Published on the web September 5, 2011
1009
Palladium-catalyzed Cross-coupling of Aryl Iodides with ¢-Trimethylsiloxy-¡-diazoesters:
A Novel Approach toward ¢-Keto-¡-arylesters
Zhibin Shu,1,2 Ji Zhang,1,2 Yan Zhang,1,2 and Jianbo Wang*1,2
1Beijing National Laboratory for Molecular Sciences (BNLMS), Peking University, Beijing 100871, P. R. China
2Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education,
College of Chemistry, Peking University, Beijing 100871, P. R. China
(Received June 15, 2011; CL-110499; E-mail: wangjb@pku.edu.cn)
Palladium-catalyzed cross-coupling of ¢-trimethylsiloxy-
¡-diazoesters with aryl iodides provides a new approach to
¢-keto-¡-arylesters. It is shown that the ¢-trimethylsiloxy group
can significantly suppress the direct 1,2-hydride shift from
palladium carbene.
PhI
Pd(0)Ln
H
H
HO
Ph
HO
Ph
H
HO
Ph
migratory
insertion
PhPdILn-2
CO2Et
CO2Et
CO2Et
Ph
PdILn-2
N2
1a
PhPdILn-3
2
3
1,2-H shift
Palladium-catalyzed cross-coupling reaction has been de-
veloped into one of the most powerful methods for C-C bond
formation.1 In the Pd-catalyzed cross-coupling reactions, the
nucleophiles are in general organometallic compounds, such as
Grignard reagents, boron reagents, zinc reagents, tin reagents,
and silicon reagents. The corresponding electrophiles are usually
halides or pseudo-halides. Recently, a new type of Pd-catalyzed
cross-coupling has emerged, in which diazo compounds serve as
cross-coupling partner.2-9 In this type of cross-coupling reaction,
the key steps are believed to involve the formation of Pd-
carbene species, which is followed by migratory insertion of the
carbon ligand (eq 1).2 This type of cross-coupling is general,
and the migratory groups include aryl,3 benzyl,4 vinyl,5 allyl,6
acyl,7 alkynyl,8 and allenyl9 groups. As a continuation of our
interest in this area, we report in this paper the Pd-catalyzed
cross-coupling of aryl iodides with ¢-trimethylsiloxy-¡-diazo-
esters. The reaction provides a new approach toward ¢-keto-
¡-arylesters.
OH
O
CO2Et
CO2Et
Ph
Ph
H
4
5a
Scheme 1. Migratory insertion vs. 1,2-H shift.
O
CO2Et
1) Ph-I (1.2 equiv)
[Pd2dba3] (2.5 mol%)
PPh3 (10.0 mol%)
OX
5a
CO2Et
+
N2
O
Et3N (3.0 equiv)
1,4-dioxane
1a
CO2Et
0.3 M, 80 °C, 2 h
2) Silica gel or H+
6a
N2
X =
5a:6a =
H
50:50a 20:80
97%b 98%b
SiMe3 Si(i-Pr)3 SiMe2t-Bu SiPh2t-Bu
Ln-1
R
R
PdLn
Pd
31:69
85%c
33:67
90%c
34:66
91%c
ð1Þ
RPdLn
N2
a
Scheme 2. Migratory insertion vs. 1,2-H shift. All the ratios
were determined by GC. bIsolated yield of 5a and 6a combined.
cThe combined yields were determined by GC.
In the beginning, our interest is the Pd-catalyzed cross-
coupling of aryl iodide and ¢-hydroxy-¡-diazoester. We had
expected that migratory insertion will occur from Pd species 2,
affording the palladium species 3 (Scheme 1). However, a
competing process from Pd carbene species 2 is 1,2-hydride
shift, which will lead to the formation of 4 and eventually 1,3-
dicarbonyl compound 5a, without new C-C bond formation.
Previous studies have indicated that the existence of the ¢-
hydroxy group significantly enhances the 1,2-hydride shift of a
metal carbene species.10
The initial experiments indicated that this was indeed the
case. When phenyl iodide and diazo compound 1a was
catalyzed by [Pd2(dba)3] (dba: dibenzylideneacetone), a mixture
of 5a and 6a was obtained in approximately 1:1 ratio
(Scheme 2). Changing the reaction conditions, including the
Pd catalyst, ligand, and the reaction temperature seems not
significantly to affect the ratio. We then conceived that the 1,2-
hydride shift of Pd carbene might be affected by modifying the
¢-hydroxy group. Our previous studies have demonstrated that
¢-siloxy groups significantly retard the 1,2-hydride shift of
metal carbene.10a,11 To our delight, we found that this was also
the case in the current Pd-catalyzed reaction. When the ¢-
hydroxy was replaced by a trimethylsiloxy group, the ratio of
5a:6a was increased to 20:80. Further modifying the hydroxy
group by converting to triisopropylsiloxy (TIPSO), tert-
butyldimethylsiloxy (TBDMSO), or tert-butyldiphenylsiloxy
(TBDPSO) did not improve the ratio. In contrast, in all these
cases the ratios were actually diminished compared with ¢-
trimethylsiloxy-¡-diazoesters. It is noteworthy that the initially
produced enol ester is converted into the corresponding ¢-keto-
¡-arylester 6a by treatment with silica gel or protonic acid.
Palladium-catalyzed cross-coupling of 1,3-dicarbonyl com-
pounds with aryl halide has been reported previously.12 There-
fore, the possibility exists that 6a is formed by Pd-catalyzed
Chem. Lett. 2011, 40, 1009-1011
© 2011 The Chemical Society of Japan