Assembly of dimethyl acetylenedicarboxylate and phosphanes with aldehydes leading to γ-lactones bearing α-phosphorus ylides as wittig reagents

Article abstract of DOI:10.1002/ejoc.201200400

We report herein a convenient route to the synthesis of aryl-substituted γ-lactones bearing an α-phosphorus ylide moiety through the assembly of dimethyl acetylenedicarboxylate (DMAD), electron-deficient aldehydes, and triaryl-or trialkylphosphanes in moderate to good yields. The formation of γ-lactones is highly dependent on the reaction time, the phosphane nucleophile, and the molar ratio of DMAD, aldehyde, and phosphane. We found that reactions with a DMAD/aldehyde/tri-p-tolylphosphane molar ratio of 3:1:6 and more electron-deficient aldehydes, such as 4-nitrobenzaldehyde and 4-chloro-3-nitrobenzaldehyde, gave good yields. The isolated ylides reacted with aldehydes as Wittig reagents to give olefins in moderate yields.

Full text of DOI:10.1002/ejoc.201200400

Job/Unit: O20400
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Date: 27-08-12 18:50:58
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DOI: 10.1002/ejoc.201200400
Assembly of Dimethyl Acetylenedicarboxylate and Phosphanes with Aldehydes
Leading to γ-Lactones Bearing α-Phosphorus Ylides as Wittig Reagents
Jie-Cheng Deng,[a] Fu-Wei Chan,[a] Chih-Wei Kuo,[a] Chun-An Cheng,[a] Chien-Yu Huang,[a]
and Shih-Ching Chuang*[a]
Keywords: Lactones / Phosphanes / Ylides / Wittig reactions / Multicomponent reactions
We report herein a convenient route to the synthesis of aryl-
substituted γ-lactones bearing an α-phosphorus ylide moiety
through the assembly of dimethyl acetylenedicarboxylate
(DMAD), electron-deficient aldehydes, and triaryl- or trialk-
ylphosphanes in moderate to good yields. The formation of
γ-lactones is highly dependent on the reaction time, the
phosphane nucleophile, and the molar ratio of DMAD, alde-
hyde, and phosphane. We found that reactions with a
DMAD/aldehyde/tri-p-tolylphosphane molar ratio of 3:1:6
and more electron-deficient aldehydes, such as 4-nitrobenz-
aldehyde and 4-chloro-3-nitrobenzaldehyde, gave good
yields. The isolated ylides reacted with aldehydes as Wittig
reagents to give olefins in moderate yields.
Introduction
1,3-Dipolar cycloaddition is a convenient synthetic meth-
odology for the construction of cyclic molecular structures
in synthetic chemistry.[1] In this context, nucleophilic carbe-
noid species generated in situ from phosphanes and elec-
tron-deficient acetylenes have received considerable atten-
tion due to their application in the construction of hetero-
cyclic molecules.[2] Organophosphanes have been found to
mediate such reactions catalytically,[3] and asymmetric ver-
sions of the phosphane catalysis and their synthetic applica-
tions have also been studied.[4] In recent years, versatile re-
actions using phosphane catalysis have also been demon-
strated for the synthesis of useful heterocycles.[5] Important
nucleophilic reagents other than phosphanes, such as pyr-
idines,[6] isoquinolines,[7] and alkyl isocyanides,[8] have also
been used with electron-deficient alkynes to promote the
formation of 1,3-dipoles. In a previous study, Winterfeldt
and Dillinger explored the reactions of aldehydes with a
1,3-dipole Ia, generated from dimethyl acetylenedicarboxyl-
ate (DMAD) and PPh3, and they isolated dephosphanated
lactone 4a in low yield (Ͻ20%) in the 1960s (Scheme 1).[9]
The formation of 4a was proposed to occur by a dephos-
phanation step, the methoxide anion generated during the
reaction attacking the P-substituted sp2 carbon atom of in-
termediate Ic (pathway a; R = H).
Scheme 1. Mechanism for the formation of putative 3a and 4a.
We became interested in developing a new synthetic
methodology for the total synthesis of dehydrocrotonin
(DHC) analogues,[10] which have been used for the treat-
ment of gastrointestinal, kidney, and liver disorders, and
have also shown anti-ulcerogenic and anti-tumor activi-
ties.[11] Thus, we have investigated whether a putative mole-
cule 3a could become available or survive as a short-lived
intermediate for subsequent Wittig reactions. We envisaged
that the methine proton of Ic could become acidic enough
for deprotonation through the inductive effect of the phenyl
ring.
[a] Department of Applied Chemistry, National Chiao Tung
University,
1001 Ta Hsueh Rd, Hsinchu, Taiwan 30010, R.O.C
Fax: +886-3572-3764
In our recent studies we found that an electron-with-
drawing group (EWG) on the phenyl ring will make the
methine C–H more acidic,[12] and the methoxide released
during the reaction will remove the more acidic C–H proton
E-mail: jscchuang@faculty.nctu.edu.tw
Homepage: http://www.ac.nctu.edu.tw/people/bio.php?PID=63
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201200400.
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FULL PAPER
(pathway b; R = EWG). Herein we wish to report our syn-
Entries 1–6 show the absence of γ-lactones 3x,y and 4a,b
thesis of γ-lactones featuring an α-phosphorus ylide moiety when benzaldehyde or p-tolualdehyde was used as the π
by multicomponent reactions (MCRs) of DMAD, phos- electrophile for t = 24 h; neither were the products obtained
phanes, and electron-poor aldehydes in various molar ratios by using more nucleophilic phosphanes. In addition, we
and explore their reactivities as Wittig reagents.
only detected trace amounts of 3x,y and 4a,b for t = 0.5 h
(Entries 1 and 3). We then explored the reactions with the
more reactive 4-nitrobenzaldehyde, which produced 3a un-
der various conditions. We found that 3a was formed in
29% yield (39% based on converted aldehyde), ac-
companied by 15% 4c (20% based on converted aldehyde)
and 15% of the side-product 5c (21% based on converted
aldehyde) in anhydrous CH2Cl2 (Entry 7). Prolonged reac-
tion times (Entries 7–11) gave lower chemical yields of 3a
(21–29% for t = 0.5–72 h) and more of 4c (15–24% for t =
0.5–72 h) and 5c (15–28% for t = 0.5–72 h). We noticed that
3a was initially formed and then slowly transformed into
other species. We also found that THF (Entry 12) and
ODCB (Entry 13) were also suitable solvents for this reac-
tion despite the yields of 3a being slightly lower; the reac-
tion with THF as solvent, however, gave better selectivity.
The yield of 3a did not increase significantly with larger
amounts of DMAD (molar ratio of DMAD/1/2 = 1.5:1:1
and 3:1:1, respectively; Entries 14 and 15). We noted that
the reactions were moisture-sensitive, because addition of
1 equiv. of water led to a poorer reaction performance (En-
try 16). In addition, we also noticed that the fast addition
of DMAD, that is, in one portion, caused the formation of
other side-products. These side-products were structurally
the same as those investigated by Tebby and co-workers,
who noted that the 1,3-dipoles generated from DMAD and
phosphanes, in competition with aldehydes, reacted to form
1:2 (A), 2:1 (B), or 1:1 (C) adducts of DMAD/phos-
phanes.[13]
Results and Discussion
We started our investigation by revisiting the parent reac-
tion explored by Winterfeldt and Dillinger[9] to confirm the
previously observed low-yielding formation of dephosphan-
ated compound 4a and the absence of phosphane-contain-
ing compounds. We then investigated the use of more elec-
tron-poor aldehydes as electrophiles and other triaryl-
phosphanes as nucleophiles to explore the scope of the reac-
tion (Table 1).
Table 1. Reactions of DMAD with phosphanes 2a and 2c and alde-
hydes 1a–c.[a]
Entry
1
2
t [h] 3; yield [%][b] 4; Yield [%][b,c] 5; Yield [%][b,d]
1
2
3
4
5
6
7
8
1a 2a 0.5
1a 2a 24
1b 2a 0.5
1a 2c 0.5
1a 2c 24
1b 2c 0.5
1c 2a 0.5
3x; Ͻ2
3x; 0
3y; Ͻ2
3x; 0
3x; 0
4a; Ͻ2
4a; 0
4b; Ͻ2
4a; 0
4a; 0
5a; 0
5a; 0
5b; Ͻ2
5a; 0
5a; 0
We next evaluated the scope of this reaction by em-
ploying a variety of phosphanes 2a–i bearing either elec-
tron-donating or -withdrawing groups (EDG or EWG) on
their aryl rings or monoalkyl(diaryl)phosphanes (Table 2).
We observed that triarylphosphanes bearing electron-releas-
ing groups afforded γ-lactones 3a–c in higher yields based
on converted aldehyde (Table 2, Entries 1–3, 39–66%).
However, the more nucleophilic phosphane P(4-MeOPh)3
(2d) gave a lower yield and selectivity (Entry 4, 16%).
Alkyl-substituted phosphane 2e led to a higher selectivity,
but a lower reaction yield (Entry 5, 12%). We observed that
the isolated product 3e was relatively labile. In addition, we
attempted to obtain lactone 3 by using phosphites such as
P(OnPr)3 and P(OnBu)3 in this three-component reaction
instead of triarylphosphanes; however, complex mixtures
were formed. These mixtures formed a stripe of spots on
TLC plates and could not be separated by silica gel or alu-
minium oxide column chromatography. However, we iso-
lated stable 3f, obtained from P(cHex)3 (2f), in 18% yield
3y; 0
4b; 0
5b; 0
3a; 29 (39)
3a; 26 (36)
3a; 19 (26)
3a; 21 (27)
3a; 21 (26)
3a; 25 (32)
3a; 29 (44)
3a; 30 (32)
3a; 27
4c; 15 (20)
4c; 20 (27)
4c; 22 (30)
4c; 24 (30)
4c; 24 (29)
4c; 12 (16)
4c; 16 (25)
4c; 27 (29)
4c; 29
5c; 15 (21)
5c; 18 (25)
5c; 23 (31)
5c; 18 (22)
5c; 28 (34)
5c; 8 (10)
5c; 10 (15)
5c; 26 (28)
5c; 32
1c 2a
3
9[e]
10
11
1c 2a 24
1c 2a 48
1c 2a 72
12[f] 1c 2a 0.5
13[g] 1c 2a 0.5
14[h] 1c 2a 0.5
15[i]
16[j]
1c 2a 0.5
1c 2a 0.5
3a; 21 (34)
4c; 13 (20)
5c; 15 (24)
[a] All reactions were performed with DMAD (0.500 mmol), 1
(0.500 mmol), and 2 (0.500 mmol) at room temp. in anhydrous
CH2Cl2 unless otherwise noted. [b] Determined by 1H NMR spec-
troscopy using mesitylene as internal standard; the yields in paren-
theses are based on converted aldehyde. [c] See refs.[9,18] for the
known structures 4a–c. [d] See refs.[17,21] for the known structures
5a–c. [e] Reaction was carried out on the 1.0 mmol scale. [f] Reac-
tion was carried out in anhydrous THF. [g] Reaction was carried
out in anhydrous 1,2-dichlorobenzene (ODCB). [h] Molar ratio of
DMAD/1/2 = 1.5:1:1. [i] Molar ratio of DMAD/1/2 = 3:1:1. [j]
Reaction was performed with 1 equiv. of H2O as an additive.
2
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Synthesis of Lactones Bearing Phosphorus Ylides
(31% based on converted 1c) for characterization, which and selectivity (Entry 9) with larger amounts of 4c and 5c
has been attributed to the bulkier tricyclohexyl groups steri- being produced. To summarize, we found that the reaction
cally protecting the ylidic moiety (Entry 6). Reactions with with tri-p-tolylphosphane (2c) as nucleophile performed
phosphanes bearing 4-haloaryl groups, such as P(4-ClPh)3 best among the investigated phosphanes with a compromise
and P(4-FPh)3, also provided the corresponding products between yield and selectivity.
(3g and 3h, respectively) in moderate yields of 31 and 30%
Because electron-releasing phosphanes outperform elec-
(68 and 54% based on converted 1c; Entries 7 and 8), tron-withdrawing phosphanes on selectivities and yields, we
respectively, with less 4c. The reaction with electron-with- chose tri-p-tolylphosphane (2c) to carry out further optimi-
drawing tri-2-thienylphosphane (2i) gave a much lower yield zations of the reaction (Table 3). We found that the reaction
carried out in THF at 0 °C gave a higher yield and selectiv-
ity than that performed in CH2Cl2 [27 (66) vs. 33% (81%);
Table 2. Reactions of phosphanes 2a–i with DMAD and 4-ni-
Entries 1 and 2]. Reactions with higher molar ratios of
DMAD (1.5 equiv. with respect to 1c and 2c) or with a
prolonged reaction time (4 h) did not improve the yield sig-
nificantly (Entries 3–5); unreacted aldehydes were recovered
under these conditions. Parallel increments of DMAD and
2c, to give a molar ratio of DMAD/1c/2c = 2:1:2, resulted
in less recovered aldehyde and higher yields of 3c (33% for
t = 0.5 h and 50% for t = 3 h; Entries 6 and 7). It was
interesting that the reaction carried out at –60 °C (Entry 8)
gave a lower yield than that carried out at 0 °C, and a large
amount of 4c (26%) was observed under these conditions.
Adjustment of the molar ratio of DMAD/1c/2c to 2:1:4 ex-
clusively provided 3c in 66% yield for t = 3 h (Entry 9);
however, for t = 6 h, 3c was obtained in a lower yield of
56% and was accompanied by 4c in 31% yield (Entry 10).
We finally obtained 3c in up to 86% yield selectively with
a molar ratio of DMAD/1c/2c = 3:1:6 (Entry 11); these re-
action conditions were found to be quite reproducible giv-
ing yields of 76–86%.
trobenzaldehyde (1c).[a]
Entry
2: PAr3
3; yield [%][b] 4c; yield [%][b] 5c; yield [%][b]
1
2
3
4
5
6
7
8
9
2a; PPh3
2b; PPh2(pTol)
2c; P(pTol)3
2d; P(4-MeOC6H4)3
2e; PMePh2
3a; 29 (39)
3b; 29 (47)
3c; 31 (66)
3d; 16 (21)
3e; 12 (30)
3f; 18 (31)
3g; 31 (68)
3h; 30 (54)
3i; 10 (16)
15 (20)
12 (19)
4 (8)
17 (22)
0
15 (21)
12 (19)
7 (15)
4 (5)
3 (7)
2 (4)
12 (26)
15 (28)
21 (33)
2f; P(cHex)3
0
2g; P(4-ClC6H4)3
2h; P(4-FC6H4)3
2i; P(2-thienyl)3
2 (5)
9 (16)
30 (46)
With the optimized conditions in hand, we further ex-
plored the reaction scope by using other electron-deficient
aldehydes in a DMAD/aldehyde/phosphane molar ratio of
3:1:6 (Table 4). We found that aldehydes such as 3- and 2-
nitrobenzaldehydes (1d and 1e) gave 65 and 43% yields of
[a] All reactions were performed with DMAD (0.500 mmol), 1c
(0.500 mmol), and 2 (0.500 mmol) in CH2Cl2 at room temp.. [b]
Determined by 1H NMR spectroscopy using mesitylene as internal
standard; the yields in parentheses are based on converted alde-
hyde.
Table 3. Optimization of the reaction conditions.[a]
Entry
Molar ratio of DMAD/1c/2c
Temp.[°C]
Time [min]
3c; yield [%][b]
4c; yield [%][b]
5c; yield [%][b]
1[c]
2
3
4
5
6
7
8
9
1:1:1
1:1:1
1.5:1:1
1.5:1:1
1.5:1:1
2:1:2
2:1:2
2:1:2
2:1:4
2:1:4
r.t.
0
0
0
0
0
0
–60
0
0
30
30
30
27 (66)
33 (81)
31 (72)
35 (69)
28 (71)
33 (62)
50
35
66 (77)
56
4 (8)
0
0
1 (2)
0
0
23
26
0
31
0
7 (15)
4 (10)
5 (12)
4 (8)
4 (11)
5 (8)
0
13
0
0
0
240[d]
240[e]
30
180
180[f]
180
360
180
10
11
3:1:6
0
86
[a] All reactions were carried out in THF under nitrogen unless otherwise noted. The reaction time included the initial 10 min injection
1
time of a DMAD solution. [b] Determined by H NMR spectroscopy using mesitylene as internal standard; the yields in parentheses are
based on converted aldehyde. [c] The reaction was carried out in CH2Cl2. [d] DMAD in THF (10 mL) was added through a syringe
pump over 3 h and the mixture stirred for 1 h. [e] DMAD in THF (20 mL) was added through a syringe pump over 3 h and and the
mixture stirred for 1 h. [f] DMAD in THF (10 mL) was added at –60 °C in one portion and the mixture stirred at room temp. for 3 h.
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3j and 3k, respectively (72 and 56% based on converted
We also evaluated the reactions yielding ylides incorpo-
1d and 1e; Entries 2 and 3); some unreacted aldehyde was rating trialkylphosphanes 2j–m (Table 5). To our surprise,
recovered in each case. We noted that compound 3k is rela- we isolated zwitterionic intermediates 3pЈ–3sЈ in 60–64%
tively unstable upon isolation. Disubstituted benzaldehydes yields, which are precursors to the ylides 3p–3s; in these
such as 4-chloro-3-nitro- and 4-fluoro-3-nitrobenzaldehydes reactions, only trace amounts of 3p–3s were observed. In-
(1f and 1g; Entries 4 and 5) gave moderate to good yields termediates of type 3pЈ–3sЈ have recently been discovered
(78 and 52%, respectively, 84% based on converted 1g). by Kwon and co-workers.[14] The transformation of inter-
This indicates that the aryl ring of the 4-fluoro-substituted mediates 3pЈ–3sЈ into ylides 3p–3s requires an initial Cα–
aldehyde is more electron-rich than that of the 4-chloro- Cβ bond rotation (structure 3Ј in Table 5) for subsequent
substituted aldehyde. Finally, reactions with 4-cyano and 4- intramolecular lactonization. We observed that intermedi-
pyridyl aldehydes as electrophiles gave lower yields (49 and ate 3pЈ bearing tri-n-butylphosphane (2j) was transformed
37%, respectively), but moderate to good yields based on into reddish ylide 3p on slightly acidic silica gel at room
converted aldehyde (60 and 62%, Entries 6 and 7, respec- temperature over 2 d (60%, Entry 1). However, the lacton-
tively). This is likely due to their lower reactivities. In sum- ization of 3qЈ–3sЈ is less effective as these intermediates have
mary, this study of reaction scope provided reaction yields shorter alkyl chains. We found that intermediates 3rЈ and
in the range of 37–86% (56–86% based on converted alde- 3sЈ are quite stable and can be isolated in yields of 61 and
hyde).
64%, respectively (Entries 3 and 4, respectively), ac-
companied by lactones 3r and 3s as side-products (13 and
10%, respectively). To obtain 3r and 3s more efficiently, we
heated the intermediates 3rЈ and 3sЈ to give 3r and 3s in
moderate to good yields (81 and 53%, Entries 3 and 4).
This reflects the fact that intermediates with bulkier substit-
uents such as the n-butyl group are less stable due to steric
hindrance and that with methyl or ethyl groups they are
more stable at room temperature due to stronger intramo-
lecular bonding between the charged oxygen and phos-
phorus groups in intermediates 3rЈ and 3sЈ.
Table 4. Reaction of DMAD and 2c with aldehydes 1c–i.[a]
Entry
1; Ar
3; yield [%][b]
1
2
3
4
5
6
7
1c; 4-O2NC6H4
1d; 3-O2NC6H4
1e; 2-O2NC6H4
1f; 4-Cl-3-O2NC6H3
1g; 4-F-3-O2NC6H3
1h; 4-NCC6H4
3c; 86
We characterized the γ-lactones 3a–3s by IR and 1H, 31P,
and 13C NMR spectroscopy, ESI-MS, and X-ray crystal-
lography. All MS data corresponded to the expected formu-
lae of the isolated γ-lactones. In the IR spectra, the C=O
stretching band next to the ylidic carbanion appears at
around 1669–1704 cm–1, lower than that of a normal C=O
3j; 65 (72)
3k; 43 (56)
3l; 78
3m; 52 (84)
3n; 49 (60)
3o; 37 (62)
1i; 4-pyridyl
[a] All reactions were performed with DMAD (0.500 mmol),
DMAD (0.167 mmol), and 2c (1.000 mmol; DMAD/1/2c = 3:1:6)
at 0 °C; DMAD in THF (10 mL) was added through a syringe
pump over 10 min and the mixture stirred for 3 h. [b] Determined
by 1H NMR spectroscopy using mesitylene as internal standard;
the yields in parentheses are based on converted aldehyde.
stretching frequency because of resonance effects. In the 31
P
NMR spectrum of compound 3o as an example, we ob-
served a signal at δ = 13.9 ppm corresponding to a typical
1
α-ylidic γ-lactone. Its H NMR spectrum displays singlets
Table 5. Reactions of DMAD with alkylphosphanes 2j–m and aldehyde 1c.[a]
Entry
2; R
3Ј; yield [%][b]
3Ј to 3; yield [%][c]
1
2
3
4
2j; nBu
2k; nPr
2l; Et
3pЈ; 62 (82)
3qЈ; 60 (72)
3rЈ; 61 (75)
3sЈ; 64[f]
3p; 60[d]
3q; 56[d]
3r; 81[e]
3s; 53[e]
2m; Me
[a] All reactions were performed with a DMAD/1c/2 molar ratio of 1:1:1 under anhydrous conditions at room temp. unless otherwise
1
noted; phosphane 2 in THF was added through a syringe pump over 10 min and the mixture stirred for 50 min. [b] Determined by H
NMR spectroscopy using mesitylene as internal standard; the yields in parentheses are based on converted aldehyde. [c] Determined by
1H NMR spectroscopy using mesitylene as internal standard. [d] Upon completion of the reaction, solvents were removed under reduced
pressure, and ethyl acetate was added followed by further stirring at room temp. for 72 h (two-step yield). [e] The pure intermediates
3rЈ–sЈ were first isolated by flash column chromatography, and then 3rЈ–sЈ (0.300 mmol) was heated at 80 °C for 12 h to obtain 3r–s. [f]
Molar ratio of DMAD/1c/2 = 1:3:1.
4
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Synthesis of Lactones Bearing Phosphorus Ylides
at δ = 2.44 and 2.94 ppm corresponding to methyl and of phosphanes in their investigations. We noted that the re-
methoxy groups. The two signals in the 13C NMR spectrum activity of DMAD with phosphanes is higher than that of
at δ = 164.2 and 169.0 ppm (2JPC = 18.0 Hz) correspond to an enyne; this difference was observed by the slow progress
ester and lactone carbonyl resonances. The signal of the of the reactions of enynes with phosphanes at room tem-
ylidic carbon atom (C2, Figure 1) appears at δ = 54.7 ppm perature.[12a] The efficiency is lower due to the formation of
with one-bond coupling to P1 (1JPC = 135.6 Hz). We found highly polar and non-eluable dark material. However, we
that these isolated ylide compounds tend to crystallize by isolated lactone ylides 3 in yields of up to 86% under our
slow concentration of their chloroform solutions. We deter- conditions. The independent work of Nair, Alizadeh, and
mined the crystal structure of compound 3o by X-ray dif- Yavari and their co-workers[19] resulted in the isolation of
fraction (Figure 1).[15] The phosphorus atom P1 is clearly cyclopentenylphosphoranes (D),[19a] cyclopentadienylphos-
bonded to C2 with a bond length of 1.7480(3) Å. The skel- phoranes (E),[19b] or phosphorus lactone (F) through the
eton of the lactone ring is slightly distorted from planarity, reactions of triphenylphosphane, DMAD, and electron-de-
as evidenced from the torsional angle for C2–C1–O1–C4 of ficient dicyanostyrenes, 2-(nitroethenyl)benzene, or alkyl 2-
–3.1(3)°. Owing to the delocalization of negative charge chloroacetoacetates.[19f] To the best of our knowledge, these
from the ylidic carbon atom C2 to the carbonyl π bond are the first γ-lactones featuring an α-phosphorus ylide
(C1–O2), the C1–C2 bond is shorter [1.4070(5) Å] than a moiety to be obtained under our new conditions from the
normal C–C single bond.
reaction of DMAD, phosphanes, and aldehydes.[20] Our
work has provided a convenient and direct route to γ-lact-
ones possessing an α-phosphorus ylide moiety from com-
mercially available reagents in one step, namely by multi-
component reactions (MCRs).
The reactions of these isolated α-ylidic lactones as Wittig
reagents with aldehydes were interesting. We found that
both 3a and 3c reacted with aldehyde 1c to give only trace
amounts of a yellowish mixture of (E)- and (Z)-6a (Ͻ1%
Figure 1. X-ray crystal structure of compound 3o.
The reactions of DMAD, triarylphosphanes, and alde- yield; Table 6, Entries 1 and 2). After prolonging the reac-
hydes have previously been investigated by Nozaki,[16] tion time from 3 to 21 d, only 3% of (E)- and (Z)-6a was
Shi,[17] and Bayat[18] and their co-workers. However, such observed (6% based on converted ylide 3a; Entry 3). How-
lactones bearing α-phosphorus ylides were not isolated, ever, their synthetic potential becomes notable when these
likely due to longer reaction times (24 h) or lower loadings ylides bear alkylphosphanes. The ylides bearing n-butyl, n-
Table 6. Wittig reaction of ylides with aldehydes.[a]
Entry
1; X
3; R
Molar ratio of 1/3
Time
6; yield [%][b]
1
2
3
4
5
6
7
8
9
1c; 4-O2N
1c; 4-O2N
1c; 4-O2N
1c; 4-O2N
1c; 4-O2N
1c; 4-O2N
1c; 4-O2N
1d; 3-O2N
1f; 4-Cl-3-O2N
1d; 3-O2N
3a; Ph
3c; pTol
3c; pTol
3p; nBu
3q; nPr
3r; Et
3s; Me
3s; Me
3s; Me
3s; Me
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:3
72 h
72 h
21 d
72 h
72 h
72 h
72 h
72 h
72 h
72 h
6a; Ͻ1
6a; 1 (2)
6a; 3 (6)
6a; 8 (11)
6a; 13 (22)
6a; 9 (35)
6a; 30 (43)
6c; 39 (74)
6b; 18 (24)
6c; 48 (51)
10
1
[a] All reactions were performed in anhydrous toluene in a sealed tube under argon at 130 °C. [b] Determined by H NMR spectroscopy
using mesitylene as internal standard; the yields in parentheses are based on converted 3.
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S.-C. Chuang et al.
FULL PAPER
propyl, ethyl, and methyl groups (3p–s, respectively) reacted good yields. The application of this synthesis could lead to
with aldehyde 1c, with a molar ratio of 1:1, to afford yields a variety of versatile aryl-substituted γ-lactones. Further-
of 8–30% (11–43% based on converted aldehyde) at 130 °C more, the γ-lactone bearing the trimethylphosphorus ylide
in a sealed tube over 3 d (Entries 4–7). We also investigated moiety reacts with aldehydes to give olefinic compounds in
the reaction of ylide 3s with aldehyde 1d and found that moderate yields. This methodology provides a new tool for
this Wittig reaction occurred in higher yield (39%, 74% use in the synthesis of α-olefinic lactones via γ-lactone
based on converted aldehyde; Entry 8). By comparing the ylides prepared in a single pot.
results of the reactions of the ylides 1c, 1d, and 1f with the
less hindered alkylphosphanes 3p–s (Entries 4–9), we con-
cluded that the Wittig reaction between aldehyde 1d and
ylide 3s gave the highest yield (39%, 74% based on con-
verted aldehyde; Entry 8). A further increment in the molar
ratio of 3s relative to 1d provided a higher yield of 6c (48%;
Experimental Section
General Methods: All reactions were performed under nitrogen.
Anhydrous CH2Cl2 was distilled from CaH2 under argon. Anhy-
drous THF was distilled from sodium/benzophenone under argon.
51% based on converted aldehyde; Entry 10). Although the
The chemical shifts in the 31P NMR spectra are given with 85% of
outcome of this Wittig reaction is promising, we found that
the most reactive ylide 3s is unreactive towards ketones
such as 4Ј-nitroacetophenone. A higher reaction tempera-
ture does not assist the Wittig reaction with ketones, be-
H3PO4 in D2O as reference and those in the 1H and 13C NMR
spectra are referenced to TMS or CHCl3. Mesitylene was added to
the products isolated by column chromatography to determine their
1
quantity by H NMR spectroscopy. After spectroscopic measure-
cause decomposition of ylide 3s becomes notable above ment, the isolated products were dissolved in a minimum amount
of CHCl3 and precipitated with hexanes in a centrifuge tube. Pure
solids were obtained by centrifuge followed by removal of trace
solvents under vacuum. NMR, FT-IR and mass data were recorded
with Bruker DRX-300, Digilab Excalibur HE series FTS 3100 and
Varian 901-MS spectrometers, respectively.
150 °C.
Compound 6a exhibits an (E)/(Z) isomeric ratio of 3:1
(based on the crude HPLC chromatogram), and the ratio
changed to nearly 1:1 upon exposure to light for a few days.
We found that the (E) and (Z) isomers of 6a–c could not
be separated by flash column chromatography (SiO2); how-
ever, one of them, (E)- and (Z)-6a, could be separated by
recycling HPLC on the seventh cycle, as shown in the
HPLC chromatogram in Figure 2. Owing to the poor solu-
bility of 6b and 6c, we could only obtain 1H NMR spectro-
metric data for the separated (E) and (Z) isomers of 6a (see
the Supporting Information).
Typical Procedure for the Synthesis of Compound 3a in CH2Cl2:
DMAD (0.0710 g, 0.500 mmol) in CH2Cl2 (10 mL) was added to
an anhydrous dichloromethane solution of 4-nitrobenzaldehyde
(1c; 0.0760 g, 0.500 mmol) and triphenylphosphane (2a; 0.1310 g,
0.5000 mmol) through a digital syringe pump in 10 min. The mix-
ture was then stirred at room temp. for 30 min. Upon completion
of the reaction, CH2Cl2 was removed under vacuum. The mixture
was then subjected to flash chromatography. Elution with hexanes/
ethyl acetate (EA) (1:1) gave product 3a (Entry 7, Table 1).
Typical Procedure for the Synthesis of Compound 3c in THF:
DMAD (0.0710 g, 0.500 mmol) in THF (10 mL) was added to an
anhydrous THF solution (5 mL) containing molecular sieves (4 Å),
4-nitrobenzaldehyde (1c; 0.0250 g, 0.170 mmol), and tri-p-tolyl-
phosphane (2c; 0.3040 g, 1.000 mmol) through a digital syringe
pump at 0 °C over 10 min. The mixture was then stirred at 0 °C for
3 h. Upon completion of the reaction, THF was removed under
vacuum. The mixture was then subjected to flash chromatography.
Elution with hexanes/EA (1:1) gave product 3c (Entry 11, Table 3).
Typical Procedure for the Synthesis of (E)- and (Z)-6c: A pressure-
affordable reaction tube containing ylide 3s (0.1000 g,
0.2640 mmol), aldehyde 1d (0.0130 g, 0.0880 mmol), and a stirring
bar in dry toluene (15 mL) was stirred vigorously at 130 °C for
72 h. After completion of the reaction, the reaction mixture was
subjected to column chromatography with hexanes/dichlorometh-
ane (DCM) (1:3) as eluent to obtain a mixture of (E)- and (Z)-6c
(0.0160 g) in 48% yield (51% based on unreacted 1d) and hexanes/
DCM (1:2) as eluent for the recovery of unreacted 1d (0.0010 g,
8%).
Figure 2. Recycling HPLC chromatogram of (E)- and (Z)-6a (pre-
parative Buckyprep column; 2 cmϫ25 cm, eluent: toluene, 50 °C);
compound (E)-6a (shorter retention time) was eluted prior to (Z)-
6a.
Methyl 2-(4-Nitrophenyl)-5-oxo-4-(triphenyl-λ5-phosphanylidene)-
4,5-dihydrofuran-3-carboxylate (3a): Red solid. M.p. 214–216 °C. Rf
= 0.20 (EA/hexanes, 1:1). Isolated yield 29% (0.0759 g). H NMR
Conclusions
We have demonstrated that γ-lactones bearing an α-
phosphorus ylide moiety can be efficiently prepared
through multicomponent reactions (MCRs) of DMAD,
phosphanes, and electron-deficient aldehydes in one step.
Tri-p-tolylphosphane was found to be the most appropriate
1
(300 MHz, CDCl3, 25 °C): δ = 2.93 (s, OCH3), 7.53–7.59 (m, 6 H,
Ar-H), 7.63–7.76 (m, 9 H, Ar-H), 7.95 (d, J = 9.2 Hz, 2 H, Ar-H),
8.16 (d, J = 9.2 Hz, 2 H, Ar-H) ppm. 13C NMR (75.5 MHz,
CDCl3, 25 °C): δ = 50.7 (OCH3), 54.0 [d, 1J(C,P) = 135.9 Hz], 117.2
2
1
phosphane nucleophile for giving the γ-lactone products in [d, J(C,P) = 11.5 Hz], 123.4, 123.6 [d, J(C,P) = 95.0 Hz], 127.0,
6
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Synthesis of Lactones Bearing Phosphorus Ylides
3
4
2
4
128.9 [d, J(C,P) = 12.8 Hz], 133.0 [d, J(C,P) = 2.9 Hz], 133.8 [d,
2J(C,P) = 10.5 Hz], 136.0, 141.4 [d, 3J(C,P) = 12.5 Hz], 145.9, 164.0
(C=O), 169.0 [d, 2J(C,P) = 18.3 Hz, C=O] ppm. 31P NMR
3J(C,P) = 13.0 Hz], 132.0 [d, J(C,P) = 10.9 Hz], 133.0 [d, J(C,P)
3
= 2.9 Hz], 136.0, 141.5 [d, J(C,P) = 12.2 Hz], 146.1, 163.8 (C=O),
169.7 [d, 2J(C,P) = 19.2 Hz, C=O] ppm. 31P NMR (242.5 Hz,
(242.5 Hz, CDCl , 25 °C): δ = 14.6 ppm. FTIR (KBr): ν = 1685, CDCl , 25 °C): δ = 11.3 ppm. FTIR (KBr): ν = 1682, 1721 cm–1.
˜
˜
3
3
1716 cm–1. HRMS (ESI+): calcd. for C30H22NO6P [M]+ 523.1165; HRMS (ESI+): calcd. for C25H20NO6P [M]+ 461.1028; found
found 523.1185.
461.1030.
Methyl 4-[Diphenyl(p-tolyl)-λ5-phosphanylidene]-2-(4-nitrophenyl)-
5-oxo-4,5-dihydrofuran-3-carboxylate (3b): Orange solid. M.p.
194 °C. Rf = 0.18 (EA/hexanes, 1:1). Isolated yield 29% (0.0779 g).
1H NMR (300 MHz, CDCl3, 25 °C): δ = 2.45 (s, CH3), 2.93 (s,
OCH3), 7.36 (dd, J = 2.9, J = 8.2 Hz, 2 H, Ar-H), 7.52–7.76 (m,
12 H, Ar-H), 7.94 (d, J = 9.1 Hz, 2 H, Ar-H), 8.16 (d, J = 9.2 Hz,
2 H, Ar-H) ppm. 13C NMR (75.5 MHz, CDCl3, 25 °C): δ = 21.6
[d, 5J(C,P) = 1.4 Hz, CH3], 50.7 (OCH3), 54.4 [d, 1J(C,P) =
135.6 Hz], 117.4 [d, 2J(C,P) = 11.6 Hz], 119.9 [d, 1J(C,P) =
97.4 Hz], 123.4, 123.9 [d, 1J(C,P) = 95.0 Hz], 126.9, 128.9 [d,
Methyl 2-(4-Nitrophenyl)-5-oxo-4-(tricyclohexyl-λ5-phosphanylid-
ene)-4,5-dihydrofuran-3-carboxylate (3f): Orange solid. M.p. 233–
235 °C. Rf = 0.38 (EA/hexanes, 1:1). Isolated yield 18% (0.0487 g).
1H NMR (300 MHz, CDCl3, 25 °C): δ = 1.21–1.92 (m, 15 CH2),
3.03 (q, J = 12.6 Hz, 3 CH), 3.77 (s, OCH3), 7.55 (d, J = 9.0 Hz, 2
H, Ar-H), 8.15 (d, J = 8.7 Hz, 2 H, Ar-H) ppm. 13C NMR
(75.5 MHz, CDCl3, 25 °C): δ = 25.82 (CH2), 27.0 [d, 3J(C,P) =
2
1
12.5 Hz, CH2], 27.3 [d, J(C,P) = 3.0 Hz, CH2], 31.6 [d, J(C,P) =
1
40.2 Hz, CH], 52.1 (OCH3), 52.8 [d, J(C,P) = 110.4 Hz], 118.1 [d,
2J(C,P) = 9.7 Hz], 123.4, 126.1, 136.5, 139.2 [d, 3J(C,P) = 10.6 Hz],
145.4, 166.4 (C=O), 170.2 [d, 2J(C,P) = 15.1 Hz, C=O] ppm. 31P
3
4
3J(C,P) = 12.9 Hz], 129.7 [d, J(C,P) = 13.3 Hz], 132.9 [d, J(C,P)
3
3
= 3 Hz], 133.8 [d, J(C,P) = 10.3 Hz], 133.9 [d, J(C,P) = 10.3 Hz],
136.1, 141.1 [d, 3J(C,P) = 12.2 Hz], 144.0 [d, 4J(C,P) = 2.9 Hz],
145.8, 164.1 (C=O), 169.0 [d, 2J(C,P) = 18.2 Hz, C=O] ppm. 31P
NMR (242.5 Hz, CDCl , 25 °C): δ = 27.6 ppm. FTIR (KBr): ν
˜
3
= 1669, 1717 cm–1. HRMS (ESI+): calcd. for C30H40NO6P [M]+
541.2593; found 541.2592.
NMR (242.5 Hz, CDCl , 25 °C): δ = 14.1 ppm. FTIR (KBr): ν
˜
3
Methyl
2-(4-Nitrophenyl)-5-oxo-4-[tris(4-chlorophenyl)-λ5-phos-
= 1685, 1717 cm–1. HRMS (ESI+): calcd. for C31H24NO6P [M]+
phanylidene]-4,5-dihydrofuran-3-carboxylate (3g): Yellow solid.
M.p. 118–120 °C. Rf = 0.40 (EA/hexanes, 1:1.5). Isolated yield 31%
(0.0969 g). 1H NMR (300 MHz, CDCl3, 25 °C): δ = 3.10 (s, OCH3),
7.53–7.65 (m, 12 H, Ar-H), 7.93 (d, J = 8.8 Hz, 2 H, Ar-H), 8.18
(d, J = 8.7 Hz, 2 H, Ar-H) ppm. 13C NMR (75.5 MHz, CDCl3,
25 °C): δ = 51.0 (OCH3), 52.2 [d, 1J(C,P) = 138.6 Hz], 115.9 [d,
2J(C,P) = 11.4 Hz], 121.8 [d, 1J(C,P) = 98.3 Hz], 123.2, 127.6, 129.5
[d, 3J(C,P) = 13.7 Hz], 134.9 [d, 2J(C,P) = 11.6 Hz], 135.7, 140.3
[d, 4J(C,P) = 3.8 Hz], 142.5 [d, 3J(C,P) = 12.8 Hz], 146.2, 163.6
(C=O), 168.7 [d, 2J(C,P) = 19.6 Hz, C=O] ppm. 31P NMR
537.1341; found 537.1339.
Methyl 2-(4-Nitrophenyl)-5-oxo-4-(tri-p-tolyl-λ5-phosphanylidene)-
4,5-dihydrofuran-3-carboxylate (3c): Orange solid. M.p. 216–
218 °C. Rf = 0.29 (EA/hexanes, 1:1). Isolated yield 86% (0.0826 g).
1H NMR (300 MHz, CDCl3, 25 °C): δ = 2.44 (s, 3 CH3), 2.93 (s,
OCH3), 7.33–7.36 (m, 6 H, Ar-H), 7.56–7.63 (m, 6 H, Ar-H), 7.93
(d, J = 9.0 Hz, 2 H, Ar-H), 8.14 (d, J = 9.0 Hz, 2 H, Ar-H) ppm.
13C NMR (75.5 MHz, CDCl3, 25 °C): δ = 21.6 [d, 5J(C,P) = 1.0 Hz,
1
2
CH3], 50.6 (OCH3), 55.3 [d, J(C,P) = 135.2 Hz], 117.8 [d, J(C,P)
= 11.6 Hz], 120.3 [d, 1J(C,P) = 97.4 Hz], 123.3, 126.6, 129.6 [d,
3J(C,P) = 13.3 Hz], 133.7 [d, 2J(C,P) = 10.9 Hz], 136.1, 140.6 [d,
3J(C,P) = 12.3 Hz], 143.7 [d, 4J(C,P) = 2.9 Hz], 145.6, 164.2 (C=O),
169.0 [d, 2J(C,P) = 18.1 Hz, C=O] ppm. 31P NMR (242.5 Hz,
(242.5 Hz, CDCl , 25 °C): δ = 13.9 ppm. FTIR (KBr): ν = 1686,
˜
3
1716 cm–1. HRMS (ESI+): calcd. for C30H19Cl3NO6P [M]+
625.0016; found 625.0015.
CDCl , 25 °C): δ = 13.6 ppm. FTIR (KBr): ν = 1691, 1721 cm–1.
Methyl 2-(4-Nitrophenyl)-5-oxo-4-[tris(4-fluorophenyl)-λ5-phosphan-
ylidene]-4,5-dihydrofuran-3-carboxylate (3h): Yellow solid. M.p.
112–114 °C. Rf = 0.19 (EA/hexanes, 1:2). Isolated yield 30%
(0.0866 g). 1H NMR (300 MHz, CDCl3, 25 °C): δ = 3.09 (s, OCH3),
7.24–7.31 (m, 6 H, Ar-H), 7.67–7.75 (m, 6 H, Ar-H), 7.91 (d, J =
9.1 Hz, 2 H, Ar-H), 8.16 (d, J = 9.1 Hz, 2 H, Ar-H) ppm. 13C
NMR (75.5 MHz, CDCl3, 25 °C): δ = 50.9 (OCH3), 53.2 [d, 1J(C,P)
= 138.2 Hz], 116.2 [d, 2J(C,P) = 11.5 Hz], 116.5 [dd, 3J(C,P) = 10.6,
˜
3
HRMS (ESI+): calcd. for C33H28NO6P [M]+ 565.1654; found
565.1648.
Methyl
phanylidene]-4,5-dihydrofuran-3-carboxylate (3d): Red solid. M.p.
80–82 °C. Rf 0.29 (EA/hexanes, 2:1). Isolated yield 16%
2-(4-Nitrophenyl)-5-oxo-4-[tris(4-methoxyphenyl)-λ5-phos-
=
(0.0491 g). 1H NMR (300 MHz, CDCl3, 25 °C): δ = 3.00 (s, OCH3),
3.87 (s, 3 OCH3), 7.04 (dd, J = 2.3, J = 9.0 Hz, 6 H, Ar-H), 7.62
(dd, J = 8.8, J = 12.5 Hz, 6 H, Ar-H), 7.89 (d, J = 9.0 Hz, 2 H,
Ar-H), 8.14 (d, J = 9.1 Hz, 2 H, Ar-H) ppm. 13C NMR (75.5 MHz,
4
1
2J(C,F) = 21.9 Hz], 119.3 [dd, J(C,F) = 3.4, J(C,P) = 100.0 Hz],
123.3, 127.4, 135.8, 136.3 [dd, 3J(C,F) = 9.2, 2J(C,P) = 12.3 Hz],
142.1 [d, 3J(C,P) = 12.4 Hz], 146.2, 163.8 (C=O), 165.6 [dd, 4J(C,P)
= 3.2, 1J(C,F) = 257.4 Hz], 168.8 [d, 2J(C,P) = 18.8 Hz, C=O] ppm.
31P NMR (242.5 Hz, CDCl3, 25 °C): δ = 13.1 [d, 5J(P,F) =
1
CDCl3, 25 °C): δ = 50.9 (OCH3), 55.4 (OCH3), 56.6 [d, J(C,P) =
135.5 Hz], 114.4 [d, 2J(C,P) = 14.0 Hz], 114.5 [d, 1J(C,P) =
102.4 Hz], 118.1 [d, 2J(C,P) = 11.8 Hz], 123.4, 126.3, 135.6 [d,
2J(C,P) = 12.2 Hz], 136.1, 140.0 [d, 3J(C,P) = 12.2 Hz], 145.5, 163.1
[d, 4J(C,P) = 2.9 Hz], 164.4 (C=O), 169.1 [d, 2J(C,P) = 18.1 Hz,
C=O] ppm. 31P NMR (242.5 Hz, CDCl3, 25 °C): δ = 12.3 ppm.
1.5 Hz] ppm. FTIR (KBr): ν = 1686, 1717 cm–1. HRMS (ESI+):
˜
calcd. for C30H19F3NO6P [M]+ 577.0902; found 577.0899.
Methyl
2-(4-Nitrophenyl)-5-oxo-4-(tri-2-thienyl-λ5-phosphanylid-
FTIR (KBr): ν = 1685, 1717 cm–1. HRMS (ESI+): calcd. for
˜
ene)-4,5-dihydrofuran-3-carboxylate (3i): Red solid. M.p. 180 °C. Rf
C33H28NO9P [M]+ 613.1502; found 613.1498.
1
= 0.29 (EA/hexanes, 2:1). Isolated yield 10% (0.0270 g). H NMR
Methyl 4-[Methyl(diphenyl)-λ5-phosphanylidene]-2-(4-nitrophenyl)-
5-oxo-4,5-dihydrofuran-3-carboxylate (3e): Orange solid. M.p.
180 °C. Rf = 0.18 (EA/hexanes, 3:1). Isolated yield 12% (0.0277 g).
1H NMR (300 MHz, CDCl3, 25 °C): δ = 2.54 (d, J = 13.7 Hz,
CH3), 3.10 (s, OCH3), 7.57–7.77 (m, 10 H, Ar-H), 7.94 (d, J =
(300 MHz, CDCl3, 25 °C): δ = 3.14 (s, OCH3), 7.29–7.33 (m, 3 H,
Ar-H), 7.76–7.80 (m, 3 H, Ar-H), 7.91–7.95 (m, 3 H, Ar-H), 7.98
(d, J = 9.1 Hz, 2 H, Ar-H), 8.18 (d, J = 9.1 Hz, 2 H, Ar-H) ppm.
13C NMR (75.5 MHz, CDCl3, 25 °C): δ = 50.9 (OCH3), 56.5 [d,
2
1J(C,P) = 150.0 Hz], 116.1 [d, J(C,P) = 13.6 Hz], 123.3, 125.6 [d,
9.1 Hz, 2 H, Ar-H), 8.17 (d, J = 9.0 Hz, 2 H, Ar-H) ppm. 13C 1J(C,P) = 119.4 Hz], 127.4, 129.0 [d, 3J(C,P) = 16.1 Hz], 135.9,
1
4
2
NMR (75.5 MHz, CDCl3, 25 °C): δ = 13.0 [d, J(C,P) = 62.9 Hz, 136.5 [d, J(C,P) = 5.8 Hz], 139.5 [d, J(C,P) = 12.0 Hz], 141.8 [d,
1
2
CH3], 50.9 (OCH3), 55.1 [d, J(C,P) = 134.5 Hz], 116.5 [d, J(C,P)
3J(C,P) = 13.8 Hz], 146.1, 163.7 (C=O), 168.2 [d, 2J(C,P) =
20.3 Hz, C=O] ppm. 31P NMR (242.5 Hz, CDCl3, 25 °C): δ =
= 10.9 Hz], 123.3, 125.4 [d, 1J(C,P) = 94.3 Hz], 127.5, 129.2 [d,
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FULL PAPER
–8.6 ppm. FTIR (KBr): ν = 1688 cm–1. HRMS (ESI+): calcd. for
J(C,F) = 8.4 Hz], 136.7 [d, J(C,F) = 7.8 Hz], 140.8 [d, 3J(C,P) =
12.4 Hz], 143.4 [d, 4J(C,P) = 3.0 Hz], 153.9 [d, 1J(C,F) = 265.7 Hz],
163.7 (C=O), 168.8 [d, 2J(C,P) = 18.5 Hz, C=O] ppm. 31P NMR
˜
C24H16NO6PS3 [M]+ 540.9877; found 540.9876.
Methyl 2-(3-Nitrophenyl)-5-oxo-4-(tri-p-tolyl-λ5-phosphanylidene)-
4,5-dihydrofuran-3-carboxylate (3j): Orange solid. M.p. 196 °C. Rf
(242.5 Hz, CDCl , 25 °C): δ = 13.6 ppm. FTIR (KBr): ν = 1704
˜
3
(br) cm–1. HRMS (ESI+): calcd. for C33H27FNO6P [M]+ 583.1560;
1
= 0.23 (EA/hexanes, 1:1). Isolated yield 65% (0.0625 g). H NMR
found 583.1568.
(300 MHz, CDCl3, 25 °C): δ = 2.44 (s, 3 CH3), 2.98 (s, OCH3), 7.33
(m, 6 H, Ar-H), 7.48 (t, J = 8.1 Hz, 1 H, Ar-H), 7.58 (m, 6 H, Ar-
H), 8.06 (dd, J = 1.5, J = 8.1 Hz, 1 H, Ar-H), 8.11, (d, J = 8.0 Hz,
1 H, Ar-H), 8.76 (t, J = 1.8 Hz, 1 H, Ar-H) ppm. 13C NMR
(75.5 MHz, CDCl3, 25 °C): δ = 21.6 [d, 5J(C,P) = 1.1 Hz, CH3],
50.5 (OCH3), 53.1 [d, 1J(C,P) = 136.4 Hz], 115.5 [d, 3J(C,P) =
Methyl 2-(4-Cyanophenyl)-5-oxo-4-(tri-p-tolyl-λ5-phosphanylidene)-
4,5-dihydrofuran-3-carboxylate (3n): Yellow solid. M.p. 182–184 °C.
Rf = 0.19 (EA/hexanes, 1:1). Isolated yield 49% (0.0454 g). 1H
NMR (300 MHz, CDCl3, 25 °C): δ = 2.44 (s, 3 CH3), 2.91 (s,
OCH3), 7.32–7.35 (m, 6 H, Ar-H), 7.55–7.62 (m, 8 H, Ar-H), 7.90
(d, J = 6.0 Hz, 2 H, Ar-H) ppm. 13C NMR (75.5 MHz, CDCl3,
1
11.4 Hz], 120.9 [d, J(C,P) = 102.6 Hz], 121.5, 122.1, 128.7, 129.5
3
2
1
[d, J(C,P) = 13.3 Hz], 131.9, 132.8, 133.7 [d, J(C,P) = 10.8 Hz],
141.6 [d, 3J(C,P) = 12.2 Hz], 143.5 [d, 4J(C,P) = 3.1 Hz], 147.9,
164.0 (C=O), 169.1 [d, 2J(C,P) = 18.1 Hz, C=] ppm. 31P NMR
25 °C): δ = 21.5 (CH3), 50.5 (OCH3), 54.2 [d, J(C,P) = 136.0 Hz],
109.6, 116.6 [d, 2J(C,P) = 11.4 Hz], 119.3, 120.6 [d, 1J(C,P) =
97.5 Hz], 126.9, 129.6 [d, 3J(C,P) = 13.3 Hz], 131.6, 133.7 [d,
2J(C,P) = 10.9 Hz], 136.1, 141.4 [d, 3J(C,P) = 12.4 Hz], 143.6 [d,
4J(C,P) = 2.9 Hz], 164.2 (C=O), 169.1 [d, 2J(C,P) = 18.1 Hz,
C=O] ppm. 31P NMR (242.5 Hz, CDCl3, 25 °C): δ = 13.4 ppm.
(242.5 Hz, CDCl , 25 °C): δ = 13.5 ppm. FTIR (KBr): ν = 1688
˜
3
(br) cm–1. HRMS (ESI+): calcd. for C33H28NO6P [M]+ 565.1654;
found 565.1660.
FTIR (KBr): ν = 1702, 1719 cm–1. HRMS (ESI+): calcd. for
Methyl 2-(2-Nitrophenyl)-5-oxo-4-(tri-p-tolyl-λ5-phosphanylidene)-
4,5-dihydrofuran-3-carboxylate (3k): Red solid. M.p. 96–98 °C. Rf
= 0.28 (EA/hexanes, 1.5:1). Isolated yield 43% (0.0413 g). 1H NMR
(300 MHz, CDCl3, 25 °C): δ = 2.42 (s, 3 CH3), 2.94 (s, OCH3), 7.31
(dd, J = 2.8, J = 8.2 Hz, 6 H, Ar-H), 7.44 (dt, J = 1.5, J = 8.2 Hz,
1 H, Ar-H), 7.53–7.60 (m, 7 H, Ar-H), 7.69 (dd, J = 1.4, J = 7.8 Hz,
1 H, Ar-H), 7.97 (dd, J = 1.2, J = 8.1 Hz, 1 H, Ar-H) ppm. 13C
˜
C34H28NO4P [M]+ 545.1756; found 545.1779.
Methyl 5-Oxo-2-pyridin-4-yl-4-(tri-p-tolyl-λ5-phosphanylidene)-4,5-
dihydrofuran-3-carboxylate (3o): Orange solid. M.p. 216–218 °C. Rf
1
= 0.28 (EA/hexanes, 3:1). Isolated yield 37% (0.0328 g). H NMR
(300 MHz, CDCl3, 25 °C): δ = 2.44 (s, 3 CH3), 2.94 (s, OCH3), 7.33
(dd, J = 2.9, J = 8.2 Hz, 6 H, Ar-H), 7.58 (dd, J = 8.2, J = 12.9 Hz,
6 H, Ar-H), 7.65 (dd, J = 1.5, J = 4.8 Hz, 2 H, Ar-H), 8.51 (dd, J
= 1.5, J = 4.8 Hz, 2 H, Ar-H) ppm. 13C NMR (75.5 MHz, CDCl3,
5
NMR (75.48 MHz, CDCl3, 25 °C): δ = 21.6 [d, J(C,P) = 1.3 Hz,
1
2
CH3], 50.0 [d, J(C,P) = 137.1 Hz], 50.3 (OCH3), 114.2 [d, J(C,P)
1
= 10.5 Hz], 121.6 [d, J(C,P) = 98.1 Hz], 124.2, 126.5, 128.8, 129.4
5
25 °C): δ = 21.6 [d, J(C,P) = 1.1 Hz, CH3], 50.6 (OCH3), 54.7 [d,
3
2
[d, J(C,P) = 13.3 Hz], 132.1, 132.3, 133.7 [d, J(C,P) = 10.8 Hz],
141.6 [d, 3J(C,P) = 12.6 Hz], 143.2 [d, 4J(C,P) = 3.0 Hz], 148.7,
163.1 (C=O), 169.6 [d, 2J(C,P) = 18.8 Hz, C=O] ppm. 31P NMR
2
1J(C,P) = 135.6 Hz], 117.7 [d, J(C,P) = 11.7 Hz], 120.0, 120.4 [d,
3
2
1J(C,P) = 97.4 Hz], 129.5 [d, J(C,P) = 13.3 Hz], 133.7 [d, J(C,P)
3
4
= 10.9 Hz], 137.0, 139.8 [d, J(C,P) = 12.3 Hz], 143.6 [d, J(C,P) =
(242.5 Hz, CDCl , 25 °C): δ = 13.8 ppm. FTIR (KBr): ν = 1699
˜
3
2.9 Hz], 149.3, 164.2 (C=O), 169.0 [d, 2J(C,P)
= 18.0 Hz,
(br) cm–1. HRMS (ESI+): calcd. for C33H28NO6P [M]+ 565.1654;
C=O] ppm. 31P NMR (242.5 Hz, CDCl3, 25 °C): δ = 13.9 ppm.
found 565.1636.
FTIR (KBr): ν = 1684, 1717 cm–1. HRMS (ESI+): calcd. for
˜
Methyl 2-(4-Chloro-3-nitrophenyl)-5-oxo-4-(tri-p-tolyl-λ5-phosphan-
ylidene)-4,5-dihydrofuran-3-carboxylate (3l): Orange solid. M.p.
188 °C. Rf = 0.18 (EA/hexanes, 1:1). Isolated yield 78% (0.0794 g).
1H NMR (300 MHz, CDCl3, 25 °C): δ = 2.42 (s, 3 CH3), 2.92 (s,
OCH3), 7.32 (dd, J = 2.7, J = 8.1 Hz, 6 H, Ar-H), 7.42 (d, J =
6.0 Hz, 1 H, Ar-H), 7.53–7.60 (m, 6 H, Ar-H), 7.97 (dd, J = 2.1, J
= 8.7 Hz, 1 H, Ar-H), 8.47 (d, J = 2.1 Hz, 1 H, Ar-H) ppm. 13C
NMR (75.5 MHz, CDCl3, 25 °C): δ = 21.5 [d, 5J(C,P) = 1.1 Hz,
C32H28NO4P [M]+ 521.1756; found 521.1753.
Methyl 2-(4-Nitrophenyl)-5-oxo-4-(tri-n-butyl-λ5-phosphanylidene)-
4,5-dihydrofuran-3-carboxylate (3p): Orange oil. Rf = 0.48 (EA/hex-
anes, 2:1). Isolated yield (from two steps) 60% (0.1390 g). 1H NMR
(300 MHz, CDCl3, 25 °C): δ = 0.95 (t, J = 6.9 Hz, 3 CH3), 2.28
(m, 9 CH2), 3.77 (s, OCH3), 7.79 (d, J = 9.0 Hz, 2 H, Ar-H), 8.18
(d, J = 9.0 Hz, 2 H, Ar-H) ppm. 13C NMR (75.5 MHz, CDCl3,
1
1
2
25 °C): δ = 13.4 (CH3), 21.2 [d, J(C,P) = 55.3 Hz, CH2], 23.8 [d,
CH3], 50.4 (OCH3), 53.5 [d, J(C,P) = 136.0 Hz], 116.1 [d, J(C,P)
= 11.4 Hz], 120.6 [d, 1J(C,P) = 97.7 Hz], 123.7, 124.2, 129.5 [d,
3J(C,P) = 13.4 Hz], 130.1, 130.9, 131.0, 133.5 [d, 2J(C,P) =
3J(C,P) = 15.8 Hz, CH2], 23.9 [d, 2J(C,P) = 3.9 Hz, CH2], 51.6
1
2
(OCH3), 54.1 [d, J(C,P) = 119.4 Hz], 115.8 [d, J(C,P) = 9.6 Hz],
123.0, 128.2, 136.6, 141.9 [d, 3J(C,P) = 10.7 Hz], 146.0, 165.1
(C=O), 169.5 [d, 2J(C,P) = 16.7 Hz] ppm. 31P NMR (242.5 Hz,
3
4
10.8 Hz], 140.3 [d, J(C,P) = 12.2 Hz], 143.5 [d, J(C,P) = 2.9 Hz],
147.4, 163.7 (C=O), 168.7 [d, 2J(C,P) = 18.4 Hz, C=O] ppm. 31P
CDCl , 25 °C): δ = 20.9 ppm. FTIR (KBr): ν = 1683 (br) cm–1.
˜
3
NMR (242.5 Hz, CDCl , 25 °C): δ = 14.2 ppm. FTIR (KBr): ν
˜
3
HRMS (ESI+): calcd. for C24H34NO6P [M]+ 463.2124; found
= 1695 (br) cm–1. HRMS (ESI+): calcd. for C33H27ClNO6P [M]+
463.2128.
599.1265; found 599.1257.
Methyl 2-(4-Fluoro-3-nitrophenyl)-5-oxo-4-(tri-p-tolyl-λ5-phosphan- (Z)-4-Methoxy-2-(methoxycarbonyl)-1-(4-nitrophenyl)-4-oxo-3-(tri-
ylidene)-4,5-dihydrofuran-3-carboxylate (3m): Yellow solid. M.p.
208–210 °C. Rf = 0.19 (EA/hexanes, 1:1). Isolated yield 52%
(0.0516 g). 1H NMR (300 MHz, CDCl3, 25 °C): δ = 2.44 (s, 3 CH3),
2.94 (s, OCH3), 7.21 (t, J = 9.4 Hz, 1 H, Ar-H), 7.34 (dd, J = 2.6,
J = 8.0 Hz, 6 H, Ar-H), 7.55–7.62 (m, 6 H, Ar-H), 8.09–8.14 (m,
1 H, Ar-H), 8.68 (dd, J = 2.2, J = 7.3 Hz, 1 H, Ar-H) ppm. 13C
butylphosphonio)but-1-en-1-olate (3pЈ): Orange oil. Rf = 0.35 (EA).
Isolated yield 62% (0.1535 g). 1H NMR (300 MHz, CDCl3, 25 °C):
δ = 0.97 (t, J = 6.5 Hz, 3 CH3), 1.45–1.63 (m, 6 CH2), 2.18–2.39
(m, 3 CH2), 3.37 (s, OCH3), 3.75 (s, OCH3), 5.48 (d, J = 16.0 Hz,
1 H, CH), 7.48 (d, J = 8.5 Hz, 2 H, Ar-H), 8.17 (d, J = 7.9 Hz, 2
H, Ar-H) ppm. 13C NMR (75.5 MHz, CDCl3, 25 °C): δ = 13.3
NMR (75.5 MHz, CDCl3, 25 °C): δ = 21.5 [d, 5J(C,P) = 1.1 Hz, (CH3), 19.5 [d, 1J(C,P) = 45.9 Hz, CH2], 23.8 [d, 3J(C,P) = 10.9 Hz,
1
2
1
CH3], 50.3 (OCH3), 52.7 [d, J(C,P) = 136.6 Hz], 115.2 [d, J(C,P)
= 11.1 Hz], 117.6 [d, J(C,F) = 21.1 Hz], 120.7 [d, 1J(C,P) =
97.7 Hz], 124.6 [d, J(C,F) = 2.8 Hz], 127.5 [d, J(C,F) = 4.2 Hz],
CH2], 24.0 (CH2), 40.2 [d, J(C,P) = 60.6 Hz], 49.4 (OCH3), 52.5
(OCH3), 84.8, 122.3, 127.3, 146.3, 152.0, 168.6 (C=O), 170.9 [d,
2J(C,P) = 6.3 Hz, C=O], 184.0 (C=O) ppm. 31P NMR (242.5 Hz,
3
4
129.4 [d, J(C,P) = 13.3 Hz], 133.5 [d, J(C,P) = 10.7 Hz], 133.9 [d,
CDCl , 25 °C): δ = 35.2 ppm. FTIR (KBr): ν = 1674, 1720 cm–1.
˜
3
8
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Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O20400
/KAP1
Date: 27-08-12 18:50:58
Pages: 11
Synthesis of Lactones Bearing Phosphorus Ylides
HRMS (ESI+): calcd. for C25H38NO7P [M]+ 495.2386; found
495.2385.
1J(C,P) = 62.6 Hz, CH3], 51.7 (OCH3), 57.9 [d, 1J(C,P) = 129.4 Hz],
2
3
115.2 [d, J(C,P) = 10.1 Hz], 123.0, 128.8, 136.6, 142.6 [d, J(C,P)
= 11.3 Hz], 146.4, 164.9 (C=O), 168.5 [d, 2J(C,P) = 18.7 Hz,
C=O] ppm. 31P NMR (242.5 Hz, CDCl3, 25 °C): δ = 6.3 ppm.
Methyl 2-(4-Nitrophenyl)-5-oxo-4-(tri-n-propyl-λ5-phosphanylidene)-
4,5-dihydrofuran-3-carboxylate (3q): Orange solid. M.p. 129–
131 °C. Rf = 0.25 (EA/hexanes, 2:1). Isolated yield (from two steps)
56% (0.1179 g). 1H NMR (300 MHz, CDCl3, 25 °C): δ = 1.09 (t, J
= 6.8 Hz, 3 CH3), 1.53–1.64 (m, 3 CH2), 2.24–2.34 (m, 3 CH2),
3.80 (s, OCH3), 7.81 (d, J = 9.0 Hz, 2 H, Ar-H), 8.18 (d, J = 9.0 Hz,
2 H, Ar-H) ppm. 13C NMR (75.5 MHz, CDCl3, 25 °C): δ = 15.87
FTIR (KBr): ν = 1591, 1684 cm–1. HRMS (ESI+): calcd. for
˜
C15H16NO6P [M]+ 337.0715; found 337.0717.
(Z)-4-Methoxy-2-(methoxycarbonyl)-1-(4-nitrophenyl)-4-oxo-3-(tri-
methylphosphonio)but-1-en-1-olate (3sЈ): Yellow oil. Rf = 0.14 (EA/
MeOH, 5:1). Isolated yield 64% (0.1181 g). 1H NMR (300 MHz,
CDCl3, 25 °C): δ = 1.95 (d, J = 13.8 Hz, 3 CH3), 3.35 (OCH3), 3.76
(OCH3), 5.30 (d, J = 16.1 Hz, 1 H, CH), 7.49 (d, J = 8.4 Hz, 2 H,
Ar-H), 8.15 (d, J = 8.5 Hz, 2 H, Ar-H) ppm. 13C NMR (75 MHz,
CDCl3, 25 °C): δ = 8.8 [d, 1J(C,P) = 54.3 Hz, CH3], 42.2 [d, 1J(C,P)
= 65.2 Hz], 48.9 (OCH3), 52.0 (OCH3), 84.2, 121.8, 127.0, 145.7,
151.6, 167.8 (C=O), 170.0 [d, 2J(C,P) = 4.8 Hz, C=O], 183.3 [d,
2J(C,P) = 2.3 Hz, C=O] ppm. 31P NMR (242.5 MHz, CDCl3,
3
2
[d, J(C,P) = 16.6 Hz, CH3], 16.3 [d, J(C,P) = 3.8 Hz, CH2], 24.2
[d, 1J(C,P) = 54.9 Hz, CH2], 52.1 (OCH3), 54.6 [1J(C,P) =
118.9 Hz], 116.4 [d, 2J(C,P) = 9.7 Hz], 123.4, 128.6, 137.1, 142.2 [d,
3J(C,P) = 10.6 Hz], 146.4, 165.5 (C=O), 169.8 [d, 2J(C,P) =
16.5 Hz] ppm. 31P NMR (242.5 Hz, CDCl3, 25 °C): δ = 19.9 ppm.
FTIR (KBr): ν = 1590, 1678 cm–1. HRMS (ESI+): calcd. for
˜
C21H38NO6P [M]+ 421.1654; found 421.1655.
25 °C): δ = 27.4 ppm. FTIR (KBr): ν = 1635, 1718 cm–1. HRMS
˜
(Z)-4-Methoxy-2-(methoxycarbonyl)-1-(4-nitrophenyl)-4-oxo-3-(tri-
propylphosphonio)but-1-en-1-olate (3qЈ): Orange oil. Rf = 0.10 (EA).
Isolated yield 60% (0.1360 g). 1H NMR (300 MHz, CDCl3, 25 °C):
δ = 1.08–1.13 (m, 3 CH3), 1.64–1.75 (m, 3 CH2), 2.16–2.37 (m, 3
CH2), 3.37 (s, OCH3), 3.74 (s, OCH3), 5.48 (d, J = 16.0 Hz, 1 H,
CH), 7.46 (t, J = 8.6 Hz, 2 H, Ar-H), 8.17 (d, J = 8.7 Hz, 2 H, Ar-
(ESI+): calcd. for C16H20NO7P [M]+ 369.0977; found 369.0978.
Methyl 4-(4-Nitrobenzylidene)-2-(4-nitrophenyl)-5-oxo-4,5-dihydro-
furan-3-carboxylate (6a): Isolated yield 30% (0.0314 g).
Spectral Data of Compound (Z)-6a: Yellow solid. M.p. 230–232 °C.
Rf = 0.31 (DCM/hexanes, 3:1). 1H NMR (300 MHz, CDCl3,
25 °C): δ = 3.88 (s, OCH3), 7.98 (d, J = 9.0 Hz, 2 H, Ar-H), 8.15
(d, J = 7.6 Hz, 2 H, Ar-H), 8.22 (s, CH), 8.35–8.29 (m, 4 H, Ar-
3
H) ppm. 13C NMR (75 MHz, CDCl3, 25 °C): δ = 15.2 [d, J(C,P)
2
1
= 16.1 Hz, CH3], 15.7 [d, J(C,P) = 4.5 Hz, CH2], 21.5 [d, J(C,P)
= 45.5 Hz, CH2], 39.9 [d, 1J(C,P) = 60 Hz], 49.2 (OCH3), 52.3
(OCH3), 84.6, 122.1, 127.1, 146.1, 151.9, 168.4 (C=O), 170.6 [d,
1J(C,P) = 6.2 Hz, C=O], 183.7 (C=O) ppm. 31P NMR (242 MHz,
H) ppm. FTIR (KBr): ν = 1718, 1733 cm–1. HRMS (EI): calcd.
˜
for C19H22N2O8 [M]+ 396.0594; found 396.0589. Owing to poor
solubility, 13C NMR spectroscopic data were not obtained.
CDCl , 25 °C): δ = 34.1 ppm. FTIR (KBr): ν = 1633, 1722 cm–1.
˜
3
HRMS (ESI+): calcd. for C22H32NO7P [M]+ 453.1916; found
Spectral Data of Compound (E)-6a: Yellow solid. M.p. 209–210 °C.
Rf = 0.31 (DCM/hexanes, 3:1). 1H NMR (300 MHz, CDCl3,
25 °C): δ = 3.34 (s, OCH3), 7.53 (d, J = 8.9 Hz, 2 H, Ar-H), 7.61
(s, CH), 8.16–8.10 (d, J = 9.0 Hz, 2 H, Ar-H), 8.35–8.29 (m, 4 H,
453.1916.
Methyl 2-(4-Nitrophenyl)-5-oxo-4-(triethyl-λ5-phosphanylidene)-4,5-
dihydrofuran-3-carboxylate (3r): Orange oil. Rf = 0.28 (EA/MeOH,
15:1). Isolated yield 81% (0.0921 g). H NMR (300 MHz, CDCl3,
25 °C): δ = 1.14–1.28 (m, 3 CH3), 2.29–2.41 (m, 3 CH2), 3.78 (s,
OCH3), 7.80 (d, J = 9.0 Hz, 2 H, Ar-H), 8.18 (d, J = 9.0 Hz, 2 H,
Ar-H) ppm. 13C NMR (75.5 MHz, CDCl3, 25 °C): δ = 6.0 [d,
2J(C,P) = 4.8 Hz, CH3], 14.16 [d, 1J(C,P) = 56.5 Hz, CH2], 51.6
(OCH3), 52.7 [d, J(C,P) = 120.0 Hz], 115.6 [d, J(C,P) = 9.5 Hz],
122.9, 128.4, 136.6, 142.3 [d, 3J(C,P) = 10.7 Hz], 146.1, 165.0
(C=O), 169.8 [d, 2J(C,P) = 16.4 Hz, C=O] ppm. 31P NMR
1
Ar-H) ppm. FTIR (KBr): ν = 1718, 1733 cm–1. HRMS (EI): calcd.
˜
for C19H22N2O8 [M]+ 396.0594; found 396.0589. Owing to poor
solubility, 13C NMR spectroscopic data were not obtained.
Methyl 4-(4-Chloro-3-nitrobenzylidene)-2-(4-nitrophenyl)-5-oxo-4,5-
dihydrofuran-3-carboxylate (6b): Isolated yield 18% (0.0204 g).
1
2
Spectral Data of Compound (Z)-6b: Yellow solid mixture. Rf = 0.32
(DCM/hexanes, 3:1). 1H NMR (300 MHz, CDCl3, 25 °C): δ = 3.88
(s, OCH3), 7.97 (d, J = 9.0 Hz, 2 H, Ar-H), 8.13 (s, CH), 8.24 (dd,
J = 1.8, J = 9.0 Hz, 1 H, Ar-H), 8.32–8.35 (m, 2 H, Ar-H), 8.32–
8.35 (m, 1 H, Ar-H), 8.59 (d, J = 2.1 Hz, 1 H, Ar-H) ppm. FTIR
(242.5 Hz, CDCl , 25 °C): δ = 26.9 ppm. FTIR (KBr): ν = 1590,
˜
3
1678 cm–1. HRMS (ESI+): calcd. for C18H22NO6P [M]+ 379.1185;
found 379.1183.
(Z)-4-Methoxy-2-(methoxycarbonyl)-1-(4-nitrophenyl)-4-oxo-3-(tri-
ethylphosphonio)but-1-en-1-olate (3rЈ): Orange oil. Rf = 0.15 (EA/
MeOH, 15:1). Isolated yield 61% (0.1254 g). H NMR (300 MHz,
(KBr):
ν
=
1718, 1792 cm–1. HRMS (EI+): calcd. for
˜
C19H11ClN2O8 [M]+ 430.0204; found 430.0200. Only data for (Z)-
6b is given as the trace of (E)-6b is uncharacterizable. Owing to
poor solubility, 13C NMR spectroscopic data were not obtained.
1
CDCl3, 25 °C): δ = 1.27–1.38 (m, 3 CH3), 2.23–2.49 (m, 3 CH2),
3.36 (s, OCH3), 3.75 (s, OCH3), 5.48 (d, J = 16.0 Hz, 1 H, CH),
7.49 (d, J = 8.3 Hz, 2 H, Ar-H), 8.16 (d, J = 8.3 Hz, 2 H, Ar-
Methyl 4-(3-Nitrobenzylidene)-2-(4-nitrophenyl)-5-oxo-4,5-dihydro-
furan-3-carboxylate (6c): Isolated yield 48% (0.0160 g).
H) ppm. 13C NMR (75 MHz, CDCl3, 25 °C): δ = 5.9 [d, J(C,P) =
2
1
1
5.4 Hz, CH3], 12.5 [d, J(C,P) = 47.5 Hz, CH2], 39.3 [d, J(C,P) =
60.0 Hz], 49.3 (OCH3), 52.4 (OCH3), 84.4, 122.2, 127.2, 146.1,
151.9, 168.4 (C=O), 170.5 [d, 2J(C,P) = 6.2 Hz, C=O], 183.8
(C=O) ppm. 31P NMR (242 MHz, CDCl3, 25 °C): δ = 40.1 ppm.
Spectral Data of Compound (Z)-6c: Yellow solid mixture. Rf = 0.20
(DCM/hexanes, 3:1). 1H NMR (300 MHz, CDCl3, 25 °C): δ = 3.89
(s, OCH3), 7.67 (t, J = 8.0 Hz, 1 H, Ar-H), 7.98 (d, J = 8.9 Hz, 2
H, Ar-H), 8.22 (s, CH), 8.31–8.40 (m, 4 H, Ar-H), 8.84 (s, 1 H, Ar-
FTIR (KBr): ν = 1627, 1721 cm–1. HRMS (ESI+): calcd. for
˜
H) ppm. FTIR (KBr): ν = 1722, 1780 cm–1. HRMS (ESI+): calcd.
C19H26NO7P [M]+ 411.1447; found 411.1448.
˜
for C19H12N2O8 [M]+ 396.0594; found 396.0596. Only data for (Z)-
6c is given as the trace of (E)-6c is uncharacterizable. Owing to
poor solubility, 13C NMR spectroscopic data were not obtained.
Methyl 2-(4-Nitrophenyl)-5-oxo-4-(trimethyl-λ5-phosphanylidene)-
4,5-dihydrofuran-3-carboxylate (3s): Red solid. M.p. 105–108 °C. Rf
= 0.43 (EA/MeOH, 5:1). Isolated yield 53% (0.0536 g). H NMR
1
(300 MHz, CDCl3, 25 °C): δ = 2.00 (d, J = 13.8 Hz, 3 CH3), 3.79
Supporting Information (see footnote on the first page of this arti-
(s, OCH3), 7.82 (d, J = 9.1 Hz, 2 H, Ar-H), 8.19 (d, J = 9.1 Hz, 2 cle): 1H and 13C NMR data for all new compounds, X-ray crystal-
H, Ar-H) ppm. 13C NMR (75.5 MHz, CDCl3, 25 °C): δ = 13.8 [d,
lographic data for compound 3o.
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
9

Job/Unit: O20400
/KAP1
Date: 27-08-12 18:50:58
Pages: 11
S.-C. Chuang et al.
FULL PAPER
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Received: March 29, 2012
Published Online: ᭿
10
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© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O20400
/KAP1
Date: 27-08-12 18:50:58
Pages: 11
Synthesis of Lactones Bearing Phosphorus Ylides
Multicomponent Reactions
J.-C. Deng, F.-W. Chan, C.-W. Kuo,
C.-A. Cheng, C.-Y. Huang,
S.-C. Chuang* ................................. 1–11
Assembly of Dimethyl Acetylenedicarbox-
ylate and Phosphanes with Aldehydes
Leading to γ-Lactones Bearing α-Phos-
phorus Ylides as Wittig Reagents
The multicomponent assembly of dimethyl
acetylenedicarboxylate, electron-deficient
aldehydes, and triaryl- or trialkylphos-
phanes, in a DMAD/aldehyde/phosphane
molar ratio of 3:1:6, gave γ-lactones bear-
ing an α-phosphorus ylide moiety in mod-
erate to good yields. These isolated lactone
ylides, which behave as Wittig reagents, re-
act with aldehydes to give olefins in moder-
ate yields.
Keywords: Lactones / Phosphanes / Ylides /
Wittig reactions / Multicomponent reac-
tions
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
11