Impregnated copper on magnetite as recyclable catalyst for the addition of alkoxy diboron reagents to C-C double bonds

Article abstract of DOI:10.1021/jo100325e

A simple protocol for the borylation with use of impregnated copper on magnetite is described. The reactions showed a very broad scope and all type of olefins could be used with similar results. The catalyst could be easily removed by a magnet and it could be reused several times, showing similar activity.

Full text of DOI:10.1021/jo100325e

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shown its high potential and versatility in organic synthesis,
Impregnated Copper on Magnetite as Recyclable
Catalyst for the Addition of Alkoxy Diboron
Reagents to C-C Double Bonds
providing a great variety of useful functionalized com-
pounds.2 A special case is the hydroborylation of simple
olefins,3 as well as of electron-deficient ones,4 using alkoxy
diboron reagents. This conjugate borylation has been carried
out with either an organocatalyzed approach5 or different
metal complexes, such as nickel,6 rhodium,7 palladium,6b
and platinum,8 with copper complexes being the most em-
ployed ones.9,10 Besides of the indisputable success of the
copper complexes some aspects of this reaction still remain
which could be improved, including the high catalyst loading
(3-110 mol %), narrow substrate scope, high reaction
temperatures, presence of labile phosphine ligands, and
overall, the nonrecyclability of catalyst in known protocols.
In the course of our studies on the use of magnetite as
catalyst11 or as privileged support12 in organic synthesis, we
ꢀ
Rafael Cano, Diego J. Ramon,* and Miguel Yus*
´
Instituto de Sıntesis Organica (ISO) and Departamento de
ꢀ
Quımica Organica, Facultad de Ciencias, Universidad de
´
ꢀ
Alicante, Apdo. 99, E-03080-Alicante, Spain
djramon@ua.es; yus@ua.es
Received February 22, 2010
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A simple protocol for the borylation with use of impreg-
nated copper on magnetite is described. The reactions
showed a very broad scope and all type of olefins could be
used with similar results. The catalyst could be easily
removed by a magnet and it could be reused several times,
showing similar activity.
(9) (a) Takahashi, K.; Ishiyama, T.; Miyaura, N. Chem. Lett. 2000, 982–
983. (b) Ito, H.; Yamanaka, H.; Tateiwa, J.-i.; Hosomi, A. Tetrahedron Lett.
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Lett. 2006, 8, 4887–4889. (e) Lee, J.-E.; Yun, J. Angew. Chem., Int. Ed. 2008,
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Sim, H.-S.; Feng, X.; Yun, J. Chem.;Eur. J. 2009, 15, 1939–1943. (i) Lillo,
Organoboronic acid derivatives are of great importance in
organic synthesis, not only for their own special characteristics
and activities but also as organometallic key reagents in many
syntheses, such as in the well-established cross-coupling proto-
cols. Classically, they are prepared by the treatment of trialkyl
borates with a magnesium or lithium organometallic reagent.
However, this approach is restricted to substrates either with-
out additional functional groups or with those compatible with
the highly nucleophilic carbanionic center. These limitations
have forced the development of new approaches to prepare this
type of compound with highly reactive functionalities, such as
Brønsted acid or electrophilic functionalities.1
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(10) For recent examples hydroboration of electron-rich olefins with
diboron reagents, see: (a) Lee, Y.; Hoveyda, A. H. J. Am. Chem. Soc.
2009, 131, 3160–3161. (b) Noh, D.; Chea, H.; Ju, J.; Yun, J. Angew. Chem.,
Int. Ed. 2009, 48, 6062–6064.
Among the different ways to prepare organoboronate
derivatives, the catalytic addition of diboron reagents to
alkenes (or alkynes) via metal-boryl intermediates has
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1235–1240. (b) Mojtahedi, M. M.; Abaee, M. S.; Eghtedari, M. Appl.
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(1) (a) Mikhailov, B. M.; Bubnov, Y. N. Organoboron Compounds in Organic
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Stuttgart, Germany, 2005; Vol. 6, pp 677-696.
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3458 J. Org. Chem. 2010, 75, 3458–3460
Published on Web 04/21/2010
DOI: 10.1021/jo100325e
r
2010 American Chemical Society

Cano et al.
JOCNote
TABLE 1. Screening of the Reaction Conditions
FIGURE 1. Yields of compound 3a after several cycles.
entry
cat. (mol %)
Fe3O4 (86)
base (mol %)
solv.
t (h) yield (%)a
1
2
3
4
5
6
7
8
9
tBuOK (9)
THF
168
0
85
0
TABLE 2. Impregnated Copper Catalyzes the Michael-Type
Borylation Process
Cu(OH)x-Fe3O4 (5) tBuOK (9)
Cu(OH)x-Fe3O4 (5) tBuOK (9)
Cu(OH)x-Fe3O4 (5) tBuOK (9)
Cu(OH)x-Fe3O4 (5) tBuOK (9)
Cu(OH)x-Fe3O4 (5) tBuOK (9)
Cu(OH)x-Fe3O4 (5) tBuOK (9)
Cu(OH)x-Fe3O4 (5) tBuOK (9)
Cu(OH)x-Fe3O4 (5) tBuOK (9)
THF
4
48
4
THFb
THFc
THFd
MeOH
DMSO
MeCN
PhMe
PhMe
PhMe
PhMe
PhMe
75
85
70
40
60
86
30
90
20
93
40
64
95
82
99
55
0
4
4
4
4
4
10e Cu(OH)x-Fe3O4 (5) tBuOK (9)
11 Cu(OH)x-Fe3O4 (5) tBuOK (90)
12 Cu(OH)x-Fe3O4 (5)
4
0.5
24
0.5
entry
R
EWG
compd
yield (%)a
13 Cu(OH)x-Fe3O4 (5) KOH (90)
14 Cu(OH)x-Fe3O4 (5) (NH4)2CO3 (90) PhMe
0.5
0.5
0.5
0.5
0.25
0.5
1
2
3
4
5
6
7
8
Ph
H
Ph
Ph
Ph
Ph
CH2OCO
(CH2)3CO
CONH2
CONH2
COOEt
CN
COMe
COPh
3a
3b
3c
3d
3e
3f
99
99b
91
99
99
98
93
99
15 Cu(OH)x-Fe3O4 (5) Na2CO3 (90)
16 Cu(OH)x-Fe3O4 (5) K2CO3 (90)
17 Cu(OH)x-Fe3O4 (5) Cs2CO3 (90)
18 Cu(OH)x-Fe3O4 (2.5) K2CO3 (90)
19 Cu(OH)x-Fe3O4 (0.5) K2CO3 (90)
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
20
K2CO3 (90)
48
3g
3h
aIsolated yield after crystallization from CH2Cl2-hexane. bReaction
performed in the absence of MeOH. cReaction performed at 25 °C.
dReaction performed at 110 °C. eReaction performed with only 20 mol %
of MeOH.
aIsolated yield. bReaction performed for 16 h.
the previous results, with toluene giving only a marginal
improvement (see entries 6-9). Under these new reaction
conditions, whereas the reduction of the amount of either
MeOH or base decreased the yield, the increase of the
amount of base had a beneficial effect (compare entries
9-12). After that, the nature of base was tested, finding that
potassium carbonate gave the best result (compare entries
13-17). Finally, the amount of catalyst was tested, finding
that a 50% reduction had a beneficial effect, obtaining the
expected compound 3a in practically quantitative yield
after only 15 min of reaction. Meanwhile, a further decrease
of the catalyst amount produced lower yield, even in longer
reaction times (see entries 18 and 19). Finally the reaction in
the absence of catalyst failed after 2 days of reaction time
(entry 20).
Once the catalytic activity of the impregnated copper on
magnetite was demonstrated, we faced the problem of its
reuse, finding that the chemical yields were practically con-
stant in a range between 88% and >99%, after 8 cycles of
reaction, for the preparation of compound 3a (Figure 1),
with the catalyst being maintained inside the flask only by the
help of a magnet.
investigated the reaction of bis(pinacolato)diboron (1) with
cinnamamide (2a) to give the corresponding benzyl boronic
derivatives 3a (Table 1). We decided to start our study using
amides as the electrophilic partner since this type of substrate
has been scarcely used in similar reactions. In fact, there is
only one example with cinnamamide as substrate and equi-
molecular amounts of CuCl and 1,2-bis(diphenylphosphino)-
benzene as the catalytic system.9k Moreover, this substrate
is a very bad Michael-acceptor compared with other
R,β-unsaturated compounds and has two acid protons,
which could impede the nucleophilic attack of basic sub-
strates. The initial reaction with a small excess of compound
1 (140 mol %) failed after 1 week at 60 °C in THF with use of
only magnetite. However, the reaction performed with im-
pregnated copper on magnetite gave the expected product in
good yield (Table 1, entry 2). It should be pointed out that a
similar protocol but with pinacolborane failed, recovering
the starting amide 2a unchanged. The catalyst was easily
prepared by a basic precipitation-adsorption of an aqueous
solution of copper chloride on the surface of commercially
available magnetite (powder <5 μm) leading to the incor-
poration of 1.37-1.62% of Cu according to X-ray fluore-
scence (BET area: 9.15 m2 g-1).12d
Once the catalytic activity and its recyclability was proved,
the scope of the reaction was tested (Table 2), finding
excellent results for the reaction independently of the nature
of substituents in the alkene 2. The reaction could be
performed with substituted and unsubstituted R,β-unsatu-
rated carboxamides (entries 1 and 2), with other acid deri-
vatives such as an ester and a nitrile (entries 3 and 4), even
with ketones (entries 5 and 6) giving similar results. The
Once the activity of the catalyst was demonstrated, differ-
ent parameters of the reaction were optimized. The reaction
failed in the absence of methanol (Table 1, entry 3), and the
results at higher or lower temperatures did not change
significantly (compare entries 2, 4, and 5). Other solvents
used such as MeOH, DMSO, or MeCN did not improve
J. Org. Chem. Vol. 75, No. 10, 2010 3459

Cano et al.
JOCNote
SCHEME 1. Impregnated Copper Catalyzes the Borylation
of Olefins
use of a softbase inclearcontrastwiththe previous bases used.
All these facts, together with the simplicity of the protocol, the
wide scope of substrates, and their simple recycling permitted
us to anticipate a good future for the process shown in this
paper not only in the laboratory but also in industry.
Experimental Section
To a stirred solution of bis(pinacolato)diboron (1, 0.7 mmol,
178 mg) in toluene (0.5 mL) under argon atmosphere were added
Cu(OH)x/Fe3O4 (50 mg), K2CO3 (0.45 mmol, 62 mg), the
R,β-unsaturated compound or olefin (0.5 mmol) and MeOH
(1 mmol, 40 μL). The resulting mixture was stirred at 60 °C until
the end of the reaction. The catalyst was removed by a magnet
and the resulting mixture was quenched with a saturated solution
of NH4Cl and extracted with AcOEt. The organic phases were
dried over MgSO4, followed by evaporation under reduced
pressure to remove the solvent. The product was usually purified
by chromatography on silica gel (hexane/ethyl acetate). Physical
and spectroscopic data for the representative compound 3b
follow:
3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)propanamide
(3b): mp 184-188 °C; IR (KBr) ν 3418, 1676, 1549, 1315, 1115
cm-1; 1H NMR (300 MHz, CDCl3) δ 1.05 (t, J = 7.5 Hz, 2H),
1.25 (s, 12H), 2.37 ppm (t, J = 7.4 Hz, 2H), 5.3-5.5, 5.5-5.7 (2
br s, 1 and 1H, respectively); 13C NMR (300 MHz, CDCl3, C
attached to quadrupole B not observed) δ 24.8, 30.2, 83.3, 176.3
ppm; EI-MS m/z 184 (10), 141 (94), 140 (100), 139 (197), 100
(25), 99 (15), 84 (20), 83 (16), 55 (10). Anal. Calcd for
C9H18BNO3: C, 54.30; H, 9.11; N, 7.04. Found: C, 54,32; H,
9.09; N, 6.98.
yields obtained for cyclic compounds 2 were similar to those
obtained for acyclic ones (entries 7 and 8). In all cases yields
were higher than 90%.
Finally, we faced the problem of using simple olefins 4,
and gratifyingly the reaction gave selectively only (or mainly,
>95%) one regioisomer 5 (see Scheme 1). In the case of
product 5c, the low yield was due to the presence of a small
amount of the diborylation product (<15%) and the star-
ting chlorinated compound 4, with dehalogenated byproduct
not being detected. The above protocol could be used only by
increasing the reaction time from a few hours to days.
Although the possible mechanism for this process is not
clear, we believe that the reaction goes through the formation
of the corresponding copper-boryl intermediate, as was
pointed out earlier.9g This intermediate adds to the olefin
to give the most stable anionic intermediate in both cases,
with the protonation of enolic or benzylic intermediate
liberating the copper salt.
In conclusion, impregnated copper on magnetite is an
excellent catalyst for the borylation of any type of olefin in
the absence of expensive and difficult to handle phosphines,
and with one of the lowest catalyst loadings. The catalyst is
easily removed from the reaction media just by the use of a
simple magnet, and it could be reused several times without
losing its initial activity. The reaction conditions implied the
Acknowledgment. This work was supported by the
Spanish Ministerio de Ciencia y Tecnologıa (Consolider
Ingenio 2010 CSD2007-00006, CTQ2007-65218/BQU) and
by Generalitat Valenciana (G.V. PROMETEO/2009/039).
R.C. thanks to G.V. for a fellowship through the PROMETEO
program.
Supporting Information Available: Characterization and
copies of 1H and 13C for all compounds 3 and 5. This material is
available free of charge via the Internet at http://pubs.acs.org.
3460 J. Org. Chem. Vol. 75, No. 10, 2010