Lanthanum metal-assisted deoxygenative coupling of alcohols

Article abstract of DOI:10.1016/S0040-4039(02)00602-0

It was found that the deoxygenative coupling of alcohols efficiently proceeded by treatment with lanthanum metal and chlorotrimethylsilane in the presence of a catalytic amount of iodine. This coupling reaction was accelerated by the addition of a catalytic amount of copper(I) iodide.

Full text of DOI:10.1016/S0040-4039(02)00602-0

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 3689–3691
Lanthanum metal-assisted deoxygenative coupling of alcohols
Toshiki Nishino, Yutaka Nishiyama* and Noboru Sonoda*
Department of Applied Chemistry, Faculty of Engineering, Kansai University, Suita, Osaka 564-8680, Japan
Received 26 March 2002; accepted 27 March 2002
Abstract—It was found that the deoxygenative coupling of alcohols efficiently proceeded by treatment with lanthanum metal and
chlorotrimethylsilane in the presence of a catalytic amount of iodine. This coupling reaction was accelerated by the addition of
a catalytic amount of copper(I) iodide. © 2002 Elsevier Science Ltd. All rights reserved.
The reductive coupling of alkyl halides to the corre-
sponding alkanes is a useful method for constructing
carbonꢀcarbon bonds, and it can be accomplished with
Various alcohols were treated with lanthanum metal
and chlorotrimethylsilane in the presence of a catalytic
amount of iodine and copper(I) iodide in acetonitrile
1
6
various reagents. Alcohols are easily purchased from
solvent, and the results are shown in Table 1. 2,3-
commercial sources and alkyl halides are generally syn-
thesized from the corresponding alcohols. Therefore,
Diphenylbutane (2c) was obtained in 72% yield by the
reaction of a-phenethylalcohol (1c) with lanthanum
metal. For the tertiary alcohol (1b), the yield of the
deoxygenative coupling product (2b) was slightly
decreased due to the increase in the yield of 2-phenyl-
propene (4b) as a by-product. When benzyl alcohol (1d)
was treated with lanthanum metal under the same
reaction conditions as 1a, the yield of 1,2-
diphenylethane (2d) was 42% and the starting material
was 30% recovered. This transformation can be applied
to allylic alcohols. For example, similar treatment of
2-cyclohexene-1-ol (1j) with lanthanum metal produced
3,3%-bicyclohexenyl (2j) in 75% yield. Similarly, cin-
namyl alcohol (1i) was deoxygenatively coupled to give
the corresponding coupling products with a mixture of
isomers.
2
development of a deoxygenative coupling method of
alcohols in organic synthesis is of interest, however,
there are only a few reports on the transformation. To
3
the best of our knowledge, low-valent titanium and
4
niobium compounds prepared by the reduction of
metal halides are limited reagents for the deoxygenative
coupling of alcohols. We now found that lanthanum
metal assisted the deoxygenative coupling of alcohols in
the presence of chlorotrimethylsilane and a catalytic
amount of iodine to give the corresponding coupling
products in moderate to good yields. In addition, it was
clearly shown that the reaction was accelerated by the
addition of a catalytic amount of copper(I) iodide
(
Scheme 1).
When benzhydrol (1a) was treated with lanthanum
metal (1 equiv.), chlorotrimethylsilane (2 equiv.) and a
catalytic amount of iodine (0.2 equiv.) in acetonitrile
solvent at 25°C for 8 h, the deoxygenative coupling of
It is already known that the reaction of alcohols with
iodotrimethylsilane forms the corresponding iodides in
1a proceeded smoothly to give 1,1,2,2-tetraphenyl-
Me3SiCl / cat. I2 / cat. CuI
R OH
+
La
R
+
R
ethane (2a) in 51% yield along with the formation of
diphenylmethane (33%) (3a) (Scheme 2). The use of
THF, which is widely utilized in organic reaction with
lanthanoid metal compounds, as the solvent led to a
decrease in the yield of 2a (6%). It is interesting to note
that an addition of a catalytic amount of copper(I)
iodide (0.2 equiv.) markedly promoted the deoxygena5-
tive coupling of 1a to give 2a in 87% yield (Scheme 3).
CH3CN
1
2
Scheme 1.
Ph
OH
+
Ph
Me3SiCl / cat.I2
Ph
La
Ph
Ph
Ph
Ph
3
CH CN, 25 °C, 8 h
Ph
1a
2a
1 %
3a
33 %
5
*
Corresponding authors. Tel.: +81-6-6368-1121; fax: +81-6-6339-
026; e-mail: nishiya@ipcku.kansai-u.ac.jp
4
Scheme 2.
0
040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00602-0

3
690
T. Nishino et al. / Tetrahedron Letters 43 (2002) 3689–3691
Me3SiCl / cat.I2 / cat.CuI
with activated copper was completed in only 10 min,
giving the reductive coupling products in almost quan-
1
a
+
La
2a
7 %
+
3a
CH3CN, 25 °C, 10 min.
12
titative yields. These results suggested that activated
copper, which was generated by the reduction of cop-
per(I) iodide with lanthanum metal and/or low-valent
lanthanum species, accelerated the coupling reaction of
8
13 %
Scheme 3.
13
Table 1. Deoxygenative coupling of various alcohols with
alkyl iodides (Scheme 6).
a
La metal
Me3SiCl
cat.I2, cat.CuI
Ether and ester are also readily deoxygenatively cou-
OH
cat.
cat.
pled by the use of La/Me SiCl/ I / CuI system. 3-
R1
R3
Coupling
Product
3
2
+
La
+ Alkane + Alkene
Heptyloxy-cyclohexene (6) or 3-acetoxycyclohexene (7)
was treated with lanthanum metal and chlorotrimethyl-
silane in the presence of a catalytic amount of iodine,
R2
CH CN
3
1
2
3
4
copper(I) iodide and H O (0.2 equiv.) to form 3,3%-bicy-
2
1
R1
R2
R3
Yield (%)b
clohexenyl (2j) in 81 and 57% yields, respectively
14
(
Scheme 7).
2
3
4
La
I2
1
1
1
1
1
1
1
1
1
b
c
d
e
f
g
h
i
C H
CH3 CH3 2b 54
3b 13
3c 11
3d 15
3e 5
4b 29
4c 6
6
5
5
5
c
C H
CH3
H
H
H
H
H
H
H
H
2c 72
6
R
R R
R
Me3SiCl
C H
H
2d 42
2e 67
2f 59
2g 34
2h 0
–
–
–
–
–
6
LaIn
p-CH O-C H
p-CH -C H
4
p-Cl-C H4
p-CN-C H4
H
H
H
H
H
3
6
4
LaCln
3f 10
3g 18
3h 0
La
3
6
6
6
d
e
e
C H CHꢁCH
2i (71)
N.q.
N.q.
N.q.
6
5
c
e
e
j
-CHꢁCH-(CH ) -
2j 75
N.q.
2
3
R I
Me3SiI
a
Reaction conditions: alcohol (1.0 mmol), lanthanum metal (1.0
mmol), Me SiCl (2.0 mmol), I (0.2 mmol), CuI (0.2 mmol) and
3
2
CH CN (3.0 mL) at 82°C for 1 h.
GC yield. The number in parentheses indicates isolated yield.
Dl:meso=1:1.
3
b
c
R OH
Me3SiOH
HI
d
1
1
,6-Diphenyl-1,5-hexadiene:1,4-diphenyl-1,5-hexadiene:3,4-diphenyl-
,5-hexadiene=32:49:19.
R OSiMe3
R OSiMe3
e
Not quantified.
Scheme 4. A possible reaction path.
7
,8
good yields.
We have recently found that alkyl
cat.I2
iodides were reductively coupled by lanthanum metal to
give the corresponding coupling products. Based on
these results, the following reaction pathway involving
the formation of alkyl iodides was proposed: (i) the
generation of lanthanum iodide species (LnI ) by the
+
La
2d
Ph
Br
9
CH3CN, 25 °C, 5 h
5
additive: none
cat.CuI
=
=
11 %
74 %
n
reaction of lanthanum metal with iodine, (ii) halogen
exchange reaction of Me SiCl with LnI to form
Scheme 5.
3
n
1
0,11
Me SiI,
and (iii) the reaction of alcohols with
3
La
I2
Me SiI to form alkyl iodide. In the absence of copper(I)
3
iodide, alkyl iodides were reductively coupled by lan-
thanum metal and/or low-valent lanthanum species to
give the corresponding coupling products, and the lan-
Me3SiCl
LaCln
LaIn
La
thanum iodide species (LnI ) was regenerated (Scheme
n
4
). The deoxygenative coupling of alcohols was
CuI
Me3SiI
markedly promoted by the addition of a catalytic
amount of copper(I) iodide. To obtain information on
the role of copper(I) iodide, the reaction of benzyl
bromide (5) with lanthanum metal was performed in
the presence and absence of copper(I) iodide. The treat-
ment of 5 with lanthanum metal in the presence of a
catalytic amount of iodine and copper(I) iodide (0.2
equiv.) in acetonitrile at 25°C for 5 h gave 1,2-
diphenylethane (2d) in 74% yield; however, in the
absence of copper(I) iodide, the reaction was extremely
slow (11%) (Scheme 5). Ebert et al. have already
reported that the reaction of benzyl and allyl halides
Cu
R R
R OH
R OSiMe3
R
I
HI
Me3SiOH
R OSiMe3
Scheme 6. A possible path in the presence of a catalytic
amount of CuI.

T. Nishino et al. / Tetrahedron Letters 43 (2002) 3689–3691
3691
R
mg, 0.2 mmol) were placed in a three-necked flask. Alco-
O
hol (1 mmol) in CH CN (3 mL) and chlorotrimethylsi-
3
Me3SiCl / cat.I2 / cat. CuI / cat. H2O
lane (217 mg, 2.0 mmol) were added, and the mixture was
stirred at 82°C for 1 h under a nitrogen atmosphere. The
color of the solution gradually changed to gray. After the
reaction, aq. HCl (1 M, 5 mL) was added to the reaction
mixture and extracted with benzene (20 mL×5). The
+
La
2j
CH3CN, 82 °C, 1 h
R = n-C7H15 (6)
R = COCH3 (7)
81 %
57 %
organic layer was dried over MgSO . The resulting mix-
4
Scheme 7.
ture was filtered and the filtrate was concentrated. Purifi-
cation of the residue by HPLC afforded the
corresponding deoxygenative dimerization, deoxygena-
tion and dehydration products. Products were character-
In summary, it was found that the deoxygenative cou-
pling of alcohols, ethers and esters efficiently proceeded
by the treatment of lanthanum metal and chloro-
trimethylsilane in the presence of a catalytic amount of
iodine and copper(I) iodide.
1
13
ized by comparison of their spectral data ( H and
C
NMR and IR) with those of authentic samples.
7
8
. Jung, M. E.; Ornstein, P. L. Tetrahedron Lett. 1977, 18,
659.
. Me SiCl/NaI/CH CN reagent has been recognized as a
2
3
3
Acknowledgements
Me SiI equivalent and used as a versatile reagent for the
3
conversion of alcohols into organoiodide compounds,
see: (a) Olah, G. A.; Narang, S. C.; Gupta, B. G. B.;
Malhotra, R. J. Org. Chem. 1979, 44, 1247; (b) Sakai, T.;
Miyata, K.; Utaka, M.; Takeda, A. Tetrahedron Lett.
This research was supported in part by Grant-in Aid
for Science Research from the Ministry of Education,
Science and Culture, Goverment of Japan. We thank
the Santoku Co. for supplying the lanthanum metal.
1
987, 28, 3817; (c) Sakai, T.; Miyata, K.; Tsuboi, S.;
Takeda, A.; Utaka, M.; Toru, S. Bull. Chem. Soc. Jpn.
989, 62, 3537; (d) Irifune, S.; Kibayashi, T.; Ishii, Y.;
1
Ogawa, M. Synthesis 1988, 366; (e) Kanai, T.; Irifune, S.;
Ishii, Y.; Ogawa, M. Synthesis 1989, 283.
. Nishino, T.; Watanabe, T.; Nishiyama, Y.; Sonoda, N. J.
References
9
1
2
. Larock, R. C. Comprehensive Organic Transformations: A
Guide to Functional Group Preparations; VCH Publishers:
New York, 1989; pp. 47–48 and references cited therein.
. (a) Bohlmann, R. In Comprehensive Organic Synthesis;
Trost, B. M.; Fleming, I., Eds.; Oxford: Pergamon Press,
Org. Chem. 2002, 67, 966.
10. Kr u¨ erke has reported that Me SiI was generated by the
3
reaction of Me SiCl with magnesium(II) iodide in
3
CH CN. See: Kr u¨ erke, U. Chem. Ber. 1962, 95, 174.
3
11. In the absence of iodine, deoxygenative coupling of 1a
did not occur; however, the use of iodotorimethylsilane
instead of chlorotrimethylsilane gave the deoxygenative
coupling product of 1a in 41% yield. These results might
strongly suggest the generation of iodotrimethylsilane by
the reaction of chlorotrimethylsilane with lanthanum
metal in the presence of a catalytic amount of iodine.
12. Ginah, F. O.; Donovan, T. A., Jr.; Suchan, S. D.; Pfen-
nig, D. R.; Ebert, G. W. J. Org. Chem. 1990, 55, 584.
13. Active zero-valent copper has been commonly prepared
by the reduction of a copper(I) halide phosphine complex
by lithium naphthalenide. See: Reike, R. D.; Sell, M. S.;
Klein, W. R.; Chen, T.; Brown, J. D.; Hanson, M. V.
Active Metals; F u¨ rstner, A., Ed.; VCH Publishers: New
York, 1995, pp. 33–48 and references cited therein.
1
991; Vol. 6, pp. 203–223; (b) Larock, R. C. In Compre-
hensive Organic Transformations: A Guide to Functional
Group Preparations; VCH Publishers: New York, 1989;
pp. 353–360 and references cited therein.
3
. (a) van Tamelen, E. E.; Schwartz, M. A. J. Am. Chem.
Soc. 1965, 87, 3277; (b) Sharpless, K. B.; Hanzlik, R. P.;
van Tamelen, E. E. J. Am. Chem. Soc. 1968, 90, 209; (c)
van Tamelen, E. E.; Akermark, B.; Sharpless, K. B. J.
,
Am. Chem. Soc. 1969, 91, 1552; (d) McMurry, J. E.;
Fleming, M. P. J. Am. Chem. Soc. 1974, 96, 4708; (e)
McMurry, J. E.; Silvestri, M. J. Org. Chem. 1975, 40,
2
687.
4
5
. Sato, M.; Oshima, K. Chem. Lett. 1982, 157.
. When the reaction of 1a with lanthanum metal and
chlorotrimethylsilane in the presence of sodium iodide
and copper(I) iodide, 2a was obtained; however, the yield
of 2a was slightly decreased compared with that of
iodine.
14. In these reactions, it was proposed that 6 and 7 are
efficiently converted into cyclohexenyl iodide by hydro-
gen iodide generated in situ by the reaction of
15
iodotrimethylsilane with H O.
2
6
. General procedure: Lanthanum powder (139 mg, 1
mmol), iodine (51 mg, 0.2 mmol) and copper(I) iodide (36
15. Kanai, T.; Kanagawa, Y.; Ishii, Y. J. Org. Chem. 1990,
55, 3274 and Refs. 8d and 8e.