A new type of allylation: Synthesis of β,γ-unsaturated ketones from α-halogenated aryl ketones using an allyltributyltin(IV)-tin(II) dichloride-acetonitrile system

Article abstract of DOI:10.1039/a708679b

Allylation of α-halogenated aryl ketones with an allyltributyltin-tin dichloride-acetonitrile system gave β,γunsaturated ketones in high yields via selective aryl rearrangement.

Full text of DOI:10.1039/a708679b

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A new type of allylation: synthesis of b,g-unsaturated ketones from
a-halogenated aryl ketones using an allyltributyltin(iv)–tin(ii)
dichloride–acetonitrile system
Makoto Yasuda, Makihiro Tsuchida and Akio Baba*†
Department of Applied Chemistry, Faculty of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565, Japan
Allylation of a-halogenated aryl ketones with an
allyltributyltin–tin dichloride–acetonitrile system gave b,g-
unsaturated ketones in high yields via selective aryl re-
arrangement.
in which the interaction between the tin(ii) atom and the halogen
directs the aryl rearrangement.5 This type of interaction is
unlikely to occur using allyltin(iv) reagents, which have a
weaker affinity for halogen than the tin(ii) species. Allylation
using tin(iv) reagents of a-halo ketones proceeds via cyclization
of the intermediate tin alkoxides to give oxiranes exclusively,
and no rearrangement is observed.6–8 Other solvents examined
(THF, toluene, CH2Cl2, CHCl3) in the presence of SnCl2 gave
low yields of 3a (0–24% yield) at room temperature for 1 h.
These facts strongly support the participation of the allylic
tin(ii) species in the rearrangement, because our previous
report2 has already shown the efficiency of MeCN as the solvent
of choice for transmetalation of allyltributyltin 1 with SnCl2.
Allylaton of 2a in MeCN for 24 h without SnCl2 did not proceed
at all. Considering these results, we suppose that this new type
of allylation system giving the b,g-unsaturated ketone evolves
from the unique character of the tin(ii) reagents.
Allylation of carbonyl compounds has been intensively studied
for carbon–carbon bond formation, affording homoallylic
alcohols.1 We have recently reported an allylic tin(ii) species as
powerful allylation reagents toward aldehydes, ketones or
imines in preference to the corresponding tin(iv) species.2 The
tin(ii) species, which have vacant orbitals to accept electrons,
contribute to the selective carbonyl allylation via a cyclic
transition state owing to the strong affinity between the tin(ii)
atom and the carbonyl oxygen.2 The tin(ii) center would be
expected to interact even with a halogen atom because the latter
bears unshared electron pairs for coordination to tin(ii). Herein,
we report a new type of allylation system for a-halogenated aryl
ketones.3 This reaction proceeds via carbonyl allylation and
subsequent aryl rearrangement to give b,g-unsaturated ketone
derivatives in high yields, in which reaction the tin(ii) species
characteristically effects the rearrangement.
A mixture of tin dichloride (SnCl2) and 2-bromopropiophe-
none 2a in MeCN was treated with allyltributyltin 1 at room
temperature for 10 min to afford, unexpectedly, the b,g-
unsaturated ketone 3a, whereas general activation by a Lewis
acid, boron trifluoride–diethyl ether,1,4 gave the homoallyl
alcohol 4a exclusively (Scheme 1). In the allyltributyltin–SnCl2
system, migration of the phenyl group takes place as shown in
Scheme 2. The homoallylic tin alkoxide A is a key intermediate
We then explored the generality of the reaction by varying the
aryl halo ketones. As shown in Table 1, b,g-unsaturated ketones
Table 1 Synthesis of b,g-unsaturated ketones 3
R
Ar
Bu3Sn
O
3
1
SnCl2, MeCN
25 °C, t1
MeCN
+
+
80 °C, t2
R
Ar
R
X
Ar
X
SnCl2
HO
O
Ph
25 °C, 10 min
MeCN
2
4
O
3a 71%
Halo ketone 2
Yield (%)
Ph
+
Bu3Sn
Br
Entry
Ar
R
X
t1/h
t2/h
3
4
O
Ph
BF3•OEt2
2a
1
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
4-MeOC6H4
4-MeC6H4
4-PhC6H4
4-PhC6H4
Ph
4-ClC6H4
4-O2NC6H4
2-naphthyl
2-naphthyl
2-thienyl
2-thienyl
3-thienyl
3-thienyl
Ph
H
H
H
H
H
H
H
H
H
H
H
H
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Cl
Cl
Cl
1
1
1
1
1
1
1
1
1
0
98
81
65
0
60
26
0
74
0
72
0
61
0
98
71
0
0
0
0
0 °C, 6 h
CH2Cl2
HO
Br
0.5
0.5
0
0.5
0.5
0.5
1
0
0.5b
0
0.5
0
0
0.5
0
0
4a 72%
89
0
27a
16
0
95
0
76
0
Scheme 1
SnCl2
Bu3Sn
ClSn
O
–Bu3SnCl
0.25
1
1
1
24
1
Ar
X
H
83
0
Ar
Ar
Me
Me
Me
Ph
Ph
Ph
Ph
0
Aryl rearrangement
0.25
1
90c
0
X
O
O
86
Sn
Cl
A
a
2-(p-Chlorophenyl)pent-4-enal (ca. 10% yield) was obtained as a side
Scheme 2
product (see ¶). b 50 °C. c Isomeric ratio = 61:39.
Chem. Commun., 1998
563

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in dry MeCN (1.0 ml), and the mixture was stirred under the conditions
noted in the text. Et2O (100 ml) and aq. NH4F (15%; 40 ml) were added, the
organic layer was separated and washed with water (50 ml 3 2), dried
(MgSO4) and evaporated to give b,g-unsaturated ketone 3. The crude
product was further purified by flash chromatography on silica gel.
§ Since the alkyl group has a low aptitude for migration, reaction of the
intermediate with the solvent nitrile occurred.
3 were effectively obtained.‡ The aryl rearrangement often
required high temperature conditions (80 °C) because homo-
allyl alcohols 4 were formed exclusively at 25 °C (entries 4, 9,
11, 13 and 16). This result suggests that the reaction includes the
intermediate A illustrated in Scheme 2. The effect of different
aromatic substituents was interesting. Generally, the allylation
of aryl-substituted carbonyls is enhanced by an electron-
withdrawing group on the aromatic substituents since the
electrophilicity of the carbonyl group is increased. The opposite
effect was observed in entries 1–3 and 5–7 in regard to the
synthesis of 3. The unrearranged products 4 were observed in
the reaction with the substrates bearing chloro or nitro groups
(entries 6 and 7). These substituent effects are explainable by
the rate-determining migration of the aryl groups,9 as the
allyltin(ii) species have an adequate ability to promote carbonyl
allylation.2 The thienyl ring is tolerated in this reaction system
(entries 10–13), in which sulfur did not reduce the activity of the
tin(ii) reagent at all. The secondary bromo or chloro ketones
also gave 3 exclusively (entries 14, 15 and 17). The rearrange-
ment took place readily without the need for high temperatures
(entries 14 and 17). The interaction of tin(ii) with the halogen
(in A) would generate cationic halide carbon species, which are
more stable for secondary substrates.
Bu
Br
SnCl2, RCN
+
Bu3Sn
O
N
25 °C, 1 h
then 80 °C, 6 h
O
R
R = Me (22%)
R = Et (24%)
Br
Br
RCN
Bu
Bu
SnCl
O
N
O
SnCl
R
¶ The aldehyde, 2-(p-chlorophenyl)pent-4-enal, was formed via 2-allyl-
2-(p-chlorophenyl)oxirane. The transformation of oxirane to aldehyde
commonly proceeds in acidic conditions.
On the other hand, a-halogenated alkyl ketones showed a
different reaction course, without any rearrangement; allylox-
azolines were formed by the addition of solvent nitriles to the tin
alkoxide intermediate, albeit in low yields.§
This work describes a new allylation system for the synthesis
of b,g-unsaturated carbonyl compounds, in which an unusual
reaction course, including aryl rearrangement, is proposed. The
selective rearrangement is promoted by the properties of the
tin(ii) species. Further investigaton of allylic tin(ii) species is in
progress.
This work was supported by a Grant-in-Aid for Scientific
Research on Priority Area No. 09231229 from the Ministry of
Education, Science, Sports, and Culture, of the Japanese
Government. Thanks are due to Mr H. Moriguchi, Faculty of
Engineering, Osaka University, for assistance in obtaining mass
spectra.
1 A recent review: Y. Yamamoto and N. Asao, Chem. Rev., 1993, 93,
2207.
2 M. Yasuda, Y. Sugawa, A. Yamamoto, I. Shibata and A. Baba,
Tetrahedron Lett., 1996, 37, 5951.
3 a-Halogenated ketones are an important class of organic compound and
detailed information on their synthesis has been reported. N. De Kimpe
and R. Verhe´, The Chemistry of a-Haloketones, a-Haloaldehydes and
a-Haloimines, ed. S. Patai and Z. Rappoport, Wiley, Chichester, 1988.
4 Y. Naruta, S. Ushida and K. Maruyama, Chem. Lett., 1979, 919.
5 We have recently reported a similar rearrangement of a 2-oxoalkyl group
promoted by ZnCl2. In this case, however, there was no observation of the
aryl rearrangement even with the use of an aromatic substrate.
M. Yasuda, S. Tsuji, I. Shibata and A. Baba, J. Org. Chem., 1997, 62,
8282.
6 I. Pri-Bar, P. S. Pearlman and J. K. Stille, J. Org. Chem., 1983, 48,
4629.
7 K. Yano, Y. Hatta, A. Baba and H. Matsuda, Synlett, 1991, 555.
8 K. Yano, Y. Hatta, A. Baba and H. Matsuda, Synthesis, 1992, 7, 693.
9 The migratory aptitude for pinacol rearrangement of various aromatic
substituents has been reported. W. E. Bachmann and J. W. Ferguson,
J. Am. Chem. Soc., 1934, 56, 2081.
Notes and References
† E-mail: baba@ap.chem.eng.osaka-u.ac.jp
‡ Typical experimental procedure: Allyltributyltin 1 (1.0 mmol) was added
to a stirred suspension of SnCl2 (1.0 mmol) and a-halo ketone 2 (1.0 mmol)
Received in Cambridge, UK, 2nd December 1997; 7/08679B
564
Chem. Commun., 1998