.
Angewandte
Communications
DOI: 10.1002/anie.201206518
Radical Reactions
Transition-Metal-Free Alkoxycarbonylation of Aryl Halides**
Hua Zhang, Renyi Shi, Anxing Ding, Lijun Lu, Borui Chen, and Aiwen Lei*
Transition-metal-catalyzed carbonylation involving CO gas is
a very important and fundamental chemical transformation,
which not only extends the carbon chain length, but also
introduces a synthetically versatile carbonyl group. Since the
pioneering work of Heck and co-workers,[1,2] transition-metal-
catalyzed alkoxycarbonylation of organic halides with CO to
afford esters has shown synthetic potential, and been applied
in some chemical syntheses during the past several decades
(Scheme 1).[3–7] Besides, transition metals, especially palla-
Transition-metal-free processes have recently attracted
more and more attention from the synthetic community, and
we thought that it might serve as an alternative route to
addressing the above-mentioned challenge (Scheme 1). The
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key challenge of this idea is to determine how to activate C X
without the help of transition-metal catalysts. Radical activa-
tion could be an option. Recently, transition-metal-free
coupling reactions of aryl halides with arenes and alkenes
have been developed, and the combination of MOtBu and
bidentate nitrogen ligands was employed to initiate the aryl
radical by single-electron transfer (SET).[14–22] Obviously, if
aryl radicals were formed, the insertion of CO would produce
the acyl radical and further generate a carboxylic derivative.
Although known since the 1950s,[23] the potential of radical
carbonylation in chemical synthesis has not received a great
deal of attention, and in fact, only a few nice results have been
reported to date. These results usually involve a xenon
photolytic system or AIBN/tin hydride mediated radical-
chain reaction employing alkyl iodides as substrates.[24–30] To
the best of our knowledge, there is no example of employing
a transition-metal-free process in alkoxycarbonylation of aryl
halides. Herein, we disclose a protocol for accessing tert-butyl
benzoates through the transition-metal-free alkoxycarbony-
lation of aryl halides.
Scheme 1. Approach to alkoxycarbonylation.
dium- and manganese-catalyzed radical alkoxycarbonylation
of alkyl iodides under photoirradiation conditions have also
been developed to be an efficient approach towards the
synthesis of carboxylic acid esters.[8–13] However, there are still
some challenges such as the turnover numbers and turnover
frequencies, which hinder its wide industrial application.
Generally, low-valent-metal catalysts such as palladium(0)
Our experiment was initiated by treating 4-iodotoluene
(1a) with KOtBu in the presence of a high pressure CO
(Table 1). By optimizing various reaction parameters, the best
results were obtained with the combination of 40 mol% 1,10-
phenanthroline and 4 equivalents of KOtBu in benzene at
908C under 60 atm CO (Table 1, entry 1). With these reaction
conditions, a 75% yield of tert-butyl-4-methylbenzoate (2a)
was obtained after 24 hours with a biaryl by-product origi-
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are required to activate the C X bond, whereas the strong
binding ability of CO towards low-valent metals deactivate
the catalyst, which present a challenge in this transformation.
Therefore, discovering a practical alternative to transition-
metal-catalyzed carbonylation and opening a new avenue for
the carbonylation by utilizing CO gas is highly desirable.
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nating from C H arylation with the solvent (benzene). The
choice of base was essential for the reaction. NaOtBu and
LiOtBu were inefficient for this transformation (Table 1,
entries 2 and 3). Using 1,10-phenanthroline as additive gave
the highest yield, whereas other additives such as 2,9-
dimethyl-1,10-phenanthroline, DMEDA, and TMEDA
showed less or no efficiency in terms of chemical yields
(Table 1, entries 4–6). The use of 1,4-dioxane or DME as
a solvent decreased the yield dramatically (Table 1, entries 7
and 8). When benzene was replaced by DMF, only 7% yield of
2a was obtained (Table 1, entry 9). A lower loading of the
additive led to a decreased yield whereas no reaction occurred
in the absence of 1,10-phenanthroline (Table 1, entries 10 and
11). Lowering the CO pressure decreased the yield, whereas
higher CO pressures showed no improvement (Table 1,
entry 12 and 13).
[*] H. Zhang, R. Shi, A. Ding, L. Lu, B. Chen, Prof. A. Lei
The College of Chemistry and Molecular Sciences
Wuhan University, Wuhan, Hubei (P.R. China)
E-mail: aiwenlei@whu.edu.cn
Prof. A. Lei
State Key Laboratory for Oxo Synthesis and Selective Oxidation,
Lanzhou Institute of Chemistry Physics
Chinese Academy of Sciences, 730000 Lanzhou (China)
[**] This work was supported by the 973 Program (2012CB725302) and
the National Natural Science Foundation of China (21025206,
20832003, and 20972118). We are grateful for the support from the
Program for Changjiang Scholars and Innovative Research Team in
University (IRT1030). We also thank Gang Li and Hong Yi for helpful
discussions.
With the above optimized reaction conditions, a variety of
aryl iodides were tested (Table 2). Aryl iodides substituted
with a methyl group afforded the corresponding esters in
moderate to good yields (Table 2, entries 1–3). The position of
Supporting information for this article is available on the WWW
12542
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 12542 –12545