Dynamic biphasic counterion exchange in a configurationally stable aziridinium ion: Efficient synthesis and isolation of a koga C 2-symmetric tetraamine base

Organic Process Research and Development

Volumn 11, Issue 2, 2007, Pages 215-222

  Frizzle, Matthew J ^a   Caille, Sebastien ^a   Marshall, Teresa L ^a   McRae, Kenneth ^a   Nadeau, Kelly ^a   Guo, Gary ^a   Wu, Steven ^a   Martinelli, Michael J ^a   Moniz, George A ^a  

^a AMGEN INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 34247232142     PISSN: 10836160     EISSN: None     Source Type: Journal    
DOI: 10.1021/op0602371     Document Type: Article

References (28)

1. Shirai, R.; Tanaka, M.; Koga, K. J. Am. Chem. Soc. 1986, 108, 543.
2. (a) Murakata, M.; Nakajima, M.; Koga, K. J. Chem. Soc., Chem. Commun. 1990, 1657.
3. (b) Imai, M.; Hagihara, A.; Kawasaki, H.; Manabe, K.; Koga, K. J. Am. Chem. Soc. 1994, 116, 8829.
4. (c) Yamashita, Y.; Odashima, K.; Koga, K. Tetrahedron Lett. 1999, 40, 2803.
5. For reviews of asymmetric synthesis using chiral lithium amide bases, see: (a) Cox, P. J.; Simpkins, N. S. Tetrahedron: Asymmetry 1991, 2, 1.
6. (b) O'Brien, P. J. Chem. Soc., Perkin. Trans. 1 1998, 1439.
7. (c) Tomioka, K. Synthesis 1990, 541.
8. (d) Majewski, M. Adv. Asymm. Synth. 1998, 3, 39.
9. (a) Poumellec, P.; O'Brien, P. Tetrahedron Lett. 1996, 37, 5619.
10. (b) deSousa, S. E.; O'Brien, P.; Poumelec, P. J. Chem. Soc., Perkin Trans. 1 1998, 1483.
11. (c) Cuthbertson, E.; O'Brien, P.; Towers, T. Synthesis 2001, 693.
12. (d) Towers, T. D.; O'Brien, P. J. Org. Chem. 2002, 67, 304.
13. For examples of aziridinium ions in synthesis, see: (a) Liu, Q.; Marchington, A. P.;Rayner,C.M. Tetrahedron 1997, 53, 15729.
14. (b) Rayner C. M. Synlett 1997, 11.
15. (c) Okuda, M.; Tomioka, K. Tetrahedron Lett. 1994, 35, 4585.
16. (d) Gmeiner, P.; Junge, D.; Kärtner, A. J. Org. Chem. 1994, 59, 6766.
17. (c) Freedman, J.; Vaal, M. J.; Huber, E. W. J. Org. Chem. 1991, 56, 670.
18. (f) Williams, D. R.; Brown, D. L.; Benbow, J. W. J. Am. Chem. Soc. 1989, 111, 1923.
19. (g) Rosen, T.; Fesik, S. W.; Chu, D. T. W.; Pernet, A. G. Synthesis 1988, 40.
20. (h) Kametani, T.; Honda, T. Adv. Heterocycl. Chem. 1986, 39, 181.
21. (i) Couterier, C.; Blanchet, J.; Schlama, T.; Zhu, J. Org. Lett. 2006, 8, 2183.
22. Chiral purity is reported relative to both the opposite enantiomer ((S,S)-5) and the meso isomer (meso-5). Analytical standards of both (S,S)-5 and meso-5 were obtained.
23. For a review of Neighboring Group Participation in organic reactions, see: Capon, B.; McManus, S. P. Neighboring Group Participation; Plenum Press: New York, 1976.
24. 3N·HCl. The pronounced change in the form of the precipitate on warming was the event that seized the agitator in our case.
25. 1H NMR spectrum of aziridinium ion 10a is available as Supporting Information. For NMR data of an unrelated aziridinium ion, see: Liu, Q.; Marchington, A. P.; Boden, N.; Rayner, C. M. J. Chem. Soc., Perkin Trans. 1 1997, 511.
26. The intermediate β-chloroamine 12 derived from mesylates (R)-9a and (S)-9b via aziridinium ion 10a gives rise to (R,R)-5 under the reaction conditions reported by O'Brien. Thus, reversion of 12 to the aziridinium ion prior to amine trapping is required for stereochemical competence. The formation of 12 from 9a/9b has been observed previously; however neither the time course and temperature sensitivity of this interconversion nor its mechanism of formation were reported. See: Anderson, S. R.; Ayers, J. T.; DeVries, K. M.; Ito, F.; Mendenhall, D.; Vanderplas, B. C. Tetrahedron: Asymmetry 1999, 10, 2655.
27. Water was charged portionwise. An exotherm of ca. 9°C was observed following each addition, and the mixture temperature was allowed to return to 0°C between additions.
28. A% refers to the HPLC peak area % of the desired material versus all other visible impurity peaks in the appropriate assay. Chiral purity refers to the HPLC peak area % of the desired isomer (i.e., (R,R)-5) versus the enantiomer ((S,S)-5) and the meso-isomer (meso- 5).