Selective monoacylation of a diamine using intramolecular delivery by a DMAP unit

Organic Letters

Volumn 4, Issue 16, 2002, Pages 2653-2656

  Kelly, T Ross ^a   Cavero, Marta ^a  

^a BOSTON COLLEGE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 (DIMETHYLAMINE)PYRIDINE; 4-(DIMETHYLAMINE)PYRIDINE; DIAMINE; PYRIDINE DERIVATIVE;

ACYLATION; ARTICLE; CHEMICAL STRUCTURE; CHEMISTRY; ELECTRICITY;

ACYLATION; DIAMINES; ELECTROSTATICS; MODELS, MOLECULAR; PYRIDINES;

EID: 0037043539     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol026206h     Document Type: Article

References (33)

1. (a) Kelly, T. R.; de Silva, H.; Silva, R. A. Nature 1999, 400, 150.
2. (b) Kelly, T. R.; Silva, R. A.; de Silva, H.; Jasmin, S.; Zhao, Y. J. Am. Chem. Soc. 2000, 122, 6935.
3. (c) Kelly, T. R. Acc. Chem. Res. 2001, 34, 514.
4. Kelly, T. R.; Cavero, M.; Zhao, Y. Org. Lett. 2001, 3, 3895.
5. For reviews see: (a) Hassner, A.; Krespki, L. R.; Alexanian, V. Tetrahedron 1978, 34, 2069.
6. (b) Höfle, G.; Steglich, W.; Vorbrüggen, H. Angew Chem., Int. Ed. Engl. 1978, 17, 569.
7. (c) Ragnarsson, U.; Grehn, L. Acc. Chem. Res. 1998, 31, 494.
8. (d) Spivey, A.; Maddaford, A.; Redgrave, A. J. Org. Prep. Proced. Int. 2000, 32, 333.
9. (e) Sheinkman, A. K.; Suminov, S. I.; Kost, A. N. Russ. Chem. Rev. 1973, 42, 642.
10. For some recent publications involving DMAP derivatives see, inter alia: (a) Vedejs, E.; Chen, X. J. Am. Chem. Soc. 1996, 118, 1809.
11. (b) Kawabata, T.; Nagato, M.; Takasu, K.; Fuji, K. J. Am. Chem. Soc. 1997, 119, 3169.
12. (c) Sammakia, T.; Hurley, T. B. J. Org. Chem. 1999, 64, 4652.
13. (d) Fu, G. C. Acc. Chem. Res. 2000, 33, 412.
14. (e) Spivey, A. C.; Charboneau, P.; Fekner, T.; Hochmuth, D. H.; Maddaford, A.; Madalier-Jugroot, C.; Redgrave, A.; Whitehead, M. A. J. Org. Chem. 2001, 66, 7394.
15. (f) Cupperly, D.; Gros, P.; Fort, Y. J. Org. Chem. 2002, 67, 238.
16. Litvinenko, L. M.; Kirichenko, A. I. Dokl. Akad. Nauk. SSSR 1967, 176, 97 (Dokl. Chem. Engl. Transl. 1967, 763).
17. Litvinenko, L. M.; Kirichenko, A. I. Dokl. Akad. Nauk. SSSR 1967, 176, 97 (Dokl. Chem. Engl. Transl. 1967, 763).
18. There are a large number of examples in the literature of the use of DMAP or imidazole units as acylation or phosphorslation catalysts in enzyme-mimetic (and enzyme) settings which could be considered intramolecular, since the substrate and the catalyst are usually bound during catalysis. However, most of these examples deal with alcohols (see, for instance: Sculimbrene, B. R.; Miller, S. J. J. Am. Chem. Soc. 2001, 123, 10125. Faber, K.; Riva, S. Synthesis 1992, 895 and references cited therein); we have found no examples dealing wuth the selective acylation of anilines.
19. There are a large number of examples in the literature of the use of DMAP or imidazole units as acylation or phosphorslation catalysts in enzyme-mimetic (and enzyme) settings which could be considered intramolecular, since the substrate and the catalyst are usually bound during catalysis. However, most of these examples deal with alcohols (see, for instance: Sculimbrene, B. R.; Miller, S. J. J. Am. Chem. Soc. 2001, 123, 10125. Faber, K.; Riva, S. Synthesis 1992, 895 and references cited therein); we have found no examples dealing wuth the selective acylation of anilines.
20. (a) For the several reasons given in this paragraph, the design of 6 was based on the premise that the acylation would proceed by a nucleophilic catalysis mechanism. Nonetheless, some referees suggest that in this specific instance the pyridine nitrogen is operating by intramolecular general base rather than nucleophilic catalysis, citing refs 4c and 7b. While we still believe that nucleophilic catalysis is operative here [molecular modeling of low-enerey conformations of 6 (Figure 3) shows no hydrogen bond between the pyridine nitrogen and the proximate amino hydrogens: such a hydrogen bond would be necessary, at least in the transition state, if general base catalysis is operative] we agree with those referees that the verdict is not yet in. Since the objective of our study was to establish function (selective acylation), not necessarily prove mechanism, and since we were successful, more detailed mechanistic studies will be deferred until after the concepts in Figures 2 and 1 have been reduced to practice.
21. (b) Anderson, H.; Su, C.-W.; Watson, J. W. J. Am. Chem. Soc. 1969, 91, 482.
22. The barrier to full rotation around bond b is 20-25 kcal/mol.
23. (a) Preparation of 8: see ref 4c. For reactions related to the conversion of DMAP to 8 see ref 4a and: Kessar, S. V.; Singh, P.; Singh, K. N.; Dutt, M. J. Chem. Soc., Chem. Commun. 1991, 570.
24. (b) Reduction of 9 to 6: Perry, P. J.; Reszka, A. P.; Wood, A. A.; Read, M. A.; Gowan, S. M.; Dosanjh, H. S.; Trent, J. O.; Jenkins, T. C.; Kelland, L. R.; Neidle, S. J. Med. Chem. 1998, 41, 4873.
25. (c) Reduction of 11 to 7: Krishnamurthy, R.; Natarajan, S. Synth. Commun. 1992, 22, 3189.
26. 13C NMRs and HRMS. COSY and NOESY 2D spectra are also provided for compounds 6 and 7. See Supporting Information for details.
27. Reaction was finished after < 1 min (TLC). The product was isolated after a simple workup involving washing with base. The products obtained by reaction with both pivaloyl and acetyl chloride were >95% pure.
28. 1H NMR spectra. Bisacylated products (22/23, not shown) were prepared by treatment of 6 with 2 equiv of pivaloyl or acetyl chloride and were fully characterized (see Supporting Information) for comparison purposes.
29. For additional details on experimental procedures and characterization of acylation products see the Supporting Information.
30. 2′: acylation of the other amine group would result in a large chemical shift change for both hydrogens. In practice, we observed the first effect, indicating that the process was working as predicted, but we secured additional proof.
31. Robin, M. B.; Bovey, F. A.; Basch, H. In The Chemistry of Amides; Zabicky, J., Ed.; Wiley-Interscience: New York, 1970; p 1.
32. 1H NMR spectra of compounds 12 and 13 are very similar in the aromatic region and therefore structure-elucidation studies concentrated on 13 and the structure of 12 was assigned by analogy.
33. 2 = 0.2219. CCDC-185843 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/conts/ retrieving.html (or from the Cambridge Crystallographic Data Center, 12, Union Road, Cambridge CB2 1EZ, UK; fax (+44)1223-336-033; or deposit@ccdc.cam.ac.uk).