Ethyl N-Benzylideneglycinate

[40682-54-0]  · C11H13NO2  · Ethyl N-Benzylideneglycinate  · (MW 191.23)

(a-amino acid synthesis)

Alternate Name: ethyl glycinate benzalimine.

Physical Data: pale yellow liquid; bp 65-75 °C/0.001 mmHg;1 IR spectrum.1

Solubility: very sol most organic solvents; insol hexane.

Preparative Methods: condensation of ethyl glycinate with benzaldehyde.1,2

Handling, Storage, and Precautions: unstable to hydrolysis so that chromatographic treatment on silica gel produces ethyl glycinate and benzaldehyde.

a-Alkylated a-Amino Acid Synthesis.

Ethyl N-benzylideneglycinate has two acidic hydrogens at the a-position which can be metalated and then alkylated to give a-alkylated a-amino acids.2-5 Iteration of this procedure produces a,a-dialkylated a-amino acids. The use of a,o-dihaloalkanes as alkylating agents opens a good entry to cyclic a-amino acids after hydrolysis (eq 1).6-8 Alkylations using sterically bulky t-butyl a-halo esters result in unusual g-alkylation to give b-amino esters after hydrolysis (eq 2).9

Stereoselective Pyrrolidine Synthesis.

Ethyl N-benzylideneglycinate can be reversibly lithiated on treatment with Lithium Bromide-Triethylamine in THF at room temperature and the lithiated species then undergoes exclusively endo selective cycloadditions to a,b-unsaturated carbonyl compounds to give pyrrolidine esters (eq 3).10,11 The reactions with ketene dithioacetals followed by the elimination of thiol produce pyrrole or 2-pyrone derivatives, depending upon the reaction conditions (eq 4).12

Glutamic Acid Synthesis.

Under catalyzed conditions, smooth Michael additions take place with a,b-unsaturated ester acceptors, offering a convenient and direct synthetic route to glutamic esters (eq 5).13 Vinyl phosphonates can also serve as acceptor molecules.14,15

The C=N bond of ethyl N-benzylideneglycinate reacts with ketene or its equivalents to produce azetidinones.1,16 When carboxylic acids are activated by interaction with trichlorocyanuric acid, azetidinones are formed (eq 6).17 Stereoselective aldol reactions of the titanium (Z)-enolates of ethyl N-benzylideneglycinate are also known.18

Related Reagents.

Ethyl N-(Diphenylmethylene)glycinate.

1. Katagiri, N.; Miura, Y.; Niwa, R.; Kato, T. CPB 1983, 31, 538.
2. Rich, D. H.; Singh, J.; Gardner, J. H. JOC 1983, 48, 432.
3. Kinsman, R.; Lathbury, D.; Vernon, P.; Gallagher, T. CC 1987, 243.
4. Jiang, Y.; Zhou, C.; Wu, S.; Chen, D.; Ma, Y.; Liu, G. T 1988, 44, 5343.
5. Barraclough, P.; Caldwell, A. G.; Harris, C. J.; Jackson, W. P.; Whittle, B. J. R. JCS(P1) 1989, 1815.
6. Ainscow, T. A.; Belmont, M. R.; Henshall, J. L.; Hooper, R. M.; Simmonds, D. J. T 1987, 43, 115.
7. Kotha, S.; Kuki, A. TL 1992, 33, 1565.
8. Kotha, S.; Kuki, A. CL 1993, 299.
9. Harris, C. J. TL 1981, 22, 4863.
10. Tsuge, O.; Kanemasa, S.; Yoshioka, M. JOC 1988, 53, 1384.
11. Amornraksa, K.; Grigg, R.; Gunaratne, H. Q. N.; Kemp, J.; Sridharan, V. JCS(P1) 1987, 2285.
12. Balu, M. P.; Ila, H.; Junjappa, H. T 1990, 46, 6771.
13. Stork, G.; Leong, A. Y. W.; Touzin, A. M. JOC 1976, 41, 3491.
14. Minowa, N.; Fukatu, S.; Niida, T.; Takada, M.; Sato, K. TL 1983, 24, 2391.
15. Sturtz, G.; Guervenou, J. S 1991, 661.
16. Sharma, S. D.; Sunita, M.; Gupta, P. K. TL 1979, 1265.
17. Manhas, M. S.; Bose, A. K.; Khajavi, M. S. S 1981, 209.
18. Kanemasa, S.; Mori, T.; Wada, E.; Tatsukawa, A. TL 1993, 34, 677.

Shuji Kanemasa

Kyushu University, Kasuga, Japan

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