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Palladium-catalyzed synthesis of α,β-unsaturated ketones from ketones via allyl enol carbonates
Tetrahedron Letters,Vol.24,No.l7,pp Printed in Creat Britain
PALLADIUM-CATALYZED KETONES
FROM
Summary:
Ally1
chloroformate, catalyst
Institute
enol
SYNTHESIS
KETONES
Isao SHIMIZU, Tokyo
Ichiro
carbonates,
OF a,8-UNSATURATED
VIA ALLYL
MINAMI,
of Technology,
are converted
0040-403?/83/171797-04$03.00/O 01983 Pergamon Press Ltd.
1797-1800,1983
prepared
ENOL
CARBONATES
and Jiro
Meguro,
by quenching
to a,&unsaturated
TSUJI*
Tokyo
152, JAPAN
ketone
ketones
with
enolates
with
ally1
Pd(OAc)2-dppe
in CH3CN.
Regioselective an important
introduction
of a,$-unsaturation
problem. 1)
synthetic
As one method,
in unsymmetrical
direct
oxidative
ketones
is
dehydrogenation
of saturated been
ketones to a,$-unsaturated ketones, promoted by Pd(I1) salts, has 2) reported. But the conversion and selectivity are unsatisfactory. Enone
formation with
was carried salts. 3)
out regioselectively
Pd(I1)
as an intermediate
In this
to the enone
reoxidize
for making
formation enolate before
from the enolates complexes
the palladium enol
and Pd(0).
the reaction could
are prepared
a,8-unsaturated
dehydrogenation
by the reaction
the palladium
by the transmetallation
then decomposed Pd(0)
reaction,
ketones
of ally1 catalyzed
8-keto
of silyl
be carried
from Pd(0).
enol ether
complex
enol ether
with
The reaction catalytic.
of silyl
enolate
requires
out catalytically
Pd(I1)
cocatalyst
We expected
As a related
4 is formed and to
that the enone if the palladium
reaction,
we obtained
by the palladium-catalyzed decarboxylationcarboxylates. 4) In this paper, we wish to report
synthesis
of a,8-unsaturated
carbonyl
carbonates. OTMS
OPdCl Pd(lI)C12
0-
1797
,
+
\
R
compounds
via ally1
1798
Reaction
of ally1
c,B-unsaturated Careful tion. enone
selection Especially
(1 : 1)
_8 was carried
of reaction ligands,
8 was obtained
in CH3CN
enol carbonate
ketone
in the presence
was carried
important
were
addition
to dppe,
(9) in 41% yield
product
enone
1.
\ b
play decisive
ligand
When
formation.
roles.
was carried
also good
of the enone Reaction
instead
(dppe) When
product
the 2-allyland dppe
of dppe
(run 4).
In
(dppp) and 1,4-bis(diphenyl-
solvent
decreased
Enol Carbonate
two equivalents
for the enone
of Pd(OAc)2,
the protic
formation
of Ally1
ligands
The
out at 80°C
is essential.
as a major
the
dehydrogena-
reaction took place to give (run 1). 5) The ratio of Pd(OAc)2
9 was obtained
Pd2(dba) 3 or Pd(PPh3)4 was used was obtained in good yields. When
Table
to form
(Table 1).
for efficient
the reaction
1,3-bis(diphenylphosphino)propane (dppb) were
the selectivity
when
as the bidentate
for the selective
phosphino)butane
is necessary
catalyst
conditions
of Pd(OAc)2-1,2-bis(diphenylphosphino)ethane
the allylated
used,
various
out at 20°C, allylation
2-methylcyclohexanone was
Pd-phosphine
and temperature
selectively
Use of dppe
(run 2).
reaction
conditions
solvents,
most
7 with
out under
such as t-BuOH
dramatically 7 with
But when
synthesis.
the allylated
product
9
was added,
(run 3). in CH3CN a)
Pd Catalyst
ocozRI - Phosphine CH3CN
Catalyst
Run 1 c)
(ratio of Pd/Phosphine)
pd(OAc) 2-dppe
2
l/2’
yield(%)b) 9
9
41
10 8
98
0
1
9
30
60
38
57
4
3d' 4
8
2/l)
86
0
4
l/2)
69
18
10
l/l)
76
14
1
8
l/l)
80
0
9
9
l/l)
5
95
0
l/l)
5
93
2
5 6
P~(OAC)~-PP~~
7
P~(OAC)~-dppp
e)
10
a) Reactions CH3CN
were
carried
out using
(5 mL) at 80aC under
d) t-BuOH
(1 mL) was added.
argon
Pd catalyst
for 1 h.
(0.1 mmol)
b) GLC analysis.
e) Ph2P(CH2)3PPh2.
and 7 (1 mmol)
in dry
c) at 20°C for 24 h.
f) Ph2P(CH2)4PPh2.
1799
Other ally1 enol carbonates 12, 2,
20, and 22 were converted to a,8-
unsaturated carbonyl compounds 13, 17, -- 21, and 23 - respectively with Pd(OAc)2dppe catalyst in CH3CN. The enone 8 is also obtained selectively from ally1 B-keto carboxylate 11 But the reaction of
in the presence of Pd-dppe catalyst, as reported before. 4)
ally1 B-keto carboxylate 12 - which possesses an active hydrogen gave the allylated ketones as major products and the enone 13 was a minor product. Cyclopentenone (12) was not obtained from the ally1 f3-ketocarboxylate 12, and 2-allylcyclopentanone
(18) was a major product (81% yield). On the contrary, reaction of the enol carbonate 14 - from cyclohexanone gave the enone 13 - in 92% yield. Cyclopentenone (17) was obtained from ally1 enol carbonate of cyclopentanone 19 in 13% yield, but the major product was the allyl.ated product 18 (57% yield).
The
allylpalladium enolate complexes are expected to be formed from both ally1 Rketo carboxylates and ally1 enol carbonates.
The ally1 enol carbonates afford
the enones more selectively than ally1 8-keto carboxylates, especially in the case of a-unsubstituted cyclic ketones.
.
12 (13%) + 18(57"/.)
Only (E)-olefin 21 - was obtained in 76% yield by the reaction of the ally1 enol carbonate 20 prepared from cyclododecanone [NMR (CC14) 6 6.15 (d, J = 17 Hz, lH, COCH=), 6.65 (dt, J = 17 and 6 Hz, lH, CH=CH-CH2)). Reaction of the ally1 enol carbonate 22 - prepared from cyclohexanecarboaldehyde gave the cc,8unsaturated aldehyde 23 - in 90% yield.
1800
The reaction of ally1 enol carbonates of unsymmetrical ketones is regioselective.
As shown in Table 1, the reaction of the ally1 enol carbonate 7
obtained from thermodynamically stable enolate of 23 - gave 8 selectively. On the other hand, the ally1 enol carbonate 26 - obtained from kinetically generated enolate of 24 in 81% yield. Thus, this is a - gave 6-methyl-2-cyclohexenone (25) good method for selective synthesis of e,8-unsaturated ketones from the selectively generated enolates.
oco-
\ b
0
tb I
z
s
0
& I
5
Further mechanistic studies and synthetic applications of this reaction are in progress. Acknowlegement:
This research was financially supported by the Grant-in-Aids
for Scientific Research, A, No. 57430830, and Encouragement of Young Scientist, No. 56750588 from the Ministry of Education. References and Notes: 1) For a,8-unsaturated ketones from saturated ketones, see: a) P. L. Stotier, K. A. Hill, J. Org. Chem., 38,
2576 (1973).
b) H. J. Reich, J. M. Renga, I. L. Reich, J. Org. Chem., 2, 2133 (1974). c) B. M. Trost, T. N. Salzmann, K. Hiroi, J. Am. Chem. Sot., E, 4887 (1976). 2) a) R. J. Theissen, J. Org. Chem., 36, 752 (1971). b) B. Bierling, K. Kirshke, H. Oberender, J. Pratt. Chem., 314, 170 (1972). 3) a) Y. Ito, T. Hirao, T. Saegusa, J. Org. Chem., 3,
1011 (1978).
b) B. M. Trost, Y. Nishimura, K. Yamamoto, S. S. McElvain, J. Am. Chem. Sot., c,
1328 (1979).
4) I. Shimizu, J. Tsuji, J. Am. Chem. Sot., 104, 5844 (1982). 5) J. Tsuji, I. Minami, I. Shimizu, Tetrahedron Lett., the preceding paper. (Received in Japan 27 December 1982)
PALLADIUM-CATALYZED KETONES
FROM
Summary:
Ally1
chloroformate, catalyst
Institute
enol
SYNTHESIS
KETONES
Isao SHIMIZU, Tokyo
Ichiro
carbonates,
OF a,8-UNSATURATED
VIA ALLYL
MINAMI,
of Technology,
are converted
0040-403?/83/171797-04$03.00/O 01983 Pergamon Press Ltd.
1797-1800,1983
prepared
ENOL
CARBONATES
and Jiro
Meguro,
by quenching
to a,&unsaturated
TSUJI*
Tokyo
152, JAPAN
ketone
ketones
with
enolates
with
ally1
Pd(OAc)2-dppe
in CH3CN.
Regioselective an important
introduction
of a,$-unsaturation
problem. 1)
synthetic
As one method,
in unsymmetrical
direct
oxidative
ketones
is
dehydrogenation
of saturated been
ketones to a,$-unsaturated ketones, promoted by Pd(I1) salts, has 2) reported. But the conversion and selectivity are unsatisfactory. Enone
formation with
was carried salts. 3)
out regioselectively
Pd(I1)
as an intermediate
In this
to the enone
reoxidize
for making
formation enolate before
from the enolates complexes
the palladium enol
and Pd(0).
the reaction could
are prepared
a,8-unsaturated
dehydrogenation
by the reaction
the palladium
by the transmetallation
then decomposed Pd(0)
reaction,
ketones
of ally1 catalyzed
8-keto
of silyl
be carried
from Pd(0).
enol ether
complex
enol ether
with
The reaction catalytic.
of silyl
enolate
requires
out catalytically
Pd(I1)
cocatalyst
We expected
As a related
4 is formed and to
that the enone if the palladium
reaction,
we obtained
by the palladium-catalyzed decarboxylationcarboxylates. 4) In this paper, we wish to report
synthesis
of a,8-unsaturated
carbonyl
carbonates. OTMS
OPdCl Pd(lI)C12
0-
1797
,
+
\
R
compounds
via ally1
1798
Reaction
of ally1
c,B-unsaturated Careful tion. enone
selection Especially
(1 : 1)
_8 was carried
of reaction ligands,
8 was obtained
in CH3CN
enol carbonate
ketone
in the presence
was carried
important
were
addition
to dppe,
(9) in 41% yield
product
enone
1.
\ b
play decisive
ligand
When
formation.
roles.
was carried
also good
of the enone Reaction
instead
(dppe) When
product
the 2-allyland dppe
of dppe
(run 4).
In
(dppp) and 1,4-bis(diphenyl-
solvent
decreased
Enol Carbonate
two equivalents
for the enone
of Pd(OAc)2,
the protic
formation
of Ally1
ligands
The
out at 80°C
is essential.
as a major
the
dehydrogena-
reaction took place to give (run 1). 5) The ratio of Pd(OAc)2
9 was obtained
Pd2(dba) 3 or Pd(PPh3)4 was used was obtained in good yields. When
Table
to form
(Table 1).
for efficient
the reaction
1,3-bis(diphenylphosphino)propane (dppb) were
the selectivity
when
as the bidentate
for the selective
phosphino)butane
is necessary
catalyst
conditions
of Pd(OAc)2-1,2-bis(diphenylphosphino)ethane
the allylated
used,
various
out at 20°C, allylation
2-methylcyclohexanone was
Pd-phosphine
and temperature
selectively
Use of dppe
(run 2).
reaction
conditions
solvents,
most
7 with
out under
such as t-BuOH
dramatically 7 with
But when
synthesis.
the allylated
product
9
was added,
(run 3). in CH3CN a)
Pd Catalyst
ocozRI - Phosphine CH3CN
Catalyst
Run 1 c)
(ratio of Pd/Phosphine)
pd(OAc) 2-dppe
2
l/2’
yield(%)b) 9
9
41
10 8
98
0
1
9
30
60
38
57
4
3d' 4
8
2/l)
86
0
4
l/2)
69
18
10
l/l)
76
14
1
8
l/l)
80
0
9
9
l/l)
5
95
0
l/l)
5
93
2
5 6
P~(OAC)~-PP~~
7
P~(OAC)~-dppp
e)
10
a) Reactions CH3CN
were
carried
out using
(5 mL) at 80aC under
d) t-BuOH
(1 mL) was added.
argon
Pd catalyst
for 1 h.
(0.1 mmol)
b) GLC analysis.
e) Ph2P(CH2)3PPh2.
and 7 (1 mmol)
in dry
c) at 20°C for 24 h.
f) Ph2P(CH2)4PPh2.
1799
Other ally1 enol carbonates 12, 2,
20, and 22 were converted to a,8-
unsaturated carbonyl compounds 13, 17, -- 21, and 23 - respectively with Pd(OAc)2dppe catalyst in CH3CN. The enone 8 is also obtained selectively from ally1 B-keto carboxylate 11 But the reaction of
in the presence of Pd-dppe catalyst, as reported before. 4)
ally1 B-keto carboxylate 12 - which possesses an active hydrogen gave the allylated ketones as major products and the enone 13 was a minor product. Cyclopentenone (12) was not obtained from the ally1 f3-ketocarboxylate 12, and 2-allylcyclopentanone
(18) was a major product (81% yield). On the contrary, reaction of the enol carbonate 14 - from cyclohexanone gave the enone 13 - in 92% yield. Cyclopentenone (17) was obtained from ally1 enol carbonate of cyclopentanone 19 in 13% yield, but the major product was the allyl.ated product 18 (57% yield).
The
allylpalladium enolate complexes are expected to be formed from both ally1 Rketo carboxylates and ally1 enol carbonates.
The ally1 enol carbonates afford
the enones more selectively than ally1 8-keto carboxylates, especially in the case of a-unsubstituted cyclic ketones.
.
12 (13%) + 18(57"/.)
Only (E)-olefin 21 - was obtained in 76% yield by the reaction of the ally1 enol carbonate 20 prepared from cyclododecanone [NMR (CC14) 6 6.15 (d, J = 17 Hz, lH, COCH=), 6.65 (dt, J = 17 and 6 Hz, lH, CH=CH-CH2)). Reaction of the ally1 enol carbonate 22 - prepared from cyclohexanecarboaldehyde gave the cc,8unsaturated aldehyde 23 - in 90% yield.
1800
The reaction of ally1 enol carbonates of unsymmetrical ketones is regioselective.
As shown in Table 1, the reaction of the ally1 enol carbonate 7
obtained from thermodynamically stable enolate of 23 - gave 8 selectively. On the other hand, the ally1 enol carbonate 26 - obtained from kinetically generated enolate of 24 in 81% yield. Thus, this is a - gave 6-methyl-2-cyclohexenone (25) good method for selective synthesis of e,8-unsaturated ketones from the selectively generated enolates.
oco-
\ b
0
tb I
z
s
0
& I
5
Further mechanistic studies and synthetic applications of this reaction are in progress. Acknowlegement:
This research was financially supported by the Grant-in-Aids
for Scientific Research, A, No. 57430830, and Encouragement of Young Scientist, No. 56750588 from the Ministry of Education. References and Notes: 1) For a,8-unsaturated ketones from saturated ketones, see: a) P. L. Stotier, K. A. Hill, J. Org. Chem., 38,
2576 (1973).
b) H. J. Reich, J. M. Renga, I. L. Reich, J. Org. Chem., 2, 2133 (1974). c) B. M. Trost, T. N. Salzmann, K. Hiroi, J. Am. Chem. Sot., E, 4887 (1976). 2) a) R. J. Theissen, J. Org. Chem., 36, 752 (1971). b) B. Bierling, K. Kirshke, H. Oberender, J. Pratt. Chem., 314, 170 (1972). 3) a) Y. Ito, T. Hirao, T. Saegusa, J. Org. Chem., 3,
1011 (1978).
b) B. M. Trost, Y. Nishimura, K. Yamamoto, S. S. McElvain, J. Am. Chem. Sot., c,
1328 (1979).
4) I. Shimizu, J. Tsuji, J. Am. Chem. Sot., 104, 5844 (1982). 5) J. Tsuji, I. Minami, I. Shimizu, Tetrahedron Lett., the preceding paper. (Received in Japan 27 December 1982)