Consecutive cross-coupling of o-phenylenedizinc compound with acyl and/or aryl halides in the presence of Pd(0)-tris(2,4,6- trimethoxyphenyl)phosphine

Article abstract of DOI:10.1016/S0040-4039(00)00679-1

Consecutive cross-coupling of an o-phenylenedizinc compound 1 with two different acyl or aryl halides or acyl and aryl halides was accomplished in one pot by the catalysis of Pd(0)-tris(2,4,6-trimethoxyphenyl)phosphine to yield a variety of functionalized unsymmetrical 1,2-disubstituted benzenes in good yields. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)00679-1

Tetrahedron Letters 41 (2000) 4629±4632
Consecutive cross-coupling of o-phenylenedizinc compound
with acyl and/or aryl halides in the presence of
Pd(0)-tris(2,4,6-trimethoxyphenyl)phosphine
Akihiro Saiga, Kabir M. Hossain and Kentaro Takagi*
Department of Chemistry, Faculty of Science, Okayama University, Okayama 700-8530, Japan
Received 5 April 2000; accepted 21 April 2000
Abstract
Consecutive cross-coupling of an o-phenylenedizinc compound 1 with two di€erent acyl or aryl halides
or acyl and aryl halides was accomplished in one pot by the catalysis of Pd(0)-tris(2,4,6-trimethoxy-
phenyl)phosphine to yield a variety of functionalized unsymmetrical 1,2-disubstituted benzenes in good
yields. # 2000 Elsevier Science Ltd. All rights reserved.
Keywords: coupling reactions; palladium and compounds; polyaryls; zinc and compounds.
Transition metal-catalyzed cross-coupling reactions of o-dihalobenzenes with two di€erent
organometallic compounds in a step by step manner allow the introduction of discrete sub-
stituents onto the o-phenylene segment, which provides one of the most important synthetic
1
methods for 1,2-disubstituted benzenes (Fig. 1). In contrast, an electronically counter process,
the stepwise reactions of o-phenylenedimetal compounds with two electrophilic reagents, has
been little studied so far, presumably because of the diculties both in obtaining these dimetallic
2
compounds and in running the reactions regioselectively (vide infra). In the course of our study on
the synthesis and the synthetic application of arylzinc compounds, we discovered that the o-phenyl-
enedizinc compound 1 is readily available in a good yield through the reaction of o-diiodobenzene
with zinc powder.3 For the ®rst time, we then examined the successive reaction of 1 with two
discrete electrophilic reagents to explore for the novel access to 1,2-disubstituted benzenes.6
At the beginning, the reaction of 1 with 1 equiv. of benzoyl chloride 2a was tried in the presence
�5
,7
ꢀ
of Pd(PPh ) at 40 C for 3 h. I -Quenching of the resulting solution a€orded 3a in 70% yield
3
4
2
8
along with 4a and 5 (Scheme 1). While the yields of 3a were changed to a great extent, depending
9
on the Pd(0) complexes used, the Pd(0) complex containing tris(2,4,6-trimethoxyphenyl)-
phosphine ligand (Pd(0)-TTMOP) dramatically increased the yield of 3 (98%). A similar high
*
Corresponding author. Tel: +81 86 251 8492; fax: +81 86 251 8497; e-mail: takagi@cc.okayama-u.ac.jp
0040-4039/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00679-1

4
630
Figure 1. Stepwise reaction of 1,2-disubstituted benzenes
degree of regioselectivity was realized by this Pd(0) catalyst in the reaction of 1 with iodobenzene
b as the electrophilic reagents: 3b was obtained in 86% yield along with a 4% yield of 4b. On the
other hand, the Pd(PPh ) catalyst a€orded the two products in 60 and 12% yield, respectively
2
3
4
(Scheme 1). Signi®cantly, the catalytic activity of the Pd(0) complex remained after the ®rst step
reaction was completed. Hence, whenever an additional portion of electrophilic reagent was
added to the resulting mixture, catalytic reactions smoothly took place, enabling the introduction
of an electrophile onto the intermediary compounds like 6 as the second side chain. The results
using various acyl halides and/or aryl halides as the electrophilic reagents are summarized in
Table 1. It is noted that both aryl iodides and acyl chlorides, including ones containing functional
groups such as cyano, alkoxycarbonyl, chloro, or alkoxy, are arbitrarily available as the ®rst and/
or the second electrophilic reagents. As the ®rst reagent, a divalent one like 7 or 8 was also
available. Therefore, novel polyaryl compounds 9 or 10 were readily obtained by the Pd(0)-
TTMOP catalyzed reaction of 1 with 7 or 8 (molar ratio of 7 or 8/1=0.5), followed by the sub-
sequent treatment of the resulting mixture with the second electrophilic reagent (molar ratio of
2
a/1=2), respectively (Scheme 2).
Scheme 1.
In summary, an ecient and facile method for the introduction of aryl and/or acyl side chains
onto the o-phenylene segment has been established, which provides new methods to functionalized
arenes, characterized by the novelty in the electronic properties of the coupling partners.
Representative experimental procedure: to the mixture prepared by the reaction of PdCl (CH CN)
2
3
2
0
0
(
(
2
0.0033 mmol), TTMOP (0.13 mmol), and Zn powder (0.13 mmol), in N,N,N ,N -tetramethylurea
ꢀ
TMU) (0.75 mL) at ambient temperature for 30 min and then for 30 min at 40 C under nitrogen,
3
-thienoyl chloride (1.65 mmol) and the 1.8 mL-TMU solution of 1 (1.5 mmol) were successively

4
631
Table 1
Pd(0)-TTMOP-catalyzed consecutive cross-coupling of 1 with two discrete acyl and/or aryl halidesa

4
632
Scheme 2.
ꢀ
added and stirred for 3 h at 40 C. To the resulting mixture, furoyl chloride (3.0 mmol) was added
ꢀ
and stirred at 50 C for 3 h. After the treatment of the resulting mixture with aqueous HCl, the
ether extract was chromatographed on a silica-gel column, a€ording 325 mg of 2-furyl 2-(2-thienyl-
ꢀ
^1 1
methanoyl)phenyl ketone (77%). Mp 158±160 C; IR 1652 cm ; H NMR: ꢀ 6.50 (dd, J=3.6 and
1.7 Hz, 1H), 7.0±7.1 (m, 2H), 7.4±7.8 (m, 7H). Anal. calcd for C H O S: C, 68.07; H, 3.57.
16 10 3
Found: C, 68.0; H, 3.6.
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9
. Yields of 3a and 4a (utilized ligand): 35, 26 (tris(per¯uorophenyl)phosphine); 75, 6 (tris(2-tri¯uoromethylphenyl)-
phosphine); 48, 15 (tri-2-furylphosphine); 62, 15 (triphenylarsine) 91, 2 (tri(o-tolyl)phosphine). A very di€erent
e€ect of ligands was observed in the Pd(0)-catalyzed stepwise reaction of bis(iodozincio)methane with two di€erent
electrophiles. See: Utimoto, K.; Toda, N.; Mizuno, T.; Kobata, M.; Matsubara, S. Angew. Chem., Int. Ed. Engl.
1
997, 36, 2804.