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A highly enantio- and diastereoselective aldol reaction for α-heterosubstituted thioacetates
Temahedmn L&rem, Vol. 35, No. 21. pp. 48534856,
1994
Else&r Science Ltd Printed in GreatBritain oo40-4039/94 $7.00+0.00
0040-4039(94)00894-9
A Novel Method for the Synthesis of ccFhoroketones Rearrangement Vi&d
ReutrakuP,
Thong&d
Kruahong
and
Manat
via Claisen
Pohmakotr
Department of Chemistry, Faculty of Science. Mahidol University, Rama 6 Road Bangkok IWOO. Thailand.
5. Abstract: Fluorine-facilitard Claim reamngement has been employed as a key step in the synthesis of a-fluoroketones l?ift elimination of surfcnic acidjhn
the allyi ethers 3 are fleeted under FVP conditions.
In thepreaeding
communbti~n,~
we have reported ihe synthesis of fluoromethylketones
by flash vacuum pyrolysis (FVP) utilizing cr-fluoromedhyl phenyl sulfoxide 1 asa fluorinated one-carbon building block. The present letter deals with the novel synthesis of a-fluoroketones employing fluoriuefacilitated Claisen rearrangement as the key step (3 + 5).2JJ The process is summa&xl
0
Fh’
1.2LDA.
s
F
-
0
THF. HMPA
-78 OC
*
2. RCHO, -78 ‘C, 2 h
OH
E
Fw
2
1
R
+ +
1. 1.5 LDA, THF, -A
R3 X
2. RI+/ -78%.
3 h.
then Ii ovunight I
R3
P7T 1-JO
RI
AR
RZ
F
RI
0
Fvp
0
R R3
Ph’ ul
F 3
Scheme 1 4853
’ +
!
R2
in Scheme 1.5
4854
The adducts 2 were prepared in high yields ( R= CgH17,82%; using techniques
reported earlier.’
bromides or iodides in good yields,
Ph, 83%; PhCH2,91%
The ally1 ethers 3 were prepared by the alkylation
with tbe ally1
using LDA as,a base. The Claisen intexmediate 4 was generated by
FVP technique with the following conditions: reaction flask temperatum, 216 Oc and column temperature 305 OC at 0.1 mmHg. The results are smnmaked
in Table 1.
Yields of Ally1 Ethers 3 and a-FGoroketones
Table 1
a-Fhoroketones
Ally1 ethers 3, 8
R=
5.
5, %a
‘217 mBr
a)
1
98
83 93 97 28
+
CBH17C(3CW 6,
e) fi_Br,
98
50
75
83
64
82
51
84 +
71
R= Fh b)
.
&Br
a)
-1, I,
c)
PhCOC~F 7, 45
d)
pBr
0) ph -Br,0 R=
v 43
54
66
98
3 76
85
64
94
F’hCH, -Br
a) b)
-1,
98
e) WABr
)
. 87
32 + PhCH$OCH2F 8, 55 65
a Products were isolated by PLC using hexane as an elueut.
4855
The a-fluoroketones 5 are obtained in high yields except in the cases of 3d ( R= C8Ht7, Ph. PhCH2; Rt=R2= Me, R3e H ) in which the contqmnding
fluoromethylketones
are also isolate%L The
formation of the fluoroketones 6,7 and 8 could be ratlonalixed on the basis of the steric crowding of the transitionstate4 causing it to fragments instead of for&g
a new carbon-carbon bond
The reaction sequence in Scheme 1 has also been applied to a more stetically hindered aldehyde; pivalaldehyde. The fluoroketone 11 was isolated in modemte yield. The intermediates9 and 10
were synthesized in high yields ( Scheme 2).
w
B@uF
1_2LDA,THF,EJMPA -78 “C ) 2.
::
OH
PhRS
lBuCH0, -78 ‘C, 2 h
ut
F 9.82%
I
Fh-
1%
35%
WA
Br
10. 98% scheme
2
Our approach appears to be general for the synthesis of this type of fluoroketoues. The outstanding features are the ease of the syntheses of intermediates 2 and 3 in high yields, and the final product fluoroketones can be readily purified by pmparative thin-layer chmmatography @XC, silica gel).
References 1.
and
Notes
Submitted for publication. Also see this communicationfor leading references onthechemistryand biology of fluorinated compounds.
2.
For reviews on Claisen rearrangement see: a) Hill, R. K. in Aymmerric Synthesis Morrison, J. D., Ed. Academic Press, N. Y. 1984, Chapter 8. b)
1988,88, 3.
Ziegler, F. E.
Vuhte
3,
Chem. Rev.
1423. c) ‘Blechert. S. Synthesis 1989, 71.
An example of in situ generation of Claisen system (1 ,Pheterohexadiene) by the elimination of sulfenic acid has been reported: a) Mandai, T.; Ueda, M.; Hasegawa, S. I.: Kawada, M. and Tsuji, J. Tetrahedron fert l990,32,4041. For related reactions see: b) Buechi. G. and Vogel, D. E. J. Org.
Chern. 1983.48.
5406.
Tetrahedron Letf. 1991, 32, 7601. d)
c)
Paterson, I.;
Huhne, A. N. and Wallace, D. J.
Ireland, R. E.; Wipf, P.; Armstrong IJI, J. D. J. Org.
4856
Chem. 1991,56,650.e) Panek, S. J. and Clark, T. D. ibid. 1992.57, Get-hart, F.; Francais, J. P. Synthesis 1988,469. J. Tetrahedron
1988,44,
L.ett. 1988.29,
3291.
4323.
f) Kolb, M.;
g) Camps, F.; Messeguer, A. and Sanchez, F.
5 161. h) Gmuter, H.; Lang, R. W. and Romann, A. J. Tetruhedron
i) Shim&
I. and Ishii, H. Chem. Z&Z. 1989, 577. j)
Shimizu, I.;
I&ii, H. and Tasaka, A. ibid. 1989. 1127. k) Yamazaki, T.; Welch, J. T.; Plumer, J. S. and Gimi, R. H. Tetrahedron Lett. 1991,34,4267 4.
A number of publications on fluorine-facilitated
and references cited. Claisen rearrangements has appeared. a) Nonnant,
J. F.; Reboul. 0.; Sauvetre, R.; Deshayes, H.; Masure, D. and Villieras, J. Bull. Sot. Chim. Fr. 1974. 2072. 1289.
b).
Nakai, T.; Tanaka, K. Ogasawara,
K. and Ishikawa, N. Chem. Z&t. 1981,
c) Taguchi. T.; Morikawa, T.; Kitagawa, 0.; Mishima, T. and Kobayashi,
Y. Chem.
Pharm. Bull. 1985,33.5137. d) Metcalf, B. M.; Jarvi. E. t. and Burkhart, J. P. Tetrahedron Left. 19%5,24.2861.
e) Yuan, W.; Berman, R. J.; Gelb. M. H. J. Am. Chem. Sot. 1987.
109, 8071. f) Welch, J. T.; Plummer. J. S. and Chou, T. S. J. Org. Chem. 1991.56, 353.g)
Araki, IL and Welch, J. T. Tetruhedron, Mt. 5.
1993.32, 2251.
All new compounds were characterized by their spectral data and elemental analysis or HRMS molecular weight determination.
(Received in UK 7 April 1994; accepted 6 May 1994)
1994
Else&r Science Ltd Printed in GreatBritain oo40-4039/94 $7.00+0.00
0040-4039(94)00894-9
A Novel Method for the Synthesis of ccFhoroketones Rearrangement Vi&d
ReutrakuP,
Thong&d
Kruahong
and
Manat
via Claisen
Pohmakotr
Department of Chemistry, Faculty of Science. Mahidol University, Rama 6 Road Bangkok IWOO. Thailand.
5. Abstract: Fluorine-facilitard Claim reamngement has been employed as a key step in the synthesis of a-fluoroketones l?ift elimination of surfcnic acidjhn
the allyi ethers 3 are fleeted under FVP conditions.
In thepreaeding
communbti~n,~
we have reported ihe synthesis of fluoromethylketones
by flash vacuum pyrolysis (FVP) utilizing cr-fluoromedhyl phenyl sulfoxide 1 asa fluorinated one-carbon building block. The present letter deals with the novel synthesis of a-fluoroketones employing fluoriuefacilitated Claisen rearrangement as the key step (3 + 5).2JJ The process is summa&xl
0
Fh’
1.2LDA.
s
F
-
0
THF. HMPA
-78 OC
*
2. RCHO, -78 ‘C, 2 h
OH
E
Fw
2
1
R
+ +
1. 1.5 LDA, THF, -A
R3 X
2. RI+/ -78%.
3 h.
then Ii ovunight I
R3
P7T 1-JO
RI
AR
RZ
F
RI
0
Fvp
0
R R3
Ph’ ul
F 3
Scheme 1 4853
’ +
!
R2
in Scheme 1.5
4854
The adducts 2 were prepared in high yields ( R= CgH17,82%; using techniques
reported earlier.’
bromides or iodides in good yields,
Ph, 83%; PhCH2,91%
The ally1 ethers 3 were prepared by the alkylation
with tbe ally1
using LDA as,a base. The Claisen intexmediate 4 was generated by
FVP technique with the following conditions: reaction flask temperatum, 216 Oc and column temperature 305 OC at 0.1 mmHg. The results are smnmaked
in Table 1.
Yields of Ally1 Ethers 3 and a-FGoroketones
Table 1
a-Fhoroketones
Ally1 ethers 3, 8
R=
5.
5, %a
‘217 mBr
a)
1
98
83 93 97 28
+
CBH17C(3CW 6,
e) fi_Br,
98
50
75
83
64
82
51
84 +
71
R= Fh b)
.
&Br
a)
-1, I,
c)
PhCOC~F 7, 45
d)
pBr
0) ph -Br,0 R=
v 43
54
66
98
3 76
85
64
94
F’hCH, -Br
a) b)
-1,
98
e) WABr
)
. 87
32 + PhCH$OCH2F 8, 55 65
a Products were isolated by PLC using hexane as an elueut.
4855
The a-fluoroketones 5 are obtained in high yields except in the cases of 3d ( R= C8Ht7, Ph. PhCH2; Rt=R2= Me, R3e H ) in which the contqmnding
fluoromethylketones
are also isolate%L The
formation of the fluoroketones 6,7 and 8 could be ratlonalixed on the basis of the steric crowding of the transitionstate4 causing it to fragments instead of for&g
a new carbon-carbon bond
The reaction sequence in Scheme 1 has also been applied to a more stetically hindered aldehyde; pivalaldehyde. The fluoroketone 11 was isolated in modemte yield. The intermediates9 and 10
were synthesized in high yields ( Scheme 2).
w
B@uF
1_2LDA,THF,EJMPA -78 “C ) 2.
::
OH
PhRS
lBuCH0, -78 ‘C, 2 h
ut
F 9.82%
I
Fh-
1%
35%
WA
Br
10. 98% scheme
2
Our approach appears to be general for the synthesis of this type of fluoroketoues. The outstanding features are the ease of the syntheses of intermediates 2 and 3 in high yields, and the final product fluoroketones can be readily purified by pmparative thin-layer chmmatography @XC, silica gel).
References 1.
and
Notes
Submitted for publication. Also see this communicationfor leading references onthechemistryand biology of fluorinated compounds.
2.
For reviews on Claisen rearrangement see: a) Hill, R. K. in Aymmerric Synthesis Morrison, J. D., Ed. Academic Press, N. Y. 1984, Chapter 8. b)
1988,88, 3.
Ziegler, F. E.
Vuhte
3,
Chem. Rev.
1423. c) ‘Blechert. S. Synthesis 1989, 71.
An example of in situ generation of Claisen system (1 ,Pheterohexadiene) by the elimination of sulfenic acid has been reported: a) Mandai, T.; Ueda, M.; Hasegawa, S. I.: Kawada, M. and Tsuji, J. Tetrahedron fert l990,32,4041. For related reactions see: b) Buechi. G. and Vogel, D. E. J. Org.
Chern. 1983.48.
5406.
Tetrahedron Letf. 1991, 32, 7601. d)
c)
Paterson, I.;
Huhne, A. N. and Wallace, D. J.
Ireland, R. E.; Wipf, P.; Armstrong IJI, J. D. J. Org.
4856
Chem. 1991,56,650.e) Panek, S. J. and Clark, T. D. ibid. 1992.57, Get-hart, F.; Francais, J. P. Synthesis 1988,469. J. Tetrahedron
1988,44,
L.ett. 1988.29,
3291.
4323.
f) Kolb, M.;
g) Camps, F.; Messeguer, A. and Sanchez, F.
5 161. h) Gmuter, H.; Lang, R. W. and Romann, A. J. Tetruhedron
i) Shim&
I. and Ishii, H. Chem. Z&Z. 1989, 577. j)
Shimizu, I.;
I&ii, H. and Tasaka, A. ibid. 1989. 1127. k) Yamazaki, T.; Welch, J. T.; Plumer, J. S. and Gimi, R. H. Tetrahedron Lett. 1991,34,4267 4.
A number of publications on fluorine-facilitated
and references cited. Claisen rearrangements has appeared. a) Nonnant,
J. F.; Reboul. 0.; Sauvetre, R.; Deshayes, H.; Masure, D. and Villieras, J. Bull. Sot. Chim. Fr. 1974. 2072. 1289.
b).
Nakai, T.; Tanaka, K. Ogasawara,
K. and Ishikawa, N. Chem. Z&t. 1981,
c) Taguchi. T.; Morikawa, T.; Kitagawa, 0.; Mishima, T. and Kobayashi,
Y. Chem.
Pharm. Bull. 1985,33.5137. d) Metcalf, B. M.; Jarvi. E. t. and Burkhart, J. P. Tetrahedron Left. 19%5,24.2861.
e) Yuan, W.; Berman, R. J.; Gelb. M. H. J. Am. Chem. Sot. 1987.
109, 8071. f) Welch, J. T.; Plummer. J. S. and Chou, T. S. J. Org. Chem. 1991.56, 353.g)
Araki, IL and Welch, J. T. Tetruhedron, Mt. 5.
1993.32, 2251.
All new compounds were characterized by their spectral data and elemental analysis or HRMS molecular weight determination.
(Received in UK 7 April 1994; accepted 6 May 1994)