Mild and efficient allylation of aldehydes with allyltributylstannane promoted by MgI2·(OEt)n etherate

Article abstract of DOI:10.1055/s-2007-990919

Allylation of aldehydes with allyltributylstannane was promoted in the presence of MgI₂·(OEt)_n to give homoallylic alcohols. The iodide anion and a noncoordinating reaction medium (CH ₂Cl₂) are the key features

Full text of DOI:10.1055/s-2007-990919

LETTER
65
Mild and Efficient Allylation of Aldehydes with Allyltributylstannane
Promoted by MgI2·(OEt)n Etherate
Allylation of
Alde
i
hyde
s
w
n
ith Allyltrib
g
utylstannane
x
Promote
d
b
i
M
gI2a·(OEt)n n Zhang*
College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, Zhejiang 310032, P. R. of China
Fax +86(571)88320320; E-mail: zhangxx@zjut.edu.cn
Received 23 May 2007
We initiated our studies by carrying out the allylation of
benzaldehyde with allyltributylstannane using freshly
prepared MgI2·(OEt)n (1.0 M in Et2O–benzene, 1:2)12 in
CH2Cl2 at room temperature. It was noticed that the
amount of MgI2·(OEt)n catalyst had an effect on the yield
of addition products. The optimal condition was to use
100 mol% of MgI2·(OEt)n to give the desired homoallylic
alcohol in good yield (92%). Furthermore, among the var-
ious solvents screened, good yield was obtained in a non-
coordinating reaction medium such as CH2Cl2. Moderate
yield was obtained in nonpolar solvents such as benzene
or toluene. However, no reaction was noted when it was
carried out in the polar solvents, such as Et2O, DMF, THF
and MeCN.
Abstract: Allylation of aldehydes with allyltributylstannane was
promoted in the presence of MgI2·(OEt)n to give homoallylic alco-
hols. The iodide anion and a noncoordinating reaction medium
(CH2Cl2) are the key features of this catalytic system.
Key words: magnesium iodide, allylation, aldehyde, allyltributyl-
stannane
Lewis acid catalyzed carbon–carbon bond-forming reac-
tions are of great importance in organic synthesis due to
their high reactivity and selectivity under mild reaction
conditions.1–3 Among them, Lewis acid catalyzed allyla-
tion of aldehydes4–6 has been widely utilized in the con-
struction of carbon–carbon bonds to generate homoallylic
alcohols, which are important building blocks for the syn-
thesis of many natural products and pharmaceuticals.7
Generally, the preparation of homoallylic alcohols can be
accomplished either by nucleophilic addition of organo-
metallic reagents or by addition of allylsilane, allyltin or
allylborane reagents in the presence of a variety of Lewis
acids, Brønsted acids, transition metallic reagents, lan-
thanide triflates, and other catalysts.5,6,8 Recently, there
was a report on carrying out these reactions in the pres-
ence of CeCl3·7H2O9 or CeCl3·7H2O/NaI.10 However,
many of these reagents are rather expensive and difficult
to be handle on a large scale. From the viewpoints de-
scribed above, the development of less expensive, envi-
ronmentally benign and easily handled promoters for
allylation of aldehydes is still highly desirable.
Encouraged by these results, allylation of a variety of al-
dehydes has been investigated. The results are summa-
rized in Table 1. As shown in Table 1, the reaction
proceeded smoothly at room temperature and provided
good product yields. Among the various aldehydes cho-
sen, we observed that aromatic aldehydes were good sub-
strates, and provided the corresponding adducts in good to
excellent yields (Table 1, entries 1–7). Moreover, allyla-
tion of unsaturated aldehydes (Table 1, entries 8 and 9)
and aliphatic aldehydes (Table 1, entries 10–12) also af-
forded products in good yields, whereas aromatic and ali-
phatic
ketones
were
unreactive
towards
allyltributylstannane in the presence of MgI2·(OEt)n. This
was probably due to the lower reactivity of ketones, as
compared to aldehydes, towards allylstannanes.13 The
higher coordinating ability of the magnesium(II) towards
oxygen atoms of the carbonyl moiety14 is presumably re-
sponsible for the effective activation of aldehydic carbon-
yl.
In our previous paper11 we have demonstrated that
MgI2·(OEt)n could efficiently catalyze Mukaiyama-type
aldol addition of aromatic aldehydes with silyl enolates.
In continuation of our work, we wish to report herein a
mild and efficient allylation of aldehydes with allyltribu-
tylstannane mediated by MgI2·(OEt)n in good to excellent
yields (Scheme 1).
The key advantage of this method was the selective ally-
lation of aldehydes in the presence of the highly acid-sen-
sitive acetonide and Boc protecting groups (Table 1,
entries 13 and 14), which normally do not survive under
strongly acidic conditions.15 We found that, allylation of
Boc-L-phenylalanine exclusively afforded 1,2-anti-allylic
alcohol 1m in 78% yield (Table 1, entry 13). Furthermore,
this method was also useful for the selective allylation of
D-glyceraldehyde without affecting the acetonide moiety
(Table 1, entry 14) to afford a mixture of diastereoisomers
in a 1:2 ratio.
OH
MgI2⋅(OEt2)n
SnBu3
RCHO
R
+
CH2Cl2 , r.t.
1
Scheme 1 MgI2·(OEt)n-catalyzed allylation
SYNLETT 2008, No. 1, pp 0065–0068
x
x.
x
x.
2
0
0
7
Advanced online publication: 03.12.2007
DOI: 10.1055/s-2007-990919; Art ID: W10207ST
© Georg Thieme Verlag Stuttgart · New York

66
X. Zhang
LETTER
To examine the halide anion effect, halogen analogues of Table 1 Allylation of Aldehydes with Allyltributylstannane Pro-
18,19
moted by MgI2·(OEt)n
MgI2·(OEt)n, MgCl2·(OEt)n and MgBr2·(OEt)n, were com-
pared under parallel reaction conditions (100 mol% of cat-
Entry Aldehyde
Time (h) Producta Yield (%)b
alyst) in the allylation reaction of aryl aldehydes with
allyltributylstannane. It was found that MgCl2·(OEt)n was
almost inactive, while MgBr2·(OEt)n was less effective in
terms of substrate conversion and yield. Apparently, the
unique catalytic reactivity of MgI2·(OEt)n can be attribut-
ed to the dissociative character of iodide counterion to
give a more acidic cationic [MgI]+ species as a result of
Lewis base activation of Lewis acid.16 We proposed the
following pathway for this allylation reaction (Scheme 2),
which suggests that the activation of the aldehydes proba-
bly occurs via formation of an oxonium salt with
MgI2·(OEt)n due to its high oxophilic character. The cat-
ionic character17 of this more Lewis acidic Mg(II) coordi-
nation with peripheral ethereal ligands results from the
ready dissociation of iodide ion in accordance with the co-
ordination of the Lewis basic formyl group. Then, rapid
protonation of magnesium alkoxide 2 by quenching with
water generates the desired homoallylic alcohol. In addi-
tion, this allylation needed a stoichiometric amount of
MgI2·(OEt)n because of the above strong interaction with
the oxygen function.14
CHO
1
2
4
1
1a
1b
92
97
CHO
NO2
CHO
3
4
1
5
1c
95
80
O2N
CHO
1d
OMe
CHO
Cl
5
6
7
3
3
5
1e
1f
95
94
62
CHO
Cl
In summary, we have demonstrated the unique catalytic
reactivity of MgI2·(OEt)n in the allylation of aromatic al-
dehydes, unsaturated aldehydes and aliphatic aldehydes
with allyltributylstannane. This magnesium-catalyzed al-
lylation addition is mild, efficient, operationally simple
and highly selective. Iodide counterion, weakly coordi-
nating peripheral ethereal ligands for Mg(II), and a nonco-
ordinating reaction medium are critical factors for the
unique reactivity of this catalytic system. Further investi-
gations on the catalytic reactivity of MgI2·(OEt)n in other
C–C bond-constructing reactions are underway.
CHO
CHO
1g
Me
8
9
4
5
3
1h
1i
82
66
80
CHO
CHO
10
1j
11
12
5
5
1k
1l
81
74
CHO
+
O
MgI⋅(OEt2)n
H
O
O
O
MgI2⋅(OEt2)n
I–
R
H
R
H
13
14
4
4
1m
1n
78c
70d
H
SnBu3
NHBoc
CHO
O
O
Bu3SnI
a All products were identified by their 1H NMR spectra.
b Yields of products isolated by column chromatography.
c Only anti-configuration allylic alcohol was obtained.
OH
OMgI
H2O
d The product was obtained as a mixture of syn and anti isomers in a
R
R
1:2 ratio.
1
2
Scheme 2 The proposed mechanism of MgI2·(OEt)n-catalyzed
allylation
Synlett 2008, No. 1, 65–68 © Thieme Stuttgart · New York

LETTER
Allylation of Aldehydes with Allyltributylstannane Promoted by MgI2·(OEt)n
67
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Acknowledgment
Zhejiang University of Technology Scholars Program is gratefully
acknowledged.
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References and Notes
(18) Typical Procedure for the Synthesis of Homoallylic
Alcohols: To a stirred solution of benzaldehyde (0.5 mmol)
in CH2Cl2 (3 mL) was added a freshly prepared solution of
MgI2·(OEt)n in Et2O–benzene (1:2, 1.0 M, 0.5 mL) at r.t.
After stirring for 10 min, a solution of allyltributylstannane
(0.6 mmol) in CH2Cl2 (2 mL) was added dropwise via a
syringe. The resulting homogeneous reaction mixture was
stirred at r.t. for 3 h and quenched with distillated H2O.
Extractive workup with Et2O and chromatographic
purification of the crude product on silica gel gave the
homoallylic alcohol 1a in 92% yield.
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(19) Selected spectroscopic data:
Compound 1a:20 1H NMR (400 MHz, CDCl3): d = 2.13 (br
s, 1 H), 2.47–2.52 (m, 2 H), 4.72 (t, J = 6.5 Hz, 1 H), 5.11–
5.19 (m, 2 H), 5.76–5.85 (m, 1 H), 7.25–7.29 (m, 1 H), 7.32–
7.35 (m, 4 H). Compound 1b:10 1H NMR (400 MHz, CDCl3):
d = 2.15 (br s, 1 H), 2.43–2.52 (m, 1 H), 2.54–2.62 (m, 1 H),
4.85–4.89 (m, 1 H), 5.18–5.22 (m, 2 H), 5.75–5.84 (m, 1 H),
7.53 (t, J = 8.0 Hz, 1 H), 7.70 (d, J = 7.6 Hz, 1 H), 8.14 (d,
J = 8.1 Hz, 1 H), 8.25 (s, 1 H). Compound 1c:10 1H NMR
(400 MHz, CDCl3): d = 2.48–2.63 (m, 2 H), 2.82 (br s, 1 H),
4.90 (t, J = 6.2 Hz, 1 H), 5.17–5.22 (m, 2 H), 5.77–5.87 (m,
1 H), 7.56 (d, J = 8.0 Hz, 2 H), 8.21 (d, J = 8.0 Hz, 2 H).
Compound 1d:21 1H NMR (400 MHz, CDCl3): d = 2.45–2.49
(m, 2 H), 3.77 (s, 3 H), 4.65 (t, J = 6.5 Hz, 1 H), 5.08–5.16
(m, 2 H), 5.72–5.82 (m, 1 H), 6.78 (d, J = 8.2 Hz, 1 H), 6.88–
6.91 (m, 2 H), 7.23 (t, J = 8.0 Hz, 1 H). Compound 1e:22 1
H
NMR (400 MHz, CDCl3): d = 2.32–2.41 (m, 2 H), 2.58–2.63
(m, 1 H), 5.12–5.20 (m, 3 H), 5.79–5.90 (m, 1 H), 7.16–7.33
(m, 3 H), 7.54 (d, J = 7.6 Hz, 1 H). Compound 1f:9 1H NMR
(400 MHz, CDCl3): d = 2.31 (d, J = 2.9 Hz, 1 H), 2.41–2.49
(m, 2 H), 4.67–4.69 (m, 1 H), 5.12–5.16 (m, 2 H), 5.72–5.79
(m, 1 H), 7.25–7.31 (m, 4 H). Compound 1g:10 1H NMR (400
MHz, CDCl3): d = 2.21 (br s, 1 H), 2.33 (s, 3 H), 2.45–2.50
(m, 2 H), 4.66 (t, J = 6.5 Hz, 1 H), 5.08–5.16 (m, 2 H), 5.74–
5.82 (m, 1 H), 7.14 (d, J = 7.7 Hz, 2 H), 7.22 (d, J = 7.5 Hz,
2 H). Compound 1h:20 1H NMR (400 MHz, CDCl3): d = 2.09
(br s, 1 H), 2.35–2.44 (m, 2 H), 4.34 (br s, 1 H), 5.14–5.19
(m, 2 H), 5.79–5.90 (m, 1 H), 6.23 (dd, J = 7.9, 15.9 Hz, 1
H), 6.59 (d, J = 15.9 Hz, 1 H), 7.21–7.37 (m, 5 H).
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Compound 1i:23 1H NMR (400 MHz, CDCl3): d = 1.66 (br s,
1 H), 1.70 (d, J = 6.5 Hz, 3 H), 2.24–2.35 (m, 2 H), 4.08–4.15
(m, 1 H), 5.11–5.17 (m, 2 H), 5.51 (dd, J = 6.8, 15.2 Hz, 1
H), 5.65–5.73 (m, 1 H), 5.75–5.85 (m, 1 H). Compound 1j:10
1H NMR (400 MHz, CDCl3): d = 1.73–1.81 (m, 2 H), 1.89
(br s, 1 H), 2.14–2.21 (m, 1 H), 2.26–2.32 (m, 1 H), 2.64–
2.71 (m, 1 H), 2.75–2.83 (m, 1 H), 3.64–3.70 (m, 1 H), 5.10–
5.15 (m, 2 H), 5.74–5.85 (m, 1 H), 7.15–7.30 (m, 5 H).
Compound 1k:24 1H NMR (400 MHz, CDCl3): d = 0.86 (t,
J = 7.0 Hz, 3 H), 1.21–1.50 (m, 12 H), 1.65 (br s, 1 H), 2.05–
2.21 (m, 1 H), 2.27–2.38 (m, 1 H), 3.58–3.72 (m, 1 H), 5.12–
5.19 (m, 2 H), 5.77–5.95 (m, 1 H). Compound 1l:22 1H NMR
(400 MHz, CDCl3): d = 0.90 (t, J = 7.0 Hz, 3 H), 1.24–1.48
(m, 6 H), 1.72 (br s, 1 H), 2.12–2.16 (m, 1 H), 2.15–2.33 (m,
1 H), 3.60–3.65 (m, 1 H), 5.10–5.17 (m, 2 H), 5.77–5.90 (m,
1 H). Compound 1m:25 [a]24D –21.2 (c = 1.02, CHCl3). 1H
NMR (500 MHz, CDCl3): d = 1.35 (s, 9 H), 2.20–2.30 (m, 2
H), 2.83–2.94 (m, 2 H), 3.59 (td, J = 1.5, 7.0 Hz, 1 H), 3.73
(br q, J = 8.0 Hz, 1 H), 4.88 (d, J = 9.5 Hz, 1 H), 5.10–5.15
(m, 2 H), 5.70–5.80 (m, 1 H), 7.18–7.32 (m, 5 H).
Synlett 2008, No. 1, 65–68 © Thieme Stuttgart · New York

68
X. Zhang
LETTER
Compound 1n:26 [a]24D +15.1 (c = 1.0, CHCl3). 1H NMR
(500 MHz, CDCl3): d = 1.36 (s, 3 H), 1.43 (s, 3 H), 2.16–2.24
(m, 1 H), 2.25–2.37 (m, 1 H), 2.41 (br s, 1 H, OH), 3.62–3.78
(m, 1 H), 3.90–3.95 (m, 1 H), 3.98–4.06 (m, 2 H), 5.10–5.17
(m, 2 H), 5.80–5.91 (m, 1 H).
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Synlett 2008, No. 1, 65–68 © Thieme Stuttgart · New York

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