Niobium(V) chloride-mediated allylation of aldehydes. Scope and stereoselectivity

Article abstract of DOI:10.1016/S0040-4039(01)01306-5

Niobium chloride promoted the addition of allylstannanes to aromatic and aliphatic aldehydes. Excellent syn diastereoselectivity was obtained in the addition of E-cinnamylstannane to benzaldehyde (49:1). In the addition of allylstannane to racemic 2-phenylpropionaldehyde, syn diastereoselection (Cram-anti-Cram = 3:1) was observed. The same level of diastereoselection was achieved in the reaction between crotylstannane and benzaldehyde.

Full text of DOI:10.1016/S0040-4039(01)01306-5

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 6473–6476
Niobium(V) chloride-mediated allylation of aldehydes. Scope and
stereoselectivity
Carlos Kleber Z. Andrade* and Neuc ´ı rio R. Azevedo
Instituto de Qu ´ı mica, Universidade de Bras ´ı lia, C.P. 4478, 70910-970 Bras ´ı lia, DF, Brazil
Received 2 July 2001; revised 17 July 2001; accepted 19 July 2001
Abstract—Niobium chloride promoted the addition of allylstannanes to aromatic and aliphatic aldehydes. Excellent syn
diastereoselectivity was obtained in the addition of E-cinnamylstannane to benzaldehyde (49:1). In the addition of allylstannane
to racemic 2-phenylpropionaldehyde, syn diastereoselection (Cram–anti-Cram=3:1) was observed. The same level of diastereose-
lection was achieved in the reaction between crotylstannane and benzaldehyde. © 2001 Elsevier Science Ltd. All rights reserved.
The Lewis acid-mediated addition of allylstannanes to
carbonylic compounds has been extensively studied. A
In order to investigate the feasibility of the reaction,
various aldehydes were reacted with allyltri-n-butyl-
1
variety of Lewis acids have been employed successfully
in these reactions, including TiCl , BF ·OEt , SnCl ,
stannane, in the presence of NbCl . In our search for
5
the best experimental conditions the following parame-
ters were evaluated: solvent, temperature, stoichiomet-
ric relationship and the order in which the reagents
were added. The results are summarized in Table 1.
4
3
2
4
AlCl , InCl , among others.
3
3
The homoallylic alcohols so obtained, are important
and versatile intermediates in the synthesis of more
complex products since the double bond can be further
functionalized (Scheme 1).
The best results were obtained when 2 equiv. of the
allylstannane were used, at −15°C, in diethyl ether as
4
the solvent (entries 6, 10 12, 14 and 16). NbCl pro-
5
Motivated by some recent work which demonstrated
moted the ring-opening of the THF, leading to poly-
meric products (entry 7). When the more coordinating
2
2c,d,f
the Lewis acidity of niobium and tantalum
com-
pounds in organic reactions, we decided to investigate
solvents DME and CH CN were used the yields low-
3
the use of NbCl on the allylation of aldehydes. NbCl5
ered (entries 9 and 13) or the reaction failed completely
(entries 8, 11 and 15). When isobutyraldehyde was used
yields were low (ca. 20–30%), probably due to the
volatility of the product. In contrast, a much better
yield was obtained when 2-phenylpropionaldehyde was
employed (Table 2).
5
has a great oxophylicity and is readily available in our
country since Brazil accounts for about 60% of total
3
niobium production.
2b
In a similar reaction, Suzuki et al. reported the double
addition and exclusive formation of a cyclopropane
derivative when allylsilanes reacted with aldehydes, in
the presence of NbCl (Scheme 2). Such a compound
5
was never observed in the reaction with allylstannane.
These interesting results show the versatility of NbCl5
as a Lewis acid.
After establishing the best experimental conditions, we
turned our attention to the stereoselectivity of these
reactions. The Cram–anti-Cram selectivity was
addressed in the reaction between (±)-2-phenylpropi-
onaldehyde and allylstannane in the presence of NbCl5
(Table 2). The diastereofacial selectivity was low (3:1),
Scheme 1.
*
0
Corresponding author. E-mail: ckleber@unb.br
040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01306-5

6
474
C. K. Z. Andrade, N. R. Aze6edo / Tetrahedron Letters 42 (2001) 6473–6476
a
Table 1. Experimental conditions and yields of the reactions between aldehydes and allyltri-n-butylstannane
c
Entry
R
Solvent
CH Cl
Temp. (°C)
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
9
Phb
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
−78
−78
−15
−78
−15
−15
−78
−43
−15
−15
−15
−15
−15
−15
−15
−15
2.5
1.5
1
2
2
0.5
2.5
2
2
1.5
2
41
38
45
48
47
100
−
–
70
50
–
70
50
71
–
2
2
2
2
CH Cl
2
CH Cl
2
b
Et O
2
b
Et O
2
Et O
2
b
THF
b
CH CN
3
DME
10
11
12
13
14
15
16
p-OMePh
p-OMePh
p-NO Ph
Et O
2
DME
Et O
1.5
2
0.5
2
2
2
p-NO Ph
DME
2
p-ClPh
p-ClPh
2-Furyl
Et O
2
DME
Et O
0.5
50
2
m-border\−15ca=‘‘D’’\\0.5ca=‘‘D’’\\50
a
Unless otherwise noted 2 equiv. of allylstannane were employed.
Reaction with 1 equiv. of allylstannane in relation to the aldehyde.
Isolated yields of the chromatographically pure products.
b
c
Table 2. Results of the reaction between allylstannane and
9)-2-phenylpropionaldehyde in Et O
cific in that no linear product was formed under any
conditions.
(
2
It is reported that the order of addition of the reagents
in SnCl - and TiCl -mediated allylation reactions alters
4
4
the diastereomeric ratio of the homoallylic alcohol as
well as the regiochemistry of the reaction, due to
8
Yield (%)a
transmetallation. The reactions performed with normal
Entry
Temp. (°C)
Syn:anti
addition (addition of crotylstannane to a suspension of
benzaldehyde and NbCl in Et O) afforded a mixture of
1
2
−78
−15
3:1
1.6:1
63
75
5
2
9
diastereomers in good yields (Table 3, entries 1 to 3).
The best results were obtained at −15°C with shorter
reaction periods. When the reactions were performed at
lower temperatures (−78°C) or when 2 equiv. of NbCl5
were used (entry 3), no significant improvements were
achieved either in yield or in selectivity.
a
Isolated yields of the chromatographically pure products (syn/anti
mixture).
In the reactions with inverse addition (addition of
benzaldehyde to a suspension of crotylstannane and
NbCl5 in Et O), the yields and diastereoselectivities
2
were similar to those obtained with normal addition
Scheme 2.
(
entry 4). Furthermore, linear products were not
detected under any conditions, as already mentioned.
1
0
Although no spectroscopic studies were performed,
even at −78°C. These results are similar to those
obtained with other Lewis acids such as BF ·OEt and
these results suggest that the transmetallation process is
not occurring.
3
2
5
1
TiCl4. The diastereomers were identified by the
H
6
NMR chemical shifts of the methyl groups by com-
parison to those described in the literature and
quantified by GC.
In order to get a better insight on the stereochemistry
7
of the NbCl -mediated additions to aldehydes, the reac-
5
1
1
tion between E-cinnamylstannane (3-phenyl-allylstan-
nane) and benzaldehyde was studied.
Next we examined the stereo- and regioselectivity of
these NbCl -promoted allylation reactions. In this way,
crotylstannane (3-methyl-allylstannane, 1:1 mixture of
isomers) and benzaldehyde were reacted in the presence
The reaction proceeded smoothly, but in this case the
5
syn diastereomer was obtained almost exclusively, in
12
good yield (Scheme 3). This result is in sharp contrast
13
of NbCl (Table 3). The reaction proved to be regiospe-
to those obtained with ZnCl in DMF and SnCl in
2 2
5

C. K. Z. Andrade, N. R. Aze6edo / Tetrahedron Letters 42 (2001) 6473–6476
6475
a
Table 3. Results of the reaction between crotylstannane and benzaldehyde in Et O
2
Syn:anti9
Time (h)
Yield (%)
c
Entry
Temp. (°C)
Mode of addition
1
2
3
−15
−15
−15
−15
Normal
Normal
Normal
Inverse
1.9:1
2.6:1
2.5:1
2.2:1
1.5
0.3
0.3
0.3
63
91
83
91
b
4
a
In all cases 2 equiv. of crotylstannane were used.
b
c
2
equiv. of NbCl5 were used.
Isolated yields of chromatographically pure products (syn/anti mixture).
1
4
15
CH CN, which gave predominantly the anti isomer.
3
In both cases, a cyclic transition state was proposed to
explain the anti stereoselectivity. Although it is reported
13
that BF ·OEt is also syn-selective, the reaction is run
3
2
at −78°C. The advantage here is that the reaction can
be warmed up to 0°C without lowering the selectivity.
To confirm the stereochemical assignment of our major
isomer, an enriched (5:1) mixture of the anti isomer was
Figure 1. Syn-synclinal and antiperiplanar transition states for
E-cinnamylstannane.
16
prepared following the procedure of Wilson et al. The
spectroscopic data of the major isomer in the above 5:1
17
mixture matched those reported for our anti isomer
also in aldol reactions using NbCl5 will soon be
published.
whereas the data for the minor isomer in the mixture
above fully agreed with those obtained for our major
18
isomer in the NbCl -mediated reaction.
5
Acknowledgements
The mechanism of these reactions is still a matter of
much controversy. Either the antiperiplanar transition
4
state (ET2) proposed by Yamamoto or the syn-syn-
19
The authors thank the Instituto de Qu ´ı mica, Universi-
dade de Bras ´ı lia, for its financial support during the
early stages of this work. We also thank CBMM for
clinal transition state (ET1) proposed by Keck can be
invoked to explain the selective formation of the syn
2
0
isomer in this case (Fig. 1). It also seems possible that
the double bond geometry plays an important role in
the reaction diastereoselectivity.
NbCl samples, CAPES for fellowship, Professor Ant oˆ -
5
nio Gilberto Ferreira (UFSCar) for high field NMR
spectra, Professor Peter Bakuzis (UnB) and Professor
Ronaldo Pilli (UNICAMP) for helpful suggestions and
revision of this manuscript.
In conclusion, the scope and limitations of the NbCl5-
mediated allylation of aldehydes have been studied. The
methodology allows the obtention of homoallylic alco-
hols in good yields. NbCl proved to be an effective
5
Lewis acid and a promising tool in the control of
diastereoselectivity in these reactions. The exceptional
selectivity obtained with cinnamylstannane makes
NbCl5 an attractive choice when the syn isomer is
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