Investigation into the Allylation Reactions of Aldehydes Promoted by the CeCl3·7H2O-NaI System As A Lewis Acid

Article abstract of DOI:10.1021/jo035542o

The Lewis acid promoted allylation of aldehydes has become an important carbon-carbon bond forming reaction in organic chemistry. In this context, we have developed an alternative over existing catalytic processes, wherein aldehydes are subject in acetoni

Full text of DOI:10.1021/jo035542o

In vestiga tion in to th e Allyla tion Rea ction s of Ald eh yd es P r om oted
by th e CeCl3‚7H2O-Na I System a s a Lew is Acid
Giuseppe Bartoli,† Marcella Bosco,† Arianna Giuliani,‡ Enrico Marcantoni,*,‡
Alessandro Palmieri,‡ Marino Petrini,‡ and Letizia Sambri†
Dipartimento di Scienze Chimiche, Universita` di Camerino, via S. Agostino 1, I-62032 Camerino (MC),
and Dipartimento di Chimica Organica “A. Mangini”, Universita` di Bologna, viale Risorgimento 4,
I-40136 Bologna, Italy
enrico.marcantoni@unicam.it
Received October 18, 2003
The Lewis acid promoted allylation of aldehydes has become an important carbon-carbon bond
forming reaction in organic chemistry. In this context, we have developed an alternative over existing
catalytic processes, wherein aldehydes are subject in acetonitrile to reaction of allylation with
allyltributylstannane in the presence of 1.0 equiv of cerium(III) chloride heptahydrate (CeCl3‚7H2O),
an inexpensive and mild Lewis acid. The allylation has been accelerated by using an inorganic
iodide as a cocatalyst, and various iodide salts were examined. The procedure must use allylstannane
reagent instead of allylsilane reagent, desirable for environmental reasons, but high chemoselectivity
was observed, and this is opposite the results obtained with other classical Lewis acids such as
TiCl4 and Et2O‚BF3.
In tr od u ction
including mild reaction conditions, cleaner reactions,
shorter reaction times, high yield of the products, lower
catalytic loading, and simple experimental and isolation
procedures. However, these methods involve expensive
reagents; thus, recently, cerium(III) chloride has become
an attractive candidate for use as a Lewis acid in organic
chemistry for its relative nontoxicity and ready avail-
ability at a low cost. In fact, after the pioneering works
by Luche5 and Imamoto6 numerous reactions and meth-
odologies employing cerium(III) derivatives as key com-
ponents have been developed.7 It has been observed that
CeCl3 plays a fundamental role in transferring a nucleo-
phile moiety to electrophilic centers.8
Lewis acids play a vital role in organic reactions, and
in this respect, extensive efforts have been devoted to the
exploration of new generations of these compounds.1
Various kinds of Lewis acid promoted reactions were
developed, and these reactions must be carried out under
strictly anhydrous conditions. Even a small amount of
water stops reactions using these species because the
reagents immediately react with water rather than the
substrates. For this reason new types of water-tolerant
Lewis acids were developed.2 In this regard, the lan-
thanide compounds have become attractive candidates
for use as Lewis acid reagents in organic chemistry, and
have found numerous applications as promoters.3 The
introduction of electronegative ligands such as triflates
enhances the activity by increasing the Lewis acidity of
the metal.4 These catalysts offer several advantages
In the course of our program aimed to develop new
synthetic uses of CeCl3‚7H2O9 in reactions that need the
presence of a Lewis acid activator, it was found that this
salt acts as a promoter that facilitates the cleavage of
the carbon-oxygen bond10 and silicon-oxygen bond11
* To whom correspondence should be addressed. Phone: +39 0737
402255. Fax: +39 0737 637345.
(5) (a) Gemal, A. L.; Luche, J .-L. J . Am. Chem. Soc. 1981, 103, 5454-
5459. (b) Luche, J .-L.; Gemal, A. L. Tetrahedron Lett. 1981, 22, 4077-
4080. (c) Gemal, A. L.; Luche, J .-L. J . Am. Chem. Soc. 1979, 101, 5848-
5849. (d) Luche, J .-L. J . Am. Chem. Soc. 1978, 100, 2226-2227.
(6) (a) Imamoto, T. Pure Appl. Chem. 1990, 62, 747-776. (b) Immoto,
T.; Takiyama, N.; Nakamura, K.; Hatajima, T.; Kamiya, Y. J . Am.
Chem. Soc. 1989, 111, 4392-4398. (c) Immoto, T.; Takiyama, N.;
Nakamura, K. Tetrahedron Lett. 1985, 26, 4763-4766. (d) Imamoto,
T.; Kusumoto, T.; Tawarayama, Y.; Mita, T.; Hatanaka, Y.; Yokoyama,
M. J . Org. Chem. 1984, 49, 3904-3912.
(7) For a recent review on this argument see: (a) Dalpozzo, R.; De
Nino, A.; Bartoli, G.; Sambri, L.; Marcantoni, E. Recent Res. Dev. Org.
Chem. 2001, 5, 181-191. (b) Bartoli, G.; Marcantoni, E.; Sambri, L.
Seminars in Organic Synthesis; XXV Summer School “A. Corbella”,
Gargnano (BS); Italian Chemical Society: Rome, 2000; pp 117-138.
(c) Liu, H. J .; Shia, K. S.; Shang, X.; Zhu, B. Y. Tetrahedron 1999, 55,
3803-3830. (d) Imamoto, T. Lanthanides in Organic Synthesis;
Academic Press: New York, 1994. (e) Molander, G. A. Chem. Rev. 1992,
92, 29-68. (f) Imamoto, T. In Comprehensive Organic Synthesis, Trost,
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Vol. 1, pp 231-250.
† Universita` di Bologna.
‡ Universita` di Camerino.
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Oxford University Press: New York, 1999. (b) Santelli, M.; Pons, J .-
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Raton, FL, 1995. (c) Mahrwald, R. Chem. Rev. 1999, 99, 1095-1120.
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J . B. F. N.; Feringa, B. L.; Keller, E.; Otto, S. Recl. Trav. Chim. Pays-
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10.1021/jo035542o CCC: $27.50 © 2004 American Chemical Society
Published on Web 01/23/2004
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J . Org. Chem. 2004, 69, 1290-1297

Allylation Reactions of Aldehydes
synthesis.16 A number of such nucleophilic additions to
carbonyl compounds have been developed, and in par-
ticular, the reactions with allylic metals bearing IUPAC
periodic table group 14 elements in the presence of Lewis
acid have been extensively studied because of their high
reactivity and selectivity.17 However, many of these
reactions cannot be carried out in the presence of oxygen
and moisture, which can decompose or deactivate the acid
catalyst.18 To circumvent these problems, new procedures
have been developed for this conversion19 using lan-
thanide triflates20 and indium salts,21 compounds less
commonly employed for Lewis acid promoted carbon-
carbon bond formation22 as catalysts. Metal triflates are
strongly acidic and highly expensive, whereas indium
salts produce low Lewis acidity with respect to Ce(III)
salts.23 So the development of a neutral alternative such
as our CeCl3‚7H2O-NaI combination would extend the
scope of the important addition of various allylmetal
reagents to carbonyl compounds.
SCHEME 1
under neutral conditions. In particular, we have observed
that CeCl3, being a hard Lewis acid,12 is suitable to form
a weak and labile iodide ion-Lewis acid complex.10i The
nucleophile donor can enhance the electrophilicity of a
Lewis acidic promoter, a concept masterfully developed
by Denmark.13 The CeCl3‚7H2O-NaI system appears,
then, competitive and in several cases superior as a Lewis
acid to preexisting protocols. To better evaluate the
sodium iodide ability to enhance the activity of cerium
trichloride as a Lewis acid, we have here investigated
one of the most important carbon-carbon bond forming
reactions in organic chemistry, the addition of allylmetal
reagents to aldehydes.14
The allylation reaction represents one of the most
useful methods for the preparation of homoallylic alcohols
(Scheme 1), which are useful tools for the construction
of complex molecules15 and which can be easily converted
to many important building blocks for natural product
Resu lts a n d Discu ssion
We first examined the reaction of allyltrimethylsilane
with aldehydes in the presence of CeCl3‚7H2O and NaI,
but no addition proceeded in acetonitrile. An attempt to
increase the Lewis acidity of our system24 by using this
couple supported on silica gel25 also failed to give the
desired homoallylic adduct. Allylsilanes are generally
more desirable than allylmetal reagents, particularly for
environmental reasons. However, their lower reactivity26
might not be sufficient to react with aldehydes in our
reaction conditions; thus, other allylmetal reagents such
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chemical generation, and homoallylic alcohols were synthesized from
carbonyl compounds and allylic acetates, using an electrochemical
process catalyzed by iron complexes; see: Durandetti, M.; Meignein,
C.; Pe´richon, J . J . Org. Chem. 2003, 68, 3121-3124.
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(25) The CeCl3‚7H2O-NaI system dispersed on chromatography
silica gel was prepared by simple mixing of both reagents in acetonitrile
followed by complete removal of the solvent.
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Bartoli et al.
TABLE 1. Cer iu m Tr ich lor id e-Sod iu m Iod id e System
P r om oted Allyla tion of Ald eh yd es Usin g
Allyltr ibu tylsta n n a n e
F IGURE 1. The amount of NaI influences the efficiency of
the reaction.
as allylstannanes were added to the reaction mixture.
Our attention was turned to using allyltributylstannane
since it does not require rigorously dry conditions and
an inert atmosphere, and in comparison with most metals
it is relatively inexpensive and readily available.27
Benzaldehyde (3a ) was examined as a model substrate
as a ca. 0.1 M solution in acetonitrile containing 1.0 equiv
of CeCl3.7H2O and 1.0 equiv of NaI. After treatment with
allyltributylstannane (4) the resulting heterogeneous
reaction mixture was stirred and monitored by TLC and
GC/MS. A homoallylic adduct (5a ) was obtained in
moderate yield (58%) after extractive workup and chro-
matography on a silica gel column. In optimizing the
reaction conditions, we tested several combinations of
NaI amounts. The results in Figure 1 indicate that the
molecular percent of sodium iodide used is crucial, and
a significantly lower yield of homoallyl alcohol 5a was
produced using more than 30 mol % NaI. Surprisingly,
the addition of up to 20 mol % inhibits the reaction, and
the tributyltin iodide (Bu3SnI) identified by GC/MS
indicates iodide ion binding to the tin metal with result-
ing decomposition of the allyl reagent.28 Thus, the amount
of NaI is decisive for this type of allylation, and 10 mol
% has been the most appropriate. In the absence of NaI,
the aldehyde 3a reacts very slowly with the allylating
agent and the yields are generally very low. For example,
when 3a was treated with allylmetal 4 and CeCl3‚7H2O
in acetonitrile, the corresponding homoallylic alcohol 5a
was isolated in only 28% yield after 5 days.29 Likewise,
when attempts to carry out allylation of 3a with stannane
4 and NaI, in the absence of CeCl3‚7H2O, the almost
quantitative recovery of aldehyde substrate was observed.
However, addition of CeCl3‚7H2O to this mixture resulted
in the disappearance of the starting material.
Encouraged by these results, we have carried out the
allylation of a variety of aldehydes30 to understand the
scope and reactivity of our procedure, and the results are
summarized in Table 1. The good-to-excellent yields
strongly suggest that our CeCl3‚7H2O-NaI system is an
efficient Lewis acid promoter for the allylation of alde-
hydes. The reaction proved to be general and could be
applied to a broad range of aldehydes. Specifically, the
reaction proceeds smoothly under very mild conditions
a
b
All starting aldehydes were commercially available. All
products were identified by their IR, NMR, and GC/MS. c Yields
of products isolated by column chromatography. Yield by GC/
MS analysis.
d
(27) (a) Chan, T. H.; Yang, Y.; Li, C. J . J . Org. Chem. 1999, 64,
4452.4455. (b) Chataiguer, I.; Piarulli, L.; Gennari, C. Tetrahedron Lett.
1999, 40, 3633-3634. (c) Fleming, I.; Barbero, A.; Walter, D. Chem.
Rev. 1997, 97, 2063-2192.
(28) Light, J . P.; Ridenour, M.; Beard, L.; Herhberger, J . W. J .
Organomet. Chem. 1987, 326, 17-24.
(29) No reaction took place in the absence of CeCl3‚7H2O.
(30) Unfortunately, the desired allylation did not proceed well from
R,â-unsaturated carbonyl compounds (Table, entry 13).
at room temperature.31 There is no need to exclude
moisture or oxygen from the reaction system, and the
(31) See the Supporting Information (SI) for details.
1292 J . Org. Chem., Vol. 69, No. 4, 2004

Allylation Reactions of Aldehydes
SCHEME 2
SCHEME 3
removal of any excess of allyltributylstannane and other
tin byproducts by treatment with 10 mol % KF and rapid
filtration through silica gel32 clearly demonstrate these
advantages. It should be noted that the complex CeCl3‚
7H2O-NaI system promotes the allylation of both aro-
matic and aliphatic aldehydes, giving excellent yields of
product 5 in a short period. Enolizable aldehydes also
produce the corresponding homoallylic alcohol in good
yields (entries 9, 10, and 12). Furthermore, the treatment
of aldehyde 3k with allylstannane 4 in our reaction
conditions gave only the homoallylic alcohol 5k without
a trace of Z-E isomerization of the double bond, and no
oxyceriation11a of the carbon-carbon double bond is
involved. Thus, a simple Brønsted acid (HX) catalyzed
mechanism cannot explain all these observations, since
it is known that allyltributylstannanes do not react with
carbonyl compounds in the presence of halogen acids.33
Only when the above-described methodology was applied
to aldehyde 3m ,34 a low yield of adduct 5m , as identified
by GC/MS, was obtained with formation of a mixture of
unidentifiable products, and this might be attributed to
nucleophilic substitution by iodide ion (Table 1, entry 13).
It is interesting to note that a stoichiometric amount
of CeCl3‚7H2O is required for high efficiency, whereas an
excess of cerium salt leads to lower yields (Scheme 2),
and GC/MS analysis of the mixture reaction shows the
decomposition of allylstannane 4 with formation of tribu-
tyltin chloride (Bu3SnCl). We have also examined the
possibility of CeCl3‚7H2O functioning catalytically or at
least in less than stoichiometric amounts. But the best
results were obtained with an equimolar ratio of cerium
trichloride and aldehydes. To improve the efficiency of
the promoter system, we have examined different ratios
among the aldehydes, allyltributylstannane, cerium salt,
and the iodide. The best results were found (Table 1)
when the ratio [aldehyde]:[CH2dCHCH2SnBu3]:[CeCl3‚
7H2O]:[NaI] was 1:1:1:0.1. Interestingly, since an amount
of CeCl3 equivalent to that of the aldehydes gives the best
result in these allylations, we believe that an n:n
complex35 of substrate and CeCl3 would be the most
effective species.
an important component of the reaction system and does
not decrease the yield of homoallylic alcohol, as a
consequence of a possible competitive aldehyde dimer
formation. For our methodology, in fact, the cerium
trichloride has been utilized as a heptahydrate complex.
When anhydrous cerium(III) chloride salt36 was employed
in dry solvent, the rate dropped dramatically (Scheme
3). However, by adding 1 equiv of water to the dry
reaction mixture, we have obtained the same reactivity
as with the cerium salt heptahydrate. In particular, with
<1 equiv of water, decreased activity was observed, while
with 1, 4, 7, and 10 equiv of water, essentially identical
results were obtained. It is also worth noting that the
reaction of 3a with allylmetal reagent 4 in the presence
of our CeCl3‚7H2O-NaI system was significantly acceler-
ated by exposing the stirring mixture to the atmosphere.
Comparing the rate of allylation of benzaldehyde when
exposed to air (through a MgSO4 drying tube) to the rate
with the use of water added and acetonitrile as solvent
demonstrated that water, and not oxygen, accelerates the
reaction. The role of the water is not clearly understood
at this time. The reaction behaves empirically as though
an inactive complex is generated in the absence of water.
Thus, without conclusive data, we postulate that the
Having established what appeared to be the optimal
conditions, we switched our attention to the water of
crystallization of the salt. Water (from CeCl3‚7H2O) is
(32) Davies, A. G. Organotin Chemistry; Wiley-VCH: Weinheim,
Germany, 1997.
(33) Yanagisawa, A.; Morodome, M.; Nakashima, H.; Yamamoto, H.
Synlett 1997, 1309-1311.
(34) Marcantoni, E.; Mecozzi, T.; Petrini, M. J . Org. Chem. 2002,
67, 2989-2994.
(35) Analogously to Yamamoto’s work (Nakamura, H.; Ishihara, K.;
Yamamoto, H. J . Org. Chem. 2002, 67, 5124-5137), we have no
evidence that the complex consists of one aldehyde molecule and one
CeCl3 molecule. There is a possibility that a 2:2, 4:4, or n:n complex
exists.
(36) Imamoto, T.; Takeda, N. Org. Synth. 1998, 76, 228-238.
J . Org. Chem, Vol. 69, No. 4, 2004 1293

Bartoli et al.
SCHEME 4
cerium center may require ligation by 1 or more equiv of
water for generating fully active species.37 It is known,38
in fact, that very probably the water preferentially
coordinates the cerium chloride, promoting the dissocia-
tion of chloride anion to form a more active Lewis acid
species by the reaction
the solid CeCl3‚7H2O-NaI system. In fact, CeCl3‚7H2O,
which is poorly soluble in acetonitrile (ca. 0.03 M),40 and
NaI were stirred in acetonitrile for 24 h at room tem-
perature; afterward the mixture was filtered. To the
filtrate was added benzaldehyde 3a and allylmetal
reagent 4, and the solution was stirred under the same
conditions as in Table 1, entry 1. The yield of the desired
homoallylic alcohol was only 6%, and apparently, the
allylation reaction in the homogeneous phase is very
slow. Thus, we believe that the disaggregation of the
crystal lattice of CeCl3 by NaI (similarly by ZnI2, CdI2,
and KI) might lead to a notable increase in the Lewis
acidity of the cerium available at the particle surface.
Therefore, the catalytic activity of inorganic iodide salts
(MIn) seems directly dependent on their particle size, and
not on the nature of the metal M. In fact, the CeCl3‚
7H2O-ZnI2 combination, which gives a fine powder,
shows an activity similar to that of the CeCl3‚7H2O-NaI
system, and both are more active systems than CeCl3‚
7H2O-CuI, which produces a coarser powder. All this
evidence strongly suggests that the activity of the CeCl3‚
7H2O-NaI system is mainly exerted in the heteroge-
neous phase. Although there are a striking number of
chemical physics tools available,41 unfortunately, all the
effort of structural characterization of the complex was
unsuccessful, since it was impossible to obtain reliable
X-ray information. Efforts are under way in these labo-
ratories to explore the role of this Lewis acid promoter
for several organic transformations. Moreover, we decided
to investigate the use of iodine on the allylation of
aldehydes.22a We have found that when a mixture of
aldehyde 3a (1 equiv) and allylating reagent 4 (1 equiv)
is treated with CeCl3‚7H2O (1 equiv) and a catalytic
amount of elemental iodine (10 mol %), the reaction is
not more efficient than treatment with CeCl3‚7H2O alone.
This result might indicate that in our reaction conditions
the oxidization of iodide ion to iodine does not happen.
To provide a firm foundation for an understanding of
how our CeCl3‚7H2O-NaI system promotes the addition
of allyltributylstannane to aldehydes, it is essential to
establish how this reagent system interacts with the two
reaction components. For this we decided to see if the
allylstannane 4 would undergo transmetalation42 when
exposed to CeCl3 and determine the mode of complexation
CeCl3(solvent)m + H2O h
[CeCl3-n(solvent)m(H2O)]+ + Cl- (1)
The effect of solvent was then investigated. Previous
works by this group on the organic transformations
promoted by the CeCl3‚7H2O-NaI combination suggested
that acetonitrile is likely to be the solvent of choice for
this allylation.11b Other solvents were examined, and
solvents such as CH2Cl2, THF, DMF, or nitromethane
were not useful for this reaction. Similarly, without
organic solvent the allylation of aldehyde 3a was not
successful. Rather, the reaction concentration also proved
to be an important factor in obtaining the allylation
products in good yields. A concentration of ca. 0.1 M with
respect to the aldehydes is optimal. Poor yields were
obtained at concentrations greater than 0.5 M.
Next, we surveyed the acceleration effect caused by
addition of sodium iodide to CeCl3. This effect might be
rationalized by a halogen exchange reaction39 that leads
to more soluble species (eq 2).
CeCl3 + nNaI n ) 1-38 CeCl3-nIn + nNaCl (2)
However, hydrated CeI3 alone shows an activity only
slightly superior to that of CeCl3‚7H2O, but significatively
lower than that of the CeCl3‚7H2O-NaI combination.
Moreover, the system CeCl3‚7H2O-3NaI is less efficient
than CeCl3‚7H2O-0.2NaI. Then, another process might
be plausible. For this reason various inorganic iodides
were examined in the model reaction of nonal (3i) with
4 promoted by the Lewis acidity of cerium(III) chloride.
Data for the yields vs different iodides are summarized
in Scheme 4. Among them, some iodides, other than NaI,
have displayed some activity, but others such as CuI and
LiI have been revealed as ineffective.
Certainly, it is premature to speculate on the exact
mechanism provided by the anion iodide, but we have
obtained some evidence that the reaction is promoted by
(40) The Merck Index, 12th ed.; Merck & Co., Inc.: Whitehouse
Station, NJ , 1996; p 332.
(37) For the coordination chemistry of lanthanide halides, see: (a)
Evans, W. J .; Feldman, J . D.; Ziller, J . W. J . Am. Chem. Soc. 1996,
118, 4581-4584. (b) Evans, W. J .; Shreeve, J . L.; Ziller, J . W.; Doedens,
R. J . Inorg. Chem. 1995, 34, 576-585.
(41) Cope´ret, C.; Thivolle-Cazat, J .; Basset, J .-M. In Fine Chemicals
through Heterogeneous Catalysis; Sheldon, R. A., van Bekkum, H., Eds.;
Wiley-VCH: Weinheim, Germany, 2001; p 553.
(42) (a) Denmark, S. E.; Almstead, N. G. Tetrahedron 1992, 48,
5565-5578. (b) Keck, G. E.; Castellino, S.; Andrus, M. B. In Selectivities
in Lewis Acid Promoted Reactions; Schinzer, D., Ed.; Kluwer Academic
Publishers: Dodrecht, The Netherlands, 1989; pp 73-105. (c) Den-
mark, S. E.; Weber, E. J .; Wilson, T. M. Tetrahedron 1989, 111, 8136-
8141.
(38) Glinski, J .; Keller, B.; Legendziewicz, J .; Samela, S. J . Mol.
Struct. 2001, 59-66.
(39) (a) Fukuzawa, S.; Tsuruta, T.; Fujinami, T.; Sakai, S. J . Chem.
Soc., Perkin Trans. 1 1987, 1473-1477. (b) Fukuzawa, S.; Fujinami,
T.; Sakai, S. J . Chem. Soc., Chem. Commun. 1985, 777-778.
1294 J . Org. Chem., Vol. 69, No. 4, 2004

Allylation Reactions of Aldehydes
SCHEME 5
of cerium salt with aldehydes. The process was studied
using allyltributylstannane in a 0.1 M solution of CDCl3.
The addition of CeCl3 to this solution at -78 °C resulted
in 13C NMR signals very broad, and not readily identifi-
able species could be discerned from the spectra, due,
very probably, to the presence of paramagnetic Ce(III)
species.8b,43 However, signals for the starting material
remained, and no change in the 13C NMR spectra was
observed when the CeCl3 was added at -78 °C, the
mixture was placed in the spectrometer, and spectra were
observed at 30 °C intervals (approximatevely every 1/2
hour). Even after 1 day at room temperature there was
no transmetalation of the allyltributylstannane. There-
fore, we believe that CeCl3 promoted reactions of allyl-
stannanes with aldehydes do not involve allylchlorocer-
ium species originated by transmetalation. Certainly,
apart from this transmetalation reaction, allylcerium(III)
species might be generated by oxidative addition of
cerium.44 The reaction of allyl bromide with cerium
metal,45 benzaldehyde 3a , and sodium iodide, in typical
Hiyama-Nozaki conditions,46 did not show, however, the
expected homoallyl alcohol 5a . We have not detected
traces of 5a or oxidation products derived from this
adduct47 by GC/MS analysis of the crude reaction mixture
after stirring in acetonitrile for 24 h. The participation
of an allylcerium species can be ruled out even by the
fact that lower yields of homoallyl alcohol adducts are
obtained when 1.3 equiv of CeCl3‚7H2O are used (Scheme
2). In these conditions, the excess of cerium salt promotes
the decomposition of 4 to afford Bu3SnCl, as identified
by GC/MS. Given these studies we can suppose that in
our allylation of aldehydes promoted by the CeCl3‚7H2O-
NaI system the reaction does not proceed via transmeta-
lation to yield a reactive allylmetal halide, which then
reacts with the carbonyl compound. We presume that the
allylstannanes can act as allyl anion equivalents, and the
reaction may proceed via addition to a Lewis acid-
carbonyl compound complex. For this we have tried to
SCHEME 6
compared to aldehydes, toward allylstannanes.48 Of vari-
ous carbonyl substrates screened in fact, only aromatic
and aliphatic aldehydes were reactive substrates. This
chemoselectivity was further evaluated by crossover
experiments (Schemes 5 and 6) of 4 with substituted aryl
aldehydes, respectively. The reaction of a 1:1 mixture of
3b (1 equiv) and 3c (1 equiv) gave a small amount (7%
yield) of 5c along with the recovered 3c (84% yield) and
3b (>99% yield). On the other hand, the CeCl3‚7H2O-
NaI system promoted allylation of a 1:1 mixture of 3b
and 3c under Bu3SnCH2CHdCH2 (1 equiv) without
Lewis acid promoter gave after 24 h at room temperature
in the same reaction conditions as above 5c in 86% yield
along with recovered 3b (99% yield). High chemoselec-
tivity was also observed when a 1:1 mixture of 3e (1
equiv) and 3g (1 equiv) was treated with 1 equiv of 4
under the same reaction conditions as above. The ally-
lation product 5e was obtained in 47% and 90% yield,
respectively, together with 3g, which was recovered
quantitatively in both cases. This remarkable chemo-
selectivity suggests the following interesting electronic
study the complexation of aldehyde 3a with CeCl3 by 13
C
NMR spectroscopy. In this case, nevertheless, the 13C
NMR signals observed were very broad, and no identifi-
able species could be discerned from the spectra.
Although the mechanism remains unclear, the proce-
dure exhibits high chemoselectivity toward aldehydes in
the presence of ketones when the allylation is conducted
in a binary substrate system, p-tolualdehyde and pro-
piophenone; only aldehydes were allylated to the extent
of 74%, whereas the ketone was not allylated at the same
time. This is due to the lower reactivity of ketones,
(43) (a) The paramagnetism of Ce(III) precluded obtaining useful
1H NMR information: Hubert-Pfalzgraf, L. G.; Machado, L. Polyhedron
1996, 15, 545-549. Stecher, H. A., Seu, A.; Rheingold, A. L. Inorg.
Chem. 1989, 28, 3280-3282. See also ref 8b. (b) An attempt of studying
this process in more expensive acetonitrile-d3 than CDCl3 afforded
more complicated results.
(44) (a) Lee, A. S.-Y.; Wu, C.-W. Tetrahedron 1999, 55, 12531-
12542. (b) Guo, B.-S.; Doubleday: W.; Cohen, T. J . Am. Chem. Soc.
1987, 109, 4710-4711.
(45) Imamoto, T.; Kusumoto, T. Tawarayama, Y.; Sugiura, Y.; Mita,
T.; Hatanaka, Y.; Yokoyama, M. J . Org. Chem. 1984, 49, 3904-3912.
(46) (a) Hiyama, T.; Kimura, K.; Nozak, H.; Okude, Y. Bull. Chem.
Soc. J pn. 1982, 55, 561-567. (b) Okude, Y.; Hirano, S.; Hiyama, T.,
Nozaki, H. J . Am. Chem. Soc. 1977, 99, 3179-3180.
(47) (a) Schrekker, H. S.; de Bolster, m. W. G.; Orru, R. V. A.;
Wessjoham, L. A. J . Org. Chem. 2002, 67, 1975-1981. (b) Hudlick, M.
Oxidations in Organic Chemistry; Americam Chemical Society: Wash-
ington, DC, 1990.
(48) For examples of allylation reactions of ketones, see: (a) Koba-
yashi, S.; Aoyama, N.; Manabe, K. Synlett 2002, 483-485. (b) Hanawa,
H.; Kii, S.; Maruoka, K. Adv. Synth. Catal. 2001, 343, 57-61. (c)
Hamasaki, R.; Chounan, Y.; Horino, H.; Yamamoto, Y. Tetrahedron
Lett. 2000, 41, 9883-9887. (d) Casolari, S.; D’Addario, D.; Tagliavini,
E. Org. Lett. 1999, 1, 1061-1064.
J . Org. Chem, Vol. 69, No. 4, 2004 1295

Bartoli et al.
SCHEME 7
aldehydes with an electron-donating substituent. It
should be noted that, in the course of our program to
develop new synthetic Lewis acid mediated transforma-
tions, we have already found opposite effects between
CeCl3 and TiCl4.8b,53,54 This study, thus, represents
another example of how cerium(III) salts promote an
organic transformation with a chemoselectivity that is
reversed compared to that of the classical Lewis acid
mediated reactions.
At the end of these investigations it is clear that the
allylation reactions of aldehydes by allylstannanes are
particularly effective in the presence of a Lewis acid and,
most of all, the chemoselectivity depends on the nature
of the metal atom of the Lewis acid. With certain
aldehydes we have found that the CeCl3‚7H2O-NaI
system is instrumental in determining an opposite
chemoselective outcome with respect to that of TiCl4 or
BF3. In summary, the study has shown how our allylation
method may be an alternative to the previously reported
methods, and the tolerance of water and air stability of
the CeCl3‚7H2O-NaI system offers distinct advantages
over the more common Lewis acids. Further work is in
progress in our laboratories to study the regio- and
stereoselectivity, and to attempt the preparation of units
which might function as important synthetic targets in
organic chemistry. Moreover, we are currently expanding
the study of this allylation reaction of aldehydes in using
other allylmetal reagents that are desirable for environ-
mental reasons.
effects: (a) aryl aldehydes with an electron-withdrawing
substituent (i.e., NO2, CF3) react much faster than
benzaldehyde and (b) an electron-donating substituent
(i.e., CH3, OCH3) deactivated aryl aldehyde remarkably.
Seemingly, this reactivity of aldehydes is principally
dependent on the inherent electrophilicity of carbonyl,
not on the electron density of the formyl oxygen.49
Moreover, the rate observed for p-nitrobenzaldehyde is
likely to originate from its electronic effect rather than
the interfering coordination by the NO2 group.
The high coordinating ability of the cerium(III) toward
oxygen atoms of the carbonyl moiety3b,50 is presumably
responsible for the effective activation of aldehydic car-
bonyl independently of the electronic effect for aryl
aldehyde substrate. These results suggest us that the
relative reactivity of aldehydes in the CeCl3‚7H2O-NaI
promoted process is determined almost solely by the
electrophilicity of aldehydes themselves, not by the
coordinating ability of aldehydes to the cerium lantha-
noid. These findings strongly support a pathway for the
reaction (Scheme 7) where we believe that the activation
of the aldehydes probably occurs via formation of an
oxonium salt with cerium chloride for its oxophilic
character. Then, the rapid protonation of cerium alkoxide
6 by reaction with water generates the target homoallylic
alcohol 2. The alkoxides of lanthanides are notoriously
Brønsted basic, and almost instantaneous reaction with
H2O is generally observed, yielding highly insoluble
lanthanide hydroxide species.51 In addition, this allylation
reaction needs a stoichiometric amount of cerium trichlo-
ride because of the above strong interaction with the
oxygen function.52
Exp er im en ta l Section 55
The compounds 1-phenyl-3-buten-1-ol (5a ),56 1-(4-meth-
ylphenyl)-3-buten-1-ol (5b),57 1-[4-(trifluoromethyl)phenyl]-3-
buten-1-ol (5c),58 4-(1-hydroxy-3-butenyl)benzonitrile (5d ),59
1-(4-nitrophenyl)-3-buten-1-ol (5e),59 1-(4-methoxyphenyl)-3-
buten-1-ol (5g),60 1-(2-methoxyphenyl)-3-buten-1-ol (5h ),61
1-dodecen-4-ol (5i),56 1-cyclohexyl-3-buten-1-ol (5j),60 1-phenyl-
5-hexen-3-ol (5l),62 and (1E)-1-phenyl-1,5-hexadien-3-ol (5m )63
are all known, and their structures are consistent with their
published physical data.
Gen er a l P r oced u r e for th e Allyla tion (5a -m ). To a
suspension of CeCl3‚7H2O (1.0 mmol) and NaI (0.1 mmol) in
acetonitrile (12 mL) were added successively aldehydes 3a -m
(1.0 mmol) and allyltributylstannane (4) (1.1 mmol) at room
temperature. After being stirred at that temperature for the
required time, the reaction mixture was quenched with 0.1 N
HCl solution. The aqueous layer was extracted with diethyl
(53) Bartoli, G.; Bosco, M.; Dalpozzo, R.; Marcantoni, E.; Sambri,
L. Chem.sEur. J . 1997, 3, 1941-1950.
(54) For a different effect on the regioselectivities, see: Montalban,
A. G.; Wittenberg, L.-O.; McKillpo, A. Tetrahedron Lett. 1999, 40,
5893-5896.
Finally, it is worth noting that the activity of our CeCl3‚
7H2O-NaI system in the allylation reactions of aldehydes
is opposite to some extent that of strong Lewis acids, i.e.,
TiCl4 and Et2O‚BF3, which selectively activate aryl
(55) For general experimental details, see the Supporting Informa-
tion.
(56) Dussault, P. H.; Lee, H.-J .; Liu, X. J . Chem. Soc., Perkin Trans.
1 2000, 3006-3014.
(57) Ranganathan, S.; Kumar, R.; Maniktala, V. Tetrahedron 1984,
50, 1167-1178.
(49) For a mechanistic discussion, see: Asao, N.; Asano, T.; Yama-
moto, Y. Angew. Chem., Int. Ed. 2001, 40, 3206-3208 and references
therein.
(58) Zhang, Q.; Luo, Z.; Curran, D. P. J . Org. Chem. 2000, 65, 8866-
8873.
(50) For a recent review, see: (a) Molander, G. A.; Harris, C. R.
Chem. Rev. 1996, 96, 307-338. (b) Imamoto, T. Lanthanides in Organic
Aynthesis; Academic Press: New York, 1994.
(51) (a) Rogers, R. D. Inorg. Chim. Acta 1988, 149, 307-314. (b)
Rogers, R. D.; Kurihara, L. K. Inorg. Chim. Acta 1987, 130, 132-137.
(c) Barnes, J . C.; Nicoll, G. Y. R. Inorg. Chim. Acta 1985, 110, 47-50.
(52) Olah, G. A.; Krishnamurti, R.; Surya Prakash, G. K. In
Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Heathcock,
C. H., Eds.; Pergamon Press: Oxford, 1991; Vol. 3, pp 293-335.
(59) Fu¨rstner, A.; Voigtla¨nder, D. Synthesis 2000, 959-969.
(60) Shibato, A.; Itagaki, Y.; Tayama, E.; Hokke, Y.; Asao, N.;
Maruoka, K. Tetrahedron 2000, 56, 5373-5382.
(61) Yasuda, M.; Fujibayashi, T.; Baba, A. J . Org. Chem. 1998, 63,
6401-6404.
(62) Akiyama, T.; Iwai, J .; Sugano, M. Tetrahedron 1999, 55, 7499-
7508.
(63) Shibata, I.; Yoshimura, N.; Yabu, M.; Baba, A. Eur. J . Org.
Chem. 2001, 3207-3212.
1296 J . Org. Chem., Vol. 69, No. 4, 2004

Allylation Reactions of Aldehydes
ether, and the combined organic layers were stirred for 1 h
with 10% KF in H2O (10 mL). The organic phase was
separated, washed with brine, dried with Na2SO4, and con-
centrated at reduced pressure to furnish the crude product,
which was purified by silica gel chromatography (hexanes:
EtOAc).
δ 14.0, 15.8, 22.0, 28.6, 39.2, 69.9, 113.2, 126.8, 130.6, 132.6;
EI-MS m/z 154 [M+], 136, 113, 95 (100), 69, 55, 41. Anal. Calcd
for C10H18O: C, 77.87; H, 11.76. Found: C, 77.85; H, 11.29.
Ack n ow led gm en t. This work was supported by the
Ministero dell’Istruzione, dell’Universita` e della Ricerca
(MIUR, Programma di Ricerca “Stereoselezione in Sin-
tesi Organica. Metodologie ad Applicazioni”), Italy, and
the University of Camerino. M.B. gratefully acknowl-
edges the Pharmacia/Pfizer Ascoli Piceno Plant for a
postgraduate fellowship.
Da ta for 1-(3-n itr op h en yl)-3-bu ten -1-ol (5f): yellow oil
1
(yield 95%); IR (neat, cm-1) 3400, 3078, 1641, 1529, 1350; H
NMR δ 2.50-2.65 (m, 3H), 4.82-4.90 (m, 1H), 5.12-5.26 (m,
2H), 5.70-5.91 (m, 1H), 7.40-7.52 (m, 1H), 7.75 (d, 1H, J )
1.27 Hz), 8.13 (d, 1H, J ) 1.10 Hz), 8.23 (s, 1H); 13C NMR δ
40.0, 74.5, 113.6, 123.6, 124.0, 130.2, 134.6, 136.2, 139.0, 148.2;
EI-MS m/z 193 [M+], 152 (100), 105, 77, 65, 51, 41. Anal. Calcd
for C10H10NO3: C, 62.49; H, 5.24; N, 7.29. Found: C, 62.45;
H, 5.27; N, 7.32.
Da ta for (7Z)-1,7-d eca d ien -4-ol (5k ): oil (yield 93%); IR
(neat, cm-1) 3368, 3077, 1640; 1H NMR δ 0.93 (t, 3H, J ) 7.32
Hz), 1.45-1.53 (m, 2H), 1.71 (bs, 1H, OH), 1.98-2.10 (m, 5H),
2.13-2.17 (m, 1H), 3.57-3.69 (m, 1H), 5.06-5.13 (m, 2H), 5.35
(dt, 2H, J ) 8.55 and 7.34 Hz), 5.73-5.85 (m, 1H); 13C NMR
Su p p or tin g In for m a tion Ava ila ble: General methods;
experimental procedure and characterization for compounds
5f and 5k . This material is available free of charge via the
Internet at http://pubs.acs.org.
J O035542O
J . Org. Chem, Vol. 69, No. 4, 2004 1297