Chemoselective allylation of aldehydes using cerium(III) chloride: Simple synthesis of homoallylic alcohols

Article abstract of DOI:10.1016/j.tet.2004.11.029

Aldehydes undergo smooth nucleophilic addition with allyltributylstannane in the presence of CeCl₃·7H₂O in acetonitrile under extremely mild reaction conditions to afford the corresponding homoallylic alcohols in excellent yields wit

Full text of DOI:10.1016/j.tet.2004.11.029

Tetrahedron 61 (2005) 879–882
Chemoselective allylation of aldehydes using cerium(III) chloride:
simple synthesis of homoallylic alcohols
*
J. S. Yadav, B. V. S. Reddy, G. Kondaji and J. Shyam Sunder Reddy
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 30 January 2004; revised 15 October 2004; accepted 11 November 2004
Available online 30 November 2004
Abstract—Aldehydes undergo smooth nucleophilic addition with allyltributylstannane in the presence of CeCl3$7H2O in acetonitrile under
extremely mild reaction conditions to afford the corresponding homoallylic alcohols in excellent yields with high chemoselectivity. This
method is very useful especially for the allylation of aldehydes bearing acid sensitive functionalities such as TBDMS, THP ethers,
acetonides, aryl alkyl ethers and carbamates.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
promoting various organic transformations with high
performance.7
Lewis acid catalyzed carbon–carbon bond forming reactions
are of great importance in organic synthesis because of their
high selectivity and mild reaction conditions.1 In particular,
the stereo selective addition of ally metal reagents to
aldehydes is one of the most important carbon–carbon bond
forming reactions in organic synthesis.2 Consequently,
several methods have been reported for the allylation of
aldehydes with allyl metals to produce homoallylic
alcohols.3 One of the most straightforward synthetic
procedures involves the nucleophilic addition of allyltin
reagents to aldehydes in the presence of Lewis acids.4–6
However, many of these reagents are expensive, moisture
sensitive and difficult to handle, especially on a large scale.
Cerium(III) is highly oxophilic, and forms strong but labile
bonds with oxygen donar ligands. This feature has often
allowed the use of cerium(III) chloride as a potential Lewis
acid catalyst.8
2. Results and discussion
In this article, we describe an efficient and high yielding
protocol for the allylation of aldehydes with allyltributyl-
stannane using CeCl3$7H2O as a novel promoter.
Accordingly, treatment of benzaldehyde 1 with allyl-
tributylstannane 2 in the presence of an equimolar amount
of cerium(III) chloride afforded 1-phenyl-3-buten-1-ol 3a in
92% yield (Scheme 1).
Furthermore, most of these methods involve the use of
strongly acidic conditions, which limit their use in the
allylation of complex molecules containing acid labile
functionalities. Therefore, the development of an efficient
and versatile reagent for the allylation of aldehydes is an
active ongoing research area and thus there is scope for
further improvements towards milder reaction conditions
and better yields. Lanthanide salts are unique Lewis acids
that are currently of great research interest. Among these
catalysts, cerium halides are relatively non-toxic, readily
available at low cost and are fairly stable to water. Recently,
CeCl3$7H2O has emerged as an efficient Lewis acid in
The reaction proceeded smoothly at room temperature
under extremely mild conditions. Encouraged by the results
obtained with benzaldehyde, we turned our attention to
various substituted aldehydes. Interestingly, a wide range of
substrates including aromatic, aliphatic, heterocyclic and
a,b-unsaturated aldehydes reacted efficiently with allyltin
under similar reaction conditions to give the corresponding
homoallylic alcohols in excellent yields. No bis-allylated
products were obtained with methoxy-substituted aryl
aldehydes, which are normally observed in the allylation
of methoxy-benzaldehydes with allyltrimethylsilane.3c Acid
sensitive aldehydes such as furfural, and 2-phenyl
acetaldehyde (entries i and j Table 1) were also efficiently
converted into their corresponding homoallylic alcohols in
Keywords: Cerium reagents; Aldehydes; Allyltin; Homoallylic alcohols.
* Corresponding author. Tel.: C91 40 27193434; fax: C91 40 27160512;
e-mail: yadav@iict.ap.nic.in
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.11.029

880
J. S. Yadav et al. / Tetrahedron 61 (2005) 879–882
Scheme 1.
high yields by using this procedure. In the case of a,b-
unsaturated aldehyde (entry o Table 1), no 1,4-addition
product was obtained. However, 2-phenylpropanal gave a
mixture of syn and anti (3:1 ratio) products (entry m,
Table 1).6c Ketones such as acetophenone, tetralone and
cyclohexanone did not react with allyltributylstannane
under similar reaction conditions even after a long reaction
time and thus this provides a chemo selective allylation of
aldehydes without affecting keto functionality. The chemo
selectivity of the present method was further studied by
using the keto aldehydes (entry g, Table 1). It should be
noted that chiral aldehydes gave homoallylic alcohols with
complete retention of the original configuration (entries k
and l, Table 1). The major advantage of this method is in the
selective allylation of aldehydes in the presence of highly
acid sensitive acetonide, Boc, TBDMS and THP ethers
(entries b, k, l and p, Table 1), which do not survive under
strongly acidic conditions.4–6 There are many advantages in
the use of cerium(III) chloride for this conversion, which
require neither strongly acidic nor harsh conditions. In
addition, this method does not require the use of expensive
reagents or anhydrous solvents and no precautions need to
be taken to exclude moisture from the reaction medium.
Furthermore, this method is also useful for the allylation of
sugar (syn/anti products in approximately 1:1 ratio) and
Garner’s aldehyde without affecting acetonide (entries k
and l Table 1). Thus, the present method is mild to tolerate a
wide range of functionalilities. Finally, we have examined
the possibility of CeCl3$7H2O functioning catalytically or
at least, in less than stoichiometric amounts. However,
best results were obtained with an equimolar ratio of
CeCl3$7H2O. Among various Lewis acids such as CeCl3$
7H2O, InCl3, YbCl3, SmCl3 and YCl3 studied for this
transformation, cerium(III) chloride was found to be more
effective in terms of conversion and selectivity. Reactions
were also carried out using 10 mol% of Ce(OTf)3 and the
results are summarized in Table 1. The scope and generality
of this process is illustrated with respect to various
substituted aldehydes and allyltributylstannane.
4. Experimental
4.1. General
Melting points were recorded on Buchi R-535 apparatus and
are uncorrected. IR spectra were recorded on a Perkin–
Elmer FT-IR 240-c spectrophotometer using KBr optics. 1H
and 13C NMR spectra were recorded on Gemini-200
spectrometer in CDCl3 using TMS as internal standard.
Mass spectra were recorded on a Finnigan MAT 1020 mass
spectrometer operating at 70 eV. All commercially avail-
able reagent grade chemicals were purchased from Aldrich
Chemical Company and used as received without further
purification unless otherwise stated. All the solvents were
distilled, dried and stored under nitrogen prior to use. The
optical rotations were measured on a Jasco Dip 360 Digital
polarimeter.
4.1.1. Experimental section. The compounds 1-phenyl-3-
buten-1-ol (3a),2c,3c 1-(4-chlorophenyl)-3-buten-1-ol (3c),3d
1-(3-methoxyphenyl)-but-3-en-1-ol (3e),3c 1-(4-nitro-
phenyl)-3-buten-1-ol (3f),3d 1-phenyl-1-oxo-4-penten-2-ol
(3g),3e 1-cyclohexyl-3-bute-ne-1-ol (3h),3d 1-(2-furyl)-3-
buten-1-ol (3i),3a 1-(phenyl)-pent-4-en-2-ol (3j),3c 1-decen-
4-ol (3n),3d (5E)-1,5-trideca-dien-4-ol (3o),3f 1-phenyl-5-
hexen-3-ol (3q),3d and 1-(2-naphthyl)-but-3-ene-1-ol (3r),3c
all these compounds are known, and their spectroscopic data
identical to that reported in the literature.
4.2. General procedure for the synthesis 2,3-dihydro-1,5-
benzodiazepines
A mixture of aldehyde (2 mmol), allyltributylstannane
(2 mmol) and CeCl3$7H2O (2 mmol) or Ce(OTf)3$nH2O
(10 mol%) in acetonitrile (10 mL) was stirred at 27 8C for
the appropriate time (Table 1). After completion of the
reaction, as indicated by TLC, the reaction mixture was
diluted with water (20 mL) and extracted with ethyl acetate
(2!10 mL). The combined organic layers were washed
with brine, dried over anhydrous Na2SO4 and concentrated
in vacuo, and the resulting product was purified by column
chromatography on silica gel (Merck, 100–200 mesh, ethyl
acetate–hexane, 2:8) to afford pure homoallyl alcohol.
3. Conclusion
In conclusion, we describe a simple, convenient and
efficient protocol for the preparation of homoallylic alcohols
from aldehydes and allyltributylstannane using a cheap and
readily available reagent (CeCl3$7H2O) that operates under
mild conditions thereby leaving acid- and base-labile
protecting groups intact. The notable features of this
procedure are high functional group compatibility, cleaner
reaction profiles, simple operation, and high conversions,
which make it a useful and attractive strategy for the
synthesis of homoallylic alcohols.
4.2.1. 1-(4-t-Butylsilyloxy-3-methoxyphenyl)-3-buten-1-
ol (3b). Colorless oil, (536 mg, 87%). IR (KBr): nmax
3417 (br s), 2933, 2858, 1641, 1589, 1513, 1467,1432, 1354,
:
1
1280, 1219, 1156, 1038, 912, 840, 771 cmK1. H NMR
(200 MHz, CDCl3): d 0.12 (s, 6H), 0.98 (s, 9H), 1.80 (br s,
1H, OH), 2.42–2.50 (m, 2H), 3.82 (s, 3H), 4.60 (t, JZ
6.5 Hz, 1H), 5.06–5.18 (m, 2H), 5.72–5.85 (m, 1H), 6.73 (s,
2H), 6.85 (s, 1H). 13C NMR (75 MHz, CDCl3, proton
decoupled): d K4.6, 18.4, 25.7, 43.7, 55.5, 73.3, 107.9,
109.9, 118.2, 120.6, 134.6, 137.5, 144.5, 150.9. EIMS: m/z:

J. S. Yadav et al. / Tetrahedron 61 (2005) 879–882
Table 1. Cerium(III)-promoted synthesis of homoallyl alcohols from aldehydes
881
Entry
Aldehyde
Homoallyl alcohol
CeCl3$7H2O
Ce(OTf)3$nH2O
Time (h)
Yield (%)a
Time (h)
Yield (%)a
a
3.0
3.5
92
3.5
4.5
87
80
b
87
c
3.0
5.0
95
91
4.0
6.5
85
82
d
e
f
4.0
3.0
4.5
3.5
90
92
88
85
5.0
3.5
5.0
5.0
86
87
85
81
g
h
i
3.0
3.5
91
89
4.5
4.0
83
86
j
k
4.0
85b
5.0
80b
l
5.0
3.5
81
6.0
4.5
75
m
90c
85c
n
o
p
3.5
2.5
3.0
91
93
87
4.0
3.0
3.5
87
90
82
q
r
3.5
3.0
89
94
4.0
4.5
87
92
1
All the products were characterized by H NMR, IR and mass spectra.
a Isolated and unoptimized yields.
b The product was obtained as a mixture of syn and anti in a 1:1 ratio.
c 3:1 ratio of syn and anti products.

882
J. S. Yadav et al. / Tetrahedron 61 (2005) 879–882
308 (MC) 291, 267, 251, 195, 167, 136, 73. HRMS Calcd
for C17H28SiO3: 308.1807. Found: 308.1836.
(br s), 2993, 1636, 1218, 1026, 771 cmK1 1H NMR
.
(200 MHz, CDCl3): d 1.25–1.35 (m, 2H), 1.40–1.60 (m,
6H), 1.65–1.75 (m, 2H), 1.80 (br s, OH, 1H), 2.12–2.30 (m,
2H), 3.35–3.50 (m, 2H), 3.60–3.70 (m, 1H), 3.71–3.86 (m,
1H), 4.60 (t, JZ6.5 Hz, 1H), 5.15–5.25 (m, 2H), 5.75–5.90
(m, 1H). 13C NMR (75 MHz, CDCl3, proton decoupled): d
19.4, 19.5, 25.3, 25.9, 26.1, 30.5, 33.8, 41.8, 62.1, 62.2,
67.5, 134.9. EIMS: m/z: 215 (MC1 215), 203, 191, 178, 167,
154, 137, 107, 95, 85, 69, 57. HRMS Calcd for C12H22O3:
214.1568. Found: 214.1509.
4.2.2. 1-(Benzyloxycarbonyl-3-amino-4-fluorophenyl)-3-
buten-1-ol (3d). Pale yellow oil, (547 mg, 91%). IR (KBr):
nmax: 3500 (br s), 3000, 1650, 910 cmK1 1H NMR
.
(200 MHz, CDCl3): d 2.00 (br s, OH, 1H), 2.40 (t, JZ
6.9 Hz, 2H), 4.70 (t, JZ6.9 Hz, 1H), 5.0–5.05 (dd, JZ10.2,
17.3 Hz, 2H), 5.10 (s, 2H), 5.70–5.93 (m, 1H), 6.90 (br s,
NH, 1H), 7.0 (d, JZ7.9 Hz, 2H), 7.20 (s, 5H), 8.12 (d, JZ
7.20 Hz, 1H). HRMS Calcd for C18H18NO3F: 315.1270.
Found: 315.1214.
Acknowledgements
4.2.3. erythro-1,2-O-Isopropylidene hex-5-ene-1,2,3-triol
(3k). Viscous oil,4e (131 mg, 38%); [a]2D0ZC15.6 (c, 1.0,
CHCl3), {lit.4e [a]D27ZC16.0 (c, 1.0, CHCl3)}. IR (KBr):
B. V. S., G. K., J. S. S. thank CSIR, New Delhi, for the
award of fellowships.
nmax: 3468 (OH), 3078, 2888, 1656, 1352, 1201, 913 cmK1
.
1H NMR (300 MHz, CDCl3): d 1.33 (s, 3H), 1.40 (s, 3H),
1.80 (br s, 1H, OH), 2.12–2.22 (m, 1H), 2.25–2.38 (m, 1H),
3.70 (t, 1H), 3.85–4.0 (m, 3H), 5.13 (d, JZ10.32 Hz, 1H),
5.15 (d, JZ16.4 Hz, 1H), 5.90–5.75 (m, 1H). 13C NMR
(75 MHz, CDCl3, proton decoupled): d 25.2, 26.5, 37.6,
65.2, 70.5, 78.1, 109.0, 118.1, 134.0. EIMS: m/z: 157 (MC
1), 143, 101, 83, 69, 59, 43.
References and notes
1. (a) Yamamoto, Y.; Asao, N. Chem. Rev. 1993, 93, 2207. (b)
Marshall, J. A. Chem. Rev. 1996, 96, 31.
2. (a) Li, C. J.; Chan, T. H. Tetrahedron 1999, 55, 11149. (b)
Hosomi, A.; Sakurai, H. Tetrahedron Lett. 1976, 16, 1295. (c)
Takahiko, A.; Junko, I.; Megumi, S. Tetrahedron 1999, 55,
7499.
4.2.4. threo-1,2-O-Isopropylidene hex-5-ene-1,2,3-triol
(3k0). Oil liquid,4e (124 mg, 36%); [a]2D7ZC14.2 (c, 1.0,
CHCl3) {lit.4e [a]D27ZC10.2 (c, 1.0, CHCl3)}. IR (KBr):
nmax: 3482, 3129, 2988, 2883, 1695, 1379, 1218, 1070,
3. (a) Andrade, C. K. Z.; Azevedo, R. Tetrahedron Lett. 2001, 42,
6473. (b) Yanagisawa, A.; Nakashima, H.; Ishiba, A.;
Yamamoto, H. J. Am. Chem. Soc. 1996, 118, 4723. (c)
Aggarwal, V. K.; Vennall, G. P. Synthesis 1998, 1822. (d)
Davis, A. P.; Jaspars, M. J. Chem. Soc., Perkin Trans. 1 1992,
2111. (e) Takuwa, A.; Nishigaichi, Y.; Yamashita, K.; Iwamoto,
H. Chem. Lett. 1990, 1761. (f) Roush, W. R.; Hoong, L. K.;
Palmer, M. A. J.; Park, J. C. J. Org. Chem. 1990, 55, 4109.
4. (a) Hachiya, I.; Kobayashi, S. J. Org. Chem. 1993, 58, 6958. (b)
Hamasaki, S.; Chounan, Y.; Horino, H.; Yamamoto, Y.
Tetrahedron Lett. 2000, 41, 9883. (c) Ley, S. V.; Cox, L. R.
J. Chem. Soc., Perkin Trans. 1 1997, 3315. (d) Shibata, I.;
Fukuoka, S.; Yoshimura, N.; Matsuda, H.; Baba, A. J. Org.
Chem. 1997, 62, 3790. (e) Roush, W. S.; Walts, A. E.; Hoong,
L. K. J. Am. Chem. Soc. 1985, 107, 8186.
1
771 cmK1. H NMR (300 MHz, CDCl3): d 1.35 (s, 3H,),
1.42 (s, 3H), 2.18–2.26 (m, 1H), 2.40–2.60 (m, 1H), 3.38 (br
s, 1H, OH), 3.58.3.80 (m, 2H), 3.98–4.20 (m, 2H), 5.04–
5.13 (m, 2H), 5.80–6.02 (m, 1H). 13C NMR (75 MHz,
CDCl3, proton decoupled): d 24.9, 26.2, 37.8, 67.6, 71.5,
80.7, 109.0, 117.2, 134.5. EIMS: m/z: 157 (MC1K15), 143,
113, 101, 59.
4.2.5. tert-Butyl 4-(1-hydroxy-3-butenyl)-2,2-dimethyl-
1,3-oxazolane-3-carboxylate (3l). Viscous oil, (438 mg,
81%). IR (KBr): nmax: 3451 (OH), 2979, 1697, 1387, 1254,
1173, 1091, 850, 771 cmK1. 1H NMR (200 MHz, CDCl3): d
1.38 (s, 9H), 1.42 (s, 3H), 1.54 (s, 3H), 2.03–2.21 (m, 2H),
3.62–4.02 (m, 3H), 5.0–5.20 (m, 2H), 5.70–6.05 (m, 1H).
13C NMR (75 MHz, CDCl3, proton decoupled): d 26.5, 26.7,
27.7, 37.9, 64.5, 71.8, 80.6, 94.1, 117.4, 134.5. FAB: m/z:
272 (MC1), 216, 173, 149, 123, 95, 81, 69, 57. HRMS Calcd
for C14H25NO4: 271.1783. Found: 271.1723.
5. (a) Nagayama, S.; Kobayashi, S. Angew. Chem., Int. Ed. 2000,
93, 567. (b) Kobayashi, S.; Aoyama, N.; Manabe, K. Synlett
2002, 483. (c) Aspinall, H. C.; Bissett, J. S.; Greeves, N.; Levin,
D. Tetrahedron Lett. 2002, 43, 319.
6. (a) Inoue, K.; Yasuda, M.; Baba, A. Synlett 1997, 699. (b)
Naruta, Y.; Ushida, S.; Maruyama, K. Chem. Lett. 1979, 919. (c)
Andrade, C. K. Z.; Azevedo, N. R. Tetrahedron Lett. 2001, 42,
6473. (d) Andrade, C. K. Z.; Azevedo, N. R.; Oliveira, G. R.
Synthesis 2002, 928. (e) Choudary, B. M.; Sridhar, Ch.; Sekhar,
Ch. V. R. Synlett 2002, 1694–1696.
4.2.6. 2-Phenyl-5-hexene-3-ol (3m). Colorless liquid,3d
(316 mg, 90%). IR (KBr): nmax: 3466 (br s), 2925, 2856,
1736, 1640, 1455, 1329, 1159, 1094, 814, 702, 664 cmK1
.
1H NMR (400 MHz, CDCl3): d 1.32 (d, JZ7.2 Hz, 3H),
1.57 (br s, OH, 1H), 1.96–2.20 (m, 2H), 2.70–2.80 (m, 1H),
3.62–3.73 (m, 1H), 5.06–5.16 (m, 2H), 5.72–5.85 (m, 1H),
7.16–7.32 (m, 5H). 13C NMR (75 MHz, CDCl3, proton
decoupled): d 16.3, 39.5, 45.4, 75.0, 117.9, 126.4, 127.7,
128.4, 135.0, 144.4. EIMS: m/z: 176 MC, 135, 117, 107,
106, 105, 91, 79, 65, 71, 51, 43, 41.
7. Bartoli, G.; Marcantoni, E.; Sambri, L. Synlett 2003, 2101.
8. (a) Bartoli, G.; Bosco, M.; Marcantoni, E.; Sambri, L.;
Torregiani, E. Synlett 1998, 209. (b) Bartoli, G.; Bellucci,
M. C.; Bosco, M.; Cappa, A.; Marcantoni, E.; Sambri, L.;
Orregiani, E. J. Org. Chem. 1999, 64, 5696. (c) Marcantoni, E.;
Nobili, F.; Bartoli, G.; Bosco, M.; Sambri, L. J. Org. Chem.
1997, 62, 4183. (d) Yadav, J. S.; Reddy, B. V. S. Synlett 2000,
1275.
4.2.7. 7-Tetrahydro-2H-2-pyranyloxy-1-hepten-4-ol
(3p). Colorless oil, (372 mg, 87%). IR (KBr): nmax: 3454