N-Phenylselenophthalimide1

[71098-88-9]  · C14H9NO2Se  · N-Phenylselenophthalimide  · (MW 302.20)

(reagent for electrophilic phenylselenenylation of alkenes, dienes, enols, and other nucleophiles)

Alternate Name: NPSP.

Physical Data: mp 171-175 °C (dec).

Form Supplied in: colorless solid.

Preparative Methods: prepared in 87% yield by the reaction of Benzeneselenenyl Chloride with potassium Phthalimide in hexane.1

Handling, Storage, and Precautions: indefinitely stable when stored at -20 °C in the dark. Use in a fume hood.

Selenenylation.

N-Phenylselenophthalimide is a very mild reagent for electrophilic selenenylation and reacts with a wide variety of organic substrates to provide products bearing the PhSe group. The generalized stepwise conversion of an alkene to a functionalized selenide with this reagent is shown in eq 1.

Various alkenes have been found to react in the intermolecular sense with nucleophiles in condensation reactions mediated by NPSP. Representative examples are given in eqs 2 and 3.1-3

Dialkenes react with NPSP in the presence of water in a closely related manner to provide cyclic ethers with the net incorporation of two PhSe moieties (eq 4).3

NPSP is a very efficient reagent for effecting the cyclization of unsaturated substrates containing internal nucleophiles and has been used for macrocyclizations (eqs 5-10)3 as well as cyclizations of homogeranic acid derivatives.4 In addition, NPSP has been used to effect annulations leading to carbohydrates.5

In several instances the use of NPSP has been found advantageous when compared to the more classical reagents Benzeneselenenyl Bromide or Benzeneselenenyl Chloride. In this connection the latter reagents have been reported to be useful for the selenenylative cyclization of unsaturated alcohols,6 carboxylic acids,7 thio compounds,8 and urethanes.9

Selenolactonization of alkynoic acids also proceeds efficiently in the presence of NPSP (eq 11).10

In addition, suitably disposed b-keto ester moieties can be induced to stereoselectively cyclize onto alkenes in the presence of NPSP (eq 12).11

Heterocyclizations leading to oxazolidine derivatives have been reported to proceed efficiently via the selenenylation of alkenyl amides by NPSP (eq 13).12 Danishefsky and collaborators have reported an interesting phenylselenenylation-radical functionalization sequence using NPSP13 and have also used this reagent in the synthesis of mitomycin congeners.14

Ley and co-workers have published extensively on the use of NPSP in the presence of Lewis acids to effect carbocyclizations (e.g. eq 14).15 In addition, these authors have utilized NPSP for the synthesis of spiroacetals.16 For the majority of the preceding transformations, NPSP has been found the superior reagent both in terms of chemical efficiency as well as the mild nature of the reaction conditions that are typically employed.17

Alcohols and carboxylic acids have been found to condense with NPSP in the presence of Tri-n-butylphosphine to provide the corresponding selenoethers (eq 15) and acyl phenyl selenides (eq 16), respectively.18-20

Sequential hydrozirconation-phenylselenenylation of conjugated enynes has provided a convenient route to stereodefined dienyl selenides (eq 17).21

Related Reagents.

Benzeneselenenyl Bromide; Benzeneselenenyl Chloride; Benzeneselenenyl Trifluoromethanesulfonate; Benzenesulfenyl Chloride; N,N-Diethylbenzeneselenenamide; 2-Pyridineselenenyl Bromide.


1. Nicolaou, K. C.; Petasis, N. A.; Claremon, D. A. T 1985, 41, 4835.
2. Saluzzo, C.; Alvernhe, G.; Anker, D. TL 1990, 31, 663.
3. Nicolaou, K. C.; Claremon, D. A.; Barnette, W. E.; Seitz, S. P. JACS 1979, 101, 3704.
4. (a) Rouessac, A.; Rouessac, F.; Zamarlik, H. TL 1981, 22, 2641. (b) Rouessac, F.; Zamarlik, H. TL 1981, 22, 2643.
5. Suzuki, K.; Mukaiyama, T. CL 1982, 683.
6. Nicolaou, K. C.; Magolda, R. L.; Sipio, W. J.; Barnette, W. D.; Lysenko, Z.; Joullie, M. M. JACS 1980, 102, 3784. Nicolaou, K. C.; Lysenko, Z. TL 1977, 1257. Clive, D. L. J.; Chittattu, G.; Wong, C. K. CJC 1977, 55, 3894. Clive, D. L. J.; Chittattu, G.; Curtis, N. J.; Kiel, W. A.; Wong, C. K. CC 1977, 725.
7. Nicolaou, K. C.; Seitz, S. P.; Sipio, W. J.; Blount, J. F. JACS 1979, 101, 3884. Nicolaou, K. C.; Lysenko, Z. JACS 1977, 99, 3185. Clive, D. L. J.; Chittattu, G. CC 1977, 484. Clive, D. L. J.; Russell, C. G.; Chittattu, G.; Singh, A. T 1980, 36, 1399.
8. Nicolaou, K. C.; Barnette, W. E.; Magolda, R. L. JACS 1978, 100, 2567.
9. Clive, D. L. J.; Farina, V.; Singh, A.; Wong, C. K.; Kiel, W. A.; Menchen, S. M. JOC 1980, 45, 2120. Clive, D. L. J.; Wong, C. K.; Kiel, W. A.; Menchen, S. M. CC 1978, 379.
10. Toru, T.; Fujita, S.; Saito, M.; Maekawa, E. JCS(P1) 1986, 1999.
11. Brussani, G.; Ley, S. V.; Wright, J. L.; Williams, D. J. JCS(P1) 1986, 303.
12. Chrétien, F.; Chapleur, Y. JOC 1988, 53, 3615.
13. Webb, R. R. II; Danishefsky, S. TL 1983, 24, 1357.
14. Danishefsky, S.; Berman, E. M.; Ciufolini, M.; Etheredge, S. J.; Segmuller, B. E. JACS 1985, 107, 3891.
15. (a) Jackson, W. P.; Ley, S. V.; Morton, J. A. CC 1980, 1028. (b) Jackson, W. P.; Ley, S. V.; Whittle, A. J. CC 1980, 1173. (c) Jackson, W. P., Ley, S. V.; Morton, J. A. TL 1981, 22, 2601. (d) Ley, S. V.; Lygo, B.; Molines, H.; Morton, J. A. CC 1982, 1251. (e) Ley, S. V.; Murray, P. J.; Palmer, B. D. T 1985, 41, 4765; Ley, S. V.; Murray, P. J. CC 1982, 1252.
16. Ley, S. V.; Lygo, B. TL 1982, 23, 4625.
17. For a comprehensive review, see: Harring, S. R.; Edstrom, E. D.; Livinghouse, T. In Advances in Heterocyclic Natural Product Synthesis; Pearson, W. H. Ed.; JAI: Greenwich, CT, 1992; Vol. 2, pp 299-376.
18. (a) Grieco, P. A.; Gilman, S.; Nishizawa, M. JOC 1976, 41, 1485. (b) Nicolaou, K. C.; Petasis, N. A. Selenium in Natural Products Synthesis; CIS: Philadelphia, PA, 1984.
19. (a) Ley, S. V.; Simpkins, N. S.; Whittle, A. J. CC 1981, 1001 and 1983, 503. (b) Ley, S. V.; Neuhaus, D.; Simpkins, N. S.; Whittle, A. J. JCS(P1) 1982, 2157.
20. Grieco, P. A.; Jaw, J. Y.; Claremon, D. A.; Nicolaou, K. C. JOC 1981, 46, 1215.
21. Fryzuk, M. D.; Bates, G. S.; Stone, C. JOC 1991, 56, 7201.

Tom Livinghouse

Montana State University, Bozeman, MT, USA



Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.