N. Miyoshi, T. Matsuo, M. Wada
SHORT COMMUNICATION
and slightly increasing the amount of methyl iodide previous studies,[12] the results for the alkylation of alde-
(3.0 molar amounts), the corresponding product was af- hydes that have an α proton or of imines that are derived
forded in good yield (Entry 4 in Table 1). In each case, we from enolizable aldehydes were poor. One of the reasons
did not obtain the dihydride product (α-methylstyrene). Al- may be that alkylstrontium halide analogues have a strong
though we also tried the reaction under similar conditions nucleophilicity, as well as a strong basicity, which obstructs
using magnesium metal, good and easily reproducible re- the alkylation of these kinds of aldehydes or imines. How-
sults were hard to obtain. In contrast, our method is simple ever, in this case, when using enolizable esters, dialkylated
and easy, and good results can consistently be obtained.
alcohols were obtained in good yields. Thus, the reason may
Next, the scope and versatility of the present reaction be that the acidities of α protons in esters are lower than
were investigated by using various alkyl iodides, and the those of aldehydes or imines.
results are summarized in Table 2. Methyl benzoate reacted
In summary, alkyl halides react with metallic strontium
with primary alkyl iodides to afford the corresponding ad- to produce alkylstrontium halide analogues that feature
ducts in good yields. However, the reactions of the ester strong nucleophilicity as well as strong basicity, which pres-
with a sec-alkyl or tert-alkyl iodide, such as isopropyl iodide ents some difficulty in controlling their reactions. Neverthe-
or tert-butyl iodide, were sluggish and gave the correspond- less, the Barbier-type alkylation of esters with alkyl iodides
ing adducts in very low yields.
proceeded smoothly at room temperature under argon to
afford the corresponding dialkylated alcohols in good
yields. Investigation of the reaction mechanism and further
applications are now in progress.
Table 2. Dialkylation of methyl benzoate with various alkyl iodides.
Supporting Information: Representative experimental
procedures, and NMR and IR spectra of all products (see
footnote on the first page of this article).
Entry
R
Molar amounts (Sr, RI)/ester
Yield [%]
[1] a) N. A. Bell (“Beryllium”), N. A. Lindsell (“Magnesium, Cal-
cium, Strontium and Barium”), in Comprehensive Organome-
tallic Chemistry (Eds.: G. Wilkinson, F. G. A. Stone, E. W.
Abel), Pergamon Press, Oxford, 1982, vol. 1, chapter 3, p. 121,
and chapter 4, p. 155; b) W. E. Lindsell, “Beryllium, Magne-
sium, Calcium, Strontium and Barium”, in Comprehensive Or-
ganometallic Chemistry II (Eds.: E. W. Abel, F. G. A. Stone, G.
Wilkinson), Pergamon Press, Oxford, 1995, vol. 1, chapter 3,
p. 57, and references cited therein; c) N. Miyoshi, “Product
Class 8: Strontium Compounds”, in Methods of Molecular
Transformation, Science of Synthesis (Houben-Weyl) (Ed.: H.
Yamamoto), Thieme, Stuttgart, 2004, vol. 7, p. 685; and see
also “Product Class 5, 6, 7, and 9”, in Science of Synthesis, vol.
7, for Beryllium, Magnesium, Calcium and Barium, respec-
tively.
[2] For the synthesis of alkylcalcium halide and the reaction using
Rieke calcium, see: a) K. Mochida, S. Ogura, T. Yamanishi,
Bull. Chem. Soc., Jpn. 1986, 59, 2633; b) T. Wu, H. Xiong,
R. D. Rieke, J. Org. Chem. 1990, 55, 5045; c) R. A. O’Brien, T.
Chen, R. B. Rieke, J. Org. Chem. 1992, 57, 2667.
[3] For the reaction using Rieke barium, see; a) A. Yanagisawa, S.
Habaue, H. Yamamoto, J. Am. Chem. Soc. 1991, 113, 8955; b)
1
2
3
4
5
6
Me
Et
nBu
iBu
iPr
2.5
2.5
3.0
3.0
3.0
3.0
96
80
84
96
[a]
–
–
[a]
tBu
[a] The reactions were sluggish and the desired products were ob-
tained only in negligible amounts. In these cases, we obtained small
amounts of the p-alkylated product (the 1,6-adduct of the benzo-
ate). See ref.[12a]
.
The generality of the present reaction was investigated
by using various esters and methyl iodide, and the results
are summarized in Table 3. It should be noted that func-
tional groups such as olefin or bromide remain intact under
the reaction conditions. Interestingly, the reactions pro-
ceeded smoothly to give the products in good yields with
esters that have an α proton (Entries 3–7 in Table 3). In
Table 3. Dimethylation of various esters with methyl iodide.
Entry
R1
R2
Molar amounts (Sr, MeI)/ester
Yield [%]
1
2
3
4
5
6
7
p-ClC6H4
p-CH3OC6H4
PhCH2
PhCH2CH2
CH3(CH2)14
CH2=CH(CH2)8
Br(CH2)5
Me
Me
Me
Et
Me
Me
Et
3.0
2.5
2.5
3.0
3.0
3.0
3.0
90
52[a]
81
90
84
87
84
[a] Dehydrated olefin was obtain in 19% yield.
4254
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2005, 4253–4255