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Palladium dichloride catalyzed cope rearrangements of functionalized acyclic 1,5-dienes
Tetrahedron Letters,Vo1.24,No.35,pp Printed in Great Britain
PALLADIUM
DICHLORIDE
CATALYZED
FUNCTIONALIZED
Larry
REARRANGEMENTS
OF
1,5-DIENESl
and Alfred
F. Renaldo
University
of Chemistry, Irvine,
COPE
ACYCLIC
E. Overman*
Department
0040-4039183 $3.00 + .OO 01983 Pergamon Press Ltd.
3757-3760,1983
California
of California
92117
The Cope rearrangement of acyclic 1,5-dienes having an electronSummary: is effecwithdrawing group at carbon-3 and an alkyl substituent at carbon-2 to This reaction can be employed tively catalyzed by palladium dichloride. achieve clean r-allylation of vinyl esters and acids. Palladium were
first
dichloride
reported
demonstrated3 occurs The
via
use
of
reported studies this
recently
good
this
catalytic
yields
related
to
method by
other is
to In
method.
undergo at by
with
thermal
4o"c.5
in
an
acyclic
of
? 1980.L
We
have
enantiomerically
virtually
complete
oxy-Cope rearrangements 4 One of the aims investigators. determine this
the
Letter, group
functional we
at carbon-3,
dichloride
Importantly,
catalyzed
these
carbon-carbon
Cope rearrangements.
report
group that
of
substrate chirality.
has of
also our
been
current
compatibility
of
acyclic
1,5-dienes
and an alkyl
substituent
Cope
transformations
double
1,5-dienes subsequently
pure
transfer
catalyze
palladium
competing
rearrangements
of
rearrangement
topology
area
Cope
laboratories
an electron-withdrawing
carbon-2,
complicated
these
the
chair this
in
containing at
that a
catalyzed
from
migrations,
rearrangements (eq which
1) can
are
in not
plague
6,7
PdC12 (0.1
equiv) 4o”c
The results tic
of our preliminary
rearrangements
were
conducted
study at
0.1
3751
are M
summarized in CH2C12
in the Table. using
0.1 equiv
Catalyof bis-
3758
(acetonitrile)palladium dichloride. GC analysis, silica gel residue was
After the reaction was judged complete by
(1 g/25 mg of catalyst) was added, the concentrated
layered on top of a silica gel chromatography
column,
ducts8 were eluted with mixtures of hexane and ethyl acetate. ment
of 2
though
(R=COOEt) could be
the rate was
somewhat
successfully conducted slower2
and pro-
The rearrange-
in THF or
toluene, al-
than
in CH2C12. Diene products were 1 typically characterized' by their diagnostic' high field H NMR spectra, and 10 in the case of 9 by preparation from 4-methyl-6-hexen-3-one. The reported E/Z ratios do not reflect kinetic stereoselectivities, since pure samples of 11 equilibration when trea-
Z-A(R=COOEt) and E-4(R=COOEt) underwent significant ted at 40°C for 3 h with 0.1 equiv of PdC12 (MeCN)2. This acid,
and
catalyzed nitrile
reorganization substituents,
substrate was less clean. amide substituent may
proceeds although
with
the
ester,
carboxylic
ketone,
rearrangement
of
the
nitrile
The failure of the rearrangement with a tertiary
in part reflect binding
of the catalyst by
the amide
3(R=COOEt) was 2ca 10 times slower in the group, since the rearrangement of presence of 1.0 equiv of N,N-dimethylformamide. The advantages of the palladium dichloride
catalyzed method
are nicely
illustrated by
the high
yielding
rearrangements of -5 and 7. Conia has reported6 thermal Cope rearrangements of these dienes at 220-240°C, and ene cyclizations (Conia reaction) of the product diene mixtures at 3OO'C.
A major complication6 of the thermal Cope rear12 rangements of 5 and 7 is the formation of major amounts of the B,y-unsatur13 ated isomers of 5 and 8. 14 Many of the dienes employed in this study were prepared by a-alkylation Thus, a-allylation of the corresponding a,B-unsaturated starting material. followed by palladium dichloride catalyzed Cope rearrangement provides a twoThis sestep procedure for clean y-allylation 15 of vinyl esters and acids. quence is illustrated for an ester substrate in eq. 1.
Me Me
LDA-HMPA
E tOOCAMe l3r-
-
Me PdC12
*
83%
(1)
75%
Acknowledgment. The financial support of the National Science Foundation (CHR 82-03366 and Departmental Instrumentation Grants) is gratefully acknowledged. We thank Johnson Matthey, Inc., for loans of palladium dichloride.
3159
TABLE: CATALYZED
PALLADIUM DICHLORIDE COPE REARRANGEMENTS Conditions Time
Reaction
‘2
-
‘3
R=COOEt
5h
63
R=COMe
5.5h
94
R=CN
36hb
(77%jC
R=COOH
24h
64
R=CONz
36h
I
Mey
-
Me+
-M&
65
35
66
31
-
75
25
-
65
35
c Me
Me00
/
-
Me \
:tooc
I
no reaction
2.5h
77
-
50
50
4h
61
-
50
50
5h
90
-
24
76
4h
00d
25
54
, 2h
76d
,g
66,
Ma
Me ,
AeOOC
MOM%
Product Ratios E-2 Z-2
-
4
3
Me
Yielda
,
Me \ “;9 Me Me
EtOOC ,
XL ’
'-3\
Me
E~OOC&lle
L
EtOOC$I
9 a
Isolated
was
yield
GC analysis), ed. of
of
reversible).
unless
' A 91% weight uncharacterized
ducts
was
stereoisomer
the
Other
unchanged
mixture
otherwise recovery
byproducts. upon
assignments.
, of
compounds
stereoisomers were
noted. of
11,
1 if the rearrangement -2 (and present to the extent of <5% (capillary b 0.3 Equiv of PdC12(MeCN)2 was employ-
with 15% Cope product, which was contaminated d The ratio of starting material to Cope pro-
resubmission
of
the
product
mixture.
e
Tentative
3760
References
and Notes
1.
Catalyzed Sigmatropic Rearrangements. Renaldo, A.F. Tetrahedron Lett. 1983,
2.
Overman,
L.E.;
Knoll,
3.
Overman,
L.E.;
Jacobsen,
4.
Bluthe,
5.
at carbon-3 Acyclic 1,5-dienes containing electron-withdrawing groups and alkyl substituents at carbon-5 do not undergo catalyzed Cope rearrangements under these conditions, see reference 1.
6.
Rhoades,
7.
Conia, Cf. 278-281
8.
N.; Malacria,
S.J.;
F.M.
J.-M.;
J. Am. Chem.
S. Org. Reactions,
P.
Bull.
102,
SOC. 1982,
J. Tetrahedron
LePerchec,
7, see:
Sot. 1980,
E.J. J. Am. Chem.
M.; Gore,
Rawling,
8. For part in press.
Lett.
1975,
22,
Sot. Chim.
Overman,
L.E.;
865-867.
104,
7225-7231.
1983,
2,
1157-1160.
l-107. Fr.
273-277;
1966,
1 H NMR and mass spectra consistent with New compounds showed IR, 250 MHz Stereoisomeric products were typically separtheir assigned structures. followed from diagnosated by preparative GC and their stereostructures tic' chemical
shift differences
of the B-substituents. SpeCtrOS-
9.
L.M.; Sternhell, S. "Nuclear Magnetic Resonance Cf. Jackman, copy in Organic Chemistry"; Pergamon: Oxford, 1969, pp 222-225.
10.
Shimoji, K.; Taguchi, H.; Oshima, Chem. Sot. 1974, 96, 1620-1621.
11.
Approximately 1:l.
12.
of -6 comprises 28% and 65% of the Cope mixture at 220°C and 240°C, respectively, while the deconjugated 7 of S is the major Cope product at 22O'C. The
35%
deconjugated
equilibration,
K.;
Yamamoto,
assuming
that
H.;
the
Nozaki,
H.
equilibrium
ratio
isomer
to the
extent
of
J. Am.
is
product isomer
in the catalyzed
13.
Deconjugated isomers were present rearrangements of 2 and 1.
14.
Herrmann, J.L.; Kieczykowski, 1973, 2433-2436.
15.
For recent examples and leading references, see, inter alia, Majewski, M.; Mpango, G.B.; Thomas, M.T.; Wu, A.; Snieckus, V. J. Org. Chem. 1981, J.A. J. Org. Chem. E, Savu, P.M.; Katzenellenbogen, 5, 2029-2045. Fleming, I.; Goldhill, J.; Paterson, I. Tetrahedron Lett. 46, 239-250. D.; Lee, S.J.; Liebskind, Kende, A.S.; Constantinides, 1979, 3207-3210. L. Ibid. 1975, 405-408.
(Received
in USA
16 May
1983)
G.R.;
Schlessinger,
R.H.
Tetrahedron
Lett.
PALLADIUM
DICHLORIDE
CATALYZED
FUNCTIONALIZED
Larry
REARRANGEMENTS
OF
1,5-DIENESl
and Alfred
F. Renaldo
University
of Chemistry, Irvine,
COPE
ACYCLIC
E. Overman*
Department
0040-4039183 $3.00 + .OO 01983 Pergamon Press Ltd.
3757-3760,1983
California
of California
92117
The Cope rearrangement of acyclic 1,5-dienes having an electronSummary: is effecwithdrawing group at carbon-3 and an alkyl substituent at carbon-2 to This reaction can be employed tively catalyzed by palladium dichloride. achieve clean r-allylation of vinyl esters and acids. Palladium were
first
dichloride
reported
demonstrated3 occurs The
via
use
of
reported studies this
recently
good
this
catalytic
yields
related
to
method by
other is
to In
method.
undergo at by
with
thermal
4o"c.5
in
an
acyclic
of
? 1980.L
We
have
enantiomerically
virtually
complete
oxy-Cope rearrangements 4 One of the aims investigators. determine this
the
Letter, group
functional we
at carbon-3,
dichloride
Importantly,
catalyzed
these
carbon-carbon
Cope rearrangements.
report
group that
of
substrate chirality.
has of
also our
been
current
compatibility
of
acyclic
1,5-dienes
and an alkyl
substituent
Cope
transformations
double
1,5-dienes subsequently
pure
transfer
catalyze
palladium
competing
rearrangements
of
rearrangement
topology
area
Cope
laboratories
an electron-withdrawing
carbon-2,
complicated
these
the
chair this
in
containing at
that a
catalyzed
from
migrations,
rearrangements (eq which
1) can
are
in not
plague
6,7
PdC12 (0.1
equiv) 4o”c
The results tic
of our preliminary
rearrangements
were
conducted
study at
0.1
3751
are M
summarized in CH2C12
in the Table. using
0.1 equiv
Catalyof bis-
3758
(acetonitrile)palladium dichloride. GC analysis, silica gel residue was
After the reaction was judged complete by
(1 g/25 mg of catalyst) was added, the concentrated
layered on top of a silica gel chromatography
column,
ducts8 were eluted with mixtures of hexane and ethyl acetate. ment
of 2
though
(R=COOEt) could be
the rate was
somewhat
successfully conducted slower2
and pro-
The rearrange-
in THF or
toluene, al-
than
in CH2C12. Diene products were 1 typically characterized' by their diagnostic' high field H NMR spectra, and 10 in the case of 9 by preparation from 4-methyl-6-hexen-3-one. The reported E/Z ratios do not reflect kinetic stereoselectivities, since pure samples of 11 equilibration when trea-
Z-A(R=COOEt) and E-4(R=COOEt) underwent significant ted at 40°C for 3 h with 0.1 equiv of PdC12 (MeCN)2. This acid,
and
catalyzed nitrile
reorganization substituents,
substrate was less clean. amide substituent may
proceeds although
with
the
ester,
carboxylic
ketone,
rearrangement
of
the
nitrile
The failure of the rearrangement with a tertiary
in part reflect binding
of the catalyst by
the amide
3(R=COOEt) was 2ca 10 times slower in the group, since the rearrangement of presence of 1.0 equiv of N,N-dimethylformamide. The advantages of the palladium dichloride
catalyzed method
are nicely
illustrated by
the high
yielding
rearrangements of -5 and 7. Conia has reported6 thermal Cope rearrangements of these dienes at 220-240°C, and ene cyclizations (Conia reaction) of the product diene mixtures at 3OO'C.
A major complication6 of the thermal Cope rear12 rangements of 5 and 7 is the formation of major amounts of the B,y-unsatur13 ated isomers of 5 and 8. 14 Many of the dienes employed in this study were prepared by a-alkylation Thus, a-allylation of the corresponding a,B-unsaturated starting material. followed by palladium dichloride catalyzed Cope rearrangement provides a twoThis sestep procedure for clean y-allylation 15 of vinyl esters and acids. quence is illustrated for an ester substrate in eq. 1.
Me Me
LDA-HMPA
E tOOCAMe l3r-
-
Me PdC12
*
83%
(1)
75%
Acknowledgment. The financial support of the National Science Foundation (CHR 82-03366 and Departmental Instrumentation Grants) is gratefully acknowledged. We thank Johnson Matthey, Inc., for loans of palladium dichloride.
3159
TABLE: CATALYZED
PALLADIUM DICHLORIDE COPE REARRANGEMENTS Conditions Time
Reaction
‘2
-
‘3
R=COOEt
5h
63
R=COMe
5.5h
94
R=CN
36hb
(77%jC
R=COOH
24h
64
R=CONz
36h
I
Mey
-
Me+
-M&
65
35
66
31
-
75
25
-
65
35
c Me
Me00
/
-
Me \
:tooc
I
no reaction
2.5h
77
-
50
50
4h
61
-
50
50
5h
90
-
24
76
4h
00d
25
54
, 2h
76d
,g
66,
Ma
Me ,
AeOOC
MOM%
Product Ratios E-2 Z-2
-
4
3
Me
Yielda
,
Me \ “;9 Me Me
EtOOC ,
XL ’
'-3\
Me
E~OOC&lle
L
EtOOC$I
9 a
Isolated
was
yield
GC analysis), ed. of
of
reversible).
unless
' A 91% weight uncharacterized
ducts
was
stereoisomer
the
Other
unchanged
mixture
otherwise recovery
byproducts. upon
assignments.
, of
compounds
stereoisomers were
noted. of
11,
1 if the rearrangement -2 (and present to the extent of <5% (capillary b 0.3 Equiv of PdC12(MeCN)2 was employ-
with 15% Cope product, which was contaminated d The ratio of starting material to Cope pro-
resubmission
of
the
product
mixture.
e
Tentative
3760
References
and Notes
1.
Catalyzed Sigmatropic Rearrangements. Renaldo, A.F. Tetrahedron Lett. 1983,
2.
Overman,
L.E.;
Knoll,
3.
Overman,
L.E.;
Jacobsen,
4.
Bluthe,
5.
at carbon-3 Acyclic 1,5-dienes containing electron-withdrawing groups and alkyl substituents at carbon-5 do not undergo catalyzed Cope rearrangements under these conditions, see reference 1.
6.
Rhoades,
7.
Conia, Cf. 278-281
8.
N.; Malacria,
S.J.;
F.M.
J.-M.;
J. Am. Chem.
S. Org. Reactions,
P.
Bull.
102,
SOC. 1982,
J. Tetrahedron
LePerchec,
7, see:
Sot. 1980,
E.J. J. Am. Chem.
M.; Gore,
Rawling,
8. For part in press.
Lett.
1975,
22,
Sot. Chim.
Overman,
L.E.;
865-867.
104,
7225-7231.
1983,
2,
1157-1160.
l-107. Fr.
273-277;
1966,
1 H NMR and mass spectra consistent with New compounds showed IR, 250 MHz Stereoisomeric products were typically separtheir assigned structures. followed from diagnosated by preparative GC and their stereostructures tic' chemical
shift differences
of the B-substituents. SpeCtrOS-
9.
L.M.; Sternhell, S. "Nuclear Magnetic Resonance Cf. Jackman, copy in Organic Chemistry"; Pergamon: Oxford, 1969, pp 222-225.
10.
Shimoji, K.; Taguchi, H.; Oshima, Chem. Sot. 1974, 96, 1620-1621.
11.
Approximately 1:l.
12.
of -6 comprises 28% and 65% of the Cope mixture at 220°C and 240°C, respectively, while the deconjugated 7 of S is the major Cope product at 22O'C. The
35%
deconjugated
equilibration,
K.;
Yamamoto,
assuming
that
H.;
the
Nozaki,
H.
equilibrium
ratio
isomer
to the
extent
of
J. Am.
is
product isomer
in the catalyzed
13.
Deconjugated isomers were present rearrangements of 2 and 1.
14.
Herrmann, J.L.; Kieczykowski, 1973, 2433-2436.
15.
For recent examples and leading references, see, inter alia, Majewski, M.; Mpango, G.B.; Thomas, M.T.; Wu, A.; Snieckus, V. J. Org. Chem. 1981, J.A. J. Org. Chem. E, Savu, P.M.; Katzenellenbogen, 5, 2029-2045. Fleming, I.; Goldhill, J.; Paterson, I. Tetrahedron Lett. 46, 239-250. D.; Lee, S.J.; Liebskind, Kende, A.S.; Constantinides, 1979, 3207-3210. L. Ibid. 1975, 405-408.
(Received
in USA
16 May
1983)
G.R.;
Schlessinger,
R.H.
Tetrahedron
Lett.