Metal-free catalytic hydrogenation of imines with recyclable [2.2]paracyclophane-derived frustrated lewis pairs catalysts

Article abstract of DOI:10.1002/adsc.201301007

A series of [2.2]paracyclophane-derived frustrated Lewis pairs (FLPs) with reversible, metal-free hydrogen activation was synthesized and successfully applied in the hydrogenation of imines in moderate to good yields. The high stability of the novel FLP system enables effective recycling of the metal-free catalysts. This reaction could also be compatible with a larger scale and developed into a pharmaceutical synthesis of cinacalcet {(R)-N-[1-(1-naphthyl) ethyl]-3-[3-(trifluoromethyl)phenyl]propan-1-amine} without heavy metal residues.

Full text of DOI:10.1002/adsc.201301007

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DOI: 10.1002/adsc.201301007
Metal-Free Catalytic Hydrogenation of Imines with Recyclable
[2.2]Paracyclophane-Derived Frustrated Lewis Pairs Catalysts
Guan Wang,a Cheng Chen,a Tieqi Du,a and Weihui Zhonga,*
a
Key Laboratory of Pharmaceutical Engineering of Ministry of Education, College of Pharmaceutical Sciences, Zhejiang
University of Technology, Hangzhou 310014, Peopleꢀs Republic of China
Fax : (+86)-571-8887-1087; phone: (+86)-571-8887-1087; e-mail: weihuizhong@zjut.edu.cn
Received: November 12, 2013; Revised: February 6, 2014; Published online: May 7, 2014
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201301007.
Abstract: A series of [2.2]paracyclophane-derived
frustrated Lewis pairs (FLPs) with reversible,
metal-free hydrogen activation was synthesized and
successfully applied in the hydrogenation of imines
in moderate to good yields. The high stability of the
novel FLP system enables effective recycling of the
metal-free catalysts. This reaction could also be
compatible with a larger scale and developed into
a pharmaceutical synthesis of cinacalcet {(R)-N-[1-
(1-naphthyl)ethyl]-3-[3-(trifluoromethyl)phenyl]pro-
pan-1-amine} without heavy metal residues.
has been extended to demonstrate new reactivity, ulti-
mately leading to new approaches in catalysis. The
advent of this new concept in reactivity presents both
opportunities and challenges for chemists in general.
Using steric hindrance as a critical design element,
numerous inter- and intramolecular combinations of
bulky Lewis acid-base pairs were effectively probed
for the heterolytic cleavage of hydrogen. Due to their
high molecular weights, such FLP compounds are cer-
tainly not suited for H2 storage. But the given low
energy pathways for H2 activation may show new di-
rections to efficient catalyst development. In particu-
lar, we thought it necessary to acquire more insight
into the conditions for reversibility of the underlying
chemical processes, so as to have more efficient appli-
cations of the reduction reaction, which avoids heavy
metal pollution in chemical products.
Keywords: frustrated Lewis pairs; hydrogenation;
imines; metal-free conditions; ACHTUNTRGNEUNG[2.2]paracyclophane
Due to the limitations of many catalysts, such as
Frustrated Lewis pairs (FLPs), i.e., pairs of reactive low activity, substrate limitations, poor stability, diffi-
but sufficiently bulky Lewis acids and Lewis bases cult recovery, the synthesis of effective and stable
that avoid neutralizing strong adduct formation, have FLPs for application in hydrogenation reactions was
been shown to react with a variety of small mole- envisioned as being worthwhile. [2.2]Paracyclophane,
cules.[1] Activation of H2 by heterolytic splitting and with a unique framework of benzene rings connected
utilization of the resulting FLP bound H+/HÀ pair in at the para-positions by two ethylene chains, has
metal-free catalytic hydrogenation is one prominent shown its special properties in many aspects.[13] In ad-
feature,[2,3] but FLPs were also shown to bind to al- dition, Paradies and co-workers have shown that
kenes and alkynes,[4] to various carbonyl compounds,[5] planar-chiral bisphosphines are viable Lewis bases for
to nitrogen oxides (N2O,[6] NO[7]), and even to CO2
the activation of hydrogen by frustrated Lewis
[8]
or SO2,[9] which has rarely been used in chemical reac- pairs.[14] Herein, we report on some [2.2]paracyclo-
tions. Research on so-called “frustrated Lewis pairs” phane-derived frustrated Lewis pairs (PFLPs) with
(FLPs) has witnessed a tremendous increase during reversible, metal-free hydrogen activation that have
the last eight years, since Stephanꢀs first report on the been synthesized and successfully applied in the hy-
ability of the intramolecular phosphine-borane FLP drogenation of imines 1 and active pharmaceutical in-
system para-(Mes)2PACTHUNGTRENN(UG C6F4)BACHTUGNTNER(NUNG C6F5)2 (Mes=2,4,6-tri- gredients (APIs) in moderate to good yields
methylphenyl) to cleave H2 under certain conditions (Scheme 1).
in the year 2006.[2] Later this remarkable capacity of
At the beginning of this study, non-linked FLP
FLPs was then exploited in metal-free hydrogenation combinations based on [2.2]paracyclophane were
procedures by Erker,[10] as well as Repo and chosen as exploratory catalysts, which were supposed
Rieger.[11] Application to commercial reductions have to be easier to synthesize than linked FLPs. There are
been described firstly in 2011.[12] This concept of FLPs three steps for the synthesis of the [2.2]paracyclo-
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Table 1. Hydrogenation of N-(1-phenylethylidene)aniline 1a
using PFLPs.
Entry[a] Cat.
Press.
[MPa]
Temp.
[oC]
Time
[h]
Yield
[%][b]
Scheme 1. ACHTUNGTRENNUNG[2.2]Paracyclophane-derived frustrated Lewis
pairs (PFLPs) in the catalytic hydrogenation of imines.
1
2
PFLP1 5.0
PFLP1 5.0
120
100
120
120
100
100
80
50
100
50
22
30
18
16
24
12
18
30
6
75
30[c]
82
3
4
5
6
7
8
9
10
11
12
PFLP2 5.0
PFLP3 5.0
PFLP3 2.0
PFLP4 2.0
PFLP4 2.0
PFLP4 2.0
PFLP5 2.0
PFLP5 2.0
PFLP5 2.0
80
78
92
85
46[c]
93
12
26
30
92
25
120
88
B
(C6F5)3 5.0
13[c]
[a]
Reaction conditions: under an N2 atmosphere, catalyst
(0.1 mmol), dry toluene (10 mL) and 1a (1 mmol) were
transferred to a stainless steel autoclave.
Isolated yields.
[b]
[c]
Containing residual starting material.
clophane-phosphine plays an important role in
PFLP1–3 (Table 1, entry 12). Using steric hindrance
as a critical design element, two other intermolecular
combinations of bulky Lewis acid-base pairs PFLP2
Scheme 2. Synthesis of non-linked [2.2]paracyclophane-de-
rived frustrated Lewis pairs (PFLPs).
phane monophosphine donor. Firstly, racemic 4- and PFLP3 were probed for the hydrogenation; they
bromo[2.2]paracyclophane 4 was prepared through were synthesized by using a similar strategy as shown
ACHTUNGTRENNUNG
bromination from commercially available [2.2]paracy- in Scheme 2. In contrast to PFLP1, under the similar
clophane 3 in the solution of bromine catalyzed by conditions, PFLP2 and PFLP3 were more active to
iron. Then lithiation of compound 4 using n-BuLi and promote this reaction, requiring 18 h and 16 h, respec-
nucleophilic substitution with chlorodiphenylphos- tively (Table 1, entries 3 and 4). In addition, the
phine afforded racemic diphenyl
phanylphosphine P1 in 65% yield (Scheme 2). Finally, those with the original catalyst PFLP1. To further
we mixed P1 with one equivalent B(C6F5)3 to obtain demonstrate that the activity of the catalyst was
ACHUTGTNREN[UNG 2.2]paraACHTUNGTNERcNUGN yclo- achieved yields in these reactions are better than
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
the catalyst PFLP1, which displayed no changes com- better, PFLP3 was tested at a lower hydrogen pres-
pared to the individual NMR spectra, hence P1–3 in sure (2.0 Mpa) and lower temperature (1008C) and,
combination with B
G
although the reaction time became longer, the yield
In order to test the performance of the catalysts could not be improved; this experiment proves that
PFLPs, hydrogenation of N-(1-phenylethylidene)ani- under milder conditions this catalyst was still able to
line 1a was chosen as a model reaction. In the pres- active hydrogen easily and revealed good activity as
ence of 10 mol% PFLP1 at 1208C and 5.0 MPa hy- a catalyst for metal-free hydrogenation (Table 1,
drogen pressure, N-(1-phenylethylidene)aniline 1a entry 5). At the present stage, we believe that steric
was transformed into the secondary amine 2a in 75% hindrance in the catalyst skeleton strengthens its cata-
yield (Table 1, entry 1). Under similar conditions, lytic ability in the hydrogenation reaction.
when we reduced the reaction temperature to 1008C,
The initial examples with non-linked FLP combina-
we found that the yield dramatically reduced to 30% tions PFLP1–3 confirmed the effectiveness of this cat-
(Table 1, entry 2). When the experiment was per- alyst structure. However, the stability of the Lewis
formed in the absence of paracyclophane-phosphine acid emerged as a major drawback. For the further in-
a 13% yield was obtained, which showed that paracy- vestigations a linked FLP derived from [2.2]paracyclo-
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Metal-Free Catalytic Hydrogenation of Imines
with much residual starting material at 508C, giving
2a in a low yield. This is, perhaps, because it does not
reach the activation energy needed. Furthermore, by
observing the change in the catalyst during storage,
we found that the stability of the catalyst was also en-
hanced, while the activity did not degenerate during
two weeks when it was stored under a nitrogen at-
mosphere. To further optimize the catalyst, we consid-
ered increasing the steric hindrance between the
atoms B and P, using the same strategy as for PFLP4,
PFLP5 was synthesized, whenr the (Mes)2P group
was introduced instead of the Ph2P group in the
[2.2]paracyclophane skeleton. Similarly, we found that
PFLP5, used as a metal-free catalyst in the hydroge-
nation of imines 1, worked smoothly at various reac-
tion temperatures (25–1008C) in toluene. The results
are summarized in entries 9–11 of Table 2. Therefore,
Scheme 3. Synthesis of linked [2.2]paracyclophane-derived PFLP5 is the most effective of all our previous cata-
frustrated Lewis pairs.
lysts PFLP1–4 in the catalytic hydrogenation of
imines. In addition, we would like to focus on the ac-
tivity of the catalyst PFLP5 that was still working
phane was considered to be a more suitable structural well at room temperature (258C), although it needed
motif. In addition, the stability of this novel catalyst is a longer reaction time (26 h) (Table 1, entry 11).
expected to be strongly enhanced with retained activi-
Having the best catalyst, PFLP5, in hand, we con-
ty, due to the comparable Lewis acidity of the borane tinued our investigations by seeking the optimal reac-
fragment. Simultaneously, we found that Rieger and tion conditions for the hydrogenation of N-(1-phenyl-
Repo[15] described intramolecular FLP with high air- ethylidene)aniline 1a, using PFLP5 based on the re-
and moisture-stability recently. The synthesis of the
intramolecular
phosphine-borane
[2.2]paracyclo-
Table 2. Hydrogenation of N-(1-phenylethylidene)aniline 1a
catalyzed by PFLP5.
phane-derived FLP catalyst PFLP4 is presented in
Scheme 3. Reaction of [2.2]paracyclophane 3 with
NBS gave the corresponding product 1-bromo-
ACHTUNGTRENNUNG[2.2]paracyclophane 5 triggered by azodiisobutyroni-
trile (AIBN). Subsequent dehydrobromination using
potassium tert-butoxide/DMSO resulted in [2.2]para-
cyclophan-1-ene 6 in 62% yield.[16] Then treatment of
olefin 6 with chlorodiphenylphosphine at room tem-
perature in anhydrous THF afforded 1-diphenylphos-
phine-2-chloro
Next the same type of reaction (dehydrochlorination)
afforded 1-diphenylphosphine[2.2]paracyclophane-1-
ene 9. Finally, hydroboration of the unsaturated com-
pound 9 using Piersꢀ borane [bis(pentafluorophenyl)-
borane] in anhydrous n-hexane at 408C provided 1-di-
ACHTUNGTRENNUNG[2.2]paracyclophane 7 in 48% yield.
Entry[a] Solvents Cat.
[mol%] [MPa] [oC]
Press.
Temp. Time Yield
[h]
[%][b]
AHCTUNGTRENNUNG
1
2
3
4
5
6
7
8
toluene 10
hexane 10
CH3OH 10
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
1.0
3.0
4.0
50
50
50
50
50
50
40
60
80
50
50
50
12
15
48
48
8
92
78
trace
trace
95
phenylphosphine-2-bis(perfluorophenyl)boryl
ACHTUNGTRNE[NUNG 2.2]-
THF
toluene 20
toluene
10
A
ACHTUNGTRENNUNG
(Scheme 3). PFLP4 could be fully characterized by
multinuclear NMR analysis as shown in the Support-
ing Information.
5
24
14
10
9
78
84
87
85
toluene 10
toluene 10
toluene 10
toluene 10
toluene 10
toluene 10
In order to prove our hypothesis, PFLP4 was also
applied in the same model reaction to compare it
with the previous intermolecular catalysts PFLP1–3,
which are shown in the Table 1, entries 6–8. It should
be pointed out that the parameters of PFLP4, includ-
ing H2 pressure, temperature, as well as yield, were
much better than the ones of PFLP1–3. It also should
be emphasized here that the reaction became sluggish
9
10
11
12
30
10
6
82
90
88
[a]
Reaction conditions: under an N2 atmosphere, PFLP5,
dry solvent (10 mL) and 1a (1 mmol), were transferred to
a stainless steel autoclave.
[b]
Isolated yields.
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Table 4. Hydrogenation of imines 1 catalyzed by PFLP5.
sults of Table 1. Several solvents were tested in the re-
action of imine 1a, catalyzed by PFLP5 at 508C and
2 MPa hydrogen pressure. Toluene, one of the most
popular solvents used in FLP catalytic hydrogenation,
was the most suitable solvent, as it gave reduction
products 2a in 92% yield within 12 h (Table 2,
entry 1). n-Hexane is another commonly used solvent
for FLP catalytic hydrogenation, but it was less suita-
ble than toluene and gave 2a in 78% yield (Table 2,
entry 2). On the other hand, methanol and THF, used
most in metal catalytic hydrogenations, could not
make the reaction go smoothly (Table 2, entries 3 and
4). Decreasing the amount of PFLP5 from 20 to
5 mol% led to a decrease in the yield of 2a from 92 to
78%, and an increase of the reaction time from 8 to
24 h (Table 2, entries 1, 5 and 6). According to our ex-
perimental results, the pressure and temperature
mainly affected the reaction time, having little effect
on the yield (Table 2, entries 7–12). In summary, the
best conditions involved use of toluene at about 508C
and 2.0 MPa hydrogen pressure, giving 2a in 92%
yield (Table 1, entry 1). The recyclability of catalyst
PFLP5 was also investigated in more detail in the hy-
drogenation of imine 1a (Table 3). After the first hy-
drogenation experiment, catalyst PFLP5 was precipi-
tated when the volume of reaction mixture was con-
centrated to half, the supernatant solution was sepa-
rated and analyzed, showing a yield of 92% (Table 3,
entry 1). The recycled solid catalyst PFLP5 was subse-
quently retransferred to the stainless steel autoclave,
mixed with toluene and substrate, and pressurized
with 2.0 MPa hydrogen. Two consecutive runs demon-
strated a constant yield of over 90%, confirming the
effectiveness and stability of the novel [2.2]paracyclo-
phane-derived FLP catalyst (Table 3, entries 1–4).
Entry[a] R1
R2 R3
Me Ph
Time 2,
[h]
Yield [%][b]
1
Ph
12
6
8
2a, 92
2b, 83
2c, 85
2d, 87
2e, 75
2f, 84
2g, 93
2h, 78
2i, 77
2j, 74
2m, 83
2n, 84
2o, 88
2p, 86
2q, 92
2r, 94
2s, 91
2t, 90
2
Ph
H
H
Ph
Ph
3
p-MeC6H4
4
5
Ph
Ph
Me o-MeOC6H4 12
Me p-NO2C6H4 10
6
p-MeC6H4 Me Ph
12
7
8
p-MeC6H4 Me o-MeOC6H4 18
p-MeC6H4 Me p-NO2C6H4 16
9
p-NO2C6H4 Me Ph
8
10
11
12
13
14
15
16
17
18
p-NO2C6H4 Me o-MeOC6H4 12
p-BrC6H4
p-BrC6H4
p-ClC6H4
Ph
2-naphthyl Me Ph
2-naphthyl Me o-MeOC6H4 20
Me o-MeOC6H4 14
Me Ph 12
Me o-MeOC6H4 15
Et o-MeOC6H4 12
18
Ph
Ph
Ph Ph
Ph o-MeOC6H4 18
15
[a]
Reaction conditions: under an N2 atmosphere, PFLP5
(10 mol%), dry toluene (10 mL) and imine (1 mmol),
were transferred to a stainless steel autoclave and react-
ed at 508C and 2.0 MPa hydrogen pressure.
Isolated yields.
[b]
the substrates 1 with electron-donoring groups on the
With these optimal reaction conditions, we turned aromatic ring gave the corresponding secondary
our attention to examine the scope of the catalytic hy- amines 2 in better yields than those with electron-
drogenation with respect to a variety of imines using withdrawing groups, in contrast those with electron-
catalyst PFLP5. The results were summarized in withdrawing groups required shorter reaction times.
Table 4. The corresponding secondary amines 2 were We suspect that this phenomenon may be related to
obtained in moderate to good yields of 74–94% substrate stability. Moreover, we further confirmed
(Table 4, entries 1–22). Obviously, it was found that that imines made from aldehydes were more easily re-
duced than imines made from ketone (Table 4, en-
tries 2 and 3). It should be noted that a clean hydro-
genation took place when the substrates contain more
aromatic rings, and we easily isolated the products in
good yields (90–94%) (Table 4, entries 19–22).
Table 3. Recycling experiments of catalyst PFLP5.
Entry[a]
Catalyst run
Time [h]
Yield [%][b]
To our surprise, when the temperature of the reac-
tion was increased to 808C, the substrates 1k and 1l
could give the secondary amines 2a and 2d in yields
of 83% and 89%. In addition, when the pressure was
merely raised to 4.0 MPa, similar results were ob-
served (Table 5, entries 1–4). Upon replacing the fluo-
rine function with other halogens, we found that the
expected products from the hydrogenations of 1m, 1n,
1o could be isolated in yields of 83%, 84% and 88%
(Table 4, entries 11–13).
1
2
3
4
1st
12
13
15
30
92
90
2nd
3rd
4th
90
73[c]
[a]
Reaction conditions: under an nitrogen atmosphere,
PFLP5 (10 mol%), dry solvent (60 mL) and imine
(6 mmol), were transferred to a stainless steel autoclave
and reacted at 508C and 2.0 MPa hydrogen pressure.
Isolated yields.
[b]
[c]
Containing residual starting material.
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Metal-Free Catalytic Hydrogenation of Imines
Table 5. Unexpected hydrogenation of imines 1 catalyzed by
PFLP5.
Entry[a]
R
Time [h]
2, Yield [%][b]
1[c]
2[c]
3
Ph
8
12
8
2k, 79
2l, 81
2a, 83
2d, 89
o-MeOC6H4
Ph
o-MeOC6H4
4
12
[a]
Reaction conditions: under an N2 atmosphere, PFLP5
(10 mol%), dry toluene (10 mL) and imine (1 mmol),
were transferred to a stainless steel autoclave and react-
ed at 808C and 2.0 MPa hydrogen pressure.
Isolated yields.
Scheme 5. Mechanism for the hydrogenation of imines 1 cat-
alyzed by PFLP5.
[b]
[c]
Reacted at 508C.
mechanism for this hydrogenation was proposed as
shown in Scheme 5 in accord with a review of the lit-
The utility of the metal-free catalytic hydrogenation erature.[18]
was demonstrated in a synthesis of the calcimimetic
drug cinacalcet 14 {(R)-N-[1-(1-naphthyl)ethyl]- [2.2]paracyclophane-derived frustrated Lewis pairs
3-[3-(trifluoromethyl)phenyl]propan-1-amine}[17]
with reversible, metal-free hydrogen activation that
A
In conclusion, we have described a series of
(Scheme 4). Reaction of (R)-(1-naphthyl)ethylamine was successfully applied in hydrogenation reactions,
11 with 3-[3-(trifluoromethyl)phenyl]propionaldehyde providing a mild and general procedure for the reduc-
12 by means of the TiCl4/MS 4ꢂ system gave the cor- tion of imines to the corresponding amines. Moreover,
responding imine 13, which was finally hydrogenated a broader view suggests that the organic chemistry
with PFLP5 to afford cinacalcet in 80% yield.
community may the opportunity to exploit FLP in
In order to gain insight into the hydrogenation pro- novel ways.
cess, PFLP5 was exposed to a hydrogen atmosphere
at 508C and 2.0 MPa, affording the phosphonium hy-
dridoborate zwitterion PFLP5–2H which was detect- Experimental Section
ed by mass spectroscopy, and which also could reduce
amines. With the above results in hand, a plausible Typical Procedure for the PFLP-Catalyzed
Hydrogenation of Imines
Under a nitrogen atmosphere, imine (1.0 mmol), PFLP
(0.1 mmol), and dry toluene (10 mL) were transferred to
a stainless steel autoclave. The autoclave was purged three
times with hydrogen and finally pressurized to 2.0 MPa. The
reaction mixture was stirred at 508C for the indicated
period of time. After completion of the reaction, the reac-
tion mixture was filtered, and the residue washed with tolu-
ene (2*5 mL). The filtrate was dried over anhydrous Na2SO4
and concentrated under vacuum. The crude product was
subject to column chromatography (silica gel, hexane-
EtOAc, 15:1) to furnish the pure product.
Procedures and analytical data for all compounds are
given in the Supporting Information.
Acknowledgements
Scheme 4. Application of the hydrogenation in the synthesis
of 14.
We thank the National Natural Science Foundation of China
(No. 21076194 and 21276238) for financial support.
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References
Daniliuc, S. Grimme, D. W. Stephan, G. Kehr, G.
Erker, Chem. Sci. 2013, 4, 213.
[1] D. W. Stephan, G. Erker, Angew. Chem. 2010, 122, 50;
Angew. Chem. Int. Ed. 2010, 49, 46.
[10] P. Spies, S. Schwendemann, S. Lange, G. Kehr, R. Frçh-
lich, G. Erker, Angew. Chem. 2008, 120, 7654; Angew.
Chem. Int. Ed. 2008, 47, 7543.
[11] V. Sumerin, F. Schulz, M. Atsumi, C. Wang, M. Nieger,
M. Leskela, T. Repo, P. Pyykko, B. Rieger, J. Am.
Chem. Soc. 2008, 130, 14117.
[12] D. W. Stephan, S. Greenberg, T. W. Graham, P. Chase,
J. J. Hastie, S. J. Geier, J. Farrell, C. C. Brown, Z. M.
Heiden, G. C. Welch, M. Ullrich, Inorg. Chem. 2011,
50, 12338.
[13] a) Modern Cyclophane Chemistry, (Eds.: G. Gleiter, H.
Hopf), Wiley-VCH, Weinheim, 2004; b) Cyclophanes,
(Eds.: F. Diederich), Royal Society of Chemistry, Cam-
bridge, 1991.
[14] L. Greb, P. OÇa-Burgos, A. Kubas, F. C. Falk, F.
Breher, K. Finkc, J. Paradies, Dalton Trans. 2012, 41,
9056.
[15] V. Sumerin, K. Chernichenko, M. Nieger, M. Leskelꢃ,
B. Rieger, T. Repo, Adv. Synth. Catal. 2011, 353, 2093.
[16] H. Hopf, M. Psiorz, Chem. Ber. 1986, 119, 1836.
[17] L. A. Sorbera, R. M. Castaner, M. Bayes, Drugs Future
2002, 27, 831.
[2] a) G. C. Welch, R. S. Juan, J. D. Masud, D. W. Stephan,
Science 2006, 314, 1124; b) G. C. Welch, D. W. Stephan,
J. Am. Chem. Soc. 2007, 129, 1880; c) P. A. Chase, G. C.
Welch, T. Jurca, D. W. Stephan, Angew. Chem. 2007,
119, 8196; Angew. Chem. Int. Ed. 2007, 46, 8050.
[3] H. Wang, R. Frçhlich, G. Kehr, G. Erker, Chem.
Commun. 2008, 5966.
[4] J. B. Sortais, T. Voss, G. Kehr, R. Frçhlich, G. Erker,
Chem. Commun. 2009, 7417.
[5] C. M. Mçmming, G. Kehr, R. Frçhlich, G. Erker,
Dalton Trans. 2010, 39, 7556.
[6] E. Otten, R. C. Neu, D. W. Stephan, J. Am. Chem. Soc.
2009, 131, 9918.
[7] M. Sajid, A. Stute, A. J. P. Cardenas, B. J. Culotta,
J. A. M. Hepperle, T. H. Warren, B. Schirmer, S.
Grimme, A. Studer, C. G. Daniliuc, R. Frçhlich, J. L.
Petersen, G. Kehr, G. Erker, J. Am. Chem. Soc. 2012,
134, 10156.
[8] M. A. Dureen, D. W. Stephan, J. Am. Chem. Soc. 2010,
132, 13559.
[9] M. Sajid, A. Klose, B. Birkmann, L. Liang, B. Schirmer,
T. Wiegand, H. Eckert, A. J. Lough, R. Frçhlich, C. G.
[18] D. W. Stephan, Org. Biomol. Chem. 2008, 6, 1535.
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Adv. Synth. Catal. 2014, 356, 1747 – 1752