Alternative method for alkylation of arylpolyhalomethanes with trialkylborane in the presence of magnesium

Article abstract of DOI:10.1016/j.jorganchem.2009.09.022

Reduction of benzal halide derivatives and α,α,α,-trichloromethylbenzene by magnesium powder in DMAc affords α-halocarbanions which then react with triethylborane to give alkylated products. After oxidation with H₂O₂-NaOH, secondary

Full text of DOI:10.1016/j.jorganchem.2009.09.022

Journal of Organometallic Chemistry 695 (2010) 32–35
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Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Alternative method for alkylation of arylpolyhalomethanes with trialkylborane
in the presence of magnesium
*
Sylvie Condon , Jean-Yves Nédélec
Equipe Electrochimie Synthèse Organique, Institut de Chimie des Matériaux Paris Est (ICMPE)-Université Paris 12, UMR 7182, 2 rue Henry-Dunant 94320, Thiais, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 6 July 2009
Received in revised form 17 September
2009
Accepted 18 September 2009
Available online 26 September 2009
Reduction of benzal halide derivatives and
a,a,a,-trichloromethylbenzene by magnesium powder in
DMAc affords
oxidation with H2O2–NaOH, secondary or tertiary alcohols are obtained. Under the same conditions,
1,1-diphenylpropane is obtained from -dichlorodiphenylmethane.
Ó 2009 Elsevier B.V. All rights reserved.
a-halocarbanions which then react with triethylborane to give alkylated products. After
a,a
Keywords:
Alkylation
Trialkylborane
Arylpolyhalomethanes
1. Introduction
and activated olefins in the presence of magnesium powder sus-
pended in DMF. Under these conditions, the generated -haloorg-
anomagnesium intermediate reacts faster with the activated olefin
a
We have recently described the electrochemical reaction of de-
cyl dihalo- and trihalo-acetate with trialkylborane leading to
than it decomposes by
ing carbene [8].
a-elimination of MgX2 into the correspond-
a-alkylated esters [1]. The reaction was conducted in an undivided
cell fitted with a sacrificial zinc anode, at 20–40 °C in DMAc. We
next found that the electrochemical reaction can be applied to
the alkylation of benzal chloride (Scheme 1) and after the oxidative
work up with hydrogen peroxide, 1-phenyl-propan-1-ol was ob-
tained. Because the potential reduction [2] of benzal chloride
(À2.2 V/ECS) is more negative than that of dihalo- and trihalo-ace-
tates (À1.6 V/ECS), zinc rod was replaced by magnesium to allow
the formation of the active nucleophilic species. Thus, the reaction
presumably occurs by the electrochemical reduction of benzal
In continuation of our study on the behaviour of nucleophilic
species generated in unusual solvent from polyhalomethylcom-
pounds and magnesium powder in the presence of electrophiles,
we wish to report herein the results obtained with triethylborane
as the electrophile (Scheme 3).
2. Results and discussion
chloride to give
a-chlorobenzylmagnesium chloride. The a-halo
Initially, the reaction was performed at room temperature by
anion then reacts with trialkylborane to form an organoborate
which evolves by 1,2-alkyl transfer to give a new alkylborane as
in the mechanism proposed by Brown [3]. The alkyl arylcarbinol
is obtained after oxidation.
adding dropwise one-third of the mixture of
a-benzal chloride
(3.5 mmol; 0.45 mL) and triethylborane (1 N in THF, 1.14 equiv.)
to a suspension of magnesium powder in the co-solvent (THF,
DMAc, DMF, AN) (volume in mL as given in Table 1). The temper-
ature was allowed to rise to 30–35 °C. Then the remaining solution
was slowly added by keeping the reaction temperature below
35 °C. After the end of the addition, the reaction mixture was stir-
red for 30 min at room temperature. The consumption of benzal
chloride was checked by GC. The excess of magnesium was filtered
off and the oxidation reaction by hydrogen peroxide/sodium
hydroxide was performed. The results are reported in Table 1.
Two key parameters are indicated: the nature of the co-solvent
and the concentration of benzal chloride.
Such
a-halo anions are usually generated from polyhalo com-
pounds by metal–halogen exchange with t-buthyllithium [4], by
hydrogen–metal exchange with strong bases [5] or electrochemi-
cally [6].
In this laboratory, Oudeyer et al. [7] have shown that, alterna-
tively to the electrochemical route, the cyclopropane formation
(Scheme 2) can be performed under Barbier type protocol from
polyhalomethyl compounds (PhCHCl2, PhCCl3, PhCHBr2, CCl3CO2R)
THF, which is the usual solvent for the preparation of organo-
magnesium as well as for the metal–halogen exchange involving
* Corresponding author. Tel.: +33 1 49 78 11 26; fax: +33 0 1 49 78 11 48.
E-mail address: condon@icmpe.cnrs.fr (S. Condon).
0022-328X/$ - see front matter Ó 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2009.09.022

S. Condon, J.-Y. Nédélec / Journal of Organometallic Chemistry 695 (2010) 32–35
33
1. e- (Mg anode)
Cl
Cl
C
H
Mg
(1)
OH
Ph CH Et
2. H2O2, OH-
ArCHCl2
Cl
Ar C MgCl
H
Ar
Et
Et3B
PhCHCl2
10.5 mmol
+
- MgCl
Scheme 1.
Et
Cl
Et
(3)
Et3B
(2)
Ar C B Et
Ar C B Et
Ar
C
H
Et
H
H
Ph
R
Ph
Mg (3 eq)
H2O2/OH-
CCl2
+
(4)
EWG
DMF, -5°C
R
EWG
Et
Ar C OH
H
or CCl3CO2Et
Et
Ar C H +
H
R: H, Cl, Ph
Scheme 2.
Scheme 4.
1. Mg powder
2. H2O2, OH-
OH
Ph C Et
R
Ph
the formation of 1-phenyl-propan-1-ol is not observed in acetoni-
trile (Table 1, entry 7) and this may be due to the acidity of this
solvent.
Et3B
CCl2
+
R
R: H, Ph, Cl
Regarding the reducing metal, the same rate in the consump-
tion of benzal chloride is observed by replacing magnesium by zinc
powder. However traces of 1-phenyl-propan-1-ol (5% in GC) are
detected along with toluene, dibenzyle, E and Z-stilbene as the
main products.
Scheme 3.
Table 1
The mechanism of the reaction involves in the first step
(Scheme 4, (1)) the reduction of benzal chloride by Mg leading to
Preliminary results for the reaction of benzal chloride with triethylborane in the
presence of magnesium powder.
the a-haloanion.
1. Mg (6 eq), 30-35°C
Et
ArCH
Cl
2. H2O2/OH-
Then this carbanion reacts with triethylborane to give a new
alkylborane (Scheme 4, (2) and (3)) which after oxidation (Scheme
4, (4)) affords 1-phenyl-propan-1-ol. Byproducts resulting from
dimerization of the intermediate anion such as (Z) and (E) stilbene
(6%, GC), dibenzyle (2%, GC) and from protonolysis of the newly
formed trialkylborane such as 1-phenylpropane (10%, GC) were
detected.
Et3B
+
ArCH
OH
Cl
1.14 equiv
3.5 mmol
Entrya
Co-solvent (V, mL)
Isolated yield% in alcohol
1
2
3
4
5
6
7
THF (5.5 mL)
DMF (2 mL)
8
3.5
Moreover a-haloanions are precursors of carbenes (Scheme 5).
In order to limit the formation of byproducts, the reaction con-
ditions have been improved by several changes in the protocol. In
order to favour the reaction of a-halocarbanion with triethylbora-
ne, benzal chloride (3.5 mmol) in DMAc (1 mL) was added drop-
wise to the mixture of 1.14 equiv. triethylborane (1 N in THF,
4 mL) and magnesium in DMAc (1 mL). The reaction temperature
was maintained at 32 °C for all over the addition. After the oxida-
tion step, 1-phenyl-propan-1-ol was obtained with 41% isolated
yield (Table 2, entry 1). Other results obtained from benzal halide
derivatives are also reported in Table 2.
DMAc (5.5 mL)
DMAc (2 mL)
DMAc (1 mL)
DMAc (20 mL)b
CH3CN (1 mL)
20
31 (59%)c
29
0
0
a
Conditions: slow addition of benzal chloride, triethylborane (1 N in THF) to
magnesium powder suspended in DMAc (V, mL).
Reaction performed in the same reaction conditions as electrochemical alkyl-
ation reaction of decyl dihalo- and trihalo-acetate.
b
c
Determined by GC.
The reaction has been extended to benzal chloride derivatives
bearing various substituents (F, CH3, and OCH3) on the aryl moiety.
The isolated yield is higher when F is at para position (Table 2, en-
try 4) rather than at meta position (Table 2, entry 6). The best re-
sults were found by performing the reaction with 6 equiv. of
magnesium (Table 2, entries 4 and 5) and the reaction is also effi-
cient with methyl and methoxy groups as substituents (Table 2,
entries 7 and 8). Under these new standard conditions, 1-phenyl-
propan-1-ol was not detected by using benzal bromide as starting
benzal halides [9] or haloform [10], is not suited under this proto-
col (Table 1, entry 1) since the reaction is not ended after 30 min.
This is consistent with the results of Kabalka and co-workers [9],
who reported that the reaction of
a-haloorganomagnesium chlo-
ride, generated from -dichloroarylmethane, with trialkylborane
a,a
(1 N in THF) in THF is slowly achieved in 10–36 h at room temper-
ature. We also noticed that the reaction cannot be conducted in
DMF (Table 1, entry 2) which is a very common solvent allowing
formation of organometallic species in electrochemical processes
and the solvent for the cyclopropanation reaction in the chemical
version [7]. The reaction is best performed in DMAc (Table 1, en-
tries 4 and 5) used as the co-solvent. This evidences that the sol-
vent has a strong influence on the nature and the reactivity of
the nucleophilic intermediate species. Also to notice, the course
of the reaction is very sensitive to the instant concentration of ben-
zal chloride which must be rather high in the reaction mixture (Ta-
ble 1, entries 3–6). Also, the reaction conditions for the
reagent. We can assume that the
a-bromo anion is less stable than
the -chloro anion. However, we found that the slow addition of
a
benzal bromide along with a careful control of the reaction tem-
perature and use of lower amount of magnesium (Table 2, entries
Cl
C
H
Ar
+
C
H
Cl
Ar
electrochemical
a-alkylation of decyl dichloro- and trichloro-ace-
tate is not adapted (Table 1, entries 6) for benzal halides. Finally,
Scheme 5.

34
S. Condon, J.-Y. Nédélec / Journal of Organometallic Chemistry 695 (2010) 32–35
Table 2
1. Et3B, Mg (6 equiv.)
DMAC-THF
Ph2CCl2
Ph CH Ph
Preparation of various alkylarylcarbinols
Et
Et
Cl
1. Mg, DMAc
74% isolated
Et B
+
FG-ArCH
3
FG-ArCH
2. H2O2/OH-
OH
Cl
Scheme 8.
1.14 eq
3.5 mmol
Entrya
FG
Temperature (°C)
Metal powder
Isolated yield%
Ph
C
H O
Ph
Ph
Ph
Et
1
2
3
4
5
6
7
8
H
30
13
27
32
34
33
33
32
Mg (6 equiv.)
Mg (3 equiv.)
Mg (3 equiv.)
Mg (6 equiv.)
Mg (3 equiv.)
Mg (6 equiv.)
Mg (6 equiv.)
Mg (6 equiv.)
41
19c
58
55
43
36
42
56
B(Et)2
C
H
+
H O B(Et)2
Hb
Et
Hb
H
pF
pF
mF
pCH3
mOCH3
Scheme 9.
room temperature or by NaOH/tetrabutylammonium hydroxide
[12]. Because of the particular position of boron atom in the newly
formed trialkylborane, the dealkylation occurred easily in the pres-
ence of HCl 1 N affording 1,1-diphenylpropane as the main product
in 74% yield. This product was identified by comparison with an
authentic commercial sample.
a
b
c
FG-ArCHCl2: 3.5 mmol.
Benzal bromide.
In the previous reaction conditions, the yield was 0%.
1. Et3B, Mg
(3 equiv.)
The proposed mechanism for the formation of 1,1-diphenylpro-
pane is depicted in Scheme 9.
DMAC-THF
Et
2. H2O2, OH-
Ph
Et
O
PhCCl3
Ph C Et
OH
+
3. Conclusions
We have shown that benzal chloride and its derivatives can be
reduced in the presence of trialkylborane by magnesium powder in
DMAc to give after oxidation step secondary alcohols. Compared to
Kabalka and co-workers reaction conditions [9], the reaction time
is shortened thanks to the addition of DMAc as co-solvent. The
scope of this improved method covers the alkylation of benzal bro-
28% (isolated)
Scheme 6.
2 and 3) allows to get 1-phenyl-propan-1-ol with 58% isolated
yield.
With the successful results obtained in the benzal halides series,
we attempted a similar transformation by testing commercially
mide,
a
,a,a
,-trichlorotoluene and
was also reported that
a,a-dichlorodiphenylmethane. It
-bromo(chloro)benzyl anions can be pre-
a
pared by in situ deprotonation of benzal halide derivatives with
dicyclohexylamide [5b]. Compared to our method carried out at
room temperature in one step, this faster method required the
use of strong base and the control of the temperature (À78 °C).
Magnesium powder cannot be replaced by weaker reducing re-
agent such as zinc powder.
available
a
,a,a
-trichlorotoluene and
a,a-dichlorodiphenylmethane.
In the reaction of
a,a,a
-trichlorotoluene with trialkylborane fol-
lowed by the oxidation step (Scheme 6), toluene (15%, GC), 1-phe-
nyl-propan-1-ol (3%, GC), 3-phenylpentan-3-ol (51%, GC) and
1-phenylpropan-1-one (12%, GC) were identified by mass spec-
trometry. The main product 3-phenylpentan-3-ol was isolated in
28% yield.
4. Experimental
These products are coming from the same newly formed trial-
kylborane intermediate (Scheme 7). During the H2O2/OHÀ treat-
ment, either trialkylborane intermediate is oxidized to give gem
chlorhydrine (way A) which transforms into ketone or a second al-
kyl transfer reaction mediated by H2O2/OHÀ occurs (way B) before
the completion of the oxidation step.
In the reaction of dichlorodiphenylmethane with triethylborane
(Scheme 8), the standard hydrogen peroxide procedure does not
lead to the expected alcohol. Indeed, it has previously been noted
that trialkylboranes, able to yield stable carbanions after deborona-
tion, are readily protonolyzed by base (NaOH in diglyme) [11] at
Unless indicated, all solvents and reagents were purchased from
commercial sources and used as received. N,N-dimethylacetamide
(DMAc) was stored under argon. 3-Fluoro-, 4-fluoro-, 4-methyl-
and 3-methoxy-benzal chlorides were prepared according to the
known procedures [13]. 1H, 13C, 19F spectra were recorded on a
Brucker Avance-II 400 MHz. Chemical shifts are quoted in parts
per million (ppm). Mass spectra were obtained with a GCQ Ther-
moquest Spectrometer coupled to a chromatograph fitted with a
25-m CPSIL5 CB capillary column. The infrared spectra were
recorded on a Perkin–Elmer FT-IR Spectrometer 1720X. Elemental
Cl
Ph C B
Cl Et
Cl
C
Cl
Et
Et
Et
(Mg)
2 e
Et3B
Et
PhCCl3
Ph
O
Ph C B
-Cl
-Cl
Et
Cl
H2O2, OH-
Et
Et
Et
Et O-OH
Ph C B
Et O-OH
way B
way A
OH
Ph C OH
Cl
Ph
C
Ph C OH
Et
major
Ph C B
Et
Et
Cl Et
Et
Scheme 7.

S. Condon, J.-Y. Nédélec / Journal of Organometallic Chemistry 695 (2010) 32–35
35
analyses and high resolution mass spectral analyses were made by
the Service Central d’Analyse (CNRS, Lyon).
J = 7.40 Hz). 13C NMR (100 MHz, CDCl3) d ppm: 140.6, 136.1, 128.0,
124.9, 74.8, 30.8, 20.1, 9.2. MS: m/z (%) 150, 133, 121 (100%), 105,
Typical procedure: the synthesis of 1-(3-fluorophenyl)propan-1-ol is
representative. To a suspension of magnesium powder (21 mmol) in
DMAc (1 mL) is added triethylborane (1 N in THF, 4 mmol). The tem-
perature is allowed to rise to 32 °C in few minutes. The solution of 3-
fluorobenzal chloride (0.63 g; 3.5 mmol) in DMAc (1 mL) is slowly
added (7 drops per minutes). The reaction temperature rises slowly
for a while; the reaction mixture turns to yellow. Then the reaction
temperature is controlled and maintained below 35 °C. After
30 min, the remaining magnesium is filtered off. NaOH (3 N, 2 mL)
and H2O2 (3 mL) are carefully added at 0 °C to the filtrate, while
keeping the temperature below 50 °C. After stirring for 1 h at
50 °C, the mixture is cooled down; saturated NaHCO3 aqueous solu-
tion (30 mL) and diethylether are added. The aqueous layer is ex-
tracted twice with diethylether (30 mL). The collected organic
layers are washed with distilled water and NaCl saturated solution.
The product is dried over MgSO4 and after the evaporation of the sol-
vent, is purified by column chromatography.
93, 91, 77. IR (NaCl): m 3363, 2962, 2926, 2874, 1513, 1455, 1097,
1039, 1011, 813 cmÀ1. HRMS (M+Na) m/z: Calcd for C10H14ONa
calcd 173.0942; found: 173.0945.
1-(3-Methoxyphenyl)propan-1-ol: Oil; 1H MR (400 MHz, CDCl3) d
ppm: 7.19 (t, 1H, J = 8.09 Hz), 6.84 (m, 2H), 6.74 (m, 1H), 4.50 (t,
1H, J = 6.58 Hz), 3.74 (s, 3H), 1.71 (m, 2H), 1.20 (sbroad, 1H), 0.85
(t, 3H, J = 7.42 Hz). 13C NMR (100 MHz, CDCl3) d ppm: 159.7,
146.4, 129.4, 118.3, 112.9, 111.4, 76.0, 55.2, 31.8, 10.2. MS: m/z
(%) 166, 137, 109 (100%), 94, 77, 51. HRMS (M+Na) m/z: Calcd for
C10H14O2Na calcd 189.0891; found: 189.0893.
Appendix A. Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.jorganchem.2009.09.022.
1-(3-Fluorophenyl)propan-1-ol: Oil; 1H NMR (400 MHz, CDCl3) d
ppm: 7.16 (m, 1H), 6.93 (m, 3H), 4.38 (t, 1H, J = 6.52 Hz), 3.00
(sbroad, 1H, OH), 1.58 (m, 2H), 0.75 (t, 3H, J = 7.42 Hz). 19F NMR
(380 MHz, CDCl3) d ppm: À113.13. 13C NMR (100 MHz, CDCl3) d
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ppm: 162.10 (d, JC–F = 233.9 Hz), 146.35 (d, JC–F = 8.10 Hz),
3
4
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(sbroad, 1H, OH), 1.85–1.66 (m, 2H), 0.88 (t, 3H, J = 7,42 Hz).
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4
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(NaCl):
m 3353, 2966, 2933, 2878, 1604, 1500, 1460, 1220,
832 cmÀ1. Anal. Calc. for C9H11FO: C, 70.11; H, 7.19; F, 12.32. Found:
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ppm: 7.14 (d, 2H, J = 7.82 Hz), 7.07 (d, 2H, J = 7.82 Hz), 4.46 (t, 1H,
J = 6.60 Hz), 2.26 (s, 3H), 1.86 (sbroad, 1H), 1.68 (m, 2H), 0.82 (t, 3H,
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