Use of allenylphosphonates as new substrates for phosphane-catalyzed [3+2] and [4+2] annulations

Article abstract of DOI:10.1002/ejoc.200800347

The suitability of allenylphosphonates as substrates in phosphane-catalyzed annulation reactions has been investigated. Despite their lower reactivity relative to allenyl esters, allenylphosphonates overall display the anticipated behavior: pyrrolines, te

Full text of DOI:10.1002/ejoc.200800347

FULL PAPER
DOI: 10.1002/ejoc.200800347
Use of Allenylphosphonates as New Substrates for Phosphane-Catalyzed [3+2]
and [4+2] Annulations
Armen Panossian,[a] Nicolas Fleury-Brégeot,[a] and Angela Marinetti*[a]
Keywords: Phosphanes / Organocatalysis / Phosphonates / Allenes / Asymmetric catalysis
The suitability of allenylphosphonates as substrates in phos-
phane-catalyzed annulation reactions has been investigated.
Despite their lower reactivity relative to allenyl esters, allen-
ylphosphonates overall display the anticipated behavior:
pyrrolines, tetrahydropyridines, and cyclopentenes bearing
phosphoryl functions were obtained from imines, α,β-unsatu-
rated esters, and enones in Bu3P- or iBu3P-promoted re-
actions. Enantioselective variants of these cyclization reac-
tions afforded enantiomeric excesses of up to 90% when
phosphepine A2 was used as the chiral catalyst.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2008)
rated esters, and enones catalyzed by nucleophilic phos-
phanes and preliminary results on the use of enantiomeri-
cally pure promoters in the same reactions.
Introduction
A number of literature reports show that electron-de-
ficient allenes are suitable substrates for a range of phos-
phane-catalyzed transformations.[1] These involve the ad-
dition of a phosphorus nucleophile to the central carbon
atom of the allene moiety as a key step, followed by reac-
tion of the resulting dipole with electron-deficient sub-
strates such as olefins (α,β-unsaturated esters, ketones, ni-
triles, sulfones, and nitroalkenes),[2] imines,[3] and alde-
hydes[4] in both inter- and intramolecular[2g] processes. In
other instances, the zwitterionic phosphane–allene adduct
causes deprotonation of weak acids and allows addition of
the conjugated base to the allenic substrate in an “umpo-
lung” approach.[5] The synthetic usefulness of these meth-
ods has been widely demonstrated[2g,6] and some enantiose-
lective variants have been envisioned.[7]
So far, mainly buta-2,3-dienoates and, more recently, all-
enic ketones[7h,8] have been used as substrates in these phos-
phane-catalyzed processes. Thus, to extend the scope of the
methodology, we have considered using allenylphosphon-
ates as new substrates. Their transformations through phos-
phane-promoted reactions would give rise to versatile syn-
thetic intermediates[9] as well as to a variety of unprece-
dented phosphoryl-functionalized compounds, including
cyclic and heterocyclic frameworks, potentially relevant to
agrochemical and medicinal chemistry.[10]
Results and Discussion
Dialkyl allenylphosphonates are readily available in
multigram quantities from propargylic alcohols and dialkyl
chlorophosphites[11] by thermally induced SNiЈ-type re-
arrangement of the intermediate 2-propynyl phosphites.
Therefore they represent inexpensive and suitable starting
materials in phosphonate chemistry.[12] The outcomes of
their phosphane-promoted reactions with unsaturated elec-
tron-deficient substrates can be anticipated as a result of
the possible activation of the allenic phosphonates by phos-
phane addition to the β-carbon atoms (Scheme 1).[1,3b] The
resulting zwitterionic phosphonium salts are expected to re-
Herein, we report our investigations on the annulation
reactions of allenylphosphonates with imines, α,β-unsatu-
[a] Institut de Chimie des Substances Naturelles,
CNRS UPR 2301,
1, av. de la Terrasse, 91198 Gif-sur-Yvette Cedex, France
Fax: +33-1-69077247
E-mail: angela.marinetti@icsn.cnrs-gif.fr
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
Scheme 1. Activation of allenylphosphonates by nucleophilic phos-
phanes.
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© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Phosphane-Catalyzed [3+2] and [4+2] Annulations
act then with electron-poor substrates (X=CHRЈЈ in
Scheme 1, with X = NTs, CHCO2R, CHCOR, etc.) via
either their α- or γ-carbanionic forms I and II, respectively.
Subsequent annulation would lead to the cyclic phos-
phonate derivatives.
In order to check the suitability of allenylphosphonates
for such annulation processes, the reactivity of the allenyl-
phosphonate 1a was investigated first in the [3+2] cycliza-
tion reaction with N-tosylbenzaldimine (2a) (Scheme 2).
With tributylphosphane as the catalyst, the reaction led to
the anticipated pyrroline 3a by formal addition of the α-
carbanionic intermediate I to the imine, followed by cycliza-
tion, according to the reaction pathway postulated by Xu
and Lu for allenic esters.[3b]
Scheme 3. Triisobutylphosphane-catalyzed [3+2] annulations of al-
lenylphosphonates with imines. Conditions: 1:2 phosphonate/imine
ratio. Conversion rates refer to the amount of pyrroline in the crude
reaction mixture (1H NMR) with respect to the total amount of
phosphonate derivatives. Total conversion of the starting phos-
[a]
[b]
phonate was mainly observed. Isolated yields: 40%; 20–30%;
[c]
not determined.
chromatography and, consequently, only moderate-to-low
yields (20–40%) of the pure pyrrolines 3 could be obtained.
The alkyne byproduct 4 could not be further converted into
the desired pyrroline, even after prolonged heating at
120 °C in the presence of N-tosylbenzaldimine and PBu3, at
variance with the known behavior of but-2-ynoates, which
usually undergo phosphane-promoted cyclizations.[3b]
Better results were obtained in a second series of experi-
ments (Scheme 4) in which the α-substituted diethyl buta-
2,3-dienylphosphonate (1c)[15] was treated with various im-
ines with the aim of accessing functionalized tetrahydropyr-
idines.[3c] The anticipated formal [4+2] cyclization reactions
are supposed to involve addition of the γ-carbanion II
(Scheme 1) to the imine and subsequent cyclization.
Scheme 2. [3+2] Annulation of diethyl allenylphosphonate (1a)
with N-tosylbenzaldimine (2a).
The allenylphosphonate displayed, however, much lower
reactivity than the corresponding allenic ester: at room tem-
perature, a reaction time of 4 d was required to afford total
conversion of the starting allene. Moreover, the reaction led
to an 18:82 mixture of the pyrroline 3a and prop-1-ynylphos-
phonate 4a, which shows that prototropic isomerization of
the allenyl phosphonate, known to proceed in the presence
of organic bases,[11c,13] may occur as a major competitive
reaction. Changing the reaction conditions improved, how-
ever, the product distribution. Thus, for instance, running
the reaction at 80 °C in THF improved the product distri-
bution up to a 50:50 ratio of 3a/4a. Finally, the highest con-
version rate was attained when the reaction was run at high
temperature (120 °C) in toluene in the presence of excess
imine (allenylphosphonate/imine ratio = 1:2) with P(iBu)3
as the catalyst. Under these conditions, the amount of 3a
obtained increased to 69%. Total conversion was achieved
after 5 h.
The optimized conditions above were then applied in fur-
ther experiments in which the arylimine reactant and the
phosphonate ester moiety were varied in order to evaluate
the scope of the reaction (Scheme 3).
Scheme 4. [4+2] Annulation reactions of allenylphosphonate 1c
with imines.
Starting from the p-nitrobenzaldimine 2b, the desired
pyrroline 3b was predominantly formed (85:15 ratio of 3b/
As shown in Scheme 4, the expected 3-phosphoryl-tetra-
4a), whereas with imines 2c and 2d the side-reaction that hydropyridines 6a,c,d were obtained in good yields. PBu3 is
leads to the isomerization product predominates over the a suitable catalyst leading to total conversion of 1c after
cyclization reaction. Therefore, only moderate conversion 24 h at 120 °C, whereas P(iBu3) displayed rather moderate
rates to 3c and 3d were observed. The cyclic phosphonate catalytic activity (60% conversion of 1c into 6a under the
1b[14] displayed lower reactivity than 1a.
same conditions). Of the four imines tested so far, only the
The formation of the alkyne byproduct 4 thus represents p-nitrophenyl-substituted imine 2b failed to react in the
a major drawback of the above reactions, all the more so [4+2] cyclization reaction, although its electron-poor char-
because the mixture of 3 and 4 is difficult to separate by acter would be expected to favor nucleophilic additions. In-
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A. Panossian, N. Fleury-Brégeot, A. Marinetti
FULL PAPER
hibition of the reaction might result from extra stabilization
The cyclopentenylphosphonate 8 was isolated as a single
of a zwitterionic intermediate by the electron-withdrawing diastereomer. The trans stereochemistry was assigned to
p-NO2-phenyl moiety. this compound on the basis of the coupling constants of the
The phosphane-promoted annulations of allenylphos- ring hydrogen atoms and by analogy to literature data.[2a,19]
phonates were then extended to electrophilic alkenes as cy- The α,β-unsaturated enones 9a–f also underwent formal
clization partners. Since the pioneering work of Zhang and [3+2] cycloaddition reactions with 1a to afford the corre-
Lu,[2a] alkenes bearing electron-withdrawing substituents sponding cyclopentenones 10 with excellent regio- and
are known to react with electron-deficient allenes under stereoselectivity. The geometry of the starting olefins is re-
phosphane catalysis to give cyclopentenes through formal tained in the cyclization reactions, which thus give the trans
[3+2] cycloaddition reactions.[2d,2e,7d] Analogous reactions isomers of 10.[20] If we assume that a stepwise mechanism
were performed therefore starting from the allenylphos- is taking place here,[21] it appears that 10 results from attack
phonate 1a (Scheme 5).
of the γ-carbanionic form II of the dipole intermediate
(Scheme 1) on the enone substrate. Potentially competitive
α-addition processes were not unambiguously noticed in
these experiments: small amounts of side-products were ob-
served in the crude reaction mixtures, but they were not
isolated in pure form. In the analogous cyclization reactions
of allenic esters with electron-poor olefins both α and γ
additions were reported, with products ratios ranging from
1 to 30. As a general trend, α addition took place preferen-
tially when terminal olefins were used as cyclization part-
ners,[2a,2d,7a] whereas chalcone and other substituted olefins
mainly afforded the γ-addition products.[7d,7i]
Having determined that the behavior of allenylphos-
phonates in phosphane-promoted reactions with both
imines and electron-poor olefins parallels that of the corre-
sponding allenic esters, we next envisioned an enantioselec-
tive version of the same cyclization reactions. As a prelimi-
nary investigation, we explored the use of phosphepines
A[22] as chiral catalysts for the same transformations.
Scheme 5. [3+2] Annulations of allenylphosphonate 1a with elec-
tron-poor alkenes. Reaction conditions: experiments were per-
formed in toluene at 120 °C for 24 h with an allenylphosphonate/
olefin ratio of 1:2 at a phosphonate concentration of 0.1 . Conver-
sion rates refer to the amount of 8 or 10 in the crude reaction
mixture.
Phosphepines A have previously been used in enantiose-
lective [3+2] cyclization reactions between buta-2,3-dien-
In the reaction of the allenylphosphonate 1a with diethyl oates and both imines[7g] and chalcones[7d] as well as in
fumarate, a mixture of the desired cyclopentenylphosphon- [4+2] annulations.[7c] In this work, the potential of phos-
ate 8 and the alkyne 4a were obtained, the relative amounts phepines (S)-A1 and (S)-A2 as chiral catalysts was evaluated
of which were highly dependent on the reaction conditions in the cyclization reactions that lead to phosphonates 3, 5,
(catalyst, temperature, solvent, and dilution). Optimized 8, and 10 (Table 1).
conditions involve a high temperature (120 °C), the use of
Phosphepines A displayed moderate-to-low conversion
toluene as solvent,[16] a 0.1  concentration of substrates, rates because of the above-mentioned isomerization of the
and 10 mol-% of P(iBu)3 as the catalyst. Total conversion allenylphosphonates to the corresponding alkynes, which
of the starting allene was achieved after 5 h and an 8/4a here becomes highly competitive. A high reaction tempera-
ratio of 90:10 was observed in the crude reaction mixture ture was required to ensure total conversion of the starting
(entry 3). The higher efficiency of P(iBu)3 (entry 3 vs. 2) material as well as to reduce the amount of alkyne side-
might be assigned to its lower basicity [pKa (MeNO2) = product. Nevertheless, despite the harsh reaction condi-
7.97][17] with respect to PBu3 [pKa (MeNO2) = 8.43], as tions, high enantioselectivities could be attained, in some
more basic phosphanes are expected to favor the competi- instances at least, when using the tert-butyl-substituted
tive isomerization of the allenylphosphonate to diethyl pro- phosphepine A2 as the catalyst (Table 1).
pynylphosphonate.[18] The amount of phosphane catalyst
could be reduced to 5% without a significant decrease in were performed at 120 °C with phosphepine A2 as the cata-
the conversion rate or the 8/4a ratio. lyst, pyrrolines 3a and 3c were obtained in moderate enan-
When the reactions between 1a and imines 2a and 2c
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Phosphane-Catalyzed [3+2] and [4+2] Annulations
Table 1. Asymmetric [3+2] cyclization reactions of allenylphos- investigated. The use of the binaphthyl-derived phosphep-
phonates 1a and 1b promoted by phosphepines (S)-A2.
ine (S)-A2 allowed asymmetric versions of the [3+2] annu-
lations to be performed with moderate-to-high enantio-
selectivity levels.
Experimental Section
Diethyl (propa-1,2-dienyl)phosphonate (1a),[11a] (5,5-dimethyl-2-
oxo-2-propa-1,2-dienyl)-1,3,2-dioxaphosphinane (1b)[14] and di-
ethyl (buta-2,3-dien-2-yl)phosphonate (1c)[15] were prepared by
thermal rearrangement of the corresponding 2-propynyl phosphites
as described in the literature.
Entry
Product Reaction conditions[a] Conv. (% yield)
% ee
1
2
3
4
5
6
7
8
3a
3a
dioxane, 80 °C
dioxane, 120 °C
dioxane, 120 °C
dioxane, 120 °C
toluene, 120 °C
toluene, 120 °C[b]
toluene, 120 °C
toluene, 120 °C
25
45
25
68
57
58
65
91
89
85
81
3c
5a
[3+2] Cyclization Reactions between Allenylphosphonates and Im-
ines. Typical Procedure: The allenylphosphonate (0.3 mmol, 53 mg
of 1a or 56 mg of 1b) and the imine (0.3 mmol, e.g., 78 mg of N-
tosylbenzaldimine) were dissolved in anhydrous solvent (1 mL) un-
der argon in an oven-dried 5 mL vial. A 1  solution of the phos-
phane catalyst in toluene (30 µL, 0.03 mmol) was added. The vial
was capped and the reaction mixture was heated at the given tem-
perature for 24 h. The solvent was removed and the conversion rate
and product ratio were determined by 1H NMR analysis. The final
pyrroline was purified by column chromatography. Enantiomeric
excesses were determined by chiral HPLC.
30
8
70 (55)
35
61 (35)
9
10a
10c
10f
[a] Reaction time: 24 h, 10 mol-% catalyst, 1:2 reactant ratio. Enan-
tiomeric excesses (ee) were determined by chiral HPLC. [b] Reac-
tion time: 48 h.
Diethyl (2-Phenyl-1-tosyl-2,5-dihydro-1H-pyrrol-3-yl)phosphonate
(3a): Purification was performed by silica gel column chromatog-
raphy with heptane/ethyl acetate (2:8) as the eluent (Rf = 0.3). Pale-
tiomeric excesses (57 and 58%, respectively, entries 2 and
3). The ee was slightly higher at a lower temperature (3a: ee
68% at 80 °C, entry 1). The P-phenyl-substituted phos-
phepine A1 afforded very low enantioselectivities. As an ex-
ample, when the cyclization leading to 3a was performed
with A1 as the catalyst at 80 °C in THF, an ee of Ͻ10%
was obtained.
In the [3+2] cyclization between 1a and diethyl fumarate,
cyclopentenylphosphonate 8 was obtained in up to 91% ee
(entry 5). For comparison purposes it is worth noting that
the analogous reaction of ethyl buta-2,3-dienoate with di-
ethyl fumarate, promoted by phosphepine (S)-A2, afforded
triethyl cyclopent-3-ene-1,2,3-tricarboxylate[2a,7a] in com-
parable ee (93% ee).[23]
The annulations between phosphonate 1a and the enones
(entries 6–8) led to enantiomeric excesses of up to 89%,
which are fully comparable to those obtained by Wilson
and Fu[7d] in the reactions between ethyl buta-2,3-dienoate
and enones with phosphepine (S)-A2 as the catalyst. Enones
9d and 9e failed to react under the above conditions.
From these preliminary experiments it appears that phos-
phepine (S)-A2 is a suitable catalyst for enantioselective an-
nulations of allenylphosphonate 1a with electron-poor ole-
fins, as far as enantioselectivity levels are concerned. These
reactions are hampered, however, by rather moderate con-
version rates.
1
yellow oil. 31P NMR (CDCl3): δ = 13 ppm. H NMR (CDCl3): δ
3
3
= 0.91 (t, J = 7.0 Hz, 3 H, Me), 1.18 (t, J = 7.0 Hz, 3 H, Me),
2.39 (s, 3 H, Me), 3.44–3.52 (m, 1 H, OCH2), 3.7–3.8 (m, 2 H,
2
OCH2), 3.8–3.9 (m, 1 H, OCH2), 4.40 (m, JAB = 12 Hz, 1 H,
NCH2), 4.51 (m, JAB = 12 Hz, 1 H, NCH2), 5.67 (1 H, NCHPh),
2
3
3
6.68 (d, JH,P = 11.8 Hz, 1 H, C=CH), 7.17 (d, J = 8.0 Hz, 2 H,
Ts), 7.2–7.4 (5 H, Ph), 7.46 (d, 3J = 8.0 Hz, 2 H, Ts) ppm. 13C
3
3
NMR (CDCl3): δ = 15.7 (d, JC,P = 7.1 Hz, Me), 16.1 (d, JC,P
=
3
6.6 Hz, Me), 21.4 (Me), 55.8 (d, JC,P = 22.9 Hz, NCH2), 61.8 (d,
2JC,P = 8.5 Hz, OCH2), 62.1 (d, JC,P = 8.8 Hz, OCH2), 71.1 (d,
2
2JC,P = 19.7 Hz, NCHPh), 127.1, 127.7, 128.1, 128.3, 129.4, 134.1
1
2
(d, JC,P = 196 Hz, =C,P), 135.4 (C), 139.1 (C), 140.1 (d, JC,P
=
11.8 Hz, CH=C), 143.4 (C-Me) ppm. HRMS: calcd. for
C21H26NNaO5PS 458.1167; found 458.1201. HPLC: Kromasil col-
umn, n-heptane/iPrOH (8:2), 1 mL/min, 14 and 16 min (major).
Diethyl [2-(p-Nitrophenyl)-1-tosyl-2,5-dihydro-1H-pyrrol-3-yl]phos-
phonate (3b): Purification was performed by silica gel column
chromatography with heptane/ethyl acetate (2:8) as the eluent (Rf
1
= 0.3). Pale-yellow oil. 31P NMR (CDCl3): δ = 9 ppm. H NMR
3
3
(CDCl3): δ = 0.97 (t, J = 7.0 Hz, 3 H, Me), 1.16 (t, J = 7.0 Hz,
3 H, Me), 2.41 (s, 3 H, Me), 3.6–3.7 (m, 1 H, OCH2), 3.8–4.0 (m,
2 H, OCH2), 4.0–4.1 (m, 1 H, OCH2), 4.50 (2 H, NCH2), 5.71 (1
3
3
H, NCHPh), 6.72 (d, JH,P = 10.9 Hz, 1 H, C=CH), 7.25 (d, J =
3
3
8.1 Hz, 2 H, Ts), 7.46 (d, J = 8.6 Hz, 2 H), 7.54 (d, J = 8.1 Hz,
2 H, Ts), 8.16 (d, J = 8.6 Hz, 2 H) ppm. 13C NMR (CDCl3): δ =
3
3
3
15.9 (d, JC,P = 6.7 Hz, Me), 16.2 (d, JC,P = 6.3 Hz, Me), 21.5
(Me), 56.1 (d, JC,P = 17.2 Hz, NCH2), 62.1 (d, JC,P = 5 Hz,
OCH2), 62.2 (d, JC,P = 5 Hz, OCH2), 70.3 (d, JC,P = 19.5 Hz,
3
2
2
2
1
NCHPh), 123.5, 127.2, 128.7, 129.8, 133.2 (d, JC,P = 197 Hz,
Conclusions
=C,P), 134.7 (C), 140.7 (d, 2JC,P = 11.5 Hz, CH=C), 144.2 (C-Me),
146.7 (C), 148.1 (C) ppm. HRMS: calcd. for C21H25N2NaO7PS
503.1018; found 503.1006.
We have shown that allenic phosphonates can be used
as substrates in some phosphane-catalyzed [3+2] and [4+2]
annulation reactions leading to new phosphonate deriva-
Diethyl [2-(p-Methoxyphenyl)-1-tosyl-2,5-dihydro-1H-pyrrol-3-yl]-
tives. The scope and limitations of these reactions have been phosphonate (3c): Purification was performed by silica gel column
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A. Panossian, N. Fleury-Brégeot, A. Marinetti
FULL PAPER
chromatography with heptane/ethyl acetate (2:8) as the eluent (Rf
4.48 (m, 2 H, NCH2), 5.79 (1 H, NCHPh), 6.73 (d, 3JH,P = 11.9 Hz,
1
3
3
= 0.3). Pale-yellow oil. 31P NMR (CDCl3): δ = 10 ppm. H NMR
1 H, C=CH), 7.23 (d, J = 8.0 Hz, 2 H, Ts), 7.48 (d, J = 8.5 Hz,
3
3
(300 MHz, CDCl3): δ = 0.95 (t, J = 7.0 Hz, 3 H, Me), 1.17 (t, J
2 H), 7.52 (d, 3J = 8.0 Hz, 2 H, Ts), 8.14 (d, 3J = 8.5 Hz, 2 H) ppm.
= 7.0 Hz, 3 H, Me), 2.38 (s, 3 H, Me), 3.5–3.6 (m, 1 H, OCH2), 13C NMR (CDCl3): δ = 21.3 (Me), 21.5 (Me), 32.3 (d, JC,P
=
=
3
3
2
3.7–3.9 (m, 3 H, OCH2), 3.78 (s, 3 H, OMe), 4.34 (m, 1 H, NCH2),
6.4 Hz, CMe2), 56.1 (d, JC,P = 16.9 Hz, NCH2), 70.0 (d, JC,P
4.48 (m, 1 H, NCH2), 5.62 (1 H, NCHPh), 6.62 (d, 3JH,P = 12.0 Hz, 20.5 Hz, NCHPh), 75.9 (d, 2JC,P = 108.8 Hz, OCH2), 75.9 (d, 2JC,P
1 H, C=CH), 6.78 (d, 3J = 8.7 Hz, 2 H), 7.13 (d, 3J = 8.7 Hz, 2
H), 7.17 (d, 3J = 8.2 Hz, 2 H, Ts), 7.46 (d, 3J = 8.2 Hz, 2 H,
Ts) ppm. 13C NMR (CDCl3): δ = 15.8 (d, 3JC,P = 7.0 Hz, Me), 16.2
= 109.1 Hz, OCH2), 123.6, 127.2, 128.8, 129.9, 131.6 (d, JC,P
=
1
2
196 Hz, =C,P), 134.5 (C), 141.6 (d, JC,P = 11.1 Hz, CH=C), 144.2
(C-Me), 146.0 (C), 147.8 (C) ppm. HRMS: calcd. for C22H26N2Na-
O7PS 515.1018; found 515.1003.
3
3
(d, JC,P = 6.6 Hz, Me), 21.5 (Me), 55.3 (OMe), 55.6 (d, JC,P
=
=
2
2
17.4 Hz, NCH2), 61.9 (d, JC,P = 6 Hz, OCH2), 62.0 (d, JC,P
[4+2] Cyclization Reactions Between Diethyl (Buta-2,3-dien-2-yl)-
phosphonate (1c) and Imines. Typical Procedure: Diethyl (buta-2,3-
dien-2-yl)phosphonate (1c) (0.3 mmol, 60 mg) and the imine
(0.3 mmol) were dissolved in anhydrous toluene (1 mL) under Ar
in an oven-dried 5 mL vial. A 1  solution of the phosphane cata-
lyst in toluene (30 µL, 0.03 mmol) was then added. The vial was
capped and the reaction mixture heated at 120 °C for 24 h. The
solvent was removed and the final product was purified by column
chromatography.
2
6 Hz, OCH2), 70.6 (d, JC,P = 19.8 Hz, NCHPh), 113.6, 127.1,
128.9, 129.4, 131.3 (C), 134.0 (d, 1JC,P = 196 Hz, =C,P), 135.5 (C),
2
139.8 (d, JC,P = 11.8 Hz, CH=C), 143.3 (C-Me), 159.5 (C-
OMe) ppm. HRMS: calcd. for C22H28NNaO6PS 488.1273; found
488.1272. HPLC: Chiracel AD, heptanes/iPrOH (80:20), 1 mL/min,
15.0 (major) and 17.2 min.
Diethyl [2-(o-Tolyl)-1-tosyl-2,5-dihydro-1H-pyrrol-3-yl]phosphonate
(3d): Purification was performed by silica gel column chromatog-
raphy with heptane/ethyl acetate (2:8) as the eluent (Rf = 0.3). Pale-
yellow solid, m.p. 90 °C. 31P NMR (CDCl3): δ = 10 ppm. 1H NMR
Diethyl
(6-Phenyl-1-tosyl-1,2,5,6-tetrahydropyridin-3-yl)phos-
phonate (6a): Column chromatography on silica gel with heptane/
ethyl acetate (2:8) as the eluent afforded 94 mg (70% yield) of 6a
(Rf = 0.3) as a colorless solid, m.p. 81 °C. 31P NMR (CDCl3): δ =
3
3
(300 MHz, CDCl3): δ = 0.89 (t, J = 7.0 Hz, 3 H, Me), 1.18 (t, J
= 7.1 Hz, 3 H, Me), 2.38 (s, 3 H, Me), 2.49 (s, 3 H, Me), 3.4 (m, 1
2
H, OCH2), 3.7–3.9 (m, 3 H, OCH2), 4.42 (m, JAB = 16 Hz, 1 H,
1
3
15.6 ppm. H NMR (CDCl3): δ = 1.11 (t, J = 7.2 Hz, 3 H, Me),
2
NCH2), 4.54 (m, JAB = 16 Hz, 1 H, NCH2), 6.02 (1 H, NCHPh),
3
1.31 (t, J = 7.0 Hz, 3 H, Me), 2.43 (4 H, Me, CH2), 2.63 (d, J =
18 Hz, 1 H, CH2), 3.34 (d, JAB = 19 Hz, 1 H, NCH2), 3.8 (m, 1
3
6.69 (d, JH,P = 11.6 Hz, 1 H, C=CH), 6.9–7.1 (4 H, CHTol), 7.14
2
3
3
(d, J = 8.4 Hz, 2 H, Ts), 7.40 (d, J = 8.4 Hz, 2 H, Ts) ppm. 13C
H, OCH2), 3.9 (m, 1 H, OCH2), 4.0 (m, 2 H, OCH2), 4.29 (dd,
3
3
NMR (CDCl3): δ = 15.7 (d, JC,P = 6.9 Hz, Me), 16.1 (d, JC,P
=
2JAB = 19, J = 5.2 Hz, 1 H, NCH2), 5.34 (d, 3J = 6.4 Hz, 1 H,
6.3 Hz, Me), 19.0 (Me), 21.4 (Me), 55.8 (d, 3JC,P = 22.9 Hz, NCH2),
3
NCHPh), 6.81 (d, JH,P = 21 Hz, 1 H, C=CH), 7.2–7.3 (7 H), 7.70
2
2
61.8 (d, JC,P = 5 Hz, OCH2), 61.9 (d, JC,P = 5 Hz, OCH2), 67.1
(d, 2JC,P = 20 Hz, NCHPh), 126.0, 127.0, 127.8, 128.0, 129.4, 130.5,
134.0 (d, JC,P = 199 Hz, =C,P), 135.7 (C), 136.2 (C), 137.3 (C),
(d, 3J = 8.0 Hz, 2 H, Ts) ppm. 13C NMR (CDCl3): δ = 16.1 (d,
3
3JC,P = 6.1 Hz, Me), 16.3 (d, JC,P = 6.5 Hz, Me), 21.5 (Me), 26.5
1
3
2
(d, JC,P = 15.5 Hz, CH2), 39.8 (d, JC,P = 17.4 Hz, NCH2), 52.0
2
140.0 (d, JC,P = 12.2 Hz, CH=C), 143.2 (C-Me) ppm. HRMS:
2
2
(NCHPh), 61.8 (d, JC,P = 5.1 Hz, OCH2), 61.9 (d, JC,P = 5.4 Hz,
OCH2), 125.9 (d, 1JC,P = 184 Hz, =C,P), 127.0, 127.1, 127.2, 127.9,
128.5, 129.7, 137.5 (C), 137.9 (C), 139.8 (d, 2JC,P = 7.9 Hz, CH=C),
143.5 (C-Me) ppm. HRMS: calcd. for C22H28NNaO5PS 472.1324;
found 472.1313.
calcd. for C22H28NNaO5PS 472.1324; found 472.1313.
5,5-Dimethyl-2-oxo-2-(2-phenyl-1-tosyl-2,5-dihydro-1H-pyrrol-3-yl)-
1,3,2-dioxaphosphinane (5a): Purification was performed by silica
gel column chromatography with heptane/ethyl acetate (3:7) as the
eluent (Rf = 0.2). Colorless solid, m.p. 186 °C. 31P NMR (CDCl3):
Diethyl [6-(p-Methoxyphenyl)-1-tosyl-1,2,5,6-tetrahydropyridin-3-
yl]phosphonate (6c): Purification by column chromatography on sil-
ica gel with heptane/ethyl acetate (2:8) as the eluent afforded
107 mg (74% yield) of 6c (Rf = 0.3) as a colorless solid, m.p. 92 °C.
1
δ = 5 ppm. H NMR (CDCl3): δ = 0.70 (s, 3 H, Me), 0.98 (s, 3 H,
Me), 2.37 (s, 3 H, Me), 3.40 (t, JH,H = JH,P = 11 Hz, 1 H, OCH2),
3.43 (t, JH,H = JH,P = 11 Hz, 1 H, OCH2), 3.76 (t, JH,H = JH,P
=
1
31P NMR (CDCl3): δ = 15.7 ppm. H NMR (CDCl3): δ = 1.15 (t,
11 Hz, 1 H, OCH2), 3.92 (t, JH,H = JH,P = 11 Hz, 1 H, OCH2),
2
2
3
3J = 7.0 Hz, 3 H, Me), 1.33 (t, J = 7.0 Hz, 3 H, Me), 2.43 (4 H,
4.39 (m, JAB = 16.5 Hz, 1 H, NCH2), 4.89 (m, JAB = 16.5 Hz, 1
3
2
H, NCH2), 5.75 (1 H, NCHPh), 6.73 (d, JH,P = 12.5 Hz, 1 H,
Me, CH2), 2.58 (br. d, 1 H, CH2), 3.34 (d, JAB = 19 Hz, 1 H,
3
C=CH), 7.16 (d, J = 8.0 Hz, 2 H, Ts), 7.3–7.4 (5 H, Ph), 7.43 (d,
NCH2), 3.79 (s, 3 H, OMe), 3.8 (m, 1 H, OCH2), 3.9 (m, 1 H,
OCH2), 4.0 (m, 2 H, OCH2), 4.28 (dd, 2JAB = 19, J = 6.0 Hz, 1 H,
NCH2), 5.30 (d, 3J = 7.0 Hz, 1 H, NCH), 6.8 (3 H, C=CH,
3J = 8.0 Hz, 2 H, Ts) ppm. 13C NMR (CDCl3): δ = 21.1 (Me), 21.5
3
3
(Me), 21.6 (Me), 32.2 (d, JC,P = 6.7 Hz, CMe2), 55.7 (d, JC,P
17.2 Hz, NCH2), 70.9 (d, JC,P = 20.6 Hz, NCHPh), 75.8 (d, JC,P
=
2
2
3
3
CHo-Me), 7.20 (d, J = 8.5 Hz, 2 H, Ar), 7.27 (d, J = 8.0 Hz, 2 H,
2
Ar), 7.71 (d, J = 8.5 Hz, 2 H, Ts) ppm. 13C NMR (CDCl3): δ =
16.1 (d, JC,P = 5.5 Hz, Me), 16.3 (d, JC,P = 5.9 Hz, Me), 21.5
(Me), 26.8 (d, JC,P = 15.3 Hz, CH2), 39.7 (d, JC,P = 17.3 Hz,
NCH2), 51.6 (NCH), 55.3 (OMe), 61.8 (d, JC,P = 4.8 Hz, OCH2),
3
= 85.0 Hz, OCH2), 75.9 (d, JC,P = 85.1 Hz, OCH2), 127.1, 128.1,
128.4, 129.6, 132.6 (d, 1JC,P = 194 Hz, =C,P), 135.2 (C), 138.7 (C),
3
3
2
3
2
141.4 (d, JC,P = 11.3 Hz, CH=C), 143.5 (C-Me) ppm. HRMS:
2
calcd. for C22H26NNaO5PS 470.1167; found 470.1187. HPLC: Chi-
ralpak AD column, heptane/2-propanol (80:20), 1 mL/min, 18.9
(major) and 24.9 min.
2
1
61.9 (d, JC,P = 5.2 Hz, OCH2), 113.8 (CHo-MeO), 126.0 (d, JC,P
=
184 Hz, =C,P), 127.0, 128.5, 129.7, 129.9 (C), 137.6 (C), 139.9 (d,
2JC,P = 7.7 Hz, CH=C), 143.5 (C-Me), 159.2 (C-OMe) ppm.
HRMS: calcd. for C23H30NNaO6PS 502.1429; found 502.1397.
5,5-Dimethyl-2-oxo-2-[2-(p-nitrophenyl)-1-tosyl-2,5-dihydro-1H-pyr-
rol-3-yl]-1,3,2-dioxaphosphinane (5b): Purification was performed
by silica gel column chromatography with heptane/ethyl acetate
(3:7) as the eluent (Rf = 0.2). Pale-yellow oil. 31P NMR (CDCl3):
Diethyl [6-(o-Tolyl)-1-tosyl-1,2,5,6-tetrahydropyridin-3-yl]phosphon-
ate (6d): Purification by column chromatography on silica gel with
heptane/ethyl acetate (2:8) as the eluent afforded 103 mg (75%
yield) of 6d (Rf = 0.25) as a colorless oil. 31P NMR (CDCl3): δ =
1
δ = 4 ppm. H NMR (CDCl3): δ = 0.82 (s, 3 H, Me), 0.97 (s, 3 H,
Me), 2.40 (s, 3 H, Me), 3.48 (t, JH,H = JH,P = 11 Hz, 1 H, OCH2),
1
3
3.63 (t, JH,H = JH,P = 11 Hz, 1 H, OCH2), 3.86 (t, JH,H = JH,P
=
15.7 ppm. H NMR (CDCl3): δ = 1.13 (t, J = 7.0 Hz, 3 H, Me),
11 Hz, 1 H, OCH2), 4.06 (t, JH,H = JH,P = 11 Hz, 1 H, OCH2), 1.31 (t, 3J = 7.0 Hz, 3 H, Me), 2.33 (s, 3 H, Me), 2.45 (s, 3 H, Me),
3830
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 3826–3833

Phosphane-Catalyzed [3+2] and [4+2] Annulations
2
3
3
2.3–2.5 (2 H, CH2), 3.24 (d, JAB = 19.0 Hz, 1 H, NCH2), 3.8 (m, (d, 3JC,P = 6.9 Hz, Me), 16.3 (d, JC,P = 6.6 Hz, Me), 42.9 (d, JC,P
3
2
1 H, OCH2), 3.9 (m, 1 H, OCH2), 4.0 (m, 2 H, OCH2), 4.17 (dd, = 19.9 Hz, CH2), 49.6 (d, JC,P = 10.3 Hz, CHPh), 61.4 (d, JC,P
=
2JAB = 19, J = 6.0 Hz, 1 H, NCH2), 5.43 (d, 3J = 6.5 Hz, 1 H, 12.8 Hz, CHCOPh), 61.7 (d, JC,P = 5.7 Hz, OCH2), 62.1 (d, JC,P
2
2
NCHPh), 6.71 (d, 3JH,P = 20.5 Hz, 1 H, C=CH), 6.9–7.0 (2 H), 7.1– = 5.3 Hz, OCH2), 126.8, 127.1, 128.6, 128.9, 129.0, 132.1 (d, JC,P
1
7.2 (4 H), 7.65 (d, 3J = 8.0 Hz, 2 H, Ts) ppm. 13C NMR (CDCl3): δ = 189.4 Hz, CH=C,P), 133.3, 136.8 (C), 145.0 (C), 150.7 (d, JC,P
2
3
3
= 16.2 (d, JC,P = 6.2 Hz, Me), 16.4 (d, JC,P = 6.5 Hz, Me), 19.9
(Me), 21.5 (Me), 27.2 (d, JC,P = 15.3 Hz, CH2), 40.1 (d, JC,P
= 14.0 Hz, CH=C,P), 200.0 (COPh) ppm. HRMS: calcd. for
C22H25NaO4P 407.1388; found 407.1390. HPLC: Kromasil 3-cellu-
coat column, heptane/2-propanol (97:3), 1 mL/min, 12.7 and
14.4 min (major).
3
2
=
16.8 Hz, NCH2), 50.0 (NCH), 61.9 (OCH2), 125.5, 125.9, 126.1 (d,
1JC,P = 138 Hz, =C,P), 127.5, 128.3, 129.5, 131.4, 136.0 (C), 136.9
2
(C), 138.0 (C), 140.6 (d, JC,P = 8.2 Hz, CH=C), 143.6 (C-
Diethyl (5-Acetyl-4-phenylcyclopenten-1-yl)phosphonate (10b): Puri-
fication by column chromatography with heptane/ethyl acetate
(2:8) as the eluent (Rf = 0.2) afforded 55 mg of 10b as a pale-yellow
oil (34% yield; contains 8% of the minor isomer). 31P NMR
(CDCl3): δ = 14 ppm. H NMR (300 MHz, CDCl3): δ = 1.32 (t, J
= 7.0 Hz, 3 H, Me), 1.33 (t, J = 7.0 Hz, 3 H, Me), 2.25 (s, Me),
2.69 (m, JAB = 18.3 Hz, 1 H, CH2), 3.16 (dddt, JAB = 18.3, J =
9.0, J = 4.2, J = 2.4 Hz, 1 H, CH2), 3.70 (dt, J = 9.0, J = 5.4 Hz,
1 H, CH,Ph), 3.95–4.0 (1 H, CHCOMe), 4.0–4.2 (4 H, OCH2), 6.91
Me) ppm. HRMS: calcd. for C23H30NNaO5PS 486.1480; found
486.1462.
Synthesis of Diethyl 3-(Diethoxyphosphoryl)cyclopent-3-ene-1,2-di-
carboxylate (8): The allenylphosphonate 1a (0.5 mmol, 88 mg), di-
ethyl fumarate (0.17 g, 1.0 mmol), and degassed toluene (5 mL)
were introduced into a Schlenk tube under argon. The mixture was
purged with argon and the phosphane catalyst [P(iBu)3, 0.05 mmol,
1  solution in toluene] was added. The reaction mixture was
heated at 120 °C for 24 h. After evaporation of the solvent, the
conversion rate and the 8/4a ratio was evaluated by 1H NMR of
the crude material. The final product was purified by column
chromatography on silica gel with heptanes/AcOEt (2:8) as the elu-
ent. Rf = 0.2. Yield 0.14 g (80%). Pale-yellow oil. 31P NMR
1
3
3
2
2
3
3
2
(dq, JH,P = 11.1, J = 2.1 Hz, 1 H, CH=C,P), 7.2–7.35 (Ph) ppm.
3
3
13C NMR (CDCl3): δ = 16.3 (d, JC,P = 6.8 Hz, Me), 16.4 (d, JC,P
3
= 6.6 Hz, Me), 30.6 (COMe), 42.7 (d, JC,P = 19.7 Hz, CH2), 48.5
(d, JC,P = 10.6 Hz, CH,Ph), 61.9 (d, JC,P = 5.7 Hz, OCH2), 62.1
(d, JC,P = 5.4 Hz, OCH2), 67.4 (d, JC,P = 13.1 Hz, CHCOMe),
126.7, 127.0, 129.0, 131.7 (d, JC,P = 190.4 Hz, CH=C,P), 144.5
(C), 150.3 (d, JC,P = 13.6 Hz, CH=C,P), 208.4 (COMe) ppm.
HRMS: calcd. for C17H23NaO4P, 345.1232; found 345.1241.
3
2
2
2
1
1
(300 MHz, CDCl3): δ = 16 ppm. H NMR (CDCl3): δ = 1.22–1.32
(12 H, Me), 2.83 (dddt, JAB = 18.3, J = 6.3, J = 3.6, J = 2.4 Hz,
2
2
3
2
3
1 H, CH2), 2.99 (dddt, JAB = 18.3, J = 9.3, J = 3.6, J = 2.7 Hz,
1 H, CH2), 3.54 (dt, 3J = 9.3, 3J = 6.3 Hz, 1 H, 1-H), 3.9–4.3 (9
Diethyl
[5-Benzoyl-4-(p-nitrophenyl)cyclopenten-1-yl]phosphonate
3
(10c): Purification by column chromatography with diethyl ether/
ethanol (80:1) as the eluent afforded 75 mg (35% yield) of 10c (Rf
= 0.25) as a pale-yellow oil. 31P NMR (CDCl3): δ = 13 ppm. 1H
H, OCH2, 2-H), 6.75 (dq, JH-P = 11.1, J = 2.2 Hz, 1 H,
=CH) ppm. 13C NMR (CDCl3): δ = 14.1 (Me), 14.2 (Me), 16.3 (d,
3
3
3JC,P = 6 Hz, Me), 16.3 (d, JC,P = 6 Hz, Me), 37.0 (d, JC,P
=
=
3
3
2
NMR (300 MHz, CDCl3): δ = 1.16 (t, J = 7.0 Hz, 6 H, Me), 2.7
19.6 Hz, CH2), 47.3 (d, JC,P = 10.6 Hz, C-1), 54.8 (d, JC,P
(m, 2JAB = 18.3 Hz, 1 H, CH2), 3.3 (m, 2JAB = 18.3 Hz, 1 H, CH2),
2
14.1 Hz, C-2), 61.3 (OCH2), 61.4 (OCH2), 62.0 (d, JC,P = 5.7 Hz,
OCH2), 62.1 (d, 2JC,P = 5.4 Hz, OCH2), 131.0 (d, 1JC,P = 192.8 Hz,
CH=C,P), 149.5 (d, 2JC,P = 13.6 Hz, CH=C,P), 172.6 (CO2), 173.2
(CO2) ppm. HRMS: calcd. for C15H25NaO7P 371.1236; found
371.1228. HPLC: Chiracel OD-H, heptane/iPrOH (90:10), 1 mL/
min, 7.2 (major) and 8.5 min.
2
3.8–4.0 (m, 5 H, 4-H, OCH2), 4.83 (1 H, CHCO), 6.99 (m, JH,P
11.1 Hz, 1 H, CH=C,P), 7.35 (d, J = 8.4 Hz, 2 H, Ar), 7.4 (2 H),
=
3
3
3
7.56 (1 H, Ph), 7.87 (d, J = 8.4 Hz, 2 H, Ar), 8.15 (d, J = 8.7 Hz,
2 H, Ar) ppm. 13C NMR (CDCl3): δ = 16.1 (d, JC,P = 6.9 Hz,
3
3
3
Me), 16.3 (d, JC,P = 6.5 Hz, Me), 42.6 (d, JC,P = 19.9 Hz, CH2),
3
2
49.1 (d, JC,P = 10.5 Hz, CHAr), 60.8 (d, JC,P = 13.1 Hz,
[3+2] Cyclization Reactions between 1a and α,β-Unsaturated
Ketones. Typical Procedure: The allenylphosphonate 1a (0.5 mmol,
88 mg), the enone (1 mmol), and degassed toluene (2.5 mL) were
introduced into a Schlenk tube under argon. The mixture was
purged with argon and the phosphane catalyst [P(iBu)3, 0.05 mmol,
1  solution in toluene] was added. The flask was dipped in an oil
bath at 120 °C and the mixture was stirred for 24 h. After evapora-
tion of the solvent, the conversion rate and the 10/4a ratios were
evaluated by 1H NMR of the crude material. When significant
amounts of residual allenylphosphonate 1a or alkyne 4a were ob-
served in the final mixture, they were removed by Kugelrohr distil-
lation (ca. 90 °C/6ϫ10–5 bar). The final product was purified by
column chromatography on silica gel. The same procedure was ap-
plied to the reactions of 1a (0.3 mmol) with enones 9a, 9c, and 9f
(1.2 mmol) in the presence of phosphepine (S)-A2 (11 mg,
0.03 mmol).
CHCOPh), 61.8 (d, 2JC,P = 5.9 Hz, OCH2), 62.2 (d, 2JC,P = 5.5 Hz,
1
OCH2), 124.3, 127.7, 128.7, 128.8, 132.5 (d, JC,P = 190.5 Hz,
CH=C,P), 133.7, 136.5 (C), 147.1 (C), 149.9 (d, JC,P = 13.8 Hz,
CH=C,P), 152.3 (C), 199.3 (COPh) ppm. HRMS: calcd. for
C22H24NNaO6P 452.1239; found 452.1246. HPLC: Chiracel OD-
H, heptane/2-propanol (93:7), 1 mL/min, retention times 24.1
(major) and 28.1 min.
2
Diethyl [5-Benzoyl-4-(p-methoxyphenyl)cyclopenten-1-yl]phosphon-
ate (10d): Purification by column chromatography with diethyl
ether/ethanol (100:1) as the eluent afforded 82 mg (40% yield) of
10d (Rf = 0.2) as a pale-yellow oil. 31P NMR (CDCl3): δ = 14 ppm.
1H NMR (300 MHz, CDCl3): δ = 1.16 (t, J = 7.0 Hz, 6 H, Me),
3
2.65 (m, JAB = 18.3 Hz, 1 H, CH2), 3.20 (m, 2JAB = 18.3 Hz, 1 H,
2
CH2), 3.67 (dt, 3J = 8.7, J = 4.2 Hz, 1 H, 4-H), 3.77 (s, 3 H, OMe),
3
3.9–4.0 (4 H, OCH2), 4.8 (m, 1 H, CHCO), 6.81 (d, J = 8.7 Hz, 2
H, Ar), 6.99 (m, JH,P = 11.1 Hz, 1 H, CH=C,P), 7.09 (d, 3J =
2
Diethyl (5-Benzoyl-4-phenylcyclopenten-1-yl)phosphonate (10a): Pu-
rification by column chromatography with heptane/ethyl acetate
(3:7) as the eluent afforded 95 mg (50% yield) of 10a (Rf = 0.3) as
8.7 Hz, 2 H, Ar), 7.3–7.55 (3 H), 7.9 (2 H, Ph) ppm. 13C NMR
3
3
(CDCl3): δ = 16.2 (d, JC,P = 6.9 Hz, Me), 16.3 (d, JC,P = 6.7 Hz,
Me), 43.1 (d, JC,P = 19.9 Hz, CH2), 49.0 (d, JC,P = 10.2 Hz,
3
3
a pale-yellow oil. 31P NMR (CDCl3): δ = 14 ppm. 1H NMR CHAr), 55.4 (OMe), 61.7 (d, JC,P = 12 Hz, CHCOPh), 61.7 (d,
2
(300 MHz, CDCl3): δ = 1.19 (t, 3J = 6.9 Hz, 6 H, Me), 2.72 (m,
2JC,P = 6 Hz, OCH2), 62.1 (d, 2JC,P = 5.2 Hz, OCH2), 114.3, 127.8,
2JAB = 18.3 Hz, 1 H, CH2), 3.26 (m, JAB = 18.3 Hz, 1 H, CH2), 128.6, 128.9, 132.0 (d, JC,P = 193.4 Hz, CH=C,P), 133.3, 136.9
3.75 (m, 1 H, 4-H), 3.9–4.0 (4 H, OCH2), 4.86 (1 H, 5-H), 7.03 (d, (C), 137.2 (C), 150.7 (d, 2JC,P = 13.8 Hz, CH=C,P), 158.6 (COMe),
2JH,P = 11.1 Hz, 1 H, CH=C,P), 7.2–7.3 (5 H, Ph), 7.4 (2 H, Ph), 200.1 (COPh) ppm. HRMS: calcd. for C23H27NNaO6P 437.1494;
2
1
7.55 (1 H, Ph), 7.88 (2 H, Ph) ppm. 13C NMR (CDCl3): δ = 16.1
found 437.1492.
Eur. J. Org. Chem. 2008, 3826–3833
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3831

A. Panossian, N. Fleury-Brégeot, A. Marinetti
FULL PAPER
F. Zhu, C. E. Henry, O. Kwon, Tetrahedron 2005, 61, 6276–
6282; f) X. Tang, B. Zhang, Z. He, R. Gao, Z. He, Adv. Synth.
Catal. 2007, 349, 2007–2017; g) S. Castellano, H. D. G. Fiji,
S. S. Kinderman, M. Watanabe, P. de Leon, F. Tamanoi, O.
Kwon, J. Am. Chem. Soc. 2007, 129, 5843–5845.
a) X.-F. Zhu, C. E. Henry, J. Wang, T. Dudding, O. Kwon, Org.
Lett. 2005, 7, 1387–1390; b) X.-F. Zhu, A.-P. Schaffner, R. C.
Li, O. Kwon, Org. Lett. 2005, 7, 2977–2980.
Diethyl [5-Benzoyl-4-(2-furyl)cyclopenten-1-yl]phosphonate (10e):
Purification by column chromatography with diethyl ether/ethanol
(100:1) as the eluent afforded 47 mg (25% yield) of 10e (Rf = 0.3) as
a yellow oil. 31P NMR (CDCl3): δ = 14 ppm. 1H NMR (300 MHz,
3
3
CDCl3): δ = 1.13 (t, J = 7.0 Hz, 3 H, Me), 1.14 (t, J = 7.0 Hz, 3
[4]
[5]
[6]
2
2
H, Me), 2.80 (m, JAB = 18.0 Hz, 1 H, CH2), 3.10 (dddt, JAB
=
18.0, 3J = 8.4, J = 4.2, J = 2.1 Hz, 1 H, CH2), 3.9–4.0 (5 H, OCH2,
4-H), 4.9 (m, 1 H, CHCO), 6.03 (d, 3J = 3.0 Hz, 1 H, CHfuryl), 6.26
a) C. Zhang, X. Lu, Synlett 1995, 645–646; b) C. Lu, X. Lu,
Org. Lett. 2002, 4, 4677–4679; c) D. Virieux, A.-F. Guillouzic,
H.-J. Cristaux, Tetrahedron 2006, 62, 3710–3720.
3
3
2
(dd, J = 3.0, J = 1.8 Hz 1 H, CHfuryl), 6.95 (m, JH,P = 11.1 Hz,
1 H, CH=C,P), 7.31 (1 H), 7.4–7.6 (3 H), 7.98 (2 H) ppm. 13C
NMR (CDCl3): δ = 16.1 (d, JC,P = 7.3 Hz, Me), 16.2 (d, JC,P
3
3
=
=
a) Y. Du, X. Lu, J. Org. Chem. 2003, 68, 6463–6465; b) Y. S.
Tran, O. Kwon, Org. Lett. 2005, 7, 4289–4291; c) A. T. Ung,
K. Schafer, K. B. Lindsay, S. G. Pyne, K. Amornraksa, R.
Wouters, I. Van der Linden, I. Biesmans, A. S. J. Lesage, B. W.
Skelton, A. H. White, J. Org. Chem. 2002, 67, 227–233.
a) G. Zhu, Z. Chen, Q. Jiang, D. Xiao, P. Cao, X. Zhang, J.
Am. Chem. Soc. 1997, 119, 3836–3837; b) Z. Chen, G. Zhu, Q.
Jiang, D. Xiao, P. Cao, X. Zhang, J. Org. Chem. 1998, 63,
5631–5635; c) R. P. Wurz, G. C. Fu, J. Am. Chem. Soc. 2005,
127, 12234–12235; d) J. E. Wilson, G. C. Fu, Angew. Chem. Int.
Ed. 2006, 45, 1426–1429; e) L. Jean, A. Marinetti, Tetrahedron
Lett. 2006, 47, 2141–2145; f) A. Scherer, J. A. Gladysz, Tetrahe-
dron Lett. 2006, 47, 6335–6337; g) N. Fleury-Brégeot, L. Jean,
P. Retailleau, A. Marinetti, Tetrahedron 2007, 63, 11920–11927;
h) D. J. Wallace, R. L. Sidda, R. A. Reamer, J. Org. Chem.
2007, 72, 1051–1054; i) B. J. Cowen, S. J. Miller, J. Am. Chem.
Soc. 2007, 129, 10988–10989.
3
3
7.1 Hz, Me), 39.4 (d, JC,P = 19.8 Hz, CH2), 43.1 (d, JC,P
2
10.8 Hz, CHAr), 58.3 (d, JC,P = 13.2 Hz, CHCOPh), 61.7 (d,
2JC,P = 5.6 Hz, OCH2), 62.1 (d, JC,P = 5.2 Hz, OCH2), 105.2
2
1
(C=CHfuryl), 110.3 (C=CH=CHfuryl), 128.6, 128.9, 131.9 (d, JC,P
[7]
= 191.8 Hz, CH=C,P), 133.4, 136.9 (C), 141.9 (OCH=CHfuryl),
2
150.2 (d, JC,P = 13.7 Hz, CH=C,P), 156.5 (O-Cfuryl), 200.0
(COPh) ppm. HRMS: calcd. for C20H23NaO5P, 397.1181; found
397.1176.
Diethyl
[5-Benzoyl-4-(1-naphthyl)cyclopenten-1-yl]phosphonate
(10f): Purification by column chromatography with heptane/ethyl
acetate (2:8) as the eluent afforded 91 mg (42% yield) of 10f (Rf =
0.4) as a pale-yellow oil. 31P NMR (CDCl3): δ = 14 ppm. 1H NMR
3
3
(300 MHz, CDCl3): δ = 1.16 (t, J = 6.9 Hz, 3 H, Me), 1.18 (t, J
2
= 6.9 Hz, 3 H, Me), 2.81 (m, JAB = 18.6 Hz, 1 H, CH2), 3.4–3.6
(m, JAB = 18.6 Hz, 1 H, CH2), 4.0 (m, 4 H, OCH2), 4.55 (m, 1 H, [8]
2
G.-L. Zhao, M. Shi, Org. Biomol. Chem. 2005, 3, 3686–3694.
P. Savignac, B. Iorga, Modern Phosphonate Chemistry, CRC
Press, Boca Raton, FL, 2003.
K. Moonen, I. Laureyn, C. V. Stevens, Chem. Rev. 2004, 104,
6177–6215.
2
4-H), 5.1 (m, 1 H, CHCO), 7.07 (m, JH,P = 10.1 Hz, 1 H, [9]
CH=C,P), 7.3–7.5 (7 H), 7.8 (1 H), 7.9 (4 H) ppm. 13C NMR
3
3
[10]
[11]
(CDCl3): δ = 16.2 (d, JC,P = 6.9 Hz, Me), 16.3 (d, JC,P = 6.6 Hz,
3
3
Me), 42.8 (d, JC,P = 20.2 Hz, CH2), 45.3 (d, JC,P = 7.1 Hz,
CHAr), 60.2 (d, 2JC,P = 13 Hz, CHCOPh), 61.8 (d, 2JC,P = 5.8 Hz,
a) V. Mark, Tetrahedron Lett. 1962, 3, 281–285; b) R. S. Mac-
omber, E. R. Kennedy, J. Org. Chem. 1976, 41, 3191–3197; c)
B. Iorga, F. Eymery, D. Carmichael, P. Savignac, Eur. J. Org.
Chem. 2000, 3103–3115.
a) A. J. Zapata, Y. Gu, G. B. Hammond, J. Org. Chem. 2000,
65, 227–234; b) S. Ma, H. Guo, F. Yu, J. Org. Chem. 2006, 71,
6634–6636; c) H. Guo, Z. Zheng, F. Yu, S. Ma, A. Holuigue,
D. S. Tromp, C. J. Elsevier, Y. Yu, Angew. Chem. Int. Ed. 2006,
45, 4997–5000; d) M. Chakravarty, K. C. K. Swamy, J. Org.
Chem. 2006, 71, 9128–9138; e) K. C. K. Swamy, E. Balaraman,
N. S. Kumar, Tetrahedron 2006, 62, 10152–11016.
I. Morita, M. Tsuda, M. Kise, M. Sugiyama, Chem. Pharm.
Bull. 1988, 36, 1139.
J. C. Guillemin, P. Savignac, J. M. Denis, Inorg. Chem. 1991,
30, 2170–2173.
H.-J. Altenbach, R. Korff, Tetrahedron Lett. 1981, 22, 5175–
5178.
Conversion rates of 35 and 47% are obtained at 80 and 120 °C,
respectively, in dioxane.
2
OCH2), 62.1 (d, JC,P = 5.3 Hz, OCH2), 123.3, 123.6, 125.6, 125.7,
126.2, 127.6, 128.5, 128.8, 129.1, 130.9 (C), 132.4 (d, JC,P
1
=
2
191.4 Hz, CH=C,P), 133.4, 134.2, 136.8, 140.4 (C), 150.7 (d, JC,P
= 13.9 Hz, CH=C,P), 200.5 (COPh) ppm. HRMS: calcd. for
C26H27NaO4P 457.1545; found 457.1540. HPLC: Kromasil 3-cellu-
coat heptane/2-propanol (97:3), 1 mL/min, retention times 18.1
(major) and 23.7 min.
[12]
Supporting Information (see also the footnote on the first page of
this article): 13C NMR spectra for compounds 3a–d, 5a,b, 6a,c,d,
8, 10a–f.
[13]
[14]
[15]
[16]
Acknowledgments
We are very grateful to Dr. Thomas Riermeier and Dr. Renat Kad-
yrov (Evonik Degussa GmbH, Hanau, Germany) for a generous
gift of the chiral phosphepines A.
[17]
[18]
R. S. Drago, Organometallics 1995, 14, 3408–3417.
Heating of the allenylphosphonate 1a at 120 °C for 5 h with
10% nBu3P or iBu3P affords mixtures of the starting allene and
the corresponding alkyne 4a in 15:85 and 50:50 ratios, respec-
tively.
[1] a) X. Lu, C. Zhang, Z. Xu, Acc. Chem. Res. 2001, 34, 535–
544; b) J. L. Methot, W. R. Roush, Adv. Synth. Catal. 2004,
346, 1035–1050.
[19]
The coupling constants for vicinal hydrogen atoms in the cyclo-
[2] a) C. Zhang, X. Lu, J. Org. Chem. 1995, 60, 2906–2908; b) K.
Kumar, A. Kapur, M. P. S. Ishar, Org. Lett. 2000, 2, 787–789;
c) K. Kumar, R. Kapoor, A. Kapur, M. P. S. Ishar, Org. Lett.
2000, 2, 2023–2025; d) Y. Du, X. Lu, Y. Yu, J. Org. Chem.
2002, 67, 8901–8905; e) X. Lu, Z. Lu, X. Zhang, Tetrahedron
2006, 62, 457–460; f) Y. S. Tran, O. Kwon, J. Am. Chem. Soc.
2007, 129, 12632–12633; g) C. E. Henry, O. Kwon, Org. Lett.
2007, 9, 3069–3307.
[3] a) Z. Xu, X. Lu, Tetrahedron Lett. 1997, 38, 3461–3464; b) Z.
Xu, X. Lu, J. Org. Chem. 1998, 63, 5031–5041; c) X.-F. Zhu,
J. Lan, O. Kwon, J. Am. Chem. Soc. 2003, 125, 4716–4717; d)
G.-L. Zhao, M. Shi, J. Org. Chem. 2005, 70, 9975–9984; e) X.-
pentene ring of compound 8 are Jcis = 9.3 Hz and Jtrans
=
6.3 Hz. The observed coupling constant for CH(1) to CH(2) is
6.3 Hz.
[20]
[21]
Assignment based on the coupling constants of ring hydrogen
1
3
atoms in the H NMR spectra, Jcis being usually larger than
3Jtrans
.
a) T. Dudding, O. Kwon, E. Mercier, Org. Lett. 2006, 8, 3643–
3646; b) E. Mercier, B. Fonovic, C. Henry, O. Kwon, T. Dud-
ding, Tetrahedron Lett. 2007, 48, 3617–3620; c) Y. Xia, Y. Li-
ang, M. Wang, L. Jiao, F. Huang, S. Liu, Y. Li, Z.-X. Yu, J.
Am. Chem. Soc. 2007, 129, 3470–3471; d) a concerted mecha-
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© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 3826–3833

Phosphane-Catalyzed [3+2] and [4+2] Annulations
nism can also be postulated: Y. Du, X. Lu, Y. Yu, J. Org. Chem.
2002, 67, 8901–8905.
[22] a) S. Gladiali, A. Dore, D. Fabbri, O. De Lucchi, M. Man-
assero, Tetrahedron: Asymmetry 1994, 5, 511–514; b) K. Junge,
G. M. Oehme, A. T. Riermeier, U. Dingerdissen, M. Beller, Tet-
rahedron Lett. 2002, 43, 4977–4980.
[23] Unpublished results.
Received: April 3, 2008
Published Online: June 13, 2008
Eur. J. Org. Chem. 2008, 3826–3833
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3833