3
592
J . Org. Chem. 1999, 64, 3592-3594
Electr osp r a y Ion iza tion Ma ss Sp ectr om etr y Detection of
In ter m ed ia tes in th e P a lla d iu m -Ca ta lyzed Oxid a tive Self-Cou p lin g
of Ar en ebor on ic Acid s
Mar ´ı a A. Aramend ´ı a* and Fernando Lafont
Mass Spectrometry Service and Organic Chemistry Department, University of Cordoba, C o´ rdoba, Spain
Marcial Moreno-Ma n˜ as,* Roser Pleixats, and Anna Roglans
Department of Chemistry, Universitat Aut o` noma de Barcelona, Cerdanyola, 08193-Barcelona, Spain
Received November 4, 1998
Several intermediates of the oxidative coupling of areneboronic acids to afford biaryls have been
identified by electrospray ionization mass spectrometry. Knowledge has been gained about the
steps occurring after the biaryl formation and leading to the recovery of the catalytic species.
In tr od u ction
The palladium-catalyzed preparation of biphenyl by
Sch em e 1. Stu d ied P d -Ca ta lyzed Self-Cou p lin g
Rea ction s
oxidative coupling of phenylboronic acid was reported by
1
Suzuki in 1987. The reaction was performed in the
presence of palladium(II) and copper(II) acetates. Later,
2
this self-coupling was further developed by others. The
coupling can be performed whether in the presence of
dibromo compounds2
a,b,d
or Cu(II), or in the absence of
2c
to 12, and 12 to 2). As a matter of fact, conventional
chemical knowledge suggests that thermodynamics do
any added oxidizing agent, but the inert atmosphere is
then detrimental.2 The Pd-catalyzed self-coupling of
c
2
not favor mechanistic steps involving direct (HO)
B(OH) elimination with respect to other requiring borate
elimination.
B-
4
-(trifluoromethyl)phenylboronic acid, 3b (Scheme 1),
2
was studied by some of us under different experimental
conditions and monitoring the reaction by 1 F NMR. As
a result, we proposed a mechanistic cycle3 which is
reproduced in more detail in Figure 1. Formation of
biaryls X-Ph-Ph by phenyl scrambling from triphenylphos-
9
On the other hand, electrospray ionization mass spec-
trometry (ESI-MS) has become a powerful tool in the
identification of organic and organometallic reaction
4
intermediates. The very mild ionization conditions per-
3
phine ligand was also discussed and will not be consid-
mit data to be acquired directly from solutions where
reactions are taking place. They also allow the detection
of molecular peaks without fragmentation, thus making
intermediate identification possible. ESI-MS has been
applied to intermediate detection of palladium-catalyzed
ered here. Oxidative addition of areneboronic acids to
Pd(0) species (2 + 3 to 5) was considered to be achieved
by an initial acid-base reaction (2 + 3 to 4) followed by
1
,2 arene migration to an electron-deficient palladium
5
6
atom (4 to 5). From 5 + 3 to 7 the same sequence of steps
occurs. Then, intermediate 7 gives very fast reductive
elimination to afford biaryls and intermediate 9. Recovery
reactions such as cross-couplings and the Heck reaction.
Resu lts a n d Discu ssion
2
of the catalytic species PdL , 2, from 9 was not detailed
We decided to perform the self-couplings shown in
Scheme 1. Our procedure was to monitor the reactions
by sampling at different times and analysis with ESI-
MS (positive ionization, see Experimental Section for
conditions). Peaks due to intermediates containing pal-
ladium are immediately detected by the characteristic
isotope distribution of the metal. Isotopic abundance of
clusters was compared with calculated values.
3
in our first paper, but we suggested that this could be
the slow step of the catalytic cycle. Nevertheless, step 4
to 5 (and 6 to 7) is reminiscent of the Wagner-Meerwein
rearrangement. Therefore, electron-withdrawing substit-
uents should slow it down, this step being also a
candidate to be rate-determining for certain substituents
at the arene ring.
A more-detailed consideration of the recovery of 2 from
First of all, reaction 1 (Table 1) was studied at 15, 30,
9
suggests that it takes place in three steps (9 to 11, 11
4
5, 60, 105, and 135 min. There was only one palladium-
containing species detected by a cluster of peaks at m/z
*
Corresponding authors. Prof. Marcial Moreno-Ma n˜ as. Phone: 34-
35811254. Fax: 34-935811265. E-mail: iqorb@cc.uab.es. Prof. Mar ´ı a
A. Aramend ´ı a. Fax: 34-957218606. E-mail: qo1maruj@uco.es.
)
734-744. This intermediate was observed between 30
9
(
(
1) Miyaura, N.; Suzuki, A. Main Group Metal Chem. 1987, 10, 295.
2) (a) Song, Z. Z.; Wong, H. N. C. J . Org. Chem. 1994, 59, 33. (b)
(4) Wilson, S. R.; P e´ rez, J .; Pasternak, A. J . Am. Chem. Soc. 1993,
115, 1994.
(5) Aliprantis, A. O.; Canary, J . W. J . Am. Chem. Soc. 1994, 116,
6985.
(6) (a) Ripa, L.; Hallberg, A. J . Org. Chem. 1996, 61, 7147. (b) Brown,
J . M.; Hii, K. K. Angew. Chem., Int. Ed. Engl. 1996, 35, 657. (c) Hii,
K. K.; Claridge, T. D. W.; Brown, J . M. Angew. Chem., Int. Ed. Engl.
1997, 36, 984.
Ye, X. S.; Wong, H. N. C. J . Org. Chem. 1997, 62, 1940. (c) Smith, K.
A.; Campi, E. M.; J ackson, W. R.; Marcuccio, S.; Naeslund, C. G. M.;
Deacon, G. B. Synlett 1997, 131. (d) Yamaguchi, S.; Ohno, S.; Tamao,
K. Synlett 1997, 1199.
(3) Moreno-Ma n˜ as, M.; P e´ rez, M.; Pleixats, R. J . Org. Chem. 1996,
6
1, 2346.
1
0.1021/jo982210o CCC: $18.00 © 1999 American Chemical Society
Published on Web 04/27/1999