C O M M U N I C A T I O N S
Table 3. Tunable Stereoselective Olefination of
spectra for products. This material is available free of charge via the
Allylidenetriphenylphosphoranes with N-Sulfonyl Iminesa
References
(1) (a) Takeda, T. Modern Carbonyl Olefination; Wiley-VCH, Weinheim,
Germany, 2004. (b) Williams, J. M. J. Preparation of Alkenes: A Practical
Approach; Oxford University Press: Oxford, UK, 1996. (c) Kelly, S. E. In
ComprehensiVe Organic Synthesis; Trost, B. M., Fleming, I., Eds.;
Pergamon: Oxford, UK, 1991; Vol. 1, p 729.
(2) (a) Maerckar, A. Org. React. 1965, 14, 270. (b) Maryanoff, B. E.; Reitz,
A. B. Chem. ReV. 1989, 89, 863. (c) Ju, Y. In Modern Organic Reactions
(in Chinese); Hu, Y.-F., Lin, G.-Q., Eds.; Chemical Industry Press: Beijing,
China, 2008; Vol. 3, p 413.
entry
R1
R2
R
product
yield (%)b
Z/Ec
1
2
3
4
5
6
7
8
Ph
H
H
H
H
H
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeC6H4
E5aa
E5ba
E5ea
E5fa
E5ma
E3na
E5bb
E5fb
E5hb
E5mb
E3nd
E5nb
E5ob
E5qb
77
88
76
90
71
78
78
74
73
77
82
87
64
69
71
68
77
74
69
73
<1:99
<1:99
<1:99
<1:99
<1:99
<1:99
<1:99
<1:99
<1:99
<1:99
<1:99
<1:99
<1:99
<1:99
>99:1
>99:1
>99:1
>99:1
>99:1
>99:1
4-CIC6H4
4-O2NC6H4
4-MeOC6H4
2-pyridyl
Ph
4-CIC6H4
4-MeOC6H4
2-CIC6H4
2-pyridyl
2-naphthyl
(3) Robiette, R.; Richardson, J.; Aggarwal, V. K.; Harvey, J. N. J. Am. Chem.
Ph Me
Ph Me
Ph Me
Ph Me
Ph Me
Ph Me
Soc. 2006, 128, 2394.
(4) (a) Huo, C.; He, X.; Chan, T. H. J. Org. Chem. 2008, 73, 8583. (b) Wang,
Q.; Khoury, M. E.; Schlosser, M. Chem.sEur. J. 2000, 6, 420. (c)
Tsukamoto, M.; Schlosser, M. Synlett 1990, 605.
9
(5) Ackermann, M.; Berger, S. Tetrahedron 2005, 61, 6764.
(6) (a) McNulty, J.; Das, P. Eur. J. Org. Chem. 2009, 4031. (b) McNulty, J.;
Das, P. Tetrahedron Lett. 2009, 50, 5737. (c) Tamura, R.; Saegusa, K.;
Kakihana, M.; Oda, D. J. Org. Chem. 1988, 53, 2723. (d) Tamura, R.;
Kato, M.; Saegusa, K.; Kakihana, M.; Oda, D. J. Org. Chem. 1987, 52,
4121. (e) Vedejs, E.; Fang, H. W. J. Org. Chem. 1984, 49, 210.
(7) Wang, Z.; Zhang, G.; Guzei, I.; Verkade, J. G. J. Org. Chem. 2001, 66,
3521.
10
11
12
13
14
15
16
17
18
19
20
(E)-PhCHdCH Ph Me
n-C6H13
cyclohexyl
Ph
2-pyridyl
2-naphthyl
Ph Me
Ph Me
Ph 2,6-Cl2C6H3 Z3na
Ph 2,6-Cl2C6H3 Z5mb
Ph 2,6-Cl2C6H3 Z3nd
(8) Aggarwal, V. K.; Fulton, J. R.; Sheldon, C. G.; de Vicente, J. J. Am. Chem.
Soc. 2003, 125, 6034.
(E)-PhCHdCH Ph 2,6-Cl2C6H3 Z5nb
n-C6H13
cyclohexyl
(9) For some examples on E selective olefinations, see: (a) Pachali, S.;
Hofmann, C.; Rapp, G.; Schobert, R.; Baro, A.; Frey, W.; Laschat, S. Eur.
J. Org. Chem. 2009, 2828. (b) Bestmann, H. J.; Schobert, R. Angew. Chem.,
Int. Ed. Engl. 1985, 24, 791. (c) Bestmann, H. J.; Kellermann, W. Synthesis
1994, 1257. (d) Chakor, N. S.; Musso, L.; Dallavalle, S. J. Org. Chem.
2009, 74, 844.
Ph 2,6-Cl2C6H3 Z5ob
Ph 2,6-Cl2C6H3 Z5qb
a Reaction conditions: phosphonium salt 4 (0.60 mmol), X ) Br (For
entries 6-20, X ) Cl), LDA (0.65 mmol), THF (1.0 mL), -78 °C, 1 h;
then imine 1 (0.50 mmol), THF (1.0 mL), -78 °C to rt. b Isolated yield.
(10) (a) Bestmann, H. J.; Seng, F. Angew. Chem., Int. Ed. 1963, 2, 393. (b)
Bestmann, H. J.; Seng, F. Tetrahedron 1965, 21, 1373. (c) Bestmann, H. J.
Angew. Chem., Int. Ed. 1965, 4, 830.
(11) (a) Liu, D.-N.; Tian, S.-K. Chem.sEur. J. 2009, 15, 4538. (b) Li, H.-H.;
Jin, Y.-H.; Wang, J.-Q.; Tian, S.-K. Org. Biomol. Chem. 2009, 7, 3219.
(12) A stepwise process involving initial carbon-carbon bond formation leading
to a betaine intermediate was proposed for the formal [2+2] cycloaddition.
Alternatively, the 1,2-azaphosphetane intermediate can be generated directly
through a four-center transition state analogous to that suggested for the
Wittig reaction (see refs 2b, c, and 3).
c
1
Determined by H NMR analysis.
Scheme 2. Stereoselective Synthesis of DMU-212 (E6) and Its
Isomer Z6
(13) (a) Liu, C.-R.; Li, M.-B.; Yang, C.-F.; Tian, S.-K. Chem. Commun. 2008,
1249. (b) Liu, C.-R.; Li, M.-B.; Yang, C.-F.; Tian, S.-K. Chem.sEur. J.
2009, 15, 793. (c) Liu, C.-R.; Li, M.-B.; Cheng, D.-J.; Yang, C.-F.; Tian,
S.-K. Org. Lett. 2009, 11, 2543.
(14) Yamanaka, M.; Nishida, A.; Nakagawa, M. J. Org. Chem. 2003, 68, 3112.
references therein. .
(15) The reaction was quenched with water upon completion, and byproduct
iminophosphorane was decomposed by water to give triphenylphosphine
oxide and a primary sulfonamide.
(16) The Z/E ratios of the alkene products were determined by 1H NMR analysis
within 3 days owing to the isomerization of (Z)-alkenes under the influence
of light and air at room temperature. For a relevant study, see: Ren, Y.;
Che, Y.; Ma, W.; Zhang, X.; Shen, T.; Zhao, J. New J. Chem. 2004, 28,
1464.
(17) According to the proposed mechanism depicted in Scheme 1, the interactions
of the sulfonyl group, phenyl group, R1 group, and Ar group contribute to
the stereoselectivity for the formation of the 1,2-azaphosphetane intermedi-
ate leading to an alkene product. Since the electronic and steric properties
of an aryl group, alkenyl group, and alkyl group are significantly different
from each other, it is plausible that each type of imine shown in Table 2
needs a different N-sulfonyl group to control the stereoselectivity syner-
gically in its olefination reaction with a benzylidenetriphenylphosphorane.
(18) (a) Sale, S.; Verschoyle, R. D.; Boocock, D.; Jones, D. J. L.; Wilsher, N.;
Ruparelia, K. C.; Potter, G. A.; Farmer, P. B.; Steward, W. P.; Gescher,
A. J. Br. J. Cancer 2004, 90, 736. (b) Sale, S.; Tunstall, R. G.; Ruparelia,
K. C.; Potter, G. A.; Steward, W. P.; Gescher, A. J. Int. J. Cancer 2005,
115, 194. (c) Ma, Z.; Molavi, O.; Haddadi, A.; Lai, R.; Gossage, R. A.;
Lavasanifar, A. Cancer Chemother. Pharmacol. 2008, 63, 27.
(19) Gosslau, A.; Pabbaraja, S.; Knapp, S.; Chen, K. Y. Eur. J. Pharmacol.
2008, 587, 25.
imines bearing appropriate N-sulfonyl groups smoothly undergo
olefination reaction with various benzylidenetriphenylphosphoranes
or allylidenetriphenylphosphoranes under mild reaction conditions
to afford an array of both Z- and E-isomers of conjugated alkenes
in good to excellent yields and with greater than 99:1 stereoselec-
tivity. Moreover, this tunable protocol has been successfully applied
to the highly stereoselective synthesis of two anticancer agents,
DMU-212 and its Z-isomer.
(20) (a) Alonso, F.; Riente, P.; Yus, M. Tetrahedron Lett. 2009, 50, 3070. (b)
Moro, A. V.; Cardoso, F. S. P.; Correia, C. R. D. Tetrahedron Lett. 2008,
49, 5668. (c) Robinson, J. E.; Taylor, R. J. K. Chem. Commun. 2007, 1617.
(d) Hilt, G.; Hengst, C. J. Org. Chem. 2007, 72, 7337. (e) Cross, G. G.;
Eisnor, C. R.; Gossage, R. A.; Jenkins, H. A. Tetrahedron Lett. 2006, 47,
2245. (f) Murias, M.; Handler, N.; Erker, T.; Pleban, K.; Ecker, G.; Saiko,
P.; Szekeres, T.; Ja¨ger, W. Bioorg. Med. Chem. 2004, 12, 5571. (g) Azzena,
U.; Dettori, G.; Idini, M. V.; Pisano, L.; Sechi, G. Tetrahedron 2003, 59,
7961. (h) Cushman, M.; Nagarathnam, D.; Gopal, D.; Chakraborti, A. K.;
Lin, C. M.; Hamel, E. J. Med. Chem. 1991, 34, 2579.
Acknowledgment. We are grateful for the financial support
from the National Natural Science Foundation of China (20972147,
20732006, and 20672105), National Basic Research Program of
China (973 Program 2010CB833300), and Chinese Academy of
Sciences.
Supporting Information Available: General information, experi-
mental procedures, characterization data, and copies of 1H and 13C NMR
JA910238F
9
5020 J. AM. CHEM. SOC. VOL. 132, NO. 14, 2010