Cesium Hydroxide Promoted Chemoselective N-Alkylation for the Generally Efficient Synthesis of Secondary Amines

Organic Letters

Volumn 1, Issue 12, 1999, Pages 1893-1896

  Salvatore, Ralph N ^a   Nagle, Advait S ^a   Schmidt, Shaun E ^a   Jung, Kyung Woon ^a  

^a H LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 0001642792     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol9910417     Document Type: Article

References (39)

1. (a) Mitsunobu, O. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon: London, 1991; Vol. 6, p 65.
2. (b) Gibson, M. S. In The Chemistry of the Amino Group; Patai, S., Ed.; Interscience Publishers: New York, 1968; p 37.
3. (c) Sandler, S. R.; Karo, W. In Organic Chemistry; Wasserman, H. H., Ed.; Academic Press: San Diego, 1983; Vol. 12, p 377.
4. (a) Szardenings, A. K.; Burkoth, T. S.; Look, G. C.; Campbell, D. A. J. Org Chem. 1996, 61, 6720 and references therein.
5. (b) Pillai, R. B. C. J. Mol. Catal. 1993, 84, 125.
6. (c) Gribble, G. W.; Nutaitis, C. F. Synthesis 1987, 709.
7. (d) Gribble, G. W.; Jasinski, J. M.; Pellicone, J. T.; Panetta, J. A. Synthesis 1978, 766.
8. (e) Marchini, P.; Liso, G.; Reho, A. J. Org. Chem. 1975, 40, 3453.
9. (f) Rische, T.; Kitsos-Rzychon, B.; Eilbracht, P. Tetrahedron 1998, 54, 2723.
10. (a) Phanstiel, IV, O.; Wang, Q. X.; Powell, D. H.; Ospina, M. P.; Leeson, B. A. J. Org. Chem. 1999, 64, 803.
11. (b) Croce, P. D.; La Rosa, C.; Ritieni, A. J. Chem. Research (S) 1988, 346.
12. (a) Spialter L.; Pappalardo, J. A. In The Acyclic Aliphatic Tertiary Amines; The Macmillan Company: New York, 1965; p 14.
13. (b) O'Meara, J. A.; Gardee, N.; Jung, M.; Ben, R. N.; Durst, T. J. Org. Chem. 1998, 63, 3117.
14. (c) Koh, K.; Ben, R. N.; Durst, T. Tetrahedron Lett. 1993, 34, 4473.
15. (d) Valot, F.; Fache, F.; Jacquot, R.; Spagnol, M.; Lemaire, M. Tetrahedron Lett. 1999, 40, 3689.
16. (e) Suga, K.; Watanabe, S.; Fujita, T.; Pan, T. P. Bull. Chem. Soc. Jpn. 1969, 42, 3606.
17. For our O-alkylations, see: (a) Dueno, E. E.; Chu, F.; Kim, S.-I.; Jung, K. W. Tetrahedron Lett. 1999, 40, 1843.
18. (b) Chu, F.; Dueno, E. E. Jung, K. W. Tetrahedron Lett. 1999, 40, 1847.
19. (c) Kim, S.-I.; Chu, F. Dueno, E. E.; Jung, K. W. J. Org. Chem. 1999, 64, 4578.
20. (d) Parrish, J. P.; Sundaresan, B.; Jung, K. W. Synth. Commun. 1999, 29, 4423.
21. When molecular sieves were not activated, yields and selectivities diminished. Further studies on optimization of reaction conditions will be subject to future publication in the format of a full paper.
22. Galli, C. Org. Prep. Proced. Int. 1992, 24, 287 and references therein.
23. Rationale for reversal of normally observed alkylation rates is proposed to orginate from the amine-cesium ion complexes. Amine protons in complex i should be sufficiently acidic to be abstracted by bases. On the other hand, owing to the increased sterics in quatenary salt ii compared to i, access of bases to available protons would be minimized, inhibiting the alkylation of secondary amines. (Matrix presented) (a) Constable, E. C. In Metals and Ligand Reactivity; VCH Publishers: New York 1996; p 102.
24. (b) Dehmlow, E. V.; Thieser, R.; Zahalka, H. A.; Sasson, Y. Tetrahedron Lett. 1985, 26, 297.
25. (c) Santhanalakshmi, J.; Raja, T. Bull. Chem. Soc. Jpn. 1997, 70, 2829.
26. (d) Ando, T.; Yamawaki, J. Chem. Lett. 1979, 45.
27. (e) Onaka, M.; Ishikawa, K.; Izumi, Y. Chem. Lett. 1982, 1783.
28. (f) Blum, Z. Acta Chem. Scand. 1989, 43, 248.
29. (g) Soong, L.-L.; Leroi, G. E.; Popov, A. I. J. Solut. Chem. 1989, 18, 561.
30. Side reactions including elimination were not observed within our detection limits.
31. Bromination of the corresponding dibenzylamino alcohols was developed in our laboratories, which will be published elsewhere. We found that DMF catalyzed bromination using thionyl bromide in cyclohexane. and the desired product was easily isolated on an even larger scale by either precipitation as the hydrobromide salt or separation of the DMF layer containing only the desired bromide.
32. (a) Gray, B. D.; Jeffs, P. W. J. Chem. Soc., Chem. Commun. 1987, 1329.
33. (b) Bhatt, U.; Mohamed, N.; Just, G. Tetrahedron Lett. 1997, 38. 3679.
34. (c) Maurer, P. J.; Takahata, H.; Rapoport, H. J. Am. Chem. Soc. 1984, 706, 1095.
35. (d) Bowman, W. R.; Coghlan, D. R. Tetrahedron 1997, 53, 15787.
36. (a) Andrés, J. M.; Barrio, R.; Martínez, M. A.; Pedrosa, R.; Pérez-Encabo, A. J. Org. Chem. 1996, 61, 4210.
37. (b) Reetz, M. T.; Drewes, M. W.; Schmitz, A. Angew. Chem., Int. Ed. Engl. 1987, 26, 1141.
38. Optical rotations of the synthetic samples were matched with the known values; see ref 11d. Observed values for pentenyl and benzyl derivatives were -49.5° and -10.0°, respectively, whereas the reported values were -50.2° and -9.9° for the same compounds.
39. Representative Experimental Procedure: To activated powdered 4 Å molecular sieves (500 mg) in anhydrous N,N-dimethylformamide (8.3 mL), was added cesium hydroxide monohydrate (280 mg, 1.7 mmol), and then the white suspension was vigorously stirred for 10 min. After phenethylamine 3 (0.21 mL, 1.7 mmol) was added and followed by additional 30 min of stirring, 1-bromobutane (0.21 mL, 2.0 mmol) was added into the white suspension. The reaction was stirred for 20 h, filtered to remove the molecular sieves and undissolved inorganic salts, and rinsed several times with EtOAc. After the filtrate was concentrated to a nominal volume by blowing air, the residue was taken up in 1 N NaOH, and extracted with EtOAc (4 × 20 mL). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. Flash column chromatography (EtOAc-EtOH, 9:1 v/v) afforded the secondary amine 4 (260 mg, 1.5 mmol; 89%) as a colorless oil as well as tertiary amine 5 (40 mg, 0.17 mmol; 10%) as a pale yellow oil.