Iron-catalyzed electrochemical allylation of carbonyl compounds by allylic acetates

Article abstract of DOI:10.1021/jo026782r

Homoallylic alcohols were synthesized from aldehydes or ketones and allylic acetates, using an electrochemical process catalyzed by iron complexes. We first studied the reactivity of allyl acetate, using N,N-dimethylformamide (DMF) or acetonitrile (AN) as solvent, FeBr₂ as catalyst, and Fe as the sacrificial anode. Then we tested the regioreactivity of crotyl acetate and other allylic derivatives.

Full text of DOI:10.1021/jo026782r

Ir on -Ca ta lyzed Electr och em ica l Allyla tion of Ca r bon yl Com p ou n d s
by Allylic Aceta tes
Muriel Durandetti,* Clotilde Meignein, and J acques Pe´richon
Laboratoire d’Electrochimie, Catalyse et Synthe`se Organique, UMR 7582 CNRS,
2 rue Henri-Dunant, 94320 Thiais, France
durandetti@glvt-cnrs.fr
Received November 29, 2002
Homoallylic alcohols were synthesized from aldehydes or ketones and allylic acetates, using an
electrochemical process catalyzed by iron complexes. We first studied the reactivity of allyl acetate,
using N,N-dimethylformamide (DMF) or acetonitrile (AN) as solvent, FeBr2 as catalyst, and Fe as
the sacrificial anode. Then we tested the regioreactivity of crotyl acetate and other allylic derivatives.
In tr od u ction
or reducing salt.14 Another access to allylic anions is their
electrochemical generation. An electrochemical activation
of allyl bromide with use of catalytic amounts of tin has
also been reported15 to yield homoallylic alcohols. In our
laboratory, we have already describe some electrochemi-
cal processes for the synthesis of homoallylic alcohols.16
We recently described17 an electrosynthetic process for
the Reformatsky reaction, catalyzed by iron complexes
and using a sacrificial iron anode, that afford â-hydroxy-
esters with good to high yields from R-haloester and a
variety of carbonyl compounds. We intend to show that
this electrochemical method can be suitable for the
activation of allyl acetates. We present in this paper the
investigation of the iron-catalyzed electroreductive coup-
ling reaction from allyl acetates with carbonyl compounds
(Scheme 1), leading to homoallylic alcohols. The chem-
istry of allylic compounds also includes the additional
regiochemical aspect.
Synthesis of homoallylic alcohols by allylation of car-
bonyl compounds is one of the most important processes
in organic synthesis1 since the homoallylic alcohols can
be easily converted to many important building blocks
for natural product synthesis.2 Different methods have
been developed based essentially on the nucleophilic
character of the allylmetal obtained from allyl bromides
and metallic species3-7 (metal ) Li, Mg, Al, Zn, Ni, ...).
More recently, other allylic organometallic compounds
have been examined, such as allylchromium,8 -indium,9
-manganese,10 -silane,11 -boronate,12 -stannane,13 etc. The
allylation reaction with these new allylic organometallic
compounds has been studied mostly with aldehydes but
rarely with ketones because of the difference of reactivity
between these two carbonyl groups. Whereas allylation
reactions from allyl halides seem to proceed without
major difficulties, the use of allylic acetate necessitates
palladium as catalyst, in the presence of another metal
Resu lts a n d Discu ssion
(1) Yamamoto, Y.; Asao, N. Chem. Rev. 1993, 93, 2207-2293.
(2) (a) Ramachandran, P. V.; Reddy, M. V. R.; Brown, H. B.
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P.; Hoch, N.; Ramachandran, P. V. Org. Lett. 2001, 3, 19-20.
(3) (a) Katzenellenbogen, J . A.; Lenox, R. S. J . Org. Chem. 1973,
38, 326-335. (b) Alonso, E.; Guijarro, D.; Ramon, D. J .; Yus, M.
Tetrahedron 1999, 55, 11027-11038.
We thus first conducted a series of experiments with
allyl acetate and various carbonyl compounds (1-9) in
the reaction conditions previously used for the Refor-
matsky reaction17 (DMF at room temperature, with a
current intensity of 250 mA, and having an iron rod as
the sacrificial anode). Results are given in Table 1.
Chemical yields are moderate to good. Therefore, the use
of iron salts obtained during a preelectrolysis allows the
cross-coupling between allyl acetate and carbonyl com-
(4) Barbot, F.; Miginiac, Ph. J . Organomet. Chem. 1977, 132, 445-
454.
(5) Gaudemar, M. Bull. Soc. Chim. Fr. 1962, 5, 974-987.
(6) (a) Abenhaim, D.; Henry-Bash, E.; Freon, P. Bull. Soc. Chim.
Fr. 1969, 11, 4038 and 4043. (b) Ranu, B. C.; Majee, A.; Das, A. R.
Tetrahedron Lett. 1995, 36, 4885-4888.
(7) Yamamoto, Y.; Maruyama, K. J . Org. Chem. 1983, 48, 1564-
1565.
(13) (a) Kamble, R. M.; Singh, V. K. Tetrahedron Lett. 2001, 42,
7525-7526. (b) Nokami, J .; Otera, J .; Sudo, T.; Okawara, R. Organo-
metallics 1983, 2, 191-193.
(8) (a) Nowotny, S.; Tucker, C. E.; J ubert, C.; Knochel, P. J . Org.
Chem. 1995, 60, 2762-2772. (b) Baati, R.; Gouverneur, V.; Mioskowski,
C. J . Org. Chem. 2000, 60, 1235-1238.
(14) (a) Masuyama, Y.; Kinugawa, N.; Kurusu, Y. J . Org. Chem.
1987, 52, 3704-3706. (b) Araki, S.; Kamei, T.; Hirashita, T.; Yama-
mura, H.; Kawai, M. Org. Lett. 2000, 2, 847-849.
(9) (a) Khan F. A.; Prabhudas, B. Tetrahedron 2000, 56, 7595-7599.
(b) Lombardo, M.; Girotti, R.; Morganti, S.; Trombini, C. Org. Lett.
2001, 3, 2981-2983.
(15) Torii, S.; Uneyama, K.; Matsuda, H. Tetrahedron Lett. 1984,
25, 6017-6020.
(10) Fu¨rstner, A.; Brunner, H. Tetrahedron Lett. 1996, 37, 7009-
7012.
(16) (a) Durandetti, S.; Sibille, S.; Pe´richon, J . J . Org. Chem. 1989,
54, 2198-2204. (b) Rollin, Y.; Derien, S.; Du`nach, E.; Gebehenne, C.;
Pe´richon, J . Tetrahedron 1993, 49, 7723-7732. (c) Durandetti, M.;
Ne´delec, J .-Y.; Pe´richon, J . Org. Lett. 2001, 3, 2073-2076.
(17) Durandetti, M.; Meignein, C.; Pe´richon, J . Org. Lett. 2003, 5,
317-320.
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2111-2118. (b) Yadav, J . S.; Chand, P. K.; Anjaneyulu, S. Tetrahedron
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10.1021/jo026782r CCC: $25.00 © 2003 American Chemical Society
Published on Web 03/13/2003
J . Org. Chem. 2003, 68, 3121-3124
3121

Durandetti et al.
SCHEME 2. Ad d ition of Allyl Aceta te to
Cycloh exa n on e via Ir on Ca ta lysis, Usin g Allyl
Aceta te a s Liga n d
SCHEME 1. Ad d ition of Allyl Aceta te to Ca r bon yl
Com p ou n d s via a n Ir on Ca ta lysis
CHART 1. Ca r bon yl Com p ou n d s
SCHEME 3. P r op osed Mech a n ism of th e
Ir on -Ca ta lyzed Electr och em ica l Ad d ition of Allyl
Aceta te to Ca r bon yl Com p ou n d s, Usin g Allyl
Aceta te a s Liga n d
TABLE 1. Ir on -Ca ta lyzed Electr or ed u ctive Cou p lin g
betw een Allyl Aceta te a n d Ca r bon yl Com p ou n d sa
(Table 1, entry 9), homoallylic alcohol is obtained together
with its acetate. In all cases, a portion of the allyl acetate
is recovered after the electrochemical reaction. Particu-
larly, in the case of aldehydes, 20 mmol of allyl acetate
is initially introduced, and 7 mmol was recovered.
Lower yields were obtained with 2-cyclohexen-1-one 2
even if the ketone is totally consumed (Table 1, entry 2),
and no other products were detected. No conjugated
addition was observed, thus indicating that the reaction
is regiospecific.
We previously have shown that allyl acetate also could
be used as a ligand instead of 2,2′-bipyridine.17 Because
of the environmental interest in avoiding 2,2′-bipyridine,
we have tried to realize the cross-coupling reaction
between cyclohexanone 1 and allyl acetate, using this
compound as the reagent as well as the ligand of iron
salts (Scheme 2). In this case, DMF could be replaced by
acetonitrile.
We obtained, with 3 equiv of allyl acetate, an isolated
yield of 73% of coupling product, instead of 78% with 2,2′-
bipyridine (Table 1, entry 1), with the consumption of
only 1 equiv of allyl acetate. So, chemical yields are
similar with either 2,2′-bipyridine or allyl acetate as the
ligand. Therefore, the substitution of 2,2′-bipyridine by
allyl acetate does not significantly affect the chemical
yield of the cross-coupling reaction. It is therefore obvious
that, in this coupling reaction, the allyl acetate itself coor-
dinates to iron salts, thus leading to an FeI- - - allylOAc
intermediate, which is probably transformed into a
π-allyl-iron complex before reacting with carbonyl com-
pounds (Scheme 3).
Further investigations are necessary to determine
which kind of organoiron species are involved. Moreover,
we have run the reaction without carbonyl compounds.
We only obtained, in this case, the formation of hexadi-
ene, thus confirming the formation of the π-allyl-iron
complex.
a
Typical procedure: carbonyl compounds (10 mmol), allyl
acetate added constantly to the solution at 4.7 mmol/h, FeBr2
obtained electrochemically by reduction of CH2Br-CH2Br (1
mmol), 2,2′-bipyridine (5 mmol), DMF (40 mL) + NBu4BF4 (0.6
mmol), room temperature, constant current intensity (250 mA),
Q ) 4 F/mol of carbonyl compounds, under argon, iron anode, and
b
nickel-sponge cathode. Isolated yields, based on initial carbonyl
compounds. All products gave satisfactory analytical data. c No
d
1,4-addition product was detected. 20 mmol of allyl acetate
initially introduced, and RCHO was added via the syringe pump
to minimize the direct reduction.
pounds. This method is efficient with aliphatic and cyclic,
as well as aromatic ketones (Table 1, entries 1-7).
In the case of aldehydes (Table 1, entries 8 and 9),
chemical yields are moderate due to pinacolization, and
addition of the aldehyde via a syringe pump to the
reaction mixture is necessary. With benzaldehyde 9
Then we wanted to test the regioreactivity of this
coupling reaction. So we have run a series of experiments
3122 J . Org. Chem., Vol. 68, No. 8, 2003

Iron-Catalyzed Allylation of Carbonyl Compounds
SCHEME 4. Regioselectivity of th e Ir on -Ca ta lyzed
Electr och em ica l Ad d ition of Cr otyl Aceta te to
Ca r bon yl Com p ou n d s
corresponding pinacol. Thus, the reaction was conducted
with 2 equiv of 1-methyl prop-2-enyl acetate initially in
the solution, and an addition of the aldehyde via a syringe
pump. Yields are good with this procedure. With alde-
hydes, the reaction is regiospecific (B/L ) 100/0), since
the linear product was not detected.
In the case of dissymmetric carbonyl compounds (Table
2, entries 6-8 and 10-12), we obtained the coupling
product, as two couples of diastereoisomers, with moder-
ate diastereoselectivity. The erythro/threo ratio is about
60/40, depending on the nature of the carbonyl com-
pounds.
TABLE 2. Ir on -Ca ta lyzed Electr or ed u ctive Cou p lin g
betw een Allylic Com p ou n d s a n d Ca r bon yl Com p ou n d sa
It is interesting to note that the coupling is more
efficient with crotyl acetate than with allyl acetate.
Results with crotyl chloride are also reported. Better
yields were obtained with allylic acetates than with
allylic chlorides (Table 2, compare entries 3 and 5, entries
6 and 8), as well as shorter reaction times and less re-
agent. Nevertheless, the regioreactivity and the stereo-
selectivity are identical (same B/L and erythro/threo
ratio).
Allylic chlorides are more reactive toward electrogen-
erated FeI than allylic acetates, so the dimerization of
this compound occurs preferentially instead of the coup-
ling reactions.
We finally applied the reaction to other allylic com-
pounds: cynnamyl and prenyl acetate. Cross-coupling
product is obtained in good yield and high regioselectivity
with use of only 1 equiv of cynnamyl acetate (Table 2,
entry 13). Prenyl acetate is a poor reagent, since products
were obtained with lower yields (<50%) (Table 2, entries
14 and 15). This may be due to the occurrence of steric
hindrance in the branched product obtained more with
prenyl acetate than with other allylic compounds. Here
again, no linear isomer was detected.
yield (%) of
carbonyl
entry compd
coupling
ratio
B/L
allylic compd (neq
)
productb
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
1
1
7
7
7
3
3
3
10
4
9
8
1
10
1
CH3CHdCHCH2OAc (1.3)
CH2)CHCH(CH3)OAc (1.2)
CH3CHdCHCH2OAc (1.8)
CH2)CHCH(CH3)OAc (1.4)
CH3CHdCHCH2Cl (3.2)
CH3CHdCHCH2OAc (1)
CH2dCHCH(CH3)OAc (1)
CH3CHdCHCH2Cl (3.2)
CH3CHdCHCH2OAc (2.4)
CH3CHdCHCH2OAc (2)
CH2dCHCH(CH3)OAc (2)g
CH2dCHCH(CH3)OAc (2)g
PhCHdCHCH2OAc (1)
92
91
60
56
98/2
98/2
97/3
96/4
97/3
99/1
99/1
99/1
98/2
35c
93d
88d
64d
87
87e
58f
63d
57
99/1
100/0
100/0
100/0
100/0
100/0
(CH3)2CdCHCH2OAc (1)
(CH3)2CdCHCH2OAc (0.64)
16
46
a
Typical procedure: carbonyl compounds (10 mmol), allylic
compounds added constantly to the solution at 4.0 mmol/h, FeBr2
obtained electrochemically by reduction of CH2Br-CH2Br (1
mmol), 2,2′-bipyridine (5 mmol), DMF (40 mL) + NBu4BF4 (0.6
mmol), room temperature, constant current intensity (250 mA),
Q ) 4 F/mol of carbonyl compounds, under argon, iron anode, and
b
nickel-sponge cathode. Isolated yields, based on initial carbonyl
compounds. All products gave satisfactory analytical data. c 58%
d
of unreacted ketone is recovered. Product B: erythro/threo 57/
43. e Product B: erythro/threo 50/50. f Product B: erythro/threo 63/
g
37. 20 mmol of allylic acetate initially introduced, and RCHO
was added via the syringe pump to minimize the direct reduction.
Con clu sion
We have reported in this paper an original method of
efficient cross-coupling of allylic acetates with carbonyls
compounds, enabling the preparation of valuable target
molecules: homoallylic alcohols. The method is efficient
with aldehydes as well as with ketones. The efficiency of
iron salts in this process has been clearly demonstrated.
The method is also very easy, cheap, and nontoxic,
compared to the other methods described in the litera-
ture, where palladium complexes, in the presence of
another reducing salt, must be used to activate allyl
acetate. In addition, iron salts are released by oxidation
of the anode, thus avoiding the use of FeBr2, which is
air and moisture sensitive. The reduction of FeII at the
cathode probably leads to FeI, which is stabilized by 2,2′-
bipyridine, or allyl acetate itself. Reactions are regiose-
lective: the branched product B is the major product, and
sometimes the only one.
with the same experimental procedure, using crotyl
acetate (or its allylic isomer) instead of allyl acetate.
Reactions involving allylic derivatives generally give
two isomeric products due to allylic transposition
(Scheme 4).
The ratio of branched to linear alcohol (B/L) is known
to depend mainly on the nature of the metal in the
organometallic reagent.1,18 However, in this method, the
major product formed in theses reactions is the branched
product B, with a ratio B/L of 98/2 (Table 2).
With ketones the yields are good to excellent and do
not seem to greatly depend on the nature of the butenyl
acetate (crotyl or its isomer) (Table 2, entries 1-4, 6, and
7). So, crotyl acetate and 1-methyl prop-2-enyl acetate
have the same efficiency in this coupling reaction: same
yield, and same B/L ratio.
We also applied this procedure to aldehydes (Table 2,
entries 11 and 12). Here again, aldehydes are slightly
more reactive than ketones. Therefore, the slow addition
of the aldehyde to the reaction mixture was used to avoid
the direct reductive coupling of the aldehyde into the
Exp er im en ta l Section
GC analysis was carried out using a 25-m capillary column.
Mass spectra were recorded with a spectrometer coupled to a
gas chromatograph. Column chromatography was performed
on silica gel 60, 70-230 mesh. H and 13C NMR spectra were
1
recorded in CDCl3 at 200 MHz with TMS as an internal
standard.
(18) Ito, A.; Kishida, M.; Kurusu, Y.; Masuyama, Y. J . Org. Chem.
2000, 65, 494-498.
J . Org. Chem, Vol. 68, No. 8, 2003 3123

Durandetti et al.
The electrochemical cell has been described previously.19
All solvents and reagents were purchased and used without
further purification. DMF and acetonitrile were stored under
argon.
at room temperature within 15 min to generate a small
amount of iron ions. Then the current was turned off. 2,2′-
Bipyridine (5 mmol), carbonyl compounds (10 mmol), and a
portion of the allyl acetate (ca. 0.3 mmol) were added. The
excess of allyl acetate was introduced via a syringe pump at a
rate of ca. 4 mmol/h. The electrosynthesis was run at constant
current density (0.25 A). The reaction was monitored by GC
and stopped after carbonyl compounds was consumed (ca. 4.5
h). A charge of 4 F‚mol-1 was used in most reactions described
in this paper. The mixture was then hydrolyzed with 1 N
hydrochloric acid and diluted with diethyl ether. The aqueous
layer was extracted with diethyl ether, the combined organic
layers were washed with water and saturated NaCl solution
and dried over MgSO4, and the solvent was evaporated. The
oil thus obtained was purified by column chromatography to
give the desired compounds.
2,2′-Bipyridine was used as obtained commercially.
NBu4BF4 was dried by heating overnight at 70 °C in a vacuum.
P r ep a r a tion of Allylic Aceta te. Crotyl, 1-methyl prop-2-
enyl, and prenyl acetates were prepared from the commercially
available corresponding alcohols via esterification reaction.20
Cr otyl a ceta te (100%): 1H NMR (CDCl3) δ 1.73 (d, J ) 5
Hz, 3H), 2.07 (s, 3H), 4.55 (d, J ) 5 Hz, 2H), 5.33-6.17 (m,
2H); MS 115 (M + 1, base), 61, 55, 43.
1-Meth yl p r op -2-en yl a ceta te (75%): 1H NMR (CDCl3) δ
1.31 (d, J ) 6.4 Hz, 3H), 2.06 (s, 3H), 5.13 (dd, J ) 10.5, 1.2
Hz, 1H), 5.24 (dd, J ) 17.2, 1.2 Hz, 1H), 5.25 (qd, J ) 6.4, 5.9
Hz, 1H), 5.85 (ddd, J ) 17.2, 10.5, 5.9 Hz, 1H), MS 115 (M +
1, base), 55.
Chemical Abstracts Registry Numbers, in brackets, sup-
plied by the author: (2-propenyl)-1-cyclohexanol [1123-34-
8]; 1-allylcyclohex-2-en-1-ol [65995-76-8]; 2-phenyl-pent-4-en-
2-ol [4743-74-2]; 2-[2]thienyl-pent-4-en-2-ol [116021, Beilstein];
4,8-dimethyl-nona-1,7-dien-4-ol [17920-92-2]; 4-methyl-nona-
1-en-4-ol [40674-50-8]; 1-allyl-cyclopentanol [36399-21-0]; 1-do-
decen-4-ol [77383-04-1]; 1-phenyl but-3-en-1-ol [936-58-3]; 1-(1-
methyl-2-propenyl)-cyclohexanol [36971-11-6]; 1-(but-3-en-2-
yl)-cyclopentan-1-ol [52922-26-6]; 2-phenyl-3-methyl-4-penten-
2-ol [61967-11-1]; 3-ethyl-4-methyl-hex-5-en-3-ol [25201-42-7];
2-(2-thienyl)-3-methyl-4-penten-2-ol [128081-10-7]; 2-methyl-
1-phenylbut-3-en-1-ol [25201-44-9]; 3-methyl-dodec-1-en-4-ol
[114067-39-9]; 1-(1-phenyl-2-propenyl)cyclohexanol [79801-99-
3]; 3-ethyl-4,4-dimethyl-hex-5-en-3-ol [55629-20-4]; 1-(1,1-di-
methyl-allyl)-cyclohexanol [36971-12-7].
P r en yl a ceta te (87%): 1H NMR (CDCl3) δ 1.71 (s, 3H), 1.76
(s, 3H), 2.04 (s, 3H), 4.56 (d, J ) 7.2 Hz, 2H), 5.35 (t, J ) 7.2
Hz, 1H); MS 128 (M), 73, 59 (base).
Allyl and cynnamyl acetate were commercial products.
Gen er a l P r oced u r e for th e F e(II)-Ca ta lyzed Elec-
tr osyn th esis. In an undivided cell equipped with a nickel
sponge (area 20 cm2) as the cathode and an iron rod as the
anode, under argon, tetrabutylammonium tetrafluoroborate
(0.6 mmol) was dissolved as supporting electrolyte in DMF (40
mL). 1,2-Dibromoethane (1.25 mmol) was introduced. A short
electrolysis was run at constant current density (0.3 A) and
(19) (a) Chaussard, J .; Troupel, M.; J acob, G.; J uhasz, J . P. J . Appl.
Electrochem. 1989, 19, 345-348. (b) Chaussard, J .; Folest, J . C.;
Ne´de´lec, J . Y.; Pe´richon, J .; Sibille, S.; Troupel, M. Synthesis 1990, 1,
369-381.
(20) Durandetti, M.; Ne´de´lec, J .-Y.; Pe´richon, J . J . Org. Chem. 1996,
61, 1748-1755.
J O026782R
3124 J . Org. Chem., Vol. 68, No. 8, 2003