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H. Mahdavi, J. Amani / Tetrahedron Letters 50 (2009) 5923–5926
Acknowledgment
We are grateful to the Research Council of the University of
Tehran.
References and notes
1. Ley, S. V.; Baxendale, I. R.; Bream, R. N.; Jackson, P. S.; Leach, A. G.; Longbottom,
D. A.; Nesi, J. S.; Storer, R. I.; Taylor, S. J. J. Chem. Soc., Perkin Trans. 1 2000, 3815.
2. Mitsunobu, O. Synthesis 1981, 1.
3. Maryanoff, R. Chem. Rev. 1989, 89, 863.
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437.
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1983, 48, 3721.
7. Shuttleworth, S. J.; Allin, S. M.; Sharma, P. K. Synthesis 1997, 27, 1217.
8. Sherrington, D. C.; Hodge, P. In Synthesis and Separations Using Functional
Polymers; John Wiley & Sons: New York, 1988.
Figure 1. Imine formation using polymeric phosphine reagents.
9. Wentworth, P., Jr.; Janda, K. D. Curr. Opin. Biotechnol. 1998, 9, 109–115.
10. Booth, R. J.; Hodges, J. C. Acc. Chem. Res. 1999, 32, 18–26.
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12. Han, H.; Wolfe, M. M.; Brenner, S.; Janda, K. D. Proc. Natl. Acad. Sci. U.S.A. 1995,
92, 6419.
N-benzylidenebenzylamine in high yield (91%). During the reac-
tion, nitrogen evolution was quite rapid and the phosphine oxide
by-product precipitated as the reaction proceeded. The product
was obtained by filtration and evaporation of the solvent. Interest-
ingly, there was no signal in the 31P NMR spectrum of the THF solu-
tion related to the polymeric reagent. In a similar fashion, several
other imines were produced in high yields (Table 2). Analysis by
NMR and GC–MS indicated that the conversion was over 94% in
all the reactions.
In parallel, a direct comparison between this new liquid-phase
approach with 2 and a procedure involving the use of a solid-phase
triphenylphosphine reagent was undertaken. The yields of the imi-
nes obtained after various reaction times using copolymer 2 in THF
were compared with those obtained from analogous reactions
13. Phelps, J. C.; Bergbreiter, D. E. Tetrahedron Lett. 1989, 30, 3915.
14. Mahdavi, H.; Amani, J. Tetrahedron Lett. 2008, 49, 2204–2207.
15. Procedure for the synthesis of poly(styrene-co-3-maleimidophenyldiphenyl
phosphine) 2: In a 70 mL pressure tube, copolymer 1 (2 mmol, 1.1 g) was
dissolved in anhydrous degassed p-dioxane (50 mL) under an argon
atmosphere. To this solution were added N,N-dimethylaniline (2.5 mL,
20 mmol) and trichlorosilane (2.0 mL, 20 mmol) at room temperature. The
reaction mixture was then stirred vigorously at 110 °C for 15 h. The solution
was cooled to ambient temperature and then poured into MeOH (120 mL) with
vigorous stirring to precipitate the copolymer. The copolymer suspension was
filtered, rinsed with H2O and MeOH and then placed in a vacuum oven at 70 °C
for 20 h. Copolymer-supported triphenylphosphine 2 was obtained as a white
solid (100% yield). IR (KBr) (m
max, cmÀ1): 1712, 1487, 1435, 1380, 1126, 725,
690, 545. 31P NMR (202.4 MHz, CDCl3): d À4.44 (1P, s).
16. Representative experimental procedure for the preparation of N-
benzylidenebenzylamine (3): To a stirred solution of copolymer 2 (184 mg,
0.38 mmol) in THF (10 mL) was added benzaldehyde (40 mg, 0.38 mmol). Next
benzyl azide (50 mg, 0.38 mmol) was added and the reaction mixture was
stirred at room temperature for 22 h (43 h for the cinnamyl derivatives). The
copolymer became insoluble as the reaction proceeded, and at the end of the
reaction, the copolymer beads were collected by filtration and washed with
THF (60 mL). The solvent was evaporated to afford N-benzylidenebenzylamine
(67 mg, 91%).17 1H NMR (300 MHz, CDCl3) d 8.38 (s, 1H), 7.77 (m, 2H), 7.19–741
(br s, 8H), 4.82 (s, 2H); 13C NMR (75 MHz, CDCl3) d 162.09, 139.25, 136.70,
130.84, 128.61, 128.51, 128.30, 128.04, 127.0, 65.1.
using
a
cross-linked polymer-supported triphenylphosphine
(Fig. 1). These data showed that the reactivity of the soluble
reagent 2 was superior to that of the insoluble cross-linked poly-
mer-supported phosphine.
In conclusion, a new linear copolymer-supported triphenyl-
phosphine 2 has been synthesized and its utility as a reagent/acti-
vating agent in the Staudinger/aza-Wittig reaction is described.
This copolymer has a reasonably high loading and allows stoichi-
ometric reactions to take place between azides and aldehydes.
The use of this novel liquid-phase reagent offers considerable
advantages over solution-based methodologies. Although it is con-
sidered generally that soluble polymeric reagents are wasteful in
terms of the volumes of solvents required to precipitate the poly-
mer support at the end of the reaction, the side-product of this
new soluble reagent, the corresponding triphenylphosphine oxide,
precipitates spontaneously during the reaction and is removed by
filtration.
17. Enholm, E. J.; Forbes, D. C.; Holub, D. P. Synth. Commun. 1990, 20, 981.
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Tetrahedron 1992, 48, 6985–7012.
20. Charette, A. B.; Boezio, A. A.; Janes, M. K. Org. Lett. 2000, 2, 3777.
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22. Saoudi, A.; Benguedach, A.; Benhaoua, H. Synth. Commun. 1995, 25, 2349.
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24. Alvarez, S. G.; Alvarez, M. T. Synthesis 1997, 413.
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26. Dyall, L. K.; Suffolk, P. M.; Dehean, W.; L’abbé, G. J. Chem. Soc., Perkin Trans. 2
1994, 2115.
Oxide 1 can be converted back to 2 and recycled at least for four
times without loss of efficiency.
27. Lindsay, R. O.; Allen, C. F. H. Org. Synth. 1955, 3, 710.