A highly efficient Cu catalyst system for the radical reactions of α-bromocarbonyls

Article abstract of DOI:10.1039/c7cc01790a

In this communication, we established highly efficient Cu-catalyzed ARGET-ATRS (atom-transfer radical substitution) of alpha-bromocarbonyls with styrenes to produce tert-alkylated styrenes. The maximum TON was up to 12 000. Hünig's base was very important to regenerate active Cu^I. Moreover, a Cu-catalyzed C-C cleavage reaction via S_H2′ and intermolecular C-H cyclization of α-bromoimide was found.

Full text of DOI:10.1039/c7cc01790a

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Marilyn M. Olmstead, Alan L. Balch, Josep M. Poblet, Luis Echegoyenet al.
Reactivity differences of Sc
first methanofullerene derivatives of Sc
3
N@C2n (2n
=
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3
N@D5h-C80
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DOI: 10.1039/C7CC01790A
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Highly Efficient Cu Catalyst System for the Radical Reactions of α-
Bromocarbonyls
Received 00th January 20xx,
Accepted 00th January 20xx
Yushi Noda, Takashi Nishikata
DOI: 10.1039/x0xx00000x
www.rsc.org/
9
In this paper, we established highly efficient Cu-catalyzed ARGET- effective to increase the copper catalyst activities . Cu-
ATRS
(atom-transfer
radical substitution) of alpha- catalyzed intramolecular ATRA reactions by using
1
achieved low catalyst loadings .
0
bromocarbonyls and styrenes to produce tert-alkylated styrenes. ascorbic acid or KBH
4
The maximum TON is up to 12000. Hünig’s base was very Immobilized Cu catalysts are also effective. For example,
I
important to regenerate active Cu . Moreover, Cu-catalyzed C-C Cu metal embedded in siloxane gels or polymer realized
1
1
cleavage reaction via S
H
2’ and intermolecular C-H cyclization of α– recyclable reaction systems . Amine reductants are
I
another option to generate active Cu species from the
bromoimide were found.
II 12
reduction of Cu . Highly efficient Cu catalyst systems
Atom-transfer radical addition (ATRA) using α–
bromocarbonyls is one of the most useful reactions and
for ATRA, and ATRP, whereas atom-transfer radical
substitution (ATRS) have not yet been established. In
this context, we envisaged to develop the reaction of α-
1
various modified reactions have been reported . α–
Bromocarbonyl compound reacts with a metal catalyst
bromocarbonyls
styrene products
presence of amine as an activator for Cu (Scheme 1).
1
and styrenes 2 to obtain alkylated
with low Cu catalyst loadings in the
n
M ) to generate a radical species and M
n+1
(
and the
resulting radical reacts with olefins to generate diverse
3
1
functional molecules . Although transition metal
complexes including Ru, Fe, Ni and Cu have been
applied to the reactions as a catalyst, a large amount of
catalyst loadings (10 – 30 mol%) might be limited to
2
-5
develop the protocol for industrial processes . Many
reports describes that high catalyst loadings are due to a
II 1
generation of inactive metal species, such as Cu . In this
6
context, continuous activator regeneration (ICAR) or
7
activators regenerated by electron transfer (ARGET)
process has been developed as the solution to this
Scheme 1 ARGET-ATRS.
problem, in which AIBN(α,α'-azobisisobutyronitrile), V-
7
0(2,2′-azobis(4-methoxy-2,4-dimethylvaleronitrile)) or
We previously reported that atom-transfer radical
addition followed by elimination reaction to give Heck
an inorganic reductant is employed as an electron donor.
The research for the activity of a copper catalyst is one of
the main streams in this area. For example, the intra- and
intermolecular additions of carbon halides to olefins in
the presence of a Cu catalyst and AIBN or V-70 resulted
13
like olefin product (ATRS) . Similar to ATRA, the
drawback of our reactions is that the large amount of
catalyst (>10 mol% Cu salt) required to achieve the high
yields of the products. At the first stage of this research,
we re-optimized the reaction conditions in the presence
of 100 ppm (0.01 mol%) of Cu catalyst (Table 1).
Although the reaction did not occur under the conditions
II
in TON’s of over 10000, in which inactive Cu species is
8
reduced to active Cu during the reaction . The
combination of UV light and those additives is also
I
(
temperature) (Runs 1 and 2), PMDETA, Me TREN and
no catalyst, no multidentate nitrogen ligand, at room
6
TPMA gave TONs of 2100, 3500 and 4500 (Runs 3-5).
We screened various amines and found that iPr EtN
2
(
Hünig’s base) gave the best yield with TON of 5200
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(Runs 6-9). The product 3a was not obtained without occurred to produce 3l in the yield of up to 73% with
amines, which implies that amine plays an import role for TON’s of up to 3650, in which stable cumyl radical is a
I
the generation of active Cu species continuously. leaving group.
Solvent effect is a little bit important and 1,2-
dimethoxyethane gave the best yield (Run 10). When the Table 2 Substrate scope .
reaction carried out with 200 and 400 ppm of CuI, 72%
a
R" R'
and 88% of 3a with TONs of 3600 and 2200 were
obtained (Runs 11 and 12).
OR
1
2
CuI (0.01 mol%)
TPMA (2 mol%)
iPr2EtN (1.5 equiv)
Br
R'''
R" R'
O
+
OR
3
Ar
R'''
a
Table 1 Optimization .
O
(MeOCH2)2/MeCN
Ar
6
0 oC, 20 h
Yield of 3 (%) / TON
R'''=H
MeO
CO2Et
CO2Et
CO2Me
MeO
3c: 70% (44 h)b
TON:7000
MeO
b: 89% (44 h)b
3d: 88% (44 h)b
3
TON:8900
TON:8800
CO2Et
CO2Et
MeO
MeO
CO2Et
CO2Et
MeO
OMe
e: 81% (44 h)b
3g: 87% (44 h)b
3
3f: 69%
TON:6900
TON:8100
TON:8700
CO2Et
R'''=Me
CO2Et
CO2Et
CO2Me
N
Et
h: 61%
TON:6100
3i: 43% (90 : 10)c
3j: 61% (90 : 10)c
TON:6100
3
TON:2150
(CuI 0.02 mol%)
CO2Et
CO2Et
2
CO Et
Cl
Br
3l: 46% (90 : 10)c
TON:2300
(CuI 0.02 mol%)
3m: 54% (93 : 7)c
TON:2700
(CuI 0.02 mol%)
3
k: 83% (90 : 10)c
TON:4150
(CuI 0.02 mol%)
a
All reactions were carried out at 100 ºC for 20 h with 0.01 mol%
-4
a
Cu salt (5 x 10
M
in MeCN), Ligand (20 mol%), amine (1.2
All reactions were carried out in (MeOCH
2
)
2
at 100 ºC for 20 h
-4
equiv), 1a (2.0 equiv.) and 2a (1.0 equiv.). Yields were with 0.01 mol% CuI (5 x 10
M
in MeCN), TPMA (2 mol%),
1
determined by HNMR. The 3a was trans. 0.02 mol% CuI was iPr
b
2
EtN (1.2 equiv),
1
(2.0 equiv.) and 2 (1.0 equiv.). Yields were
c
used. 0.04 mol% CuI was used.
b
isolated. The 3b-3h were trans. Reaction was carried out at 60
c
ºC. The ratio is endo:exo.
Under optimal conditions, ATRS proceeded smoothly by
using low catalyst loadings (Table 2). The reaction of
various α–bromoesters
internal alkene products (3b
to 8900. Interestingly, the reaction of α–bromoamide
and did not give any olefination products but
intramolecular C-H cyclization product oxindole
derivatives) was obtained quantitatively when 200 pm of Scheme 2 C-H cyclization.
1
and styrene derivatives
2 to give
-
3h) achieved TON’s of up
4
2
3
5
(
1
4
CuI was used (Scheme 2) . This C-H reaction occurred
in the presence of 50 ppm of CuI and the maximum TON
was 25000. We also applied this reaction conditions to
the reaction of α–methylstyrene derivatives
result, typical substrates gave the corresponding allylic
compounds (3a 3i 3m) in moderate to good yields with
TON’s of up to 6100. In this case, endo- and exo-isomers
1. As the
,
-
1
3b
were obtained
alkylstyrene possessing cumyl group
olefination product was not obtained (Scheme 3). In
this case, C-C cleavage reaction (S
.
We also examined other α–
6
but the desired Scheme 3 C-C bond cleavage.
3
H
2’ like reaction)
2
| J. Name., 2012, 00, 1-3
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2
3
4
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Finally, we checked the maximum TON for the reaction
of 1a and 2b in the presence of 100, 50, 20 and 10 ppm
of CuI (Table 3). Although 50 ppm of CuI gave TON of
7
800 (Trun 3), better TON was obtained in the reaction
5
6
with 20 ppm of CuI (TON=12000) (Run 4). The reaction
was stopped when 10 ppm of CuI was employed (run 5).
Additionally, when 5 mmol scale reaction was carried
out in the presence of 100 ppm of CuI, 75% yield of 3b
7
8
15
with TON of 7500 was obtained (Run 2) .
(a) W. T. Eckenhoff, T. Pintauer, Inorg. Chem., 2007, 46,
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1
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0
1
1
1
2
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at 60 ºC for 44 h 13 (a) T. Nishikata, S. Ishikawa, Synlett, 2015, 716; (b) T.
in MeCN), TPMA (2 mol%), iPr EtN (1.2
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3,
1
a
2 2
All reactions were carried out in (MeOCH )
-4
with CuI (5 x 10
M
2
2
equiv), 1a (2.0 equiv.) and 2b (1.0 equiv.). The 3b was
b
trans.Yields were isolated. 5 mmol scale.
,
,
3
Conclusions
7
In conclusion, we discovered that Hünig’s base improves
the catalyst activity of CuI in ARGET-ATRS. In this
1
1
4
5
1
5
reaction, various alkylated styrenes
TON’s up to 12000. Moreover, α–bromoimide
H cyclization product in high yield with high TON.
3
were obtained with
We used dimethyl 2,2’-azobis(isobutyrate) instead of the Cu
catalyst but no reaction occurred. This result could show that
our reaction is not chain reaction.
4
gave C-
5
These results are useful to carry out ATRS with the
minimal amounts of cheap Cu metals. Further
improvements including our original ligand design and
activator for a Cu catalyst will be described in due
course.
Acknowledgements
Financial support provided by program to disseminate
tenure tracking system, MEXT, Japan and the Sasakawa
Scientific Research Grant from The Japan Science
Society is gratefully acknowledgement.
Notes and references
1
(a) T. Pintauer, K. Matyjaszewski, Chem. Soc. Rev., 2008, 37
087; (b) T. Pintauer, Eur. J. Inorg. Chem., 2010, 2249; (c)
W. T. Eckenhoff, T. Pintauer, Catal. Rev.: Sci. Eng., 2010,
, 1; (d) W. T. Eckenhoff, A. B. Biernesser, T. Pintauer,
Inorg. Chem., 2012, 51, 11917; (e) A. J. Clark, Eur. J. Org.
Chem., 2016, 2231.
,
1
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