ETHYLMAGNESIUM BROMIDE MEDIATED DESULFINYLATION OF α-HALO-β-KETOSULFOXIDES GIVING α-HALOKETONES, AND TRAPPING OF THE MAGNESIUM ENOLATE INTERMEDIATE

Article abstract of DOI:10.1016/0040-4039(91)80094-M

Treatment of α-halo-β-ketosulfoxides with EtMgBr gives α-haloketones in high yields after protonation of the magnesium enolates.Trapping of the magnesium enolates with various electrophiles is also carried out.

Full text of DOI:10.1016/0040-4039(91)80094-M

Tetra'he&on Letters, Vo132, No 40, pp 5599-5600, 1991
Printed m Great Britain
0040-4039/91 $3.00 + 00
Pergamon Press ple
ETHYLMAGNESIUM BROMIDE MEDIATED DESULFINYLATION OF
~-HALO-B-KETOSULFOXIDES
GIVING e-HALOKETONES, AND TRAPPING OF THE MAGNESIUM ENOLATE INTERMEDIATE
Tsuyoshi Satoh, Ken-ichi Onda, Norifumi Itoh, and Koji Yamakawa*
Faculty of Pharmaceutical Sciences, Science University of Tokyo,
Ichigaya-funagawara-machi, Shlnjuku-ku, T o k y o 162, J a p a n
Summary
Treatment of e-halo-8-ketosulfoxides with EtMgBr gives e-haloketones
Trapping of the
in high ylelds a f t e r protonation of the magnesium enolates.
m a g n e s i u m enolates with varlous electrophiles is also carried out.
Since the pioneering work of T r o s t and others, sulfoxides have been exten-
sively used in m o d e r n synthetic organic chemistry. ~
we 4 recently reported the r e a c t i o n of sulfoxldes with alkylmetals to give new
alkylmetals or desulfinylated products. These new reactions are thought to
be useful for the exploiting the use of sulfoxides in organic synthesis. In
continuation of our studies on the use of 1-haloalkyl aryl sulfoxides in
organic synthesls, we report here novel method for synthesizing m-halo-
ketones from l-haloalkyl aryl sulfoxides and aldehydes via the E t M g B r
m e d i a t e d desulfinylation of e-halo-8-ketosulfoxides 4. We also r e p o r t
trapping of the m a g n e s i u m enolate intermediate with d e u t r i u m oxide, e t h y l
Furukawa, 2 0 k a m u r a , 3 and
a
6
1
2
a
5
chloroformate, chlorotrimethylsilane, and benzaldehyde as s h o w n in Scheme i.
r
O X
O X O H
O X O
[
X
.OMgSr
EtMgBr
ArS-CH 1) LDA
. . . .
Swern
. . . . .
A r S - C - C H R2
=
A r S - C - C - R2
h'
2) R CHO
R1
ox,(J.
1
2
3
4
5
X=F,CI,Br
~Me3SiCI
]
,X 0
x o .
I
X
OE
R I - C - C - R2
R I - C - C - R2
5
i
R1~ - ' ~ R 2
(D20)
H(D)
PhCHOH
8
6
7
S c h e m e
1
1-Chlorohutyl
/~tolyl sulfoxide s (I: Ar=Tol,
X=Cl,
RI:(CHz),CH~)
was
treated with LDA at -78 °C in THF followed by 3-phenylpropanal to a f f o r d the
8-chloroalcohol 3e (Ar=Tol, RI=(CH~)2CH~, Rz=CH2CH2Ph; see Table i) in 99%
y i e l d as
Swern's condition gave B-ketosulfoxide 4e in 96% yield.
was treated with I.I equivalents of /2-BuLl In ether at -78 °C (5 min) and
a f t e r q u e n c h i n g with water, 4-chloro-l-phenyl-3-heptanone 6e (X=CI, R I=
(CH2)~CH3, R2:CH2CH2Ph) was isolated in 86% yield. No product from the re-
a c t i o n with carhonyl g r o u p in 4e was detected. This reaction was carried out
a
mixture of two diastereomers.
O x i d a t i o n of this mixture u n d e r
8-Ketosulfoxlde 4e
with o t h e r alkylmetals u n d e r several conditions, and E t M g B r (1.1 equivalents)
in e t h e r at -78 °C was f o u n d to be the optimal condition to afford 6e in 91%
yield.
The results of the synthesis of u-fluoro-, u-chloro-, and u-bromoketones
by thzs procedure are summarized in Table 1.
roketones" (entry a-d) were obtained in high overall yields.
unstable nature of the compounds containing bromine, the yields
It is w o r t h noting that ~-fluo-
Because of the
for the
synthesis of e-bromoketones were somewhat lower than for o t h e r ~-haloketones.
5599

5600
This
late.
desulflnylation r e a c t i o n was thought to take p l a c e t h r o u g h an eno-
Indeed, by q u e n c h i n g the r e a c t i o n of 4e with EtMgBr with D20 instead
of water, regloselectively deutrated a-chloroketone
y i e l d (Scheme i). In o r d e r to further substantiate
clarify the u s a g e of this r e a c t l o n in new synthetic method, the reaction was
carried out with some electrophiles. A f t e r the treatment of 4e with EtMgBr
6
(D) was obtained In 87%
the enolate and to
in e t h e r at -78
°C, C I C O 2 E t was a d d e d and the mixture was stlrred at
0
°C
(2.5 h) and then at room temperature (i h) to a f f o r d enol carbonate
7
(E=
CO2Et) in 86% y i e l d (E/Z-mlxture). 9
in the presence of Et3N and HMPA (0 °C
give s i l y l enol e t h e r (E=SiMe3; detected by ~H NMR) and it was converted to
Q u e n c h i n g the enolate with benzaldehyde at -78 °C
(syn/anti-mlxture) in 80% yield.
The enolate 5e was t r e a t e d with ClSiMe~
1
h, then room temperature h) to
2
7
6e by acid hydrolysis.
afforded cleanly the a l d o l
8
Table 1. Syn~esls of a-HNoketone 6 ~om 1-HNobutyl Aryl sulfox,de 1 (RI=(CH2)2CH3) and Aldehyde 2
1
2
3
4
6
X
Ar
Ph
R2
Yield (%)
Yleld (%) ~)
Yleid (%) b)
a
Fc)
C1
PhCH2CH2
CH3(CH2) 8
Ph
97
95
94
80
99
82
92
91
95
99
90
90
93
85
97
89
96
92
83
94
73
90
94
72
79
90
82
85
91
93
78
95
68
70
56
59
b
c
d
e
f
g
h
i
Cyc-Hex
PhCH2CH2
CH3(CH2) 8
Ph
Tel
Cyc-Hex
PhCH2CH2
CH3(CH2) 8
Ph
Brd) Tel
3
k
1
Cyc-Hex
Conversion ~eld. b) Isol~edyleld. c) Preparedaccor~ng m He me~odbyWunk.6
~Prep~edaccordmgtothe me~od~ponedby ~uch~lma.7
References and Notes
i. B. M. Trost, Chem. Rev., 78, 353 (1978); E. Block, "Reactions of Organo-
sulfur Compounds" A c a d e m i c Press: New York 1978; S. Patai, Z. Rappoport,
C. Stirling, Eds. "The Chemistry of Sulphones and Sulphoxides" John W i l e y
and Sons: Chlchester, 1988.
2. N. Furukawa, T. Shibutanl, K. Matsumura, H. Fu3ihara, and S. Oae,
Tet~ahedron left., 27, 3899 (1986); N. Furukawa, T. Shibutani, and H.
Fujihara, 2 b J ~ , 28, 2727 (1987).
3. P. G. T h e o b a l d and W. H. Okamura, J. Org. Chem., 55, 741 (1990).
4. T. Satoh, Y. Kaneko, and K. Yamakawa, Tetrahed~on left., 27, 2379 (1986);
idem, Bull. Chem. SoC. Jpn., 59, 2463 (1986); T. Satoh, T. Oohara, Y.
Ueda, and K. Yamakawa, Tetrahed2-on Zett., 29, 313 (1988); T. Satoh, T.
Oohara, and K. Yamakawa, i b i S , 29, 2851 (1988); idem, i b i ~ , 29, 4093
(1988); T. Satoh, T. Oohara, Y. Ueda, and K. Yamakawa, Jo Orff. Chem., 54,
3130 (1989); T. Satoh, T. Sate, T. Oohara, and K. Yamakawa, I b i S , 54,
3973 (1989).
5. T. Satoh, K. Onda, and K. Yamakawa, Tetrahedron left., 31, 3567 (1990);
idem, J. Org. Chem. in press.
6. S. F. Wunk and M. J. Roblns, J. Org. Chem., 55, 4757 (1990).
7. S. Iriuchljima and G. Tsuchihashi, Synthesis, 1970, 588.
8. S. R o z e n and R. Flller, Tet2ahed~on, 41, IIii (1985).
9. T. Satoh, A. Suglmoto, M. Itoh, and K. Yamakawa, Bull. Chem. Soc. Jpn.,
62, 2942 (1989).
(RecelvedmJapan19June1991)