Photoredox/Nickel Dual Catalysis for the C(sp3)–C(sp3) Cross-Coupling of Alkylsilicates with Alkyl Halides

Article abstract of DOI:10.1002/ejoc.201601571

Alkylsilicates were engaged under photoredox/nickel dual catalysis conditions with alkyl halides for the first time. The C(sp³)–C(sp³) cross-coupling products were obtained in moderate yields and were accompanied by the homocoupling

Full text of DOI:10.1002/ejoc.201601571

A Journal of
Accepted Article
Title: Photoredox/Nickel Dual Catalysis for the Csp3-Csp3 Cross-
Coupling of Alkylsilicates with Alkyl Halides
Authors: Louis Gabriel Fensterbank, Cyril Ollivier, Christophe Lévêque,
Vincent Corcé, and Ludwig Chenneberg
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201601571
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10.1002/ejoc.201601571
European Journal of Organic Chemistry
COMMUNICATION
Photoredox/Nickel Dual Catalysis for the Csp3-Csp3 Cross-
Coupling of Alkylsilicates with Alkyl Halides
Christophe Lévêque,[a] Vincent Corcé,[a] Ludwig Chenneberg,[a] Cyril Ollivier*[a] and Louis
Fensterbank*[a]
To Michèle Bertrand
Abstract: Alkylsilicates have been engaged under photoredox/nickel
dual catalysis conditions with alkyl halides for the first time. Csp3-
concerned Csp3-Csp2 (aryl or vinyl) cross couplings. While we
were developing Csp3-Csp3 coupling reactions,[11] a recent
Csp3 cross coupling products have been obtained in moderate yields, report by MacMillan and coworkers of such transformations
accompanied by homocoupling products of the alkyl halide
derivatives. These promising findings are strongly suggestive of the
high synthetic potential of the dual catalytic approach for the forging
of alkyl carbon-carbon bonds.
using carboxylates,[12] prompted us to disclose now our own
findings.
Csp2
Csp3-Csp2 cross-coupling
Ar
or
X
R
Ar
Introduction
Photocatalyst
Ni(0) or Ni(II)
Ligand
X
or
refs. 8
& 10
O
O
R
The formation of carbon-carbon bonds has been at the heart of
the preoccupations of the organic synthetic chemists since the
origin of organic chemistry. In fact, most name reactions belong
to the category of carbon-carbon bond forming reactions.[1]
Besides cycloadditions, a good part of these transformations
have involved organometallic reagents or radical species, which
have progressively matured into catalytic processes like for
instance transition metal catalyzed cross coupling processes.[2]
The latter generally involves a nucleophilic organometallic
component (R-M) and an electrophilic partner (R-X). More
recently, the alternative coupling between two electrophiles (R-
X) and (R’-X) in the presence of reducing agents has been
worked out.[3] However, both approaches suffer from severe
weaknesses. In the first case, a tamed nucleophile, compatible
with functionality, is needed; in the second one, electrophiles
with different reactivity profiles are combined and an over
stoichiometric amount of reducing agent is required. The very
recent third strategy,[4] involving a radical precursors and a R-X
electrophilic partner also referred as single electron
transmetalation,[5] consists in merging the photocatalytic
formation of radical entities with a nickel catalyzed cross-
coupling event. This approach alleviates all the previous issues
and therefore constitutes a versatile alternative.[6] Among the
different parameters at work in this type of reactions, the choice
of the precursors of C-centered radical is certainly a key factor.
Initially reported with carboxylates,[4a] dimethylaniline[4a] and
trifluoroborates,[4b],[7] we[8],[9] and the group of Molander[10]
introduced silicates as very versatile sources of radicals. They
notably display lower oxidation potentials than trifluoroborates.
All examples of dual catalysis involving silicates have so far
R
Si
+
O
DMF, blue LEDs
K
Csp3
O
Csp3-Csp3 cross-coupling
Alk
Alk
Csp3
X
This work
R
Scheme 1. Photoredox/nickel dual catalysis with alkylsilicates for cross-
coupling reactions.
Results and Discussion
We initially focused on the coupling of the n-hexylsilicate 1a with
bromoester 2a which involve two fragments of distinct polarities
and facilitates the isolation of the various (cross coupling and
homocoupling) adducts. A rapid screening of the previously
used photocatalysts[8],[10] (Table 1, entries 1-3) gave a mixture of
expected product 3aa accompanied however by homocoupling
product 4a which was in the three cases the major product.
Since the iridium photocatalyst proved superior to the two other
ones, we kept it in the following coupling reactions. We then
varied the reaction conditions in order to invert the cross
coupling – homocoupling ratio. Decreasing the loading of
iridium(III) to 2 mol% proved quite detrimental (entry 4) however
slightly increasing the number of equivalents of silicates from 1.2
to 1.5 equiv allowed the major generation of the cross coupling
derivative, in yields above 40% (entry 5). Restoring the
photocatalyst loading to 5 mol% turned out to give the best
conditions (entry 6) while changing to 2 equiv of silicate (entry 7)
or using a nickel(II) precatalyst proved to be less effective. It can
be mentioned that no reaction was observed in acetonitrile or
1,3-dimethyl-2-imidazolidinone (DMI)[13]
even at higher
[a]
Christophe Lévêque, Vincent Corcé, Ludwig Chenneberg, Cyril
Ollivier*, Louis Fensterbank*
Sorbonne Universités, UPMC Univ Paris 06, CNRS
Institut Parisien de Chimie Moléculaire, UMR 8232
4 place Jussieu, 75005 Paris
concentration (1 M). A 0.01 M concentration results in lower
yields in 3aa (25%) and 4a (26%).
E-mail: cyril.ollivier@upmc.fr; louis.fensterbank@upmc.fr
Supporting information for this article is given via a link at the end of
the document.((Please delete this text if not appropriate))
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10.1002/ejoc.201601571
European Journal of Organic Chemistry
COMMUNICATION
Table 1. Optimisation of reaction conditions.[a]
Equivalents
of Silicate
Photocatalyst
(mol%)
Yield[b] [%]
(3aa%/4a%)
Entry
Ni complex
3aa: 34%
4a: 38%
1
2
3
4
5
6
7
8
1.2
1.2
1.2
1.2
1.5
1.5
2
[IrIII] (5)
[RuII] (5)
4CzIPN (5)
[IrIII] (2)
Ni(COD)2
Ni(COD)2
Ni(COD)2
Ni(COD)2
Ni(COD)2
Ni(COD)2
Ni(COD)2
NiCl2.dme
3aa: 22%
4a: 36%
3aa: 22%
4a: 25%
3aa: 29%
4a: 52%
Scheme 2. Ancillary ligand screening
[IrIII] (2)
3aa: 42%
4a: 50%
[IrIII] (5)
[IrIII] (5)
3aa: 43%
4a: 38%
3aa: 44%
4a: 42%
3aa: 26%
4a: 30%
1.5
[IrIII] (5)
[a] Reaction conditions: 1a (0.36, 0.45 or 0.6 mmol), 2a (0.3 mmol), Ni
complex (5 mol%), bipyridine (5 mol%), photocatalyst (2 or 5 mol%), DMF (0.1
M), 24h at room temperature, under blue LEDs irradiation. [b] Isolated yields.
Scheme 3. Electrophile screening
Variation on the silicate partner (Scheme 4) provided
consistent results and delivered coupling adducts 3ba-3ma
bearing different types of useful functionalities from low to
moderate yields (from 9 to 38%). An α-amino substituted radical
could be successfully engaged (product 3ia, 38% yield) while
the corresponding α-oxygenated and α-chloro radicals did not
react properly. Of note, cross-coupling reactions are less
efficient with ammonium cyclohexyl- and cyclopentylsilicates
(1g’ and 1m) for the formation of adducts 3ga and 3ma.
Some reports have evidenced an important effect of the
ancillary ligand of nickel[7a,e],[12] on the efficiency of the process.
Therefore, we tested a series of them (Scheme 2). Di-tert-butyl
bipyridine or terpyridine ligands gave the same yield (42%) of
product 3aa. However, no reaction was observed with di-
methoxy bipyridine. BIOX and pybox ligands proved to be less
productive (Scheme 2). For the rest of the study, we therefore
kept the simplest bipyridine ligand.
Finally, we also engaged different bromides (Scheme 5).
Primary and secondary bromides reacted more or less efficiently
(27-37% and 16-35% respectively). No reaction was observed
with cyclopropyl bromide. Hexenyl bromide 2g provided a
mixture of direct Csp3-Csp3 cross coupling products 3lg/3lg’ and
5-exo-trig – cross coupling tandem 3lg’’. The later presumably
indicates the generation of the 5-hexenyl radical from 2g and its
further interception by nickel to enter the cross coupling catalytic
Scheme 3 also shows that the best electrophile is the
bromide 2a. No coupling was observed with the corresponding
chloride or tosylate while the iodo ester gave a poor yield of 3aa
(11%) with a major formation of 4a (14%).
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10.1002/ejoc.201601571
European Journal of Organic Chemistry
COMMUNICATION
cycle. This radical generation from the alkyl bromide partner
might also be at the origin of the homocoupling product.[14]
A
better understanding of the mechanism of this dual catalysis is
highly desirable and further studies are still ongoing in our
laboratory.
Conclusions
Among all strategies to form C-C bonds, Csp3-Csp3 cross
coupling reactions have more recently represented a very
attractive option. For that purpose, the single electron
transmetalation approach is still in its infancy. Our report
introduces silicates as radical precursors in photoredox/nickel
dual catalysis process. Although moderate yields of cross
coupling products have been obtained, plagued notably by the
formation of homocoupling products, feasibility of the approach
is confirmed. Of note, these reactions are highly tolerant of
functionality. Clearly, all this opens new synthetic perspectives in
this very active field and poses intriguing mechanistical
questions.
Scheme 5. Bromide screening.
Experimental Section
To a Schlenk flask was added hexylsilicate 1a (1.5 eq., 0.45 mmol, 284
mg), the iridium photocatalyst [IrIII] (5 mol%, 15 µmol, 15 mg) and 2,2’-
bipyridine (5 mol%, 15 µmol, 2.3 mg). Ni(COD)2 (5 mol%, 15 µmol, 4.1
mg) was then added in the glovebox. The Schlenk flask was sealed with
a rubber septum, removed from the glovebox, and evacuated / purged
with vacuum / argon three times. Degassed DMF (3 mL) was introduced
followed by addition of ethyl 4-bromobutyrate 2a (0.3 mmol, 43 µl) and
the reaction mixture was irradiated with blue LEDs (477 nm) at room
temperature for 24h under an argon atmosphere. The reaction mixture
was diluted with diethyl ether (50 mL), washed with aqueous saturated
Na2CO3 solution (2 times), brine (2 times), dried over MgSO4 and
evaporated under reduced pressure. The crude residue was purified by
flash column chromatography on silica gel (pentane/diethyl ether, 98/2 to
pentane/diethyl ether, 90/10) to afford the coupling adduct, ethyl
decanoate 3aa (26 mg, 43%) as a colorless oil and the homocoupling
product diethyl, octanedioate 4a as a colorless oil (26 mg, 38%). The
spectroscopic data are in agreement with those reported in the literature.
3aa.[15] 1H NMR (400 MHz, CDCl3): δ 4.12 (q, J = 7.1 Hz, 2H), 2.30 – 2.26
(m, 2H), 1.65 – 1.58 (m, 2H), 1.35 – 1.25 (m, 12H), 1.25 (t, J = 7.1 Hz,
3H), 0.88 (t, J = 6.8 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 174.1, 60.3,
34.6, 32.0, 29.6, 29.4, 29.4, 29.3, 25.2, 22.8, 14.4, 14.2. 4a.[16] 1H NMR
(400 MHz, CDCl3): δ 4.12 (q, J = 7.1 Hz, 4H), 2.28 (t, J = 7.5 Hz, 4H),
1.66 – 1.58 (m, 4H), 1.35 – 1.31 (m, 4H), 1.25 (t, J = 7.1 Hz, 6H). 13C
NMR (100 MHz, CDCl3): δ 173.9 (2 C), 60.3 (2 C), 34.4 (2 C), 28.9 (2 C),
24.9 (2 C), 14.4 (2 C).
Scheme 4. Silicate screening.
Acknowledgements
We thank CNRS, UPMC, IUF, MSER (ASN PhD grant to CL),
LABEX MiChem (ANR-11-IDEX-0004-02), La Région Martinique
(PhD grant to LC), ANR NHCX (11-BS07-008, postdoc grant to
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COMMUNICATION
Chem. Int. Ed. 2016, 55, 14106; h) A. Gutierrez-Bonet, J. C. Tellis, J. K.
Matsui, B. A. Vara, G. A. Molander, ACS Catal. 2016, 6, 8004; see
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Chem. Soc. 2016, 138, 12312.
VC) and COST Action CM1201. Omar Khaled is also
acknowledged for HRMS.
Keywords: photoredox catalysis • nickel • cross coupling •
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European Journal of Organic Chemistry
COMMUNICATION
COMMUNICATION
Csp3-Csp3 cross coupling
Christophe Lévêque, Vincent Corcé,
Ludwig Chenneberg, Cyril Ollivier* and
Louis Fensterbank*
R
Ir(III) + Ni(0)
visible light
Csp3-Csp3
Si
+
Alk X
R
Alk
O
O
cross coupling
O
O
Page No. – Page No.
We introduce bis-catecholato silicates as radical precursors in photoredox/nickel
dual catalysis process. Moderate yields of Csp3-Csp3 cross-coupling products have
been obtained thus confirming the feasibility of this approach.
Photoredox/Nickel Dual Catalysis for
the Csp3-Csp3 Cross-Coupling of
Alkylsilicates with Alkyl Halides
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