7124
diphenylmethane or ¯uorene, produced 26 or 27 in 10 and 8% yield, respectively. This could be a
t
.
consequence of BuO preferentially reacting with the weaker (benzylic) C±H bonds in diphenyl-
methane and ¯uorene (compared to toluene) resulting in a low concentration of the captodative
radical (derived from 8a).
In all reactions, no products derived from dialkylation of glycine 8a were observed. Indeed,
attempts to alkylate alanine 10a or phenylalanine 11a by photolysis with toluene/peroxide resul-
ted in typically ꢀ1% yield of dialkylated product 28. Similarly, the presence of a second ester
served to hinder the alkylation of malonate 29 and photolysis in the presence of di-tert-butyl
peroxide (2 equiv.) and toluene (5 equiv.) produced 30 in 13% yield (or 58% yield based on
recovered 29). The reaction also produced a small amount (3%) of phenylalanine 11a,
presumably derived from photo-decarboxylation of 30.
This work has demonstrated that a variety of glycine derivatives can be alkylated to form
phenylalanines, on photolysis in the presence of substituted toluenes. Whereas related anionic
alkylations are often complicated by polyalkylation, this mild free radical method of alkylation
allows the selective formation of monoalkylated products.
Acknowledgements
We thank A. H. Marks and Co. Ltd and the EPSRC for funding (research grant, GR/L58538).
References
1. Tetrahedron Symposia-in-Print No. 33; Ed. O'Donnell, M. J. 1988, 44, 5253±5614.
2. (a) Easton, C. J. Chem. Rev. 1997, 97, 53±82. (b) Easton, C. J.; Hutton, C. A. Synlett 1998, 457±466.
3. (a) Elad, D.; Sperling, J. J. Chem. Soc. (C) 1969, 1579±1585. (b) Sperling, J.; Elad, D. J. Am. Chem. Soc. 1971, 93,
967±971.
4. Schwarzberg, M.; Sperling, J.; Elad, D. J. Am. Chem. Soc. 1973, 95, 6418±6426.
5. (a) Obata, N.; Niimura, K. J. Chem. Soc., Chem. Commun. 1977, 238±239. (b) Viehe, H. G.; Merenyi, R.; Stella,
L.; Janousek, Z. Angew. Chem., Int. Ed. Engl. 1979, 18, 917±932. (c) Benson, O.; Demirdji, S. H.; Haltiwanger,
R. C.; Koch, T. H. J. Am. Chem. Soc. 1991, 113, 8879±8886.
6. Burgess, V. A.; Easton, C. J.; Hay, M. P.; Steel, P. J. Aust. J. Chem. 1988, 41, 701±710.
7. All new compounds exhibited satisfactory spectral and analytical (high resolution mass) data.
8. There was no evidence for benzylic radical formation on photolysis of related amines, e.g. PhNHCbz or
tBuNHCbz (under similar conditions).
9. Alternative photosensitisers, such as 4,40-dimethoxybenzophenone, were less eective.
10. Photolysis of N-acetylglycine methyl ester with benzophenone or 4,40-dimethoxybenzophenone gave the tertiary
alcohol in much lower yield (i.e. 7.7 and 6.4% yield, respectively). Deseke, E.; Nakatani, Y.; Ourisson, G. Eur. J.
Org. Chem. 1998, 243±251.