Olefination of ketenes for the enantioselective synthesis of allenes via an ylide route

Article abstract of DOI:10.1016/j.tet.2007.05.053

Pseudo-C₂-symmetric chiral phosphorus ylide is designed and synthesized for the enantioselective preparation of allenic esters, amides, ketone, and nitrile. Up to 92% ee is achieved.

Full text of DOI:10.1016/j.tet.2007.05.053

Tetrahedron 63 (2007) 8046–8053
Olefination of ketenes for the enantioselective synthesis
of allenes via an ylide route
Chuan-Ying Li,a Ben-Hu Zhu,b Long-Wu Ye,a Qing Jing,a Xiu-Li Sun,a
b,
Yong Tanga, and Qi Shen
*
*
aState Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, China
bSchool of Chemistry and Chemical Engineering, Suzhou University, Suzhou 215123, China
Received 5 February 2007; revised 14 May 2007; accepted 15 May 2007
Available online 18 May 2007
Abstract—Pseudo-C2-symmetric chiral phosphorus ylide is designed and synthesized for the enantioselective preparation of allenic esters,
amides, ketone, and nitrile. Up to 92% ee is achieved.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
phosphorus ylide bearing 10-phenylsulfonylisoborneol re-
acted with methylketene to give penta-2,3-dienoic ester
with excellent diastereoselectivity.7e
In recent years, optically active allenes have been used as
versatile chiral building blocks in organic synthesis due to
their high reactivity and the unique ability that they can
transfer the axial chirality to final products efficiently.1 In
addition, allenes are important subunits in a variety of natu-
ral products and biologically active compounds.2 Thus, the
development of synthetic methodology for enantiomerically
enriched allenes is of great interest and several strategies
have been developed. One of the most commonly used
approaches is substitution or isomerization of chiral propar-
gylic derivatives.3 Asymmetric catalysis4 and kinetic resolu-
tion5 also provide accesses to optically active allenes.
Phosphorus ylides are good reagents for the synthesis of
allenes by olefination of ketenes,6 but only a few examples
were reported for its asymmetric version.7 The first example
was described by Bestmann in 1964,7a in which a stabilized
phosphorus ylide containing a chiral alcohol was docu-
mented to react with acyl chloride to afford optically active
allenes. Later on, they reported a reaction of racemic phos-
phorus ylides with enantiomerically enriched acyl chloride
and found that the resulting chiral allenes were obtained
with up to 31% ee.7b Pure ketenes were first used as sub-
strates by Musierowicz and his co-workers in the enantio-
selective synthesis of allenes. They found that the reaction
between chiral phosphinate ester and ketenes afforded
allenes with 23% ee.7c Tanaka et al. described that optically
active 4,4-disubstituted allenic esters could be prepared with
binol-derived HWE reagents in 21–71% yields with 23–89%
ee’s.7d Melo and his co-workers documented that a
In a previous study on ylide chemistry in organic synthesis,8
we were interested in developing asymmetric ylide-medi-
ated synthesis of optically active allenes and communicated
that newly designed chiral phosphorus ylides could react
with ketenes to afford enantiomerically enriched allenic es-
ters.9 Recently, we modified the chiral ylides and found that
the enantioselectivities were further improved in some cases.
We also extended this method to the synthesis of chiral al-
lenic ketones, amides, nitrile, and 4-monosubstituted allenic
esters. In this paper, we wish to report the synthesis and the
modification of the phosphorus ylides, the scope, and limita-
tion in detail.
2. Results and discussion
2.1. Design and synthesis of phosphorus salts
In a previous study, we demonstrated that chiral telluronium
salts 1 could react smoothly with a,b-unsaturated ketones,
esters, and imines to afford optically active vinylcyclopro-
pane derivatives with high diastereoselectivities and enan-
tioselectivities.8c,f It is envisioned that phosphonium salt 2
with a similar structure is a potential reagent for the enantio-
selective synthesis of allenes (Fig. 1). One attractive advan-
tage of salt 2 is its high flexibility since substituents R1, R2,
and R3 are readily variable. Another advantage is that the
chiral phosphine oxide produced in the reaction is possible
to be recovered and reused.
* Corresponding authors. E-mail: tangy@mail.sioc.ac.cn
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.05.053

C.-Y. Li et al. / Tetrahedron 63 (2007) 8046–8053
8047
R1
with methanesulfonyl chloride, followed by reaction with
dilithium phenylphosphate 7a to afford 6a and 6b, respec-
tively. Phosphines 6a and 6b reacted with the corresponding
bromides to give the desired phosphonium salts 2a, 2b, and
2c, respectively.
Br
R2
Te+CH2CH=CHR
P
R3
BPh4
R1
2
1
Figure 1. Design of phosphorus salt.
2.2. Effects of reaction conditions on the
asymmetric olefination
Phosphorus salts 2a–2c are readily prepared from the corre-
sponding diketones. As shown in Scheme 1, hexane-2,5-
dione 3a was reduced by baker’s yeast to the corresponding
diol 4a in 60% yield with excellent de and ee.10a And 1,4-
diphenylbutane-1,4-dione could be easily reduced by
proline-derived chiral borane10b or by asymmetric hydro-
genation10c in gram scale to give the desired diol 4b in
high yield with excellent selectivity. Diols 4a and 4b reacted
Initially, the reaction of phosphonium salt 2b with phenyl
ethyl ketene 9a was chosen as a model reaction to optimize
the reaction conditions. As shown in Table 1, the cation of
the base influenced both the yield and the selectivity
strongly. The base bearing K+ furnished the desired products
in moderate yields with moderate ee’s (entries 4 and 6). Al-
though n-BuLi, LiHMDS, and LiTMP gave the allenes with
good enantioselectivities (entries 1, 2, and 5), the yields were
O
OH
OMs
R1
condition a or b or c
R1
MsCl, Et3N
R1
R1
R1
R1
CH2Cl2
O
OH
OMs
3a, R1 = Me
4a, R1 = Me, condition a, 60%, >99% de
4b, R1 = Ph, condition b, 98%, 99% de, 98% ee
condition c, 95%, 90% de, 99% ee
5a, R1 = Me, 97%
3b, R1 = Ph
5b, R1 = Ph, 72%
R1
R1
BrCH2COOR2
Et2O, 25 °C, 15 h
Ph
O
PhPLi2, 7a
THF
Ph
P
P
Br
R2
O
R1
R1
6a, R1 = Me, 70%
6b, R1 = Ph, 54%
2a, R1 = Me, R2 = Et, 91%
2b, R1 = Ph, R2 = Et, 95%
2c, R1 = Ph, R2 = t-Bu, 94%
Scheme 1. Synthesis of phosphonium salts 2a–2c. Condition a: baker’s yeast. Condition b: (2S)-2-(Diphenylhydroxymethyl) pyrrolidine, B(OMe)3, BH3$SMe2,
THF. Condition c: RuCl2(R3P)2[(S,S)-DPEN], i-PrOH, t-BuOK, H2.
Table 1. Effects of reaction conditions on the asymmetric olefination of ketenes
Ph
Et
additive
-78 °C
Ph
Ph
Ph
•
O
9a
O
Ph
H
Et
O
Br
P
solvent
rt
P
•
+ base
EtO
EtO
EtOOC
Ph
Ph
2b
Ph
8b
10a
Entry
Base
Additive
Solvent (v/v)
Yielda (%)
eeb (%)
1
2
3
4
5
6
7
8
n-BuLi
LiHMDS
NaHMDS
KHMDS
LiTMP
t-BuOK
NaH
NaH
NaH
NaH
NaH
NaH
NaH
NaH
NaH
NaH
NaH
NaH
NaH
None
None
None
None
None
None
None
NaBr (0 equiv)
NaBr (1 equiv)
NaBr (2 equiv)
LiBr (1 equiv)
LiBr (2 equiv)
Et3N$HCl (2 equiv)
None
None
None
None
None
None
None
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
60
67
80
47
63
42
73
69
73
56
67
42
14
56
26
46
67
67
65
37
80
80
81
70
79
59
80
64
80
80
80
81
70
64
70
39
56
52
50
60
9
10
11
12
13
14
15
16
17
18
19
20
THF
DME/THF (5/1)
Ether
n-Butyl ether
CH2Cl2
ClCH2CH2Cl/CH2Cl2 (10/7)
Toluene
Hexane
NaH
a
Isolated yield.
Determined by chiral HPLC.
b

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C.-Y. Li et al. / Tetrahedron 63 (2007) 8046–8053
Table 3. Asymmetric synthesis of allenes 10 from phosphonium salt 2ba
only moderate. In our screened conditions, NaHMDS was
the optimal (entry 3).
Ph
H
R3
Ph
i, NaHMDS, 25 °C, THF
R3
O
•
10
Br
P
R2OOC
R2 = Et
R4
R2O
‘Salt effects’ were observed in this reaction. Et3N$HCl dete-
riorated both the yield and the selectivity greatly (entry 13).
Addition of NaBr improved the enantioselectivities (entries
8–10). LiBr could also increase the ee but decreased the
yield (entries 11 and 12). Solvent effect was also examined.
It was found that the reaction proceeded well in toluene and
dichloromethane (entries 17 and 19). The best result was
achieved in THF (entry 7).
ii,
, -78 °C
O
•
Ph
2b
R4
9
Entry
Ketene 9 (R3/R4)
Allene 10
Yieldb (%)
eec (%)
1
2
3
4
5
6
9a (Et/Ph)
9b (Me/Ph)
9c (n-Pr/Ph)
9d (n-Bu/Ph)
9e (i-Pr/Ph)
9f (i-Bu/Ph)
9g (Allyl/Ph)
9h (3-Butenyl/Ph)
9i (Bn/Ph)
9j (Et/o-Me–C6H4)
9k (Et/p-MeO–C6H4)
9l (Et/p-Cl–C6H4)
10a
10b
10c
10d
10e
10f
10g
10h
10i
80
61
78
70
76
71
46
59
51
53
78
75
81
45
80
64
71
85
61
65
52
25
91
85
2.3. Effects of phosphonium salts
7d
8d
9d
10
11
12
Having established the optimal reaction conditions, the
effects of various phosphonium salts were examined. As
shown in Table 2, 2a gave the desired allene in moderate
yields and ee’s (entries 1 and 4). Replacement of methyl
group in 2a with phenyl group improved both the yield
and enantioselectivity (entry 1 vs 2 and entry 4 vs 5).
When ethyl ester was replaced by tert-butyl ester, 92% ee
could be achieved but the yield decreased to 51% (entry 3).
10j
10k
10l
a
Reactions were carried out in THF at ꢀ78 ꢁC under N2 with 0.2 mmol of
salt 2b (0.2 M in THF, 1.0 mL), 0.2 mmol of NaHMDS, and 0.2 mmol of
ketene 9.
Isolated yield.
Determined by chiral HPLC.
b
c
d
Ketene was prepared in situ from 0.4 mmol of the corresponding acyl
chloride and 0.6 mmol Et3N.
2.4. Scope and limitation
Under the optimal conditions, the generality of the reaction
was studied by investigating the reaction of various ketenes
with 2b. As shown in Table 3, 2-aryl-1-buten-1-one gave
4-aryl-2,3-hexadienoic esters in high yields with high enan-
tioselectivities (entries 1, 11, and 12) and up to 91% ee was
obtained. However, replacement of ethyl groups on ketene
9a with other alkyl groups such as isopropyl, benzyl, and
allyl groups decreased the enantiomeric excesses greatly
(entries 5, 7–9). Ketene 9j, with an o-methoxylbenzyl group,
afforded the corresponding allene in low yield with poor
selectivity probably due to the steric effects (entry 10).
Table 4 vs entry 9 in Table 3). 2-Ethylhexanoyl chloride
gave the corresponding allene in 51% yield with good ee
(entry 2). By this protocol, monosubstituted allenic esters
could be obtained in good yields with moderate enantio-
selectivities (entries 3 and 4). 2-Bromopropanoyl chloride
was also a good substrate to give bromoallene 10q in 61%
yield with 30% ee (entry 5).
Further studies showed that allenic ketone, nitrile, and am-
ides could also be synthesized by this method in good yields
with moderate to good enantioselectivities. As shown in
Table 5, phosphane 6b reacted with bromides 12a–12d in
THF, followed by deprotonation with NaHMDS and then
treated with ketene 9a to afford the desired allenes.
Since dialkyl ketene and monosubstituted ketene are not so
stable and could not be purified as ketene 9a is, we devel-
oped a one-pot protocol. It was found that, in the presence
of triethylamine, the reactions of acyl chlorides with phos-
phonium salt 2b proceeded well to give the desired allenic
esters in moderate yields with moderate enantioselectivities.
As shown in Table 4, compared with the use of ketene gen-
erated in situ, one-pot procedure gave lower ee (entry 1 in
2.5. Further modification of the olefination
For the Wittig reaction, traditionally, oxaphosphetane is
recognized as a key intermediate and the selectivity could
Table 2. Effects of phosphonium saltsa
R1
H
R3
R4
Ph
i, NaHMDS, 25 °C, THF
R3
O
•
10
Br
P
R2OOC
R2
O
R1
ii,
, -78 °C
O
•
R4
9
2
Entry
R1/R2 (salts 2)
R3/R4 (ketene 9)
Product
Yieldb (%)
eec (%)
1
2
Me/Et (2a)
Ph/Et (2b)
Ph/t-Bu (2c)
Me/Et (2a)
Ph/Et (2b)
Et/Ph (9a)
Et/Ph (9a)
Et/Ph (9a)
n-C10H21/H (9o)
n-C10H21/H (9o)
10a
10a
10m
10o
10o
56
80
51
20
53
43
81
92
19
55
3
4d
5d
a
Reactions were carried out in THF at ꢀ78 ꢁC under N2 with 0.2 mmol of salt 2 (0.2 M in 1.0 mL of THF), 0.2 mmol of NaHMDS, and 0.2 mmol of ketene 9.
b
c
d
Isolated yield.
Determined by chiral HPLC.
Ketene is prepared in situ, and the reaction was carried out at ꢀ20 ꢁC.

C.-Y. Li et al. / Tetrahedron 63 (2007) 8046–8053
Table 4. One-pot enantioselective synthesis of allenes 10a
8049
Ph
Ph
Ph
O
Ph
R3
R4
O
H
Br
P
NaHMDS
25 °C, THF
1
.
Et3N
R4
P
•
R2O
EtO
Cl
O
R2OOC
R2 = Et
Ph
2b
Ph
2.
10
8b
R3
11
Entry
Acyl chloride 11 (R3/R4)
Allene 10
T (ꢁC)
Yieldb (%)
eec (%)
1
2
3
4
5
11a (Bn/Ph)
10i
0
ꢀ20
0
57
51
53
57
61
45
63
55
17
30
11b (n-Bu/Et)
11c (n-C10H21/H)
11d (t-Bu/H)
11e (Br/Me)
10n
10o
10p
10q
0
0
a
Reactions were carried out in THF under N2 with 0.2 mmol of salt 2b (0.2 M in THF, 1 mL), 0.2 mmol of NaHMDS, 0.3 mmol of Et3N, and 0.24 mmol of acyl
chloride.
Isolated yield.
Determined by chiral HPLC.
b
c
Table 5. Asymmetric synthesis of allenic amides, nitrile, and ketonea
model to account for the selectivity in the reaction of
stabilized phosphorus ylide with aldehyde.12 Based on their
mechanistic insights, we developed a stereochemical model
in the previous communication9 to explain the configuration
of the allenic esters formed (Scheme 2).
Ph
Ph
•
O
9a
Ph
Et
X
THF
NaHMDS
rt, 1.5h
Et
Ph
P
+ BrCH2X
12
•
13
rt, 15h
-20 °C, 24h
6b
Ph
Based on the stereochemical model developed, it is envi-
sioned that replacement of the phenyl of salt 2b by
a more bulky substituent should be beneficial to the enan-
tioselectivity. And thus, we designed phosphanes 6c–6f.
However, several attempts to synthesize 6c and 6d failed
due to the low yield for the synthesis of diketone 3c and
the poor selectivity for the reduction of 3d (Scheme 3). For-
tunately, the reactions of 5b with dilithium arylphosphate
7b and 7c proceeded well to afford the desired phosphines
6e and 6f, respectively. The reactions of 6e and 6f with
ethyl bromoacetate gave the corresponding phosphonium
salts 2d and 2e, respectively, in excellent yields as shown
in Scheme 4. Compared with 2b, the newly designed phos-
phonium salts 2d and 2e gave allenes in similar yields
under the optimal conditions.
Entry
X (BrCH2X 12)
Allene 13
Yieldb (%)
eec (%)
1
CON(CH2)4 (12a)
CONEt2 (12b)
CN (12c)
13a
13b
13c
13d
69
76
65
65
32
60
20
40
2d
3
4
COPh (12d)
a
Reactions were carried out in THF at ꢀ20 ꢁC under N2 with 0.2 mmol of
chiral phosphine 6 (0.2 M in THF, 1.0 mL), 0.2 mmol of BrCH2X 12,
0.2 mmol of NaHMDS, and 0.2 mmol of ketene.
Isolated yield.
Determined by chiral HPLC.
0.3 mmol of phosphine 6 and 0.3 mmol of BrCH2X 12 were used.
b
c
d
be explained by 1,2- and 1,3-steric interactions in the four-
center transition state.11 Recently, Aggarwal and his co-
workers developed an elegant dipole–dipole interaction
O
P
O
O
Ph
P
P
•
9a
H
H
H
or
-78 °C, THF
O
O
O
R
O
O
O
R
R
8b R = Et
8c R = t-Bu
Ab (minor)
Aa (major)
O
P
H
•
H
Ph
ROOC
Et
O
O
10a R = Et
10m R = t-Bu
R
Ba
Scheme 2. A proposed stereochemical model.

8050
C.-Y. Li et al. / Tetrahedron 63 (2007) 8046–8053
R1
6c: Ar = Ph, R = -naphthyl
6d: Ar = Ph, R = mesityl
Ar
P
R1
HO
OH
N
H
Ph
R1
Ph
R1
O
B(OMe)3, BH3·SMe2, THF
OH
R1
R1
4d: R = mesityl
yield: 48%, 11% de, 53% ee
O
3c: R1 = b-naphthyl 10% yield
3d: R1 = mesityl, 78% yield
RuCl2(R3P)2[(S,S)-DPEN)]
no reaction
i-PrOH, t-BuOK, H2
Scheme 3. Attempt for the synthesis of 6c and 6d.
THF, -78 °C, 1h,
then 25 °C, 18h
moderate to high enantioselectivities in moderate to good
yields. By employing one-pot strategy, 4-monosubstituted,
4-dialkylsubstituted allenic esters, and bromoallene could
be readily synthesized. Besides allenic esters, utilizing the
corresponding salts prepared in situ, optically allenic am-
ides, ketone, and nitrile could also be obtained. The easily
available phosphonium salts, in particular the recovery and
the reuse9 of chiral phosphines make the present method
potentially useful.
OMs
Ph
+
ArPLi2
Ph
Ar
5b
OMs
7b, Ar = 3,5-dimethylphenyl
7c, Ar = 2,4,6-trimethylphenyl
Ph
P
Ph
Ar
O
BrCH2COOEt/Et2O
25 °C, 15h
P
Br
Et
O
Ph
Ph
6e, Ar = 3,5-dimethylphenyl, 33%
6f, Ar = 2,4,6-trimethylphenyl, 16%
2d, Ar = 3,5-dimethylphenyl, 90%
2e, Ar = 2,4,6-trimethylphenyl, 90%
Scheme 4. Synthesis of phosphonium salts 2d and 2e.
4. Experimental
4.1. General
Table 6. Asymmetric olefination with phosphonium salts 2d and 2ea
Ph
H
R3
Ar
i, NaHMDS, 25 °C, THF
R3
O
•
10
Br
All reactions were carried out under N2 unless otherwise
noted. All solvents were purified according to standard
P
EtOOC
R4
EtO
ii,
, -78 °C
O
•
Ph
2d: Ar = 3,5-dimethylphenyl; 2e: Ar = 2,4,6-trimethylphenyl
Entry Salt 2 Ketene 9 (R3/R4) Allene 10 Yieldb (%) eec (%)
1
R4
9
methods prior to use. H NMR, 13C NMR, and 31P NMR
spectra were recorded in chloroform-d3 on a VARIAN Mer-
cury 300.
4.1.1. Representative procedure for the preparation
of phosphonium salts. Preparation of (2S,5S)-1-ethoxy-
carbonylmethyl-1-(3,5-dimethylphenyl)-2,5-diphenyl
phospholanium bromide (2d). (1R,4R)-1,4-Bis(methane-
sulfonyloxy)-1,4-diphenylbutane (5b) was prepared accord-
ing to a literature procedure.14
1
2
3
4
2d
2d
2d
2d
2d
2d
2e
2e
9b (Me/Ph) 10b
9k (Et/p-CH3OC6H4) 10k
54 (61)
80 (78)
77 (71)
49 (53)
64 (75)
51 (57)
47 (53)
56 (57)
65 (45)
92 (91)
91 (85)
58 (25)
90 (85)
25 (17)
45 (25)
25 (17)
9f (i-Bu/Ph)
10f
10j
10l
10p
10j
10p
9j (Et/o-Me–C6H4)
9l (Et/p-Cl–C6H4)
9p (t-Bu/H)
5
6d
7
9j (Et/o-Me–C6H4)
9p (t-Bu/H)
8d
a
Preparation of (2S,5S)-2,5-diphenyl-1-(3,5-dimethylphenyl)
phospholane 6e. To a slurry of Li2PAr 7b (17 mmol) in THF
(110 mL) was added dropwise (1R,4R)-1,4-bis(methanesul-
fonyloxy)-1,4-diphenylbutane 5b (7.3 g, 18.3 mmol) in THF
(60 mL) at ꢀ78 ꢁC. The mixture was allowed to stir at
ꢀ78 ꢁC for 1 h and then for further 18 h at 25 ꢁC. After fil-
tration through a short silica gel column under N2, the filtrate
was concentrated and the residue was extracted with n-hex-
ane (100 mL). The hexane layer was collected, followed by
concentration in vacuo yielding the crude product as pale
yellow oil, which was used directly for the following reac-
tion without further purification. Yield: 33%. 1H NMR
(300 MHz, CDCl3/TMS) d 2.14 (s, 6H), 2.04–2.36 (m,
3H), 2.67–2.78 (m, 1H), 3.73–3.84 (m, 1H), 3.99–4.08 (m,
1H), 6.66–7.10 (m, 7H), 7.19–7.41 (m, 6H); 31P NMR
(121.5 MHz, CDCl3) d 21.5.
Reactions were carried out in THF at ꢀ78 ꢁC under N2 with 0.2 mmol of
salt 2d or 2e (0.2 M in THF, 1.0 mL), 0.2 mmol of NaHMDS, and
0.2 mmol of ketene 9.
Isolated yield, number in bracket is the isolated yield when salt 2b was
used.
Determined by chiral HPLC. Number in bracket is the ee when salt 2b was
used.
Ketene was prepared in situ and the reaction was carried out at ꢀ20 ꢁC.
b
c
d
As expected, the enantioselectivities were improved for
most substrates although they are not good enough (Table
6). Compared with 2e, 2d gave the allene with higher ee
(entry 4 vs entry 7). These results further supported the
stereochemical model proposed above.
3. Conclusion
In summary, we have developed an efficient method for the
preparation of optically active allenes. Using salt 2b, 2d or
2e, 4-alkyl-4-aryl-2,3-allenic esters could be prepared with
To a vigorously stirred solution of 6e (10 mmol) in petro-
leum ether (20 mL) at ꢀ15 ꢁC was added dropwise 10%
H2O2 (20 mmol) within 1 h. After 4 h at ꢀ15 ꢁC, the

C.-Y. Li et al. / Tetrahedron 63 (2007) 8046–8053
8051
reaction mixture was diluted with CHCl3 (40 mL). The or-
ganic layer was separated and the aqueous layer was ex-
tracted with CHCl3 (3ꢂ30 mL). The combined organic
extracts were washed with H2O, dried (Na2SO4), and con-
centrated in vacuo. The residual oil was purified by flash
column chromatography (CH2Cl2/CH3OH¼100/1) to afford
(2S,5S)-(ꢀ)-1-r-oxo-2,5-diphenyl-1-(3,5-dimethylphenyl)
phospholane 14b. Yield: 50%. [a]2D0 ꢀ64.2 (c 0.4, CHCl3).
IR (KBr) n/cmꢀ1 2943 (m), 1602 (vs), 1496 (vs), 1451 (vs),
758 (s), 697 (vs); 1H NMR (300 MHz, CDCl3/TMS) d 2.17
(s, 6H), 2.22–2.37 (m, 1H), 2.50–2.74 (m, 3H), 3.45–3.56
(m, 1H), 3.79–3.94 (m, 1H), 6.92–7.30 (m, 13H); 13C NMR
(75 MHz, CDCl3) d 137.28, 137.12, 135.87, 135.82, 135.59,
135.52, 132.95, 132.91, 130.37, 129.19, 128.60, 128.53,
128.49, 128.22, 127.82, 126.90, 126.84, 126.58, 126.06,
51.18, 50.36, 46.88, 46.07, 31.20, 31.10, 27.68, 27.57,
20.79; 31P NMR (121.5 MHz, CDCl3) d 54.2; MS (EI, m/z,
rel intensity) 360 (11.0), 107 (21.0), 91 (20.6), 84 (100.0),
77 (13.3), 47 (30.3); HRMS (MALDI/DHB) M+Na+ calcd
for C24H25OPNa+: 383.1537. Found: 383.1535.
4.1.3. Representative procedure using ketenes prepared
in situ (Table 3). Preparation of 4-phenyl-hepta-2,3,6-tri-
enoic acid ethyl ester 10g. To a solution of phosphonium
salt 2b (0.2 mmol) in THF (1.0 mL) was added NaHMDS
(1 M in THF, 0.2 mL). After stirring for 1 h at room temper-
ature, the reaction mixture was cooled to ꢀ78 ꢁC and stirred
for further 2 h to give the ylide solution.
A mixture of trifluoromethyl-benzene (BTF, 1.0 mL), Et3N
(61 mg, 0.6 mmol), and 2-phenyl-pent-4-enoyl chloride
(0.4 mmol) was stirred for 2 h at room temperature, and
then was filtered under N2. The filtrate was concentrated in
vacuo to give a light yellow oil, which was dissolved in
THF (0.5 mL) and then added into the ylide solution pre-
pared above. The resulting mixture was allowed to stir for
further 48 h at ꢀ78 ꢁC. After quenching with water, the re-
action mixture was diluted with petroleum ether and filtered.
The filtrate was concentrated and the residue was purified by
flash chromatography to give 10g as pale yellow oil. Yield:
1
46%. 61% ee. H NMR (300 MHz, CDCl3/TMS) d 1.28 (t,
J¼6.9 Hz, 3H), 3.29–3.33 (m, 2H), 4.17–4.26 (m, 2H),
5.13 (dd, J¼1.5, 10.5 Hz, 1H), 5.23 (dd, J¼1.5, 17.1 Hz,
1H), 5.88–6.00 (m, 2H), 7.26–7.42 (m, 5H).9
Pure 6e was obtained by reduction of the corresponding
oxide 14b according to a literature procedure.13,14
Preparation of phosphonium salts 2d. A mixture of phos-
phine 6e (2.5 mmol) and BrCH2COOEt (2.7 mmol) in Et2O
(5 mL) was stirred at 25 ꢁC for 15 h. The resulting solid
was collected, washed with ether, and dried in vacuo to
give phosphonium salt 2d. Yield: 90%. [a]2D0 ꢀ95.7 (c 0.83,
CHCl3). IR (KBr) n/cmꢀ1 3031 (w), 1735 (vs), 1601 (m),
4.1.4. Representative one-pot protocol (Table 4). Prepa-
ration of 4-ethyl-octa-2,3-dienoic acid ethyl ester 10n.
To a solution of phosphonium salt 2b (0.2 mmol) in THF
(1.0 mL) was added NaHMDS (1 M in THF, 0.2 mL) at
room temperature. The reaction mixture was stirred for
1 h and then Et3N (31 mg, 0.3 mmol) and acid chloride
11b (0.24 mmol) were added in turn, at ꢀ20 ꢁC. The re-
sulting mixture was stirred at ꢀ20 ꢁC for 24 h. After
quenching with water, the reaction mixture was diluted
with petroleum ether and then filtered. The filtrate was
concentrated and the resulting oil was purified by flash
chromatography to give 10n as pale yellow oil. Yield:
1
1496 (m), 761 (m), 701 (m); H NMR (300 MHz, CDCl3/
TMS) d 0.88 (t, J¼6.9 Hz, 3H), 2.25 (s, 6H), 2.47–3.00 (m,
3H), 3.13–3.24 (m, 1H), 3.61–3.78 (m, 2H), 4.17–4.27 (m,
1H), 4.37–4.46 (m, 1H), 5.21–5.32 (m, 1H), 5.74–5.86 (m,
1H), 7.10–7.40 (m, 11H), 7.74 (d, J¼7.2 Hz, 2H); 13C
NMR (75 MHz, CDCl3) d 163.81, 163.75, 139.52, 139.41,
135.96, 135.91, 132.18, 132.11, 132.03, 129.95, 129.84,
129.31, 129.25, 129.18, 128.95, 128.89, 128.44, 128.40, 128.25,
128.21, 127.93, 127.88, 116.07, 115.08, 62.17, 44.88, 44.31,
42.62, 42.03, 31.79, 31.69, 31.36, 31.24, 28.81, 28.15, 20.98,
13.39; 31P NMR (121.5 MHz, CDCl3) d 41.6; MS (ESI, pos-
itive mode, m/z) 431.1 (MꢀBrꢀ); HRMS (MALDI/DHB)
MꢀBrꢀ calcd for C28H32O2P+: 431.2129. Found: 431.2134.
1
51%. 63% ee. H NMR (300 MHz, CDCl3/TMS) d 0.89
(t, J¼7.2 Hz, 3H), 1.03 (t, J¼7.2 Hz, 3H), 1.27 (t, J¼
7.2 Hz, 3H), 1.31–1.48 (m, 4H), 1.99–2.18 (m, 4H), 4.17
(q, J¼7.2 Hz, 2H), 5.57 (t, J¼3.0 Hz, 1H).9
4.1.5. Representative procedure for the synthesis of allenic
ketone, nitrile, and amide (Table 5). Preparation of 4-
phenyl-1-pyrrolidin-1-yl-hexa-2,3-dien-1-one (13a). To a
solution of chiral phosphine 6b (0.2 mmol) in THF (1.0 mL)
was added BrCH2CON(CH2)4 12a (0.2 mmol), and the reac-
tion mixture was stirred at room temperature for 15 h. To the
reaction system, NaHMDS (1 M in THF, 0.2 mL) was added
and the resulting mixture was stirred for 1.5 h. After the reac-
tion mixture was stirred at ꢀ20 ꢁC for 0.5 h, ketene 9a
(0.2 mmol) was added, and the mixturewas stirred for further
24 h at ꢀ20 ꢁC. The reaction mixture was quenched with wa-
ter, diluted with petroleum ether, and then filtered. The filtrate
was concentrated and the residue was purified by flash chro-
matography to givechiral allene 13a as paleyellow oil. Yield:
69%. [a]2D0 +73.0 (c 0.78, CHCl3). 32% ee. IR (KBr) n/cmꢀ1
2970 (m), 2874 (m), 1942 (m), 1634 (vs), 1624 (vs), 1494
(w); 1H NMR (300 MHz, CDCl3/TMS) d 1.19 (t, J¼7.2 Hz,
3H), 1.80–1.97 (m, 4H), 2.50–2.60 (m, 2H), 3.48–3.57 (m,
4H), 6.22 (t, J¼3.3 Hz, 1H), 7.22–7.43 (m, 5H); 13C NMR
(75 MHz, CDCl3) d 210.3, 163.3, 134.6, 128.4, 127.4,
126.2, 111.2, 93.1, 47.1, 46.4, 26.2, 24.1, 22.8, 12.3; MS
(EI, m/z, rel intensity) 241 (9.4), 226 (21.0), 128 (18.2), 98
4.1.2. Representative procedure using ketenes (Table 3).
Preparation of S-4-phenyl-hexa-2,3-dienoic acid ethyl es-
ter (10a). To asolutionof phosphonium salt 2b(0.2 mmol) in
THF (1.0 mL) was added NaHMDS (1 M in THF, 0.2 mL).
After stirring for 1 h at room temperature, the reaction mix-
ture was cooled to ꢀ78 ꢁC and stirred for further 2 h. To
the mixture was added ketene 9a (0.2 mmol), and the result-
ing mixture was allowed to stir for further 48 h at ꢀ78 ꢁC.
After quenching with water, the reaction mixture was diluted
with petroleum ether and filtered. The filtrate was concen-
trated and the residue was purified by flash chromatography
to give 10a as pale yellow oil. Yield: 80%. [a]2D0 +124.2 (c
1
0.74, CHCl3). 81% ee. H NMR (300 MHz, CDCl3/TMS)
d 1.18 (t, J¼7.2 Hz, 3H), 1.28 (t, J¼6.9 Hz, 3H), 2.51–2.59
(m, 2H), 4.17–4.26 (m, 2H), 5.96 (t, J¼3.6 Hz, 1H), 7.25–
7.41 (m, 5H).9
The filter cake was submitted to column chromatography to
recover phosphine oxide 14a.

8052
C.-Y. Li et al. / Tetrahedron 63 (2007) 8046–8053
2004; For recent reviews, see: (a) Zimmer, R.; Dinesh, C. U.;
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(56.9), 55 (100.0). Anal. Calcd for C16H19NO: C, 79.63; H,
7.94; N, 5.80. Found: C, 79.69; H, 7.79; N, 5.36.
4.1.5.1. 4-Phenyl-hexa-2,3-dienoic acid diethylamide
13b. Pale yellow oil. Yield: 76%. [a]2D0 132.5 (c 0.52,
CHCl3). 60% ee. IR (KBr) n/cmꢀ1 2971 (s), 2933 (m),
1945 (m), 1635 (vs), 1494 (m), 1456 (s); 1H NMR
(300 MHz, CDCl3/TMS) d 1.13–1.21 (m, 9H), 2.45–2.63
(m, 2H), 3.38–3.49 (m, 4H), 6.26 (t, J¼3.3 Hz, 1H), 7.21–
7.43 (m, 5H); 13C NMR (75 MHz, CDCl3) d 209.9, 164.1,
134.8, 128.3, 127.2, 126.1, 111.2, 91.4, 42.6, 40.6, 22.8,
14.4, 12.8, 12.2; MS (EI, m/z, rel intensity) 243 (3.5), 215
(20.8), 100 (68.9), 72 (100.0). Anal. Calcd for C16H21NO:
C, 78.97; H, 8.70; N, 5.76. Found: C, 78.47; H, 8.83; N, 5.37.
4.1.5.2. 4-Phenyl-hexa-2,3-dienenitrile 13c. Pale yel-
low oil. Yield: 65%. [a]2D0 +61.6 (c 0.68, CHCl3). 20% ee.
IR (KBr) n/cmꢀ1 2972 (vs), 2213 (vs), 1947 (w), 1617
1
(m), 1599 (m), 1494 (s), 1446 (s); H NMR (300 MHz,
4. (a) Matsumoto, Y.; Naito, M.; Uozumi, Y.; Hayashi, T. J. Chem.
Soc., Chem. Commun. 1993, 1468; (b) Tillack, A.; Koy, C.;
Michalik, D.; Fischer, C. J. Organomet. Chem. 2000, 603,
116; (c) Ogasawara, M.; Ikeda, H.; Nagano, T.; Hayashi, T.
J. Am. Chem. Soc. 2001, 123, 2089; (d) Han, J. W.;
Tokunaga, N.; Hayashi, T. J. Am. Chem. Soc. 2001, 123,
12915; (e) Ogasawara, M.; Ueyama, K.; Nagano, T.;
Mizuhata, Y.; Hayashi, T. Org. Lett. 2003, 5, 217; (f)
Hayashi, T.; Tokunaga, N.; Inoue, K. Org. Lett. 2004, 6, 305.
5. For recent examples, see: (a) Imada, Y.; Nishida, M.; Kutsuwa,
K.; Murahashi, S.-I.; Naota, T. Org. Lett. 2005, 7, 5837; (b)
Trost, B. M.; Fandrick, D. R.; Dinh, D. C. J. Am. Chem. Soc.
2005, 127, 14186.
CDCl3/TMS) d 1.19 (t, J¼7.2 Hz, 3H), 2.53–2.62 (m, 2H),
5.61 (t, J¼3.3 Hz, 1H), 7.26–7.44 (m, 5H); 13C NMR
(75 MHz, CDCl3) d 216.5, 132.4, 128.7, 128.5, 126.5,
114.1, 113.4, 70.6, 22.8, 11.9; MS (EI, m/z, rel intensity)
169 (32.7), 154 (100.0), 129 (43.7), 113 (30.2), 51 (43.4);
HRMS (EI) calcd for C12H11N: 169.0891. Found: 169.0888.
4.1.5.3. 1,4-Diphenyl-hexa-2,3-dien-1-one 13d. Pale
yellow oil. Yield: 65%. [a]2D0 +45.5 (c 0.40, CHCl3). 40%
ee. IR (KBr) n/cmꢀ1 2970 (w), 1933 (m), 1654 (vs), 1597
1
(m), 693 (m); H NMR (300 MHz, CDCl3/TMS) d 1.15 (t,
J¼7.2 Hz, 3H), 2.53–2.62 (m, 2H), 6.71 (t, J¼3.3 Hz, 1H),
7.20–7.33 (m, 1H), 7.33–7.41 (m, 6H), 7.41–7.60 (m, 1H),
7.87 (d, J¼7.5 Hz, 2H); 13C NMR (75 MHz, CDCl3) d
215.0, 191.5, 137.6, 133.9, 132.5, 128.6, 128.5, 128.2, 127.7,
126.3, 111.6, 97.3, 23.0, 12.2; MS (EI, m/z, rel intensity) 248
(1.8), 105 (100.0), 77 (41.8), 51 (11.3). Anal. Calcd for
C18H16O: C, 87.06; H, 6.49. Found: C, 86.81; H, 6.44.
6. (a) Bestmann, H. J.; Hartung, H. Chem. Ber. 1966, 99, 1198; (b)
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€ €
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€
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ꢀ
24, 3299; (c) Musierowicz, S.; Wroblewski, A. E.; Krawczyk,
H. Tetrahedron Lett. 1975, 437; (d) Yamazaki, J.; Watanabe,
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Acknowledgements
~
Gonsalves, A. M.; Pessoa, J. C.; Paixao, J. A.; Beja, A. M.
Eur. J. Org. Chem. 2004, 4830.
We are grateful for the financial support from the National
Natural Science Foundation of China, the Major State
Basic Research Development Program (Grant No.
2006CB806105), and the Science and Technology Commis-
sion of Shanghai Municipality. We also thank Professor
Kuiling Ding for his fruitful discussion on the asymmetric
hydrogenation.
8. (a)Huang, Z.-Z.;Ye, S.;Xia, W.;Tang, Y. Chem. Commun. 2001,
1384; (b) Ye, S.; Huang, Z.-Z.; Xia, C.-A.; Tang, Y.; Dai, L. X. J.
Am. Chem. Soc. 2002, 124, 2432; (c) Liao, W.-W.; Li, K.; Tang,
Y. J. Am. Chem. Soc. 2003, 125, 13030; (d) Li, K.; Deng, X.-M.;
Tang, Y. Chem. Commun. 2003, 2074; (e) Liao, W.-W.; Deng,
X.-M.; Tang, Y. Chem. Commun. 2004, 1516; (f) Zheng, J.-C.;
Liao, W.-W.; Tang, Y.; Sun, X.-L.; Dai, L.-X. J. Am. Chem.
Soc. 2005, 127, 12222; (g) Zheng, J.-C.; Liao, W.-W.; Sun, X.-
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2005, 7, 5789; (h) Deng, X.-M.; Cai, P.; Ye, S.; Sun, X.-L.;
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Chem. Soc. 2006, 128, 9730; (i) Ye, L.-W.; Sun, X.-L.; Zhu,
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X.-B.; Sun, X.-L.; Tang, Y.; Zheng, J.-C.; Xu, Z.-H.; Zhou, Y.-
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Supplementary data
Characterization data for new compounds, HPLC spectra of
chiral allenes, and synthetic procedures (PDF) for key com-
pounds are available. This material is available free of
charge via the Internet at http://pubs.acs.org. Supplementary
data associated with this article can be found in the online
version, at doi:10.1016/j.tet.2007.05.053.
9. Li, C.-Y.; Sun, X.-L.; Jing, Q.; Tang, Y. Chem. Commun. 2006,
2980.
References and notes
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