Catalyst-free synthesis of skipped dienes from phosphorus ylides, allylic carbonates, and aldehydes via a one-pot SN2′ allylation-wittig strategy

Article abstract of DOI:10.1021/jo500375q

A catalyst-free allylic alkylation of stabilized phosphorus ylides with allylic carbonates via a regioselective S_N2′ process is presented. Subsequent one-pot Wittig reaction with both aliphatic and aromatic aldehydes as well as ketenes provides structurally diverse skipped dienes (1,4-dienes) in generally high yields and moderate to excellent stereoselectivity with flexible substituent patterns. This one-pot S _N2′ allylation-Wittig strategy constitutes a convenient and efficient synthetic method for highly functionalized skipped dienes from readily available starting materials.

Full text of DOI:10.1021/jo500375q

Note
pubs.acs.org/joc
Catalyst-Free Synthesis of Skipped Dienes from Phosphorus Ylides,
Allylic Carbonates, and Aldehydes via a One-Pot SN2′ Allylation−
Wittig Strategy
Silong Xu,*,† Shaoying Zhu,‡ Jian Shang,† Junjie Zhang,† Yuhai Tang,† and Jianwei Dou*,‡
‡
†Department of Chemistry, School of Science, and College of Pharmacy, Xi’an Jiaotong University, Xi’an 710049, P. R. China
S
* Supporting Information
ABSTRACT: A catalyst-free allylic alkylation of stabilized
phosphorus ylides with allylic carbonates via a regioselective
SN2′ process is presented. Subsequent one-pot Wittig reaction
with both aliphatic and aromatic aldehydes as well as ketenes
provides structurally diverse skipped dienes (1,4-dienes) in
generally high yields and moderate to excellent stereoselectivity
with flexible substituent patterns. This one-pot SN2′ allylation−
Wittig strategy constitutes a convenient and efficient synthetic method for highly functionalized skipped dienes from readily
available starting materials.
kipped dienes (1,4-dienes) are embedded as ubiquitous
components in a vast array of biologically important natural
of stabilized phosphorus ylides with allylic carbonates via a
distinct SN2′ approach could be realized, and subsequent one-
pot Wittig reaction would give easy access to 1,4-dienes
(Scheme 1, eq c). In contrast to the well-established Michael
and alkylation reactions of P-ylides, to our knowledge, the SN2′
reaction of P-ylides with allylic compounds has been scarcely
explored.39,40 Herein, we report the results from such an
investigation.
S
products1−4 like polyunsaturated fatty acids.1 They are also
versatile synthetic building blocks in organic syntheses of many
important molecules.5−7 Because of their great utility, many
powerful synthetic methods for the construction of 1,4-dienes
have been developed,8 including various transition-metal-
catalyzed cross-couplings,9−12 ene reactions,13,14 olefina-
tions,15−20 Morita−Baylis−Hillman transformations,21,22 and
so on. Despite the effectiveness of the existing processes,
developing stereoselective and practical assembly of structurally
diverse 1,4-dienes from readily available starting materials
remains an important objective.
The Morita−Baylis−Hillman (MBH) carbonates 141,42 were
selected as the allylation agents in our investigations. We
expected that the electrophilic CC bond and the good
leaving group tert-butoxycarbonyloxy of MBH carbonates 1
should favor a SN2′ reaction of P-ylides. In addition, tert-butyl
oxide anion generated in situ by the SN2′ reaction may act as a
strong base to promote subsequent Wittig reaction under salt-
free conditions (see discussion on mechanism below). In the
initial investigation, the reaction of MBH carbonate 1a with P-
ylide 2a was performed in chloroform at 60 °C for 20 h, which
was followed by the Wittig reaction with paraformaldehyde (2.0
equiv) at room temperature for 2 h. To our delight, the
anticipated SN2′ allylation−Wittig product, diethyl 2-benzyli-
dene-4-methylenepentanedioate (3a), was obtained in 99%
yield with excellent E/Z selectivity (E/Z = 20:1) (eq 1, and
Stabilized phosphorus ylides (P-ylides) represent an
important class of intermediates in synthetic organic chemistry.
In addition to their vital role in the Wittig reaction for building
alkenes, P-ylides have been widely utilized as nucleophiles in
Michael type and alkylation reactions.23−28 An elegant work by
Chen and co-workers29 has unveiled that P-ylides can be used
as nucleophiles in an organocatalytic Mannich reaction, which,
followed by a Wittig reaction with formaldehyde, affords β-
amino-α-methylene carbonyl compounds (Scheme 1, eq a). By
employing activated alkenes such as nitroolefins and vinyl
ketones as the Michael acceptors, the corresponding tandem
Michael−Wittig reactions including intramolecular variants
have been established.30−37 Recently, You17 and Tian20 have
developed novel Pd-catalyzed allylation reactions of P-ylides
with allylic carbonates or amines, which afforded functionalized
1,4-dienes by a follow-up Wittig reaction (Scheme 1, eq b).
More recently, Zhu and co-workers19 have demonstrated
similar organocatalytic allylation-Wittig reaction in the presence
of chiral amine catalyst. Intrigued by these elegant studies, and
a pioneering Wittig olefination between phosphines, allylic
carbonates, and aldehydes for the construction of conjugated
1,3-dienes,38 we envisaged that a catalyst-free allylation reaction
Table 1, entry 1). Notably, the regiodifferentiated diene
product, diethyl 2,4-dimethylene-3-phenylpentanedioate
Received: February 16, 2014
Published: March 25, 2014
© 2014 American Chemical Society
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The Journal of Organic Chemistry
Note
Scheme 1. Tandem Reaction Patterns of Phosphorus Ylides as Nucleophiles
a
Table 1. Investigations on Reaction Conditions
chloroform still served as the best solvent in terms of the yield,
stereoselectivity, and time. It was found that temperature had
significant impact on the SN2′-allylation reaction, as the
reaction at room temperature required much longer time for
a complete transformation (entry 11). In addition, the reaction
was found to be hardly affected by the changes in concentration
of the reactants (entries 12 and 13). Finally, it was verified that
MBH acetate, ethyl 2-(acetoxy(phenyl)methyl)acrylate 1a′, was
also effective for the SN2′ allylation reaction but additional base
should be employed to promote subsequent Wittig reaction
(entry 14).
b
c
entry
solvent
CHCl3
time (h)
3a, yield (%)
E/Z
1
2
3
4
5
6
7
8
9
10
20
6
99
97
20:1
12:1
20:1
17:1
20:1
20:1
12:1
10:1
15:1
CH2Cl2
EtOAc
CH3CN
toluene
1,4-dioxane
DMSO
DMF
34
18
30
23
25
27
24
48
72
20
20
48
96
95
Under the optimized conditions, the substrate scope of the
SN2′ allylation−Wittig reaction was studied (Table 2). First,
with P-ylide 2a as a reactant, a range of structurally different
MBH carbonates 1 were studied. Aromatic MBH carbonates
featuring either an electron-donating or an electron-with-
drawing group on the ortho-, meta-, or para-position of the
benzene ring all worked well under the standard conditions,
delivering the 1,4-dienes 3a−e in excellent yields (91−99%)
and good selectivity (E/Z 5:1 to 20:1) (entries 1−5).
Heteroaromatic MBH carbonate 1f was also effective to
produce the 1,4-diene 3f in 80% yield and 12:1 E/Z ratio
(entry 6). Notably, aliphatic MBH carbonates are also feasible
in the SN2′ allylation−Wittig reaction giving the corresponding
1,4-dienes in good yields and moderate E/Z selectivity (entries
7−10). For a nonsubstituted MBH carbonate 1i (R1 = H, entry
9), a symmetrical skipped diene 3i was generated in 71% yield,
which is an important precursor for bioactive compounds.43 E-
Styryl MBH carbonate 1j could also participate in the reaction
giving triene 3j in 92% yield and good stereoselectivity (entry
10). In addition, MBH carbonates 1 bearing different electron-
withdrawing groups (EWG), e.g., methoxycarbonyl (1k), cyano
(1l), and acetyl (1m), were compatible with the SN2′
allylation−Wittig reaction (entries 11−13). In these cases,
however, the cyano MBH carbonate 1l afforded a low E/Z ratio
(2:1), while the acetyl counterpart 1m provided a modest yield
(43%). Subsequently, variation of the electron-withdrawing
groups (EWG′) of P-ylides 2 was investigated. It was found that
both benzoxycarbonyl P-ylide (2b) and benzoyl P-ylide (2c)
worked well with all selected MBH carbonates 1 (R = aryl,
alkyl, or H), producing the corresponding 1,4-dienes 3n−s in
good yields and high stereoselectivity (entries 14−19).
However, under the standard conditions, cyano P-ylide 2d
97
96
92
71
THF
35
EtOH
trace
91
d
11
CHCl3
CHCl3
CHCl3
CHCl3
20:1
20:1
20:1
15:1
e
12
f
96
13
98
g
14
81
a
MBH carbonate 1a (0.5 mmol) and phosphorus ylide 2a (0.6 mmol)
were stirred in the specified solvent (2.0 mL) at 60 °C (40 °C for
entry 2) under N2 atmosphere. After the consumption of 1a,
paraformaldehyde (1.0 mmol) was added and stirred for another 2 h
b
c
at room temperature. Overall yields based on 1a. Determined by 1H
d
e
NMR assay. The reaction was conducted at room temperature. 5.0
f
g
mL of solvent was used. 1.0 mL of solvent was adopted. Ethyl 2-
(acetoxy(phenyl)methyl)acrylate 1a′ was used instead of 1a, and
K2CO3 (0.6 mmol) was added.
3a′,19,21,22 could not be detected in the reaction mixture, which
suggested a highly regioselective SN2′ allylation process
occurred in the reaction.
The reaction parameters were further investigated using the
above reaction as a probe (Table 1). The reaction was
compatible with a variety of solvents such as dichloromethane,
ethyl acetate, acetonitrile, toluene, 1,4-dioxane, and DMSO,
which all furnished excellent yields (92−99%), albeit with
somewhat decreased E/Z ratios observed in dichloromethane,
acetonitrile, and DMSO (entries 2−7). However, THF and
DMF as the solvents afforded poor results, and ethanol
completely shut down the reaction (entries 8−10). Therefore,
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Note
a
Table 2. Substrate Scope of MBH Carbonates 1 and P-Ylides
2
Table 3. Substrate Scope of Aldehydes
a
c
3, yield
(%)
b
b
d
entry
R1
R2
time (h)
dr
time
(h)
3, yield
c
entry
1
R1, EWG in 1
EWG′ in 2
(%)
E/Z
1
2
3
4
5
6
7
8
C6H5 (1a) C6H5
31 (11)
30 (9)
3t, 55
3u, 58
3v, 61
6:1
10:1
>20:1
20:1
11:1
1.3:1
4:1
C6H5, CO2Et (1a)
CO2Et
(2a)
20
23
19
25
24
30
14
36
7
3a, 99
3b, 91
3c, 92
3d, 98
3e, 96
3f, 80
3g, 51
3h, 84
20:1
20:1
5:1
C6H5 (1a) 3-NO2C6H4
C6H5 (1a) 4-CH3C6H4
C6H5 (1a) 4-ClC6H4
C6H5 (1a) C2H5
28 (10)
30 (10)
27 (9)
2
4-CH3C6H4, CO2Et
(1b)
CO2Et
(2a)
3w, 49
3x, 50
3y, 48
3a, 49
3j, 71
3
3-NO2C6H4, CO2Et
(1c)
CO2Et
(2a)
C2H5 (1h) C2H5
26 (10)
21 (9)
e
4
4-ClC6H4, CO2Et (1d) CO2Et
(2a)
12:1
9:1
H (1i)
H (1i)
C6H5
(E)-PhCHCH
22 (11)
1.4:1
5
2-ClC6H4, CO2Et (1e) CO2Et
(2a)
a
b
For details, see the Experimental Section. Total time for two steps;
the value in parentheses corresponds to the time for the second step.
Overall yields based on 1. Refers to the major (E,E)-3 versus the
sum of others and determined by H NMR assay. E/Z ratio.
6
2-furyl, CO2Et (1f)
CH3, CO2Et (1g)
C2H5, CO2Et (1h)
H, CO2Et (1i)
CO2Et
12:1
8:1
c
d
(2a)
e
1
7
CO2Et
(2a)
8
CO2Et
(2a)
5:1
bearing aryl, alkyl, or hydrogen substituents readily incorpo-
rated with both aromatic and aliphatic aldehydes in the
presence of ylide 2e, producing the corresponding polysub-
stituted 1,4-dienes 3 in acceptable yields and good stereo-
selectivity with flexible substituents at the 1,5-positions (entries
1−6). An exceptionally low stereoselectivity was observed in
the construction of 1,5-dialkyl skipped diene 3y (entry 6).
Interestingly, the SN2′ allylation−Wittig reaction of non-
substituted MBH carbonate 1i with benzaldehyde or (E)-
cinnamaldehyde produced the same products (3a and 3j) as
those generated from substituted MBH carbonates 1a or 1j
with paraformaldehyde, albeit with lower yields and stereo-
selectivity (entries 7 and 8 of Table 3 vs entries 1 and 10 of
Table 2). Under similar conditions, however, ketones such as
acetones and acetophenone failed in giving any diene products.
The structure of all the dienes 3 listed in Tables 2 and 3 was
d
9
CO2Et
(2a)
3i, 71
e
10
11
12
13
14
15
16
17
18
19
(E)-PhCHCH,
CO2Et (1j)
CO2Et
38
21
20
24
36
54
18
13
60
72
3j, 92
3k, 97
3l, 95
3m, 43
3n, 98
3o, 92
3p, 87
3q, 98
3r, 83
3s, 46
7:1
20:1
2:1
(2a)
C6H5, CO2Me (1k)
CO2Et
(2a)
C6H5, CN (1l)
CO2Et
(2a)
C2H5, COMe (1m)
C6H5, CO2Et (1a)
CO2Et
(2a)
>20:1
20:1
20:1
8:1
CO2Bn
(2b)
4-CH3C6H4, CO2Et
(1b)
CO2Bn
(2b)
CH3, CO2Et (1g)
CO2Bn
(2b)
H, CO2Et (1i)
CO2Bn
(2b)
well identified by H and 13C{1H} NMR, IR, and HRMS, and
the stereochemistry was confirmed by NOESY analysis for
representative products 3a, 3v, and 3x (see the Supporting
Information).
1
C6H5, CO2Et (1a)
CH3, CO2Et (1g)
COPh
(2c)
>20:1
8:1
COPh
(2c)
f
To further demonstrate the scope, the SN2′ allylation−Wittig
reaction with in situ generated ketenes as the carbonyl
compound was briefly studied. Under the standard conditions,
the reaction between MBH carbonate 1a, P-ylide 2a, and acetyl
chloride or propionyl chloride in the presence of triethylamine
readily proceeded, producing synthetically important44,45
allenoates 4 in good yields and moderate stereoselectivity (eq
2).
20
C6H5, CO2Et (1a)
CH3, CO2Et (1g)
CN (2d)
CN (2d)
72
72
f
21
a
b
For details, see the Experimental Section. Overall yields based on 1.
c
d
Determined by 1H NMR assay. Diene 3i is a known compound; see
e
f
ref 22. Refers to the major (E,E)-3j versus the sum of others. The
reaction gave a complex mixture.
failed to produce the desired products but afforded complex
mixtures, probably due to severe ylide hydrolysis encountered
in the reaction (entries 20 and 21).
Further extension of the scope of the SN2′ allylation−Wittig
reaction to aromatic or aliphatic aldehydes failed under the
standard conditions. Noteworthy is that these aldehydes were
rarely explored in previous P-ylide initiated tandem reac-
tions,17,20,29−37 probably due to their lower reactivity compared
to formaldehyde. We conceived that the switch of triphenyl-
phosphorus ylide to a more reactive trialkylphosphorus ylide
may compensate for the low reactivity of the aldehydes.
Gratifyingly, with in situ generated tributylphosphorus ylide 2e
as a reactant, the desired SN2′ allylation−Wittig reaction with
aromatic or aliphatic aldehydes was successfully realized (Table
3). Under similar conditions, representative MBH carbonates 1
The above results clearly demonstrated that the SN2′
allylation−Wittig reaction has a broad substrate scope, and
gives generally high yields and good stereoselectivity. The
MBH allylic carbonates 1 can be conveniently prepared from
the Morita−Baylis−Hillman adducts41,42 by a simple one-step
operation.46 Phosphorus ylides 2 can also be easily prepared (or
generated in situ) from the corresponding bromides and
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Note
phosphines with a base. Therefore, this one-pot catalyst-free
SN2′ allylation−Wittig reaction constitutes a simple, efficient,
and general method for the stereoselective synthesis of
functionalized 1,4-dienes. In addition, the substitution patterns
of the obtained 1,4-dienes are quite flexible and different from
those in previous reports.17,19−22 Finally, the SN2′ allylation−
Wittig reaction also exhibits excellent regioselectivity; none of
regioisomeric diene products of type 3a′ could be detected in
all cases.
To gain insight into the mechanism for the SN2′ allylation−
Wittig reaction, a 31P{1H} NMR tracking experiment was
conducted. When MBH carbonate 1a (0.05 mmol) and P-ylide
2c (0.05 mmol) were mixed in CDCl3 (0.6 mL) at 60 °C for 12
h in an NMR tube, a new signal at δ 17.2 ppm was observed in
the 31P{1H} NMR measurement. Upon addition of parafor-
maldehyde (0.05 mmol) into the tube at room temperature for
2 h, the signal basically decayed while another signal at 29.2
ppm corresponding to OPPh3 appeared instead (for 31P{1H}
NMR tracking spectra, see the Supporting Information). This
result indicated that the signal at δ 17.2 ppm most likely
corresponded to the in situ generated phosphorus ylide
intermediate 5a47 (eq 3). Based on the experimental results
of homoallylic allenoates in good yields. Due to its simplicity,
high efficiency, broad substrate scope, and readily available
starting materials, this method for preparation of 1,4-dienes is
expected to find wide applications in organic synthesis.
EXPERIMENTAL SECTION
■
Unless otherwise noted, all reactions were carried out in nitrogen
atmosphere under anhydrous conditions. Solvents were purified
according to standard procedures. MBH carbonates 1 was prepared
from Morita−Baylis−Hillman alcohols with Boc2O/DMAP according
to a reported procedure.46 P-Ylides 2 were generated from phosphines
and corresponding bromides with K2CO3 according to the literature.49
Liquid aldehydes were redistilled prior to use. Other reagents from
commercial sources were used without further purification. 1H,
13C{1H}, 31P{1H}, and NOESY NMR spectra were recorded in
CDCl3 with tetramethylsilane (TMS) as the internal standard. IR
spectra were recorded on a FT-IR spectroscopy (KBr). HRMS data
were obtained in ESI mode (positive ion) with the mass analyzer of
TOF used. Column chromatography was performed on silica gel
(200−300 mesh) using a mixture of petroleum ether (bp 60−90 °C)/
ethyl acetate as the eluant.
General Procedures for the Synthesis of 1,4-Dienes 3.
Procedure A (for Table 2). Under N2 atmosphere, to a solution of
MBH carbonates 1 (0.5 mmol) in chloroform (2.0 mL) in a Schlenk
tube (25 mL) was added phosphorus ylide 2 (0.6 mmol) at room
temperature. The reaction mixture was stirred at 60 °C until the MBH
carbonates 1 disappeared, as monitored by TLC. Paraformaldehyde
(30 mg, 1.0 mmol) was then added and stirred for 2 h at room
temperature. All volatile components were removed on a rotary
evaporator under reduced pressure. The residue was purified by
column chromatography on silica gel (eluted with gradient petroleum
ether/ethyl acetate, v/v 20:1 to 5:1) to afford the 1,4-dienes 3a−s.
Procedure B (for Table 3). Under N2 atmosphere and at room
temperature, a mixture of tributylphosphine (150 μL, 0.6 mmol), ethyl
bromoacetate (66 μL, 0.6 mmol), and anhydrous K2CO3 (83 mg, 0.6
mmol) in chloroform (2.0 mL) was stirred for 10 min in a Schlenk
tube (25 mL) for the in situ generation of tributylphosphorus ylide 2e.
After MBH carbonate 1 (0.5 mmol) was introduced, the mixture was
stirred at 60 °C until 1 was consumed. Aldehydes (0.5 mmol) were
then added, and the mixture was further stirred at 60 °C until no
transformation could be observed. The solvent was removed under
reduced pressure, and the residue was subjected to column
chromatography on silica gel (eluted with gradient petroleum ether/
ethyl acetate, v/v 30:1 to 5:1) to afford the 1,4-dienes 3t−y.
and relative literatures,19,38,39,46,48 a plausible mechanism for
the formation of 1,4-dienes 3 is depicted in Scheme 2. Initially,
Scheme 2. Possible Mechanism for the Formation of 1,4-
Dienes 3
Diethyl 2-Benzylidene-4-methylenepentanedioate (3a). Follow-
ing general procedure A, the diene 3a was obtained from MBH
carbonate 1a, P-ylide 2a, and paraformaldehyde as a colorless oil in
143 mg, 99% yield, E/Z ratio = 20:1 (Table 2, entry 1); following the
general procedure B, the diene 3a was obtained from MBH carbonate
1i, P-ylide 2e, and benzaldehyde in 71 mg, 49% yield, E/Z ratio = 4:1
(Table 3, entry 7): NMR data for (E)-3a, 1H NMR (400 MHz,
CDCl3) δ 7.82 (s, 1H), 7.43−7.05 (m, 5H), 6.19 (s, 1H), 5.41 (s, 1H),
4.23−4.11 (m, 4H), 3.48 (s, 2H), 1.25−1.19 (m, 6H); 13C{1H} NMR
(100 MHz, CDCl3) δ 167.6, 166.6, 141.4, 138.3, 134.9, 129.1, 128.9,
128.8, 128.5, 124.3, 60.9, 60.8, 29.6, 14.09, 14.05, selected NMR data
for (Z)-3a, 1H NMR (400 MHz, CDCl3) δ 6.67 (s, 1H), 5.60 (s, 1H),
4.01 (q, J = 7.2 Hz, 2H), 3.36 (s, 2H), 1.08 (t, J = 7.1 Hz, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 168.7, 166.4, 135.9, 128.1, 127.9,
P-ylide 2 as a nucleophile undertakes a regioselective SN2′
attack on the MBH carbonates 1. With the release of one
molecule of CO2, the phosphonium tert-butoxide salt 6 is
produced. Deprotonation by the tert-butoxide anion then
generates the phosphorus ylides 5, which undergoes the salt-
free, E-selective Wittig reaction with aldehydes to deliver the
functionalized 1,4-dienes 3.
In conclusion, a catalyst-free regioselective SN2′ allylation of
stabilized phosphorus ylides with Morita−Baylis−Hillman
carbonates has been developed. The synthetic utility was
demonstrated by a follow-up salt-free Wittig reaction with both
aliphatic and aromatic aldehydes which provides an efficient
synthesis of 1,2,4,5-tetrasubstituted skipped dienes (1,4-dienes)
in good overall yields, moderate to excellent stereoselectivity,
and high variability of substituents. This one-pot SN2′
allylation−Wittig process has been extended to the synthesis
127.7, 126.6, 60.7, 60.5, 37.0, 13.6; IR (KBr) νmax = 2982, 1713, 1633,
1452, 1262, 764, 700 cm−1; HRMS calcd for C17H20O4Na+ requires
311.1259, found 311.1265.
Diethyl 2-(4-Methylbenzylidene)-4-methylenepentanedioate
(3b). Following general procedure A, the diene 3b was obtained as a
colorless oil in 137 mg, 91% yield, E/Z ratio = 20:1: NMR data for
1
(E)-3b, H NMR (400 MHz, CDCl3) δ 7.88 (s, 1H), 7.24 (d, J = 8.1
Hz, 2H), 7.17 (d, J = 8.1 Hz, 2H), 6.27 (d, J = 0.9 Hz, 1H), 5.48 (d, J
= 0.9 Hz, 1H), 4.29−4.20 (m, 4H), 3.56 (s, 2H), 2.36 (s, 3H), 1.36−
1.28 (m, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ 167.9, 166.9,
141.6, 139.1, 138.3, 132.2, 129.3, 129.2, 128.2, 124.4, 60.92, 60.89,
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Note
29.7, 21.3, 14.24, 14.19; selected NMR data for (Z)-3b, 1H NMR (400
MHz, CDCl3) δ 6.71 (s, 1H), 5.68 (s, 1H), 4.12 (q, J = 7.1 Hz, 2H),
3.43 (s, 2H), 2.33 (s, 3H); IR (KBr) νmax = 2980, 1712, 1631, 1445,
1255, 812, 755 cm−1; HRMS calcd for C18H22O4Na+ requires
325.1416, found 325.1421.
1.80 (d, J = 7.1 Hz, 3H), 1.31 (t, J = 7.2 Hz, 3H), 1.27 (t, J = 7.1 Hz,
3H); 13C{1H} NMR (100 MHz, CDCl3) δ 167.3, 166.9, 139.9, 137.6,
130.0, 124.5, 60.7, 60.4, 28.0, 14.4, 14.15, 14.13; selected NMR data
1
for (Z)-3g, H NMR (400 MHz, CDCl3) δ 6.20 (d, J = 1.2 Hz, 1H),
6.10 (q, J = 7.2 Hz, 1H), 5.55−5.53 (m, 1H), 3.27 (s, 2H), 2.02 (dt, J
= 7.2, 0.9 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 167.3, 166.8,
139.4, 138.8, 129.8, 125.7, 60.6, 60.1, 36.0, 15.7; IR (KBr) νmax = 2970,
1718, 1270, 879 cm−1; HRMS calcd for C12H18O4Na+ requires
249.1103, found 249.1113.
Diethyl 2-Methylene-4-(3-nitrobenzylidene)pentanedioate (3c).
Following general procedure A, the diene 3c was obtained as a yellow
1
oil in 153 mg, 92% yield, E/Z ratio =5:1: NMR data for (E)-3c, H
NMR (400 MHz, CDCl3) δ 8.24−8.17 (m, 2H), 7.89 (s, 1H), 7.65 (d,
J = 7.9 Hz, 1H), 7.59−7.56 (m, 1H), 6.31 (d, J = 0.7 Hz, 1H), 5.51 (d,
J = 0.7 Hz, 1H), 4.33−4.19 (m, 4H), 3.54 (s, 2H), 1.36−1.29 (m, 6H);
13C{1H} NMR (100 MHz, CDCl3) δ 166.8, 166.2, 148.2, 138.3, 137.8,
Diethyl 2-Methylene-4-propylidenepentanedioate (3h). Follow-
ing general procedure A, the diene 3h was obtained as a colorless oil in
1
101 mg, 84% yield, E/Z ratio = 5:1: NMR data for (E)-3h, H NMR
(400 MHz, CDCl3) δ 6.86 (t, J = 7.5 Hz, 1H), 6.09 (d, J = 1.2 Hz,
1H), 5.34 (d, J = 1.2 Hz, 1H), 4.15 (q, J = 7.2 Hz, 2H), 4.10 (q, J = 7.2
Hz, 2H), 3.26 (s, 2H), 2.16−2.05 (m, 2H), 1.23 (t, J = 7.2 Hz, 3H),
1.19 (t, J = 7.2 Hz, 3H), 0.97 (t, J = 7.5 Hz, 3H); 13C{1H} NMR (100
MHz, CDCl3) δ 167.3, 166.8, 146.5, 138.0, 128.4, 124.3, 60.6, 60.4,
28.1, 22.0, 14.08, 14.07, 13.0; selected NMR data for (Z)-3h, 1H NMR
(400 MHz, CDCl3) δ 6.12 (s, 1H), 5.89 (t, J = 7.4 Hz, 1H), 5.46 (d, J
= 1.3 Hz, 1H), 3.19 (s, 2H), 2.45−2.37 (m, 2H); 13C{1H} NMR (100
MHz, CDCl3) δ 167.2, 166.7, 146.3, 138.8, 128.3, 125.6, 60.6, 60.0,
35.9, 22.9, 13.7; IR (KBr) νmax = 2979, 1717, 1267, 847 cm−1; HRMS
calcd for C13H20O4Na+ requires 263.1259, found 263.1270.
136.5, 134.5, 132.2, 129.5, 124.7, 123.6, 123.2, 61.2, 60.9, 29.5, 14.00,
13.99; selected NMR data for (Z)-3c, 1H NMR (400 MHz, CDCl3) δ
8.14−8.11 (m, 2H), 6.80 (s, 1H), 5.71 (s, 1H), 4.13 (q, J = 7.1 Hz,
2H), 3.49 (s, 2H), 1.11 (t, J = 7.1 Hz, 3H); 13C{1H} NMR (100 MHz,
CDCl3) δ 167.4, 166.1, 147.8, 137.6, 137.1, 134.3, 134.2, 133.5, 128.8,
127.1, 123.0, 122.3, 60.8, 36.9, 13.6; IR (KBr) νmax = 2983, 1714, 1630,
1531, 1351, 1254, 763, 730 cm−1; HRMS calcd for C17H19NO6Na+
requires 356.1110, found 356.1118.
Diethyl 2-(4-Chlorobenzylidene)-4-methylenepentanedioate
(3d). Following general procedure A, the diene 3d was obtained as a
colorless oil in 158 mg, 98% yield, E/Z ratio =12:1: NMR data for (E)-
Diethyl 2,4-Dimethylenepentanedioate (3i).22 Following general
procedure A, the diene 3i was obtained as a colorless oil in 75 mg, 71%
yield: 1H NMR (400 MHz, CDCl3) δ 6.26 (s, 2H), 5.59 (d, J = 0.9 Hz,
2H), 4.20 (q, J = 7.1 Hz, 4H), 3.34 (s, 2H), 1.29 (t, J = 7.1 Hz, 6H);
13C{1H} NMR (100 MHz, CDCl3) δ 166.6, 138.0, 126.5, 60.7, 33.7,
14.1.
1
3d, H NMR (400 MHz, CDCl3) δ 7.84 (s, 1H), 7.33 (d, J = 8.6 Hz,
2H), 7.27 (d, J = 8.6 Hz, 2H), 6.28 (d, J = 0.8 Hz, 1H), 5.48 (d, J = 0.8
Hz, 1H), 4.29−4.21 (m, 4H), 3.54 (s, 2H), 1.35−1.29 (m, 6H);
13C{1H} NMR (100 MHz, CDCl3) δ 167.4, 166.5, 140.0, 138.1, 134.7,
133.4, 130.2, 129.8, 128.7, 124.4, 61.0, 60.9, 29.6, 14.10, 14.07;
1
selected NMR data for (Z)-3d, H NMR (400 MHz, CDCl3) δ 7.19
Diethyl 2-Methylene-4-(3-phenylallylidene)pentanedioate (3j).
Following general procedure A, the triene 3j was obtained from
MBH carbonate 1j, P-ylide 2a, and paraformaldehyde as a colorless oil
in 144 mg, 92% yield, dr =7:1, with (E,E)-3j as the major isomer
(Table 2, entry 10). Following general procedure B, 3j was obtained
from MBH carbonate 1i, P-ylide 2e, and (E)-cinnamaldehyde in 111
mg, 71% yield, dr =1.4:1 (Table 3, entry 8): NMR data for (E,E)-3j,
1H NMR (400 MHz, CDCl3) δ 7.44 (d, J = 11.2 Hz, 1H), 7.40−7.37
(m, 2H), 7.29−7.19 (m, 3H), 6.95 (dd, J = 15.5, 11.2 Hz, 1H), 6.82
(d, J = 15.5 Hz, 1H), 6.13 (d, J = 1.1 Hz, 1H), 5.41 (d, J = 1.1 Hz,
1H), 4.18−4.11 (m, 4H), 3.46 (s, 2H), 1.24−1.19 (m, 6H); 13C{1H}
NMR (100 MHz, CDCl3) δ 167.5, 166.8, 140.5, 140.3, 138.0, 136.2,
128.8, 128.7, 128.1, 127.1, 125.2, 123.6, 60.8, 60.6, 28.6, 14.2, 14.1;
(d, J = 8.4 Hz, 1H), 6.70 (s, 1H), 5.68 (s, 1H), 4.11 (q, J = 7.1 Hz,
2H), 3.44 (s, 2H), 1.12 (t, J = 7.1 Hz, 3H); 13C{1H} NMR (100 MHz,
CDCl3) δ 168.3, 166.3, 137.5, 134.7, 134.3, 133.6, 132.1, 129.5, 128.1,
126.8, 60.8, 60.7, 37.0, 13.7; IR (KBr) νmax = 2978, 1715, 1625, 1580,
1491, 1262, 807, 762 cm−1; HRMS calcd for C17H19ClO4Na+ requires
345.0870, found 345.0876.
Diethyl 2-(2-Chlorobenzylidene)-4-methylenepentanedioate
(3e). Following general procedure A, the diene 3e was obtained as a
colorless oil in 155 mg, 96% yield, E/Z ratio = 9:1: NMR data for (E)-
3e, 1H NMR (400 MHz, CDCl3) δ 7.97 (s, 1H), 7.45−7.38 (m, 1H),
7.30−7.16 (m, 3H), 6.26 (s, 1H), 5.49 (s, 1H), 4.27 (q, J = 7.1 Hz,
2H), 4.21 (q, J = 7.1 Hz, 2H), 3.45 (s, 2H), 1.32 (t, J = 7.1 Hz, 3H),
1.29 (t, J = 7.1 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 167.0,
166.4, 138.4, 138.3, 134.0, 133.6, 131.3, 129.7, 129.5, 129.2, 126.6,
1
selected NMR data for a minor isomer, H NMR (400 MHz, CDCl3)
1
124.4, 61.0, 60.8, 29.4, 14.1, 14.0; selected NMR data for (Z)-3e, H
δ 7.84 (dd, J = 15.6, 11.3 Hz, 1H), 6.65 (d, J = 15.6 Hz, 1H), 6.56 (d, J
= 11.3 Hz, 1H), 6.16 (s, 1H), 5.51 (d, J = 1.3 Hz, 1H), 3.31 (s, 2H);
13C{1H} NMR (100 MHz, CDCl3) δ 166.8, 166.7, 142.0, 139.2, 138.7,
136.6, 128.6, 128.5, 127.5, 127.1, 126.0, 125.6, 60.7, 60.3, 36.0; IR
(KBr) νmax = 2981, 1711, 1614, 1448, 1141, 750, 691 cm−1; HRMS
calcd for C19H22O4Na+ requires 337.1416, found 337.1418.
5-Ethyl 1-Methyl 2-benzylidene-4-methylenepentanedioate (3k).
Following general procedure A, the diene 3k was obtained as a
colorless oil in 133 mg, 97% yield, E/Z ratio =20:1: NMR data for (E)-
3k, 1H NMR (400 MHz, CDCl3) δ 7.83 (s, 1H), 7.34−7.16 (m, 5H),
6.19 (d, J = 0.7 Hz, 1H), 5.40 (d, J = 0.7 Hz, 1H), 4.15 (t, J = 7.1 Hz,
2H), 3.70 (s, 3H), 3.48 (s, 2H), 1.22 (t, J = 7.1 Hz, 3H); 13C{1H}
NMR (100 MHz, CDCl3) δ 168.1, 166.6, 141.7, 138.2, 134.8, 128.9,
128.8, 128.7, 128.5, 124.3, 60.8, 52.0, 29.6, 14.0; selected NMR data
for (Z)-3k, 1H NMR (400 MHz, CDCl3) δ 6.66 (s, 1H), 5.59 (s, 1H),
3.52 (s, 2H); IR (KBr) νmax = 2952, 1718, 1632, 1435, 1267, 768, 698
cm−1; HRMS calcd for C16H18O4Na+ requires 297.1103, found
297.1112.
NMR (400 MHz, CDCl3) δ 7.38−7.33 (m, 1H), 6.90 (s, 1H), 6.31 (s,
1H), 5.73 (s, 1H), 4.25−4.23 (m, 2H), 4.01 (q, J = 7.1 Hz, 2H), 3.49
(s, 2H), 0.98 (t, J = 7.1 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ
167.5, 166.4, 137.7, 135.3, 134.6, 133.2, 132.7, 129.7, 128.9, 128.8,
126.7, 126.0, 60.4, 36.2, 13.5; IR (KBr) νmax = 2981, 1716, 1635, 1590,
1468, 1256, 755, 738 cm−1; HRMS calcd for C17H19ClO4Na+ requires
345.0870, found 345.0876.
Diethyl 2-(Furan-2-ylmethylene)-4-methylenepentanedioate (3f).
Following general procedure A, the diene 3f was obtained as a brown
1
oil in 111 mg, 80% yield, E/Z ratio = 12:1: NMR data for (E)-3f, H
NMR (400 MHz, CDCl3) δ 7.62 (s, 1H), 7.50 (d, J = 1.6 Hz, 1H),
6.60 (d, J = 3.4 Hz, 1H), 6.47 (dd, J = 3.4, 1.6 Hz, 1H), 6.16 (d, J = 1.0
Hz, 1H), 5.39 (d, J = 1.0 Hz, 1H), 4.32−4.19 (m, 4H), 3.75 (s, 2H),
1.35−1.27 (m, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ 167.7,
167.0, 151.0, 144.5, 137.7, 127.7, 125.5, 123.8, 115.5, 112.0, 60.9, 60.7,
1
29.7, 14.6, 14.1; selected NMR data for (Z)-3f, H NMR (400 MHz,
CDCl3) δ 7.39 (d, J = 1.6 Hz, 1H), 6.55 (s, 1H), 6.42 (dd, J = 3.4, 1.6
Hz, 1H), 6.27 (s, 1H), 5.66 (s, 1H), 3.42 (s, 2H); 13C{1H} NMR (100
MHz, CDCl3) δ 142.9, 126.7, 124.5, 113.1, 111.8, 60.8, 60.6, 37.0,
14.1; IR (KBr) νmax = 1710, 1632, 1269, 944 cm−1; HRMS calcd for
C15H18O5Na+ requires 301.1052, found 301.1059.
Diethyl 2-Ethylidene-4-methylenepentanedioate (3g). Following
general procedure A, the diene 3g was obtained as a colorless oil in 58
mg, 51% yield, E/Z ratio = 8:1: NMR data for (E)-3g, 1H NMR (400
MHz, CDCl3) δ 7.05 (q, J = 7.1 Hz, 1H), 6.18 (dd, J = 2.7, 1.3 Hz,
1H), 5.42 (dd, J = 3.1, 1.7 Hz, 1H), 4.25−4.14 (m, 4H), 3.35 (s, 2H),
Ethyl 4-Cyano-2-methylene-5-phenylpent-4-enoate (3l). Follow-
ing general procedure A, the diene 3l was obtained as a colorless oil in
1
114 mg, 95% yield, E/Z ratio = 2:1: NMR data for (E)-3l: H NMR
(400 MHz, CDCl3) δ 7.78−7.70 (m, 2H), 7.43−7.39 (m, 3H), 7.06 (s,
1H), 6.40 (s, 1H), 5.82 (d, J = 0.9 Hz, 1H), 4.22 (q, J = 7.1 Hz, 2H),
3.39 (s, 2H), 1.30 (t, J = 7.1 Hz, 3H); 13C{1H} NMR (100 MHz,
CDCl3) δ 165.7, 145.3, 136.0, 133.4, 130.1, 128.7, 128.6, 128.5, 118.2,
1
108.1, 60.9, 38.0, 14.0; selected NMR data for (Z)-3l: H NMR (400
MHz, CDCl3) δ 6.44 (s, 1H), 5.78 (d, J = 1.1 Hz, 1H), 3.49 (s, 2H);
3700
dx.doi.org/10.1021/jo500375q | J. Org. Chem. 2014, 79, 3696−3703

The Journal of Organic Chemistry
Note
13C{1H} NMR (100 MHz, CDCl3) δ 165.7, 146.0, 135.7, 133.4, 129.5,
127.9, 127.1, 119.7, 111.9, 61.0, 32.0, 13.9; IR (KBr) νmax = 2982,
2211, 1716, 1633, 1496, 1145, 750, 693 cm−1; HRMS calcd for
C15H15NO2Na+ requires 264.1000, found 264.1010.
135.0, 132.3, 129.6, 129.3, 129.1, 128.9, 128.6, 128.2, 125.4, 61.0, 30.0,
14.3; IR (KBr) νmax = 2979, 1709, 1658, 1447, 1264, 748, 694 cm−1;
HRMS calcd for C21H20O3Na+ requires 343.1310, found 343.1320.
Ethyl 4-Benzoyl-2-ethylidenepent-4-enoate (3s). Following gen-
eral procedure A, the diene 3s was obtained as a yellow oil in 59 mg,
Ethyl 4-Acetyl-2-methylenehept-4-enoate (3m). Following general
1
46% yield, E/Z ratio = 8:1: NMR data for (E)-3s, H NMR (400
procedure A, the diene 3m was obtained as a colorless oil in 45 mg,
1
MHz, CDCl3) δ 7.70−7.63 (m, 2H), 7.49−7.43 (m, 1H), 7.38−7.32
(m, 2H), 7.01 (q, J = 7.1 Hz, 1H), 5.66 (s, 1H), 5.53 (s, 1H), 4.12 (q, J
= 7.1 Hz, 2H), 3.41 (s, 2H), 1.78 (d, J = 7.1 Hz, 3H), 1.19 (t, J = 7.1
Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 197.9, 167.3, 145.2,
140.1, 137.6, 132.2, 130.0, 129.5, 128.1, 125.5, 60.5, 28.5, 14.5, 14.2;
43% yield, E/Z ratio >20:1: NMR data for (E)-3m, H NMR (400
MHz, CDCl3) δ 6.79 (t, J = 7.3 Hz, 1H), 6.13 (d, J = 1.2 Hz, 1H), 5.30
(d, J = 1.2 Hz, 1H), 4.22 (q, J = 7.1 Hz, 2H), 3.31 (s, 2H), 2.33 (s,
3H), 2.29−2.18 (m, 2H), 1.31 (t, J = 7.1 Hz, 3H), 1.08 (t, J = 7.5 Hz,
3H); 13C{1H} NMR (100 MHz, CDCl3) δ 198.8, 167.0, 147.7, 138.2,
138.0, 124.2, 60.8, 27.1, 25.6, 22.5, 14.2, 13.1; IR (KBr) νmax = 2964,
1717, 1672, 1269, 1138, 805 cm−1; HRMS calcd for C12H18O3Na+
requires 233.1154, found 233.1162.
1
selected NMR data for (Z)-3s, H NMR (400 MHz, CDCl3) δ 6.11
(q, J = 7.2 Hz, 1H), 5.76 (s, 1H), 5.56 (s, 1H), 3.34 (s, 2H), 1.95 (d, J
= 7.2 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 197.6, 146.2,
129.5, 126.5, 60.1, 36.6, 15.8; IR (KBr) νmax = 2979, 1709, 1655, 1444,
1276, 745, 691 cm−1; HRMS calcd for C16H18O3Na+ requires
281.1154, found 281.1161.
1-Benzyl 5-Ethyl 4-benzylidene-2-methylenepentanedioate (3n).
Following general procedure A, the diene 3n was obtained as a
colorless oil in 172 mg, 98% yield, E/Z ratio = 20:1: NMR data for
1
(E)-3n, H NMR (400 MHz, CDCl3) δ 7.81 (s, 1H), 7.28−7.17 (m,
Diethyl 2,4-Dibenzylidenepentanedioate (3t). Following general
procedure B, the diene 3t was obtained as a slightly yellow oil in 100
mg, 55% yield, dr = 6:1, with (E,E)-3t as the major isomer: NMR data
10H), 6.23 (s, 1H), 5.43 (s, 1H), 5.12 (s, 2H), 4.12 (q, J = 7.1 Hz,
2H), 3.50 (s, 2H), 1.17 (t, J = 7.1 Hz, 3H); 13C{1H} NMR (100 MHz,
CDCl3) δ 167.6, 166.4, 141.5, 138.0, 135.8, 134.9, 129.0, 128.9, 128.8,
128.5, 128.4, 128.1, 127.9, 125.0, 66.5, 60.9, 29.6, 14.1; selected NMR
data for (Z)-3n, 1H NMR (400 MHz, CDCl3) δ 6.61 (s, 1H), 5.78 (s,
1H), 5.09 (s, 2H), 3.36 (s, 2H), 1.09 (t, J = 7.1 Hz, 3H); IR (KBr) νmax
= 2980, 1714, 1633, 1496, 1264, 747, 693 cm−1; HRMS calcd for
C22H22O4Na+ requires 373.1416, found 373.1431.
1
for (E,E)-3t, H NMR (400 MHz, CDCl3) δ 7.60 (s, 2H), 7.28−7.26
(m, 10H), 4.21 (q, J = 7.1 Hz, 4H), 3.92 (s, 2H), 1.27 (t, J = 7.1 Hz,
6H); 13C{1H} NMR (100 MHz, CDCl3) δ 168.1, 139.0, 135.4, 131.1,
129.3, 128.21, 128.16, 60.8, 26.2, 14.2; selected NMR data for a minor
1
isomer, H NMR (400 MHz, CDCl3) δ 7.73 (s, 1H), 4.29 (q, J = 7.1
Hz, 2H), 3.68 (s, 2H), 1.11 (t, J = 7.1 Hz, 3H); IR (KBr) νmax = 2980,
1709, 1632, 1446, 1248, 767, 697 cm−1; HRMS calcd for C23H24O4Na+
requires 387.1572, found 387.1571.
1-Benzyl 5-Ethyl 4-(4-methylbenzylidene)-2-methylenepentane-
dioate (3o). Following general procedure A, the diene 3o was
obtained as a yellow oil in 167 mg, 92% yield, E/Z ratio = 20:1: NMR
Diethyl 2-Benzylidene-4-(3-nitrobenzylidene)pentanedioate (3u).
Following general procedure B, the diene 3u was obtained as a yellow
oil in 109 mg, 58% yield, dr = 10:1, with (E,E)-3u as the major isomer:
1
data for (E)-3o, H NMR (400 MHz, CDCl3) δ 7.88 (s, 1H), 7.41−
7.33 (m, 5H), 7.23 (d, J = 8.1 Hz, 2H), 7.15 (d, J = 8.1 Hz, 2H), 6.32
(d, J = 0.8 Hz, 1H), 5.52 (d, J = 0.8 Hz, 1H), 5.24 (s, 2H), 4.23 (q, J =
7.1 Hz, 2H), 3.59 (s, 2H), 2.35 (s, 3H), 1.29 (t, J = 7.1 Hz, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 167.9, 166.6, 141.7, 139.2, 138.1,
135.9, 132.1, 129.3, 129.2, 128.5, 128.2, 128.1, 128.0, 125.1, 66.6, 60.9,
1
NMR data for (E,E)-3u, H NMR (400 MHz, CDCl3) δ 8.11−8.04
(m, 2H), 7.59−7.57 (m, 2H), 7.52 (d, J = 7.7 Hz, 1H), 7.44−7.38 (m,
1H), 7.31−7.26 (m, 3H), 7.23−7.19 (m, 2H), 4.25 (q, J = 7.2 Hz,
2H), 4.21 (q, J = 7.2 Hz, 2H), 3.87 (s, 2H), 1.30 (t, J = 7.2 Hz, 3H),
1.28 (t, J = 7.2 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 167.6,
167.4, 148.0, 139.7, 137.2, 136.2, 135.1, 134.6, 134.2, 130.4, 129.2,
129.0, 128.5, 128.3, 123.7, 122.7, 61.2, 61.0, 25.9, 14.16, 14.15;
1
29.7, 21.3, 14.2; selected NMR data for (Z)-3o, H NMR (400 MHz,
CDCl3) δ 6.68 (s, 1H), 5.72 (d, J = 1.2 Hz, 1H), 5.21 (s, 2H), 4.10 (q,
J = 7.1 Hz, 2H), 3.45 (s, 2H), 2.33 (s, 3H); IR (KBr) νmax = 2979,
1701, 1632, 1455, 1271, 742, 697 cm−1; HRMS calcd for C23H24O4Na+
requires 387.1572, found 387.1578.
1
selected NMR data for a minor isomer, H NMR (400 MHz, CDCl3)
δ 7.60 (d, J = 8.0 Hz, 1H), 3.73 (s, 1H); IR (KBr) νmax = 2962, 1710,
1632, 1575, 1493, 1260, 736, 699 cm−1; HRMS calcd for
C23H23NO6Na+ requires 432.1423, found 432.1429.
1-Benzyl 5-Ethyl 4-ethylidene-2-methylenepentanedioate (3p).
Following general procedure A, the diene 3p was obtained as a
colorless oil in 125 mg, 87% yield, E/Z ratio = 8:1: NMR data for (E)-
Diethyl 2-Benzylidene-4-(4-methylbenzylidene)pentanedioate
(3v). Following general procedure B, the diene 3v was obtained as a
yellow oil in 115 mg, 61% yield, dr > 20:1, with (E,E)-3v as the major
1
3p, H NMR (400 MHz, CDCl3) δ 7.33−7.22 (m, 5H), 6.96 (q, J =
7.1 Hz, 1H), 6.14 (s, 1H), 5.36 (s, 1H), 5.11 (s, 2H), 4.06 (q, J = 7.1
Hz, 2H), 3.28 (s, 2H), 1.67 (d, J = 7.1 Hz, 3H), 1.15 (t, J = 7.1 Hz,
3H); 13C{1H} NMR (100 MHz, CDCl3) δ 167.1, 166.6, 139.9, 137.3,
135.9, 129.9, 128.4, 128.04, 127.97, 125.0, 66.4, 60.4, 28.0, 14.3, 14.1;
1
isomer: NMR data for (E,E)-3v, H NMR (400 MHz, CDCl3) δ 7.53
(s, 1H), 7.50 (s, 1H), 7.21−7.18 (m, 5H), 7.10 (d, J = 8.1 Hz, 2H),
7.00 (d, J = 8.1 Hz, 2H), 4.16−4.09 (m, 4H), 3.85 (s, 2H), 2.26 (s,
3H), 1.20−1.17 (m, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ 168.2,
168.1, 139.1, 138.9, 138.3, 135.4, 132.5, 131.3, 130.3, 129.41, 129.36,
129.0, 128.20, 128.18, 60.8, 60.7, 26.3, 21.3, 14.16, 14.15; IR (KBr)
νmax = 2959, 1713, 1632, 1443, 1258, 766, 697 cm−1; HRMS calcd for
C24H26O4Na+ requires 401.1729, found 401.1735.
1
selected NMR data for (Z)-3p, H NMR (400 MHz, CDCl3) δ 6.17
(s, 1H), 5.98 (q, J = 7.1 Hz, 1H), 5.49 (s, 1H), 5.09 (s, 2H), 3.20 (s,
2H), 1.90 (d, J = 7.1 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ
166.5, 139.4, 138.5, 129.6, 127.9, 126.3, 66.3, 60.0, 35.9, 15.6; IR
(KBr) νmax = 2985, 1716, 1637, 1451, 1269, 761, 699 cm−1; HRMS
calcd for C17H20O4Na+ requires 311.1259, found 311.1270.
Diethyl 2-Benzylidene-4-(4-chlorobenzylidene)pentanedioate
(3w). Following general procedure B, the diene 3w was obtained as
a colorless oil in 98 mg, 49% yield, dr = 20:1, with (E,E)-3w as the
1-Benzyl 5-Ethyl 2,4-dimethylenepentanedioate (3q). Following
general procedure A, the diene 3q was obtained as a colorless oil in
1
1
134 mg, 98% yield: H NMR (400 MHz, CDCl3) δ 7.39−7.29 (m,
major isomer: NMR data for (E,E)-3w, H NMR (400 MHz, CDCl3)
5H), 6.31 (s, 1H), 6.24 (s, 1H), 5.62 (s, 1H), 5.57 (s, 1H), 5.19 (s,
2H), 4.18 (q, J = 7.1 Hz, 2H), 3.36 (s, 2H), 1.26 (t, J = 7.1 Hz, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 166.4, 166.3, 137.9, 137.7, 135.8,
128.4, 128.1, 127.9, 127.1, 126.6, 66.4, 60.7, 33.7, 14.0; IR (KBr) νmax
= 2989, 1718, 1635, 1500, 1271, 734, 687 cm−1; HRMS calcd for
C16H18O4Na+ requires 297.1103, found 297.1119.
δ 7.52 (s, 1H), 7.44 (s, 1H), 7.24−7.15 (m, 5H), 7.13 (d, J = 8.5 Hz,
2H), 7.08 (d, J = 8.5 Hz, 2H), 4.17−4.09 (m, 4H), 3.80 (s, 2H), 1.21−
1.17 (m, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ 167.81, 167.78,
139.2, 137.6, 135.3, 134.0, 133.8, 131.8, 130.8, 130.4, 129.2, 128.4,
128.3, 128.2, 60.9, 60.8, 26.0, 14.1(2C); selected NMR data for a
1
minor isomer, H NMR (400 MHz, CDCl3) δ 4.20 (q, J = 7.1 Hz,
Ethyl 4-Benzoyl-2-benzylidenepent-4-enoate (3r). Following
2H), 4.03 (q, J = 7.0 Hz, 2H), 3.41 (s, 2H); IR (KBr) νmax = 2959,
1714, 1633, 1592, 1446, 1259, 773, 693 cm−1; HRMS calcd for
C23H23ClO4Na+ requires 421.1183, found 421.1183.
general procedure A, the diene 3r was obtained as a yellow oil in
1
133 mg, 83% yield, E/Z ratio >20:1: NMR data for (E)-3r, H NMR
(400 MHz, CDCl3) δ 7.88 (s, 1H), 7.71 (d, J = 8.4 Hz, 2H), 7.50−
7.44 (m, 1H), 7.40−7.25 (m, 7H), 5.71 (d, J = 1.6 Hz, 1H), 5.62 (s,
1H), 4.21 (q, J = 7.1 Hz, 2H), 3.64 (s, 2H), 1.25 (t, J = 7.1 Hz, 3H);
13C{1H} NMR (100 MHz, CDCl3) δ 197.8, 167.9, 145.6, 141.7, 137.5,
Diethyl 2-Benzylidene-4-propylidenepentanedioate (3x). Follow-
ing general procedure B, the diene 3x was obtained as a yellow oil in
79 mg, 50% yield, dr = 11:1, with (E,E)-3x as the major isomer: NMR
data for (E,E)-3x, 1H NMR (400 MHz, CDCl3) δ 7.67 (s, 1H), 7.42−
3701
dx.doi.org/10.1021/jo500375q | J. Org. Chem. 2014, 79, 3696−3703

The Journal of Organic Chemistry
Note
7.34 (m, 5H), 6.66 (t, J = 7.4 Hz, 1H), 4.21 (q, J = 7.1 Hz, 2H), 4.13
(q, J = 7.1 Hz, 2H), 3.62 (s, 2H), 2.09−1.95 (m, 2H), 1.29 (t, J = 7.1
Hz, 3H), 1.22 (t, J = 7.1 Hz, 3H), 0.93 (t, J = 7.5 Hz, 3H); 13C{1H}
NMR (100 MHz, CDCl3) δ 168.0, 167.8, 145.0, 138.9, 135.7, 131.7,
129.6, 129.1, 128.3, 128.2, 60.7, 60.4, 25.1, 21.8, 14.13, 14.10, 12.9;
selected NMR data for a minor isomer: 1H NMR (400 MHz, CDCl3)
δ 7.73 (s, 1H), 6.95 (t, J = 7.5 Hz, 1H), 4.28 (q, J = 7.1 Hz, 2H), 3.34
(s, 2H), 1.35 (t, J = 7.1 Hz, 3H), 1.07 (t, J = 7.5 Hz, 3H); IR (KBr)
νmax = 2978, 1713, 1637, 1446, 1244, 766, 698 cm−1; HRMS calcd for
C19H24O4Na+ requires 339.1572, found 339.1570.
ASSOCIATED CONTENT
■
S
* Supporting Information
1H and 13C{1H} NMR spectra for 3 and 4, NOESY spectra for
3a, 3v, and 3x, and 31P{1H} NMR tracking spectra. This
material is available free of charge via the Internet at http://
pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Authors
*E-mail: silongxu@mail.xjtu.edu.cn.
*E-mail: djw@mail.xjtu.edu.cn.
Diethyl 2,4-Dipropylidenepentanedioate (3y). Following general
procedure B, the diene 3y was obtained as a colorless oil in 64 mg,
1
48% yield, (E,E)-3y:(E,Z)-3y = 1.3:1: NMR data for (E,E)-3y, H
NMR (400 MHz, CDCl3) δ 6.71 (t, J = 7.4 Hz, 2H), 4.15 (q, J = 7.1
Hz, 4H), 3.34 (s, 2H), 2.33−2.25 (m, 4H), 1.26 (t, J = 7.1 Hz, 6H),
1.05 (t, J = 7.5 Hz, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ 167.8,
Notes
The authors declare no competing financial interest.
1
144.9, 129.5, 60.4, 24.3, 22.0, 14.2, 13.1; NMR data for (E,Z)-3y, H
ACKNOWLEDGMENTS
NMR (400 MHz, CDCl3) δ 6.87 (t, J = 7.5 Hz, 1H), 5.76 (t, J = 7.4
Hz, 1H), 4.22−4.17 (m, 4H), 3.28 (s, 2H), 2.45−2.36 (m, 2H), 2.23−
2.15 (m, 2H), 1.30 (t, J = 7.1 Hz, 3H), 1.27 (t, J = 7.1 Hz, 3H), 1.05 (t,
J = 7.4 Hz, 3H), 0.98 (t, J = 7.5 Hz, 3H); 13C{1H} NMR (100 MHz,
CDCl3) δ 167.9, 167.6, 146.1, 143.1, 128.9, 128.5, 60.4, 60.2, 30.1,
22.9, 22.0, 14.2(2C), 13.8, 13.1; IR (KBr) νmax = 2969, 1715, 1242
cm−1; HRMS calcd for C15H24O4Na+ requires 291.1572, found
291.1573.
Synthesis of Homoallylic Allenoates 4 (eq 2). Under N2
atmosphere, the mixture of MBH carbonate 1a (0.5 mmol) and P-
ylide 2a (0.6 mmol) in chloroform (2.0 mL) was stirred at 60 °C in a
Schlenk tube (25 mL) for 20 h. After cooling, acyl chlorides (1.0
mmol) and triethylamine (139 μL, 1.0 mmol) were added sequentially
by the means of a microsyringe. The mixture was stirred at room
temperature for 2 h. All volatile components were removed under
reduced pressure, and the residue was purified by column
chromatography on silica gel (eluted with petroleum ether/ethyl
acetate, v/v 10:1) to give the allenoates 4.
Diethyl 2-Benzylidene-4-vinylidenepentanedioate (4a). Colorless
oil, 91 mg, 61% yield, E/Z = 3:1: NMR data for (E)-4a, 1H NMR (400
MHz, CDCl3) δ 7.82 (s, 1H), 7.39−7.30 (m, 5H), 5.13 (t, J = 4.1 Hz,
2H), 4.29−4.22 (m, 4H), 3.49 (t, J = 4.1 Hz, 2H), 1.34−1.28 (m, 6H);
13C{1H} NMR (100 MHz, CDCl3) δ 213.2, 167.7, 166.6, 140.8, 136.4,
135.2, 129.1, 128.7, 128.5, 99.7, 80.7, 61.2, 60.9, 26.6, 14.3, 14.2;
selected NMR data for (Z)-4a, 1H NMR (400 MHz, CDCl3) δ 6.81 (s,
1H), 5.17 (t, J = 2.6 Hz, 2H), 4.10 (q, J = 7.1 Hz, 2H), 3.38 (br s, 2H),
1.10 (t, J = 7.1 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 214.2,
168.5, 166.5, 136.0, 131.0, 129.2, 128.3, 128.0, 127.8, 98.2, 79.7, 61.2,
60.6, 34.1, 13.8; IR (KBr) νmax = 2980, 1967, 1708, 1636, 1447, 1259,
759, 699 cm−1; HRMS calcd for C18H20O4Na+ requires 323.1259,
found 323.1259.
■
This work was supported by the National Natural Science
Foundation of China (No. 21305107) and the Fundamental
Research Funds for the Central Universities (No. 08143076).
We gratefully thank Prof. Zhengjie He (Nankai University) for
constructive discussions and long-term support.
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