Regioselectivity in nucleophilic addition of siloxyalkenes to an alkylideneallyl cation

Article abstract of DOI:10.1246/cl.2006.382

Alkylideneallyl cation generated from Lewis acid-mediated ring-opening reaction of alkylidenecyclopropanone acetal was employed for the reaction with siloxyalkenes to give [3 + 2] cycloaddition and acyclic addition products. All the products are the resul

Full text of DOI:10.1246/cl.2006.382

3
82
Chemistry Letters Vol.35, No.4 (2006)
Regioselectivity in Nucleophilic Addition of Siloxyalkenes to an Alkylideneallyl Cation
ꢀ
Morifumi Fujita, Koji Fujiwara, and Tadashi Okuyama
Graduate School of Material Science, Himeji Institute of Technology, University of Hyogo,
Kohto, Kamigori, Hyogo 678-1297
(Received January 31, 2006; CL-060133; E-mail: fuji@sci.u-hyogo.ac.jp)
Alkylideneallyl cation generated from Lewis acid-mediated
ring-opening reaction of alkylidenecyclopropanone acetal was
employed for the reaction with siloxyalkenes to give [3 þ 2]
cycloaddition and acyclic addition products. All the products
O
R1
+
H
Me3SiO
R3
O
2
R
2
R1
are the result of nucleophilic addition to the sp center of the
2
R1
R2
R3
R3
R
TiCl4
O
7
alkylideneallyl cation, and there is no sign of the nucleophilic
addition to the sp center. The regioselectivity is independent
of the electronic and steric effects of siloxyalkene nucleophiles,
and is compatible with charge distribution of the allylic cation.
6
1
+
CH2Cl2
OSiMe3
5
R3
O
a: R ,R = Me, R3 = OMe
1
2
R3
O
+
1
2
R3
b: R = Me, R = H, R3 = OMe
1
2
R
R
c: R ,R = H, R3 = Me
1
2
1
O
R
R2
d: R ,R = H, R3 = Ph
1
2
Alkylideneallyl cations can be described as a hybrid of res-
onance structures of 1-vinyl-substituted vinyl cation and allenyl-
9
8
2
Scheme 3.
methyl cation, and thus contains two reaction sites, sp and sp
1
,2
carbons, for nucleophilic attack (Scheme 1). Relative electro-
philicity of this ambident electrophile has been evaluated from
acyclic adduct depending on the reaction conditions. These
results are summarized in this communication.
Reaction of 1 with TiCl4 was carried out in the presence of
siloxyalkene 5 (Scheme 3) and the results are summarized in
Table 1. In the reaction with ketene silyl acetals 5a and 5b at
1
13
the charge distribution calculated as well as the C chemical
2
shift measured at low temperature under superacidic conditions.
The charge distributions are affected by substituents of the cati-
2
on: The sp carbon is more positive than the sp one when two
2
ꢂ
ꢁ
78 C, ꢀ-ketoesters 6a and 6b were obtained instead of chlo-
ride product 3 which is a major product in the absence of 5.
methyl groups are introduced at the sp carbon.
The product 6 is rationalized by a result of trapping of alkylide-
2
neallyl cation 2 with 5 at the sp carbon, followed by hydrolysis
sp
under acidic conditions. In contrast, the reactions with silyl enol
ethers 5c and 5d gave no acyclic product 6, but gave cyclopen-
tanone derivatives 7–9. The GC analysis of the reaction mixture
from 5c showed siloxycyclopentanone 7c was a major product
sp2
Scheme 1.
(
a mixture of mainly three cyclopentanone derivatives, cylopen-
Entry 3), but the attempted isolation of the product resulted in
We have recently developed a novel method for generation
of alkylideneallyl cation 2 from alkylidenecyclopropanone ace-
tal 1 (Scheme 2). This method provides a nice opportunity to
3
tenone 8c and double addition product 9c in addition to 7c (Entry
4
). Use of excess amounts of 5c and TiCl4 increased the yield of
the double addition product 9c (Entry 5). Reaction with 5d also
gave cyclopentenone 8d, which were isolated in a good yield
examine regioselectivity of nucleophilic addition to the ambi-
dent cation. The previous report showed different regioselectiv-
ity observed between the methanol and chloride additions to the
2
cation intermediate: Methanol selectively attacks at the sp car-
a
Table 1. Reaction of 1 with siloxyalkene 5
bon to give 4 while chloride gives the sp-addition product 3. To
further examine the regioselectivity, siloxyalkenes are employed
for nucleophiles. The nucleophilic addition selectively proceeds
3
10 [TiCl4]/
Yield/%
Entry
5b
ꢁ3
mol dm
6
7
8
9
2
at the sp carbon to give the [3 þ 2] cycloadduct as well as an
1
2
3
4
5
6
5a(0.07)
5b(0.10)
5c(0.02)
5c(0.03)
5c(0.25)
5d(0.04)
5a(0.05)
14
41
15
14
120
20
70
90
81
<1
72 <1
c
<1
37c 12c
37
<1
OMe
Cl-
Cl
38
73
41
24
c;d
acid
3
sp
OMe
e
c
OMe
7
0
OSiMe3
sp2
a
ꢁ3
Reaction of 1 (0.01 mol dm ) was carried out in CH2Cl2 at
MeOH
1
2
ꢂ
b
O
ꢁ78 C for 10 min, and yields were determined by GC. The
H
ꢁ3
values in parentheses are the concentration of 5 (mol dm ).
OMe
c
d
Yield of isolated products. The crude mixture obtained was
further treated with TiCl4, and then purified to give the prod-
uct. Reaction was carried out at 0 C.
4
e
ꢂ
Scheme 2.
Copyright Ó 2006 The Chemical Society of Japan

Chemistry Letters Vol.35, No.4 (2006)
383
8
of 5a.
a could be obtained at higher temperature from the reaction
8
R3
O
6
In summary, the alkylideneallyl cation 2 generated from al-
kylidenecyclopropanone acetal 1 was employed for the reaction
R1
R
2
OMe
Me3SiO
R3
9
sp2-addition
with siloxyalkenes. The [3 þ 2] cycloaddition product and acy-
sp
clic addition product were obtained depending on the reaction
conditions, and all the products are the result of nucleophilic at-
1
R2
R
OMe
OMe
sp2
7
2
2
Me3SiO
tack at the sp center of alkylideneallyl cation 2. The regioselec-
1
0
OMe
3
R
tivity is compatible with charge distribution of the allylic cation
despite of varying the electronic nature and steric bulkiness of
the nucleophile from the simple alcoholic nucleophile.3
R1
2
R
,10
8, 9
R3
R1
O
References and Notes
1
a) H.-U. Siehl, H. Mayr, J. Am. Chem. Soc. 1982, 104, 909.
b) H.-U. Siehl, in Dicoordinated Carbocations, ed. by Z.
Rappoport, P. J. Stang, John Wiley & Sons, New York,
2
R
Scheme 4.
1
997, Chap. 5, pp. 189–236.
after further treatments of the reaction mixture with TiCl4 to
convert to a stable form 8d (Entry 6). Structures of these cyclo-
adducts were determined by two-dimensional NMR including
2
a) H.-U. Siehl, S. Brixner, J. Phys. Org. Chem. 2004, 17,
1039. b) H.-U. Siehl, T. M u¨ ller, J. Gauss, J. Phys. Org.
Chem. 2003, 16, 577. c) Y. Apeloig, T. M u¨ ller, in Dicoordi-
nated Carbocations, ed. by Z. Rappoport, P. J. Stang, John
Wiley & Sons, New York, 1997, Chap. 2, pp. 9–104.
M. Fujita, K. Fujiwara, H. Mouri, Y. Kazekami, T.
Okuyama, Tetrahedron Lett. 2004, 45, 8023.
The orientation of the five-membered ring of 7–9 is also
confirmed by the conversion reaction from 7 to 8 and 9.
The diene structure of 8 indicates that the siloxy of 7 is at
allylic position.
4
HMBC and HMQC measurements after isolation, and any other
1
regioisomers were not detected by GC or H NMR measure-
ments of the reaction mixtures. Judging from these structures,
3
4
8
and 9 must be secondary products derived from 7. To deter-
mine the pathways for formation of 8 and 9, some transforma-
tions of 7 were carried out by using the isolated 7c. Reaction
of 7c with TiCl4 gave 8c in 98% yield, and the TiCl4-mediated
reaction in the presence of 5c gave 9c in 91% yield. Thus, 8 and
9
should be the secondary products.
A plausible mechanism for the reactions of alkylideneallyl
5
6
A siloxy derivative of 2 could be generated from 1, but the
reaction of 1 with TiCl4 in the absence of 5 gives 3 selective-
ly. This suggests the allylic cation contains methoxy group.
a) [3 þ 2] cycloadditions via trimethylenemethane inter-
mediate have been reported in the reaction of 1,1-dialkoxy-
2-methylenecyclopropane with electron-deficient olefins.
The ring-opening reaction of the cyclopropane substrate
takes place between the C1 and C3, and is different from
the reaction of 1. b) E. Nakamura, S. Yamago, Acc. Chem.
Res. 2002, 35, 867, and references cited therein.
The vacant orbital at the sp carbon of 2 may be shielded by
the cyclohexane ring, but some nucleophiles including chlo-
ride and furans prefer the sp attack. So, the present selectivity
may be controlled mainly by the charge distribution.
cation 2 with siloxyalkenes 5 is illustrated in Scheme 4. The
5
cation 2 generated from 1 is trapped by siloxyalkene at the
2
sp position to give the cationic intermediate 10 stabilized by
the oxy group(s). Desilylation from 10 results in formation of
acyclic adduct 6, and intramolecular cyclization of 10 gives
6
the cycloadduct with such regioisomeric orientation. If the
6
b
stepwise [3 þ 2] cycloaddition were initiated by the addition at
the sp carbon of 2, the different orientation of the cycloadduct
should have been obtained. Thus, all the products 6–9 are the
7
8
2
result of nucleophilic attack at the sp carbon of 2. The regiose-
2
lective addition at the sp carbon of 2 is rationalized by the
charge distribution estimated from calculations and C NMR:
13
2
the sp carbon is more positive than the sp carbon of 2,5-dimeth-
ylhexa-3,4-dien-2-yl cation (2,5-dimethylhexa-2,4-dien-3-yl
cation).1
effect of the siloxyalkenes employed, and the reaction with
dimethylketene silyl acetal 5a allows the smooth connection of
the two contiguous quaternary carbon centers.
For the reaction with 5a, alternative pathways for the cyclic
product 8a are also possible owing to the symmetric nature
of the five-membered ring. However, the common pathways
in the cycloadditions of 5a–5d are limited, and one of the
simple pathways to cycloadducts is shown in Scheme 4.
Mukaiyama–Michael addition of 5 to 7 can be an alternative
pathway to the double addition product 9. Although some
details during the formation of 8 and 9 are uncertain, the
a,2a,7
The regioselectivity is not affected by the steric
The reaction with silyl enol ether 5c and 5d gave only the
[
3 þ 2] cycloadducts in comparison with effective formation
2
of acyclic adduct 6 in the reaction with ketene silyl acetal 5a
and 5b at lower reaction temperature. This can be explained
by the reactivity of cationic intermediates 10: The intermediate
from 5c and 5d is more reactive owing to lower stabilization
by oxy group than that from 5a, 5b, and reacts with the internal
allene more efficiently to give the cycloadduct(s). Cyclic product
electrophilic reaction site of 2 is the sp center.
9
Lewis acid-mediated reactions of cyclopropanes with
siloxyalkenes, see: a) M. Ohno, S. Matsuoka, S. Eguchi,
J. Org. Chem. 1986, 51, 4553. b) K. Saigo, S. Shimada, T.
Shibasaki, M. Hasegawa, Chem. Lett. 1990, 1093.
10 C. A. Grob, R. Spaar, Helv. Chim. Acta 1970, 53, 2119.
Published on the web (Advance View) March 11, 2006; DOI 10.1246/cl.2006.382