Pd-Catalyzed Oxidative Biaryl Bond Formation
COMMUNICATION
118.59 (CH), 122.59 (CH), 124.62 (CH), 125.46 (CH), 138.41 (C), 139.94
(C), 141.10 (C), 147.16 (C), 154.83 (C), 177.63 (C=O), 213.27 ppm
AHCTUNGTRENNUNG
(C=O); ESI-MS: 416 [M+H]+ for the 106Pd isotope (see Figure 4).
Acknowledgements
We are grateful to the Deutsche Forschungsgemeinschaft for financial
support (grant KN 240/16–1).
Scheme 8. Reductive elimination of the palladium(II) complex 32. Re-
agents and conditions: a) HOAc, air, 808C, 30 min.
À
Keywords: C H activation · metallacycles · palladium ·
reaction mechanisms · X-ray diffraction
palladium was observed. The present result unequivocally
confirmed that the palladacycle 32 is capable of generating
a catalytically active species and thus, represents itself an
active intermediate in this catalysis.
[1] Reviews: a) E. M. Beccalli, G. Broggini, M. Martinelli, S. Sottocor-
nte, A. R. Kapdi, Angew. Chem. 2009, 121, 9976–10011; Angew.
Chem. Int. Ed. 2009, 48, 9792–9826; c) S.-L. You, J.-B. Xia, Top.
Curr. Chem. 2010, 292, 165–194; d) W. Han, A. R. Ofial, Synlett
2011, 1951–1955.
In conclusion, our present results provide valuable in-
À
sights into the mechanism of C H bond activation. We have
provided direct evidence that the palladium(II)-catalyzed
À
oxidative C C coupling of arenes to biaryls by double aryl
À
C H bond activation proceeds via an intermediate diaryl
[2] B. ꢀkermark, L. Eberson, E. Jonsson, E. Pettersson, J. Org. Chem.
1975, 40, 1365–1367.
palladium(II) complex. The isolated palladium(II) complex
has been characterized by X-ray crystallography and was
proven to be catalytically active. Further studies on the
mechanism of the palladium(II)-catalyzed coupling to biar-
yls are currently in progress in our laboratories. Moreover,
the regiodirecting effect of the pivaloyloxy, acetyl, and relat-
ed directing groups on the electrophilic palladation can be
exploited for applications in natural product synthesis.
b) H.-J. Knçlker, Curr. Org. Synth. 2004, 1, 309–331; c) W. Frçhner,
M. P. Krahl, K. R. Reddy, H.-J. Knçlker, Heterocycles 2004, 63,
2393–2407; d) H.-J. Knçlker, K. R. Reddy in The Alkaloids, Vol. 65
(Ed.: G. A. Cordell), Academic Press, Amsterdam, 2008, pp. 1–430;
e) K. K. Gruner, H.-J. Knçlker in Heterocycles in Natural Product
Synthesis (Eds.: K. C. Majumdar, S. K. Chattopadhyay), Wiley-
VCH, Weinheim, 2011, pp. 341–376.
Furukawa, M. Yogo, C. Ito, T.-S. Wu, C.-S. Kuoh, Chem. Pharm.
A. M. F. Oliveira-Campos, M.-J. R. P. Queiroz, P. V. R. Shannon, J.
[5] a) J. M. Takacs, X.-t. Jiang, Curr. Org. Chem. 2003, 7, 369–396; b) J.
Tsuji, Palladium Reagents and Catalysts, Wiley, Chichester, 2004,
pp. 27–35.
[7] H.-J. Knçlker, N. OꢄSullivan, Tetrahedron 1994, 50, 10893–10908.
[8] H.-J. Knçlker in Advances in Nitrogen Heterocycles, Vol. 1 (Ed.:
C. J. Moody), JAI Press, Greenwich (CT), 1995, pp. 173–204.
[9] a) B. ꢀkermark, J. D. Oslob, U. Heuschert, Tetrahedron Lett. 1995,
36, 1325–1326; b) H. Hagelin, J. D. Oslob, B. ꢀkermark, Chem. Eur.
M. P. Krahl, T. Krause, G. Schlechtingen, H.-J. Knçlker, Synlett
2007, 268–272; g) T. A. Choi, R. Czerwonka, R. Forke, A. Jꢂger, J.
Knçll, M. P. Krahl, T. Krause, K. R. Reddy, S. G. Franzblau, H.-J.
Knçlker, Synlett 2008, 1698–1702; i) M. Schmidt, H.-J. Knçlker, Syn-
lett 2009, 2421–2424; j) M. Fuchsenberger, R. Forke, H.-J. Knçlker,
Synlett 2011, 2056–2058.
Experimental Section
Experimental procedure for the palladium(II)-catalyzed cyclization of
the diarylamine 27:
A
solution of the diarylamine 27 (80.2 mg,
(OAc)2 (46.8 mg,
0.258 mmol), Pd(OAc)2 (5.9 mg, 0.026 mmol), CuCAHTUNGTRENNNUG
N
0.258 mmol), and K2CO3 (3.6 mg, 0.026 mmol) in pivalic acid (500 mg)
was stirred under air at 1208C for 13 h. After cooling, the reaction mix-
ture was filtered through a short path of Celite, which was subsequently
washed with Et2O. The combined filtrates were washed first with a satu-
rated aqueous solution of NaHCO3, then with a saturated aqueous solu-
tion of NaCl and dried with MgSO4. Removal of the solvent and purifica-
tion of the residue by flash chromatography on silica gel (eluent: 8–33%
of EtOAc in pentane) afforded in the following order of polarity the dia-
rylamine 27 (4.9 mg, 6% yield), and the carbazoles 29 (23.9 mg, 30%
yield), 28 (18.4 mg, 23%), and 30 (12.8 mg, 16%). For spectroscopic char-
acterization (1H NMR, 13C NMR, HMBC, HSQC, and NOESY) of the
carbazoles 28–30, see the Supporting Information. The carbazole 31
could be detected using GC-MS.
Synthesis of the palladacycle 32: A solution of the diarylamine 27
(159 mg, 0.511 mmol) and PdACHTNUGTRNEUNG(OAc)2 (115 mg, 0.512 mmol) in acetic acid
(2.5 mL) was stirred under air at room temperature for 60 h. The reaction
mixture was filtered. Evaporation of the solvent and purification of the
residue by flash chromatography on silica gel (eluent: 3–33% of EtOAc
in pentane) provided in the following order of polarity the complex 32
(4 mg, 2% yield), diarylamine 27 (88 mg, 55%), the carbazoles 29
(10.2 mg, 7%), 28 (15.6 mg, 10%), and 30 (4.2 mg, 3%). Crystallization
of the palladium complex 32 from EtOAc/pentane afforded red crystals;
1H NMR (600 MHz, CDCl3): d=1.42 (s, 9H), 2.72 (s, 3H), 6.60 (d, J=
7.9 Hz, 1H), 6.68 (dd, J=7.9, 0.8 Hz, 1H), 6.86 (s, 1H), 6.87 (d, J=
7.9 Hz, 1H), 7.09 (t, J=7.9 Hz, 1H), 7.12 (t, J=7.5 Hz, 1H), 7.28 ppm (d,
J=7.2 Hz, 1H); 13C NMR and DEPT (150 MHz, CDCl3): d=24.62
(CH3), 27.24 (3 CH3), 40.14 (C), 107.31 (CH), 110.35 (C), 110.80 (CH),
2481–2483; b) R. Forke, M. P. Krahl, F. Dꢂbritz, A. Jꢂger, H.-J.
Knçlker, Synlett 2008, 1870–1876.
Chem. Eur. J. 2012, 18, 770 – 776
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