d-Glucose: An Efficient Reducing Agent for a Copper(II)-Mediated Arylation of Primary Amines in Water

Article abstract of DOI:10.1002/cssc.201600801

A copper-catalyzed Ullmann-type amination with primary amines in water with a combination of copper(II) triflate [Cu(OTf)₂], dipivaloylmethane, and d-glucose is reported. The mild conditions and the use of an inexpensive catalyst as well as a renewable feedstock (d-glucose and the surfactant TPGS-750-M, which is derived from vitamin E) make this protocol a safe and convenient strategy for efficient C?N bond formation. This easy-to-handle procedure is extremely competitive compared to palladium-based reactions and may be used to synthesize N-containing molecules, such as drugs or organic light-emitting diodes (OLEDs).

Full text of DOI:10.1002/cssc.201600801

DOI: 10.1002/cssc.201600801
Full Papers
d-Glucose: An Efficient Reducing Agent for a Copper(II)-
Mediated Arylation of Primary Amines in Water
Maud Bollenbach,[a] Patrick Wagner,[a] Pedro G. V. Aquino,[a, b] Jean-Jacques Bourguignon,[a]
Frꢀdꢀric Bihel,[a] Christophe Salomꢀ,[a, c] and Martine Schmitt*[a]
A
copper-catalyzed Ullmann-type amination with primary
a safe and convenient strategy for efficient CÀN bond forma-
tion. This easy-to-handle procedure is extremely competitive
compared to palladium-based reactions and may be used to
synthesize N-containing molecules, such as drugs or organic
light-emitting diodes (OLEDs).
amines in water with a combination of copper(II) triflate
[Cu(OTf)2], dipivaloylmethane, and d-glucose is reported. The
mild conditions and the use of an inexpensive catalyst as well
as a renewable feedstock (d-glucose and the surfactant TPGS-
750-M, which is derived from vitamin E) make this protocol
Introduction
Transition-metal-catalyzed reactions have a prominent place in
the arsenal of synthetic chemists.[1] These reactions have tradi-
tionally been performed in conventional organic solvents. Cur-
rently, the design of sustainable protocols involving green cat-
alysis is emphasized.[2] The use of water as a solvent has many
advantages because it is the most economical, safe, and envi-
ronmentally friendly solvent.[3] The formation of micelles in the
presence of the nonionic amphiphile polyoxyethanyl-a-
tocopheryl succinate (TPGS-750-M) helps solubilize organic re-
agents.[4a] The viability of this surfactant-promoted chemistry
was demonstrated by Lipshutz et al. Indeed, in 2008, they re-
ported the use of this new methodology for metathesis[4] and
important cross-coupling reactions such as Suzuki–Miyaur-
a,[4a,d,e,5] Heck,[4d–f,6] CÀH activation,[4a,e] Sonogashira,[4a,7] and
Buchwald–Hartwig reactions.[4a,e,8] Recently, our group further
investigated the Buchwald–Hartwig reaction,[9] as the forma-
tion of CÀN bonds is one of the most useful reaction types in
medicinal chemistry and materials science.[10] Thus, we report-
ed a universal catalytic system for Buchwald–Hartwig reactions
under micellar conditions.[11] However, the industrial use of
these methods may be limited by the high cost, scarcity, and
toxicity of palladium. As an alternative, copper-based Ullmann
aminations attracted our attention owing to the low cost, low
toxicity, and high abundance of copper.
Copper-mediated arylation was discovered several decades
before the Buchwald–Hartwig reaction, but its use was limited
for a long time because several drawbacks restricted its indus-
trial application. Originally, it required stoichiometric amounts
of copper, high reaction temperatures, and high-boiling-point
polar solvents.[12] Moreover, the scope of the reaction was also
restricted to electron-poor aromatic substrates.[13a–c] In 2001,
the discovery of new copper/bidentate-ligand systems led to
a spectacular renewed interest in Ullmann reactions.[10b,13] The
milder conditions of the new copper-catalyzed aminations en-
larged the scope in terms of substrate tolerance, chemoselec-
tivity, and enantioselectivity.[13e,14] Despite the emergence of
green chemistry, copper-catalyzed coupling reactions with
water as the solvent have been described only rarely. Only
a few examples of copper-catalyzed N-arylation in aqueous
media have been reported with heterocyclic amines,[15a–l] ali-
phatic amines,[15g–h,l,n] amino acids,[15h,m] or ammonia.[15n,o] To be
efficient, these reactions required temperatures between 80
and 1308C. Herein, we describe an efficient and highly selec-
tive copper-catalyzed N-arylation or heteroarylation with pri-
mary amines under micellar conditions at much lower temper-
atures [room temperature (RT, 258C) or 508C].
[a] M. Bollenbach, P. Wagner, P. G. V. Aquino, Dr. J.-J. Bourguignon, Dr. F. Bihel,
Dr. C. Salomꢀ, Dr. M. Schmitt
Laboratoire d’Innovation Thꢀrapeutique
University of Strasbourg
74 route du Rhin
BP60024, 67401 Illkirch (France)
E-mail: mschmitt@unistra.fr
[b] P. G. V. Aquino
Results and Discussion
Laboratꢁrio de Pesquisa em Recursos Naturais
Universidade Federal de Alagoas
Maceiꢁ, AL (Brazil)
In our initial screening experiments, 3-iodotoluene (1a) and 3-
phenylpropylamine (2) were used as model substrates to es-
tablish the most suitable conditions (Figure 1). Seven commer-
cially available classical ligands such as b-diketones, diamines,
and phenanthroline were tested with CuI (10%) as the catalyst.
NaOtBu was selected as a suitable base, and the reactions
were performed in water supplemented with TPGS-750-M
[c] Dr. C. Salomꢀ
SpiroChem AG, c/o ETH-Zꢂrich
Vladimir-Prelog-Weg 3
8093 Zꢂrich (Switzerland)
Supporting Information for this article can be found under:
http://dx.doi.org/10.1002/cssc.201600801.
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ing agent was added to regenerate the copper(I) catalyst
in situ. Sodium ascorbate (NaAsc) was chosen for its ability to
reduce copper(II) and its well-known use in the “click” reac-
tion.[16] It is also often used for cross-coupling arylations with
ammonia,[15o] amides,[17] and disulfides.[18] Significantly im-
proved yields (50%) were obtained in the presence of NaAsc
with the b-diketone ligands L1 and L2 (Figure 1). This result en-
couraged us to favor the use of copper(II) catalysts in the pres-
ence of reducing agents.
The influences of eight different copper(II) salts and leaving
groups were studied in combination with either L1 or L2
(Figure 2). Surprisingly, for L1, bromo derivatives appeared sys-
tematically more reactive than the corresponding iodo ones.
This result was quite unexpected because bromoaryls are gen-
erally less reactive in Ullmann-type reactions than iodo deriva-
tives. In contrast, L2 appeared systematically more effective
with 3-iodotoluene (1a) than with 3-bromotoluene (1b).
However, it is important to note that the yields for L2 never
exceeded 50%, whereas L1 led to yields greater than 70%. Fur-
ther explorations revealed the nonefficacy of chloro, O-triflate,
and O-tosylate leaving groups. Although copper(II) oxide
showed a modest activity, the other copper(II) salts, that is,
copper(II) triflate [Cu(OTf)2], Cu(NO3)2·3H2O, and CuBr2, afforded
good yields of up to 75% yield. On the basis of these results,
we selected 1b with L1 in combination with Cu(OTf)2,
Cu(NO3)2.3H2O, or CuBr2 to continue our study.
Figure 1. Impact of various ligands in the copper-catalyzed amination of 3-
iodotoluene in TPGS-750-M in the presence or absence of NaAsc. Reaction
conditions: CuI (10 mol%), ligand (20 mol%), NaOtBu (2 equiv.), 3-iodoto-
luene (1 equiv.), 3-phenylpropylamine (1.2 equiv.), TPGS-750-M (2 wt%),
508C, 24 h. [a] Average yield of two experiments. Yields were determined by
HPLC with a UV detector and benzophenone as an external standard. W/L:
without ligand.
We have previously highlighted the importance of reducing
agents in this copper-catalyzed amination under micellar con-
ditions. Without a reducing agent, no reaction was observed
with the copper(II) catalyst (Supporting Information, Figure S2).
To optimize this parameter, three classical reducing agents
were used [sodium ascorbate, hydroquinone, and tris(2-
carboxyethyl)phosphine (TCEP)] as well as three reducing
sugars (d-glucose, d-fructose, and d-galactose) at two different
temperatures (RT and 508C, Figure 3 and Figure S1). In the
presence of Cu(OTf)2, no reaction was observed with TCEP at
both temperature or with NaAsc at room temperature. All
other reducing agents led to the desired product 3b in moder-
ate-to-excellent yields, even at room temperature. In particular,
(2 wt%) as the surfactant. In the absence of ligand (W/L), no
reaction was observed, and the nitrogen-based ligands (L3–L7)
were poorly active or inactive. Both b-diketones dipivaloylme-
thane (L1, THMD) and 2-isobutyrylcyclohexanone (L2) showed
promising effects and afforded the product in approximately
25% yield. To explain this modest yield, we could consider the
possible oxidation of the copper(I) catalyst to form an inactive
copper(II) species in water. To validate this hypothesis, a reduc-
Figure 2. Impact of copper(II) salts and leaving groups in combination with either L1 or L2. Reaction conditions: copper(II) salt (10 mol%), L1 or L2 (20 mol%),
NaAsc (10 mol%), NaOtBu (2 equiv.), ArX (1 equiv.), 3-phenylpropylamine (1.2 equiv.), TPGS-750-M (2 wt%), 508C, 24 h. [a] Average yield of two experiments.
Yields were determined by HPLC with a UV detector and benzophenone as an external standard.
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Figure 3. Screening of reducing agents. Reaction conditions: Cu(OTf)2 (10 mol%), L1 (20 mol%), reducing agent (10 mol%), NaOtBu (2 equiv.), 3-bromotoluene
(1 equiv.), 3-phenylpropylamine (1.2 equiv.), TPGS-750-M (2 wt%), 508C or RT, 24 h. [a] Average yield of two experiments. Yields were determined by HPLC
with a UV detector and benzophenone as an external standard.
d-glucose afforded the desired product in 84% yield at room
temperature. Similar results were obtained with Cu(NO3)2.3H2O
and CuBr2 in the presence of sodium ascorbate and d-glucose.
However, the Cu(OTf)2L1/d-glucose catalytic system was the
best combination for this green Ullmann-type amination. To
the best of our knowledge, d-glucose has been used rarely as
a reducing agent in organic chemistry. It has been reported for
the one-pot assembly of N-fused imidazoles,[19] the reductive
homocoupling of aryl halides,[20] and the formation of quino-
lines involving a three-steps cascade.[21] Therefore, this seems
to be the first report of the use of d-glucose as a reducing
agent in a copper-catalyzed reaction in an aqueous medium.
Its abundance and nontoxicity make d-glucose the perfect ad-
ditive for sustainable chemistry approaches. This aspect is
strengthened by the efficiency of the Cu(OTf)2L1/d-glucose cat-
alytic system at room temperature, which is a positive parame-
ter in terms of energy saving.
tion needed to be heated to 508C to obtain a yield of 48%.
For aryl rings bearing bromine and chlorine substituents (3 f
and 4e), the reaction only occurred at the brominated posi-
tion. It is particularly noteworthy that the reaction proceeds
successfully to provide the desired products in moderate-to-
high yields without the protection of the functional group,
even in the presence of sensitive substituents [i.e., CN (3i),
CONH2 (3j), CO2tBu (3k), MeCO (3l), CHO (3m), or nitro (3o)].
Starting from an acetal moiety, the aminated product 3n was
isolated as the sole product from the reaction at RT. However,
at 508C, a partial deprotection of the acetal was observed, and
the corresponding aldehyde 3mb formed in 22% yield. We
then turned our attention to various bromoheterocyclic sys-
tems such as pyridine (4a–e), pyrimidine (4 f and 4g), pyrazine
(4h), and thiophene (4i), which were efficiently N-arylated with
numerous primary amines (Figure 4). If the bromine atom was
at the meta position, the reaction proceeded under the opti-
mized conditions (2 wt% of TPGS-750-M at RT) with good-to-
excellent yield, even with a strongly hindered amine (4c and
4d). Good yields were also obtained with 2-bromopyrazine, 2-
bromopyrimidine, and 3-bromothiophene (4h, 4 f, and 4i). Un-
fortunately, no reaction was observed with iminochlorides such
as 2-chloropyridine. Next, a representative series of cyclohexyl-
or piperidinyl-containing amines were used with different
steric bulk at the amino group (3t–x). As illustrated in Figure 4,
the reaction proceeded even with bulky a-branched primary
amines, but it is necessary to work at 508C to reach 60% yield
(3x–y). Interestingly, for substrates bearing both primary and
secondary amine moieties, only the primary amine reacted
(3za and 3zb).
Several other parameters were further evaluated including
different bases (Figure S3), various b-diketones (Figure S4), the
Cu/ligand ratio (Figure S5), the catalyst loading (Figure S5), the
molar ratio of the reducing agent (Figure S2), the surfactant
(Figure S6), the quantity of surfactant (Figure S7), and the at-
mosphere (Figure S8). On the basis of the results from all of
these experiments, a combination of Cu(OTf)2 (10 mol%), L1
(20 mol%), d-glucose (10 mol%), and NaOtBu (2 equiv.) was se-
lected as the best catalytic system to perform this Ullmann-
type amination at room temperature in an aqueous medium
supplemented with TPGS-750-M (2 wt%).
With the optimal conditions in hand, the scope of the reac-
tion was investigated with a diverse set of substituted amines
and aryl or heteroaryl bromides. The results are summarized in
Figure 4. The reaction was efficient for aryl bromides with
either electron-donating groups at the ortho (3ca), meta (3a,
3b, 3cb, and 3n), or para (3cc, 3d, and 3e) position or elec-
tron-withdrawing groups (3 f–m, 3o–q). For a bulky substitu-
ent at the ortho position of the aryl bromide (3ca), the reac-
As shown in Figure 4, our methodology is compatible with
free hydroxy functions. Starting from 4-bromobenzyl alcohol,
the N-coupling product with phenylpropylamine was formed
in 74% yield at RT (3d, 74%). The yield could be increased
slightly at 508C. Unfortunately, no reaction was observed with
3-aminopropanol, even in the presence of an excess of amine.
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Figure 4. Expanded scope of amination with aryl bromides. Reaction conditions : Cu(OTf)2 (10 mol%), L1 (20 mol%), d-glucose (10 mol%), NaOtBu (2 equiv.),
ArBr (1 equiv.), RNH2 (1.2 equiv.), TPGS-750-M (2 wt%), RT, 24 h. [a] Yields refer to isolated product. [b] Previously unreported products were characterized by
NMR spectroscopy and HRMS. [c] TPGS-750-M (5 wt%). [d] Reaction performed at 508C. [e] RNH2 (5 equiv.). [f] RNH2 (3 equiv.). [g] 22% of 3mb. n.r.: no reac-
tion.
The lack of reaction may be explained by the chelation of the
aminoalcohol to the copper center. To verify this hypothesis,
the same reaction was performed with 6-aminohexan-1-ol,
a higher homologue, and we were pleased to isolate the ex-
pected coupling product in a satisfactory yield (3sb, 60%). If
the alcohol was protected as an ether group, the desired prod-
uct 3sc was obtained with a moderate yield of 61%. No reac-
tion was observed with other amines such as anilines, secon-
dary amines, or benzamides. From 4-bromobenzonitrile, the
corresponding product 3i was formed in a yield of only 29%
owing to the poor solubility of the reactant. We overcame this
issue by using either 5 wt% of TPGS-750-M at RT or 2 wt% of
TPGS-750-M at 508C, which improved the yield to 87 and 71%,
respectively. The same conditions were applied with (3,4,5-tri-
fluorophenyl)methylamine (3gb), 2-bromopyridine (4a and
4b), and 5-bromopyrimide (4g) to overcome the solubility
issues. In contrast, for a highly water-soluble amine, such as
n-propylamine, an excess of amine was needed (5 equiv.) to
reach a yield of 67% (3r).
In the absence of surfactant, our model reaction was still
successful, and 75% yield was obtained instead of 85% with
TPGS-750-M (2%, see Figure S7). This important result shows
that this copper-catalyzed reaction is likely to occur in water
rather than inside the micelles. However, with crystalline
educts, the surfactant was crucial to help solubilize the reac-
tants in the aqueous medium and enhance the yield of the re-
action. This is particularly true for 3i, 4a, 4b, and 4g, for
which 5% of TPGS-750-M was required for optimal yield. To
demonstrate the efficacy of our catalytic system and thereby
its potential industrial application as a sustainable process, the
reaction was next attempted on a multigram scale. Thus,
5 mmol of 1b and 3-phenylpropylamine (2) in TPGS-750-M
(2 wt%) successfully led to 3b in 86% yield under our condi-
tions.
Finally, the kinetic parameters of this reaction were moni-
tored (Figure 5). Firstly, at 508C, the reaction with d-glucose as
the reducing agent was faster than that with NaAsc. Indeed,
after 30 min, 20% conversion was observed (purple), and the
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Figure 5. Kinetics of the reaction at RT and 508C with d-glucose and sodium ascorbate. Reaction conditions: Cu(OTf)2 (10 mol%), L1 (20 mol%), reducing
agent (10 mol%), NaOtBu (2 equiv.), 3-bromotoluene (1 equiv.), 3-phenylpropylamine (1.2 equiv.), TPGS-750-M (2 wt%), 508C or RT. [a] Average yield of two
runs. Yields were determined by HPLC with a UV detector and benzophenone as an external standard.
conversion reached 60% after 2 h. In contrast, with NaAsc, a la-
tency time of 4 h was necessary before the formation of 3b
(orange). It is notable that the conversion rate after this latency
time is similar to the rate observed for the reaction with
d-glucose. Interestingly, a latency time of 6 h was also ob-
served (green) if the reaction was performed with d-glucose at
room temperature. We hypothesized that this period is re-
quired to reduce the inactive CuII species into the active CuI
species. This induction period might also suggest the forma-
tion of nanoparticles as the active catalysts for two reasons:
(1) A CÀN cross-coupling reaction was achieved recently with
copper nanoparticles[22] as a catalyst.
(2) d-Glucose is an excellent reducing agent for the formation
of copper nanoparticles in water.[23]
However, different experiments performed in our laboratory
invalidated this hypothesis (see Supporting Information, pp.
S12–S13).
Scheme 1. Proposed mechanism of the copper cross-coupling reaction in
the presence of d-glucose.
Finally, a reasonable mechanism has been proposed to ex-
plain the different observations described in the Supporting In-
formation (see pp. S14–S15). The CuI species is generated
in situ from the CuII species and d-glucose. The nucleophilic
substitution of the CuI species by the amine leads to the for-
mation of [CuINu] (intermediate A). The oxidative addition of
the aryl halide to intermediate A then generates a transient
CuIII species (B). Finally, the CÀN bond is formed by reductive
elimination from B to form the target compound and regener-
ate the initial CuI species (Scheme 1).
simple, yet robust and cheap. The use of renewable feedstocks
(d-glucose and TPGS-750-M, which is composed of vitamin E),
the absence of organic solvent, and the economy of energy
make these conditions environmentally friendly and adaptable
to industrial production. This easy-to-handle procedure is ex-
tremely competitive compared to palladium-based reactions
and may be used to synthesize N-containing molecules such
as drugs or organic light-emitting diodes (OLEDs).
Experimental Section
Conclusions
General procedure
We have developed the first Ullmann-type reaction at low tem-
perature [room temperature (RT) or 508C] under micellar con-
ditions for primary aliphatic amines. These mild conditions are
The amine (1.2 equiv.) and aryl or heteroaryl halide (1 equiv.) were
added to an aqueous solution of TPGS-750-M (2 wt%,
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1 mLmmolÀ1). The mixture was degassed with bubbling argon
(5 min). NaOtBu (97% purity, 2 equiv.), Cu(OTf)2 (10%), dipivaloyl-
methane (20%), and d-glucose (10%) were added, and the result-
ing mixture was stirred (at 1200 rpm) at RT or 508C (20 h). The mix-
ture was extracted twice with ethyl acetate (3 mL). The combined
organic layers were evaporated, and the crude residue was purified
by silica gel column chromatography with n-heptane and ethyl
acetate as the eluent.
e) M. Negwer, H.-G. Scharnow, Organic-Chemical Drugs and Their Syno-
nyms, Wiley-VCH, Weinheim, 2001; f) T. Eicher, S. Hauptmann, A. Speich-
er, The Chemistry of Heterocycles: Structures, Reactions, Synthesis and Ap-
plications, 3rd ed., Wiley-VCH, Weinheim, 2012; g) S. D. Roughley, A. M.
Jordan, J. Med. Chem. 2011, 54, 3451–3479; h) M. S. Butler, J. Nat. Prod.
2004, 67, 2141–2153.
[11] P. Wagner, M. Bollenbach, C. Doebelin, F. Bihel, J.-J. Bourguignon, C.
Salomꢀ, M. Schmitt, Green Chem. 2014, 16, 4170–4178.
[12] C. Reichardt, T. Welton, Solvents and Solvent Effects in Organic Chemistry,
Wiley-VCH, Weinheim, 2010, pp. 65–106.
[13] a) C. Sambiagio, S. P. Marsden, A. J. Blacker, P. C. McGowan, Chem. Soc.
Rev. 2014, 43, 3525–3550; b) F. Monnier, M. Taillefer, Angew. Chem. Int.
Ed. 2009, 48, 6954–6971; Angew. Chem. 2009, 121, 7088–7105; c) F.
Monnier, M. Taillefer in Topics in Organometallic Chemistry Vol. 46: Ami-
nation and Formation of sp2 CÀN Bonds (Eds.: M. Taillefer, D. Ma), Spring-
er, Berlin, 2013, pp. 173–204; d) G. Evano, N. Blanchard, Copper-Mediat-
ed Cross-Coupling Reactions, Wiley, Hoboken, 2014; e) S. Buchwald, A.
Klapars, J. Antilla, G. Job, M. Wolter, F. Kwong, G. Nordmann, E. Hennes-
sy, Copper-Catalyzed Formation of Carbon–Heteroatom and Carbon–
Bonds, WO02085838 (A1), 2002; f) H.-J. Cristau, C. Bouchitte, M. Taillefer,
J.-F. Spindler, T. Schlama, Method for Preparing a Polyaromatic Com-
pound, WO0158834 (A1), 2001.
N-Benzyl-3-methylaniline (3a)
Compound 3a was prepared by the general procedure with
Cu(OTf)2 (18.0 mg, 0.050 mmol), dipivaloylmethane (20.9 mL,
0.100 mmol), d-glucose (9.0 mg, 0.050 mmol), 3-bromotoluene
(60.6 mL, 0.500 mmol), benzylamine (65.6 mL, 0.600 mmol), and
NaOtBu (99 mg, 1.00 mmol) in aqueous TPGS-750-M (2 wt%,
0.50 mL), followed by purification by column chromatography
(SiO2) with n-heptane/ethyl acetate (95:5), to yield 3a as a yellow
1
oil (81 mg, 82%). H NMR (400 MHz, CDCl3) d=2.30 (s, 3H), 3.90–
4.06 (br s, 1H), 4.34 (s, 2H), 6.46–6.59 (m, 3H), 7.09 (t, J=7.5 Hz,
1H), 7.27–7.41 ppm (m, 5H); 13C NMR (100 MHz, CDCl3) d=21.7,
48.4, 110.0, 113.6, 118.6, 127.2, 127.6, 128.6, 129.2, 139.1, 139.6,
148.3 ppm.
[14] M. Taillefer, H. J. Cristau, P. Cellier, J. F. Spindler, Formation of Carbon– or
Carbon–Heteroatom Bonds Comprises Reaction of an Unsaturated Com-
pound with a Nucleophile in the Presence of a Metal–Bidentate Ligand
Catalyst, FR2833947 (A1), 2003.
[15] a) D. Wang, F. Zhang, D. Kuang, J. Yu, J. Li, Green Chem. 2012, 14, 1268–
1271; b) C. Mukhopadhyay, P. K. Tapaswi, R. J. Butcher, Org. Biomol.
Chem. 2010, 8, 4720–4729; c) F.-F. Yong, Y.-C. Teo, S.-H. Tay, B. Y.-H. Tan,
K.-H. Lim, Tetrahedron Lett. 2011, 52, 1161–1164; d) S. Liu, J. Zhou, New
J. Chem. 2013, 37, 2537–2540; e) Y. Wang, Z. Wu, L. Wang, Z. Li, X.
Zhou, Chem. Eur. J. 2009, 15, 8971–8974; f) J. Peng, M. Ye, C. Zong, F.
Hu, L. Feng, X. Wang, Y. Wang, C. Chen, J. Org. Chem. 2011, 76, 716–
719; g) K. Swapna, S. N. Murthy, Y. V. D. Nageswar, Eur. J. Org. Chem.
2010, 6678–6684; h) X. Li, D. Yang, Y. Jiang, H. Fu, Green Chem. 2010,
12, 1097–1105; i) Z.-J. Liu, J.-P. Vors, E. R. F. Gesing, C. Bolm, Green Chem.
2011, 13, 42–45; j) L. Liang, Z. Li, X. Zhou, Org. Lett. 2009, 11, 3294–
3297; k) J. Engel-Andreasen, B. Shimpukade, T. Ulven, Green Chem.
2013, 15, 336–340; l) X. Zhu, L. Su, L. Huang, G. Chen, J. Wang, H.
Song, Y. Wan, Eur. J. Org. Chem. 2009, 635–642; m) S. Rçttger, P. J. R.
Sjçberg, M. Larhed, J. Comb. Chem. 2007, 9, 204–209; n) J. Jiao, X.-R.
Zhang, N.-H. Chang, J. Wang, J.-F. Wei, X.-Y. Shi, Z.-G. Chen, J. Org.
Chem. 2011, 76, 1180–1183; o) Z. Quan, H. Xia, Z. Zhang, Y. Da, X.
Wang, Chin. J. Chem. 2013, 31, 501–506.
[16] Z.-J. Quan, Q. Xu, Z. Zhang, Y.-X. Da, X.-C. Wang, Tetrahedron 2013, 69,
881–887.
[17] Z.-J. Quan, H.-D. Xia, Z. Zhang, Y.-X. Da, X.-C. Wang, Tetrahedron 2013,
69, 8368–8374.
[18] M. Martinek, M. Korf, J. Srogl, Chem. Commun. 2010, 46, 4387.
[19] S. K. Guchhait, A. L. Chandgude, G. Priyadarshani, J. Org. Chem. 2012,
77, 4438–4444.
[20] A. Monopoli, V. Calꢂ, F. Ciminale, P. Cotugno, C. Angelici, N. Cioffi, A.
Nacci, J. Org. Chem. 2010, 75, 3908–3911.
Keywords: amination · amines · carbohydrates · copper ·
micelles
[1] a) Transition Metals for Organic Synthesis (Eds.: M. Beller, C. Bolm), Wiley-
VCH, Weinheim, 1998; b) Transition Metals for Organic Synthesis (Eds.:
M. Beller, C. Bolm), Wiley-VCH, Weinheim, 2004.
[2] R. A. Sheldon, I. W. C. E. Arends, U. Hanefeld, Green Chemistry and Catal-
ysis, Wiley-VCH, Weinheim, 2007.
[3] a) M.-O. Simon, C.-J. Li, Chem. Soc. Rev. 2012, 41, 1415–1427; b) A.
Chanda, F. F. Fokin, Water in Organic Synthesis, Georg Thieme, Stuttgart,
2012; c) J. M. DeSimone, Science 2002, 297, 799–803; d) S. Narayan, J.
Muldoon, M. G. Finn, V. V. Fokin, H. C. Kolb, K. B. Sharpless, Angew.
Chem. Int. Ed. 2005, 44, 3275–3279; Angew. Chem. 2005, 117, 3339–
3343.
[4] a) B. H. Lipshutz, S. Ghorai, A. R. Abela, R. Moser, T. Nishikata, C. Duplais,
A. Krasovskiy, R. D. Gaston, R. C. Gadwood, J. Org. Chem. 2011, 76,
4379–4391; b) B. H. Lipshutz, S. Ghorai, Org. Lett. 2009, 11, 705–708;
c) B. H. Lipshutz, G. T. Aguinaldo, S. Ghorai, K. Voigtritter, Org. Lett. 2008,
10, 1325–1328; d) B. H. Lipshutz, S. Ghorai, Aldrichimica Acta 2008, 41,
59–72; e) B. H. Lipshutz, S. Ghorai, Aldrichimica Acta 2012, 45, 3–16;
f) B. H. Lipshutz, S. Ghorai, W. W. Y. Leong, B. R. Taft, D. V. Krogstad, J.
Org. Chem. 2011, 76, 5061–5073.
[5] a) B. H. Lipshutz, T. B. Petersen, A. R. Abela, Org. Lett. 2008, 10, 1333–
1336; b) T. Nishikata, B. H. Lipshutz, J. Am. Chem. Soc. 2009, 131, 12103–
12105; c) N. A. Isley, F. Gallou, B. H. Lipshutz, J. Am. Chem. Soc. 2013,
135, 17707–17710.
[6] B. H. Lipshutz, B. R. Taft, Org. Lett. 2008, 10, 1329–1332.
[7] B. H. Lipshutz, D. W. Chung, B. Rich, Org. Lett. 2008, 10, 3793–3796.
[8] a) B. H. Lipshutz, D. W. Chung, B. Rich, Adv. Synth. Catal. 2009, 351,
1717–1721; b) N. A. Isley, S. Dobarco, B. H. Lipshutz, Green Chem. 2014,
16, 1480–1488.
[21] N. Anand, T. Chanda, S. Koley, S. Chowdhury, M. S. Singh, RSC Adv. 2015,
5, 7654–7660.
[22] a) M. B. Gawande, A. Goswami, F.-X. Felpin, T. Asefa, X. Huand, R. Silva,
X. Zou, R. Zboril, R. S. Varma, Chem. Rev. 2016, 116, 3722–3811; b) A. R.
Hajipour, F. Dordahan, F. Rafiee, M. Mahdavi, Appl. Organomet. Chem.
2014, 28, 809–813.
[23] a) M. Sabbaghan, J. Beheshtian, R. N. Liarjdame, Mater. Lett. 2015, 153,
1–4; b) J. Mondal, A. Biswas, S. Chiba, Y. Zhao, Sci. Rep. 2015, 5, 8294.
[9] C. Salomꢀ, P. Wagner, M. Bollenbach, F. Bihel, J.-J. Bourguignon, M.
Schmitt, Tetrahedron 2014, 70, 3413–3421.
[10] a) G. Evano, M. Toumi, A. Coste, Chem. Commun. 2009, 4166–4175;
b) G. Evano, N. Blanchard, M. Toumi, Chem. Rev. 2008, 108, 3054–3131;
c) T. P. Bender, J. F. Graham, J. M. Duff, Chem. Mater. 2001, 13, 4105–
4111; d) H. B. Goodbrand, N.-X. Hu, J. Org. Chem. 1999, 64, 670–674;
Received: June 15, 2016
Published online on && &&, 0000
&
ChemSusChem 2016, 9, 1 – 7
www.chemsuschem.org
6
ꢁ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!

FULL PAPERS
A spoonful of sugar: A low-tempera-
ture Ullmann-type reaction under micel-
lar conditions in water is developed for
the coupling of primary aliphatic
M. Bollenbach, P. Wagner, P. G. V. Aquino,
J.-J. Bourguignon, F. Bihel, C. Salomꢀ,
M. Schmitt*
&& – &&
amines. The use of renewable feed-
stocks (d-glucose and the surfactant
TPGS-750-M, which is composed of vita-
min E), the absence of organic solvent,
and the economy of energy make these
conditions environmentally friendly and
adaptable to industrial production.
d-Glucose: An Efficient Reducing
Agent for a Copper(II)-Mediated
Arylation of Primary Amines in Water
ChemSusChem 2016, 9, 1 – 7
www.chemsuschem.org
7
ꢁ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
These are not the final page numbers! ÞÞ