(Phenylseleno)acetic Acid


[17893-46-8]  · C8H8O2Se  · (Phenylseleno)acetic Acid  · (MW 215.12)

(dianion reacts with electrophiles, such as aldehydes1 and epoxides;2,3 especially useful for the preparation of 2(5H)-furanones)

Physical Data: white prisms, mp 35.5-36.5 °C (from 5% ether/hexane).1 IR,1,4 1H NMR,1,4 and 13C NMR5 spectra have been reported. The pKa (25 °C) has been calculated to be 3.75.6

Solubility: sol THF, ether, and alcohol; crystallizes from hexane.

Preparative Methods: the best methods involve the displacement of a halogen atom from an a-haloacetic acid molecule by a phenylselenide moiety. The selenide anion can be obtained by reduction of Diphenyl Diselenide (eqs 1 and 2)1,4 or from Benzeneselenol in basic medium (eq 3).4

The best yield is described from benzeneselenol through a thallium(I) benzeneselenolate intermediate (eq 4).4 This method has also been applied to the preparation of 2-phenylselenopropanoic acid.

Handling, Storage, and Precautions: may be kept in crystalline form in the refrigerator for several months. Use in a fume hood.

Synthesis of Alkenes.

The dianion of a-phenylselenoacetic acid, usually prepared by deprotonation with Lithium Diisopropylamide, may be employed as a Wittig reagent equivalent for the synthesis of alkenes from aldehydes (eq 5).1 The reductive elimination of PhSeOH proceeds with high anti stereospecificity under very mild conditions compatible with virtually all functionalities.

Synthesis of a,b-Unsaturated Esters and Lactones.

The reaction of the dianion of a-phenylselenoacetic acid with epoxides leads to g-hydroxy acids, which can be dehydrated either with 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Hydrochloride2 or under acidic conditions;3 the oxidation of the a-phenylselenolactone and subsequent pyrolysis of the selenoxide yields 2(5H)-furanones, i.e. a,b-butenolides (eq 6).

Although a similar route has been described using (Phenylthio)acetic Acid,7 the selenium pathway allows the pyrolysis step to take place in milder conditions. An additional advantage is the possibility of carrying out the oxidation in the presence of other oxidizable heteroatoms such as nitrogen or sulfur (eq 7).3

When optically pure epoxides are used as the starting electrophiles, no loss of the sense of chirality has been observed.2 Therefore the method has been successfully applied to the synthesis of various natural products, including mevinic acids,8 ionomycin,9,10 and cladospolide A.11 In this last case an a,b-unsaturated ester was prepared instead of a lactone (eq 8).

Related Reagents.

2-Phenylselenopropanoic acid4,12 has been used as a masked acrylate unit in a crucial step of the synthesis of frullanolide (eq 9).13 In that example an allylic halide acted as the electrophile and the elimination of the selenoxide resulted in the formation of the exocyclic double bond. Interestingly, in an analogous situation, sulfoxides led exclusively to the formation of an endocyclic double bond (eq 10).7 See also (Phenylthio)acetic Acid.

1. Reich, H. J.; Chow, F.; Shah, S. K. JACS 1979, 101, 6638.
2. Hanessian, S.; Hodges, P. J.; Murray, P. J.; Sahoo, S. P. CC 1986, 754.
3. Figueredo, M.; Font, J.; Virgili, A. T 1987, 43, 1881.
4. Detty, M. R.; Wood, G. P. JOC 1980, 45, 80.
5. Mullen, G. P.; Dunlap, R. B.; Odom, J. D. B 1986, 25, 5625.
6. Barnes, D.; Laye, P. G.; Pettit, L. D. JCS(A) 1969, 2073.
7. Iwai, K.; Kosugi, H.; Uda, H.; Kawai, M. BCJ 1977, 50, 242.
8. Hanessian, S.; Roy, P. J.; Petrini, M.; Hodges, P. J.; Di Fabio, R.; Carganico, G. JOC 1990, 55, 5766.
9. Hanessian, S.; Cooke, N. G.; DeHoff, B.; Sakito, Y. JACS 1990, 112, 5276.
10. Hanessian, S.; Murray, P. J. T 1987, 43, 5055.
11. Maemoto, S.; Mori, K. CL 1987, 109.
12. Petragnani, N.; Ferraz, H. M. C. S 1978, 476.
13. Petragnani, N.; Ferraz, H. M. C. S 1985, 27.

Josep Font & Marta Figueredo

Universitat Autònoma de Barcelona, Spain

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