Communications
DOI: 10.1002/anie.200803814
Bond Activation
Cross-Coupling of Aryl/Alkenyl Pivalates with Organozinc Reagents
À
through Nickel-Catalyzed C O Bond Activation under Mild Reaction
Conditions**
Bi-Jie Li, Yi-Zhou Li, Xing-Yu Lu, Jia Liu, Bing-Tao Guan, and Zhang-Jie Shi*
Biaryls have been widely applied in the syntheses of natural
products, polyaromatic molecules, and pharmaceuticals.[1,2]
Transition-metal-catalyzed cross-coupling reactions are
among the most powerful tools used to construct such
structural units. In the last decades, significant effort has
been directed towards cross-coupling reactions, thus allowing
the coupling partners to be extended from aryl iodides,
bromides, and triflates to relatively unreactive chlorides and
tosylates/mesylates.[3] The complexes of first-row transition
metals, such as iron, cobalt, and nickel, also exhibited
promising catalytic reactivities to take the place of late-
transition-metal complexes.[4] Despite these noteworthy
advances, aryl carboxylates (one family of the most easily
available and useful compounds) have not yet been success-
fully employed as coupling partners in cross-coupling reac-
tions.[5] Their simplicity as well as ready availability make
carboxylates particularly attractive for use in synthetic
chemistry. For example, aryl/alkenyl carboxylates can be
easily derived from phenols and carbonyl compounds in a
single step.[6] Also, the application of carboxylates in coupling
reactions could reduce the use of halides, which are environ-
mentally unfriendly. Ironically, the inertness of aryl carboxy-
lates has long been viewed as a vivid testimony of their
functional group tolerance in many reactions. Owing to their
stability, carboxylates such as acetates and pivalates are
generally applied to synthetic chemistry as protecting groups.
After the pioneering studies of Wenkert et al. on nickel-
catalyzed arylation of aryl/vinyl methyl ethers in the late
recent appearance of several impressive examples. It is
apparent that a renaissance in the activation of an unreactive
À
C O bond is on the way. The studies of Dankwardt and co-
workers have greatly broadened the substrate scope to a wide
range of nonactivated aromatic ethers in nickel-catalyzed
coupling with Grignard reagents.[7c] Kakiuchi et al. first
reported chelation-assisted ruthenium-catalyzed coupling of
aromatic ethers with organoboron reagents.[7d] Very recently,
Chatani and co-workers made advances in the nickel-
catalyzed cross-coupling between aromatic methyl ethers
and arylboronic esters.[7e] Our recent studies also showed that
nickel catalyzed the efficient alkylation of aromatic as well as
benzylic methyl ethers with Grignard reagents.[7f,g] As part of
À
a program aimed at the activation of otherwise unreactive C
O bond to enable synthetically useful transformations, we
have disclosed the first successful cross-coupling of aryl
carboxylates with aryl boroxines.[8] However, several issues
remained to be addressed such as high catalyst loading and
elevated temperature. Given their easy preparation and high
functional group tolerance, organozinc reagents have proved
to be quite useful in cross-coupling reactions to construct
biaryl and aryl–vinyl structural scaffolds.[9] To the best of our
knowledge, aryl carboxylates have never been used to couple
with organozinc reagents. Herein, we reported the unprece-
dented cross-coupling of aryl/alkenyl pivalates with arylzinc
À
reagents to construct C C bonds under mild reaction
conditions.
On the basis of our previous studies, 2-naphthyl carboxy-
1970s,[7a,b] the field of C O bond activation remained dormant
lates 1 were chosen as model substrates because of their
À
[8]
À
for nearly three decades. The vast synthetic potential of this
activation-type chemistry has been rarely explored until the
higher reactivity in related C O activation transformations.
Gratifyingly, when 2-naphthyl acetate (1a) was used as a
substrate, the desired coupling product 3a was obtained in the
presence of a catalytic amount of [NiCl2(PCy3)2] in DMA,
albeit in a low yield, accompanied by the hydrolyzed 2-
naphthol as a by-product (Table 1, entry 1). The increased
steric bulk of the carboxylates dramatically improved the
yield of the reaction, presumably by inhibiting the direct
attack of the arylzinc reagents on carbonyl groups (Table 1,
entry 3 versus entries 1 and 2). When 2-naphthyl pivalate (1c)
was applied, the reaction reached full conversion and gave the
isolated product in 84% yield. Other ligands such as PPh3,
P(nBu)3, and P(tBu)3 were tested but gave lower yields
(Table 1, entries 4–7), thus suggesting that the PCy3 ligand
had a balance between both steric and electronic effects.
Furthermore, other nonpolar solvents were not appropriate
for this transformation, meanwhile the polar solvents such as
DMF and NMP were efficient (Table 1, entries 8–12). Nota-
bly, the reaction proceeded at as low as 308C without
[*] Prof. Dr. Z.-J. Shi
State Key Laboratory of Organometallic Chemistry
Chinese Academy of Sciences, Shanghai 200032 (China)
Fax: (+86)10-6276-0890
E-mail: zshi@pku.edu.cn
B.-J. Li, Y.-Z. Li, X.-Y. Lu, J. Liu, B.-T. Guan
Beijing National Laboratory of Molecular Sciences (BNLMS), PKU
Green Chemistry Centre and Key Laboratory of Bioorganic
Chemistry and Molecular Engineering of the Ministry of Education,
College of Chemistry, Peking University, Beijing 100871 (China)
[**] Support of this work by a starter grant from the Peking University
and by a grant from the National Sciences of Foundation of China
(Grant Nos. 20542001, 20521202, 20672006) is gratefully acknowl-
edged.
Supporting information for this article is available on the WWW
10124
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2008, 47, 10124 –10127