C O M M U N I C A T I O N S
Table 3. Synthesis of Unsymmetrical Diarylamines from Aryl
Halides and Ammonia
(2) (a) Ley, S. V.; Thomas, A. W. Angew. Chem., Int. Ed. 2003, 42, 5400.
(b) Kunz, K.; Schloz, A.; Ganzer, D. Synlett 2003, 2428.
(
3) (a) Wolfe, J. P.; Buchwald, S. L. J. Am. Chem. Soc. 1997, 119, 6054. (b)
Desmarets, C.; Schneider, R.; Fort, Y. J. Org. Chem. 2002, 67, 3029. (c)
Omar-Amrani, R.; Thomas, A.; Brenner, E.; Schneider, R.; Fort, Y. Org.
Lett. 2003, 5, 2311. (d) Chen, C.; Yang, L.-M. Org. Lett. 2005, 7, 2209.
(e) Kelly, R. A., III; Scott, N. M.; D ´ı ez-Gonz a´ lez, S.; Stevens, E. D.;
Nolan, S. P. Organometallics 2005, 24, 3442.
(
4) (a) Wolfe, J. P.; Åhman, J.; Sadighi, J. P.; Singer, R. A.; Buchwald, S. L.
Tetrahedron Lett. 1997, 38, 6367. (b) Jaime-Figuerosa, S.; Liu, Y.;
Muchowski, J. M.; Putman, D. G. Tetrahedron Lett. 1998, 39, 1313. (c)
Hori, K.; Mori, M. J. Am. Chem. Soc. 1998, 120, 7651. (d) Lim, C. W.;
Lee, S.-G. Tetrahedron 2000, 56, 5131. (e) Huang, X. H.; Buchwald, S.
L. Org. Lett. 2001, 3, 3417. (f) Lee, S.; Jørgensen, M.; Hartwig, J. F.
Org. Lett. 2001, 3, 2729. (g) Lee, D. Y.; Hartwig, J. F. Org. Lett. 2005,
7, 1169.
(
5) For recent examples see: (a) Denni-Dischert, D.; Marterer, W.; B a¨ nziger,
M.; Yusuff, N.; Batt, D.; Ramsey, T.; Geng, P.; Michael, W.; Wang, R.-
M. B.; Taplin, F., Jr.; Versace, R.; Cesarz, D.; Perez, L. B. Org. Process
Res. DeV. 2006, 10, 70. (b) Li, Q.; et al. Bioorg. Med. Chem. Lett. 2006,
a
Conditions: Pd2dba3, 1 mol %; ligand 4, 5 mol %; NaOt-Bu, 2.8 equiv;
b
NH3, 5 equiv; 1,4-dioxane; 80 °C, 3 h. Conditions: (i) -NH3, (ii) reduce
volume, (iii) Ar′Y, 0.9 equiv; ligand 5, 5 mol %; 80 °C, 16 h.
1
6, 2000. (c) Huang, H. C.; et al. J. Med. Chem. 2005, 48, 5853. (d)
Humphries, A. C.; Gancia, E.; Gilligan, M. T.; Goodacre, S.; Hallett, D.;
Merchant, K. J.; Thomas, S. R. Bioorg. Med. Chem. Lett. 2006, 16,
1518.
Table 4. Synthesis of Unsymmetrical Triarylamines from Aryl
Halides and Ammonia
(
6) For recent examples see: (a) Kang, H.; Facchetti, A.; Jiang, H.; Cariati,
E.; Righetto, S.; Ugo, R.; Zuccaccia, C.; Macchioni, A.; Stern, C. L.;
Liu, Z.; Ho, S.-T.; Brown, E. C.; Ratner, M. A.; Marks, T. J. J. Am. Chem.
Soc. 2007, 129, 3267. (b) Lukey, C. A.; Tymichova, M.; Brown, H. R. J.
Polym. Sci., Part A: Polym. Chem. 2007, 45, 1282. (c) Agou, T.;
Kobayashi, J.; Kawashima, T. Org. Lett. 2006, 8, 2241. (d) Flatt, A. K.;
Chen, B.; Taylor, P. G.; Chen, M.; Tour, J. M. Chem. Mater. 2006, 18,
4
513. (e) Kang, H.; Facchetti, A.; Stern, C. L.; Rheingold, A. L.; Kassel,
W. S.; Marks, T. J. Org. Lett. 2005, 7, 3721.
(
7) For selected examples see: (a) Sato, H.; Fujihara, T.; Obora, Y.; Tokunaga,
M.; Kiyosu, J.; Tsuji, Y. Chem. Commun. 2007, 269. (b) Bolm, C.; Frison,
J-C.; Le Paih, J.; Moessner, C.; Raabe, G. J. Organomet. Chem. 2004,
6
89, 3767. (c) Ball, P. J.; Shtoyko, T. R.; Bauer, J. A. K.; Oldham, W. J.;
Connick, W. B. Inorg. Chem. 2004, 43, 622. (d) Liu, Y.; McWhorter, W.
W., Jr. J. Am. Chem. Soc. 2003, 125, 4240.
(8) Willis, M. C. Angew. Chem., Int. Ed. 2007, 46, 3402.
(
9) For synthesis of di- and triarylamines from aryl halides and urea in a
process that may involve the in situ generation of ammonia: (a) Artamkina,
G. A.; Sergeev, A. G.; Shtern, M. M.; Beletskaya, I. P. Russian J. Org.
Chem. 2006, 42, 1683. (b) Artamkina, G. A.; Sergeev, A. G.; Shtern, M.
M.; Beletskaya, I. P. Synlett 2006, 235.
a
Conditions: Pd2dba3, 1 mol %; ligand 4, 5 mol %; NaOt-Bu, 4.2 equiv;
b
NH3, 5 equiv; 1,4-dioxane; 80 °C, 3 h. Conditions: (i) -NH3, (ii) reduce
volume, (iii) Ar′Y 0.9, equiv; ligand 5, 5 mol %; 80 °C, 3 h. Conditions:
c
(
10) Shen, Q.; Hartwig, J. F. J. Am. Chem. Soc. 2006, 128, 10028.
Ar′′Z, 0.9 equiv; 100 °C, 16 h.
(11) Anderson, K. W.; Ikawa, T.; Tundel, R. E.; Buchwald, S. L. J. Am. Chem.
Soc. 2006, 128, 10694.
(
12) (a) Shirota, Y. J. Mater. Chem. 2000, 10, 1. (b) Shirota, Y. J. Mater.
Chem. 2005, 15, 75.
13) (a) Thayumanavan, S.; Barlow, S.; Marder, S. R. Chem. Mater. 1997, 9,
321. (b) Harris, M. C.; Buchwald, S. L. J. Org. Chem. 2000, 65, 5327.
(c) Nozaki, K.; Takahashi, K.; Nakano, K.; Hiyama, T.; Tang, H. Z.; Fujiki,
M.; Yamaguchi, S.; Tamao, K. Angew. Chem., Int. Ed. 2003, 42,
2051.
reaction vessel (Tables 3 and 4). The key to success was to remove
excess ammonia from the solution of the aniline initially formed
and to reduce the solvent volume before addition of the second
(
14
aryl halide and 5. It is interesting that 5 can efficiently displace
4
from the palladium center; this is presumably due to the smaller
15
size of the cyclohexyl- versus tert-butylphosphino substituents.
(14) General procedure for the synthesis of unsymmetrical triarylamines: Pd
2
-
dba (4.6 mg, 0.005 mmol), ligand 4 (8.5 mg, 0.025 mmol), sodium tert-
3
Under these conditions functional groups such as alkenes and THP-
protected phenols and heterocycles such as pyridines and pyrroles
were tolerated. Of particular note is the ability to make the diamine
TPD, a molecule which has numerous applications as an organic
photoconductor and hole transporter.16
In summary we have developed new systems for the palladium-
catalyzed coupling of ammonia with aryl halides which allow the
selective synthesis of either anilines or di- or triarylamines as
desired.
butoxide (202 mg, 2.1 mmol), and aryl halide a (0.5 mmol) (if solid)
were weighed into an oven-dried test-tube which was sealed with a Teflon
screw cap. The tube was then evacuated and back-filled with argon. 1,4-
Dioxane (5 mL), ammonia (3 mL of a 0.5 M solution in 1,4-dioxane, 1.5
mmol), and the aryl halide a (0.5 mmol) (if liquid) were then added by
syringe. The tube was then placed in a preheated oil bath at 80 °C for 3
h. At the end of this time the tube was removed from the bath and allowed
to cool, and the tube was evacuated and ultrasonicated until the total
solvent volume was reduced to approximately 3 mL and back-filled with
argon. The Teflon screw cap was then briefly removed, and ligand 5 (11.9
mg, 0.025 mmol) and aryl halide b (0.45 mmol) (if solid) were added. If
liquid aryl halide b (0.45 mmol) was then added by syringe. The tube
was then evacuated, back-filled with argon, and replaced in the oil bath
at 80 °C for 3 h. At the end of this time the tube was removed from the
bath and allowed to cool. If aryl halide c were solid the Teflon screw cap
was removed and aryl halide c (0.45 mmol) was added. The tube was
then evacuated and back-filled with argon. If aryl halide c was a liquid,
the Teflon screw cap was not removed and the aryl halide c (0.45 mmol)
was added by syringe. The tube was then placed in a preheated oil bath
at 100 °C for 16 h. At the end of this time the tube was removed from the
bath, the contents diluted with EtOAc, and the mixture filtered through a
plug of silica. The solution was then concentrated under reduced pressure,
and the residue was purified on the Biotage SP4.
Acknowledgment. We thank the National Institutes of Health
(Grant GM-058160) for supporting this work. We thank Merck,
Amgen, and Boehringer Ingelheim for additional unrestricted
support. We thank Saltigo for a gift of 5. D.S.S. thanks the Royal
Commission for the Exhibition of 1851 for a Research Fellowship.
Supporting Information Available: Complete refs 5b and 5c and
experimental information and spectral data for all compounds. This
material is available free of charge via the Internet at http://pubs.acs.org.
(15) Yang, Q.; Ney, J. E.; Wolfe, J. P. Org. Lett. 2005, 7, 2575.
(
16) TPD ) N,N′-bis(3-methylphenyl)-N,N′-diphenylbenzidine, for example:
Shen, Y.; Klein, M. W.; Jacobs, D. B.; Scott, J. C.; Malliaras, G. G. Phys.
ReV. Lett. 2001, 86, 3867.
References
(
1) Jiang, L.; Buchwald, S. L. In Metal-Catalyzed Cross-Coupling Reactions,
nd ed.; de Meijere, A., Diederich, F., Eds.; Wiley-VCH: Weinheim,
Germany, 2004, p 699.
2
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J. AM. CHEM. SOC.
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