Scandium(III) triflate catalyzed synthesis of primary homoallylic alcohols via carbonyl-ene reaction

Article abstract of DOI:10.1016/j.tetlet.2013.01.046

Scandium trifluoromethanesulfonate can efficiently catalyze the formation of homoallylic alcohols from olefins and paraformaldehyde in good yields.

Full text of DOI:10.1016/j.tetlet.2013.01.046

Tetrahedron Letters 54 (2013) 1576–1578
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Tetrahedron Letters
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Scandium(III) triflate catalyzed synthesis of primary homoallylic alcohols
via carbonyl-ene reaction
⇑
Sabera Sultana, Somasekhar Bondalapati, Kiran Indukuri, Paramartha Gogoi, Pipas Saha, Anil K. Saikia
Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Scandium trifluoromethanesulfonate can efficiently catalyze the formation of homoallylic alcohols from
olefins and paraformaldehyde in good yields.
Received 2 November 2012
Revised 9 January 2013
Accepted 11 January 2013
Available online 17 January 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Scandium(III) triflate
Catalyst
Homoallylic alcohols
Carbonyl-ene reaction
The carbonyl-ene reactions are powerful tool for the carbon–
carbon bond forming reactions. The Lewis acids such as BF3ÁEt2O,1
aluminum chloride derivatives,2 scandium triflate,3 copper com-
plexes,4 palladium complexes,5 indium chloride,6 and platinum
complexes7 catalyzed carbonyl-ene reactions are well known for
the synthesis of homoallylic alcohols. These homoallylic alcohols
are important building blocks in organic synthesis particularly
for the synthesis of various oxygen heterocyclic compounds of syn-
thetic8 and pharmaceutical importance.9 There are different re-
agents for the synthesis of homoallylic alcohols such as zeolite,8a
BF3ÁEt2O, 1 di- and trimethylaluminum chloride,2 zirconium-mont-
morllonite clay,10 copper (II) complexes,4 palladium complexes,5
scandium(III) triflate,3 platinum complexes,7 and others.11
Although alkyl and aryl aldehydes are good starting material for
the synthesis of various substituted homoallylic alcohols, the
methods for the synthesis of primary homoallylic alcohols from
paraformaldehyde have often encountered some difficulties. The
reaction of alkenes with paraformaldehyde under Lewis acidic con-
ditions produce mostly the Prins cyclization product 1,3-dioxane.12
There are only a few procedures for the synthesis of primary homo-
allylic alcohols in the literature.1,2,10 In continuation of our interest
in the synthesis of oxygen heterocyclic compounds8c–g from homo-
allylic alcohols and aldehydes we were in search of an efficient
methodology for the synthesis of primary homoallylic alcohols.
Herein, we report an efficient method for the synthesis of primary
homoallylic alcohols from paraformaldehyde and alkenes cata-
lyzed by scandium trifluoromethanesulfonate.
In an initial investigation prop-1-en-2-ylbenzene was treated
with paraformaldehyde in acetonitrile in the presence of 5 mol %
of Sc(OTf)3 at room temperature and 3-phenyl-but-3-en-1-ol was
obtained in 71% yield.13 The reaction was also carried out in differ-
ent reaction conditions and the results are summarized in Table 1.
It was observed from Table 1 that Lewis acids Sc(OTf)3, AlCl3, and
Ce(OTf)4ÁnH2O provided the homoallylic alcohols with yields 71%,
27%, and 22%, respectively. Lewis acids BF3ÁEt2O, InCl3, In(OTf)3,
TMSOTf, and Bi(OTf)3 yielded only 1,3-dioxane 4, which was con-
firmed by comparison with the known product.8b On the other
hand, Lewis acids Zn(OTf)2, CeCl3Á7H2O, and Cu(OTf)2 failed to give
any product. Therefore Sc(OTf)3 is the best catalyst among them.
The activity of the reagent was also studied in dichloromethane
but it gave low yield, 40%. The catalytic activity of Sc(OTf)3 was
studied with different quantities such as 5, 10, and 20, and
5 mol % was found to be the best. Therefore, 5 mol % of scandium
triflate in acetonitrile is the best combination for the synthesis of
homoallylic alcohols. There was no improvement of yield upon
addition of additive such as molecular sieves. On the other hand
addition of base like Na2CO3 did not give any product.
The scope of the reaction was investigated by using different
types of olefins (Table 2). It was found that the reaction proceeds
smoothly with terminal and internal olefins in good yields without
giving any 1,3-dioxanes. The aromatic terminal alkenes such as a-
methylstyrenes (entries a–c) and methylene cyclohexene (entry e)
gave single products 2a–c and 2e, respectively. Compound 1f gave
two inseparable diastereomers 2fa and 2fb with a ratio of 1:1 and
overall 85% yield. On the other hand, the aliphatic terminal alkene
(entry i) gave three isomeric products 2ia–ic of which 2ia and 2ib
are inseparable geometric (E,Z) isomers with a ratio of 3:2 and a
⇑
Corresponding author.
E-mail address: asaikia@iitg.ernet.in (A.K. Saikia).
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.01.046

S. Sultana et al. / Tetrahedron Letters 54 (2013) 1576–1578
1577
Table 1
Optimization of reaction
O
O
Lewis acid
OH
+
(HCHO)n
+
Solvent / rt
12h
4
2
3
1
Entry
Lewis acid (equiv)
Solvent
Product
Yielda (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Sc(OTf)3 (5 mol %)
Sc(OTf)3 (10 mol %)
Sc(OTf)3 (20 mol %)
BF3ÁEt2O (1 equiv)
InCl3 (1 equiv)
In(OTf)3 (10 mol %)
Zn(OTf)2 (10 mol %)
AlCl3 (1 equiv)
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH2Cl2
CH3CN
CH3CN
3
3
3
4
4
4
—
3
4
—
3
3
4
—
71
67
63
75
20
79
—
27
81
—
TMSOTf (10 mol %)
CeCl3Á7H2O (1 equiv)
Ce(OTf)4ÁnH2O (10 mol %)
Sc(OTf)3 (5 mol %)
22
40
83
—
Bi(OTf)3 (10 mol %)
Cu(OTf)2 (10 mol %)
a
Yields refer to isolated yield. The compounds are characterized by IR, 1H, 13C NMR and comparison with known compounds.
Table 2
Synthesis of homoallylic alcohols
R
Sc(OTf)3 (5 mol %)
R
(HCHO)n
+
OH
CH3CN / rt
12h
R'
R'
2
1
Entry
a
Alkene 1
Products 2
Yielda (%)
71
OH
OH
b
c
78
73
Cl
Br
Cl
Br
OH
OH
OH
d
e
70b
55
da
db
= 2:3
2da:2db
OH
OH
OH
OH
OAc
Br
f
85b
OAc
OAc
Br
2fa:2fb
= 1:1
g
71
(continued on next page)

1578
S. Sultana et al. / Tetrahedron Letters 54 (2013) 1576–1578
Table 2 (continued)
Entry
Alkene 1
Products 2
Yielda (%)
65
h
i
OH
OAc
OH
OH
OH
OAc
OAc
OAc
2ia 2ib
70b
Z
E
2ic
= 46%
:
= 3:2 (24%)
Br
Br
OH
j
81
0
S
S
OH
k
O2N
O2N
a
Yields refer to isolated yield. The compounds are characterized by IR, 1H, 13C NMR, and elemental analysis.
Ratio is determined by 1H and 13C NMR.
b
7. Dohetry, S.; Knight, J. G.; Mehdi-Zodeh, H. Tetrahedron: Asymmetry 2012, 23,
209–216.
regio isomer 2ic. All other internal olefins except 1d provided a sin-
gle isomer. The alkene 1d yielded two inseparable regioisomers
2da and 2db with a ratio of 2:3. The olefin having strong elec-
tron-withdrawing group (entry k) on the aromatic ring failed to
give product.14 The reaction is mild and the groups like acetyl, sul-
fide, and bromides are unaffected under these reaction conditions.
All the products were characterized by spectroscopic methods.
In conclusion we have developed a methodology for the synthe-
sis of primary homoallylic alcohols from alkenes and paraformal-
dehyde catalyzed by scandium trifluoromethanesulfonate in good
yields. The reaction is mild and the groups such as acetate, bro-
mide, and sulfide are unaffected under the reaction conditions.
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Acknowledgment
Authors are grateful to the Council of Scientific and Industrial
Research (CSIR) New Delhi for financial support (Grant No.
01(2332)/09/EMR-II).
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Supplementary data
Supplementary data associated with this article can be found, in
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