Tandem UPS: Sequential mono- and dialkylation of resin-bound glycine via automated synthesis

Tetrahedron Letters

Volumn 38, Issue 51, 1997, Pages 8821-8824

  Griffith, David L ^a   O'Donnell, Martin J ^b   Pottorf, Richard S ^b   Scott, William L ^c   Porco Jr , John A ^a  

^a Argonaut Technologies   (United States)

^b INDIANA UNIVERSITY   (United States)

^c ELI LILLY AND COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID DERIVATIVE; GLYCINE DERIVATIVE;

ALKYLATION; ARTICLE; AUTOMATION; DRUG SYNTHESIS; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; TECHNIQUE;

EID: 0030776587     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(97)10484-1     Document Type: Article

References (19)

1. For recent reviews on solid-phase organic synthesis, see: (a) Balkenhohl, F.; von dem Bussche-Hünnefeld, Lansky, A.; Zechel, C. Angew. Chem. Int. Ed. Engl. 1996, 35, 2288.
2. (b) Thompson, L. A.; Ellman, J. A. Chem. Rev. 1996, 96, 555.
3. (c) Früchtel, J. S.; Jung, G. Angew. Chem., Int. Ed. Engl. 1996, 35, 17.
4. (d) Hermkens, P. H. H.; Ottenheijm, H. C. J.; Rees, D. Tetrahedron 1996, 52, 4527.
5. (e) DeWitt, S. H.; Czarnik, A. W. Acc. Chem. Res. 1996, 29, 114.
6. O'Donnell, M. J.; Zhou, C.; Scott, W. L. J. Am. Chem. Soc. 1996, 118, 6070.
7. Scott, W. L.; Zhou, C.; Fang, Z.; O'Donnell, M. J. Tetrahedron Lett. 1997, 38, 3695.
8. For a review on new strategies for α-alkylated α-amino acids, see: Wirth, T. Angew. Chem., Int. Ed. Engl. 1997, 36, 225.
9. Abbreviations: BEMP: 2-[(1,1-dimethylethyl)imino]-N,N-diethyl-2,2,3,4,5,6-hexahydro-1,3-dimethyl-1,3, 2-diazaphosphorin-2(1H)-amine; NMP: 1-methyl-2-pyrrolidinone; TFA: trifluoroacetic acid; PyBrOP: bromo-tris-pyrrolidino-phosphonium hexafluorophosphate; LDA: lithium diisopropylamide; KHMDS: potassium hexamethyldisilazane; HMPA: hexamethylphosphoramide; DMPU: 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone
10. O'Donnell, M. J.; Lugar, C. W.; Pottorf, R. S.; Zhou, C.; Scott, W. L.; Cwi, C. L. Tetrahedron Lett., 1997, 38, 7163.
11. 2 (6x), and the resin dried in a vacuum desiccator overnight.
12. For related solution-phase studies, see: (a) Phase-transfer catalyzed (PTC) dialkylation of benzophenone imines using activated halides: López, A.; Moreno-Mafias, M.; Pleixats, R.; Roglans, A.; Ezquerra, J.; Pedregal, C. Tetrahedron, 1996, 52, 8365.
13. (b) General discussion of the control of the frequentioselective mono-and dialkylation of Schiff bases esters: O'Donnell, M. J.; Esikova, I. A.; Mi, A.; Shullenberger, D. F.; Wu, S. "Amino Acid and Peptide Synthesis Using Phase Transfer Catalysis," Phase-Transfer Catalysis (ACS Symposium Series 659), Halpern, M., Ed., ACS: Washington, D. C., Chapter 7, 1996.
14. (c) Use of sequential anhydrous ethylations of Schiff base ester to prepare α,α-diethylglycine: Denmark, S. E.; Stavenger, R. A.; Faucher, A. -M.; Edwards, J. P. J. Org. Chem. 1997, 62, 3375.
15. For alkylations using iminophosphorane bases, see: (a) Pietzonka, T.; Seebach, D. Chem. Ber. 1991, 124, 1837.
16. (b) Schwesinger, R.; Willaredt, J.; Schlemper, H.; Keller, M.; Schmidt, D.; Fritz, H. Chem. Ber. 1994, 127, 2435.
17. Seebach, D.; Henning, R.; Mukhopadhyay, T. Chem. Ber. 1982, 115, 1705.
18. 2O (2:1) (10m, 3x), and THF (3x).
19. 2NEt (10 eq.) in NMP for 24 h.