Novel cross-coupling reactions between organotellurides and Grignard reagents employing a MnCl2/CuI catalytic system

Article abstract of DOI:10.1016/j.tetlet.2012.04.134

We present a general protocol for the cross-coupling reaction of Grignard reagents and organic tellurides. Aryl Grignard reagents react stereospecifically with vinyl tellurides in the presence of a catalytic amount of manganese (II) chloride and copper (I) iodide to produce good yields of the corresponding cross-coupling products.

Full text of DOI:10.1016/j.tetlet.2012.04.134

Tetrahedron Letters 53 (2012) 3556–3559
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Novel cross-coupling reactions between organotellurides and Grignard
reagents employing a MnCl2/CuI catalytic system
Marcio S. Silva a, Renan S. Ferrarini a, Bruno A. Sousa a, Fabiano T. Toledo a, João V. Comasseto a,
,
⇑
Rogério A. Gariani b,
⇑
a Instituto de Química, Universidade de São Paulo, Av. Professor Lineu Prestes, 748, Cx.P. 26077, CEP: 05508-000 São Paulo, Brazil
b GAPAM, Departamento de Química, Universidade do Estado de Santa Catarina, R. Paulo Malschitzki, S/N, CEP: 89219-710 Santa Catarina, Brazil
a r t i c l e i n f o
a b s t r a c t
Article history:
We present a general protocol for the cross-coupling reaction of Grignard reagents and organic tellurides.
Aryl Grignard reagents react stereospecifically with vinyl tellurides in the presence of a catalytic amount
of manganese (II) chloride and copper (I) iodide to produce good yields of the corresponding cross-cou-
pling products.
Received 13 March 2012
Revised 27 April 2012
Accepted 29 April 2012
Available online 3 May 2012
Ó 2012 Published by Elsevier Ltd.
Keywords:
Manganese (II) chloride
Cross-coupling reaction
Organometallic reagents
Catalysis
Organic tellurides
Introduction
development and the synergism between MnCl2 and CuI remains
unclear.7,8
Over the past two decades, organotellurium compounds have
been the focus of a large number of studies. Some of these com-
pounds have proven to be valuable synthetic intermediates.1,2
Most of the methods that lead to the formation of carbon–carbon
bonds from organotellurium compounds are stoichiometric pro-
cesses and involve Te/metal exchange reactions,3 leading to a reac-
tive organometallic intermediate, like organolithium4 or
organocopper5 reagents. Recently, the use of iron salts to replace
palladium or nickel complexes as catalysts has emerged as a very
promising area for sustainable development. From both economic
and environmental standpoints, manganese salts can be a valuable
alternative in metallic catalysis.6
From the perspective of green chemistry, the development of
catalytic methods to promote carbon–carbon bond formation is
not only environmentally friendly but also of great importance
for synthetic methods. In this context, manganese salts are rela-
tively cheap and nontoxic and can be used as an alternative
catalyst to replace or complement the well established palladium
or nickel complexes.6,7 However, the chemistry of manganese-
catalyzed cross-coupling reactions is still in its early stage of
Results and discussion
We report here the cuprous iodide/manganese chloride cata-
lyzed cross-coupling reaction of vinyl tellurides with aryl Grignard
reagents. Initially, we screened different reaction conditions to
evaluate the influence of the corresponding salts in the catalytic
system. The use of CuI in this system is empirical, since the mech-
anism of the reaction is not known and Cu(I) salts are known as
good co-catalytic reducing agents in metal-catalyzed reactions.
The solvent and the temperature remained the same, and the
amounts of MnCl2 and CuI were varied as described in Table 1 (en-
tries 1–9).
Searching for better conditions to perform the coupling reac-
tion, we then tested several different compositions of the MnCl2/
CuI catalytic system and PhMgCl. Initially the reaction was per-
formed in the absence of MnCl2 and subsequently in the absence
of CuI (Table 1, entries 2 and 3). The results showed that MnCl2
has a small influence in the conversion of 1 into 2 while copper salt
appears have an important role in this reaction, leading to a higher
yield. When 20 mol % of both salts were employed, the resulting
conversion was acceptable but still inconclusive about the effect
of the combination of both salts (entry 4). In comparison to entry
4, the yield was slightly increased when 1 equiv of each salt was
used (entry 1).
⇑
Corresponding authors. Tel.: +55 11 3091 1180 (J.V.C.), +55 47 4009 7840
(R.A.G.).
E-mail addresses: jvcomass@iq.usp.br (J.V. Comasseto), dqm2rag@joinville.
udesc.br (R.A. Gariani).
0040-4039/$ - see front matter Ó 2012 Published by Elsevier Ltd.
http://dx.doi.org/10.1016/j.tetlet.2012.04.134

M. S. Silva et al. / Tetrahedron Letters 53 (2012) 3556–3559
3557
Table 1
Initial screening for the reaction conditionsa
Te
O
1
O
2
E
MnCl2 / CuI
PhMgCl
O
Ph
O
Z
THF, temp.
Entry
MnCl2 (mol %)
CuI (mol %)
PhMgCl (mmol)
T (°C)
Yield of 2a (%)
1
2
3
4
5
6
7
8
9
100
20
—
20
10
10
5
100
—
2.0
2.0
2.0
2.0
2.0
1.5
1.5
1.1
1.1
0
0
0
0
0
0
0
0
rt
65
10
30
45
50
55
51
78
48
20
20
10
10
5
5
5
5
5
a
All the reactions were conducted under anhydrous nitrogen atmosphere.
The decrease in the amount of salts and of the Grignard reagent
The homo-coupling by-product (Ph–Ph) was also observed, and
despite the impairment, no bad smelling compounds were in-
volved during the workup, even with the presence of
butyl(phenyl)tellane or any other organic telluride that might be
formed in small amounts.
The developed strategy was applied to the coupling of telluride
3, in which the double bond was not capable of isomerization,
leading to the formation of the coupling product 4 in a modest
yield (Table 2, entry 2). On the other hand, when the alcohol 5
was submitted to the same conditions, the expected coupling prod-
uct 6 was not observed.
(Table 1, entries 5, 6 and 7) resulted in a small increment in the yield.
Reduction of the amount of the Grignard reagent was the most
important parameter (Table 1, entries 5 and 6). The next experiment
was designed based on a nearly equimolar addition (1.1 equiv) rel-
ative to substrate 1 (entry 8). This experiment again provided a sig-
nificant yield increment, showing that the most important
parameter in the reaction is the molarity of the Grignard reagent.
However, the highest yields were obtained when smaller
amounts of both salts were employed. More specifically, the best
result was achieved when 5 mol % of both salts were used at 0 °C,
and with a smaller excess of the Grignard reagent (entry 8). There
is also no increase in the conversion when the reaction was con-
ducted at room temperature (entry 9). Coupling of 1 with PhMgCl
gave the expected product 2, but the reaction was not stereoreten-
tive, leading to the total inversion of the double bond configuration
to the E isomer, a fact that was also observed by Uemura.9
In order to extend this methodology, different tellurides were
prepared and submitted to the optimal condition found in Table
1, leading to the expected coupling products in a single isomer Z
(except for Table 2, entry 1), in good yields.
As reported in the literature, halogenoenynes have also been
studied as substrates for Mn-catalyzed cross-coupling reactions.10
Table 2
Cross coupling reaction of tellurides with PhMgCl
MnCl2 (5 mol %)
CuI (5 mol %)
nBuTe
R1
R3
R2
Ph
R1
R3
R2
PhMgCl (1.1 eq.)
THF, 0 ˚C - r.t.
Entry Telluride
Product
Yield Entry Telluride
Product
OTHP
Yield Entry Telluride
Product
Yield
0%
O
TenBu
O
OTHP
TenBu
N
Ph
18
EtO
Ph
TenBu
Ph
52%
1
2
78%
60%
5
6
9
EtO
N
9
10
2
4
1
17
TenBu
O
O
Ph
Ph
TenBu Ph
Ph
Ph
Ph
78% 10
45%
60%
19
20
TenBu
TenBu
Ph
11
12
3
OH
TenBu
Ph
OH
OH
OH
Ph
Ph
TenBu Ph
OEt O
Ph
OEt
3
4
0%
7
8
62%* 11
13
14
Ph
O
21
22
5
6
OMe
OMe
N
OH
OH
O
N
7
TenBu O
N
Ph
N
N
N
TenBu Ph
OEt
Ph
8
79%
56% 12
50%
MeO
N
TenBu MeO
N
Ph
O
O
OEt
23
24
16
15
All the reactions were performed in a 1 mmol scale, under anhydrous nitrogen atmosphere and at the same temperature (see Experimental Section/Supplementary data).
*
Yield determined by GC.

3558
M. S. Silva et al. / Tetrahedron Letters 53 (2012) 3556–3559
Table 3
double bond geometry for compound 24. Likewise, a strong NOE
Cross coupling reaction with telluride and p-XPhMgCl
between the b-proton and the methine aldol 22 was also observed.
We also evaluated the scope of the corresponding catalyzed
cross-coupling reaction in the presence of Grignard reagents bear-
ing a methoxyl as an electron donating group (EDG) and a fluoro as
an electron withdrawing group (EWG), employing both tellurides 1
and 23, as shown in Table 3.
X
MnCl2 (5 mol %)
nBuTe
R3
R2
CuI (5 mol %)
R3
R2
p-X-PhMgCl
R1
R1
THF, 0 ˚C - r.t.
The results in Table 3 above show that both electron withdraw-
ing and electron donating groups can be employed in this method-
ology, leading to the expected products in reasonable yields.
However, for a detailed discussion of the influence of these substit-
uents, a mechanistic approach should be considered.
Entry Telluride
nBuTe
x
F
Product
Yield
81%
O
O
OEt
1
O
25
1
F
Conclusions
O
OEt
2
OMe
58%
54%
In conclusion, the reaction of vinyl tellurides with organomag-
nesium compounds catalyzed by MnCl2/CuI provides a reasonable
alternative to coupling reactions that makes use of the more
expensive and toxic palladium and nickel compounds as catalysts.
Further studies of the presented cross-coupling reaction promoted
by MnCl2 will be reported in due course.
26
MeO
F
OH
OH
nBuTe
3
4
F
O
OEt
23
O
OEt
27
OH
Experimental section
OMe
69%
Typical procedure for coupling reaction: (E)-ethyl cinnamate (2).
To a suspension of MnCl2 (6.3 mg, 0.05 mmol) and CuI (9.5 mg,
0.05 mmol) in THF (3 mL) and (Z)-1 (284 mg, 1 mmol), a solution
of phenylmagnesium chloride (1.2 mmol, 2 mol LÀ1 in THF) was
added dropwise at 0 °C. After the completion of the Grignard addi-
tion, the mixture was warmed to room temperature and kept un-
der stirring for an additional 20 min. The reaction mixture was
washed with ammonium chloride (10 mL) and extracted with
ethyl acetate (3 Â 5 mL). The combined organic layers were
washed with brine (10 mL), dried over MgSO4, and concentrated
under vacuum. Purification by chromatography on silica gel, eluent
hexane : ethyl acetate (9:1), gave 0.137 g (78%) of 2 as a colorless
oil. 1H NMR: (300 MHz, CDCl3, ppm) d 7.69 (d, J = 16.2 Hz, 1H);
7.50–7.54 (m, 2H); 7.36–7.40 (m, 3H); 6.44 (d, J = 16.2 Hz, 1H);
4.27 (q, J = 7.2 Hz, 2H); 1.34 (t, J = 7.2 Hz, 3H). 13C NMR (75 MHz,
CDCl3, ppm) d 167.0; 144.6; 134.5; 130.2; 128.9; 128.5; 128.0;
127.7; 118.3; 60.5; 14.3. LREIMS m/z (rel. int.) 176 (M+,63); 148
MeO
O
OEt
28
In this context, we decided to employ equivalent tellurides (9 and
11) in this protocol. As can be seen in Table 2, entries 5 and 6, the
tellurides 9 and 11, respectively, led to the expected cross-coupling
products in reasonable yields.
It is also important to comment on the stereochemistry of this
reaction. Since the telluride 1 was the only substrate that leads
to a total inversion of the configuration on the double bond geom-
etry, a different mechanistic pathway shall not be discarded. One
possibility is that this specific reaction proceeds through a conju-
gate addition of the corresponding organocopper reagent, followed
by elimination of the butyltellanyl moiety. On the other hand, the
same reaction conditions also lead to the same average yields
when employing non-activated olefins (7 and 11, for example).
However, these observations are not conclusive and mechanistic
studies are necessary.
(33); 130 (100); 104 (73); 77 (61); 51 (46). IR
3053, 2957, 1646, 1370.
t
max, neat (cmÀ1):
As can be seen in Table 2, a considerable number of tellurides
containing different functional groups were tested and most of
them were tolerated. Apparently this reaction is not very sensitive
to the steric environment, since the coupling product can be ob-
tained even from tetra-substituted sp2 hybridized tellurides (Table
2, entry 12).
Acknowledgment
We would like to thank FAPESP, CNPq, and CAPES for financial
support.
The following Figure 1 shows the key NOE enhancements ob-
served for the compounds Z-22 and Z-24, both obtained as single
isomers.
It is possible to observe a strong NOE for both the methine aldol
and the b-methyl protons, providing unquestionable proof of the Z
Supplementary data
Supplementary data (The experimental procedure and NMR
spectra of all the products are available free of charge via the Inter-
net at www.journals.elsevier.com.) associated with this article can
be found, in the online version, at http://dx.doi.org/10.1016/
j.tetlet.2012.04.134.
References and notes
Ph
O
Ph
O
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Figure 1. Key NOE enhancements observed for compounds 22 and 24 in the double
bond geometry elucidation.

M. S. Silva et al. / Tetrahedron Letters 53 (2012) 3556–3559
3559
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