Nickel complexes of a pincer NN2 ligand: Multiple carbon-chloride activation of CH2Cl2 and CHCl3 leads to selective carbon-carbon bond formation

Article abstract of DOI:10.1021/ja8025938

A new pincer-type bis(amino)amine (NN₂) ligand and its lithium and nickel complexes, including Ni(II) methyl, ethyl, and phenyl complexes, were synthesized. The Ni(II) alkyl complexes react cleanly with alkyl halides including chlorides to form C-C coupled products and Ni(II) halides. More interestingly, the Ni(II) alkyls undergo unprecedented reactions with CH₂Cl₂ and CHCl₃ to cleave all the C-Cl bonds and replace them with C-C bonds. The reactions are highly selective and lead to the first efficient catalytic coupling of CH₂Cl₂ with alkyl Grignards. A conversion of 82% and a turnover number of 47 are achieved within minutes. Coupling of CD₂Cl₂ and 1,1-dichloro-3,3-dimethylbutane with ⁿBuMgCl is also realized. Preliminary mechanistic study suggests a radical initiated process for these reactions. Copyright

Full text of DOI:10.1021/ja8025938

Published on Web 06/04/2008
Nickel Complexes of a Pincer NN2 Ligand: Multiple Carbon-Chloride
Activation of CH2Cl2 and CHCl3 Leads to Selective Carbon-Carbon Bond
Formation
Zsolt Csok, Oleg Vechorkin, Seth B. Harkins,† Rosario Scopelliti, and Xile Hu*
Laboratory of Inorganic Synthesis and Catalysis, Institute of Chemical Sciences and Engineering, Ecole
Polytechnique Fe´de´rale de Lausanne, EPFL-ISIC-LSCI, BCH 3305, Lausanne CH 1015, Switzerland
Received April 9, 2008; E-mail: xile.hu@epfl.ch
Significant advance has been made for transition-metal-catalyzed
carbon-carbon coupling reactions employing aryl and alkenyl
halides and pseudohalides as the electrophiles.1 However, catalytic
coupling of unactivated alkyl halides remains a challenge.2 This is
often attributed to the reluctance of alkyl halides to undergo
oxidative addition and the tendency of metal alkyl intermediates
to undergo ꢀ-H elimination, producing undesired products. These
limitations are severe for unactivated alkyl chlorides. There are only
a few reported examples of efficient C-C coupling catalysis
employing these cheap and readily available starting materials.3
Coupling of a di- or polychloroalkane to an organometallic reagent
to form new C-C bonds is even more scarce. The only example
we are aware of is the Ag-catalyzed insertion of carbene into one
C-Cl bond of CH2Cl2, CHCl3, and CCl4.4 Only one new C-C
bond was formed, and all chlorines remained in the products. Herein
we report a new class of isolated and well-characterized nickel(II)
alkyl complexes that are able to cleave all the C-Cl bonds in
CH2Cl2 and CHCl3 under mild conditions. Most significantly, these
reactions yield exclusively the C-C coupled products in which each
chlorine atom has been replaced by an organic group originating
from the nickel alkyl species. To the best of our knowledge, this is
the first time that such transformation has been observed, which
leads to the first efficient double alkyl-alkyl coupling of CH2Cl2.
We recently set out to develop the coordination chemistry of a
new pincer-type amido bis(amine) ligand MeNN2. This is inspired
by the fascinating chemistry that has been unfolded lately on metal
complexes of analogous amido or pyridyl bis(phosphine) ligands
(NP2). The NP2 ligands combine structural rigidity and electronic
flexibility and stabilize nucleophilic and electron-rich late metal
centers. This leads to a broad range of applications in N2,5 C-H,6
and N-H7 activation, hydrogenation, and C-C bond forming
reactions.8,9 Replacing two phosphine donors with amine donors
in NN2 significantly increases the “hardness” of the ligand and
should stabilize metals in higher oxidation states. A few related
cyclometalated bis(amine) and amido bis(quinoline) ligands are
known and show interesting reactivities.10,11 However, the chem-
istry of late metal complexes of pincer amide/amine ligands remains
to be explored.
Figure 1. Synthesis of the new NN2 ligand and its Li and Ni complexes.
Figure 2. Crystal structure of complex 4. Selected bond lengths (Å):
Ni1-N2, 1.8907(17); Ni1-N1, 1.970(2); Ni1-N3, 1.982(2); Ni1-C17,
1.959(2).
1 reacts smoothly with Ni(dme)Cl2 to produce the Ni(II) complex
[(MeNN2)NiCl] (2). The monomeric structure of 2 was indicated
by the presence of only one singlet 1H NMR signal for the methyl
groups of MeNN2 and was confirmed by an X-ray single-crystal
diffraction study.13 Reactions of 2 with alkyl and aryl Grignards
yield the corresponding Ni(II)-R species (R ) Me (3), Et (4), and
Ph (5)). These organometallic Ni(II) species are stable under an
inert atmosphere, even for 4 which contains ꢀ-hydrogens. This
suggests that dissociation of one amine donor to give an open
coordination site is either slow or does not occur in complexes 3-5.
The crystal structure of 4 is shown in Figure 2.
The protonated form of ligand MeNN2 is accessible through a
Pd-catalyzed C-N coupling12 of N,N-dimethylaminoaniline with
o-N,N-dimethylaminobromobenzene (Figure 1).13 Lithiation of
HMeNN2 produced [(MeNN2)Li]2 (1). The dimeric structure of 1
was first inferred by the presence of two methyl singlets corre-
3 reacts cleanly with alkyl halides to give the C-C coupled
products (eq 1).13 In general, the reaction rates follow the order of
RI > RBr > RCl and benzyl > octyl > cyclohexyl.13 Although
Ni-based catalysts have been used for C-C coupling reactions,2,14,15
well-defined Ni alkyl compounds that react with alkyl halides,9,15
especially alkyl chlorides, to give the alkyl-alkyl coupled prod-
ucts15 as shown in eq 1 are rare. These reactions suggest that similar
Ni(II) alkyl compounds can be the active species in Kumada
coupling of alkyl halides with Grignards. Interestingly, reactions
of 3 with aryl halides are slower than those with alkyl halides. 3
reacts with 10 equiv of PhI at room temperature for 3 h to give
1
sponding to the diastereotopic methyl groups of MeNN2 in its H
NMR spectrum. The structure was confirmed by an X-ray crystal-
lographic analysis.13 Similar structure was found previously for the
bis(quinolinyl)amide complex [(BQA)Li]2.10
† Current address: KPL, Inc. Gaithersburg, MD 20878.
9
8156 J. AM. CHEM. SOC. 2008, 130, 8156–8157
10.1021/ja8025938 CCC: $40.75
2008 American Chemical Society

C O M M U N I C A T I O N S
Table 1. Catalytic Alkyl-Alkyl Coupling of Dichloroalkanesa
50% conversion. The metal-containing products are 5 (25%) and
MeNN2Ni-I (15%). No toluene was formed.
2nBuMgCl + RCl2 cat 2 8 Bu-R-Bu
solvent
[(MeNN2)Ni-Me] + R ′ X f [(MeNN2Ni-X] + Me-R′
(1)
entry equiv of halide
R
mol % of catalyst temp (°C) time (h) yield (%)b
Most surprisingly, 3 reacts rapidly with CH2Cl2 and CHCl3 (eqs
2 and 3) at room temperature, giving 2 as the main metal-containing
product in more than 95% yield. The only detectable organic
products are the fully C-C coupled products. Thus, in reactions
with CH2Cl2 and CHCl3, propane and isobutane are formed
exclusively and respectively. While it was difficult to quantify the
yields for gases, the observed yields for the products that remained
in the solution mixture were ca. 50% for propane and 55% for
isobutane, underscoring the high selectivity for the multiple C-C
bond forming reactions. Formation of partially methylated products
such as CH3CH2Cl, CH3CHCl2, or (CH3)2CHCl were not observed,
even when an excess of CH2Cl2 or CHCl3 was used. Monitoring
1
2
3
4
5
6
7
8
0.5c
25d
100d
25d
25d
25d
25d
25d
25d
25d
25d
25d
1c,e
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CD2
3
3
20
20
24
24
5
15
11
17
25
44
16
59
82
47
0.4
84
42
3
20
24
3
3
3
3
6
12
1
0
12
12
20
0
0.5
0.5
0.1
0.5
0.1
0.1
0.5
0.5
0.1
0.1
-20
-40
-20
-20
-20
-20
-20
0
9
10
11
12
13
neo-hexyl
1
by H NMR,13 the reactions of 3 with CH2Cl2 and CHCl3 were
a With 0.95 mmol of nBuMgCl (2.0 M solution in THF) as the
limiting reagent. b GC yields relative to nBuMgCl. c THF as the solvent.
d BuMgCl was added dropwise to 1.5 mL of CH2Cl2 (CD2Cl2) solution
of catalyst. e BuRRBu formed.
found to be approximately first and second order in the concentra-
tion of 3, respectively. Similar reactivity patterns were found for
ethyl complex 4. The phenyl complex 5 is however inert under the
same conditions.
Acknowledgment. We thank EPFL for start up funds and Profs.
Waser and Gademann for insightful discussions.
2[(MeNN2)Ni-R] + CH2Cl2 f 2[(MeNN2)Ni-Cl] + R2CH2
(2)
3[(MeNN2)Ni-R] + CHCl3 f 3[(MeNN2)Ni-Cl] + R3CH (3)
Supporting Information Available: Experimental and crystal-
lographic details. This material is available free of charge via the
Internet at http://pubs.acs.org.
R)Me, Et
These reactions are unusual in several ways. They take place
under very mild conditions and are the first examples of late metal
alkyl compounds that react with CH2Cl2 and CHCl3 to give fully
alkylated organic products in high yields.9,16 The selectivity is
impressive as the overall process involves the cleaVage of up to
three C-Cl bonds to form three new C-C bonds at the same
carbon center. Concerning the mechanism, a radical pathway is
proposed based on the following observations: (1) CH2Cl2 and
CHCl3 react faster than octyl-Cl; (2) reaction of 3 with CH2Cl2
was retarded in the presence of radical trap TEMPO and TEMPO-
CH3 was formed during the reaction; (3) 1-pentene was formed in
the reaction of 3 with bromomethylcyclopropane.
References
(1) Metal-Catalyzed Cross-Coupling Reactions, 2nd ed.; de Meijere, A.,
Diederich, F., Eds.; Wiley-VCH: Weinheim, Germany, 2004.
(2) Frisch, A. C.; Beller, M. Angew. Chem., Int. Ed. 2005, 44, 674–688.
Netherton, M. R.; Fu, G. C. AdV. Synth. Catal. 2004, 346, 1525–1532.
(3) (a) Martin, R.; Furstner, A. Angew Chem., Int. Ed. 2004, 43, 3955–3957.
(b) Zhou, J. R.; Fu, G. C. J. Am. Chem. Soc. 2003, 125, 12527–12530. (c)
Frisch, A. C.; Shaikh, N.; Zapf, A.; Beller, M. Angew. Chem., Int. Ed.
2002, 41, 4056–4059. (d) Kirchhoff, J. H.; Dai, C. Y.; Fu, G. C. Angew.
Chem., Int. Ed. 2002, 41, 1945–1947. (e) Terao, J.; Watanabe, H.; Ikumi,
A.; Kuniyasu, H.; Kambe, N. J. Am. Chem. Soc. 2002, 124, 4222–4223.
(4) Dias, H. V. R.; Browning, R. G.; Polach, S. A.; Diyabalanage, H. V. K.;
Lovely, C. J. J. Am. Chem. Soc. 2003, 125, 9270–9271.
(5) (a) Fryzuk, M. D.; Haddad, T. S.; Rettig, S. J. J. Am. Chem. Soc. 1990,
112, 8185–8186. (b) Fout, A. R.; Basuli, F.; Fan, H. J.; Tomaszewski, J.;
Huffman, J. C.; Baik, M. H.; Mindiola, D. J. Angew. Chem., Int. Ed. 2006,
45, 3291–3295.
The multiple C-C coupling reactions described here are ap-
plicable in organic synthesis if they can be rendered catalytic.
Indeed, our preliminary study demonstrates that CH2Cl2 can be
doubly coupled to an alkyl Grignard (nBuMgCl) using 2 as the
precatalyst (Table 1). Higher yields were obtained when CH2Cl2
was in excess and the optimal CH2Cl2:nBuMgCl ratio is 25:1 (entries
1-3). The optimal temperature is -20 °C, and the catalysis is
complete within 30 min (entries 4-10). Higher loadings of catalyst
increase both the reaction rates and yields but decrease the turnover
numbers (entries 8-10). A conversion of 82% was achieved in 5
min at -20 °C using 12 mol % of catalyst (entry 9), and a TON of
47 was obtained in 30 min at -20 °C using 1 mol % of catalyst
(entry 10). Control experiment shows that, without the precatalyst,
the product yield is negligible (entry 11). CD2Cl2 can be used and
gives BuCD2Bu in 84% yield (entry 12). Coupling of 1,1-dichloro-
(6) (a) Liang, L. C.; Chien, P. S.; Huang, Y. L J. Am. Chem. Soc. 2006, 128,
15562–15563. (b) Fan, L.; Parkin, S.; Ozerov, O. V. J. Am. Chem. Soc.
2005, 127, 16772–16773. (c) Bailey, B. C.; Huffman, J. C.; Mindiola, D. J.
J. Am. Chem. Soc. 2007, 129, 5302–5203. (d) Walstrom, A.; Pink, M.;
Tsvetkov, N. P.; Fan, H. J.; Ingleson, M.; Caulton, K. G. J. Am. Chem.
Soc. 2005, 127, 16780–16781. (e) Ben-Ari, E.; Leitus, G.; Shimon, L. J. W.;
Milstein, D. J. Am. Chem. Soc. 2006, 128, 15390–15391.
(7) Fafard, C. M.; Adhikari, D.; Foxman, B. M.; Mindiola, D. J.; Ozerov, O. V.
J. Am. Chem. Soc. 2007, 129, 10318–10319.
(8) Zhang, J.; Leitus, G.; Ben-David, Y.; Milstein, D. Angew. Chem., Int. Ed.
2006, 45, 1113–1115.
(9) Liang, L. C.; Chien, P. S.; Lin, J. M.; Huang, M. H.; Huang, Y. L.; Liao,
J. H. Organometallics 2006, 25, 1399–1411.
(10) Peters, J. C.; Harkins, S. B.; Brown, S. D.; Day, M. W. Inorg. Chem. 2001,
40, 5083–5091.
(11) Albrecht, M.; van Koten, G. Angew. Chem., Int. Ed. 2001, 40, 3750–3781.
(12) (a) Alcazar-Roman, L. M.; Hartwig, J. F.; Rheingold, A. L.; Liable-Sands,
L. M.; Guzei, I. A. J. Am. Chem. Soc. 2000, 122, 4618–4630. (b) Wolfe,
J. P.; Tomori, H.; Sadighi, J. P.; Yin, J. J.; Buchwald, S. L. J. Org. Chem.
2000, 65, 1158–1174.
n
3,3-dimethylbutane (RCl2) with BuMgCl is possible, with 42%
yield of BuRRBu rather than BuRBu though (entry 13).
(13) See Supporting Information.
(14) Phapale, V. B.; Bunuel, E.; Garcia-Iglesias, M.; Cardenas, D. J. Angew.
Chem., Int. Ed. 2007, 46, 8790–8795.
(15) Jones, G. D.; Martin, J. L.; McFarland, C.; Allen, O. R.; Hall, R. E.; Haley,
A. D.; Brandon, R. J.; Konovalova, T.; Desrochers, P. J.; Pulay, P.; Vicic,
D. A. J. Am. Chem. Soc. 2006, 128, 13175–13183.
(16) Liang et al. reported that (NP2)Ni(II) alkyls reacted slowly with CH2Cl2
(765 equiv of CH2Cl2 at 110°C, completion after 113 h). No organic product
was identified. See ref 9.
In summary, using nickel alkyl complexes of a new pincer NN2
ligand, we have discovered a new type of multiple C-Cl activation
reactions on CH2Cl2 and CHCl3. The reactions lead to selective
C-C bond formations which enable the first catalytic couplings of
CH2Cl2 with Grignard reagents. We are currently investigating the
mechanistic details of these intriguing transformations and exploring
the scope and utility of their catalytic applications.
JA8025938
9
J. AM. CHEM. SOC. VOL. 130, NO. 26, 2008 8157