Regioselective allylation reactions using crotyl Grignard reagent-CeCl3 systems

Article abstract of DOI:10.1016/S0040-4039(02)02741-7

Regioselective allylation reactions using crotyl Grignard reagent-CeCl₃ systems are described. Regioselectivity depends on the lanthanide salts: α-product was predominantly produced with light rare earth elements such as La, Ce, Pr, Nd, whereas

Full text of DOI:10.1016/S0040-4039(02)02741-7

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 1007–1010
Regioselective allylation reactions using crotyl Grignard
reagent–CeCl3 systems
Satoru Matsukawa,* Yohei Funabashi and Tsuneo Imamoto
Department of Chemistry, Faculty of Science, Chiba University, Inage-ku, Chiba 263-8522, Japan
Received 18 October 2002; revised 20 November 2002; accepted 29 November 2002
Abstract—Regioselective allylation reactions using crotyl Grignard reagent–CeCl3 systems are described. Regioselectivity depends
on the lanthanide salts: a-product was predominantly produced with light rare earth elements such as La, Ce, Pr, Nd, whereas
g-product was formed when heavy rare earth elements were used. © 2003 Elsevier Science Ltd. All rights reserved.
The reactions in Grignard reagents–CeCl3 systems with
carbonyl compounds have become important car-
bonꢀcarbon bond forming reactions in organic synthe-
sis because these combined reagent systems effectively
suppress undesired reactions such as enolization, reduc-
tion, condensation, conjugate addition, and pinacol
coupling.1,2 Although reported examples using this sys-
tem number in the hundreds, the mechanisms underly-
ing these reactions remain unclear. In order to gain
insight into the mechanism of the generation of the
reactive intermediates, allylation reactions using crotyl
Grignard reagent–CeCl3 systems were examined. Allyl-
ation reactions represent one of the most fundamental
carbonꢀcarbon bond forming reactions in modern
organic synthesis.3 In general, reactions involving
unhindered carbonyl compounds with substituted
allylic organometallic reagents such as M=Li, Mg, Cu,
Zn, Cd, B, Al, Si, Sn, Ti, Zr, Cr, and Mn result in the
predominant formation of g-adducts in which the
allylic group is attached at the more highly substituted
position. On the other hand, a-selective allylation reac-
tions are also of great importance and to date, a
number of important studies have been carried out. For
example, it has been reported that allylic organometal-
lic reagents such as M=Mg–AlCl3,4 SPh–LDBB–
CeCl3,5 Ba,6 Sn–CoCl2,7 yield a-adducts.8 We report
herein regioselective allylation reactions of carbonyl
compounds using crotyl Grignard reagent–CeCl3
systems.
We examined allylation reactions that use crotyl Grig-
nard reagents with benzaldehyde in the presence of
various lanthanide salts. Reactions were carried out via
an addition of crotyl Grignard reagent to a suspension
of dry lanthanide salt in THF at 0°C. After 30 min,
benzaldehyde was added to the reaction mixture at
−78°C. The reaction was monitored by TLC.
Hydrolytic work-up with 3% AcOH, followed by
column chromatography, afforded the allylated
product. Results are summarized in Table 1 and Figure
1. Regioselectivity could be classified into three groups
based on increasing atomic number. A high level of
a-regioselectivity was observed with light rare earth
elements such as La, Ce, Pr and Nd. The configuration
of a-adducts was highly stereoselective for the trans
conformation. Gd, Tb, Dy and Ho afforded the a-
product to a medium degree. In contrast, g-regioselec-
tivity was observed when heavy rare earth elements: Er,
Tm, Yb and Lu were used. YbCl3, in particular
afforded the g-product almost exclusively. It is note-
worthy that high level of g-regioselectivity was also
observed when ScCl3 was used.
In order to clarify the origin of this selectivity, the
structure of reactive species in these reactions was
investigated. Tsutsui,9 Wu,10,11 Brunelli,12 and Evans13
independently reported on the synthesis and structure
of the allyllanthanide complexes: Cp2LnC3H5,9
Ln(C3H5)5Li2,10 (C3H5)5LnCl5Mg2(tmed)2,11 Ln(C3H5)4-
Li,12 and Cp*LnC3H5.13 Each structure has been
2
shown to possess a h3-allyl moiety using IR and/or
X-ray analysis. We then attempted to isolate the reac-
tive species of this reaction. Allyl or crotyl Grignard
reagent was added to a suspension of dry CeCl3 in THF
at 0°C. After stirring for 30 min, the resultant
Keywords: allylation; cerium and compounds; Grignard reagents;
regiocontrol.
* Corresponding author. Present address: Department of Science
Education, Faculty of Education, Ibaraki University, Mito, Ibaraki
310-8512, Japan.
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)02741-7

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S. Matsukawa et al. / Tetrahedron Letters 44 (2003) 1007–1010
Table 1. Regioselective allylation reactions of benzaldehyde by using crotyl Grignard reagent–rare earth chloride systemsa
Figure 1.

S. Matsukawa et al. / Tetrahedron Letters 44 (2003) 1007–1010
1009
Scheme 1. A plausible mechanism of the regioselective allylation reaction.
mixture was allowed to stand for 10 h at room temper-
ature and the supernatant was transferred to a cen-
trifuge tube. After centrifugation, the supernatant was
taken up and evaporated to give a dark brown pow-
der.14 Although, X-ray analysis was unsuccessful, struc-
tural information was obtained from the IR spectra.
The IR spectra of 1 and 2 in Nujol mulls show bands at
1540 cm−1 for 1 and 1560 cm−1 for 2, which could be
assigned to the delocalized CꢀC stretch characteristic of
h3-allyl moieties, according to the reported IR spectra
of the above allyllanthanide complexes (Fig. 1). In
contrast, the intermediate prepared from YbCl3 was
obtained as a white powder and the IR spectra did not
show any bands at 1540–1560 cm−1. These results sug-
gest that the reaction intermediate prepared from CeCl3
is an h3-allyl lanthanide complex, whereas that pre-
pared from YbCl3 is an another species. It is well
known that Sc(III) and Yb(III) have exceptionally high
catalytic activities in numerous Lewis acid-catalyzed
reactions.15 Their high Lewis acidities prevent
transmetallation due to strong MꢀCl bonds. The model
reaction was examined using dibenzylketone and n-
BuMgBr. The addition products were obtained in excel-
lent yields (98%) with CeCl3. On the other hand,
combined use of YbCl3 and n-butylmagnesium bromide
resulted in a lower yield (24%), probably because of
sluggish transmetalation.
Liu, H.-J.; Shia, K. S.; Shang, X.; Zhu, B.-Y. Tetrahedron
1999, 55, 3803; (e) Takeda, N.; Imamoto, T. Org. Synth.
1999, 76, 228; (f) Imamoto, T. Lanthanides in Organic
Synthesis; Academic Press: London, 1994; p. 80; (g)
Molander, G. A. Chem. Rev. 1992, 92, 29; (h) Imamoto,
T. In Comprehensive Organic Synthesis; Trost, B. M.;
Fleming, I.; Heathcock, C. H., Eds.; Pergamon Press:
Oxford, UK, 1991; Vol. 1, p. 231.
2. (a) Imamoto, T.; Takiyama, N.; Nakamura, K.; Hata-
jima, T.; Kamiya, Y. J. Am. Chem. Soc. 1989, 111, 4392;
(b) Imamoto, T.; Kusumoto, T.; Tawarayama, Y.; Sug-
iura, Y.; Mita, T.; Hatanaka, Y.; Yokoyama, M. J. Org.
Chem. 1984, 49, 3904.
3. For reviews, see: (a) Yamamoto, Y.; Asao, N. Chem.
Rev. 1993, 93, 2207; (b) Roush, W. R. In Comprehensive
Organic Synthesis; Trost, B. M.; Fleming, I.; Heathcock,
C. H., Eds.; Pergamon Press: Oxford, UK, 1991; Vol. 2,
p. 1; (c) Biellmann, J. F.; Ducep, J. B. Org. React. 1982,
27, 1; (d) Courtrois, G.; Miginiac, L. J. Organomet.
Chem. 1974, 69, 1.
4. Yamamoto, Y.; Maruyama, K. J. Org Chem. 1983, 48,
1564.
5. Guo, B.-S.; Doubleday, W.; Cohen, T. J. Am. Chem. Soc.
1987, 109, 4710.
6. (a) Yanagisawa, A.; Habaue, S.; Yamamoto, H. J. Am.
Chem. Soc. 1991, 113, 8955; (b) Yanagisawa, A.; Habaue,
S.; Yasue, K.; Yamamoto, H. J. Am. Chem. Soc. 1994,
116, 6130.
A plausible mechanism of this regioselective allylation
reaction is shown in Scheme 1. Transmetallation of
crotyl Grignard reagent to CeCl3 via the SE2% process
results in an h3-allylcerium species. Carbonyl com-
pounds react with the h3-allylcerium species at a steri-
cally less hindered site to give the a-allylated product.
7. Iqbal, J.; Joseph, S. Tetrahedron Lett. 1989, 30, 2421.
8. For other excellent examples on a-selective allylation
reactions, see: (a) Masuyama, Y.; Kishida, M.; Kurusu,
Y. J. Chem. Soc., Chem. Commun. 1995, 1405; (b)
Miyake, H.; Yamaura, K. Chem. Lett. 1992, 1369; (c)
McNeill, A. H.; Thomas, E. J. Tetrahedron Lett. 1992,
33, 1369; (d) Kanagawa, Y.; Nishiyama, Y.; Ishii, Y. J.
Org. Chem. 1992, 57, 6988; (e) Gambaro, A.; Boaretto,
A.; Marton, D.; Tagliavini, G. J. Organomet. Chem.
1984, 260, 255; (f) Yamamoto, Y.; Maeda, N.;
Maruyama, K. J. Chem. Soc., Chem. Commun. 1983, 742;
(g) Gambaro, A.; Gains, P.; Marton, D.; Peruzzo, V.;
Tagliavini, G. J. Organomet. Chem. 1982, 231, 307.
Sn(OTf)2-catalyzed a-regioselective allylation reaction of
homoallylic alcohols has been reported. See: (h) Nokami,
J.; Yoshizane, K.; Matsuura, H.; Sumida, S. J. Am.
Chem. Soc. 1998, 120, 6609.
In summary, we have demonstrated regioselective allyl-
ation reactions using crotyl and prenyl Grignard
reagent–CeCl3 systems. Regioselectivity was found to
depend on the lanthanide salts. The structures of the
intermediates were investigated based on IR spectra,
and the h3-allylcerium complex is suggested. These
results indicate that the organocerium species, written
as ‘RCeCl2’, are produced from Grignard reagent and
CeCl3, and is one of the active species in Grignard
reagent–CeCl3 systems.
9. Tsutsui, M.; Ely, N. J. Am. Chem. Soc. 1990, 97, 3551.
10. Huang, Z. E.; Chen, M. Q.; Qiu, W. J.; Wu, W. L. Inorg.
Chim. Acta 1987, 131, 742.
11. Wu, W. L.; Chen, M. Q.; Zhou, P. Organometallics 1991,
10, 98.
12. Brunelli, M.; Poggio, S.; Pedretti, U.; Ligli, G. Inorg.
Chim. Acta 1987, 131, 281.
13. Evans, W. J.; Ulibarri, T. A.; Ziller, J. W. J. Am. Chem.
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