.58
1-benzyl-4-[(E)-2-(2-furyl)vinyl]-1H-pyrrol-2-ylphosphonate
4J
3J
N
(H,P)=5.2 Hz, 1H; NCH), 7.08 (dd, 4J=1.8 Hz,
ACHTREUNG
U
A
A
R
5.8 Hz; 2”OCH3), 119.1 (d, 3J(C,P)=226.1 Hz; CP), 119.4 (d, 2J
AHTCREUGN ACHTREUNG
E
17.3 Hz; NCCH), 120.8 (CHCHPh), 121.1 (d, 3J
A
2
3
A
U
122.3 (d, J
(C,P)=17.3 Hz; NCCH), 122.7 (CHCHPh), 123.4 (d, J
A
A
N
15.0 Hz; NCHC), 126.0 (2”CHarom), 126.3 (CHCHPh), 127.0 (CHarom),
127.3 (2”CHarom), 127.6 (d, 3J
(C,P)=11.5 Hz; NCH), 127.9 (CHarom),
G
A
ACHTREUNG
3
4
A
A
128.7 (2”CHarom), 128.8 (2”CHarom), 137.5 (Carom), 137.9 ppm (Carom);
31P NMR (121 MHz, CDCl3): d=12.97, 13.03 ppm; IR (film): n˜ =1639,
1254 (P=O), 1028 cmÀ1 (P-O); MS: m/z (%): 368.8 [M+H]+ (100); chro-
matography: (hexane/EtOAc 0:1): Rf =0.44; elemental analysis (%) calcd
for C21H22NO3P: C 68.66, H 6.04, N 3.81; found: C 68.41, H 6.16, N 3.71.
E
ACHTREUNG
G
A
ACHTREUNG
A
ACHTREUNG
AHCTREUNG
4-Methyl-N-prop-2-ynylbenzenesulfonamide
(15):
Propargylamine
(1.97 g, 36.4 mmol) and dry dichloromethane (25 mL) were added to an
oven-dried round-bottomed flask. Tosyl chloride (6.58 g, 34.5 mmol) and
pyridine (3.16 g, 40 mmol) were then added to this solution. The reaction
mixture was stirred for 16 h at room temperature and was then poured
into a separating funnel and washed with aq HCl (”3, 5 mL, 0.5m). The
combined aqueous layers were extracted once with CH2Cl2 (10 mL) and
the combined organic phases were dried by using MgSO4. 4-Methyl-N-
prop-2-ynylbenzenesulfonamide was obtained as a white solid after filtra-
tion and evaporation of the solvent. Yield: 92%; m.p. 768C (lit.[33] m.p.
AHCTREUNG
NCCH), 119.5 (NCHCCH), 119.0 (d, 1J
A
1J
3J
ACHTREUNG ACHTRENUG
(C,P)=227.3 Hz; CP), 123.06 (d, 3J
N
ACHTREUNG
(2”CHarom), 127.31 (2”CHarom), 127.48 (CHarom), 127.64 (d, 3J
A
ACHTREUNG
(OCH), 152.84 (OC), 153.64 ppm (OC); 31P NMR (121 MHz, CDCl3):
d=12.97, 12.91 ppm; IR (film): n˜ =1640, 1252 (P=O), 1027 cmÀ1; MS:
m/z (%): 358.8 [M+H]+ (100); chromatography (hexane/EtOAc 4:6):
Rf =0.18; elemental analysis (%) calcd for C19H20NO4P: C 63.86, H 5.64,
N 3.92; found: C 63.56, H 5.83, N 3.93
768C); 1H NMR (300 MHz, CDCl3): d=2.05 (dt, 4J
A
5J
3J
G
4
0.8 Hz, 1H; NCHAHB), 4.76 (brs, 1H; NH), 7.32 (d, 3J
U
Dimethyl 1-benzyl-3-methyl-4-[(E)-2-phenylvinyl]-1H-pyrrol-2-ylphosph-
onate (13c): Yield: 85%; 1H NMR (300 MHz, CDCl3): d=2.38 (s, 3H;
2H; 2”CHarom), 7.78 ppm (d, 3J
ACHTREUNG
13C NMR (75 MHz, CDCl3): d=21.7 (CH3), 33.0 (NCH2), 73.1 (CH), 78.0
(C), 127.5 (2”CHarom), 129.8 (2”CHarom), 136.6 (CH3Cq), 144.0 ppm
(SCq); IR (KBr): n˜ =1596 (C=C), 2131 (alkyne), 3270 cmÀ1 (NH); MS:
m/z (%): 227.7 [M+NH4]+ (100), 210.7 [M+H]+ (18).
CH3), 3.56 (d, 3J
6.76 (d, 3J
CHCHPh), 7.12–7.44 ppm (m, 11H; 2”Ph+NCH); 13C NMR (75 MHz,
CDCl3): d=10.9 (CH3), 52.2 (d, 2J
(C,P)=4.6 Hz; 2”OCH3), 52.7
(NCH2), 114.8 (d, 1J
(C,P)=225.0 Hz; CP), 120.2 (CHCHPh), 122.6 (d,
3J
(C,P)=15.0 Hz; NCHC), 126.0 (2”CHarom), 126.2 (d, J
NCH), 126.4 (CHPh), 127.0 (CHarom), 127.1 (2”CHarom), 127.6 (CHarom),
128.7 (4”CHarom), 131.5 (d, 2J
(C,P)=18.5 Hz; CCH3), 138.2 (Carom),
ACHTREUNG
A
ACHTREUNG
AHCTREUNG
N-[(2Z)-4-Chlorobut-2-enyl]-4-methyl-N-prop-2-ynylbenzenesulfonamide
(16g): Yield: 62%; 4-methyl-N-prop-2-ynylbenzenesulfonamide (0.50 g,
2.39 mmol) and acetone (25 mL) were added to an oven-dried round-bot-
tomed flask. (2Z)-1,4-Dichloro-2-butene (0.45 g, 3.58 mmol) and K2CO3
(1.32 g, 9.56 mmol) were then added to this solution and the reaction
mixture was refluxed for 16 h. After this time, the reaction mixture was
cooled and filtered. The product was coated on silica gel by removal of
the solvent in vacuo and purified by flash chromatograhy. N-4-Methyl-N-
[(2E)-3-phenylprop-2-enyl]-N-prop-2-ynylbenzenesulfonamide was ob-
ACHTREUNG
3
A
ACHTRE(UNG C,P)=11.5 Hz;
AHCTREUNG
138.2 ppm (NCH2Carom); 31P NMR (121 MHz, CDCl3): d=14.4 ppm; IR
(film): n˜ =1250 (P=O), 1046, 1023 cmÀ1; MS: m/z (%): 382.2 [M+H]+
(100); chromatography (hexane/EtOAc 2:8): Rf =0.46; elemental analysis
(%) calcd for C22H24NO3P: C 69.28, H 6.34, N 3.67; found: C 69.17, H
6.39, N 3.67.
tained as an oil. 1H NMR (300 MHz, CDCl3): d=2.05 (t, 4J
2.6 Hz, 1H; CHalkyne), 2.44 (s, 3H; CH3), 3.92 (dd, 3J
(H,H)=7.3 Hz,
4J(H,H)=1.3 Hz, 2H; CH2Cl), 4.09 (d, 4J
(H,H)=2.6 Hz, 2H; NCH2C),
4.11 (dd, 3J(H,H)=8.2 Hz, 4J
(H,H)=0.8 Hz, 2H; NCH2), 5.58 (dtt,
3J(H,H)=10.7 Hz, 3J(H,H)=8.2 Hz, 4J
(H,H)=1.3 Hz, 1H; NCH2CH),
5.88 (dtt, 3J(H,H)=10.7 Hz, 3J(H,H)=7.3 Hz, 4J
(H,H)=0.8 Hz, 1H;
CHCH2Cl), 7.31 (d, 3J(H,H)=8.1 Hz, 2H; 2”CHarom), 7.73 ppm (d, 3J-
(H,H)=8.1 Hz, 2H; 2”CHarom); 13C NMR (75 MHz, CDCl3): d=21.7
ACHTREUNG(H,H)=
Dimethyl
(13d): Yield: 48%; 1H NMR (300 MHz, CDCl3): d=0.92 (t, 3H,
3J(H,H)=7.2 Hz; CH3), 1.45 (sextet, 2H, 3J
(H,H)=7.2 Hz; CH2CH3),
(H,P)=11.3 Hz; 2”OCH3),
(H,H)=15.7 Hz, 3J
(H,H)=7.2 Hz, 1H;
(H,P)=1.0 Hz, 1H; CHCH), 6.83
(H,P)=5.4 Hz, 1H; NCH), 6.91 (dd, 4J
(H,H)=
(H,P)=3.4 Hz, 1H; NCCH), 7.12–7.15 (m, 2H, 2”CHarom),
7.27–7.35 ppm (m, 3H, 3”CHarom); 13C NMR (75 MHz, CDCl3): d=13.8
(CH3), 22.77 (CH2CH3), 35.1 (CHCH2), 52.4 (NCH2), 52.8 (d, 2J
(C,P)=
5.8 Hz; 2”OCH3), 117.7 (d, 1J(C,P)=222.2 Hz; CP), 119.2 (d, 2J
(C,P)=
18.5 Hz; NCCH), 121.6 (CHCH), 123.7 (d, 3J
(C,P)=15.0 Hz; NCHC),
1-benzyl-4-[(1E)-pent-1-enyl]-1H-pyrrol-2-ylphosphonate
ACHTREUNG
ACHTREUNG
A
G
N
ACHTREUNG
2.04–2.30 (m, 2H; CHCH2), 3.60 (d, 6H, 3J
U
A
ACHTREUNG
5.28 (s, 2H; NCH2), 5.93 (dt, 3J
A
T
G
A
ACHTREUNG
3
5
CHCH2), 6.18 (dd, J
(H,H)=15.7 Hz, J
A
ACHTREUNG
(dd, 4J
(H,H)=1.8 Hz, 4J
N
H
ACHTREUNG
1.8 Hz, 3J
T
(CH3), 36.1 (NCH2C), 38.5 (NCH2), 42.6 (CH2Cl), 74.2 (CHalkyne), 76.4
(Calkyne), 127.7 (NCH2CH), 127.9 (2”CHarom), 129.7 (2”CHarom), 131.1
(HCCH2Cl), 135.7 (CH3Cq), 143.9 ppm (SCq); IR (film): n˜ =1598 (C=C),
2120.8 cmÀ1 (alkyne); MS: m/z (%): 298.7/300.7 [M+H]+ (100); chroma-
tography: (hexane/EtOAc 7:3); Rf =0.51; elemental analysis (%) calcd
for C14H16ClNO2S: C 56.46, H 5.42, N 4.70; found: C 56.50, H 5.30, N
4.81.
AHCTREUNG
A
ACHTREUNG
AHCTREUNG
126.4 (d, 3J
ACHTREUNG(C,P)=10.4 Hz; NCH), 127.3 (2”CHarom), 127.8 (CHCH2),
128.5 (CHarom), 128.7 (2”CHarom), 137.8 ppm (Carom); 31P NMR (121 MHz,
CDCl3): d=13.37 ppm; IR (film): n˜ =1673, 1255 (P=O), 1029 cmÀ1 (P
À
N-[(2Z)-4-Bromobut-2-enyl]-4-methyl-N-prop-2-ynylbenzenesulfonamide
(16h): 4-Methyl-N-prop-2-ynylbenzenesulfonamide (0.50 g, 2.39 mmol)
and acetone (25 mL) were added to an oven-dried round-bottomed flask.
(2Z)-1,4-Dibromo-2-butene (0.77 g, 3.58 mmol) and K2CO3 (1.32 g,
9.56 mmol) were then added to this solution and the reaction mixture
was refluxed for 16 h. After this time, the reaction mixture was cooled
and filtered. The product was coated on silica gel by removal of the sol-
vent in vacuo and was then purified by flash chromatography. N-[(2Z)-4-
Bromobut-2-enyl]-4-methyl-N-prop-2-ynylbenzenesulfonamide was ob-
tained as a solid. Yield: 73%; 1H NMR (300 MHz, CDCl3): d=2.04 (t,
O); MS: m/z (%): 334.0 [M+H]+ (100); chromatography (hexane/EtOAc
1:1): Rf =0.24; elemental analysis (%) calcd for C18H24NO3P: C 64.85, H
7.26, N 4.20; found: C 64.60, H 7.29, N 4.41.
Dimethyl
1-benzyl-4-[(E)-2-phenylvinyl]-1H-pyrrol-2-ylphosphonate
(13e): Yield: 82%; trans/cis 82:18; 1H NMR (300 MHz, CDCl3): d=3.54
(d, 3J(H,P)=11.3 Hz, 6H; 2”OCH3), 3.63 (d, 3J
ACHTREUNG ACHTRE(UNG H,P)=11.3 Hz, 6H; 2”
OCH3), 5.22 (s, 2H; NCH2), 5.26 (s, 2H; NCH2), 6.34 (d, 3J
A
3
12.1 Hz, 1H; CHCHPh), 6.40 (d, J
N
ACHTREUNG ACRTHENUG ACHTRENUG
(dd, 4J(H,H)=1.8 Hz, 4J(H,P)=3.4 Hz, 1H; NCH), 6.73 (dd, 4J
1.8 Hz, 3J
(H,P)=5.4 Hz, 1H; NCCH), 6.82 (d, 3J
A
4J(H,H)=2.5 Hz, 1H; CHalkyne), 2.43 (s, 3H; CH3), 3.84 (d, 3J
AHTCREUGN ACHTREUNG
CHCHPh), 6.92 (d, 3J
U
6.7 Hz, 2H; NCH2), 3.92 (d, 3J
ACHTREUNG
212
www.chemeurj.org
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 203 – 214

Synthesis of 2-Phosphono Pyrroles
FULL PAPER
4J
15.1 Hz, 1H; NCH2CH), 5.94 (dt, 3J
1H; CHCH2Br), 7.30 (d, 3J
(H,H)=8.5 Hz, 2H; 2”CHarom), 7.95 ppm (d,
3J(H,H)=8.5 Hz, 2H; 2”CHarom); 13C NMR (75 MHz, CDCl3): d=21.8
(CH3), 31.3 (CH2Br), 36.2 (NCH2C), 47.5 (NCH2), 74.1 (CHalkyne), 76.5
(Calkyne), 127.8 (2”CHarom), 128.8 (NCH2CH), 129.7 (2”CHarom), 131.5
(HCCH2Br), 135.9 (CH3Cq), 143.8 ppm (SCq); IR (film): n˜ =1597 (C=C),
2120.8 cmÀ1 (alkyne); MS: m/z (%): 342.3/344.3 [M+H]+ (100); chroma-
tography: (hexane/EtOAc 7:3); Rf =0.44; elemental analysis (%) calcd
for C14H16BrNO2S: C 49.13, H 4.71, N 4.09; found: C 48.99, H 5.03, N
4.19.
C
G
U
160–1618C; 1H NMR (300 MHz, CDCl3): d=2.01 (t, 4J
2H; 2”CCH), 2.43 (s, 6H; 2”CH3), 3.93 (d, 3J
(H,H)=4.7 Hz, 4H; 2”
NCH2), 4.07 (d, 4J(H,H)=2.5 Hz, 4H; 2”NCH2C), 5.61 (t, 3J
(H,H)=
ACHTRE(UNG H,H)=2.5 Hz,
G
U
ACHTREUNG
N
C
ACHTREUNG
4.7 Hz, 2H; 2”NCH2CH), 7.26–7.73 ppm (m, 8H; 8”CHarom); 13C NMR
(75 MHz, CDCl3): d=21.6 (2”CH3), 36.4 (2”NCH2C), 43.2 (2”
NCH2CH), 74.0 (2”CHalkyne), 76.9 (2”Calkyne), 127.9 (4”CHarom), 129.1
(2”NCH2CH), 129.6 (4”CHarom), 135.9 (2”Cq,arom), 143.8 ppm (SCq); IR
(KBr): n˜ =1598 (C=C), 2119 cmÀ1 (alkyne); MS: m/z (%): 471.3 [M+H]+
(100); elemental analysis (%) calcd for C24H26N2O4S2: C 61.25, H 5.57, N
5.95; found: C 61.21, H 5.56, N 6.24.
Synthesis of 1-[(4-Methylphenyl)sulfonyl]-2,5-dihydro-1H-pyrroles 17:
Sulfonamide 16 (0.70 mmol) and benzene (10 mL) were added to an
oven-dried round-bottomed flask. The solution was refluxed under a ni-
N-[(2Z)-4-(4-Chlorophenoxy)but-2-enyl]-4-methyl-N-prop-2-ynylbenze-
nesulfon amide (16i): 4-Methyl-N-prop-2-ynylbenzenesulfonamide
(0.50 g, 2.39 mmol) and acetone (25 mL) were added to an oven-dried
round-bottomed flask. (2Z)-4-Chlorobut-2-enyl 4-chlorophenyl ether
(0.78 g, 3.58 mmol) and K2CO3 (1.32 g, 9.56 mmol) were then added to
this solution and the reaction mixture was refluxed for 16 h. After this
time, the reaction mixture was cooled and filtered. The product was
coated on silica gel by removal of the solvent in vacuo and purified by
flash chromatography. N-[(2Z)-4-(4-chlorophenoxy)but-2-enyl]-4-methyl-
N-prop-2-ynylbenzenesulfonamide was obtained as an oil. 1H NMR
trogen atmosphere and Grubbs second-generation catalyst
2
(0.034 mmol, 5 mol%) was added. The reaction mixture was then further
refluxed for 1 h. The product was coated on silica gel by removal of the
solvent in vacuo and purified by flash chromatography.
3-[(1E)-3-Chloroprop-1-enyl]-1-[(4-methylphenyl)sulfonyl]-2,5-dihydro-
1H-pyrrole (17g): Yield: 86%; 1H NMR (300 MHz, CDCl3): d=2.43 (s,
3H; CH3), 4.09 (d, 3J
CH2NCH2), 5.59 (dt, 3J
CHCH2Cl), 5.66 (s, 1H; CH=C), 6.33 (d, 3J
CH), 7.33 (d, 3J(H,H)=8.1 Hz, 2H; 2”CHarom), 7.73 ppm (d, 3J
ACHTREUNG
ACHTREUNG
A
ACHTREUNG
(300 MHz, CDCl3): d=1.98 (t, 4J
3H; CH3), 3.94 (brd, 2H, 3J(H,H)=7.3 Hz; NCH2), 4.11 (d, 4J
2.5 Hz, 2H; NCH2C), 4.59 (dd, 3J(H,H)=6.0 Hz, 4J
(H,H)=1.1 Hz, 2H;
OCH2), 5.63 (dtt, 3J(H,H)=10.6 Hz, 3J(H,H)=7.3 Hz, 4J
(H,H)=1.5 Hz,
1H; NCH2CH), 5.93 (dtt, 3J(H,H)=10.6 Hz, 3J(H,H)=6.0 Hz, 4J
(H,H)=
1.1 Hz, 1H; CHCH2O), 6.77–6.84 (m, 2H; CHarom), 7.30 (d, 3J
(H,H)=
ACHTREUNG
AHCTREUNG
A
ACHTREUNG
E
8.1 Hz, 2H; 2”CHarom); 13C NMR (75 MHz, CDCl3): d=21.6 (CH3), 44.6
(CH2Cl), 53.7 (NCH2), 55.1 (NCH2), 125.0 (HC=C), 127.1 (CH=CH),
127.5 (2”CHarom), 127.8 (CH2ClCH), 130.0 (2”CHarom), 134.0 (C=CH),
136.0 (CH3Cq), 143.8 ppm (SCq); IR (film): n˜ =1597 cmÀ1 (C=C); MS:
m/z (%): 298.3/300.3 [M+H]+ (100); chromatography: (hexane/EtOAc
8:2): Rf =0.19; elemental analysis (%) calcd for C14H16ClNO2S: C 56.46,
H 5.42, N 4.70; found: C 56.40, H 5.07, N 4.69.
A
ACHTREUNG
A
N
ACHTREUNG
A
N
ACHTREUNG
AHCTREUNG
8.1 Hz, 2H; 2”CHTos), 7.32–7.36 (m, 2H; CHarom), 7.73 ppm (d, J=
8.1 Hz, 2H; 2”CHTos); 13C NMR (75 MHz, CDCl3): d=21.67 (CH3),
36.09 (NCH2C), 43.28 (NCH2), 63.86 (OCH2), 74.09 (Cq,alkyne), 77.36
(CHalkyne), 116.05 (2”CHarom), 125.97 (CqCl), 127.25 (NCH2CH), 127.88
(2”CHarom), 129.44 (2”CHarom), 129.70 (2”CHarom), 130.64 (HCCH2O),
135.74 (CH3Cq), 143.90 (SCq), 157.01 ppm (OCq); IR (film): n˜ =1596 cmÀ1
(C=C); MS: m/z (%): 390.2/392.3 [M+H]+ (100); chromatography:
(hexane/EtOAc 7:3): Rf =0.38; elemental analysis (%) calcd for
C20H20ClNO3S: C 61.61, H 5.17, N 3.59; found: C 61.47, H 5.06, N 3.61.
Yield: 81%.
3-[(1E)-3-Bromoprop-1-enyl]-1-[(4-methylphenyl)sulfonyl]-2,5-dihydro-
1H-pyrrole (17h): Yield: 76%; 1H NMR (300 MHz, CDCl3): d=2.43 (s,
3H; CH3), 3.99 (d, 3J
ACHTREUNG
A
ACHTREUNG
AHCTREUNG
A
ACHTREUNG
8.4 Hz, 2H; 2”CHarom); 13C NMR (75 MHz, CDCl3): d=21.6 (CH3), 32.3
(CH2Br), 53.6 (NCH2), 55.1 (NCH2), 125.2 (HC=C), 127.5 (HC=CH+2”
CHarom), 128.2 (CH2BrCH), 130.0 (2”CHarom), 134.0 (C=CH), 136.0
(CH3Cq), 143.8 ppm (SCq); IR (film): n˜ =1597 cmÀ1 (C=C); MS: m/z (%):
342.3/344.3 [M+H]+ (100); chromatography: (hexane/EtOAc 7:3): Rf =
0.28; elemental analysis (%) calcd for C14H16BrNO2S: C 49.13, H 4.71, N
4.09; found: C 49.25, H 4.92, N 4.31.
N-4-methyl-N-[(2E)-3-phenylprop-2-enyl]-N-prop-2-ynylbenzenesulfona-
mide
(16j):
4-Methyl-N-prop-2-ynylbenzenesulfonamide
(0.50 g,
2.39 mmol) and acetone (25 mL) were added to an oven-dried round-bot-
tomed flask. Cinnamylbromide (0.71 g, 3.58 mmol) and K2CO3 (1.32 g,
9.56 mmol) were then added to this solution and the reaction mixture
was refluxed for 16 h. After this time, the reaction mixture was cooled
and filtered. The product was coated on silica gel by removal of the sol-
vent in vacuo and purified by flash chromatography. N-4-Methyl-N-
[(2E)-3-phenylprop-2-enyl]-N-prop-2-ynylbenzenesulfon amide is ob-
3-[(E)-2-(4-Chlorophenoxy)vinyl]-1-[4-methylphenyl)sulfonyl]-2,5-dihy-
dro-1H-pyrrole (17i trans/cis 63:37): Yield: 73%; 1H NMR (300 MHz,
CDCl3): d=2.43 (s, 3H; CH3), 2.45 (s, 3H; CH3), 4.19–4.23 (m, 8H;
solid. Yield: 71%; m.p. 73–748C, lit.[34] m.p. 79–818C;
(H,H)=2.5 Hz, 1H; CHalkyne),
CH2NCH2), 4.53 (brd, 2H, 3J
3J
5.66 (dt, 3J
3J(H,H)=11.8 Hz, 3J
11.8 Hz, 1H; HC=CH), 6.39 (d, 3J
AHCTREUNG
(H,H)=5.7 Hz; CH2O), 4.56 (brd, 2H,
(H,H)=6.5 Hz; CH2O), 5.58 (brs, 1H; HC=C), 5.63 (brs, 1H; HC=C),
(H,H)=16.0 Hz, 3J
(H,H)=5.7 Hz, 1H; OCH2CH), 5.79 (dt,
(H,H)=6.5 Hz, 1H; OCH2CH), 6.02 (d, 3J
(H,H)=
(H,H)=16.0 Hz, 1H; HC=CH), 6.74–
tained as
1H NMR (300 MHz, CDCl3): d=2.05 (t, 4J
2.42 (s, 3H; CH3), 3.99 (d, 3J
(H,H)=6.9 Hz, 2H; NCH2CH), 4.13 (d,
4J(H,H)=2.5 Hz, 2H; NCH2C), 6.07 (dt, 3J(H,H)=15.7 Hz, 3J
(H,H)=
6.9 Hz, 1H; NCH2CH), 6.57 (d, J(H,H)=15.7 Hz, 1H; CHPh), 7.23–7.35
(m, 7H; CHarom), 7.76 ppm (d, 3J
(H,H)=8.5 Hz, 2H; 2”CHarom);
a
AHCTREUNG
AHCTREUNG
AHCTREUNG
G
ACHTREUNG
A
G
ACHTREUNG
A
G
ACHTREUNG
3
AHCTREUNG
AHCTREUNG
6.85 (m, 4H; 4”CHarom), 7.14–7.38 (m, 4H; 4”CHarom), 7.69–7.77 ppm
(m, 4H; 4”CHarom); 13C NMR (75 MHz, CDCl3): d=21.6 (2”CH3), 53.8
(NCH2), 54.8 (NCH2), 55.2 (NCH2), 55.9 (NCH2), 65.0 (OCH2), 68.2
(OCH2), 116.1 (2”CHarom), 116.8 (2”CHarom), 124.2 (HC=C), 124.6 (HC=
CH), 125.9 (HC=C), 126.0 (HC=CH), 126.1 (2”CqCl), 127.0 (OCH2CH),
127.5 (2”CHarom), 128.7 (OCH2CH), 129.5 (2”CHarom), 130.0 (2”
CHarom), 134.1 (C=CH), 135.1 (C=CH), 136.3 (2”CH3Cq), 143.7 (SCq),
143.8 (SCq), 156.8 (OCq), 157.0 ppm (OCq); IR (film): n˜ =1581 (C=C),
1596 cmÀ1 (C=C); MS: m/z (%): 390.2/392.3 [M+H]+ (100); chromatog-
raphy: (hexane/EtOAc 7:3): Rf =0.17; elemental analysis (%) calcd for
C20H20ClNO3S: C 61.61, H 5.17, N 3.59; found: C 61.77, H 5.37, N 3.62.
13C NMR (75 MHz, CDCl3): d=21.7 (CH3), 36.0 (NCH2C), 48.7 (NCH2),
74.0 (CHalkyne), 76.7 (Calkyne), 123.0 (NCH2CH), 126.7 (2”CHarom), 127.9
(2”CHarom), 128.2 (CHarom), 128.7 (2”CHarom), 129.7 (2”CHarom), 135.0
(HCPh), 136.1 (Cq,arom), 136.2 (Cq,arom), 143.8 ppm (SCq); IR (KBr): n˜ =
1598 (C=C), 2116 cmÀ1 (alkyne); MS: m/z (%): 326.4 [M+H]+ (100);
chromatography: (hexane/EtOAc 6:4): Rf =0.58.
4-Methyl-N-{(2Z)-4-[prop-2-ynyl-(toluene-4-sulfonyl)amino]but-2-enyl}-
N-prop-2-ynylbenzenesulfonamide (32): Yield: 89%; 4-Methyl-N-prop-2-
ynylbenzenesulfonamide (0.50 g, 2.39 mmol) and acetone (25 mL) were
added to an oven-dried round-bottomed flask. (2Z)-1,4-Dibromo-2-
butene (0.27 g, 1.19 mmol) and K2CO3 (1.32 g, 9.56 mmol) were then
added to this solution and the reaction mixture was refluxed for 16 h.
After this time, the reaction mixture was cooled and filtered. The residue
was dissolved in a minimal amount of warm THF and placed in the freez-
1-[(4-Methylphenyl)sulfonyl]-3-[(E)-2-phenylvinyl]-2,5-dihydro-1H-pyr-
role (17j): Yield: 89%; 1H NMR (300 MHz, CDCl3): d=2.42 (s, 3H;
CH3), 4.18–4.25 (m, 2H; NCH2), 4.32–4.43 (m, 2H; NCH2), 5.69 (brs,
1H; NCH2CH), 6.33 (d, 3J
3J
7.76 ppm (d, 3J
ACHTREUNG
er.
4-Methyl-N-{(2Z)-4-[prop-2-ynyl(toluene-4-sulfonyl)amino]but-2-
ACHTREUNG
enyl}-N-prop-2-ynylbenzenesulfonamide was obtained as a solid. M.p.
AHCTREUNG
Chem. Eur. J. 2007, 13, 203 – 214
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
213

C. V. Stevens et al.
C6D6): d=1.85 (s, 3H; CH3), 4.04–4.06 (m, 2H; NCH2), 4.27–4.31 (m,
2H; NCH2), 4.97 (brs, 1H; NCH2CH), 6.04 (d, 3J
(H,H)=16.2 Hz, 1H;
HC=CH), 6.39 (d, 3J(H,H)=16.2 Hz, 1H; HC=CH), 6.77 (d, 3J
(H,H)=
8.1 Hz, 2H; 2”CHarom), 7.00–7.15 (m, 5H; Ph), 7.79 ppm (d, 3J
(H,H)=
[13] G. C. Lloyd-Jones, R. G. Margue, J. G. de Vries, Angew. Chem. 2005,
117, 7608–7613; Angew. Chem. Int. Ed. 2005, 44, 7442–7447.
[14] H.-Y. Lee, H. Y. Kim, H. Tae, B. G. Kim, J. Lee, Org. Lett. 2003, 5,
3439–3442.
AHCTREUNG
A
ACHTREUNG
AHCTREUNG
8.1 Hz, 2H; 2”CHarom); 13C NMR (75 MHz, CDCl3): d=21.6 (CH3), 53.9
(NCH2), 55.3 (NCH2), 121.6 (HC=C), 123.5 (NCH2CH), 126.6 (2”
CHarom), 127.6 (2”CHarom), 128.3 (CHarom), 128.8 (2”CHarom), 129.9 (2”
CHarom), 131.5 (CHPh), 134.2 (C=CH), 136.5 (CH3Cq), 137.3 (Cq,arom),
143.7 (SCq); IR (film): n˜ =1596 cmÀ1 (C=C); MS: m/z (%): 326.3
[M+H]+ (100); elemental analysis (%) calcd for C19H19NO2S: C 70.12, H
5.88, N 4.30; found: C 70.24, H 6.09, N 4.48.
[15] D. E. Fogg, E. N. dos Santos, Coord. Chem. Rev. 2004, 248, 2365–
2379.
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Lett. 2001, 3, 2045–2048; c) R. Grigg, A. Hodgson, J. Morris, V.
Sridharan, Tetrahedron Lett. 2003, 44, 1023–1026; d) H. Y. Lee,
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e) B. Schmidt, J. Org. Chem. 2004, 69, 7672–7687; f) W. A. L. van
Otterlo, G. L. Morgans, L. G. Madeley, S. Kuzvidza, S. S. Moleele, N.
Thornton, C. B. de Koning, Tetrahedron 2005, 61, 7746–7755;
g) W. A. L. van Otterlo, E. Coyanis, E. Mabel, J. L. Panayides, C. B.
de Koning, M. A. Fernandes, Synlett 2005, 501–505; h) S. Beligny, S.
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[19] For a recent review on the use of RCM for the synthesis of nitro-
gen-containing heterocycles see: A. Deiters, S. F. Martin, Chem.
Rev. 2004, 104, 2199–2238.
1-[(4-Methylphenyl)sulfonyl]-3-{(E)-2-[1-(4-methylphenyl)sulfonyl)-2,5-
dihydro-1H-pyrrol-3-yl]vinyl}-2,5-dihydro-1H-pyrrole (40): Yield: 74%;
m.p. 180–2008C (decomp); 1H NMR (300 MHz, CDCl3): d=2.42 (s, 6H;
2”CH3), 4.18 (s, 8H; 2”CH2NCH2), 5.66 (s, 2H; 2”NCH2CH), 5.99 (s,
2H; CH=CH), 7.31 (d, 3J
ACHTREUNG
ACHTREUNG
3J
(2”CH3), 53.5 (2”NCH2), 55.3 (2”NCH2), 124.2 (HC=CH), 125.0 (2”
HC=C), 127.5 (4”CHarom), 129.9 (4”CHarom), 134.1 (2”HC=C), 136.7
(2”CH3Cq), 143.7 ppm (2”SCq); IR (KBr): n˜ =1597 cmÀ1 (C=C); MS:
m/z (%): 471.3 [M+H]+ (100); chromatography: (hexane/EtOAc 1:1):
Rf =0.49; elemental analysis (%) calcd for C24H26N2O4S2: C 61.25, H
5.57, N 5.95; found: C 61.39, H 5.60, N 5.99.
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Acknowledgements
Financial support from the BOF (Bijzonder Onderzoeksfonds Universi-
teit Gent, Research Fund Ghent University) and the FWO (Fonds voor
Wetenschappelijk Onderzoek Vlaanderen, Fund for Scientific research
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