Iron porphyrin-catalyzed olefination of ketenes with diazoacetate for the enantioselective synthesis of allenes

Article abstract of DOI:10.1021/ja068642v

In the presence of Ph₃P and catalytic Fe(TCP)Cl, ketenes could react with EDA to give allenes in high yields under neutral conditions for the first time. By employing chiral phosphine instead of PPh₃, allenes could be synthesized with high enantioselectivity (93-98% ee) in good yields. Copyright

Full text of DOI:10.1021/ja068642v

Published on Web 01/18/2007
Iron Porphyrin-Catalyzed Olefination of Ketenes with Diazoacetate for the
Enantioselective Synthesis of Allenes
Chuan-Ying Li,† Xiao-Bing Wang,‡ Xiu-Li Sun,† Yong Tang,*,† Jun-Cheng Zheng,† Zheng-Hu Xu,†
Yong-Gui Zhou,*,‡ and Li-Xin Dai†
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of
Sciences, 354 Fenglin Lu, Shanghai 200032, China, and Dalian Institute of Chemical Physics, Chinese Academy of
Sciences, 457 Zhongshan Road, Dalian 116023, China
Received December 1, 2006; E-mail: tangy@mail.sioc.ac.cn; ygzhou@dicp.ac.cn
Table 1. Olefination of Ketenes with EDA Catalyzed by
The Wittig reaction and its variants are the most powerful
approaches for constructing carbon-carbon double bonds in organic
synthesis due to their unambiguous positioning and good stereo-
selectivity.1 Of the recent developments,2-4 much attention has been
paid to ylide olefination of aldehydes3 and ketones4 under neutral
conditions by transition metal complex-catalyzed decomposition
of diazo compounds to generate ylide in situ. In our studies on
ylide reactions in organic synthesis,2b-e,5 we are interested in
developing an efficient method for the synthesis of allenes via
olefination of ketenes, unstable carbonyl compounds,6 with diazo-
acetate in the presence of transition metal complex. Fortunately,
we found that such an olefination process could be achieved
smoothly in the presence of PPh3 and 0.5 mol % of tetra(p-
chlorophenyl)porphyrin iron chloride (Fe(TCP)Cl). In particular,
when chiral phosphine was used, optically active allenes could be
prepared with high enantioselectivities in high yields. In this
communication, we wish to report the preliminary results.
Allenes are of great importance due to their occurrence7 in natural
products and biologically active compounds, and they are valuable
intermediates8 in organic synthesis. Although many synthetic
methods have been developed, a practical and mild process, in
particular, for the synthesis of optically active ones,9 is still a
challenge. Gratifyingly, it was found that allenic ester 1a could be
synthesized in nearly quantitative yield when the reaction of
2-phenylprop-1-en-1-one with ethyl diazoacetate was carried out
in toluene at 0 °C in the presence of PPh3 and 0.5 mol % of Fe-
(TCP)Cl (Table 1, entry 1). Further studies showed that a variety
of ketenes with different structures are good substrates for this
olefination. As shown in Table 1, pure disubstituted ketenes gave
good to excellent yields (entries 1-8). Disubstituted ketenes,
prepared in situ from acyl chlorides without further purification,
also worked well to afford the trisubstituted allenes in good yields
(entries 9 and 10). A one-pot strategy has also been developed for
some unstable ketenes. For example, 4-monosubstituted and 4,4-
disubstituted allenic esters 1k-1o could be obtained in good yields
when Et3N and acyl chloride were added sequentially10 into the
ylide generated in situ from phosphine and diazoacetate (entries
11-15). Thus, various 4-monosubstituted and 4,4-disubstituted
allenic esters could be synthesized (even in gram scale, entry 2 in
Table 1) by the current protocol.
Fe(TCP)Cla
entry
R1
R2
method
1
yield (%)b
1
2
3
4
5
6
7
8
Ph
Ph
Ph
Ph
Me
Et
i-Pr
n-Bu
Et
Et
A
A
A
A
A
A
A
A
A
A
B
B
B
B
B
1a
1b
1c
1d
1g
1h
1i
1j
1e
1f
1k
1l
1m
1n
1o
99
99 (94d)
99
98
98
92
95
83
53
75
77
80
56
59
74
p-Cl-C6H4
p-MeO-C6H4
o-Me-C6H4
COOEt
Ph
Et
i-Bu
allyl
3-butenyl
H
H
H
9c
10c
11
12
13
14
15
Ph
n-C5H11
n-C10H21
Ph
Br
n-Bu
Me
Et
a For detailed procedures of methods A and B, please see the Supporting
Information. b Isolated yield. c Ketenes were prepared in situ. d In 7 mmol
scale, and 0.25 mol % of Fe(TCP)Cl was used.
Scheme 1. Possible Pathways for the Olefination of Aldehydes
via Transition-Metal-Catalyzed Decomposition of Diazoacetate
mechanistic insight, it is envisaged that chiral allenes could be
prepared enantioselectively just by the use of chiral phosphine
instead of triphenylphosphine. To our delight, a variety of optically
active allenic esters could be synthesized with excellent enantio-
selectivities (93-98% ee) in high yields by employing chiral
diphosphine compound 4 under the optimal conditions, as shown
in Table 2.11 These results also proved clearly that the mechanism
of the present olefination involves the generation of an ylide through
catalytic transfer of an iron(II) carbene ligand to phosphine.
Compound 4 is a diphosphine, and the molar ratio of EDA to 4
used in the current reaction is 2:1. Therefore, both monoylide 6a
and diylide 6b are possible intermediates of this reaction. To
elucidate the real intermediate, ylides 6a and 6b were synthesized
For the olefination of aldehydes with diazo compounds catalyzed
by transition metal complex, there are two mechanistic pathways
in the literature,3,4 as shown in Scheme 1, depending on the metal
complex. In the case of Fe(TCP)Cl employed, Woo and his co-
workers3g,4a documented that the mechanism involved the formation
of a free ylide (Path B in Scheme 1). On the basis of this
† Shanghai Institute of Organic Chemistry.
‡ Dalian Institute of Chemical Physics.
9
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J. AM. CHEM. SOC. 2007, 129, 1494-1495
10.1021/ja068642v CCC: $37.00 © 2007 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Enantioselective Synthesis of Allenesa
active allenic esters. In addition, the results described here confirmed
that the mechanism involves ylide olefination. The high enantio-
selectivity, the neutral condition, and the fact that the phosphine
could be recovered and reused make the current method potentially
useful in organic synthesis.
Acknowledgment. We are grateful for the financial support
from the Natural Sciences Foundation of China, the Major State
Basic Research Development Program (Grant No. 2006CB806105),
and The Science and Technology Commission of Shanghai
Municipality.
entry
R1
R2
1
yield (%)b
ee (%)c
1
2
3
4
5
6
7
Ph
Ph
Ph
Me
Et
n-Pr
Et
Et
Et
1a
1bd
1r
1i
1h
1g
1s
72
90
87
86
81
83
80
93
97
93
97
96
97
98
o-Me-C6H4
p-MeO-C6H4
p-Cl-C6H4
p-Br-C6H4
Supporting Information Available: Detailed experimental pro-
cedures and characterization data for all new compounds (PDF). This
material is available free of charge via the Internet at http://pubs.acs.org.
Et
a For detailed procedures, please see the Supporting Information.
b Isolated yield. c Determined by chiral HPLC. d 1b was assigned as
S-configuration by comparing its optical rotation with the literature.
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from their corresponding salts 5a and 5b, respectively. It was found
that ylide 6a gave the desired product 1b in 88% yield with 96%
ee, which is consistent with the experimental observation (entry 2,
Table 2). However, diylide 6b afforded the enantiomer of 1b in
37% yield with -20% ee. These results, together with the fact that
83% of monophosphine oxide 7 was isolated in the reaction of
2-phenylpent-1-en-1-one with ylide generated in situ (entry 3 in
Table 2), showed clearly that the monoylide 6a is the intermediate
and further confirmed the mechanism Woo et al. proposed.
Noticeably, the recovered chiral phosphine oxide could be readily
reduced by HSiCl3 and reused. For example, 1r could be obtained
with 94% ee in 83% yield using the recovered compound 4 as the
phosphine (Scheme 3), comparable to the results when phosphine
4 was first used (entry 3 in Table 2).
In summary, we have developed an efficient method for the
synthesis of allenes under neutral conditions by olefination of
ketenes with EDA in the presence of Ph3P and catalytic Fe(TCP)-
Cl for the first time. We have also realized its asymmetric version
and found that, by employing chiral phosphine instead of PPh3,
chiral allenes could be synthesized with high enantioselectivities
(93-98% ee) in good yields, providing an easy access to optically
(10) For detailed procedure, please see Supporting Information.
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T. M. Synthesis 2002, 579. (c) Lertpibulpanya, D.; Marsden, S. P.;
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(d) Dai, W.-M.; Wu, A.; Wu, H. Tetrahedron: Asymmetry 2002, 2187.
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