Preparation of chiral, C-protected α-amino aldehydes of high optical purity and their use as condensation components in a linear synthesis strategy

Journal of the American Chemical Society

Volumn 121, Issue 36, 1999, Pages 8401-8402

  Myers, Andrew G ^a   Kung, Daniel W ^a   Zhong, Boyu ^a   Movassaghi, Mohammad ^a   Kwon, Soojin ^a  

^a HARVARD UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALDEHYDE; ALPHA AMINO ACID;

AMINATION; ARTICLE; CHIRALITY; COMPLEX FORMATION; CYCLIZATION; DERIVATIZATION; DRUG SYNTHESIS; ENANTIOMER; OPTICAL DENSITY; POLYMERIZATION;

EID: 0033568504     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja9911824     Document Type: Article

References (29)

1. For leading references, see: Remers, W. A. The Chemistry of Antitumor Antibiotics; Wiley-Interscience: New York, 1988; Vol. 2, Chapter 3.
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6. For leading references to prior work describing the preparation of acetal-, thioacetal-, and aminal-protected a-amino aldehydes, see: (a) Bringmann, G.; Geisler, J.-P. Synthesis 1989, 608-610.
7. (b) Thiam, M.; Chastrette, F. Tetrahedron Lett. 1990, 31, 1429-1432.
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11. (f) Alexakis, A.; Lensen, N.; Tranchier, J.-P.; Mangeney, P.; Feneau-Dupont, J.; Declercq, J. P. Synthesis 1995, 1038-1049.
12. The amino nitrile function has been widely used to enable a variety of synthetic transformations. For examples, see: (a) Overman, L. E.; Jacobsen, E. J. Tetrahedron Lett. 1982, 23, 2741-2744.
13. (b) Ksander, G.; Bold, G., Lattmann, R.; Lehmann, C.; Fruh, T.; Xiang, Y.-B.; Inomata, K.; Buser, H.-P.; Schreiber, J.; Zass, E.; Eschenmoser, A. Helv. Chim. Acta 1987, 70, 1115-1172.
14. (c) Stork, G. S. Pure Appl. Chem. 1989, 61, 439-442.
15. Bonin, M.; Grierson, D. S.; Royer, J.; Husson, H.-P. Org. Synth. 1992, 70, 54-59.
16. (e) Corey, E. J.; Gin, D. Y.; Kania, R. S. J. Am. Chem. Soc. 1996, 118, 9202-9203.
17. Myers, A. G.; Schnider, P.; Kwon, S.; Kung, D. W. J. Org. Chem. 1999, 64, 3322-3327.
18. 3 (LAB).
19. See Supporting Information for preparation and for ee and de determinations.
20. Two diastereomeric (six-membered ring) amino nitrile dimers were formed. α-(2-Pyridyl)amino cyanohydrins (Reynaud, P.; Tupin, T.; Delaby, R. Bull. Soc. Chim. Fr. 1957, 718-721. Podhorez, D. E. J. Heterocycl. Chem. 1991, 28, 971-976) and hindered secondary α-amino cyanohydrins (Davidsen, S. K.; Chu-Moyer, M. Y. J. Org. Chem. 1989, 54, 5558-5567) have been reported.
21. Two diastereomeric (six-membered ring) amino nitrile dimers were formed. α-(2-Pyridyl)amino cyanohydrins (Reynaud, P.; Tupin, T.; Delaby, R. Bull. Soc. Chim. Fr. 1957, 718-721. Podhorez, D. E. J. Heterocycl. Chem. 1991, 28, 971-976) and hindered secondary α-amino cyanohydrins (Davidsen, S. K.; Chu-Moyer, M. Y. J. Org. Chem. 1989, 54, 5558-5567) have been reported.
22. Two diastereomeric (six-membered ring) amino nitrile dimers were formed. α-(2-Pyridyl)amino cyanohydrins (Reynaud, P.; Tupin, T.; Delaby, R. Bull. Soc. Chim. Fr. 1957, 718-721. Podhorez, D. E. J. Heterocycl. Chem. 1991, 28, 971-976) and hindered secondary α-amino cyanohydrins (Davidsen, S. K.; Chu-Moyer, M. Y. J. Org. Chem. 1989, 54, 5558-5567) have been reported.
23. The newly formed stereocenters, represented with a wavy line in structure 2, were typically formed with little selectivity. See Supporting Information for details of stereochemical determinations.
24. 2NCHRCH(CN)NR′R″, see: (a) Cook, A. H.; Smith, E. J. Chem. Soc. 1949, 3001-3007.
25. (b) Herranz, R.; Suarez-Gea, M.; Vinuesa, S.; Garcia-Lopez, M. T. J. Org. Chem. 1993, 58, 5186-5191.
26. For simplicity in the analysis, only a single diastereomer of 2i was employed, tentatively assigned as the (S,S)-diastereomer.
27. Imine formation and the subsequent transformations were also conducted with (R)-10 to confirm that the source of isomerism was the α-center.
28. Analogous condensation reactions with N-Fmoc alaninal (≥95% ee) led to significant epimerization of the α-center. The rate of epimerization of N-protected α-amino aldehydes is well-appreciated to vary with the side chain (see ref 2).
29. In no event was scrambling of the amino nitrile center observed.