Suzuki-miyaura cross-coupling of benzylic carbonates with arylboronic acids

Article abstract of DOI:10.1021/ol050078q

(Chemical Equation Presented) The cross-coupling of benzylic carbonates with arylboronic acids gave the corresponding diarylmethanes in high yields by use of the palladium catalyst generated in situ from [Pd(n³-C ₃H₅)Cl]₂ and 1,5-bis(diphenylphosphino)pentane (DPPPent). The Suzuki-Miyaura reaction using DPPPent-palladium catalyst is applicable to syntheses of a broad range of functionalized diarylmethanes.

Full text of DOI:10.1021/ol050078q

ORGANIC
LETTERS
2005
Vol. 7, No. 5
945-947
Suzuki−Miyaura Cross-Coupling of
Benzylic Carbonates with Arylboronic
Acids
Ryoichi Kuwano* and Masashi Yokogi
Department of Chemistry, Graduate School of Siences, Kyushu UniVersity,
6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan
rkuwascc@mbox.nc.kyushu-u.ac.jp
Received January 14, 2005
ABSTRACT
The cross-coupling of benzylic carbonates with arylboronic acids gave the corresponding diarylmethanes in high yields by use of the palladium
catalyst generated in situ from [Pd( Miyaura reaction using DPPPent
3-C3H5)Cl]2 and 1,5-bis(diphenylphosphino)pentane (DPPPent). The Suzuki
palladium catalyst is applicable to syntheses of a broad range of functionalized diarylmethanes.
η
−
−
During the last several years, tremendous progress has been
made in palladium-catalyzed cross-couplings of organo-
metallic compounds with unactivated aryl chlorides,1 which
had been regarded as unsuitable electrophilic coupling
partners. The catalytic cross-coupling can now be conducted
even with alkyl chloride.2 However, the use of carboxylate
functionality as a leaving group on an electrophilic substrate
is unexplored except for the reactions of allylic esters.3 The
acyl C-O bond of carboxylate is usually cleaved by
palladium(0) complex (path a), and aryl carboxylates are
often employed in the catalytic acylation of organometallic
compounds (Figure 1).4 The oxidative addition of the C-O
formation of A through path b has been reported in the
reaction of benzyl trifluoroacetate with palladium(0) com-
plex.5,6
Recently, we reported catalytic benzylic substitutions of
benzylic carbonates, where a DPPF-ligated palladium com-
plex was found to be the best catalyst.7 The catalytic reaction
may involve the formation of (η3-benzyl)palladium through
path b, and it suggests that the DPPF-palladium catalyst is
efficient for the activation of the benzylic C-O bond. The
(1) Reviews: (a) Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed. 2002,
41, 4176-4211. Examples: (b) Littke, A. F.; Fu, G. C. Angew. Chem., Int.
Ed. 1998, 37, 3387-3388. (c) Old, D. W.; Wolfe, J. P.; Buchwald, S. L. J.
Am. Chem. Soc. 1998, 120, 9722-9723. (d) Kataoka, N.; Shelby, Q.;
Stambuli, J. P.; Hartwig, J. F. J. Org. Chem. 2002, 67, 5553-5566.
(2) (a) Kirchhoff, J. H.; Dai, C.; Fu, G. C. Angew. Chem., Int. Ed. 2002,
41, 1945-1947. (b) Frisch, A. C.; Shaikh, N.; Zapf, A.; Beller, M. Angew.
Chem., Int. Ed. 2002, 41, 4056-4059. (c) Zhou, J.; Fu, G. C. J. Am. Chem.
Soc. 2003, 125, 12527-12530. (d) Frisch, A. C.; Rataboul, F.; Zapf, A.;
Beller, M. J. Organomet. Chem. 2003, 687, 403-409.
(3) Examples: (a) Del Valle, L.; Stille, J. K.; Hegedus, L. S. J. Org.
Chem. 1990, 55, 3019-3023. (b) Uozumi, Y.; Danjo, H.; Hayashi, T. J.
Org. Chem. 1999, 64, 3384-3388. (c) Bouyssi, D.; Gerusz, V.; Balme, G.
Eur. J. Org. Chem. 2002, 2445-2448.
Figure 1. Oxidative Addition of Carboxylate to Palladium(0).
(4) (a) Kakino, R.; Shimizu, I.; Yamamoto, A. Bull. Chem. Soc. Jpn.
2001, 72, 371-376. (b) Tatamidani, H.; Kakiuchi, F.; Chatani, N. Org.
Lett. 2004, 6, 3597-3599.
bond leading to (alkyl)(carboxylato)palladium A (path b) is
desirable for the development of the cross-coupling using
an ester, but the C-O bond is difficult to activate by a low-
valent metal complex in general. Only one example of the
(5) Nagayama, K.; Shimizu, I.; Yamamoto, A. Bull. Chem. Soc. Jpn.
1999, 72, 799-803.
(6) Narahashi, H.; Yamamoto, A.; Shimizu, I. Chem. Lett. 2004, 33, 348-
349.
10.1021/ol050078q CCC: $30.25
© 2005 American Chemical Society
Published on Web 02/04/2005

Table 1. Effect of Phosphine-Palladium Complex on the
Cross-Coupling of Benzyl Methyl Carbonate with Phenylboronic
Acida
Table 2. Cross-Coupling of Benzylic Carbonates (1) with
Arylboronic Acids (2)a
entry
ligand
DPPF
[Pd]
yield, %b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
[Pd(η3-C3H5)(cod)]BF4
[Pd(η3-C3H5)(cod)]BF4
[Pd(η3-C3H5)(cod)]BF4
[Pd(η3-C3H5)(cod)]BF4
[Pd(η3-C3H5)(cod)]BF4
[Pd(η3-C3H5)(cod)]BF4
[Pd(η3-C3H5)(cod)]BF4
[Pd(η3-C3H5)(cod)]BF4
[Pd(η3-C3H5)(cod)]BF4
[Pd(η3-C3H5)(cod)]BF4
PdBr2(cod)
3
2
0
0
1
PPh3
P(C6H4-o-Me)
P(t-Bu)3
DPPBz
DPPE
DPPP
3
1
DPPB
24
32
13
16
23
<1
50 (89c)
DPPPent
DPPHex
DPPPent
DPPPent
DPPPent
DPPPent
Pd(OAc)2
Pd(dba)2
[Pd(η3-C3H5)Cl]2
a Reactions were conducted in DMF (1.0 mL) at 80 °C for 3 h. The
ratio of 1a (0.2 mmol):2a:K2CO3:[Pd]:ligand was 20:30:60:1:1. b GC yield
(average of two runs). c GC yield at 24 h.
above consideration prompted us to develop a new class of
cross-couplings using benzylic carbonates as electrophiles.
In this paper, we report the Suzuki-Miyaura cross-coupling
of benzylic carbonates.8,9 The catalytic reaction offered a new
straightforward approach to diverse diarylmethanes,10 which
is a ubiquitous structural constituent of pharmacologically
interesting compounds.11
First, we attempted the cross-coupling of benzyl methyl
carbonate (1a) with phenylboronic acid (2a) in the presence
of DPPF-[Pd(η3-C3H5)(cod)]BF4, which was the most
(7) (a) Kuwano, R.; Kondo, Y.; Matsuyama, Y. J. Am. Chem. Soc. 2003,
125, 12104-12105. (b) Kuwano, R.; Kondo, Y. Org. Lett. 2004, 6, 3545-
3547.
(8) Reviews: (a) Miyaura, N.; Suzuki, A. Chem. ReV. 1995, 95, 2457-
2483. (b) Bellina, F.; Carpita, A.; Rossi, R. Synthesis 2004, 2419-2440.
(9) Examples of cross-coupling of benzyl halides with organoboron
compounds: (a) Chowdhury, S.; Georghiou, P. Tetrahedron Lett. 1999,
40, 7599-7603. (b) Langle, S.; Abarbri, M.; Ducheˆne, A. Tetrahedron Lett.
2003, 44, 9255-9258. (c) Chahen, L.; Doucet, H.; Santelli, M. Synlett 2003,
1668-1672.
(10) Examples of diarylmethane synthesis through cross-coupling: (a)
Negishi, E.-i.; King, A. O.; Okukado, N. J. Org. Chem. 1977, 42, 1821-
1823. (b) Vanier, C.; Lorge´, F.; Wagner, A.; Mioskowski, C. Angew. Chem.,
Int. Ed. 2000, 39, 1679-1683. (c) Molander, G. A.; Ito, T. Org. Lett. 2001,
3, 393-396. (d) Itami, K.; Mineno, M.; Kamei, T.; Yoshida, J. Org. Lett.
2002, 4, 3635-3638.
(11) (a) Wai, J. S.; Egbertson, M. S.; Payne, L. S.; Fisher, T. E.; Embrey,
M. W.; Tran, L. O.; Melamed, J. Y.; Langford, H. M.; Guare, J. P., Jr.;
Zhuang, L.; Grey, V. E.; Vacca, J. P.; Holloway, M. K.; Naylor-Olsen, A.
M.; Hazuda, D. J.; Felock, P. J.; Wolfe, A. L.; Stillmock, K. A.; Schleif,
W. A.; Gabryelski, L. J.; Young, S. D. J. Med. Chem. 2000, 43, 4923-
4926. (b) Long, Y.-Q.; Jiang, X.-H.; Dayam, R.; Sanchez, T.; Shoemaker,
R.; Sei, S.; Neamati, N. J. Med. Chem. 2004, 47, 2561-2573.
a Reactions were conducted in DMF (1.0 mL) at 80 °C. The ratio of 1
(1.0 mmol):2:K2CO3:[Pd(η3-C3H5)Cl]2:DPPPent was 100:110:220:0.5:1.
b Isolated yield. c Reactions were conducted with 2 mol % palladium.
effective catalyst for the benzylation of malonate carbanions
by benzylic carbonate.7a However, the reaction failed to yield
diphenylmethane (3a). We evaluated a broad range of
phosphine ligands, palladium catalyst precursors, bases, and
solvents. Selected results are shown in Table 1. The
palladium catalyst generated in situ from [Pd(η3-C3H5)Cl]2
and bidentate bisphosphine 1,5-bis(diphenylphosphino)pen-
946
Org. Lett., Vol. 7, No. 5, 2005

tane (DPPPent) recorded the highest yield of 3a. The choice
of a phosphine ligand is essential for the catalysis. Mono-
phosphine-ligated palladium complexes exhibited poor cata-
lytic activity for the cross-coupling. Bidentate phosphine
ligands possessing a small bite angle were ineffective, while
increasing the ligand bite angle enhanced the reaction rate
and the yield of 3a. The yield of 3a reached a maximum
when DPPPent was used. DPPHex, providing a larger
P-Pd-P angle, was less effective than DPPPent.12 [Pd(η3-
C3H5)Cl]2 was superior to the other palladium catalyst
precursors. DMF was the solvent of choice. K3PO4 and
Cs2CO3, as well as K2CO3, were suitable bases for the cross-
coupling of 1a with 2a, but K2CO3 is economically pre-
ferred.13 The catalyst loading was successfully reduced to 2
mol % palladium at a high concentration of 1a (1.0 M) under
the optimal reaction conditions, and 3a was obtained in 80%
isolated yield (Table 2, entry 1).
The optimal palladium catalyst and reaction conditions
proved to be useful for cross-couplings of diverse benyzlic
carbonates and boronic acids, as shown in Table 2. Both
electron-rich and electron-poor benzylic esters, 1c and 1d,
respectively, were more reactive than 1a,14 and their reactions
with 2a afforded diarylmethane 3c and 3d in high yields at
a catalyst loading of 1 mol % palladium. On the other hand,
the rate of the reaction of electron-rich boronic acid 2b was
almost equal to that of 2a, but the electron-withdrawing
group on arylboronic acid 2c accelerated the cross-coupling.14
The ortho substitutents of arylboronic acids 2d and 2e did
not hinder the catalytic reaction. A variety of diarylmethanes
bearing chloro, carboxylate, aldehyde, carbamate, alcohol,
and nitro functionalities were prepared in high yields by
means of the DPPPent-palladium catalyst. Alkenylboronic
acid 2k was transformed into allylarene 3o in high yield,
and no undesirable migration of the double bond was
observed. However, alkylboronic acids failed to react with
1a, and the desired cross-coupling product was not obtained.
Xylene-R,R′-diol dicarbonates 4 and 5 underwent two-
directional cross-coupling with 2a, as shown in Scheme 1,
and yielded p- (6) and m-dibenzylbenzene (7), respectively.
Scheme 2. Proposed Mechanism
DPPPent-ligated palladium(0) B, and (η1-benzyl)(alkoxo)-
palladium intermediate C was formed through decarboxyl-
ation of the carbonate leaving group. The alkoxo ligand on
palladium is more effective for transmetalation with organo-
boron 2 than acetato and halo ligands.15 No cross-coupling
of benzyl acetate with 2a occurred in the presence of the
DPPPent-palladium catalyst. The resulting (alkyl)(benzyl)-
palladium D provides diarylmethane 3 and regenerates
palladium(0) B through reductive elimination.
In conclusion, we have proved that benzylic carbonates
are a new class of coupling partners in Suzuki-Miyaura
cross-coupling. The palladium catalyst generated from
[Pd(η3-C3H5)Cl] and bidentate bisphosphine DPPPent is most
effective for the cross-coupling using benzylic carbonates.
The catalytic reaction showed high functional group compat-
ibility, and a wide range of arylboronic acids are now
commercially available. Therefore, this methodology devel-
oped by us will offer a fruitful and general synthetic method
for diarylmethanes.
Acknowledgment. This work was supported by the
Sumitomo Foundation and a Grant-in-Aid for Young Sci-
entists (A) (No. 16685011) from MEXT.
Supporting Information Available: Experimental pro-
cedures and characterization data for all new compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
OL050078Q
Scheme 1. Syntheses of Dibenzylbenzenes
(12) We speculate that the cleavage of the benzylic C-O bond proceeded
through a pathway similar to the formation of (η3-allyl)palladium from allylic
ester. The activation energy of the process would depend on the potential
energy of (η3-benzyl)palladium. The angle of P-Pd-P was 104.37° in the
DFT-optimized structure (B3LYP/6-31G(d) & LANL2DZ for Pd) of [(H3P)2-
Pd(η3-benzyl)]+. DPPPent might provide a bite angle close to 104.37° and
might form undistorted (η3-benzyl)palladium, which immediately isomerized
to (η1-benzyl)palladium.
(13) When the reaction was conducted with 1.0 equiv of Cs2CO3 to 2a,
no formation of 3a was observed. The acidic proton of boronic acid might
cause hydrolysis of Pd-OR bond of the intermediate C in Scheme 2.
(14) Relative reactivities of 1a,c,d and 2a,b,c were estimated by
competitive experiments using 2a and 1a, respectively. See Supporting
Information.
A proposed mechanism of the present reaction is shown
in Scheme 2. The benzylic C-O bond of 1 is cleaved by
(15) Miyaura, N.; Yamada, K.; Suginome, H.; Suzuki, A. J. Am. Chem.
Soc. 1985, 107, 972-980.
Org. Lett., Vol. 7, No. 5, 2005
947