Enantioselective synthesis of allenic esters via an ylide route

Article abstract of DOI:10.1039/b603659g

Pseudo-C₂-symmetric chiral phosphorus ylides have been designed and synthesized for the enantioselective preparation of allenic esters, and up to 92% ee has been achieved. The Royal Society of Chemistry 2006.

Full text of DOI:10.1039/b603659g

View Article Online / Journal Homepage / Table of Contents for this issue
COMMUNICATION
www.rsc.org/chemcomm | ChemComm
Enantioselective synthesis of allenic esters via an ylide route{
Chuan-Ying Li, Xiu-Li Sun, Qing Jing and Yong Tang*
Received (in Cambridge, UK) 10th March 2006, Accepted 22nd May 2006
First published as an Advance Article on the web 7th June 2006
DOI: 10.1039/b603659g
smoothly with ethyl phenyl ketene at 278 uC to afford chiral allene
Pseudo-C2-symmetric chiral phosphorus ylides have been
designed and synthesized for the enantioselective preparation
of allenic esters, and up to 92% ee has been achieved.
6a with 81% ee in 80% yield. Further studies showed that the
enantioselectivity could be improved to 92% ee when ethyl ester
was replaced by tert-butyl ester (Scheme 2). This result encouraged
us to study the generality of the reaction by investigating a variety
of ketenes with different structures. As shown in Table 1, the
substituents on the ketene proved to strongly influence both the
yields and the enantioselectivities. For example, 2-aryl-1-buten-1-
one gave 4-aryl-2,3-hexadienoic esters in high yields with high
enantioselectivities (Table 1, entries 1 and 6–7), and up to 91% ee
was obtained. Replacement of the ethyl group on ketene 5a with
other alkyl groups, such as iso-propyl, benzyl and allyl, decreased
the enantiomeric excess greatly (Table 1, entries 2 and 4–5). As
dialkyl ketene 5h and monosubstituted ketene 5i are not stable and
could not be purified, as could ketenes 5a–5c, we developed a one-
pot strategy,11 finding that in the presence of triethylamine, the
reaction of acid chloride with phosphonium salt 4a worked well,
giving the desired allenic esters in good yields with moderate
enantioselectivities (Table 1, entries 8–9).
Chiral ylides have developed into excellent reagents for the
synthesis of optically active epoxides,1 cyclopropanes,2 aziridines3
and olefins.4 Although the Wittig or Horner–Wadsworth–
Emmons (HWE) reaction is good for the preparation of allenes,5
which are versatile building blocks6, as well as the basic units of
numerous natural products and biologically-active compounds,7
only a few examples involve its asymmetric version.5c–g Recently,
Tanaka et al. described that optically-active 4,4-disubstituted
allenecarboxylates could be prepared with binol-derived HWE
reagents in 21–71% yields with 23–89% ee values.5e–5f Pinho e
Melo and his co-workers5g documented that a phosphorus ylide
bearing a 10-phenylsulfonyll-iso-borneol reacted with methyl-
ketene to give a penta-2,3-dienoic ester with excellent diastereo-
selectivity. In our studies of ylides in organic synthesis,8 we are
interested in developing the chiral ylide-mediated syntheses of
optically active allenes9 and have found that newly-designed chiral
phosphorus ylides 7a and 7b could react with ketene very well to
afford allenes with ee values up to 92%. In this communication, we
wish to report the preliminary results.
The absolute configurations of 6a and 6e were assigned as S by
chemical transformations.11 Very recently, Aggarwal and his co-
workers developed an elegant dipole–dipole interaction model to
account for the selectivity of the reaction of stabilized phosphorus
ylides with aldehydes.12 Based on their mechanistic insights, as well
as the current experimental results, a stereochemical model, shown
in Scheme 3, has been developed to explain the configuration of
the allenic esters formed. This reaction was proposed to proceed
via a p2s + p2a cycloaddition, affording the oxaphosphetane, which
then decomposed into the corresponding phosphine oxide and
chiral allene. The ketene approached the re face of ylide 7a
preferentially due to the steric hindrance between the substituents
of the ketene and the ylide. Thus allenes with S-configurations
were obtained, consistent with the experimental results.11
Phosphonium salts 4a and 4b were readily available from the
corresponding diketone on a gram scale (Scheme 1). The diketone
1 was reduced with a proline-derived chiral borane to give diol 2 in
98% yield with 98% ee.10 The diol was treated with methane-
sulfonyl chloride,10 followed by reaction with dilithium phenyl-
phosphate to afford chiral phosphine 3, which reacted with
bromoacetate to give the desired phosphonium salts 4a and 4b.
Gratifyingly, after deprotonation by NaHMDS, salt 4a reacted
One of the advantages of the current reaction is that the chiral
phosphine oxide could be recycled and reused. For example, 8 was
recovered in 81% yield and was readily reduced by LiAlH4 into
phosphine 3 in 90% yield (Scheme 4).11
In summary, we have developed an efficient method for the
preparation of optically-active 4,4-disubstituted and 4-mono-
substituted allenic esters in good yields. The easily available
phosphonium salts, good to high enantioselectivity and, in
particular, the recovery and the reuse of the phosphine oxide
Scheme 1
State Key Laboratory of Organometallic Chemistry, Shanghai Institute
of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu,
Shanghai 200032, China. E-mail: tangy@mail.sioc.ac.cn
{ Electronic Supplementary Information (ESI) available: Experimental
details. See DOI: 10.1039/b603659g
Scheme 2
2980 | Chem. Commun., 2006, 2980–2982
This journal is ß The Royal Society of Chemistry 2006

View Article Online
Table 1 Asymmetric synthesis of allenes 6 from phosphonium salts
411
Entry
1
Ketene
4
6
Yield (%)a ee (%)b
4a
80
81
Scheme 4
make the present method potentially useful. Studies on further
improving the enantioselectivity and understanding the mechanism
are in progress in our laboratory.
2
3
4a
4a
76
71
We are grateful for the financial support from the Natural
Sciences Foundation of China and the Science and Technology
Commission of Shanghai Municipality.
71
85
4c
5c
4a
4a
46
51
61
52
Notes and references
1 For reviews, see: (a) A.-H. Li, L.-X. Dai and V. K. Aggarwal, Chem.
Rev., 1997, 97, 2641; (b) L.-X. Dai, X.-L. Hou and Y.-G. Zhou, Pure
Appl. Chem., 1999, 71, 369; (c) V. K. Aggarwal and C. L. Winn, Acc.
Chem. Res., 2004, 37, 611. Selected examples, see: (d ) V. K. Aggarwal,
E. Alonso, I. Bae, G. Hynd, K. M. Lydon, M. J. Palmer, M. Patel,
M. Porcelloni, J. Richardson, R. A. Stenson, J. R. Studley, J.-L. Vasse
and C. L. Winn, J. Am. Chem. Soc., 2003, 125, 10926; (e) K. Li,
X.-M. Deng and Y. Tang, Chem. Commun., 2003, 2704; (f) M. Davoust,
J.-F. Brie`re, P.-A. Jaffre`s and P. Metzner, J. Org. Chem., 2005, 70, 4166;
(g) V. K. Aggarwal, J. P. H. Charmant, D. Fuentes, J. N. Harvey,
G. Hynd, D. Ohara, W. Picoul, R. Robiette, C. Smith, J.-L. Vassa and
C. L. Winn, J. Am. Chem. Soc., 2006, 128, 2105.
6
7
4a
4a
78
75
91
85
2 For reviews, see: (a) Y.-Z. Huang, Y. Tang and Z.-L. Zhou,
Tetrahedron, 1998, 53, 1667; (b) H. Lebel, J. F. Marcoux, C. Molinaro
and A. B. Charette, Chem. Rev., 2003, 103, 977; (c) S. Ye, Y. Tang and
X.-L. Sun, Synlett, 2005, 2720. For recent examples, see: (d ) C. D.
Papageorgious, S. V. Ley and M. J. Gaunt, Angew. Chem., Int. Ed.,
2003, 42, 828; (e) N. Bremeyer, S. C. Smith, S. V. Ley and M. J. Gaunt,
Angew. Chem., Int. Ed., 2004, 43, 2681; (f) C. D. Papageorgious,
M. A. Cubillo de Dios, S. V. Ley and M. J. Gaunt, Angew. Chem., Int.
Ed., 2004, 43, 4641; (g) R. K. Kunz and D. W. C. Macmillan, J. Am.
Chem. Soc., 2005, 127, 3240; (h) K. Huang and Z.-Z. Huang, Synlett,
2005, 1621; (i) J.-C. Zheng,
8d
4a
4a
51
52
63
55
9d
10
4b
51
92
W.-W. Liao, Y. Tang, X.-L. Sun and L.-X. Dai, J. Am. Chem. Soc.,
2005, 127, 12222.
a
b
Isolated yield. Determined by chiral HPLC. Ketene prepared in
c
3 For recent examples, see: (a) X.-F. Yang, M.-J. Zhang, X.-L. Hou and
L.-X. Dai, J. Org. Chem., 2002, 67, 8097; (b) V. K. Aggarwal and
J.-L. Vasse, Org. Lett., 2003, 5, 3987; (c) D. Morton, D. Pearson,
R. A. Field and R. A. Stockman, Org. Lett., 2004, 6, 2377; (d)
L. G. Arini, A. Sinclair, P. Szeto and R. A. Stockman, Tetrahedron
Lett., 2004, 45, 1589; (e) J.-C. Zheng, W.-W. Liao, X.-X. Sun, X.-L. Sun,
Y. Tang, L.-X. Dai and J.-G. Deng, Org. Lett., 2005, 7, 5789.
4 (a) J. Aube´, Chemtracts: Org. Chem., 1988, 1, 461; (b) M. Yamaguchi
and M. Hirama, Chemtracts: Org. Chem., 1994, 7, 401; (c) T. Rein and
O. Reiser, Acta Chem., Scand., 1996, 50, 369; (d) W.-M. Dai, A. Wu and
H. Wu, Tetrahedron: Asymmetry, 2002, 13, 2187.
d
situ. One-pot reaction.
5 (a) H. J. Bestmann and H. Hartung, Chem. Ber., 1966, 99, 1198; (b)
R. W. Lang and H. J. Hansen, Helv. Chim. Acta, 1980, 63, 438; (c)
I. To¨mo¨sko¨zi and H. J. Bestmann, Tetrahedron Lett., 1964, 1293; (d)
H. J. Bestmann and I. To¨mo¨sko¨zi, Tetrahedron, 1968, 24, 3299; (e)
K. Tanaka and K. Fuji, Tetrahedron Lett., 1996, 37, 3735; (f)
J. Yamazaki, T. Watanabe and K. Tanaka, Tetrahedron: Asymmetry,
2001, 12, 669; (g) T. M. V. D. Pinho e Melo, A. L. Cardoso, A. M.
d’A. Rocha Gonsalves, J. C. Pessoa, J. A. Paixa˜o and A. M. Beja, Eur.
J. Org. Chem., 2004, 4830.
6 For recent reviews, see: (a) N. Krause and A. Hoffmann-Roder, in
Modern Organocopper Chemistry, ed. N. Krause, Wiley-VCH,
Weinheim, 2002, pp. pp. 145–166; (b) S. Ma, Acc. Chem. Res., 2003,
36, 701; (c) S. Ma, Chem. Rev., 2005, 105, 2829; (d) M. A. Tius,
Scheme 3
This journal is ß The Royal Society of Chemistry 2006
Chem. Commun., 2006, 2980–2982 | 2981

View Article Online
Cyclizations of Allenes, in Modern Allene Chemistry, ed. N. Krause and
A. S. K. Hashmi, Wiley-VCH, Weinheim, 2004, vol. 4, pp. pp. 817–845.
7 (a) M. T. Crimmins and K. A. Emmitte, J. Am. Chem. Soc., 2001, 123,
1533; (b) N. Furuichi, H. Hara, T. Osaki, H. Mori and S. Katsumura,
Angew. Chem., Int. Ed., 2002, 41, 1023; (c) A. H. Roder and N. Krause,
Angew. Chem., Int. Ed., 2004, 43, 1196.
8 (a) S. Ye, Y. Tang and L.-X. Dai, J. Org. Chem., 2000, 65, 6257; (b)
S. Ye, Y. Tang and L.-X. Dai, J. Org. Chem., 2001, 66, 5717; (c) S. Ye,
Z.-Z. Huang, C.-A. Xia, Y. Tang and L. X. Dai, J. Am. Chem. Soc.,
2002, 124, 2432; (d) Z.-Z. Huang, S. Ye, W. Xia, Y.-H. Yu and Y. Tang,
J. Org. Chem., 2002, 67, 3096; (e) Z.-Z. Huang and Y. Tang, J. Org.
Chem., 2002, 67, 5320; (f) W.-W. Liao, K. Li and Y. Tang, J. Am.
Chem. Soc., 2003, 125, 13030; (g) W.-W. Liao, X.-M. Deng and
Y. Tang, Chem. Commun., 2004, 1516; (h) H. Jiang, X.-M. Deng,
X.-L. Sun, Y. Tang and L.-X. Dai, J. Org. Chem., 2005, 70, 10202.
9 For recent examples of the synthesis of optically-active allenes, see: (a)
P. H. Dixneuf, T. Guyot, M. D. Ness and S. M. Roberts, Chem.
Commun., 1997, 2083; (b) Z. K. Sweeney, J. L. Salsman, R. A. Andersen
and R. G. Bergman, Angew. Chem., Int. Ed., 2000, 39, 2339; (c) Z. Wan
and S. G. Nelson, J. Am. Chem. Soc., 2000, 122, 10470; (d) N. Krause
and M. Purpura, Angew. Chem., Int. Ed., 2000, 39, 4355; (e)
M. Ogasawara, H. Ikeda, T. Nagano and T. Hayashi, J. Am. Chem.
Soc., 2001, 123, 2089; (f) J. W. Han, N. Tokunaga and T. Hayashi,
J. Am. Chem. Soc., 2001, 123, 12915; (g) M. Ogasawara, K. Ueyama,
T. Nagano, Y. Mizuhata and T. Hayashi, Org. Lett., 2003, 5, 217; (h)
T. Hayashi, N. Tokunaga and K. Inoue, Org. Lett., 2004, 6, 305; (i) B.
D. Sherry and F. D. Toste, J. Am. Chem. Soc., 2004, 126, 15978.
10 D. J. Aldous, W. M. Dutton and P. G. Steel, Tetrahedron: Asymmetry,
2000, 11, 2455. Compound 2 could also be obtained from ketone 1 on a
10 g scale by asymmetric hydrogenation using Ding’s catalyst: Q. Jing,
X. Zhang, J. Sun and K. Ding, Adv. Synth. Catal., 2005, 347, 1193.
11 For detailed procedures, see the ESI{.
12 (a) R. Robiette, J. Richardson, V. K. Aggarwal and J. N.
Harvey, J. Am. Chem. Soc., 2005, 127, 13468; (b) R. Robiette,
J. Richardson, V. K. Aggarwal and J. N. Harvey, J. Am. Chem. Soc.,
2006, 128, 2394.
2982 | Chem. Commun., 2006, 2980–2982
This journal is ß The Royal Society of Chemistry 2006