Palladium-catalyzed amination of aryl dibromides with secondary amines: Synthetic and mechanistic aspects

Tetrahedron Letters

Volumn 40, Issue 35, 1999, Pages 6393-6397

  Beletskaya, Irina P ^a   Bessmertnykh, Alla G ^b   Guilard, Roger ^b  

^a MOSCOW STATE UNIVERSITY   (Russian Federation)

^b UNIVERSITÉ DE BOURGOGNE   (France)

Author keywords

Aryl amines; Aryl halides; Catalysis; Palladium

Indexed keywords

BROMINE DERIVATIVE; HALIDE; PALLADIUM; POLYCYCLIC AROMATIC HYDROCARBON DERIVATIVE;

ARTICLE; CATALYSIS; DEHALOGENATION; MOLECULAR INTERACTION; REACTION ANALYSIS; SYNTHESIS;

ARENE;

EID: 0033609777     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(99)01246-0     Document Type: Article

References (25)

1. For a review, see: (a) Frost, C. G.; Mendonça, P. J. Chem. Soc., Perkin Trans. 1 1998, 2615-2623.
2. (b) Hartwig, J. F. Angew. Chem., Int. Ed. Engl. 1998, 37, 2046-2067.
3. (c) Wolfe, J. P.; Wagaw, S.; Marcoux, J.-F.; Buchwald, S. L. Acc. Chem. Res. 1998, 31, 805-818.
4. (a) Yamamoto, T.; Nishiyama, M.; Koie, Y. Tetrahedron Lett. 1998, 39, 2367-2370.
5. (b) Sadighi, J. P.; Singer, R. A.; Buchwald, S. L. J. Am. Chem. Soc. 1998, 120, 4960-4976.
6. (c) For Pd-catalyzed polycondensation, see: Kanbara, T.; Izumi, K.; Nakadani, Y; Narise, T.; Hasegawa, K. Chem. Lett. 1997, 1185-1186.
7. Beletskaya, I. P.; Bessmertnykh, A. G.; Guilard, R. Synlett 1999, submitted for publication.
8. The factors which control the product selectivity are not clear and predictable as yet. See: Hamann, B. C.; Hartwig, J. F. J. Am. Chem. Soc. 1998, 120, 3694-3703 and references cited therein.
9. Beletskaya, I. P.; Bessmertnykh, A. G.; Mishechkin, R. A.; Guilard, R. Russ. Chem. Bull. 1998, 1416-1417.
10. Witulski, B.; Senft, S.; Thum, A. Synlett 1998, 504-506. For Pd-catalyzed polycondensation, see:
11. Kanbara, T.; Honma, A.; Hasegawa, K. Chem. Lett. 1996, 1135-1136.
12. 3=tri-o-tolylphosphine, dba=dibenzylideneacetone.
13. The reaction of o-dibromobenzene with morpholine proceeds slowly and gives after reflux (24 h) 13% of N- phenylmorpholine, 18% of bromobenzene along with starting dibromide. Piperidine readily reacts with o-dibromobenzene affording N-phenylpiperidine 2 in 93% yield. The reaction of diethylamine and o-dibromobenzene gives 75% of N,N-diethylaniline along with 15% of N-ethylindole. N-ethylindole could be formed by the following route: (1) dehydrogenation of diethylamine followed by its isomerization to the enamine derivative, (2) Heck reaction of o- dibromobenzene with this enamine, (3) intramolecular palladium-catalyzed amination affording N-ethylindole.
14. It is well-known that chelating ligands provide an enhanced selectivity for the amination over reductive dehalogenation in the catalytic reactions of aryl halides with amines as well as some of aryl polybromides with morpholine. See, e.g.: Refs. 1, 6 and Ward, Y. D.; Farina, V. Tetrahedron Lett. 1996, 37, 6993-6996.
15. The same result was obtained in the reaction of 4-tert-butylbromobenzene with N,N-di-n-butylamine. See: Marcoux, J.-F.; Wagaw, S.; Buchwald, S. L. J. Org. Chem. 1997, 62, 1568-1569.
16. (a) Wolfe, J. P.; Wagaw, S.; Buchwald, S. L. J. Am. Chem. Soc. 1996, 118, 7215-7216.
17. (b) Old, D. W.; Wolfe, J. P.; Buchwald, S. L. J. Am. Chem. Soc. 1998, 120, 9722-9723.
18. (c) Hamann, B. C.; Hartwig, J. F. J. Am. Chem. Soc. 1998, 120, 7369-7370.
19. (a) Guram, A. S.; Rennels, R. A.; Buchwald, S. L. Angew. Chem., Int. Ed. Engl. 1995, 34, 1348-1350.
20. (b) Driver, M. S.; Hartwig, J. F. J. Am. Chem. Soc. 1997, 119, 8232-8245.
21. Moreover, according to the above mechanism one may expect on the basis of the generally accepted ideas that the relative amount of the reduction products would be increased by the use of inert solvents (see, for example: Bryndza, H. E.; Tam, W. Chem. Rev. 1988, 88, 1163-1188). However, the reaction of p-dibromobenzene with morpholine gives a lower yield of reduction product when the reaction is carried out in toluene instead of dioxane (Table 1, entries 1 and 2).
22. Hartwig, J. F.; Richards, S.; Baranano, D.; Paul, F. J. Am. Chem. Soc. 1996, 118, 3626-3633.
23. 13C NMR data). However, reactions of p- and m-dibromobenzenes with piperidine in the presence of NaOt-Bu proceed very slowly (less than 40% of conversion after 3 days of refluxing) leading to mixtures of products of nucleophilic substitution (aryne mechanism).
24. Even using a 3:1 ratio of p-dibromobenzenes to morpholine only results in the formation of N-(4-bromophenyl)morpholine 3 (33%) along with diaminobenzene 2 (38%).
25. Our results do not allow us to propose a detailed mechanism of this reaction. However, it should be noted that: (1) the possibility of reduction of aryl halides with amines in the presence of Pd(0) complexes has already been shown (Imai, H.; Nishiguchi, T.; Tanaka, M.; Fukuzumi, K. J. Org. Chem. 1977, 42, 2309-2313). Although the mechanism of this reaction is not clear, the amido-coordinated palladium complexes do not seem to be involved since pyrrolidine and N- methylpyrrolidine have similar reactivity under these conditions; (2) since reduction ceases after the full consumption of the base in the reaction of p-dibromobenzene with excess of morpholine and 0.5 equiv. of NaOt-Bu (GC/MS analysis), this reduction reaction must be assisted by an external base.