PBu3-mediated vinylogous wittig reaction of α-methyl allenoates with aldehydes and mechanistic investigations

Article abstract of DOI:10.1021/jo201466k

A highly stereoselective PBu₃-mediated vinylogous Wittig olefination between α-methyl allenoates and a variety of aldehydes is presented as the first example of a practical and synthetically useful vinylogous Wittig reaction. Mechanistic experiments including deuterium-labeling, intermediate entrapment, and NMR monitoring have been deliberately conducted. On the basis of mechanistic investigations, a reliable mechanism for the vinylogous Wittig reaction is proposed, which features a water/phosphine-coassisted allylic phosphorus ylide 1,3-rearrangement pathway, rather than previous retro-Diels-Alder ones. It is noteworthy that mechanistic findings in this work also provide supportive evidence for typical mechanisms of important phosphine-mediated reactions of allenoates.

Full text of DOI:10.1021/jo201466k

ARTICLE
pubs.acs.org/joc
PBu3-Mediated Vinylogous Wittig Reaction of r-Methyl Allenoates
with Aldehydes and Mechanistic Investigations
Silong Xu, Rongshun Chen, and Zhengjie He*
The State Key Laboratory of Elemento-Organic Chemistry and Department of Chemistry, Nankai University, 94 Weijin Road,
Tianjin 300071, People's Republic of China
S Supporting Information
b
ABSTRACT: A highly stereoselective PBu3-mediated vinylogous
Wittig olefination between R-methyl allenoates and a variety of aldehydes
is presented as the first example of a practical and synthetically useful
vinylogous Wittig reaction. Mechanistic experiments including deuter-
ium-labeling, intermediate entrapment, and NMR monitoring have been
deliberately conducted. On the basis of mechanistic investigations, a
reliable mechanism for the vinylogous Wittig reaction is proposed, which features a water/phosphine-coassisted allylic phosphorus
ylide 1,3-rearrangement pathway, rather than previous retro-DielsꢀAlder ones. It is noteworthy that mechanistic findings in this work
also provide supportive evidence for typical mechanisms of important phosphine-mediated reactions of allenoates.
Scheme 1. Distinct Olefinations of r-Substituted Allenoates
’ INTRODUCTION
and Aldehydes under the Mediation of PBu3
The principle of vinylogy, first formulated by Fuson1 in 1935,
explains anomalous reactivity of some unsaturated compounds
with extended electrophilic or nucleophilic character of a func-
tional group through π systems of double or triple bonds or
aromatic moieties. Over the past decades, the vinylogy rule has
been widely applied to a number of important reactions such as
aldol,2 Mannich,3 Michael addition,4 and others5ꢀ8 as an im-
mensely useful, strategic maneuver in the art of contemporary
organic synthesis. In this context, vinylogous Wittig type reac-
tions were far less explored,9ꢀ12 although the Wittig olefination13
occupies a central position in the construction of CdC double
bonds. By principle, allylic phosphorus ylides may undergo a
vinylogous Wittig type reaction to generate regiodifferentiated
isomeric dienes. In 2007, Ghosh et al.9 first disclosed a vinylogous
HornerꢀWadsworthꢀEmmons reaction between R-cyano vi-
nylphosphonates and aldehydes, leading to a stereoselective
synthesis of densely substituted 1,3-butadienes. For the vinylo-
gous Wittig reaction, its history can be traced back to 1974 when
Corey10 recorded the first example in the olefination reaction of
(E)-3-methoxycarbonyl-2-methylallyltriphenylphosphonium
bromide with hexanal, giving a regio- and stereoisomeric mix-
ture of dienes. It is until recently that our group11 and Kwon12
independently reported two triarylphosphine-mediated viny-
logous Wittig reactions of R-methyl allenoates, albeit both with
very limited aldehydes. To our knowledge, no other vinylogous
Wittig type reactions have been reported. Despite its significant
synthetic potential as a useful complement to the normal Wittig
reaction, the vinylogous Wittig reaction is still in its infancy with
regard to the generality, stereochemistry, and mechanism.
During our investigation on the olefination reactions of in situ-
generated allylic phosphorus ylides with aldehydes,14ꢀ16 two regio-
selective olefinations between tertiary phosphines, R-substituted
allenoates, and aldehydes were observed (Scheme 1). When R1 in
allenoates 1 was a conjugative group such as ethoxycarbonyl or
phenyl, a normal Wittig olefination of aldehydes with in situ-
generated allylic phosphorus ylide I from allenoates and PBu3 readily
gave 1,2,3,4-tetrasubstituted 1,3-dienes.16 In contrast, when R-methyl
allenoate (1a, R1 = H) was employed under the same conditions, a
vinylogous Wittig olefination occurred from 1a, PBu3, and aldehydes,
producing 1,2,4-trisubstituted 1,3-dienes (Scheme 1). Further stud-
ies disclosed that this PBu3-mediated vinylogous Wittig reaction
readily proceeded with a broad array of aldehydes, constituting an
efficient and stereoselective synthesis of trisubstituted 1,3-dienes.
This reaction represents the first example of practical and syntheti-
cally useful vinylogous Wittig reaction. Herein we report our research
findings on this reaction, particularly its mechanism.
’ RESULTS AND DISCUSSION
Condition Optimization. Optimization of reaction condi-
tions was carried out using the reaction of R-methyl allenoate
(1a) and benzaldehyde (2a) as a probe (Table 1). A series of
Received: July 14, 2011
Published: August 08, 2011
r
2011 American Chemical Society
7528
dx.doi.org/10.1021/jo201466k J. Org. Chem. 2011, 76, 7528–7538
|

The Journal of Organic Chemistry
ARTICLE
Table 1. Survey of Conditions for the Vinylogous Wittig
Reactiona
Table 2. Generality of PBu3-Mediated Vinylogous Wittig
Olefination of r-Methyl Allenoatesa
entry
PR3
PBu3
solvent
CHCl3
time (h)
yield (%)b
E/Zc
entry
R2 in 2
C6H5 (2a)
time (h)
yield (%)b
E/Zc
1
12
12
12
24
24
24
24
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
83
65
30
37
8
4:1
1:1
3:1
3:1
1.5:1
ꢀ
1
12
12
12
12
12
24
24
12
36
36
36
12
12
24
12
12
36
24
12
12
24
12
12
3a, 79
3b, 96
3c, 99
3d, 71
3e, 77
3f, 96
3g, 92
3h, 82
3i, 75
3j, 77
3k, 72
3l, 65
3m, 69
3n, 44
3o, 60
3p, 40
3q, 98
3r, 87
3s, 83
3t, 60
3u, 85
3v, 56
3w, 98
6:1
5:1
5:1
5:1
5:1
4:1
5:1
6:1
5:1
4:1
5:1
3:1
3:1
4:1
4:1
4:1
4:1
5:1
4:1
4:1
3:1
5:1
6:1
2
PPhMe2
PMePh2
PTA
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CH2Cl2
toluene
THF
2
4-ClC6H4 (2b)
3
3
3-ClC6H4 (2c)
4
4
4-BrC6H4 (2d)
5
PPh3
5
2-FC6H4 (2e)
6
P(NMe2)3
P(OMe)3
PBu3
ꢀ
ꢀ
6
4-FC6H4 (2f)
7
ꢀ
7
4-IC6H4 (2g)
8
76
25
23
37
trace
26
ꢀ
4:1
3:1
3:1
3:1
ꢀ
8
3-Br-4-MeOC6H3 (2h)
2-MeOC6H4 (2i)
4-MeOC6H4 (2j)
4-MeC6H4 (2k)
3-MeO-2-NO2C6H3 (2l)
4-CO2MeC6H4 (2m)
2-CF3C6H4 (2n)
4-CF3C6H4 (2o)
3-NO2C6H4 (2p)
1-naphthyl (2q)
2-furyl (2r)
9
PBu3
9
10
11
12
13
14
15d
16e
17f
18f,g
19f,h
20f,i
21f,j
22f,k
PBu3
10
11
12
13
14
15
16d,e
17
18
19
20e
21
22e
23f
PBu3
CH3CN
DMF
PBu3
PBu3
1,4-dioxane
ethanol
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
2:1
ꢀ
PBu3
PBu3
78
78
79
58
69
77
67
80
3:1
2:1
6:1
6:1
6:1
5:1
5:1
5:1
PBu3
PBu3
PBu3
PBu3
2-thiofuryl (2s)
3-pyridyl (2t)
PBu3
PBu3
E-C6H5ꢀCHdCH- (2u)
1,4-C6H4- (2v)
PBu3
a Typical procedure: allenoate 1a (0.3 mmol) was added under N2
atmosphere to a solution of aldehyde 2a (0.2 mmol) and phosphorus
reagent (0.3 mmol) in the indicated solvent (5 mL). b Combined yield of
4-ClC6H4 (2b)
a Typical conditions: to a stirred solution of aldehyde 2 (0.2 mmol) and
PBu3 (0.3 mmol) in CHCl3 (2.0 mL) was dropwise added a solution of
allenoate 1a (0.3ꢀ0.5 mmol) in CHCl3 (3.0 mL) over 30 min, and the
resulting mixture was stirred for the specified time. b Isolated yield based
c
1
E/Z isomers based on 2a. Based on H NMR analysis of the crude
product. d 2 mL of chloroform was used. e Run at 60 °C. f Allenoate 1a
(0.3 mmol) in chloroform (3 mL) was added dropwise over 30 min to
the solution of aldehyde 2a (0.2 mmol) and PBu3 (0.3 mmol) in
c
on aldehyde 2 as a mixture of E/Z isomers. Ratio for trisubstituted
chloroform (2 mL). g BF3 Et2O (0.03 mmol, 10 mol %) was added.
alkene determined by 1H NMR assay of the crude product 3. d AcOH
(0.2 mmol) and NaOAc (0.2 mmol) were added as additives. e E/Z
ratios of the disubstituted alkene subunit were observed for 3p (5:1), 3t
3
h LiCl (0.3 mmol, 100 mol %) was added. i Water (0.3 mmol, 100 mol %)
was added. j AcOH (0.06 mmol, 20 mol %) was added. k PhOH (0.06
mmol, 20 mol %) was added.
f
(10:1), and 3v (12:1). Benzyl R-methyl allenoate 1b was employed
instead of 1a.
nucleophilic phosphorus reagents were examined. PBu3 was the
best, providing diene 3a in 83% yield with exclusive E-selectivity
for the newly formed disubstituted double bond and a 4:1 E/Z
selectivity for the trisubstituted alkene subunit (Table 1, entry 1).
PPhMe2, PMePh2, PPh3, and 1,3,5-triaza-7-phosphaadamantane
(PTA)17 were also effective but gave diene 3a in lower yields and
stereoselectivity (entries 2ꢀ5). Hexamethyl phosphorus tria-
mide (HMPT) and trimethyl phosphite, however, could not
mediate the reaction (entries 6, 7). With the choice of PBu3,
screening of common solvents revealed that halogenated solvents
such as CHCl3 and CH2Cl2 gave higher yields (entries 1, 8). Such
polar solvents as THF, CH3CN, DMF, 1,4-dioxane, and ethanol
were detrimental to the reaction (entries 10ꢀ14). A higher con-
centration of substrates or an elevated reaction temperature
resulted in the decrease of E/Z selectivity (entries 15, 16). In
contrast, slow addition of allenoate 1a to the reaction mixture to
maintain a low concentration of 1a improved E/Z selectivity of
3a (6:1) (entry 17). Addition of Lewis acid BF3 or LiCl did not
improve either E/Z selectivity or yield of product 3a (entries 18,
19). Additional protic additives such as water, acetic acid, and
phenol also failed to improve the reaction efficiency (entries
20ꢀ22). Thus, the optimized conditions were established: PBu3
used as the phosphine mediator, chloroform as the solvent, at
room temperature, and slow addition of the allenoate 1a.
Substrate Scope. Under the optimized conditions, the scope
of the PBu3-mediated vinylogous Wittig reaction of 1a was
investigated. Benzaldehydes bearing either electron-donating
or -withdrawing substituents at ortho, meta, or para positions all
worked well, giving vinylogous Wittig products 3 in fair to excel-
lent yields (Table 2, entries 1ꢀ16). 1-Naphthyl aldehyde and
heteroaromatic aldehydessuchas2-furyl, 2-thiofuryl, and 3-pyridyl
aldehydes were also effective, furnishing the corresponding
products in good yields (entries 17ꢀ20). The substrate scope
was further extended to R,β-unsaturated aldehydes and dialde-
hydes, affording the corresponding triene and tetraene products
7529
dx.doi.org/10.1021/jo201466k |J. Org. Chem. 2011, 76, 7528–7538

The Journal of Organic Chemistry
ARTICLE
Scheme 2. Investigations on r,γ-Dimethyl Allenoate 1c and
R-Methyl γ-Phenyl Allenoate 1d
Scheme 3. A Proposed Retro-DielsꢀAlder (rDA) Pathway
for Vinylogous Wittig Reaction
Scheme 4. Deuterium-Labeling Experiments
in good yields (entries 21, 22). But alkyl aldehydes such as
propyl, butyl, and neopentyl aldehydes all failed in giving the
vinylogous olefination products. Variation of the ester group of
1a did not interfere with the vinylogous Wittig reaction, as shown
in the case of benzyl R-methyl allenoate 1b (entry 23). Of note is
that substituent introduction to the γ-carbon of allenoate 1a,
however, deflected the reaction. For example, R,γ-dimethyl
allenoate 1c produced a complex mixture, while R-methyl
γ-phenyl allenoate 1d gave a dimerization product D1 under
the standard conditions (Scheme 2). Of all cases, the vinylogous
Wittig olefination exhibited exclusive E-selectivity for the newly
formed disubstituted alkene except for products 3p, 3t, and 3v
(E/Z ratios of 5:1 to 12:1, Table 2, entries 16, 20, and 22). In
contrast, the trisubstituted alkene subunit, which was regener-
ated from the allenic double bonds, showed only a modest E/Z
selectivity in all of products 3 (Table 2). The structure and
geometry assignments for dienes 3 were determined by 1D and
2D NMR spectroscopy and further confirmed by X-ray crystal-
Table 3. Entrapment and Isolation of Intermediates from the
Reaction of 1a and Phosphinesa
1
lographic analysis. H NMR data provided diagnostic evidence
on the E-configuration assignment of the disubstituted double
bonds of 3 by the coupling constant magnitude (ca. 16 Hz)
between the olefinic protons Ha and Hb. The E/Z configuration
for the trisubstituted double bonds of 3 was assigned according
to the chemical shift of the vinylic proton Hc, which is about
0.7 ppm downfield for the E isomer compared with that for the Z
isomer, and was further confirmed by NOESY analysis of product
(E,E)-3p. In addition, X-ray crystallographic analysis for (E,E)-3l
(CCDC 829382) provided unambiguous evidence for the struc-
ture and stereochemistry assignments of products 3 (see Sup-
porting Information).
Mechanism Investigation. A retro-DielsꢀAlder (rDA) path-
way, first proposed by Corey,10 was often adopted to interpret
the formation of vinylogous olefination products as well as stereo
outcomes (Scheme 3).9,12 In such a mechanism, an allylic
phosphorus ylide initially adds to an aldehyde at the γ-carbanion,
followed by a H-shift to form a six-membered 1,2-oxaphospho-
nine which subsequently undergoes a retro-DielsꢀAlder (rDA)
reaction to fulfill a vinylogous Wittig transformation. This mech-
anism benefits from the ability of allylic phosphorus ylide to
undertake γ-addition on aldehydes.18ꢀ20 Yet, theoretical or
experimental evidence for it remains elusive. To account for
formation of dienes 3 in this work, we found that the retro-
DielsꢀAlder pathway is, however, quite contradictory to the
observed distinct stereoselectivities of the di- and trisubstituted
double bonds of product 3. To pursue an accurate mechanism,
we then focused on mechanistic investigations.
entry
PR3
PBu3
HA
4, yield (%)b
5, yield (%)b, E/Zc
1
2
CF3CO2H
CF3CO2H
CF3CO2H
AcOH
4a, 99
4b, 99
4c, 94
ꢀ
ꢀ
PPhMe2
PPh3
ꢀ
3
ꢀ
4
PBu3
5a, 89, 6:1
5b, 82, 5:1
5c, 74, 10:1
5d, 94, 8:1
trace
5
PBu3
PhCO2H
PhOH
ꢀ
6
PBu3
ꢀ
7
PPhMe2
PPh3
AcOH
ꢀ
8
AcOH
ꢀ
9
PBu3
H2O
ꢀ
ꢀ
trace
10
PBu3
EtOH
ꢀ
a For details, see Experiment Section. b Isolated yield. c Determined by
31P NMR assay.
R-methyl-deuterated allenoate 1a-d3 (purity >99%) was reacted
with PBu3 and p-chlorobenzaldehyde 2b, affording a 94% yield of
3b-d5 with ca. 20% deuterium incorporations at the β, β0, and
γ-carbons. Normal allenoate 1a also afforded 3b-d5 in 87% yield
with similar deuterium distribution when 1.5 equiv of D2O was
introduced into the reaction. These results pointed to the
involvement of water in a set of proton transfers of this olefina-
tion reaction.21ꢀ23 They also suggested that the H/D exchanges
might occur prior to the olefination, for there was no detectable
deuterium incorporation at the olefinic carbon originated from
the aldehyde in 3b-d5.
First, deuterium-labeling experiments were conducted to
probe the mechanism (Scheme 4). Under standard conditions,
7530
dx.doi.org/10.1021/jo201466k |J. Org. Chem. 2011, 76, 7528–7538

The Journal of Organic Chemistry
ARTICLE
Intrigued by the results from deuterium-labeling experiments,
we intended to investigate the transformations between allenoate
1a and phosphines (PBu3, PPhMe2, and PPh3) in the presence of a
series of protic additives. To our delight, two kinds of phosphonium
salts 4 and 5 were successfully isolated with the aid of appropriately
acidic additives (Table 3). With trifluoroacetic acid (TFA), the
reactions of 1a with all three selected phosphines produced cor-
responding vinylphosphonium salts 4 in almost quantitative yields
(entries 1ꢀ3). Replacing TFA with a weakly acidic additive such as
acetic acid, benzoic acid, and phenol led to the isolation of an allylic
phosphonium salt 5 in good yield with 5:1 to 10:1 Z/E ratio from
the reaction of 1a and PBu3 (entries 4ꢀ6). In the presence of acetic
acid, PPhMe2 also afforded the corresponding allylic phosphonium
salt 5d in 94% yield and 8:1 Z/E ratio (entry 7), but weakly
nucleophilic PPh3 failed (entry 8).24ꢀ26 In contrast, using neutral
protic additives such as water and ethanol, neither corresponding
phosphonium salts 4 nor 5 could be trapped and isolated from
the reaction of 1a and PBu3 (entries 9, 10). Isolated phospho-
nium salts 4 and 5 were fully identified by spectrometric methods
To gain more mechanistic information, the reaction of 1a and
PBu3 was run in CDCl3 with acetic acid or benzoic acid used as
the additive, and monitored by 31P and 1H NMR spectroscopy
(Figures 1 and 2). Gratifyingly, the NMR monitoring experi-
ments clearly unveiled the transformation process of 1a to the
allylic phosphonium salt 5a. As shown in a 31P NMR monitoring
experiment (Figure 1), vinylphosphonium salts A and B were
detected shortly after 1a and PBu3 were mixed in an NMR tube,
and they lasted in the reaction mixture for up to 2 h. The signal of
free PBu3 diminished after 40 min, and at that time, an allylic
phosphonium salt C gradually appeared in the NMR spectra. The
signals from allylic phosphonium salt 5a as a pair of Z/E isomers
became observable after 15 min, and their intensities gradually
increased as the reaction proceeded. In the period from 60 min to
2 h, intermediates A, B, and C and product 5a accounted for all
phosphorus-containing species in the reaction. After 12 h, the
reaction was complete and exclusively gave allylic phosphonium
salt 5a.27 The transformation process of 1a to the allylic phos-
phonium salt 5a was also monitored by 1H NMR spectroscopy
(Figure 2). The assigned structures of intermediates A, B, and C
were highly consistent with both 1H and 31P NMR data. Inter-
mediate A could be identified by analogy with the well-identified
analogue4a. The assigned structure of intermediate B was strongly
supported by the signals of a singlet (δ 2.12 ppm, CH3) and a
1
including HRMS, 1D-NMR (31P, H, 13C) and 2D-COSY,
HMQC, and NOESY (see Supporting Information).
Formation of vinylphosphonium salts 4 most likely results
from the nucleophilic addition of tertiary phosphine to allenoate
1a followed by protonation with TFA; however, the occurrence
of allylic phosphonium salts 5 in which the phosphorus moiety is
attached to the β0-carbon of allenoate 1a represents an unpre-
cedented process.
1
doublet (δ 2.16 ppm, JPꢀH = 13.2 Hz, CH3) in H NMR
monitoring spectra at the time scale of 5 min to 2 h. In the
time scale of 40 min to 6 h, two doublets from olefinic protons (δ
6.47 ppm, J = 2.9 Hz and 6.42 ppm, J = 3.9 Hz, vinylic CH2) and
one multiplet at δ 4.43 ppm (CH) in 1H NMR spectra provided
diagnostic evidence for intermediate C. With benzoic acid em-
ployed as the additive, the same NMR monitoring experiments
presented a similar transformation process of 1a to 5b which,
however, proceeded in a slower pace (for detail, see Supporting
Information).
In light of the results from NMR monitoring experiments and
Table 3, we believed that the acetate or benzoate anion also acts
as a base in a set of proton transfers during the transformations
between the intermediates such as A, B, and C. An appropriate
basicity of the conjugate base of an acidic additive should be an
essential prerequisite for the conversion of 1a into allylic phos-
phonium salt 5. As a validation for this speculation, the conver-
sion of vinylphosphonium trifluoroacetate 4a or 4b into the
corresponding 5 could be readily revivified by addition of a base
Figure 1. 31P NMR monitoring of the reaction between 1a, PBu3, and
acetic acid.
Figure 2. 1H NMR monitoring of the reaction between 1a, PBu3, and acetic acid.
7531
dx.doi.org/10.1021/jo201466k |J. Org. Chem. 2011, 76, 7528–7538

The Journal of Organic Chemistry
ARTICLE
Scheme 5. DBU-Aided Formation of 5 from 4
Scheme 8. Plausible Mechanism for PBu3-Mediated Vinylo-
gous Wittig Olefination between 1a and Aldehydes
Scheme 6. Control Experiments
Scheme 9. Reactions of r-Benzyl Allenoate 1e and PBu3 in
the Presence of an Acid
Scheme 7. Formation of the Olefination Product 3b from 5a
depicted in Scheme 8, which features an allylic phosphorus ylide
1,3-rearrangement pathway. Initially, the nucleophilic attack of
PBu3 at allenoate 1a forms a resonance-stabilized zwitterionic
DBU (Scheme 5; for details, also see Supporting Information).
On the other hand, in the formation of allylic phosphonium salt
5a, as shown in Figure 1, the transformation of intermediate C
into 5a represents an allylic phosphonium 1,3-rearrangement28ꢀ30
which presumably proceeds via a phosphine-involved SN20 pathway,
rather than via an intramolecular phosphonium 1,3-migration. A 31P
NMR monitoring experiment clearly revealed that the signal of inter-
mediate C did not show up until the concentration of free PBu3
substantially decreased (Figure 1). Control experiments also provided
solid evidence for the phosphine-involved SN20 pathway (Scheme 6):
addition of PPhMe2 resulted in the formation of 5f from vinylphos-
phonium salt 4a under the mediation of DBU by interception of a
trifluoroacetate analogue of intermediate C, and no detectable
phosphine exchange was observed between 5a (an analogue of 5e)
and PPhMe2 (for detail, see Supporting Information).
The normal Wittig olefination of allylic phosphonium salt 5a
with p-chlorobenzaldehyde 2b may build a bridge between the
formation of allylic phosphonium salt 5 and the occurrence of
vinylogous Wittig olefination of allenoate 1a. Under the aid of
K2CO3, the olefination product 3b was readily obtained in 61%
yield (Scheme 7). Notably, the stereoselectivity of 3b in this
stepwise synthesis (exclusive E-configuration for newly formed
alkene and 4:1 E/Z ratio for the regenerated ones) was in good
consistency with that observed in the vinylogous Wittig reaction
of 1a and 2b (Table 2, entry 2). Additionally, with a mixture of
AcOHꢀNaOAc (1:1) used as an additive, the vinylogous Wittig
olefination of allenoate 1a and electron-deficient 3-nitrobenzal-
dehyde 2p proceeded well, giving diene 3p in 40% yield (Table 2,
entry 16). The above results strongly point to a hypothesis that
an allylic phosphonium salt such as 5a is a key intermediate for
stereoselective formation of the vinylogous Wittig product 3.
On the basis of the above mechanistic findings, a plausible
mechanism for the vinylogous Wittig reaction of this study is
intermediate 7. Through a water-aided hydrogen shift,16,21ꢀ23
7
reversibly converts into an allylic phosphorus ylide I,31 which is
subsequently protonated with adventitious protic additives, e.g.,
water, yielding allylic phosphonium salt 8. An allylic phospho-
nium 1,3-rearrangement of 8 via a PBu3-involved SN20 process
then generates phosphonium salt 9, which undergoes deproto-
nation by hydroxyl anion to produce a rearranged allylic phos-
phorus ylide II. Finally, a normal Wittig olefination of the ylide II
with aldehyde accomplishes the formation of diene 3. By this
mechanism, the high stereoselectivity of the PBu3-mediated
vinylogous Wittig olefination could be well rationalized in terms
of the Wittig reaction of a stabilized allylic phosphorus ylide II
under neutral and salt-free conditions.15,32 Although an intra-
molecular allylic phosphonium 1,3-migration process was also
proposed by Corey10 as one of three possible mechanistic path-
ways for vinylogous Wittig reaction, it was not determined how
it worked. On the basis of experimental investigations, our mech-
anism is explicitly defined as an allylic phosphorus ylide 1,3-
rearrangement pathway which encompasses an allylic phospho-
nium 1,3-rearrangement via a phosphine-involved SN20 process,
while its validity for other allylic phosphorus ylides, including
Corey’s, needs further efforts to verify.
To rationalize the distinct reactivity between R-methyl alleno-
ate 1a and R-benzyl allenoate 1e (normal Wittig reaction),16
reactions of R-benzyl allenoate 1e and PBu3 in the presence of an
acidic additive were conducted (Scheme 9). When allenoate 1e,
PBu3 and equivalent TFA were mixed, a vinylphosphonium salt
10 which is analogous to 4 was obtained in almost quantitative
yield. Interestingly, using acetic acid as the additive, an unrear-
ranged allylic phosphonium salt 11 was solely isolated in 65%
7532
dx.doi.org/10.1021/jo201466k |J. Org. Chem. 2011, 76, 7528–7538

The Journal of Organic Chemistry
ARTICLE
yield under otherwise the same conditions. Presumably, the
steric hindrance imposed by the phenyl group retards subsequent
allylic phosphonium 1,3-rearrangement of 11 which leads to a
vinylogous Wittig transformation. Furthermore, identification of
11 also corroborates the existence of the intermediates C and 8.
Mechanistic findings in this work also provide supportive evi-
dence for typical mechanisms of extensively studied phosphine-
mediated reactions of allenoates.33ꢀ35 Though generation of a
putative zwitterionic intermediate such as 7 through nucleophilic
attack of a tertiary phosphine on an allenoate has been commonly
proposed, this type of intermediate has never been directly ob-
served.36 The successful entrapment and identification of vinyl-
phosphonium salts 4 and 10 and direct NMR observation of
intermediates such as A and B (Figure 1) provide solid evidence
for the true existence of the zwitterionic intermediate 7, for these
phosphorus-containing species are most likely generated from
the in situ protonation of the zwitterionic intermediate 7 by the
corresponding acidic protic additive. In addition, formation of
the similar allylic phosphorus ylide I is commonly proposed in
the mechanisms of the phosphine-mediated reactions of R-alkyl
allenoates.16,25,26,37,38 Identification of allylic phosphonium salt
11 and the intermediates such as C (Figure 1, 2), which are most
likely generated from protonation of the corresponding allylic
phosphorus ylide I, certainly validates those plausible mechan-
isms. It is also noteworthy that NMR monitoring experiments in
this work highly corroborate the computational studies by Yu on
a water-catalyzed [1,4]-proton shift process.38
experiments were conducted in CDCl3 with 85% H3PO4 as the external
standard.
Synthesis of Benzyl 2-Methylbuta-2,3-dienoate 1b45. To a
stirred solution of (benzyloxycarbonylmethylidene)triphenylphosphorane
(12.30 g, 30 mmol) in chloroform (50 mL) was added 1.1 equiv of
iodomethane (4.69 g, 33 mmol) at room temperature. The reaction
mixture was refluxed for 24 h, and all volatile components were eva-
porated under reduced pressure. The resulting phosphonium salt was
dissolved in anhydrous dichloromethane (100 mL), and 2.2 equiv of
triethylamine (6.67 g, 66 mmol) was added. After the resulting mixture
was stirred for 2 h, a solution of 1.1 equiv of acetyl chloride (2.59 g,
33 mmol) in dichloromethane (30 mL) was dropwise added over 30 min
at 0 °C. The reaction mixture was then allowed to warm to room
temperature and stirred for additional 4 h. After most of the solvent was
carefully distilled, the residue was thoroughly extracted with petroleum
ether (bp 30ꢀ60 °C, 5 ꢁ 60 mL). The combined extract was con-
centrated, and the residue was subjected to column chromatography on
silica gel (eluant: 5% EtOAc in petroleum ether) to give allenoate 1b
as slightly yellow oil (2.65 g, yield 47%). 1H NMR (400 MHz, CDCl3)
δ 7.33 (m, 5H), 5.20 (s, 2H), 5.09 (m, 2H), 1.90 (m, 3H); 13C NMR
(100 MHz, CDCl3) δ 214.3, 167.4, 136.2, 128.5, 128.0, 127.8, 95.3, 78.0,
66.5, 14.7; HRMS-ESI calcd for C12H12O2 [M + Na]+ 211.0730, found
211.0737.
General Procedure for the Vinylogous Wittig Olefination.
A solution of allenoate 1a or 1b (0.3 mmol) in chloroform (3.0 mL) was
slowly dropwise added over 30 min to a stirred solution of PBu3 (71 μL,
0.3 mmol) and aldehyde 2 (0.2 mmol) in chloroform (2.0 mL) at room
temperature. After 12 h, aldehyde 2 was completely consumed in most
cases, as monitored by TLC. For less reactive aldehydes, additional
allenoate 1 and PBu3 (0.1ꢀ0.2 mmol) were added by means of micro-
syringe, and the reaction mixture was stirred for a further 12ꢀ24 h. A
sample was then taken from the reaction mixture for 1H NMR assay to
determine the E/Z ratio of the product 3. The solvent was removed
under reduced pressure, and the residue was purified through column
chromatography on silica gel (gradient eluant: 1ꢀ5% diethyl ether in
petroleum ether) to afford the diene 3 as a pair of E/Z isomers with
respect to its trisubstituted double bonds.
Ethyl 2-Styrylbut-2-enoate (3a). Following the general procedure,
the reaction of allenoate 1a (38 mg, 0.3 mmol), benzaldehyde (21 mg,
0.2 mmol), and PBu3 (71 μL, 0.3 mmol) was performed for 12 h to
afford 3a as an inseparable stereoisomeric mixture in 79% yield; (2E,4E)-
3a:(2Z,4E)-3a = 6:1; colorless oil; NMR data for (2E,4E)-3a: 1H NMR
(400 MHz, CDCl3) δ 7.46 (d, J = 7.5 Hz, 2H), 7.33 (m, 2H), 7.24 (m,
1H), 7.04 (d, J = 16.4 Hz, 1H), 6.90 (d, J = 16.4 Hz, 1H), 6.86 (q, J = 7.4
Hz, 1H), 4.26 (q, J = 7.1 Hz, 2H), 2.00 (d, J = 7.4 Hz, 3H), 1.33 (t, J = 7.1
Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 167.1, 138.0, 137.6, 133.5,
131.2, 128.6, 127.7, 126.5, 120.8, 60.6, 14.7, 14.3; selected NMR data for
(2Z,4E)-3a: 1H NMR (400 MHz, CDCl3) δ 7.38 (d, J = 7.5 Hz, 2H),
6.74 (d, J = 16.3 Hz, 1H), 6.60 (d, J = 16.3 Hz, 1H), 6.12 (q, J = 7.3 Hz,
1H), 4.35 (q, J = 7.1 Hz, 2H), 1.96 (d, J = 7.3 Hz, 3H), 1.38 (t, J = 7.1 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ 167.6, 137.2, 134.3, 133.8, 129.2,
127.5, 126.7, 126.4, 60.7, 15.6, 14.3; HRMS-ESI calcd for C14H16O2
[M + Na]+ 239.1042, found 239.1047.
’ CONCLUSION
We have developed a highly stereoselective PBu3-mediated
vinylogous Wittig reaction between R-methyl allenoates and a
variety of aldehydes as a facile synthetic protocol for trisubsti-
tuted 1,3-dienes. This reaction represents the first example of
practical and synthetically useful vinylogous Wittig reaction. On
the basis of a series of mechanistic investigations, a reliable mech-
anism for the vinylogous Wittig reaction is proposed, which fea-
tures a water/phosphine-coassisted allylic phosphorus ylide 1,3-
rearrangement pathway, rather than previous retro-DielsꢀAlder
ones. Mechanistic insights from this work will benefit the devel-
opment of vinylogous Wittig reactions. Mechanistic investiga-
tions of this work also provide useful experimental evidence for
typical mechanisms of actively studied phosphine-mediated
reactions of allenoates including [3 + 2] and [4 + 2] annula-
tions,39,40 γ-umpolung41ꢀ43 and β0-umpolung additions,25,26
and others.16 Isolation and identification of phosphonium salts
4, 5, 10, and 11, and direct spectrometric observation of the
transformation process between intermediates A, B, and C give
illuminating information for the better understanding those
reactions. Our future efforts will be directed toward further in-
vestigation on vinylogous Wittig reactions and developing new
phosphine-mediated synthetic reactions of allenoates.
Ethyl 2-(4-Chlorostyryl)but-2-enoate (3b). Following the general
procedure, the reaction of allenoate 1a (38 mg, 0.3 mmol), 4-chlor-
obenzaldehyde (28 mg, 0.2 mmol), and PBu3 (71 μL, 0.3 mmol) was
performed for 12 h to afford 3b as a colorless oil in 96% yield; (2E,4E)-
3b:(2Z,4E)-3b = 5:1; NMR data for (2E,4E)-3b: 1H NMR (400 MHz,
CDCl3) δ 7.38 (d, J = 8.5 Hz, 2H), 7.29 (d, J = 8.5 Hz, 2H), 7.01 (d, J =
16.4 Hz, 1H), 6.88 (q, J = 7.4 Hz, 1H), 6.87 (d, J = 16.4 Hz, 1H), 4.26 (q,
J = 7.1 Hz, 2H), 2.00 (d, J = 7.4 Hz, 3H), 1.34 (t, J = 7.1 Hz, 3H); 13C
NMR (100 MHz, CDCl3) δ 167.0, 138.5, 136.0, 133.3, 132.1, 130.9,
128.7, 127.7, 121.3, 60.7, 14.7, 14.2; selected NMR data for (2Z,4E)-3b:
1H NMR (400 MHz, CDCl3) δ 6.70 (d, J = 16.3 Hz, 1H), 6.55
’ EXPERIMENTAL SECTION
Unless otherwise noted, all reactions were carried out under a nitro-
gen atmosphere. Column chromatography was performed on silica gel
(200ꢀ300 mesh). R-Substituted allenoates 1a,cꢀe and R-methyl-
deuterated allenoate 1a-d3 are known compounds, which were prepared
by previous procedures.40,44 Allenoate 1b was prepared by a similar
method from the literature.44 1H and 13C NMR spectra were recorded in
CDCl3 with tetramethylsilane as the internal reference. 31P NMR
7533
dx.doi.org/10.1021/jo201466k |J. Org. Chem. 2011, 76, 7528–7538

The Journal of Organic Chemistry
ARTICLE
(d, J = 16.3 Hz, 1H), 6.14 (q, J = 7.3 Hz, 1H), 4.35 (q, J = 7.1 Hz, 2H),
1.96 (d, J = 7.3 Hz, 3H), 1.38 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 167.5, 140.0, 136.0, 134.5, 133.3, 130.9, 127.6, 123.7, 60.8,
15.8, 14.3; HRMS-ESI calcd for C14H15ClO2 [M + Na]+ 273.0653,
found 273.0656.
3H), 1.34 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 167.0,
162.4 (d, JCF = 247.2 Hz), 138.1, 133.7 (d, JCF = 3.2 Hz), 132.1, 131.0,
128.0 (d, JCF = 7.9 Hz), 120.5 (d, JCF = 1.9 Hz), 115.5 (d, JCF = 21.7 Hz),
60.6, 14.7, 14.2; selected NMR data for (2Z,4E)-3f: 1H NMR (400 MHz,
CDCl3) δ 7.35 (t, J = 6.1 Hz, 2H), 6.66 (d, J = 16.4 Hz, 1H), 6.56 (d,
J = 16.4 Hz, 1H), 6.12 (q, J = 7.3 Hz, 1H), 4.35 (q, J = 7.1 Hz, 2H), 1.96
(d, J = 7.3 Hz, 3H), 1.38 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz,
Ethyl 2-(3-Chlorostyryl)but-2-enoate (3c). Following the general
procedure, the reaction of allenoate 1a (38 mg, 0.3 mmol), 3-chlor-
obenzaldehyde (28 mg, 0.2 mmol), and PBu3 (71 μL, 0.3 mmol) was
performed for 12 h to afford 3c as a colorless oil in 99% yield; (2E,4E)-
3c:(2Z,4E)-3c = 5:1; NMR data for (2E,4E)-3c: 1H NMR (400 MHz,
CDCl3) δ 7.44 (s, 1H), 7.31 (d, J = 7.4 Hz, 1H), 7.22 (m, 2H), 7.01 (d,
J = 16.4 Hz, 1H), 6.91 (m, 2H), 4.26 (q, J = 7.1 Hz, 2H), 2.01 (d, J = 7.4
Hz, 3H), 1.34 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 166.8,
139.5, 139.0, 134.5, 132.0, 130.8, 129.8, 127.6, 126.2, 124.8, 122.1, 60.7,
CDCl3) δ 167.6, 162.4 (d, JCF = 247.3 Hz), 139.9, 131.8, 127.9 (d, JCF
=
8.5 Hz), 126.5 (d, JCF = 1.9 Hz), 115.1 (d, JCF = 21.5 Hz), 60.7, 15.7,
14.3; HRMS-ESI calcd for C14H15FO2 [M + Na]+ 257.0948, found
257.0952.
Ethyl 2-(4-Iodostyryl)but-2-enoate (3g). Following the general pro-
cedure, the reaction of allenoate 1a (51 mg, 0.4 mmol), 4-iodobenzal-
dehyde (46 mg, 0.2 mmol), and PBu3 (95 μL, 0.4 mmol) was performed
for 24 h to afford 3g as a colorless oil in 92% yield; (2E,4E)-3g:(2Z,4E)-
3g = 5:1; NMR data for (2E,4E)-3g: 1H NMR (400 MHz, CDCl3) δ
7.65 (d, J = 8.2 Hz, 2H), 7.18 (d, J = 8.2 Hz, 2H), 6.98 (d, J = 16.4 Hz,
1H), 6.89 (d, J = 16.4 Hz, 1H), 6.88 (q, J = 7.4 Hz, 1H), 4.26 (q, J = 7.1
Hz, 2H), 1.99 (d, J = 7.4 Hz, 3H), 1.33 (t, J = 7.1 Hz, 3H); 13C NMR
(100 MHz, CDCl3) δ 167.0, 138.7, 137.6, 137.0, 132.2, 131.0, 128.1,
1
14.7, 14.2; selected NMR data for (2Z,4E)-3c: H NMR (400 MHz,
CDCl3) δ 7.37 (s, 1H), 6.73 (d, J = 16.3 Hz, 1H), 6.54 (d, J = 16.3 Hz,
1H), 6.16 (q, J = 7.3 Hz, 1H), 4.35 (q, J = 7.1 Hz, 2H), 1.97 (d, J = 7.3 Hz,
3H), 1.38 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 167.3,
139.1, 135.1, 133.9, 131.5, 128.1, 127.7, 127.4, 126.2, 124.6, 60.8, 15.8,
14.3; HRMS-ESI calcd for C14H15ClO2 [M + Na]+ 273.0653, found
273.0656.
1
121.4, 93.0, 60.7, 14.8, 14.2; selected NMR data for (2Z,4E)-3g: H
Ethyl 2-(4-Bromostyryl)but-2-enoate (3d). Following the general
procedure, the reaction of allenoate 1a (38 mg, 0.3 mmol), 4-bromo-
benzaldehyde (37 mg, 0.2 mmol), and PBu3 (71 μL, 0.3 mmol) was
performed for 12 h to afford 3d as a colorless oil in 71% yield; (2E,4E)-
3d:(2Z,4E)-3d = 5:1; NMR data for (2E,4E)-3d: 1H NMR (400 MHz,
CDCl3) δ 7.45 (d, J = 8.4 Hz, 2H), 7.32 (d, J = 8.4 Hz, 2H), 7.00 (d, J =
16.4 Hz, 1H), 6.89 (d, J = 16.4 Hz, 1H), 6.89 (q, J = 7.4 Hz, 1H), 4.26 (q,
J = 7.1 Hz, 2H), 2.00 (d, J = 7.4 Hz, 3H), 1.34 (t, J = 7.1 Hz, 3H); 13C
NMR (100 MHz, CDCl3) δ 167.0, 138.7, 136.5, 132.2, 131.7, 130.9,
128.0, 127.9, 121.4, 60.7, 14.8, 14.3; selected NMR data for (2Z,4E)-3d:
1H NMR (400 MHz, CDCl3) δ 7.25 (d, J = 8.4 Hz, 2H), 6.72 (d, J = 16.3
Hz, 1H), 6.54 (d, J = 16.3 Hz, 1H), 6.15 (q, J = 7.3 Hz, 1H), 4.35 (q, J =
7.1 Hz, 2H), 1.96 (d, J = 7.3 Hz, 3H), 1.38 (t, J = 7.1 Hz, 3H); 13C NMR
(100 MHz, CDCl3) δ 134.7, 134.1, 132.5, 131.0, 127.5, 121.6, 60.8, 15.8,
14.4; HRMS-ESI calcd for C14H15BrO2 [M + Na]+ 317.0148, found
317.0142.
NMR (400 MHz, CDCl3) δ 7.11 (d, J = 8.2 Hz, 2H), 6.72 (d, J = 16.2
Hz, 1H), 6.52 (d, J = 16.2 Hz, 1H), 6.14 (q, J = 7.4 Hz, 1H), 4.34 (q, J =
7.1 Hz, 2H), 1.95 (d, J = 7.4 Hz, 3H), 1.37 (t, J = 7.1 Hz, 3H); 13C NMR
(100 MHz, CDCl3) δ 167.4, 137.3, 134.7, 134.0, 128.1, 128.0, 127.4,
92.7, 60.8, 15.8, 14.3; HRMS-ESI calcd for C14H15IO2 [M + Na]+
365.0009, found 365.0008.
Ethyl 2-(3-Bromo-4-methoxystyryl)but-2-enoate (3h). Following
the general procedure, the reaction of allenoate 1a (38 mg, 0.3 mmol),
3-bromo-4-methoxybenzaldehyde (43 mg, 0.2 mmol), and PBu3 (71 μL,
0.3 mmol) was performed for 12 h to afford 3h as a colorless oil in 82%
yield; (2E,4E)-3h:(2Z,4E)-3h = 6:1; NMR data for (2E,4E)-3h: 1H NMR
(400 MHz, CDCl3) δ 7.68 (d, J = 2.1 Hz, 1H), 7.33 (dd, J = 8.5, 2.1 Hz,
1H), 6.94 (d, J= 16.4 Hz, 1H), 6.84 (m, 2H), 6.77 (d, J= 16.4 Hz, 1H), 4.26
(q, J= 7.1 Hz, 2H), 3.90 (s, 3H), 2.00 (d, J = 7.4 Hz, 3H), 1.34 (t, J= 7.1 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ 167.0, 155.5, 137.9, 131.8, 131.5,
131.0, 130.9, 127.0, 120.0, 112.0, 111.8, 60.7, 56.3, 14.7, 14.3; selected NMR
data for (2Z,4E)-3h: 1H NMR (400 MHz, CDCl3) δ 7.60 (d, J = 2.1 Hz,
1H), 7.27 (m, 1H), 6.61 (d, J = 16.2 Hz, 1H), 6.48 (d, J= 16.2 Hz, 1H), 6.10
(q, J= 7.4 Hz, 1H), 4.34 (q, J= 7.1 Hz, 2H), 3.89 (s, 3H), 1.95 (d, J=7.3Hz,
3H), 1.38 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ155.3, 133.7,
131.5, 127.3, 126.8, 126.1, 60.7, 56.3, 15.7, 14.3; HRMS-ESI calcd for
C15H17BrO3 [M + Na]+ 347.0253, found 347.0247.
Ethyl 2-(2-Fluorostyryl)but-2-enoate (3e). Following the general
procedure, the reaction of allenoate 1a (38 mg, 0.3 mmol), 2-fluor-
obenzaldehyde (25 mg, 0.2 mmol), and PBu3 (71 μL, 0.3 mmol) was
performed for 12 h to afford 3e as a colorless oil in 77% yield; (2E,4E)-
3e:(2Z,4E)-3e = 5:1; NMR data for (2E,4E)-3e: 1H NMR (400 MHz,
CDCl3) δ 7.55 (t, J = 7.6 Hz, 1H), 7.24 (m, 1H), 7.17 (d, J = 16.6 Hz,
1H), 7.12 (m, 1H), 7.04 (m, 1H), 6.98 (d, J = 16.6 Hz, 1H), 6.91 (q,
J = 7.4 Hz, 1H), 4.27 (q, J = 7.1 Hz, 2H), 2.01 (d, J = 7.4 Hz, 3H), 1.34 (t,
Ethyl 2-(2-Methoxystyryl)but-2-enoate (3i). Following the general
procedure, the reaction of allenoate 1a (64 mg, 0.5 mmol), 2-methox-
ybenzaldehyde (27 mg, 0.2 mmol), and PBu3 (119 μL, 0.5 mmol) was
performed for 36 h to afford 3i as a colorless oil in 75% yield; (2E,4E)-
J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 167.0, 160.4 (d, JCF
249.8 Hz), 138.9, 134.9, 131.2, 128.9 (d, JCF = 8.3 Hz), 127.1 (d, JCF
3.5 Hz), 125.9 (d, JCF = 3.8 Hz), 124.1 (d, JCF = 3.3 Hz), 123.0 (d, JCF
=
=
=
1
3i:(2Z,4E)-3i = 5:1; NMR data for (2E,4E)-3i: H NMR (400 MHz,
10.3 Hz), 115.7 (d, JCF = 22.1 Hz), 60.7, 14.8, 14.2; selected NMR data
for (2Z,4E)-3e: 1H NMR (400 MHz, CDCl3) δ 7.47 (t, J = 7.3 Hz, 1H),
6.83 (d, J = 16.5 Hz, 1H), 6.75 (d, J = 16.5 Hz, 1H), 6.18 (q, J = 7.3 Hz,
1H), 4.36 (q, J = 7.1 Hz, 2H), 1.97 (d, J = 7.3 Hz, 3H), 1.38 (t, J = 7.1 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ 167.5, 160.2 (d, JCF = 249.8 Hz),
CDCl3) δ 7.52 (dd, J = 7.6, 1.4 Hz, 1H), 7.33 (d, J = 16.6 Hz, 1H), 7.22
(m, 1H), 6.96 (d, J = 7.6 Hz, 1H), 6.91 (d, J = 16.6 Hz, 1H), 6.85 (m,
2H), 4.26 (q, J = 7.1 Hz, 2H), 3.85 (s, 3H), 2.00 (d, J = 7.4 Hz, 3H), 1.34
(t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 167.4, 157.0, 137.6,
131.8, 128.8, 128.5, 126.5, 124.1, 121.4, 120.6, 110.8, 60.6, 55.5, 14.8,
14.3; selected NMR data for (2Z,4E)-3i: 1H NMR (400 MHz, CDCl3) δ
7.45 (dd, J = 7.6, 1.4 Hz, 1H), 6.77 (d, J = 16.4 Hz, 1H), 6.13 (q, J = 7.3
Hz, 1H), 4.35 (q, J = 7.2 Hz, 2H), 3.83 (s, 3H), 1.96 (d, J = 7.3 Hz, 3H),
1.38 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 167.4, 134.8,
133.3, 128.6, 127.1, 126.7, 126.4, 55.4, 15.7, 14.3; HRMS-ESI calcd for
C15H18O3 [M + Na]+ 269.1148, found 269.1152.
134.3, 128.7 (d, JCF = 8.5 Hz), 126.9 (d, JCF = 3.3 Hz), 125.3 (d, JCF
=
11.9 Hz), 121.5 (d, JCF = 3.5 Hz), 115.7 (d, JCF = 22.1 Hz), 60.8, 15.8,
14.3; HRMS-ESI calcd for C14H15FO2 [M + Na]+ 257.0948, found
257.0947.
Ethyl 2-(4-Fluorostyryl)but-2-enoate (3f). Following the general
procedure, the reaction of allenoate 1a (51 mg, 0.4 mmol), 4-fluor-
obenzaldehyde (25 mg, 0.2 mmol), and PBu3 (95 μL, 0.4 mmol) was
performed for 24 h to afford 3f as a colorless oil in 96% yield; (2E,4E)-
Ethyl 2-(4-Methoxystyryl)but-2-enoate (3j). Following the general
procedure, the reaction of allenoate 1a (64 mg, 0.5 mmol), 4-methox-
ybenzaldehyde (27 mg, 0.2 mmol), and PBu3 (119 μL, 0.5 mmol) was
performed for 36 h to afford 3j as a colorless oil in 77% yield; (2E,4E)-
1
3f:(2Z,4E)-3f = 4:1; NMR data for (2E,4E)-3f: H NMR (400 MHz,
CDCl3) δ 7.43 (t, J = 6.2 Hz, 2H), 7.02 (m, 3H), 6.87 (q, J = 7.3 Hz, 1H),
6.82 (d, J = 16.5 Hz, 1H), 4.27 (q, J = 7.1 Hz, 2H), 2.00 (d, J = 7.3 Hz,
1
3j:(2Z,4E)-3j = 4:1; NMR data for (2E,4E)-3j: H NMR (400 MHz,
7534
dx.doi.org/10.1021/jo201466k |J. Org. Chem. 2011, 76, 7528–7538

The Journal of Organic Chemistry
ARTICLE
CDCl3) δ 7.40 (d, J = 8.7 Hz, 2H), 6.98 (d, J = 16.4 Hz, 1H), 6.87 (d, J =
8.7 Hz, 2H), 6.80 (q, J = 7.4 Hz, 1H), 6.78 (d, J = 16.4 Hz, 1H), 4.26 (q,
J = 7.1 Hz, 2H), 3.81 (s, 3H), 1.99 (d, J = 7.4 Hz, 3H), 1.33 (t, J = 7.1 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ 167.3, 159.4, 137.0, 132.8, 131.3,
130.3, 127.7, 118.7, 114.0, 60.6, 55.2, 14.7, 14.2; selected NMR data for
(2Z,4E)-3j: 1H NMR (400 MHz, CDCl3) δ 7.32 (d, J = 8.7 Hz, 2H),
6.62 (d, J = 16.4 Hz, 1H), 6.53 (d, J = 16.4 Hz, 1H), 6.06 (q, J = 7.3 Hz,
1H), 4.35 (q, J = 7.1 Hz, 2H), 3.80 (s, 3H), 1.94 (d, J = 7.3 Hz, 3H), 1.38
(t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 167.4, 159.2, 132.5,
128.6, 127.6, 124.7, 60.7, 55.2, 15.6, 14.3; HRMS-ESI calcd for
C15H18O3 [M + Na]+ 269.1148, found 269.1144.
Ethyl 2-(4-Methylstyryl)but-2-enoate (3k). Following the general
procedure, the reaction of allenoate 1a (64 mg, 0.5 mmol), 4-methyl-
benzaldehyde (24 mg, 0.2 mmol), and PBu3 (119 μL, 0.5 mmol) was
performed for 36 h to afford 3k as a colorless oil in 72% yield; (2E,4E)-
3k:(2Z,4E)-3k = 5:1; NMR data for (2E,4E)-3k: 1H NMR (400 MHz,
CDCl3) δ 7.35 (d, J = 8.0 Hz, 2H), 7.14 (d, J = 8.0 Hz, 2H), 7.00 (d, J =
16.4 Hz, 1H), 6.86 (d, J = 16.4 Hz, 1H), 6.83 (q, J = 7.5 Hz, 1H), 4.26 (q,
J = 7.1 Hz, 2H), 2.35 (s, 3H), 2.00 (d, J = 7.5 Hz, 3H), 1.33 (t, J = 7.1 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ 167.3, 137.7, 137.5, 134.7, 133.3,
131.3, 129.3, 126.4, 119.8, 60.6, 21.2, 14.7, 14.3; selected NMR data for
(2Z,4E)-3k: 1H NMR (400 MHz, CDCl3) δ 7.28 (d, J = 8.1 Hz, 2H),
6.69 (d, J = 16.3 Hz, 1H), 6.56 (d, J = 16.3 Hz, 1H), 6.09 (q, J = 7.3 Hz,
1H), 4.35 (q, J = 7.1 Hz, 2H), 2.33 (s, 3H), 1.94 (d, J = 7.3 Hz, 3H), 1.38
(t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 167.4, 137.4, 134.5,
133.1, 129.1, 126.3, 125.7, 60.7, 15.7, 14.3; HRMS-ESI calcd for
C15H18O2 [M + Na]+ 253.1199, found 253.1205.
2-(trifluoromethyl)benzaldehyde (35 mg, 0.2 mmol), and PBu3 (95 μL,
0.4 mmol) was performed for 24 h to afford 3n as a colorless oil in 44%
yield; (2E,4E)-3n:(2Z,4E)-3n = 4:1; NMR data for (2E,4E)-3n: H
1
NMR (400 MHz, CDCl3) δ 7.74 (d, J = 7.8 Hz, 1H), 7.65 (d, J = 8.0 Hz,
1H), 7.53 (t, J = 7.5 Hz, 1H), 7.36 (m, 2H), 6.99 (q, J = 7.4 Hz, 1H), 6.89
(d, J = 16.2 Hz, 1H), 4.28 (q, J = 7.1 Hz, 2H), 2.03 (d, J = 7.4 Hz, 3H),
1.35 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 167.0, 139.8,
136.6, 131.8, 131.0, 127.6 (q, JCF = 29.8 Hz), 129.4, 127.3, 126.9, 125.8
(q, JCF = 5.8 Hz), 124.8, 124.3 (q, JCF = 273.9 Hz), 60.9, 14.9, 14.2;
selected NMR data for (2Z,4E)-3n: 1H NMR (400 MHz, CDCl3) δ 7.50
(t, J = 7.5 Hz, 1H), 6.72 (d, J = 15.8 Hz, 1H), 6.22 (q, J = 7.3 Hz, 1H),
4.35 (q, J = 7.2 Hz, 2H), 2.00 (d, J = 7.3 Hz, 3H), 1.39 (t, J = 7.2 Hz, 3H);
13C NMR (100 MHz, CDCl3) δ 167.1, 136.4, 131.7, 130.5, 127.1, 126.8,
15.8, 14.1; HRMS-ESI calcd for C15H15F3O2 [M + Na]+ 307.0920,
found 307.0920.
Ethyl 2-(4-(Trifluoromethyl)styryl)but-2-enoate (3o). Following the
general procedure, the reaction of allenoate 1a (38 mg, 0.3 mmol),
4-(trifluoromethyl)benzaldehyde (35 mg, 0.2 mmol), and PBu3 (71 μL,
0.3 mmol) was performed for 12 h to afford 3o as a colorless oil in 60%
1
yield; (2E,4E)-3o:(2Z,4E)-3o = 4:1; NMR data for (2E,4E)-3o: H
NMR (400 MHz, CDCl3) δ 7.59 (d, J = 8.4 Hz, 2H), 7.54 (d, J = 8.4 Hz,
2H), 7.11 (d, J = 16.4 Hz, 1H), 6.99 (d, J = 16.4 Hz, 1H), 6.94 (q, J = 7.4
Hz, 1H), 4.28 (q, J = 7.1 Hz, 2H), 2.03 (d, J = 7.4 Hz, 3H), 1.35 (t, J = 7.1
Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 166.8, 141.1, 139.5, 132.0,
130.8, 129.5 (q, JCF = 32.3 Hz), 126.6, 125.5 (q, JCF = 3.7 Hz), 124.2 (q,
JCF = 271.7 Hz), 123.2, 60.8, 14.8, 14.3; selected NMR data for (2Z,4E)-
3o: 1H NMR (400 MHz, CDCl3) δ 7.48 (d, J = 8.3 Hz, 2H), 6.82 (d, J =
16.3 Hz, 1H), 6.64 (d, J = 16.3 Hz, 1H), 6.21 (q, J = 7.3 Hz, 1H), 4.36 (q,
J = 7.1 Hz, 2H), 1.99 (d, J = 7.3 Hz, 3H), 1.39 (t, J = 7.1 Hz, 3H); 13C
NMR (100 MHz, CDCl3) δ 167.3, 135.9, 133.9, 129.2, 127.7, 60.8, 15.8,
14.3; HRMS-ESI calcd for C15H15F3O2 [M + Na]+ 307.0920, found
307.0918.
Ethyl 2-(3-Methoxy-2-nitrostyryl)but-2-enoate (3l). Following the
general procedure, the reaction of allenoate 1a (38 mg, 0.3 mmol),
3-methoxy-2-nitrobenzaldehyde (36 mg, 0.2 mmol), and PBu3 (71 μL,
0.3 mmol) was performed for 12 h to afford 3l as a semisolid in 65%
yield; (2E,4E)-3l:(2Z,4E)-3l = 3:1; pure (2E,4E)-3l was obtained by
recrystallization from a mixture of ethyl acetateꢀhexanes (1:20, V/V) as
Ethyl 2-(3-Nitrostyryl)but-2-enoate (3p):12. Following the general
procedure, the reaction of allenoate 1a (38 mg, 0.3 mmol), 3-nitroben-
zaldehyde (30 mg, 0.2 mmol), PBu3 (71 μL, 0.3 mmol), AcOH (12 mg,
0.2 mmol), and AcONa (16 mg, 0.2 mmol) was performed for 12 h to
afford 3p as a semisolid in 40% yield; (2E,4E)-3p:(2Z,4E)-3p:(2E,4Z)-
3p = 4:1:1; pure (2E,4E)-3p was obtained by recrystallization from a
mixture of ethyl acetateꢀhexanes (1:20, V/V) as a yellow solid, mp
57ꢀ58 °C; NMR data for (2E,4E)-3p: 1H NMR (400 MHz, CDCl3) δ
8.31 (s, 1H), 8.09 (dd, J = 8.0, 1.5 Hz, 1H), 7.75 (d, J = 8.0 Hz, 1H), 7.51
(t, J = 8.0 Hz, 1H), 7.16 (d, J = 16.4 Hz, 1H), 7.03 (d, J = 16.4 Hz, 1H),
6.98 (q, J = 7.4 Hz, 1H), 4.28 (q, J = 7.1 Hz, 2H), 2.05 (d, J = 7.4 Hz, 3H),
1.35 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 166.6, 148.6,
140.1, 139.4, 132.4, 130.9, 130.4, 129.5, 123.5, 122.2, 120.9, 60.8, 14.9,
14.3; HRMS-ESI calcd for C14H15NO4 [M + Na]+ 284.0893, found
284.0888.
1
colorless crystals, mp 52ꢀ54 °C; NMR data for (2E,4E)-3l: H NMR
(400 MHz, CDCl3) δ 7.39 (t, J = 8.2 Hz, 1H), 7.25 (d, J = 7.6 Hz, 1H),
7.00 (q, J = 7.4 Hz, 1H), 6.96 (d, J = 16.3 Hz, 1H), 6.93 (d, J = 7.8Hz, 1H),
6.86(d, J = 16.3 Hz, 1H), 4.25(q, J = 7.1Hz, 2H), 3.90 (s, 3H), 1.99(d, J =
7.4 Hz, 3H), 1.33 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ
166.6, 150.8, 140.9, 138.2, 131.1, 130.7, 130.4, 126.2, 125.5, 117.7, 111.2,
60.9, 56.4, 15.0, 14.2; selected NMR data for (2Z,4E)-3l: 1H NMR (400
MHz, CDCl3) δ 7.19 (d, J = 8.1 Hz, 1H), 6.81 (d, J = 16.0 Hz, 1H), 6.50
(d, J = 16.0 Hz, 1H), 6.27 (q, J = 7.4 Hz, 1H), 4.32 (q, J = 7.2 Hz, 2H), 3.89
(s, 3H), 2.01 (d, J = 7.4 Hz, 3H), 1.37 (t, J = 7.2 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ 166.7, 133.9, 132.1, 128.8, 126.4, 121.0, 111.0, 16.0, 14.2;
HRMS-ESI calcd for C15H17NO5 [M + Na]+ 314.0999, found 314.0993.
Ethyl 2-(4-Methoxycarbonylstyryl)but-2-enoate (3m). Following
the general procedure, the reaction of allenoate 1a (38 mg, 0.3 mmol),
methyl 4-formylbenzoate (33 mg, 0.2 mmol), and PBu3 (71 μL, 0.3
mmol) was performed for 12 h to afford 3m as a colorless oil in 69%
Ethyl 2-(2-(1-Naphthyl)vinyl)but-2-enoate (3q). Following the gen-
eral procedure, the reaction of allenoate 1a (64 mg, 0.5 mmol),
1-naphthaldehyde (31 mg, 0.2 mmol), and PBu3 (119 μL, 0.5 mmol)
was performed for 36 h to afford 3q as a colorless oil in 98% yield;
1
yield; (2E,4E)-3m:(2Z,4E)-3m = 3:1; NMR data for (2E,4E)-3m: H
NMR (400 MHz, CDCl3) δ 8.00 (d, J = 8.3 Hz, 2H), 7.51 (d, J = 8.3 Hz,
2H), 7.11 (d, J = 16.4 Hz, 1H), 7.02 (d, J = 16.4 Hz, 1H), 6.93 (q, J = 7.4
Hz, 1H), 4.28 (q, J = 7.1 Hz, 2H), 3.92 (s, 3H), 2.03 (d, J = 7.4 Hz, 3H),
1.35 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 166.9(2C),
142.0, 139.5, 135.7, 132.3, 130.0, 126.4, 126.2, 123.1, 60.8, 52.1, 14.8,
14.3; selected NMR data for (2Z,4E)-3m: 1H NMR (400 MHz, CDCl3)
δ 7.98 (d, J = 8.3 Hz, 2H), 7.44 (d, J = 8.3 Hz, 2H), 6.84 (d, J = 16.3 Hz,
1H), 6.64 (d, J = 16.3 Hz, 1H), 6.21 (q, J = 7.3 Hz, 1H), 4.36 (q, J = 7.1
Hz, 2H), 3.91 (s, 3H), 1.98 (d, J = 7.3 Hz, 3H), 1.39 (t, J = 7.1 Hz, 3H);
13C NMR (100 MHz, CDCl3) δ 167.4, 141.7, 134.1, 130.8, 129.2, 129.1,
128.8, 60.8, 15.9, 14.3; HRMS-ESI calcd for C16H18O4 [M + Na]+
297.1097, found 297.1090.
1
(2E,4E)-3q:(2Z,4E)-3q = 4:1; NMR data for (2E,4E)-3q: H NMR
(400 MHz, CDCl3) δ 8.20 (d, J = 8.1 Hz, 1H), 7.92 (d, J = 16.0 Hz, 1H),
7.87 (m, 1H), 7.83 (d, J = 8.4 Hz, 1H), 7.73 (d, J = 7.0 Hz, 1H), 7.52 (m,
3H), 6.99 (q, J = 7.4 Hz, 1H), 6.98 (d, J = 16.0Hz, 1H), 4.36 (q, J = 7.1 Hz,
2H), 2.10 (d, J = 7.4 Hz, 3H), 1.42 (t, J = 7.1 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ 167.2, 138.5, 135.4, 134.6, 133.6, 131.3, 130.8, 128.5,
128.1, 126.1, 125.8, 125.6, 123.9, 123.6, 123.4, 60.7, 14.8, 14.3; selected
NMR datafor (2Z,4E)-3q: 1H NMR(400 MHz, CDCl3) δ8.14 (d, J = 8.5
Hz, 1H), 7.66 (d, J = 7.1 Hz, 1H), 6.82 (d, J = 15.9Hz, 1H), 6.25 (q, J = 7.3
Hz, 1H), 4.44 (q, J = 7.1 Hz, 2H), 2.05 (d, J = 7.3 Hz, 3H), 1.46 (t, J = 7.1
Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 167.7, 138.1, 135.0, 134.8,
134.5, 133.5, 129.6, 127.9, 126.3, 123.7, 123.3, 121.0, 60.7, 15.7, 14.4;
HRMS-ESI calcd for C18H18O2 [M + Na]+ 289.1199, found 289.1193.
Ethyl 2-(2-(Trifluoromethyl)styryl)but-2-enoate (3n). Following the
general procedure, the reaction of allenoate 1a (51 mg, 0.4 mmol),
7535
dx.doi.org/10.1021/jo201466k |J. Org. Chem. 2011, 76, 7528–7538

The Journal of Organic Chemistry
ARTICLE
Ethyl 2-(2-(2-Furyl)vinyl)but-2-enoate (3r). Following the general
procedure, the reaction of allenoate 1a (51 mg, 0.4 mmol), 2-furylalde-
hyde (19 mg, 0.2 mmol), and PBu3 (95 μL, 0.4 mmol) was performed
for 24 h to afford 3r as a yellow oil in 87% yield; (2E,4E)-3r:(2Z,4E)-3r =
1a (76 mg, 0.6 mmol), terephthalaldehyde (27 mg, 0.2 mmol), and PBu3
(190 μL, 0.8 mmol) was performed for 12 h to afford 3v as a colorless oil
in 56% yield; (2E,4E)-3v:(2Z,4E)-3v:(2E,4Z)-3v = 10: 2: 1; NMR data
for (2E,4E)-3v: 1H NMR (400 MHz, CDCl3) δ 7.43 (s, 4H), 7.04 (d,
J = 16.4 Hz, 2H), 6.92 (d, J = 16.4 Hz, 2H), 6.86 (q, J = 7.3 Hz, 2H), 4.27
(q, J = 7.1 Hz, 4H), 2.02 (d, J = 7.3 Hz, 6H), 1.34 (t, J = 7.1 Hz, 6H); 13C
NMR (100 MHz, CDCl3) δ 167.1, 138.0, 137.1, 133.0, 131.2, 126.8,
120.7, 60.6, 14.7, 14.3; selected 1H NMR data for (2Z,4E)-3v: δ 6.75 (d,
J = 16.2 Hz, 2H), 6.58 (d, J = 16.2 Hz, 2H), 6.13 (q, J = 7.3 Hz, 2H), 4.36
(q, J = 7.1 Hz, 4H), 1.96 (d, J = 7.3 Hz, 6H), 1.39 (t, J = 7.1 Hz, 6H);
selected 1H NMR data for (2E,4Z)-3v: δ 6.63 (d, J = 12.0 Hz, 2H), 6.21
(d, J = 12.0 Hz, 2H), 4.09 (q, J = 7.1 Hz, 4H), 1.63 (d, J = 7.2 Hz, 6H),
1.16 (t, J = 7.1 Hz, 6H); HRMS-ESI calcd for C22H26O4 [M + Na]+
377.1723, found 377.1721.
1
5:1; NMR data for (2E,4E)-3r: H NMR (400 MHz, CDCl3) δ 7.38
(s, 1H), 6.99 (d, J = 16.3 Hz, 1H), 6.86 (d, J = 16.3 Hz, 1H), 6.82 (q, J =
7.4 Hz, 1H), 6.39 (m, 1H), 6.31 (d, J = 3.1 Hz, 1H), 4.26 (q, J = 7.1 Hz,
2H), 1.99 (d, J = 7.4 Hz, 3H), 1.33 (t, J = 7.1 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ 166.9, 153.3, 142.2, 138.0, 130.7, 120.9, 118.8, 111.6,
1
109.2, 60.6, 14.5, 14.3; selected NMR data for (2Z,4E)-3r: H NMR
(400 MHz, CDCl3) δ 7.35 (s, 1H), 6.67 (d, J = 16.1 Hz, 1H), 6.25 (d, J =
3.1 Hz, 1H), 6.11 (q, J = 7.4 Hz, 1H), 4.33 (q, J = 7.1 Hz, 2H), 1.95 (d, J =
7.4 Hz, 3H), 1.37 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ
167.4, 142.1, 134.2, 134.0, 125.3, 117.2, 111.5, 108.6, 60.7, 15.7, 14.3;
HRMS-ESI calcd for C12H14O3 [M + Na]+ 229.0835, found 229.0843.
Ethyl 2-(2-(2-Thiofuryl)vinyl)but-2-enoate (3s). Following the gen-
eral procedure, the reaction of allenoate 1a (38 mg, 0.3 mmol),
2-thiofurylaldehyde (22 mg, 0.2 mmol), and PBu3 (71 μL, 0.3 mmol)
was performed for 12 h to afford 3s as a colorless oil in 83% yield;
(2E,4E)-3s:(2Z,4E)-3s = 4:1; NMR data for (2E,4E)-3s: 1H NMR (400
MHz, CDCl3) δ 7.26 (d, J = 16.1 Hz, 1H), 7.18 (d, J = 4.9 Hz, 1H), 7.02
(s, 1H), 6.98 (m, 1H), 6.83 (q, J = 7.4 Hz, 1H), 6.74 (d, J = 16.1 Hz, 1H),
4.26 (q, J = 7.1 Hz, 2H), 1.99 (d, J = 7.4 Hz, 3H), 1.33 (t, J = 7.1 Hz, 3H);
13C NMR (100 MHz, CDCl3) δ 166.9, 143.1, 138.0, 134.0, 130.6, 127.6,
126.4, 124.5, 120.1, 60.6, 14.6, 14.2; selected NMR data for (2Z,4E)-3s:
1H NMR (400 MHz, CDCl3) δ 7.15 (d, J = 4.2 Hz, 1H), 6.56 (d, J = 16.1
Hz, 1H), 6.09 (q, J = 7.3 Hz, 1H), 4.34 (q, J = 7.1 Hz, 2H), 1.95 (d, J = 7.3
Hz, 3H), 1.37 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 167.4,
142.6, 133.8, 127.4, 126.3, 126.0, 124.3, 122.3, 60.7, 14.6, 14.3; HRMS-
ESI calcd for C12H14O2S [M + Na]+ 245.0607, found 245.0611.
Ethyl 2-(2-(3-Pyridyl)vinyl)but-2-enoate (3t). Following the general
procedure, the reaction of allenoate 1a (38 mg, 0.3 mmol), 3-pyridylaldehyde
(21 mg, 0.2 mmol), and PBu3 (71 μL, 0.3 mmol) was performed for 12 h to
afford 3t as a brown oil in 60% yield; (2E,4E)-3t:(2Z,4E)-3t:(2E,4Z)-3t =
8:2:1; NMR data for (2E,4E)-3t: 1H NMR (400 MHz, CDCl3) δ 8.67 (s,
1H), 8.48 (d, J = 4.6 Hz, 1H), 7.78 (d, J = 7.9 Hz, 1H), 7.27 (dd, J = 7.9, 4.9
Hz, 1H), 7.08 (d, J = 16.5 Hz, 1H), 6.97 (d, J = 16.5 Hz, 1H), 6.94 (q, J =
7.4 Hz, 1H), 4.28 (q, J = 7.1 Hz, 2H), 2.02 (d, J = 7.4 Hz, 3H), 1.35 (t, J =
7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 166.7, 148.6, 148.5, 139.3,
133.2, 132.7, 130.6, 129.7, 123.4, 122.7, 60.7, 14.7, 14.2; selected1H NMR
data for (2Z,4E)-3t: δ 6.80 (d, J = 16.3 Hz, 1H), 6.60 (d, J = 16.3 Hz, 1H),
6.21 (q, J = 7.4 Hz, 1H), 4.36 (q, J = 7.2 Hz, 2H), 1.99 (d, J = 7.4 Hz, 3H),
1.39 (t, J = 7.2 Hz, 3H); selected 1H NMR data for (2E,4Z)-3t: δ 6.62 (d,
J = 12.6 Hz, 1H), 6.34 (d, J = 12.6 Hz, 1H), 4.12 (q, J = 7.1 Hz, 2H), 1.60
(d, J = 7.2 Hz, 3H), 1.19 (t, J = 7.1 Hz, 3H); HRMS-ESI calcd for
C13H15NO2 [M + Na]+ 240.0995, found 240.0992.
Benzyl 2-(4-Chlorostyryl)but-2-enoate (3w). Following the general
procedure, the reaction of benzyl R-methyl allenoate 1b (56 mg, 0.3
mmol), 4-chlorobenzaldehyde (28 mg, 0.2 mmol), and PBu3 (71 μL, 0.3
mmol) was performed for 12 h to afford 3w as a colorless oil in 98%
1
yield; (2E,4E)-3w:(2Z,4E)-3w = 6:1; NMR data for (2E,4E)-3w: H
NMR (400 MHz, CDCl3) δ 7.44ꢀ7.33 (m, 7H), 7.28 (d, J = 8.5 Hz,
2H), 7.03 (d, J = 16.4 Hz, 1H), 6.93 (q, J = 7.4 Hz, 1H), 6.88 (d, J = 16.4
Hz, 1H), 5.24 (s, 2H), 1.99 (d, J = 7.4 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 166.6, 139.2, 136.01, 135.95, 133.3, 132.2, 130.5, 128.7, 128.5,
128.2, 128.1, 127.7, 121.1, 66.4, 14.8; selected NMR data for (2Z,4E)-
3w: 1H NMR (400 MHz, CDCl3) δ 6.69 (d, J = 16.3 Hz, 1H), 6.46 (d,
J = 16.3 Hz, 1H), 6.14 (q, J = 7.3 Hz, 1H), 5.32 (s, 2H), 1.93 (d, J = 7.3
Hz, 3H).; 13C NMR (100 MHz, CDCl3) δ 167.3, 135.7, 135.5, 135.0,
133.7, 133.1, 130.6, 128.6, 128.4, 128.0, 127.5, 127.1, 66.5, 15.8; HRMS
(ESI) calcd for C19H17ClO2 [M + Na]+ 335.0809, found 335.0810.
Diethyl cis-3-Phenyl-4-styrylcyclohex-1-ene-1,4-dicarboxylate (D1).
yield 31%; colorless oil; 1H NMR (400 MHz, CDCl3) δ 7.38ꢀ7.10 (m,
10H), 7.07 (d, J = 4.8 Hz, 1H), 6.21 (d, J = 16.4 Hz, 1H), 5.73 (d, J = 16.4
Hz, 1H), 4.41 (d, J = 4.8Hz, 1H), 4.22 (m, 4H), 2.64 (dd, J = 18.7, 5.6 Hz,
1H), 2.48 (m, 1H), 2.31 (dd, J = 13.5, 6.3 Hz, 1H), 1.89 (ddd, J = 13.5,
10.9, 6.3 Hz, 1H), 1.28 (m, 6H); 13C NMR (100 MHz, CDCl3) δ 174.1,
167.0, 139.3, 138.2, 136.9, 131.8, 130.7, 130.1, 129.4, 128.4, 127.9, 127.4,
127.2, 126.2, 61.3, 60.5, 51.2, 47.7, 24.5, 22.1, 14.2, 14.1; HRMS (ESI)
calcd for C26H28O4 [M + Na]+ 427.1880, found 427.1878.
General Procedure for Formation of Phosphonium Salts
4, 5, 10, and 11. To a stirred solution of allenoate 1a or 1e (0.2 mmol)
and an acidic additive (0.2 mmol) in anhydrous chloroform (2.0 mL)
was added phosphine (0.2 mmol) at room temperature. The resulting
reaction mixture was stirred for 12 or 24 h. After evaporation of all
volatile components under reduced pressure, the corresponding phos-
phonium salt was obtained. By the above procedure, phosphonium salts
4a, 4b, and 10 were obtained in quantitative yield and high purity. For
pure phosphonium salts 4c, 5aꢀd, and 11, purification through column
chromatography on silica gel (gradient eluant: 10ꢀ50% EtOH in
dichloromethane) was needed.
Ethyl 2-Ethylidene-6-phenylhexa-3,5-dienoate (3u). Following the
general procedure, the reaction of allenoate 1a (51 mg, 0.4 mmol),
cinnamaldehyde (26 mg, 0.2 mmol), and PBu3 (95 μL, 0.4 mmol) was
performed for 24 h to afford 3u as a yellow oil in 85% yield; (2E,4E,6E)-
3u:(2Z,4E,6E)-3u = 3:1; NMR data for (2E,4E,6E)-3u: 1H NMR (400
MHz, CDCl3) δ 7.42 (d, J = 7.4 Hz, 2H), 7.31 (t, J = 7.4 Hz, 2H), 7.23
(m, 1H), 6.90 (m, 2H), 6.79 (q, J = 7.4 Hz, 1H), 6.63 (d, J = 14.5 Hz,
1H), 6.49 (d, J = 14.6 Hz, 1H), 4.26 (q, J = 7.1 Hz, 2H), 1.96 (d, J = 7.4
Hz, 3H), 1.34 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 167.0,
137.7, 137.3, 134.0, 133.4, 131.2, 129.8, 128.6, 127.6, 126.4, 124.7, 60.6,
14.6, 14.3; selected NMR data for (2Z,4E,6E)-3u: 1H NMR (400 MHz,
CDCl3) δ 6.56 (d, J = 16.5 Hz, 1H), 6.31 (d, J = 15.7 Hz, 1H), 6.04 (q, J =
7.3 Hz, 1H), 4.34 (q, J = 7.1 Hz, 2H), 1.92 (d, J = 7.3 Hz, 3H), 1.38 (t, J =
7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 167.6, 133.6, 132.9, 130.6,
129.9, 129.0, 127.5, 126.3, 60.7, 15.7, 14.3; HRMS-ESI calcd for
C16H18O2 [M + Na]+ 265.1199, found 265.1204.
Tributyl(4-ethoxy-3-methyl-4-oxobut-1-en-2-yl)phosphonium Tri-
fluoroacetate (4a). yield 99%; colorless oil; 1H NMR (400 MHz,
CDCl3) δ 6.55 (d, JHP = 41.3 Hz, 1H), 6.41 (d, JHP = 19.6 Hz, 1H),
4.18 (m, 2H), 3.52 (dq, JHP = 14.0 Hz, J = 7.0 Hz, 1H), 2.43 (m, 6H),
1.49 (m, 15H), 1.27 (t, J = 7.1 Hz, 3H), 0.96 (t, J = 6.8 Hz, 9H); 13C
NMR (100 MHz, CDCl3) δ 171.8 (d, JCP = 4.3 Hz), 160.3 (q, JCF = 35.2
Hz), 137.3 (d, JCP = 6.0 Hz), 130.1 (d, JCP = 67.4 Hz), 116.6 (q, JCF
=
293.0 Hz), 62.0, 40.6 (d, JCP = 9.3 Hz), 23.6 (d, JCP = 16.0 Hz), 23.4 (d,
JCP = 4.4 Hz), 18.4 (d, JCP = 47.9 Hz), 17.7 (d, JCP = 4.3 Hz), 13.9, 13.2;
31P NMR (162 MHz, CDCl3) δ 33.8; HRMS-ESI calcd for C19H38O2P+
329.2604, found 329.2610.
Dimethylphenyl(4-ethoxy-3-methyl-4-oxobut-1-en-2-yl)phosphonium
1
Trifluoroacetate (4b). yield 99%; colorless oil; H NMR (400 MHz,
Diethyl 2,20-(2,20-(1,4-Phenylene)bis(ethene-2,1-diyl))dibut-2-eno-
ate (3v):46. Following the general procedure, the reaction of allenoate
CDCl3) δ 7.76 (m, 3H), 7.67 (m, 2H), 6.54 (d, JHP = 45.3 Hz, 1H), 6.36
(d, JHP = 22.6 Hz, 1H), 4.03 (m, 2H), 3.42 (dq, JHP = 13.7 Hz, J = 6.7 Hz,
7536
dx.doi.org/10.1021/jo201466k |J. Org. Chem. 2011, 76, 7528–7538

The Journal of Organic Chemistry
ARTICLE
1H), 2.41 (d, JHP = 13.7 Hz, 6H), 1.42 (d, J = 6.9 Hz, 3H), 1.17 (t, J = 7.0
Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 171.9 (d, JCP = 3.6 Hz), 160.6
(q, JCF = 33.6 Hz), 136.8 (d, JCP = 8.6 Hz), 134.6 (d, JCP = 2.8 Hz), 133.1
(d, JCP = 75.7 Hz), 131.7 (d, JCP = 10.3 Hz), 130.0 (d, JCP = 12.6 Hz),
Dimethylphenyl(2-(ethoxycarbonyl)but-2-enyl)phosphonium Acetate
(5d). yield 94%; (Z)-5d:(E)-5d = 8:1; colorless oil; NMR data for (Z)-5d:
1H NMR (400 MHz, CDCl3) δ 7.87ꢀ7.55 (m, 5H), 7.16 (m, 1H), 4.10 (d,
JHP =16.4Hz, 2H),3.93(q,J= 7.1 Hz, 2H), 2.50 (d, JHP = 14.1 Hz, 6H), 2.01
119.6 (d, JCP = 86.5 Hz), 117.0 (q, JCF = 295.3 Hz), 61.8, 41.1 (d, JCP
10.8 Hz), 16.8 (d, JCP = 5.3 Hz), 13.7, 8.9 (d, JCP = 56.2 Hz), 8.5 (d, JCP
=
=
(s, 3H), 1.90 (dd, J = 7.2, 5.0 Hz, 3H), 1.14 (t, J = 7.1 Hz, 3H); 13C NMR
(100 MHz, CDCl3) δ 176.5, 166.0, 145.8 (d, JCP = 10.0 Hz), 134.3 (d, JCP
3.0 Hz), 131.4 (d, JCP = 9.6 Hz), 129.7 (d, JCP = 12.3 Hz), 121.6 (d, JCP
=
=
56.2 Hz); 31P NMR (162 MHz, CDCl3) δ 24.5; HRMS-ESI calcd for
C15H22O2P+ 265.1352, found 265.1353.
10.8 Hz), 120.6 (d, JCP = 82.3 Hz), 61.4, 24.0 (d, JCP = 50.8 Hz), 23.8, 15.9
(d,JCP = 2.3 Hz), 14.0, 8.1 (d, JCP = 54.8 Hz); 31PNMR(162MHz, CDCl3)
δ 25.4; selected NMR data for (E)-5d: 1H NMR (400 MHz, CDCl3) δ 6.87
(m, 1H), 2.44(d,JHP = 14.1 Hz, 6H); 31P NMR (162 MHz, CDCl3) δ24.0;
HRMS-ESI calcd for C15H22O2P+ 265.1352, found 265.1358.
Triphenyl(4-ethoxy-3-methyl-4-oxobut-1-en-2-yl)phosphonium
Trifluoroacetate (4c). yield 94%; white solid; mp 131ꢀ134 °C; 1H NMR
(400 MHz, CDCl3) δ 7.88 (t, J = 6.9 Hz, 3H), 7.73 (m, 12H), 7.02 (d,
JHP = 47.2 Hz, 1H), 6.37 (d, JHP = 22.1 Hz, 1H), 3.86 (m, 1H), 3.69 (m,
1H), 3.58 (m, 1H), 1.56 (d, J = 7.1 Hz, 3H), 1.04 (t, J = 7.1 Hz, 3H); 13C
Tributyl(3-benzyl-4-ethoxy-4-oxobut-1-en-2-yl)phosphonium Tri-
1
NMR (100 MHz, CDCl3) δ 171.7 (d, JCP = 2.7 Hz), 160.1 (q, JCF
33.2 Hz), 141.8 (d, JCP = 7.7 Hz), 135.5 (d, JCP = 2.7 Hz), 134.3 (d, JCP
=
=
fluoroacetate (10). yield 99%; colorless oil; H NMR (400 MHz,
CDCl3) δ 7.30 (m, 3H), 7.18 (d, J = 6.9 Hz, 2H), 6.79 (d, JHP = 40.9
Hz, 1H), 6.61 (d, JHP = 19.6 Hz, 1H), 4.16 (m, 2H), 3.58 (m, 1H), 3.37 (dd,
J = 13.7, 6.6 Hz, 1H), 3.00 (dd, J = 13.7, 9.0 Hz, 1H), 2.33 (m, 6H), 1.42 (dt,
JHP = 14.7 Hz, J = 7.1 Hz, 6H), 1.30 (m, 6H), 1.23 (t, J = 7.1 Hz, 3H), 0.91
(t, J= 7.2 Hz, 9H); 13C NMR (100 MHz, CDCl3) δ170.7 (d, JCP =3.8Hz),
160.8 (q, JCF = 33.7 Hz), 138.8 (d, JCP = 5.6 Hz), 136.8, 129.3, 128.9, 127.9
(d, JCP = 67.1 Hz), 127.5, 116.9 (q, JCF = 294.4 Hz), 62.2, 48.0 (d, JCP = 9.1
Hz), 38.7 (d, JCP = 4.0 Hz), 23.8 (d, JCP = 16.3 Hz), 23.4 (d, JCP = 4.5 Hz),
18.4 (d, JCP = 47.5 Hz), 13.9, 13.4; 31P NMR (162 MHz, CDCl3) δ 33.8;
HRMS-ESI calcd for C25H42O2P+ 405.2917, found 405.2910.
10.3 Hz), 130.1 (d, JCP = 75.3 Hz), 130.4 (d, JCP = 12.9 Hz), 117.3 (q,
JCF = 298.2 Hz), 116.4 (d, JCP = 88.1 Hz), 61.6, 41.8 (d, JCP = 11.0 Hz),
16.9 (d, JCP = 6.0 Hz), 13.5; 31P NMR (162 MHz, CDCl3) δ 25.9;
HRMS-ESI calcd for C25H26O2P+ 389.1665, found 389.1669.
Tributyl(2-(ethoxycarbonyl)but-2-enyl)phosphonium Acetate (5a).
yield 89%; (Z)-5a:(E)-5a = 6:1; colorless oil; NMR data for (Z)-5a: 1H
NMR (400 MHz, CDCl3) δ 7.25 (m, 1H), 4.22 (q, J = 7.1 Hz, 2H), 3.87
(d, JHP = 16.1 Hz, 2H), 2.42 (m, 6H), 2.13 (m, 3H), 1.99 (s, 3H), 1.50
(m, 12H), 1.32 (t, J = 7.1 Hz, 3H), 0.96 (t, J = 6.5 Hz, 9H); 13C NMR
(100 MHz, CDCl3) δ 176.1, 166.7, 145.7 (d, JCP = 8.7 Hz), 122.2 (d,
JCP = 9.9 Hz), 61.5, 23.9 (d, JCP = 15.5 Hz), 23.8, 23.6 (d, JCP = 4.8 Hz),
19.1 (d, JCP = 46.2 Hz), 19.0 (d, JCP = 48.0 Hz), 16.0 (d, JCP = 2.0 Hz),
14.1, 13.3; 31P NMR (162 MHz, CDCl3) δ 34.4; selected NMR data for
Tributyl(3-(ethoxycarbonyl)-4-phenylbut-3-en-2-yl)phosphonium
Acetate (11). yield 65%; colorless oil; 1H NMR (400 MHz, CDCl3) δ
7.63 (d, JHP = 4.4 Hz, 1H), 7.31 (m, 3H), 7.23 (m, 2H), 4.85 (dq, JHP
=
14.5 Hz, J = 7.2 Hz, 1H), 4.09 (m, 2H), 2.47 (m, 6H), 1.99 (s, 3H), 1.55
(m, 15H), 1.02 (t, J = 7.1 Hz, 3H), 0.95 (t, J = 7.2 Hz, 9H); 13C NMR
(100 MHz, CDCl3) δ 176.7, 169.2, 140.8 (d, JCP = 10.5 Hz), 135.0 (d,
JCP =1.8 Hz), 128.6, 128.2(2C), 128.1, 61.5, 33.69 (d, JCP = 43.6 Hz),
1
(E)-5a: H NMR (400 MHz, CDCl3) δ 7.07 (m, 1H), 4.26 (q, J =
7.1 Hz, 2H), 3.86 (d, JHP = 16.0 Hz, 2H), 2.10 (m, 3H), 1.35 (t, J = 7.1
Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 61.3, 24.2 (d, JCP = 14.2 Hz),
18.8 (d, JCP = 46.5 Hz), 14.2, 13.5; 31P NMR (162 MHz, CDCl3) δ 32.1;
HRMS-ESI calcd for C19H38O2P+ 329.2604, found 329.2603.
24.9, 24.16 (d, JCP = 5.2 Hz), 24.06 (d, JCP = 4.8 Hz), 18.46 (d, JCP
=
44.8 Hz), 13.4(2C); 31P NMR (162 MHz, CDCl3) δ 36.4; HRMS-ESI
calcd for C25H42O2P+ 405.2917, found 405.2913.
Tributyl(2-(ethoxycarbonyl)but-2-enyl)phosphonium Benzoate (5b).
yield 82%; (Z)-5b:(E)-5b= 5:1;pale yellow oil;NMR data for (Z)-5b: 1H
NMR (400 MHz, CDCl3) δ 8.09 (d, J = 3.6 Hz, 2H), 7.31 (m, 3H), 7.23
(m, 1H), 4.21 (q, J = 7.1 Hz, 2H), 3.94 (d, JHP = 16.0 Hz, 2H), 2.41 (m,
6H), 2.14 (t, J = 6.2 Hz, 3H), 1.46 (m, 12H), 1.31 (t, J = 7.1 Hz, 3H), 0.92
(t, J = 6.4 Hz, 9H); 13C NMR (100 MHz, CDCl3) δ 171.4, 166.7, 145.8
(d, JCP = 9.0 Hz), 140.0, 129.3, 128.7, 127.1, 122.2 (d, JCP = 9.9 Hz), 61.5,
23.9 (d, JCP = 15.4 Hz), 23.7 (d, JCP = 4.8 Hz), 19.1 (d, JCP = 46.0 Hz),
18.9 (d, JCP = 46.4 Hz), 16.1 (d, JCP = 1.5 Hz), 14.1, 13.3; 31P NMR (162
Typical Procedure for 31P and 1H NMR Monitoring Experi-
ments. To a solution of allenoate 1a (13 mg, 0.1 mmol) and acetic acid
(6 mg, 0.1 mmol) in CDCl3 (0.5 mL) in a N2-filled NMR tube was added
PBu3 (24μL, 0.1 mmol) via a microsyringe at room temperature. The sample
was shaken up and immediately applied to 31P NMR and 1H NMR monitor-
ing. To reduce time delay, the first NMR spectrum was acquired before a
shimming operation was properly done. The sample was then continuously
scanned at certain intervals as shown in the stacked NMR spectra (Figures 1
and 2). Selected NMR data for intermediates A, B, and C are listed below.
A: 31P NMR (162 MHz, CDCl3) δ 34.2; 1H NMR data (400 MHz,
CDCl3) δ 6.51 (d, JHP = 41.0 Hz, 1H, =CH2), 6.32 (d, JHP = 18.9 Hz,
1H, =CH2), 4.11 (q, J = 7.1 Hz, 2H, OCH2CH3), 3.49 (dq, JHP = 14.0,
J = 7.0 Hz, 1H, CHCH3), 1.90 (s, 3H, OdCꢀCH3), 1.26 (t, J = 7.1 Hz,
3H, OCH2CH3); 13C NMR (100 MHz, CDCl3) δ 137.1 (d, JCP = 6.0
Hz, =CH2).
1
MHz, CDCl3) δ 34.5; selected NMR data for (E)-5b: H NMR (400
MHz, CDCl3) δ7.11 (m, 1H), 4.25 (q, J = 7.1 Hz, 2H), 3.90 (d, JHP = 16.0
Hz, 2H), 2.34 (m, 6H), 2.06 (t, J = 6.2 Hz, 3H), 1.33 (t, J = 7.1 Hz, 3H);
13C NMR (100 MHz, CDCl3) δ 148.0 (d, JCP = 9.3 Hz), 120.6 (d, JCP
=
9.8 Hz), 61.2, 23.9 (d, JCP = 15.2 Hz), 19.1 (d, JCP = 48.1 Hz), 16.6 (d,
JCP = 1.9 Hz), 14.2, 13.5; 31P NMR (162 MHz, CDCl3) δ 32.2; HRMS-
ESI calcd for C19H38O2P+ 329.2604, found 329.2609.
Tributyl(2-(ethoxycarbonyl)but-2-enyl)phosphonium Phenolate (5c).
yield 74%; (Z)-5c:(E)-5c = 10:1; pale yellow oil; NMR data for (Z)-5c: 1H
NMR(400 MHz, CDCl3) δ7.22 (m, 1H), 7.11 (t, J= 7.8 Hz, 2H), 6.95 (d,
J = 7.8 Hz, 2H), 6.69 (t, J = 7.3 Hz, 1H), 4.21 (q, J = 7.1 Hz, 2H), 3.70 (d,
JHP = 15.5 Hz, 2H), 2.32 (m, 6H), 2.10 (dd, J = 7.3 Hz, JHP = 4.4 Hz, 3H),
1.45 (m, 12H), 1.31 (t, J = 7.1 Hz, 3H), 0.93 (t, J = 6.0 Hz, 9H); 13C NMR
(100 MHz, CDCl3) δ 166.5, 157.9, 145.7 (d, JCP = 8.9 Hz), 128.8, 121.9
1
B: 31P NMR (162 MHz, CDCl3) δ 33.6; H NMR (400 MHz,
CDCl3) δ 4.20 (q, J = 7.1 Hz, 2H, OCH2CH3), 2.16 (d, JHP = 13.2 Hz,
3H, PꢀCꢀCH3), 2.12 (s, 3H, =CꢀCH3), 1.90 (s, 3H, OdCꢀCH3),
1.23 (t, J = 7.1 Hz, 3H, OCH2CH3).
1
C: 31P NMR (162 MHz, CDCl3) δ 35.1; H NMR (400 MHz,
CDCl3) δ 6.47 (d, JHP = 2.9 Hz, 1H, =CH2), 6.42 (d, JHP = 3.9 Hz,
1H, =CH2), 4.43 (m, 1H, PꢀCH), 1.90 (s, 3H, OdCꢀCH3); 13C NMR
(100 MHz, CDCl3) δ 133.1 (=CH2).
(d, JCP = 9.9 Hz), 118.3, 115.7, 61.5, 23.8 (d, JCP = 15.4 Hz), 23.5 (d, JCP
=
5.0 Hz), 19.4 (d, JCP = 48.1 Hz), 19.2 (d, JCP = 46.1 Hz), 16.5 (d, JCP = 1.8
Hz), 14.0, 13.2; 31P NMR (162 MHz, CDCl3) δ 34.4; selected NMR data
for (E)-5c: 1H NMR (400 MHz, CDCl3) δ 4.27 (q, J = 7.1 Hz, 2H), 3.66
(d, JHP = 15.5 Hz, 2H), 1.32 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 61.3, 23.8 (d, JCP = 15.3 Hz), 19.0 (d, JCP = 46.3 Hz), 14.1, 13.4;
31P NMR (162 MHz, CDCl3) δ 32.0; HRMS-ESI calcd for C19H38O2P+
329.2604, found 329.2608.
DBU-Aided Formation of 5 from 4 (Scheme 5). To a solution
of phosphonium salt 4 (0.05 mmol) in CDCl3 (0.5 mL) in a N2-filled
NMR tube was added 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) (8 mg,
0.05 mmol) at room temperature. The sample was shaken and subjected
to 31P NMR monitoring, which unveiled a clear transformation process of
4 into thecorresponding phosphonium salt 5. The yields and Z/E ratios of
5 were measured at 1 h by 31P NMR integration.
7537
dx.doi.org/10.1021/jo201466k |J. Org. Chem. 2011, 76, 7528–7538

The Journal of Organic Chemistry
ARTICLE
Control Experiments (Scheme 6). To a solution of phospho-
nium salt 4a (27 mg, 0.06 mmol) and PPhMe2 (7 mg, 0.05 mmol) in
CDCl3 (0.5 mL) in a N2-filled NMR tube was added base DBU (8 mg,
0.05 mmol) at room temperature. The resulting sample was shaken
and subjected to 31P NMR monitoring. At 1 h, 31P NMR measurement
unveiled that a phosphonium salt 5f, generated from phosphine
exchange, was formed in 25% yield along with the normal product 5e
(8% yield) and PBu3 (26% yield). In another experiment, a sample
of phosphonium salt 5a (19 mg, 0.05 mmol) and PPhMe2 (7 mg,
0.05 mmol) in CDCl3 (0.5 mL) in a N2-filled NMR tube was subjected
to 31P NMR monitoring at room temperature. 31P NMR measurement
indicated no direct phosphine exchange between 5a, and free PPhMe2
was detected over 48 h.
Formation of Olefination Product 3b from 5a (Scheme 7).
A mixture of 5a (58 mg, 0.15 mmol), K2CO3 (21 mg, 0.15 mmol), and
4-chlorobenzaldehyde (14 mg, 0.1 mmol) in chloroform (2.0 mL) was
stirred at room temperature for 12 h. The solvent was removed under
reduced pressure, and the residue was isolated by column chromatog-
raphy on silica gel (eluant: 5% diethyl ether in petroleum ether) to afford
3b as an isomeric mixture in 61% yield with a 4:1 ratio of (2E,4E)-3b
versus (2Z,4E)-3b.
(14) Xu, S.; Zhou, L.; Zeng, S.; Ma, R.; Wang, Z.; He, Z. Org. Lett.
2009, 11, 3498–3501.
(15) Zhou, R.; Wang, C.; Song, H.; He, Z. Org. Lett. 2010, 12,
976–979.
(16) Xu, S.; Zou, W.; Wu, G.; Song, H.; He, Z. Org. Lett. 2010,
12, 3556–3559.
(17) An air-stable and water-soluble phosphine, often used as a
nucleophilic trialkylphosphine. See: Tang, X.; Zhang, B.; He, Z.; Gao, R.;
He, Z. Adv. Synth. Catal. 2007, 349, 2007–2017 and references cited
therein.
(18) Vedejs, E.; Bershas, J. P.; Fuchs, P. L. J. Org. Chem. 1973, 38,
3625–3627.
(19) Shen, Y.; Wang, T. Tetrahedron Lett. 1991, 32, 4353–4354.
(20) Hatanaka, M.; Himeda, Y.; Imashiro, R.; Tanaka, Y.; Ueda, I.
J. Org. Chem. 1994, 59, 111–119.
(21) Xia, Y.; Liang, Y.; Chen, Y.; Wang, M.; Jiao, L.; Huang, F.; Liu,
S.; Li, Y.; Yu, Z.-X. J. Am. Chem. Soc. 2007, 127, 3470–3471.
(22) Liang, Y.; Liu, S.; Xia, Y.; Li, Y.; Yu, Z.-X. Chem.ꢀEur. J. 2008,
14, 4361–4373.
(23) Mercier, E.; Fonovic, B.; Henry, C.; Kwon, O.; Dudding, T.
Tetrahedron Lett. 2007, 48, 3617–3620.
(24) A β0-umpolung addition product 6 from 1a and acetic acid and
a dimerization product D2 were isolated in 37% and 41% yield, respec-
tively. Also see refs 25 and 26.
’ ASSOCIATED CONTENT
Supporting Information. Copies of 1D-NMR (1H, 13C,
S
b
31P) and 2D-NMR spectra of new compounds and NMR
monitoring spectra; X-ray crystallographic data (CIF file) for
(E,E)-3l. This material is available free of charge via the Internet
at http://pubs.acs.org.
(25) Martin, T. J.; Tran, S. Y.; Vakhshori, V. G.; Kwon, O. Org. Lett.
2011, 13, 2586–2589.
(26) Guan, X.-Y.; Wei, Y.; Shi, M. Eur. J. Org. Chem. 2011,
2673–2677.
’ AUTHOR INFORMATION
(27) The small peaks which were observable after 6 h and adjacent to
the main peaks of 5a presumably correspond to the allylic phosphorus
ylide generated from deprotonation of 5a.
Corresponding Author
*E-mail: zhengjiehe@nankai.edu.cn.
(28) Berenguer, M. J.; Castells, J.; Galard, R. M.; Moreno-Ma~nas, M.
Tetrahedron Lett. 1971, 12, 495–496.
’ ACKNOWLEDGMENT
(29) Font, J.; March, P. Tetrahedron Lett. 1978, 3601–3602.
(30) Kim, S.; Kim, Y. C. Tetrahedron Lett. 1990, 31, 2901–2904.
(31) An ethoxycarbonyl-substituted analogue of the ylide I was
observed by 31P NMR in our prior work. See ref 16.
(32) Robiette, R.; Richardson, J.; Aggarwal, V. K.; Harvey, J. N. J. Am.
Chem. Soc. 2006, 128, 2394–2409.
(33) Lu, X.; Zhang, C.; Xu, Z. Acc. Chem. Res. 2001, 34, 535.
(34) Marinetti, A.; Voituriez, A. Synlett 2010, 174.
(35) Cowen, B. J.; Miller, S. J. Chem. Soc. Rev. 2009, 38, 3102.
(36) Stable tetravalent phosphonium enolate zwitterions, which are
structurally similar to the putative zwitterionic intermediates from
nucleophilic addition of phosphines to allenoates, were prepared and
well characterized. Zhu, X.-F.; Henry, C. E.; Kwon, O. J. Am. Chem. Soc.
2007, 129, 6722–6723.
Financial support from National Natural Science Foundation
of China (grant nos. 20872063 and 21072100) is gratefully
acknowledged.
’ REFERENCES
(1) Fuson, R. C. Chem. Rev. 1935, 16, 1–27.
(2) Casiraghi, G.; Battistini, L.; Curti, C.; Rassu, G.; Zanardi, F.
Chem. Rev. 2011, 111, 3076–3154.
(3) Martin, S. F. Acc. Chem. Res. 2002, 35, 895–904.
(4) Trost, B. M.; Hitce, J. J. Am. Chem. Soc. 2009, 131, 4572–4573
and references cited therein.
(5) Fleming, I.; Morgan, I. T.; Sarkar, A. K. J. Chem. Soc., Perkin
Trans. 1 1998, 2749–2763.
(37) Tran, Y. S.; Kwon, O. J. Am. Chem. Soc. 2007, 129, 12632–
(6) Frank, S. A.; Mergott, D. J.; Roush, W. R. J. Am. Chem. Soc. 2002,
124, 2404–2405.
12633.
(38) Liang, Y.; Liu, S.; Yu, Z.-X. Synlett 2009, 905–909.
(39) Zhang, C.; Lu, X. J. Org. Chem. 1995, 60, 2906.
(40) Zhu, X.-F.; Lan, J.; Kwon, O. J. Am. Chem. Soc. 2003, 125,
4716–4717.
(41) Trost, B. M.; Li, C.-J. J. Am. Chem. Soc. 1994, 116, 3167–3168.
(42) Zhang, C.; Lu, X. Synlett 1995, 645–646.
(43) Chen, Z.; Zhu, G.; Jiang, Q.; Xiao, D.; Cao, P.; Zhang, X. J. Org.
Chem. 1998, 63, 5631–5635.
(44) Lang, R. W.; Hansen, H.-J. Org. Synth. 1990, 7, 232.
(45) 1b was reported without being fully characterized. Maity, P.;
Lepore, S. D. J. Org. Chem. 2009, 74, 158–162.
(7) Ruano, J. L. G.; Aleman, J.; Aranda, M. T.; Arevalo, M. J.; Padwa,
A. Org. Lett. 2005, 7, 19–22.
(8) Rieder, C. J.; Winberg, K. J.; West, F. G. J. Am. Chem. Soc. 2009,
131, 7504–7505.
(9) Date, S. M.; Ghosh, S. K. Angew. Chem., Int. Ed. 2007, 46,
386–388.
(10) Corey, E. J.; Erickson, B. W. J. Org. Chem. 1974, 39, 821–825.
(11) He, Z.; Tang, X.; He, Z. Phosphorus Sulfur Silicon Relat. Elem.
2008, 183, 1518–1525.
(12) Khong, S. N.; Tran, Y. S.; Kwon, O. Tetrahedron 2010,
66, 4760–4768.
(46) Self-polymerization of 3v was observed at room temperature.
(13) Maryanoff, B. E.; Reitz, A. B. Chem. Rev. 1989, 89, 863–927.
7538
dx.doi.org/10.1021/jo201466k |J. Org. Chem. 2011, 76, 7528–7538