Angewandte
Chemie
DOI: 10.1002/anie.201208364
Homogeneous Catalysis
Copper-Catalyzed Hydrodefluorination of Fluoroarenes by Copper
Hydride Intermediates**
Hongbin Lv, Yuan-Bo Cai, and Jun-Long Zhang*
À
C F bond activation attracts much attention because of the
rapid growth of fluorocarbons in pharmaceuticals, agrochem-
icals, and new materials.[1] Such transformations not only
provide new routes to the fluorinated organics, but also offer
a mechanism involving nucleophilic attack, and represents an
À
alternative strategy for copper activating C F bonds.
At the outset of our study, we searched for optimal HDF
reaction conditions for perfluoronitrobenzene (PFNB). We
first applied the our previous catalytic gold system but
replaced gold(I) with [Cu(MeCN)4PF6]. Screening silanes
(see Table S1 in the Supporting Information) such as HSi-
(OMe)3, HSiEt3, PMHS, H2SiPh2, and HSiMe2Ph, showed
that HSiMe2Ph was the best hydrogen source (conv. 40%).
Solvent screening resulted THF providing the highest yield
(60%; see Table S2 in the Supporting Information). We then
examined ligand effects and the results are listed in Table 1. In
À
a fundamental understanding for C F bond cleavage and
functionalization.[2] Previous experimental and theoretical
studies demonstrated the effectiveness of late transition
metals (group 8–10) such as Fe, Ru, Os, Co, Rh, Ir, Ni, Pd,
and Pt for their electron-rich nature and the relatively weak
[2c,3]
À
M F bonds,
which are important for catalytic function-
ality. Recently, we explored the reactivity of group 11 metal
complexes and found that gold(I) complexes have good
catalytic reactivity toward hydrodefluorination (HDF) of
fluoroarenes.[4] Despite the tremendous progress made, most
catalytic systems suffered from either low catalyst turnovers,
limited substrate scope, or harsh reaction conditions. For
example, gold(I) complexes are reactive only for the sub-
strates with strong electron-withdrawing substituents, and
their efficiency was greatly dependent on the electronic-
donating additives.[5] To address these issues, we continued to
explore the more-active group 11 metals such as copper, as we
were inspired by the success of gold. In this context, we report
herein the first example of a copper(I)-catalyzed HDF of
fluoroarenes, and it features high reactivity, good regioselec-
tivity, and a broad substrate scope.
Table 1: Optimization of copper-catalyzed HDF of PFNB.[a]
Entry Catalyst
Ligand[b]
–
Conv. Yield
[%][c]
(para/ortho)[c]
1
Cu(MeCN)4PF6
0
0
0
0
2
Cu(MeCN)4PF6 PPh3
3
Cu(MeCN)4PF6 PCy3
0
0
4
5
6
7
8
9
10
11
12
13
14
Cu(MeCN)4PF6 P(tBu)2(o-biphenyl)
Cu(MeCN)4PF6 dppe
Cu(MeCN)4PF6 binap
Cu(MeCN)4PF6 tBuXantphos
Cu(MeCN)4PF6 Xantphos
Cu(MeCN)4PF6 BDP
0
0
Since Subramanian and Manzer reported the CuF2-
mediated fluorination of aromatics,[6] copper-catalyzed C F
12
42
0
60
90
0
35
0
98
92
90 (57:43)
100 (58:42)
0
100 (61:39)
100 (48:52)
0
100 (55:45)
0
100 (60:40)
100 (58:42)
À
bond formation has been developed by the groups of Hartwig,
Lectka, and others.[7] In contrast, for catalytic C F bond
À
activation, copper has been rarely studied. Ribas and co-
workers recently showed that a CuI/CuIII redox cycle activated
CuCl
BDP
BDP
BDP
BDP
BDP
À
C X bonds (X = halogens) using triazamacrocyclic ligand,
Cu(OAc)2·H2O
CuCl2·2H2O
CuCl/KOtBu
CuCl/KOtBu[d]
thus indicating an oxidative addition mechanism.[7a] Herein,
we found that for HDF reactions, copper hydrides exhibited
À
an unprecedented reactivity toward C F bonds. Moreover,
[a] Reaction conditions: 0.015 mmol copper salt, 0.005 mmol ligand,
0.5 mmol PFNB, and 0.6 mmol HSiMe2Ph were refluxed in 2 mLTHF for
12 h. [b] Structures of ligands are shown in Scheme S1 of the Supporting
Information. [c] Conversion and yield were determined by integration of
the peaks in the 19F NMR spectra using CFCl3 as an internal standard.
[d] Reaction conditions: 0.015 mmol copper salt, 0.005 mmol ligand,
5.0 mmol PFNB, and 6.0 mmol HSiM2Ph were refluxed in THF for 48 h.
À
density functional theory (DFT) calculations suggest that C
F bond activation by copper hydrides proceeds through
[*] H. Lv, Y.-B. Cai, Prof. Dr. J.-L. Zhang
Beijing National Laboratory for Molecular Sciences
State Key Laboratory of Rare Earth Materials Chemistry and
Applications, College of Chemistry and Molecular Engineering
Peking University, Beijing 100871 (P.R. China)
E-mail: zhangjunlong@pku.edu.cn
the absence of a ligand and in the presence of monodentate
phosphine such as PPh3, PCy3, and [P(tBu)2(o-biphenyl)], no
HDF product was observed (entries 1–4). For bidentate
[**] This project was supported by the National Key Basic Research
Support Foundation of China (NKBRSFC) (2010CB912302) and
National Scientific Foundation of China (grant no. 20971007).
phosphine
ligands,
1,2-bis(diphenylphosphino)benzene
(BDP) led to a higher yield (90%; entry 9) compared to
those obtained with ligands such as dppe, binap, Xantphos,
and tBuXantphos (entries 5–8). The regioselectivity for para/
Supporting information for this article is available on the WWW
Angew. Chem. Int. Ed. 2013, 52, 3203 –3207
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3203