Ph3As-catalyzed Wittig-type olefination of aldehydes with diazoacetate in the presence of Na2S2O4

Article abstract of DOI:10.1021/jo0709899

(Chemical Equation Presented) In the presence of sodium hydrosulfite and a catalytic amount of AsPh₃ and Fe(TCP)Cl, aldehydes react with ethyl diazoacetate to give the corresponding α,β-unsaturated esters in high yields with excellent stereoselectivities (E/Z > 50/1).

Full text of DOI:10.1021/jo0709899

4
Ph3As-Catalyzed Wittig-Type Olefination of
Aldehydes with Diazoacetate in the Presence of
Na2S2O4
phosphines or arsines is required, and the reactions are not
atom-economical because of the formation of phosphine oxide
or arsine oxide. As our ongoing research project on ylide
chemistry, we are particularly interested in developing a new
6
process for this olefination using a catalytic amount of PPh3 or
AsPh3. Since triphenylphosphine oxide is very hard to be
reduced under mild conditions, PPh3 was not investigated
†
†
†
‡
Peng Cao, Chuan-Ying Li, Yan-Biao Kang, Zuowei Xie,
†
,†
Xiu-Li Sun, and Yong Tang*
7
further. During the course of our study, we fortunately found
that AsPh3 can catalyze the Wittig-type reaction of aldehydes
with diazoacetate to give the corresponding olefins with high
yields and excellent stereoselectivities in the presence of a
reducing agent. Our preliminary results are reported in this
paper.
State Key Laboratory of Organometallic Chemistry, Shanghai
Institute of Organic Chemistry, Chinese Academy of Sciences,
54 Fenglin Lu, Shanghai 200032, China, and Department of
3
Chemistry, The Chinese UniVersity of Hong Kong, Shatin, New
Territories, Hong Kong, China
8
9
tangy@mail.sioc.ac.cn
Both AsBu3 and tellurides proved to be good catalysts for
the reaction of aldehydes with bromoacetates under basic
conditions. Considering that the tellurides were found to be
ReceiVed May 18, 2007
9
c
partially decomposed to toxic tellurate, we chose stable
triphenylarsine to initiate the study. An attempted olefination
of p-chlorobenzaldehyde with ethyl diazoacetate (EDA) gave
the desired product stereoselectively (E/Z > 99/1) in 89% yield
in the presence of 1.2 equiv of AsPh3 and 1.0 mol % of
Fe(TCP)Cl (TCP ) tetra(p-chlorophenyl)porphyrinate).10 This
result encouraged us to develop a catalytic version by in situ
reduction of Ph3AsO to regenerate AsPh3. Although P(OPh)3
could reduce Ph3AsO to AsPh3 under mild conditions,8 in
order to make this olefination practical and environmentally
friendly, we evaluated inorganic salts as reducing reagents. After
many attempts, we found that sodium hydrosulfite (Na2S2O4)
,11
In the presence of sodium hydrosulfite and a catalytic amount
of AsPh and Fe(TCP)Cl, aldehydes react with ethyl diazo-
3
acetate to give the corresponding R,â-unsaturated esters in
high yields with excellent stereoselectivities (E/Z > 50/1).
11
could be used as a reducing reagent for this reaction. As shown
in Table 1, the solvent, the reaction temperature, and the loading
of Fe(TCP)Cl strongly influenced the yield of product 3a. Under
optimal conditions, p-chlorobenzaldehyde can react with EDA
to give the olefin product in 83% yield with excellent stereo-
selectivity in the presence of 10 mol % of AsPh3 and 0.5 mol
1
2
The Wittig reaction and its variants are some of the most
powerful synthetic tools for constructing carbon-carbon double
bonds in organic synthesis. Very recently, much attention has
been paid to ylide olefination of aldehydes3 and ketones with
readily accessible diazo compounds in the presence of a catalytic
amount of a transition metal complex, providing an elegant
protocol for the Wittig reaction under neutral conditions. For
all these reactions, however, a stoichiometric amount of tertiary
,4
5
%
of Fe(TCP)Cl in toluene/water biphasic system (entry 11,
Table 1). When 20 mol % of AsPh3 was used, 97% yield was
achieved (entry 10, Table 1).
To explore the generality of this reaction, a variety of
aldehydes and ketones were investigated under the optimal
conditions. As shown in Table 2, both aromatic and aliphatic
†
Chinese Academy of Sciences.
The Chinese University of Hong Kong.
‡
1) Wittig, G.; Geissler, G. Liebigs Ann. Chem. 1953, 580, 44.
(6) (a) Ye, S.; Huang, Z.-Z.; Xia, C.-A.; Tang, Y.; Dai, L. X. J. Am.
Chem. Soc. 2002, 124, 2432. (b) Liao, W.-W.; Li, K.; Tang, Y. J. Am.
Chem. Soc. 2003, 125, 13030. (c) Zheng, J.-C.; Liao, W.-W.; Tang, Y.;
Sun, X.-L.; Dai, L.-X. J. Am. Chem. Soc. 2005, 127, 12222. (d) Deng, X.-
M.; Cai, P.; Ye, S.; Sun, X.-L.; Liao, W.-W.; Li, K.; Tang, Y.; Wu, Y.-D.;
Dai, L.-X. J. Am. Chem. Soc. 2006, 128, 9730. (e) Li, C.-Y.; Sun, X.-L.;
Jing, Q.; Tang, Y. Chem. Commun. 2006, 2980. (f) Li, C.-Y.; Wang, X.-
B.; Sun, X.-L.; Tang, Y.; Zheng, J.-C.; Xu, Z.-H.; Zhou, Y.-G.; Dai, L.-X.
J. Am. Chem. Soc. 2007, 129, 1494.
3
1
3
Lebel, H.; Paquet, V.; Proulx, C. Angew. Chem., Int. Ed. 2001, 40, 2887.
g) Mirafzal, G. A.; Cheng, G.; Woo, L. K. J. Am. Chem. Soc. 2002, 124,
(7) Imamoto, T.; Kikuchi, S.; Miura, T.; Wada, Y. Org. Lett. 2001, 3,
87.
(8) Shi, L.-L.; Wang, W.-B.; Wang, Y.-C.; Huang, Y.-Z. J. Org. Chem.
1989, 54, 2027.
(
1
76. (h) Chen, Y.; Huang, L.; Ranade, M. A.; Zhang, X. P. J. Org. Chem.
003, 68, 3714. (i) Santos, A. M.; Romao, C. C.; Kuhn, F. E. J. Am. Chem.
2
Soc. 2003, 125, 2414. (j) Aggarwal, V. K.; Fulton, J. R.; Sheldon, C. G.;
de Vincente, J. J. Am. Chem. Soc. 2003, 125, 6034. (k) Santos, A. M.;
Pedro, F. M.; Yogalekar, A. A.; Lucas, I. S.; Romao, C. C.; Kuhn, F. E.
Chem.sEur. J. 2004, 10, 6313.
(9) (a) Huang, Y.-Z.; Shi, L.-L.; Li, S.-W.; Wen, X.-Q. J. Chem. Soc.,
Perkin Trans. 1 1989, 2397. (b) Huang, Z.-Z.; Ye, S.; Xia, W.; Tang, Y.
Chem. Commun. 2001, 1384. (c) Huang, Z.-Z.; Ye, S.; Xia, W.; Yu, Y.-H.;
Tang, Y. J. Org. Chem. 2002, 67, 3096. (d) Huang, Z.-Z.; Tang, Y. J. Org.
Chem. 2002, 67, 5320. (e) Li, K.; Ran, L.; Yu, Y.-H.; Tang, Y. J. Org.
Chem. 2004, 69, 3986.
(
4) Zhu, S.; Liao, Y.; Zhu, S. Org. Lett. 2004, 6, 377.
5) (a) Cheng, G.; Mirafzal, G. A.; Woo, L. K. Organometallics 2003,
(
2
2
5
2, 1468. (b) Lee, M.-Y.; Chen, Y.; Zhang, X. P. Organometallics 2003,
2, 4905. (c) Chen, Y.; Huang, L.; Zhang, X. P. J. Org. Chem. 2003, 68,
925. (d) Chen, Y.; Huang, L.; Zhang, X. P. Org. Lett. 2003, 5, 2493. (e)
(10) AsPh3 is less nucleophilic than PPh3. See: Methot, J. L.; Roush,
W. R. AdV. Synth. Catal. 2004, 346, 1035.
(11) Ph3AsO was reported to be reduced by Na2S2O4 to triphenyl arsine
in H2O. See: Lu, X.; Wang, Q.-W.; Tao, X.-C.; Sun, J.-H.; Lei, G.-X. Acta
Chim. Sinica 1985, 43, 450.
Pedro, F. M.; Santos, A. M.; Baratta, W.; Kuhn, F. E. Organometallics
007, 26, 302.
2
10.1021/jo0709899 CCC: $37.00 © 2007 American Chemical Society
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J. Org. Chem. 2007, 72, 6628-6630
Published on Web 07/27/2007

TABLE 1. Effects of Reaction Conditions on Olefination of
SCHEME 1. Two Mechanisms for the Olefination
Catalyzed by Transition Metal Decomposition of
Diazoacetate
a
p-Chlorobenzaldehyde
toluene/H2O
(v/v)
T
(°C)
Fe(TCP)Cl
(mol %)
yieldb
(%)
entry
1
2
3
4
5
6
7
8
9
10.0
4.0
2.4
1.0
2.4
2.4
2.4
2.4
2.4
2.4
2.4
70
70
70
70
60
80
90
80
80
80
80
2.0
2.0
2.0
2.0
2.0
2.0
2.0
1.0
0.5
0.5
0.5
39
78
85
69
58
88
40
90
90
SCHEME 2. Control Experiments
c
1
1
0
1
97
c,d
83
a
Conditions: the reaction was carried out under N2; 0.4 mmol (0.13
mol/L) of aldehyde, 20 mol % of AsPh3, Fe(TCP)Cl (cat.), 0.8 mmol of
Na2S2O4 were mixed with toluene and H2O, EDA (0.8 mmol) was slowly
b
added within 8 h through a syringe pump or in portions. Isolated yields.
c
Concentration of the aldehyde: 0.2 mol/L. d 10 mol % of AsPh3 was used.
TABLE 2. Catalytic Ylide Olefination under Biphasic Conditionsa
selectivity (entry 14). Both ester and alkenyl groups were well-
tolerated in this reaction (entries 5 and 13). Aliphatic aldehydes
could give the corresponding products in high yields with
excellent selectivities (entries 15 and 16). When 4-acetylbenz-
aldehyde was employed, only the aldehyde was olefinated,
suggesting that the chemoselectivity for ketone and aldehyde
is quite good (entry 17). Noticeably, this olefination was
practically useful since an excellent yield was still achieved
when the reaction was carried out in gram scale (entry 8). In
addition, trifluoromethyl ketone 1r can be readily converted to
the corresponding â-trifluoromethyl R,â-unsaturated esters with
excellent stereoselectivity in 85% yield, offering an easy access
to trifluoromethylvinyl compounds (entry 18).
yieldb
(%)
time Fe(TCP)Cl
entry
R
(h)
(mol %)
E/Zc
1
2
3
4
5
6
7
8
9
4-ClC6H4 (1a)
8
8
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.1
1.0
1.0
1.0
0.5
0.75
1.0
0.5
1.0
99/1 97
99/1 95
99/1 95
99/1 91
99/1 99
99/1 89
99/1 92
3-ClC6H4 (1b)
4-BrC6H4(1c)
8
2-BrC6H4(1d)
8
4-MeOOCC6H4 (1e)
4-CF3C6H4 (1f)
4-FC6H4 (1g)
8
8
8
d
2,4-Cl2C6H3 (1h)
2,6-Cl2C6H3 (1i)
C6H5 (1j)
4-MeC6H4 (1k)
4-MeOC6H4(1l)
2-(but-3-enyl)C6H4 (1m)
2-furyl (1n)
CH3(CH2)7 (1o)
cyclohexyl (1p)
4-CH3COC6H4 (1q)
CF3/4-ClC6H4 (1r)
8
99/1 96 (97 )
99/1 71
8
10
11
12
13
14
15
16
17
18
8
99/1 86
For olefination of aldehydes with diazoacetate catalyzed by
8
99/1 81
3-5
a transition metal complex, there are two possible mechanisms
8
99/1 81
99/1 78e
as shown in Scheme 1. In the present reaction, it was found
that the desired product was not detected in the reaction of
p-chlorobenzaldehyde with EDA in the absence of Ph3As even
when a stoichiometric amount of Fe(TCP)Cl was used. This
has ruled out the possibility of path A. In addition, the desired
product 3a was not observed in the absence of Fe(TCP)Cl
(Scheme 2).
12
8
99/1 87e
99/1 80
50/1 78
99/1 93
99/1 85
12
8
8
8
a
Conditions: carbonyl compounds (0.6 mmol), EDA (1.2 mmol),
Na2S2O4 (1.2 mmol), toluene/H2O (3 mL/1.25 mL), 80 °C. EDA was slowly
added within 8 h via a syringe pump or in portions. Isolated yield.
Determined by 300 MHz H NMR. In 6 mmol scale. Fe(TCP)Cl was
added in portions and 3.0 equiv of EDA was added within 12 h via a syringe
pump or in portions.
b
These results suggested that the aforementioned olefination
proceeds via an ylide route, similar to the mechanism proposed
c
1
d
e
3
g
in the phosphine-mediated olefination by Woo. Thus, the
reaction path is proposed in Scheme 3. Fe(TCP)Cl is first
reduced to Fe(TCP) by EDA in situ. Then it decomposes
diazoacetate to form iron-carbene intermediate A, followed by
converting AsPh3 to arsonium ylide 4. The ylide reacts with
aldehyde to afford olefin 3 and the byproduct Ph3AsO which is
reduced by Na2S2O4 in the aqueous phase to regenerate
triphenylarsine to complete the catalytic cycle.
aldehydes worked well to give the desired products with
excellent stereoselectivities in high yields. In most cases, only
E-isomers were obtained. Aromatic aldehydes with electron-
withdrawing groups afforded R,â-unsaturated esters stereose-
lectively in excellent yields (entries 1-8). The yield for 2,6-
Cl2C6H3CHO 1i decreased, probably due to steric effects (entry
9
). Although aromatic aldehydes with electron-donating groups
In summary, we have developed the first example of catalytic
Wittig-type reaction of aldehyde with diazoacetate using 20 mol
% of AsPh3, based on porphyrin iron mediated carbene transfer
under the toluene/water biphasic condition. The preliminary
mechanistic studies have shown that the olefination proceeded
3g,h
were always less reactive in ylide reactions, they were good
substrates for this olefination when 1.0 mol % of Fe(TCP)Cl
was employed (entries 11 and 12). 2-Furaldehyde also worked
well to give the desired ester in 87% yield with excellent
J. Org. Chem, Vol. 72, No. 17, 2007 6629

SCHEME 3. A Proposed Mechanism
aldehyde). Fe(TCP)Cl (2.5 mg, 0.003 mmol), Ph
3
As (37 mg, 0.12
mmol), and Na (210 mg, 1.2 mmol) were mixed in a Schlenk
2 2 4
S O
tube. The tube was evacuated and backfilled with nitrogen.
p-Bromobenzaldehyde (111 mg, 0.6 mmol) was added, followed
by toluene (3.0 mL) and water (1.25 mL). The reaction mixture
was heated to 80 °C, and 2.0 equiv of EDA (126 µL, 1.2 mmol)
was added within 8 h via a syringe pump or in portions. After the
reaction was complete, the resulting mixture was cooled to room
temperature, extracted with CH
2 2 2 4
Cl , dried with Na SO , and
concentrated. The residue was purified by flash chromatography
1
(
silica gel) to give the product 3c: 145 mg (95%); H NMR (300
MHz, CDCl /TMS) δ 7.62 (d, J ) 16.2 Hz, 1H), 7.53 (d, J ) 8.4
Hz, 2H), 7.40 (d, J ) 8.4 Hz, 2H), 6.43 (d, J ) 16.2 Hz, 1H), 4.27
3
(q, J ) 7.2 Hz, 2H), 1.34 (t, J ) 7.2 Hz, 3H).
Acknowledgment. We are grateful for the financial support
from the National Natural Science Foundation of China (NSFC),
the Major State Basic Research Development Program (Grant
No. 2006CB806105), The Chinese Academy of Sciences, the
Science and Technology Commission of Shanghai Municipality,
and NSFC and the RGC of Hong Kong Joint Research Scheme
via an ylide route, suggesting that ylide 4 and iron carbene A
are water-tolerant under the reaction conditions. The high yield,
excellent stereoselectivity, mild reaction conditions, and, in
particular, use of a catalytic amount of AsPh3 and cheap
inorganic reducing reagent make the current method practically
useful for the synthesis of R,â-unsaturated esters.
(Grant No. 20710011 to Y.T. and N_CUHK446/06 to Z.X.).
Supporting Information Available: Detailed experimental
procedures and characterization data for all new compounds (PDF).
This material is available free of charge via the Internet at
http://pubs.acs.org.
Experimental Section
Representative Procedure for Iron(III) Porphyrin and Tri-
phenylarsine-Catalyzed Olefination Reaction (For p-Bromobenz-
JO0709899
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630 J. Org. Chem., Vol. 72, No. 17, 2007