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Conjugate addition vs. vinylic substitution in palladium-catalysed reaction of aryl halides with β-substituted-α,β-enones and -enals
Vol. 45, No. 3, pp. 813 to 828, 1989
Terrakdron Printed
in Great
OO4&4020/89
CONJUGATE ADDITION
VS.
VINYLIC
OF ARYL HALIDES
A.
Istituto
Amoresea,
b)
di
A.
Stazione
Dipartimento
di
c)
di
Dip.
PALLADIUM-CATALYSED
Chimica
G.
S.
G.
REACTION
AND -ENALS
Bernocchic,
W. Fedelib,
Press plc
Cacchic*,
Ortard
Giacomello,
C.N.R.,
CP 10,
00016
Roma (Italy) Ingegneria
Chimica
e Materiali,
via
Assergi
4,
(Italy)
Studi
Attive,
Cerrinia,
Chimica,
L’Aquila
E.
Arcadib,
,
IN
R-SUBSTITUTED-a,&ENDNES
Strutturistica
Monterotondo 67100
SUBSTITUTION
WITH
S.
a)
$3.00+.00
Pergamon
Britain.
di
Chimica
Universita
degli
e
Tecnologia
Studi
“La
delle
Sapienza”,
Sostanze P.le
A.
Biologicamente
Moro
5,
00185
Roma
(Italy) d)
di
Dip. A.
Studi
Moro
5,
Universita
Farmaceutici,
00185
degli
Studi
“La
Sapienza”,
P.le
Roma (Italy)
(Received in UK 11 November 1988) Abstract aryl
-
The
reaction
investigated. dependent favour
on
the
the
The
outcome
the or
better
than
use those
reaction
the
yield
the
and
palladium
added
base.
that acetate with
of
halides
found
results
acetate
tend
to
sodium
products. comparable
bicarbonate.
or
Furthermore, strongly
afforded
been
greatly
while
substitution
containing
substitution
be
amines
products
vinylic
with
has
to
Tertiary
produced
sodium
-enals
catalyst
was
addition-type
acetate
sodium
vinylic
a
reaction
sodium aryl
groups, of
the
conjugate
obtained
of
-withdrawing the
of
of
of of
of
sodium
the
B-substituted-o,&enones
presence
nature
formation
bicarbonate Usually,
of
in
halides
in
electron-
a dramatic
increase
in
products.
Introduction It
is
complexes
well
to
give
syn-B-elimination however, our
this
hands,
amines.
Poor
Table
on
the
a
vinylic
has
not
been
extended
variety
intermediates
1.
This
nature failure
of
when
of
reacted of
the
aryl
can
be
in
the
from
with
species substitution to
with
accounted
acyclic
presence
and
halides,
Some for
by
of
a,B-unsaturated
813
a
rapid,
products.’
-enals
the tertiary
observations amines carbonyl
our
and
-enals to
catalyst
products
representative
spontaneous
To
failed
palladium
addition-type
halide).
carbon(sp’)-palladium
undergo
l3-substituted-u,O-enones
aryl
conjugate
a-bonded
which
R-substituted-a,R-enones
yields
decomposition derived
react
a-alkylpalladium form
moderate
on the
systems
to
reaction
to
olefinic
HPdX
products
(depending the
that
unstable of
indeed,
substitution
known
were
results
give and
instead are
we
reported
of
the
compounds.
knowledge, (I)‘. vinylic tertiary obtained
summarized previousl$
o-alkylpalladium The
In
competition
in
A. AMORESE et
814
between
Co-Pd
Scheme
1,a)
and
rationalyzed the
bond
and
basic
species
while
stop
quickly amounts
vinylic
substitution
confirmed to
the
triethylamine
as
a,%unsaturated
is
used
presence
the
R$H
to
(for
of
the
bond
to
(conjugate
path;
the
addition
Scheme
nature
of
electron-withdrawing
tertiary
has
type
in
the
the
1,b)
path; has
been
substituents
power
are
of
the
organic
catalytic
of (3)
cycle.
the
on
carbonyl
to
some is
reduce extent.
not
(from
suggested
high.
palladium-catalysed
to
of
yield)
previously
palladium
and and
2
intermediates efficiency the
Recently,
Michael
reaction
production poor
their
a
unless
the
after
However,
as
Therefore,
traces
o-alkyl
very
framework
formate),2*3
palladium
As
products). able
to
the
trialkylammonium
derivatives
compounds
system
leaves
amounts
(minor
amines
been
maintain
example
products
reducing
atom
catalytic
(4)
carbonyl
lactones
Co-H
substitution
palladium
addition
addition-type
a,R-unsaturated
acyclic
the
a,
derivatives
conjugate
the
related
to
necessary
conjugate
I),
(vinylic
effects
related
is
system
now (Table
give
steric
pathway
Pd(0)
of
HPdX
of
medium.
the
in
variable
of
effects
reducing
by formation of
terms
reaction to
an efficient will
in
electronic
According Pd(II)
followed
syn-R-elimination
mainly
S-carbon,
group,
breaking
al.
arylation
of
with use
of
cyclic
reported.’
X-
ArX R;N
I H-Pd-X
I
I Ar-Pd-X
I
R
0
Ar &k
R’
(4) -i
HASOR, X
=
Br,
R = alkyl, R’
= H
R2=E;,Su
J
(2)
R YU I
Ar
aryl aryl
alkyl
’
H Scheme
I
~l~adiurn-cattish
reaction of aryl halides
815
Table I - The Palladium-Catalysed Reaction of Benzalacetone with Aryl Halides in the Presence of Tributy1amine.a Vinylic substitution product f% yieldjb
Benzalacetone Conjugate addition type product recovered (X yield)b f% yieldjb
Aryl halide
Pd-catalyst
Phi
Pd(OAc)2(PPhS)2
74
14
4-MeO-C6H4-I
Pd(OAc)2(PPh3)2
47
34
4-MeO-C6H4-I
Pd(OAc12
-7c
40
22
5=
4-MeO-C6H4-I
Pd(OAc)2[Pto-To~)3]2 57
17
15=
4-HO-C6H4-I
Pd(OAc)2(PPh3)2
46
40
13c
4-MeCO-C6H4-Br
Pd(OAcf2fPPh312
84
__
__
4-MeCO-C6H4-8r
PdfOAc)2[P(o-To113]2 97
_-
__
a) Reactions were carried out at 60 OC (6 hf in DMF by using the following molar ratios: benzalacetone:ArX:n-8u3N:Pd-catalyst= 1:1.5:2.5:0.03. b) Yields refer to single, non optimized runs. c) As E/Z mixture.
Since
the
extension of the vinylic substitution reaction to 8-substituted-a,R-enones
and -enals would provide a significative widening of the scope of this methodology in organic synthesis, it seemed to us of interest to expend efforts in seeking methods to control the reactivity of (2) in order to favour
the formation of vinylic substitution
products. The results of this study are reported hereafter. Discussion Selecting benzalacetone and phenyl iodide as different yield
conditions*, by
using
NaHC03
we as
have the
succeded base
and
to
obtain
n-Bu4NCl
as
model
systems
and
after
screening
in
4,4-diphenyl-3-buten-2-one phase-transfer
catalyst
as
reported
70% by
Jeffery:**’ *
by reacting benzalacetone with phenyl iodide in the presence of palladium example, catalyst,' an excess of NaHC03, and n-Bu4FHS04 only traces (Z-4%) of the vinylic substitution product were isolated (benzalacetonewas recovered in 80 % yield; 8 h, 60 OCf suggesting a dependence of the reaction course on the nature of the anion of the ammonium salt. However, the use of LiCl instead of n-3u4NC1 afforded the vinyl& substitution derivative in 71% yield (benzalacetonewas recovered in 78 % yield; 8 h, 60 OCf showing the need for a more lipophilic cation. This result, unsatisfactory from a synthetic point of view, may be of interest if compared to the almost complete absence of products observed when the reaction was carried out in the presenee of NaHC03 alone. It merits a For
note
**
that
n-8u4WS04
reaction
of
phenyl
isolated
in
40% and
Benzalacetone obtained
only
was iodide
found with
59% yield,
to
be
less
efficient the
than
3-buten-Z-one
in
presence
respectively;
3-buten-2-one:PhI
n-8u4NCl of
NaHC03 = 1:2,
in
the
Pd-catalysed
(benzalacetone WF,
was recovered in 84% yield and the vinylic substitution in traces by substituting Pd(OAc)2(PPh3)2for Pd(OAcf2.
24
h,
was
3OV).
product
was
A.
816
.&ORESE
et al.
Pd(OAc12 n-Bu4NC1, ,h&‘Me
+
NaHC03 >
Phi DMF,
Ph
60°C
Me Scheme
These bromides
conditions
(Table
derivatives
2,
in
have entries
b,e)
in
or
by
anion
was
(Table
2,
substituting found
i,m,u).
Interestingly
the
of
n-Bu4NC1.
conditions
of
It
The
of
those -
with
amines
MeS03H with
an efficiency
type
using
with -
AcOH,
a
product
tertiary was
entry
CF3COCH or
comparable
to
entry
c).
with
other
yield
The
that
amine always also
c).
MeS03H observed
in
20% yield
in
reacted
to
be
in
the
reduction tertiary
3,
Ph
R3N, Me
+
usual
in
case
the
recovered
iodide
one -
the
and
the
a,d,g,l),
(results
Table
palladium
amines
in
entries
major
reaction, of
under
the
(benzalacetone
phenyl
CF3CODH
this
in
obtained
this
(Table
with
well
traces.
with
base
in
as
even
AcONa
that
Pd-catalyst 0
groups
than
found
with
acetate
better
the
allows
the
and
as
least
of
iodide
obtained At
entries
reaction
was
a dramatic 2,
functional
only
strongly
(Table
presence
the
and
substitution
we observed
mixture
of
iodides
containing
phenyl
was formed was
aryl
vinylic
cases,
(benzalacetone
benzalacetone
3,
obtain
reaction
with
of
halides
these
the
NaHC03
AcOH were
Table
to aryl
significantly
or
product
obtained
or
1)
when
addition-type
b,e,f,h,i,m tertiary
by
yield
increased
result
addition
acid
2,
variety
4,4-diphenyl-3-buten-2-one
a
that,
above
benzalacetone
produced
(Table
conjugate
acetic
conjugate to
of
of
the
the
a
failed
In
(Table
of
reaction
we
a,d). to
NaHC03
anion
yield),
noteworthy
acid
increase
for
preserce
entries
acetate
tributylamine
is
presence
68%
2,
for
an
n-Bu4NC1
in
unchanged).
similar
The
without
recovered
presence
the
cause
the
acetic
AcONa
to
in
(Table
by adding
entries
absence
was
yield
satisfactory However,
yield
groups
the
found
h,l,n,q,s).
satisfactory
electron-withdrawing increase
been
II
3,
very entries
combination
species
to
of occur
HCOOH.
Ph
0
J-AMe
HB
Phi
Ph
DMF, 60-80°C
56-85% R = Et,
n-Bu;
BH = A&H,
The
CF3COOH,
question of
reactivity addition
and
MeS03H
thus
arises
o-alkylpalladium
vinylic
substitution.
on
how
amines,
intermediates
acids (2)
and
and control
NaHC03 the
or
AcONa
balance
can
between
Scheme
III
affect
the
conjugate
Palladium-catalysed
Table
2 -
Vinylic Aryl
Substitution Halides
Aryl
Entry
Derivatives
and
Obtained
Reaction
Time
Vinylic
(h)
product
Ae
6
15
(70)
97:3
(--)
98:2
11
Ce
6
87
(10)
97:3
4-OHC-C6H4-Br
Ae
24
_-
(--)
11
Be
24
64
(25)
96:4
Af
24
39
(58)
91:9
Bf
24
42
(56)
94:6
Ae
6
52
(37)
91:9
Be
*
74
(12)
97:3
Af
4.5
64
(30)
98:2
Cf
3.5
78
(18)
g8:2
Phi
Af
8
73
(21)
--
II
0f
8
70
(23)
Cf
8
74
(21)
--
4-MeO-C6H4-I
Af
3.5
82
(13)
82:18
*,
Cf
3.5
84
(12)
85:15
4-HO-C6H4-I
Af
3
96
(--)
56:44
3-MeOCO-C6H4-I
Af
7
36
(56)
98:2
Bf
8
47
(48)
98:2
0
I*
(9
##
11
Reactions
,,
were
carried
out
by using
the
following
A = benzalacetone:ArX:n-Bu4NC1:Pd(OAc)2:NaHC03 B = benzalacetone:ArX:n-Bu4NCl:Pd(OAc) refer in
to
single
determined
by
reasonable amines
‘H-NMR
coordination
of
the
be
involved
anionic
in
moiety
the the of
state7
formation
carbonyl
of group
decomposition this
loose
runs,
with
based
of
= 1:1.5:1::0.03:4:1.7;
a
(2)
reaction on
the
to
high
the
anionic
addition-type
stabilize
a-alkylpalladium
are
starting
amine
conjugate to
and
recovered worked-up
be
the
of
of
may
strongly ability
analysis
ratios:
= 1:1.5:1:0.03:1.7.
the
explanation
transition
favours
to
-_
1:1.5:1:0.03:4;
2:NaHC03:AcOH
optimized
refer
pentacoordinated
the
non
parentheses
molar
=
C = benzalacetone:ArX:n-8u4NCl:Pd(OAc)2:AcONa
tertiary
relative
84
,I
of
percentagesd
6
11
A
E/Z
(% yield)b’c
Be
4-MeCONH-C6H4-I
were
substitution (4)
(1
I,
Figures
Reaction
1,
3-MeCO-C6H4-Br
Yields
Palladium-Catalysed
1,
I,
b)
the
conditions
halide
4-MeOCO-C6H4-I
c)
in
817
Benzalacetone.a
4-MeCO-C6H4-Br
a)
reaction of aryl halides
as
a the
negative proton
species.
given
for
pure
material. mixtures.
e)
assumption
source
products.
on
in
the
and on for
percentages f)
can
products charge
80°C.
that
palladium’ character
isolated
d)Relative
60°C.
the
presence
produce Co.
can
This
a
late
behaviour
be facilitated
the
Co.
The
the
protonation
of
by
acid
could of
the
818
Table
A. AMOB
3 -
Catalysts, Phenyl
Entry
Amines,
Tertiary
and
et al.
Acids,
in
the
Reaction
of
Senralacetone
with
Iodide.a
Base
Acid
Pd catalyst (5
Time
mol X)
Total
(h)
yield,
,
Products %
yield
%
Starting
Conjugate
Vinylie
material
addition
substitution 20 :7
a
EQN
ACOH
PdlC
5%
4
87
10.3
69
b
Et3N
CF3CDOtl
Pd/C
5%
4
89
24.7
67.4
7.9
C
Et3N
MeS03H
Pd/C
5%
4
07
16.7
70.7
12.6
d
n-Bu3N
ACOH
Pd/C
5%
4
65
10.8
86.2
3
e
n-Bu3N
CF3COGH
Pd/C
5%
4
55
3.1
90.8
6.1
fC
n-Bu3N
CF3CODH
PdlC
5%
4
69
5.8
94.2
Qc,d
n-Eu3N
ACDii
Pd/C
5%
15
80
8.7
91.3
herd
n-8u3N
CF3CODH
?d/C
5%
15
79
7.6
92.4
ic,e
n-Bu3N
CF3COOH
Pd~OA~~2{PPh3~2
7
90
17.1
88.9
lc,e
n-Bu3N
AcOH
Pd(OAc)2(PPh3)2f
7
76
700
mc,e
n-Su3N
CF$OOH
Pd(OAc)2(PPh3)2f
7
05
100
a)
Unless
mmal
of
otherwise phenyl
catalyst
in
DMF (Imlf
of 0.34 mmof of
The rotation
d)
(2)
under
At
allows
carried
out
tertiary
an
60°C.
the
of
argon
e> At
Ca-Pd
fl
breaking
ho-C~bond~syn-~-h~dridopa~ladium
has
already in
the
IO
been
suggested
palladium
catalysed
3.42
8.98
mmol of mm01
b)
atmosphere.
7O*C,
bond
with
amine,
the
products with
were
mmol
80aC
n-Bu4NI.
intermediates
could
at
around
compounds
15.23
protonation
addition-type
reactions
noted,
iodide,
of
benzalacetone, acid,
GLC yield.
mmol
of
cb In the presence
mol %.
to
occur
faster
than
elimination. to
8.16
0.017
allow
reaction
the
the
sequence:
Protonation
formation
of
arylmercury
amines,
the
of
8,Q
of
conjugate
and
8
aryltin
a,&-enones.
When NaHC03
and
AcONa
are
be favoured
by a reduced
substituted extent
of
for &a-W
tertiary bond
cleavage
in
the
B-elimination transition
of state
HPdX
and/or
Palladium-catalysed
a minor
availability
of
protons
HPdX
the
presence
of
these
with
phenyl
in
benzalacetone conditions
a
mixture
substitution 39-40X
yield.
conjugate-addition product
was The
observed
vinylic
vinylic
variable
shift
shifted
the
ruled
in
ring.
with Table
the
presence
Decomposition
major
palladium
promote
mixture
of for of
or
the
and
tha
and
was as
these vinylic
recovered
the
in
base,
vinylic
the
substitution
Eu(fodb that
olefinic
are
E/Z
of
of
the
in (4d)
donor
in
the
to
an
ratio
Presence
of
6 Values
(ppm;
CDC13ITMS)
6.65
6.73
-0.08
6.73
6.76
-0.03
0.4
10.83
10.83
0.00
0.8
10.63
10.47
0.16
acetate
in
medium,
however,
o-alkylpalladium acetic
be
range invariably
of
the
closer
the
of
group to
the
conformation
(products the
from results
Variable
A6 = 6E-6Z
0.0
protic
of
Eu(dpm)g
0.2
the
presence the
example,
Z isomer
a
the
4.
E isomer
of
main to
was
isomers
As Table
in
of
major
the
the
power
found
irrespective
to
in
proton
the
were
assigned.
summarized
Mixture
the
revealed
Eu(dpm)g
olefinic
protons
E-configuration
(4d)
or
the
E-isomers,
conceivably
of
species
products
independently
in
analyses
arylpalladium
substitution
showed
isomers,
anti-
stereochemistry
X-ray
of
precedented”
less
HPdX.
reagents
ratio
a
and
acid
has
does
not
intermediate been
reported
appear derived
to
occur
HPdOAc .I0
to from through
play
a
chalcone
dominant and
role. phenyl-
syn-R-elimination
of
OAc Ph
Ph&‘Ph
of
Under
yield)
Et3 N
of
reaction
AcONa.
material
observed
syn-addition
was
the
the
‘H-NMR
vinylic
ring
of
of
models,
thus
4 -&Values
of
could
fact,
shift
aromatic
Eu(dpm)3/substrate
The
71% yield
B-elimination
in
(22-24%
using
in
the
NaHC03
starting
but
ground
from
of
Dreiding
Amounts
*
derive
molar the
From
E/Z
In
mixtures
molecule;
the
the
syn-R-elimination
syn-addition/syn-B-elimination) obtained
isolated
on
paramagnetic
all
on
the
obtained.
AcONa
out
to
and E/Z
the
greater
by
The
derivatives.
of
of
site
was
give
obtained
and
derivative
was
reagent/substrate
coordination adopted
was
bond
spectra
aromatic
result
n-Bu4NCl
conditions,
NaHC03 and
products
double
0.2-1.0
on the
that
HPdX
amounts
HCODH,
the
to
only in traces.2
substitution
‘H-NMR
by
819
tendency
addition-type
related
substitution
carbon-carbon
yield)
derivative
hypothesis of
The
confirmed
conjugate
closely type
-8-elimination main
the
is
medium*.
Pd(OAcI2,
(26-29%
Under
the
bases
iodide,
of
derivative
from
reaction of aryl halides
o
- HPdOAc
+ PhH Ph
H
PhJ&
Ph 75%
A. Amom.%
820
Results The low
yield.
(5)
was
the
of
isomeric Only
observed
Whatever
the
E/Z
the
2,
of
entry
of
this
4-hydroxy
and
most
s),
the
likely
reported
were
the
result
a
of
an
vinylic
next in
E/Z
amount
phenolic
methyl
substitution
very of
isomerization
free
the
section. only
significant
the of
the
obtained
of
by
substitution
the
in
usually
favoured
may be,
affords
are
formation
as
product,
q,r)
(41) (5)
group
behaviour
entries
2,
(4a)
derivatives
syn-S-elimination
reason
(Table
compounds
substitution
(Table
real
of
presence
formed
proton
usual
analyses
vinylic in
initially
labile
X-ray
al.
et
of group.
group
derivative
for
the
in
the
ratio. 0
Ar
(5) As concerns based
on
the
containing
a).
~-al~ylpalladium 1 ,3-dienes13
have
induced
ally1
of a the
acetates
acetate
acetate
mechanisms been acetate
IV,
the
anion
o-alkylpalladium
complexes12
(Scheme of
of
Related
palladium monoxide
reduction
of
attack
IV,
carbon
effect
formation
intramolecular (Scheme
the
b), to
acetate
moiety
on
involving
a
suggested
to
migration and
of
and
for
terminal
on
reaction
and
its
the
palladium
to
palladium-catalysed the
is
seven-membered for
an
regio-
through
and
IV,
basic proposed
transition
state
stereochemistry
an unsaturated 1,4-functionaly~ation
(Scheme
explanation
tentatively
cyclic
palladium-catalysed
alkenes14
course,
decomposition
S-hydrogen
the
account
from
the
regioselective
carbon
of
ligand of
in
cyclic formate
c).
Me
a Ar
H
*&tR1+.
MeCCCti
+
Pd(O)
Me
I 0-o
3 J gi
I
oAo
b
-A-
+ +
Pd(O)
co:!
+
Pd(O)
Scheme
IV
Palladium-catalysed
R-Hydrogen agreement
abstraction
with
electronic
both
effects
(greatest
in
groups;
4-acetylphenyl entries
b and In
various
the
in
Table
2).
Table
noting
the
5 the
B-carbon
atom
aryl
halides
main
products
arising
that
the
the
to
be
and
readdition-elimination
+
of
rings
is
NaHCOS
halides
as
compounds
obtained
with
(Table
mixtures
of
5,
or
bearing and
vinylic
Ar
bases
group
acetate
m,
n).
derivatives
and
summarized.
alkyl
without
entries
with (compare
the
are an
In (6),
It
on
even
with
these most
the
cases likely
HPdX species:
ArX
W (4)
R = Et;
as
susbtrates
more
reacted anion
AcONa
in
strongly
conceivably
when
trifluoroacetate
either
is
and
containing
elimination
basic
groups
E/Z
aromatic
species
syn-S-elimination)
less
aryl
were
from
unchanged
carbonyl
results
the
derive
recovered
using
electron-withdrawing
found
R’
of
-enals
same
o-alkylpalladium
hydridopalladium
obtained or
the
with
was
a,f3-unsaturated
essentially containing
from
cases
to
products
observed
presence
results
with
were
are
these
R-substituted-a,R-enones
worth
(main
benzalacetone
bromide c,
complexed
results
effects
Furthermore,
difficult).
acetate
stereochemical
electron-withdrawing
is
by the
821
reaction of aryl halides
(6)
n-Pr
= 4-MeCO-C&H4 Scheme
In
conclusion,
palladium with
intermediates
aryl
simple
halides
and
materials
The
through
The
are
reported
derived
from
be effectively tool
subtle
stereochemistry established of
these
coordinates
listed
results
to
the
this
the
of
by
different in
paper
reaction
controlled
select
changes
in
the
show that
reactivity
of
S-substituted-a,R-enones nature
synthetic
reaction
the
of
pathways
the for
and
base the
o-alkyl-
thus
-enals
providing
a
same starting
medium.
Structure
unambiguously structures
can
efficient
Crystal
atomic
the
V
in
Table
of
by X-ray
compounds and 6.
the
thermal
vinylic crystal
exhibiting parameters
substitution structure the of
products analysis.
E configuration the
non-hydrogen
(4a)
Figure of
the atoms
and
(41)
1 shows vinylic of
the
double the
two
has
been
molecular bond. structures
The
A. AMORESE et al.
822
Table 5 - Vinylic Aryl
Substitution
Halides
and
a,&Unsaturated
Entry
carbonyl
Derivatives
Obtained
R-Substituted-a,R-Enones Aryl
halide
in
the
and
Reaction
compounds
Palladium-Catalysed
Vinylic
conditions
Reaction
of
Enals.a
substitution
product
(4)
E/Z
(% yield)b’c
relative
percentagesd
0 a
Phi
Ae
43
(55)
b
Phi
Ce
57
(39)
C
4-HO-C6H4-I
Ae
67
(30)
63:37
d
4-MeCONH-C6H4-I
Ae
84
(14)
83:17
e
4-MeCO-C6H4-Sr
Cf
46
(38)
87:13
f
Phi
Ae
81
g
3-HOCH2-C6H4-I
Ae
60
(20)
g1:g
h
4-M&O-C6H4-Sr
Af
36
(60)
8g:ll
Cf
66
(30)
gg:i
4-HO-C6H4-I
Agye
74
(20jh
5g:41
4-MeCO-C6H4-Br
Ag,f
16
(51jh
g2:8
CS,f
15
(60jh
g8:2
cg,f
17
(52jh
g6:4
,I
,,
4-MeCO-C6H4-Sr
a)
Reactions
were
carried
out
(8
h)
by using
the
following
A = benzalacetone:ArX:n-BuqNC1:Pd(OAc)2:NaHCO3 Yields
refer
c)
Unless
otherwise
d)
Relative
e)
60°C.
(41),
single
80°C.
bond
Unusual -and they
non
stated,
percentages f)
The values.
to
g)
were 24
h.
distances values can
h)
and are
Yield
the
by
of
the
valence observed
to
the
and
are
parentheses
determined
only
be ascribed
runs,
in
ratios:
= 1:1.5:1:0.03:1.7.
optimized
figures
molar
-
= 1:1.5:1:0.03:4;
C = benzalacetone:ArX:n-BuqNCl:Pd(OAc)2:AcONa b)
-
‘H-NMR E/Z
given
refer of
angles
generally
in
extreme
bad
pure
isolated
products.
the
for
recovered
starting
material.
of
worked-up
reaction
mixtures.
analysis
mixture
the
to
location
of
vinylic
fall part
the
derivative
within of
atoms,
(6).
the
the
range
of
accepted
ring
of
compound
benzene
due
to
their
large
thermal
factors. In
the
the
aromatic
the
planes
corresponding
of
solid
state,
rings
and
the
rings
values
for
of
the
molecules
the
vinylic
A and
S and
compound
(41)
of
the
moiety. that are
two In
of 58
the and
compounds
compound double 37’.
show
(4a), bond
These
a
the C(4)=C(5)
structural
similar dihedral are
arrangement angles 59
and
parameters
of
between 20”. lead
The to
a
823
PalIadium~a~alysed reaction of aryi halides
Fig.
1 -
Molecular
structures of (4a) and (41).
nearly perpendicular orientation of the two aromatic systems, being 7Q" the angle between their best planes in both the molecules.Jhe groups -COMe and -NHCOMe, substituents of the B ring of the two molecules, are almost coplanar with this ring, being 12 and 15" the angle between their planes in compound (4a) and 1411, respectively. A major
difference between the structures is found in the conformation of the -COMe
group at C(4) with respect to the rest of the molecule. The carbonyl C(21=0(3) is anti-periplanar, in f4af, and syn-periplanar, in (411, to the double bond C(4t=C(5). This conformationalvariation may be attributable to a higher efficiency of the crystal packing, which in both cases is mainly governed by Van der Waals forces. In the crystal of compound (411, molecules
related
by two-fold screw axes are also linked by intermolecular hydrogen
bonds involving N(18) and O(201, with the following geometrical parameters:N(18)....0(20)= 3.05 A, H(N(l8))....Of20) = 2.09 il,N(16)-H....0(20) = 172.6O and C(l9)=O(ZO)....H(Nfl8)~= 150.40. EXPERIMENTAL M.ps were determined with a Bijchi510 apparatus and are uncorrected. All starting materials, catalysts and solvents are commercially available and were used without further purification.
4-Acetylaminophenyl
iodide,
as
well
as
3-carbomethoxy-
and
4-carbomethoxy-
and 3-iodo and was prepared from 4-iodobenroic acids according to standard methods. I-Phenyl-I-penten-3-one commercially available l-penten-3-oneand phenyl iodide according to Jeffery.' Reactions were carried out on a 0.62-4.0 mmol scale. phenyl
iodides
were
prepared
from
commercially
available
4-aminophenyl
iodide
A. AMORESE et al.
824
Table 6 - Atomic coordinates
and isotropic
thermal parameters
with their e.s.d.'s
in parentheses.
x
Compound
Compound
(4a)
(41)
z
C(1)
-0.0905(3)
C(2) O(3) C(4) C(5) C(6) C(7) C(8) C(9) C(10) (x11) C(12) C(13) C(14) C(15) C(16) C(17) C(18) O(19) C(20)
-0.0580(3) -0.1372(2) 0.0732(2) 0.1581(2) 0.1239(2) 0.1887(3) 0.1561(3) 0.0578(3) -0.0070(3) 0.0263(3) 0.2894(2) 0.3425(3) 0.4631(3) 0.5384(2) 0.4876(2)0.3644(2) 0.6708(3) 0.7038(2) 0.7622(3)
0.0083(3) 0.0275(2) 0.0134(2) 0.0524(2) 0.1196(2) 0.1942(2) 0.1885(2) 0.2600(2) 0.3366(2) 0.3424(2) 0.2724(2) 0.1285(2) 0.0417(2) 0.0510(2) 0.1444(2) 0.2313(2) 0.2231(2) 0.1472(2) 0.0778(2) 0.2332(3)
0.1345(3) 0.2729(3) 0.3141(2) 0.3635(2) 0.3470(2) 0.2338(2) 0.1561(2) 0:0518(2) 0.0236(3) 0.0990(3) 0.2042(3) 0.4467(2) 0.5363(2) 0.6292(2) 0.6368(2) 0.5485(2) 0.4554(2) 0.7369(2) 0.8225(2) 0.7327(3)
C(1) C(2) O(3) C(4) C(5) C(6) C(7) C(8) C(9) (x10) C(ll) C(l2) C(13) C(14) CC151 C(16) C(l7) N18) C(19) O(20) cc211
0.4023(S) 0.3575(4) 0.2644(4) 0.4279(4) 0.4245(3) 0.3572(4) 0.2340(S) 0.1695(6) 0.2399(8) 0.3605(7) 0.4181(S) 0.4944(4) 0.4758(4) 0.5406(4) 0.6294(3) 0.6492(4) 0.5825(4) 0.6999(3) 0.7288(4) 0.6946(3) 0.8091(5)
-0.4406(4) -0.3036(3) -0.2341(3) -0.2626(3) -0.1402(3) -0.0188(3) 0.0552(4) 0.1719(4) 0.2016(4) 0.1331(S) 0.0218(4) -0.1211(3) -0.2176(3) -0.2005(3) -0.0857(3) 0.0119(3) -0.0049(3) -0.0591(2) -0.1474(3) -0.2668(2) -0.0873(3)
0.4124(2) 0.3880(2) 0.4199(l) 0.3222(l) 0.2921(l) 0.3250(2) 0.2892(2) 0.3239(3) 0.3914(4) 0.4239(3) 0.3920(2) 0.2235(l) 0.1710(l) 0.1067(l) 0.0934(l) 0.1454(l) 0.2087(l) 0.0294(l) -0.0225(l) -0.0199(l) -0.0832(2)
a) B(eq) = (413) Eijaiajbij.
B(eqja 6.2(l) 4.5(l) 6.4(l) 4.2(l) 3.7(l) 3.6(l) 4.4(l) 4.8(l) 5.1(l) .5.1(l) 4.5(l) 3*9(l) 4.4(l) 4.6(l) 4.0(l) 4.2(l) 4.2(l) 4.6(l) 6.5(l) 6.7(l)
7.6(l) 5*4(l) 7.8(l) 5.4(l) 4.8(l) 5.6(l) 7.9(l) 10.4(2) 10.9(2) 10.4(2) 7.5(l) 4.7(l) 5.1(l) 5.0(l) 4.6(l) 5.4(l) 5.5(l) 4.9(l) 4.0(l) 6.2(l) 6.4(l)
Palladium-catalysed
The equipped -
products with
from
Waters
eluting
‘H-NMR
spectra
IR
the
A -
iodide phenyl
of
This
(Table
5,
iodide
(0.587
mmol)
in
mmol)
in
nitrogen
DMF (1
ml).
residue
was
The
compound
(4f)
Procedure
g, is
bromide
(Table
2,
entry
bromide
(0.517
g,
2.60
AcCH
(0.166
(0.012 80
ml, 0.051
g,
“C under
purified (4b)
a
by
Procedure
C -
mmol) in
in
ml). for
HPLC eluting Reaction
with
diethyl
ether
and IR
ml)
3.47
(s,
Reaction
0.8 of
of
mixture were
with was added,
aryl
Co.)
internal
halides g,
and
phenyl mmol), g,
(0.0129
stirred
added,
with 1.92
(0.645
NaHCg
Pd(OAc12
at
the
g,
60
at
a 9515
n-hexane/AcOEt
reduced
7.68 0.0576
“C
organic
concentrated
with
of
g,
benzalacetone (0.250
1.70
under
layer
a was The
pressure. mixture
up
NaHC03 to
to
give
with
before
afforded
4-acetylphenyl
mmol),
4-acetylphenyl
(0.544
g,
a
purged
as
a 80120
with
1.70
stirring
was
Work
g,
mmol),
with
mixture
6.80
solution
nitrogen
n-hexane/AcOEt
H);
a
were
a 75125
of and
a
to
mmol), Pd(OAcj2
stirred
residue
mixture
benzalacetone
stirred the
at
at
which
give
was
compound
with
phenyl
benzalacetone
g,
1.70 of and at organic
60
5H);
iodide, g,
formic
acid
under
layer
(0.012
g, g,
(0.109 a
was
ml,
nitrogen separated,
was
; ’
H-NMR: Hz,
and
in
mmol)
atmosphere washed
for with
was 8
(4
h;
water,
16% yield) (m,
3.65
(s,
(m,
(1
g,
ml)
ml).
added h;
The 24
preparative
8.12-7.88 H);
(0.530
DMF
DMF
ml).
2H);
1.2
H);
3H).
bicarbonate
iodide in
was
51 %; mp = oil;
1.1-0.73
sodium
g,
ml)
with g,
g,
6
(0.591
for
by
(0.076
0.4
2H);
phenyl mmol)
purified
(4m) (0.246
(m,
78% yield).
DMF (0.5
residue
mmol)
2.90
in
washed
J = 6.7
nitrogen
DMF (1
separated,
acid
0.051
in
was
1.78-1.77
6.80
g,
atmosphere
cm-l
a
by preparative
bromide
mmol)
purified
mmol),
under
(0.371
mmol)
compound
(t,
formic 1.70
a
2.90 mmol)
m)
7.92
0.059
further
5.7
“C
g,
0.051
nitrogen
give
843
H);
(m,
g,
The
(4m)
entry
g,
layer to
958;
0.6
5,
g,
purified
4-acetylphenyl
OC under
not
NaHC03(0.571
Pd(OAcj2 “C
was
(0.250
mmol),
80
pressure.
1269;
2.38-1.85
(0.0133
mixture
Hz,
3H);
of
(0.665
organic
which
1606;
J = 6.7
NaHC03 at
the
(Table
60
was
4-acetyl-
(0.238
(0.012
at
which
mmol),
AcONa
Pd(OAc)2
compound
mmol),
4-acetylaminophenyl
1.70
mmol),
stirred
give
1.98
Pd(OAc)2
reduced
(6m)
to
g,
1.70
of
and
bromide
stirred
added,
1680;
solution
of
g,
a residue
g,
mmol),
and
compound
(s,
nitrogen
with
(0.250
a solution
mixture
(0.250 1.98
benzalacetone
(0.472
afforded
n-hexane/AcOEt
(t,
to
with
before
solution
water
2.55
n-8u4NC1
stirring
purged
g,
concentrated
nitrogen
mmol),
of
benzalacetone
4-acetylphenyl
nitrogen
6.13
reaction of
n-hexane/AcOEt
with
1712;
A solution
purged
to
2H);
a
and
added
h.
by the
up as
(0.550
film)
to
6 with
with
and
of
stirring
The
for
3-octen-2-one
mixture
(0.472
and
mmol), of
were
reaction
was
solution
was
Work
a 50150
and
n-Bu4NC1
)
(0.472
ml).
2.60
added
mixture h.
and
(m,
(TMS
(0.307
nitrogen water
benzalacetone
ml)
eluting
A
g,
was
The
with
(liquid
7.58-7.25
HPLC
(0.678
3.5
(MgSO4) an E/Z
DMF (1
m).
purged
HPLC eluting
spectrometer
1.92
solution
with
the of
DMF (3
exemplified
stirring
was
p(Amicon
1-phenyl-1-penten-3-one
g,
a
and
(MgS04
by
atmosphere
n-Bu4NCl
mixture dried
in
3-octen-2-one
mmol),
added
in
is
A solution 2.97
mmol)
entry
with
of
20-45
Yvon
detector
spectrometer.
compounds
of
(0.534
HPLC eluting
n-8u4NC1
2,
DMF (3
DMF (I
Jobin
index
microanalyses.
to
purged
A solution
This
iodide
atmosphere
gel
from
84% yield).
(Table
aminophenyl
silica
1-phenyl-1-penten-3-one
ether
dried
mmol),
nitrogen
g,
was
FT/IR
carbonyl
stirring
exemplified b).
mmol)
10
refractive
81% yield).
preparative
(0.377
iodide
2.90
Prep
and
EM-390
50X
reaction
of
diethyl
h;
water,
This
the
n-8u4NCl
with
by preparative
(0.453
B -
mmol),
mixture 8
with
purified
with
Varian
a,B-unsaturated
solution
added
a
satisfactory
by
A
2.88
for
washed
separated,
system
packed
a Nicolet
gave
of
f).
was
atmosphere
columns
with
exemplified g,
ml)
(Chromatospac
delivery
with
recorded
reaction
entry
DMF (4
compressed
products
is
HPLC
solvent
recorded
were
isolated
procedures
Procedure
preparative -
mixtures.
were
spectra
of
by 500A
on axially
n-hexane/AcOEt
standard).
General
purified
LC/System
Ass.)
with
All
were
a Prep
825
reaction of aryl halides
all dried
mmol),
added
The
diethyl
water,
2.60
was
mixture at
ether
once. and
(MgS04)
with was The water and
A. AMORESE et al.
826
Table
7 -
Characterization Reaction
Compound
of
of
Vinylic
Benzalacetone
M.p.
(4)
4-MeCD-C6H4
83-84
(E
Isomers)
229-230
b
the
6 ( ppm) CDCl3
1655,
1696,
from
1 H-NMR
777,
1606, 703a
1655,
826,
Derived
Halides
(cm-‘)
1680, 843,
4-CtiC-C6H4
Aryl
I.R.
V
( OC)
Ar
Products
Substitution
with
777,
1606,
7.95
(d,
7H)
6.61
10.07
703’
J=8.2
Hz,
(s,lH),
(s,
IH),
7.62-7.15
2H),
7.57-7.16
2.56
(s,3H),
7.88
(m,
(d,
J
(m, 1.87
= 8.2
7H)
(s,3H)
Hz,
2H),
7H),
6.65
(s,
IH),
1.90
(s,
9H),
6.62
(s,
IH),
2.28
(s,
3H) 4-MeDCD-C6H4
63-64
1721,
1655,
1606,
7.63-7.07
1286,859,769,703a 3-MeCD-C6H4
222-223b
1688,
1655,
802, 4-MeCONH-C6H4
121-122
777,
3312, 1589, 777,
Ph
99-l
oob
1589,
6.62
1688,
1663,
8.47
1179,
835,
(s,
4-HO-C6H4
1663,
1606,
1688,
1655,
761, 3-MeOCD-C6H4
183-184b
b)
KBr.
E/Z
As
the
(bs,
2H),
lH),
7.61-6.94
2.53 IH),
(s,
(s,
3H),
(m,
IOH
,
7.76-6.78
(m,
9H)
3H),
(s,
3H)
(m,
3H),
1.88
7.73-7.10
2.14
7.58-7.08
1589, 777,
(m, 1.88
(s,
7H),
(s,
3H)
9H),
6.60
3H)
1729,
1.86
1.85
1688,
1663,
(m,
(s,
1.68
8.25-7.92 (s,
2,4_dinitrophenylhydrazone.
c)
6.58
(s,
IH),
1.81
3H)
7.58-6.52
695’
1606,1294,761,703c
a)
(m, (s,lH),
(s,
1253,835,769,703’ 3410, 835,
oil
3H)
703a
1688,
179-180b
(s,
8.07-7.81
695’
1589,777,761,703’ 4-MeD-C6H4
(m,
3H),1.88
(s,
Ill-l),
IH),
3.82
(s,
(s,
1.32
H),
1.93
H)
(m,2H),
IH),
Liquid
6.62
3.87
7.62-7.12
(s,
film.
d)
3H),
(m,7H),
1.87
Isolated
(s,
and
6.62
3H)
analyzed
as
mixture.
concentrated eluting
at
substitution yield
reduced a
with
residue
n-hexanelethyl conjugate
product,
88 %) whose
The
pressure.
80120 relative
was
acetate
addition-type
percentages
filtered
product,
(29.5
on
mixture
%,
to and
25 %,
a
short
give
a
starting
45.5
%,
silica
gel
mixture
vinylic
benzalacetone
respectively)
column
of
(overall
were
determined
by ‘H-NMR. Reaction
of
benzalacetone
A solution n-8u4NCl (4
ml)
(0.472
g,
was added
(1
ml).
The
all
at
once.
as
before
mixture The
and 43
Crystal
%,
n-hexane
1.70
mmol),
with
stirring
was
;
was
a
starting
and
plate
NaHC03 with
measured MO-Ka unit-cell
with
radiation,
a Syntex
in e-28 were
yield
crystals
space
yellow
groups
Weissenberg
mode;
derived
(0.012
acid
a
2.91
0.051
ml,
2.90
whose
mmol),
mm011
for
conjugate relative
2.60 mmol)
mmol)
atmosphere
product, %)
g,
g,
9,
(0.109
nitrogen
93
(0.530
AcOH (0.174
Pd(OAcl2
formic
acetate
iodide
8
in
DMF
in
DMF
was added h.
Work
up
addition-type
percentages
(31
%,
by ‘H-NMR.
pale
quality,
automatic
scan
mmol),
of
sodium
determinations
and P2,
and phenyl
substitution
(overall
The
oscillation
8.55
OC under
determined
prismatic
poor
g,
acid
mmol),
and
60
vinylic
structure
colourless
dimensions
at
of
formic 1.70
solution
nitrogen
benzalacetone
shaped,
from
a
stirred
were
g, (0.923
to
dichloromethane/n-hexane.
determined
iodide,
(0.250
mixture
crystal
shaped
phenyl
purged
mixture
respectively)
data Well
with
benzalacetone
afforded
product, 26 %,
from
of
of
(4a)
and
by
compound
least-squares
of The
equipped (411
grown
Cu-K, calculations
from
compound
approximated
photographs.
diffractometer for
were
crystals
unit-cell
data
graphite
radiation of
were
was the
obtained
parameters
intensity with
dichloromethane/
(41)
were
(4a)
were
monochromator
and
used.
angular
of
The
refined
settings
of
Palladium-catalysed
Table
8 -
Characterization Reaction
Compound
of
Ph
Ph
Vinylic
and
v (cm -’
(OC) 191-192a
H
-fnals
(E
with
Isomers)
Aryl
from
the
’ H-NMR
6
)
2844,1663,1589, 1122,
Derived
Halides
I.R.
M.p. R’
Products
Substitution
l3-Substituted-o,O-Enones
(4) R
Ar
of
827
reaction of aryl halides
769,
695b
9.60
(d,
(m,
IOH),
(ppm)
J=8.2
WC13
Hz,
6.62
lH),
(d,
7.64-7.18
J
= 8.25
Hz,
0.63
H),
H),
7.63-6.50
1H) Ph
4-HO-C6H4
H
3181,1663,1639,
oil’
1606,1286, 777, 4-MeCONH-C6H4
Ph
H
248-24ga
744,
835, 703bvc
9.60
(d,
J=8.2
Hz,
(d,
J=8.2
Hz,
0.37
(m,
11H)’
3312,1663,1598,
9.56
(d,J=8.2
835,
lH),
7.82-7.18
744,
703b
J = 6.2 4-MeCO-C6H4
Ph
H
91-93
1680,1655,1598,
9.65
835,
J = 8.2
761,
695d
lH), = 9.2
(s,
Hz,
lH),
Hz,
(d,
3H) 8.02
7.64-7.22
J =8.2
(bs,
6.56
2.16
Hz,2H),
(d,
8.67
(m ,SH),
Hz,
(d,J
6.64
Hz,lH),
9.47
(d,
(m,7H),
IH),
2.60
(s,
3H) Ph
Ph
131-132a
Et
1688,1663,1589,
7.62-7.12
769,
2.25
695b
(m,
(q,
J = 6.7 3-HOCH2-C6H4
Ph
Ph
177-l
78a
1220, 777, 4-MeCO-C6H4
Ph
n-C5Hl
I
101-102a
859,
Hz,
13H),
794,
Hz,
6.62
(s,
2H),
0.93
lH), (t,
3H)
8.05-7.82
3443,1655,1598,
lOHI,
J =6.7 (m,
4.67
2H),
(s,
7.62-7.08
(m,
2.17
1H)
2H),
(bs,
703b
1688,1606,1269,
7.97
826,
(m,7H),
777,
703b
(d,
J = 8.7Hz,2H), 6.65
2.25
(t,
(m,
6H),
7.58-7.12
(s,lH),
J=6.7
2.56
Hz,
0.82
(s,3H),
2H),
1.72-0.98
J
(t,
= 6.7
Hz,
3H) 4-HO-C6H4
n-C3H7
oil’
H
3443,1663,1605,
10.17
1220,
(d,
J=8.2
8.2
Hz,0.82
835b*C
(d,
1.18
J=8.2 Hz, H),
n-C3H7
Me
19%197a
6.94
6.36
(d,
J = 8.2
(d,
J=8.2
7.5
Hz,
Hz,
1.18
1680,1598,1269,
8.05
958,
J = 8.2
826b
0.82
Et
Me
194-195a
1680,1598,1269,
8.10
958,
8.2
826b
(m,
Hz,2H), (m,
(m,
Hz,2H),
J=
2H),
7.64
6.52
(d,
(s,
2.6
lH1,
(s,
3H),
(m,
4H),
3 H) Hz,2H),
6.52
-1.18
6.15 (t,
J = 7.5
1.57-1.07
(m,
J=8.2
(t,
2H),
(d,J=8.2 Hz,2H),
2H),
H), 3.00
2.57
2H),
3H),
1.00-0.67 4-MeCO-C6H4
H),
Hz,
Hz,
3HjC
J=8.2
(s,
9.53 (d,J=
(d,J=8.2
J =8.2
1.77-1.32
(m, Hz,
H), 7.48
Hz,0.59
H),
H),
3.19-2.90 2.28
(d,
Hz,0.41
(d,
0.41 H),
7.21
H),
1.05-0.78 4-MeCO-C6H4
Hz, 0.59
2.62
2H),
7.64
(s,lH), 0.92
(d, 3.07
(s,3H), (d,
J= (t,
1.68-
J=8.2
Hz,
3H) a)
As the
mixture.
2,4_dinitrophenylhydrazone. d)
KBr.
b)
Liquid
film.
c)
Isolated
and
characterized
as
E/Z
A. AMORESEet al.
828 15 selected
reflections.
Crystal
data
b = 11.80(i), g/cm3,
k(Mo-Kc)
= 0.8
Crystal
data
b = 9.978(2),
compound i,
cm-‘,
of
sine
The
intensity
reveal
cm-‘,
sin s /X < 0.61
multisolution block-diagonal last
few
(Rw
= 0.073)
and
for
the
cycles
of
and
R =
to
dimensions
0.4x0.5x0.5
2543
for
three
data
(41).
those
the
density,
their
calculations.
(Rw
=
0.117)
atomic
for
I>20
the
= 8.042(2), DC =
1.21
which
did
the
1804
were
crystal
were
by
refined
by
located
on
kept
converged
structure
of
2327
solved
were
atoms
unique and
were
parameters
refinements
2975
(I),
parameters
hydrogen
The
a = 4,
reflections,
structures
atomic
11.65(l), DC = 1.21
mm.
Of
having The
The
calculations;
least-squares
standard
=
mm.
0.7x0.4x0.07
collections.
elucidation.
SIR-CAOS”.
electron
0.082
dimensions
using the
structure with
of
crystal
monitored
least-squares
syntheses
i-‘,
during
methods
(9x9) Fourier
the
(4a),
used
direct
difference
were
variations for
were
crystal
Mw = 279.339, monoclinic, C18H-l?ND2* 8 = 94.61, U = 1531 i3, space group P 21/a, 2
measurements
measured
respectively,
k’,
a
2 = 4,
(41):
i,
significant
reflections
/X
compound
= 6.4
monoclinic, Cl aH16OZ 1 Mw = 264.324, U = 1450 i3,space group P 21/a,
(4a):
I3 = 114.5(l),
c = 19.143(3)
g/cm 3, ~(CU-Ko) not
of
c = 11.60(2)
to (4a)
fixed
in
R =
0.047
and
(41),
respectively. All
the
calculations
crystallographic Full bond
were
software lists
distances
of
atomic
and
valence
Crystallographic
Data
Acknowledgements Istruzione
-
performed
SIR-CAOS15;
on
Data
General
scattering
and
anisotropic
coordinates angles,
a
atomic with
MV 8000
factors thermal
e.s.d.‘s,
have
II
were
computer,
taken
from
coefficients
been
deposited
at
using
the 16
literature. and
tables
the
Cambridge
of
della
Pubblica
Centre.
The
was
research
by a
supported
grant
from
Minister0
(Italy).
References 1)
Heck,
R.F.
Hegedus, Tsuji,
“Palladium “Organic
J.
2)
Cacchi,
S.;
Arcadi,
Arcadi,
A.;
Marinelli,
G.
F.;
Synthesis
(1984)
4)
Stokker,
G.E.
5)
Jeffery,
T.
6)
Benhaddou,
7)
Maitlis,
8)
Cacchi,
S.;
9)
Cacchi,
S.;
J.
E.E.;
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Org.
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Press,
London
React.
Springer
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Verlag,
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(1980)
Chem.
(1984)
268,
Sot.
Chem.
(1986)
312,
C48;
C27;
Cacchi,
Cacchi,
S.;
(1988)
247
S.;
Palmieri,
J.L.;
J.
Bystrdm, Tables
K.
33,
Sot.
Chem.
S.E.;
for
X-Ray
Vol. Lett.
39,
Comm.
1,
p.
37,
(1979
)
(1981
) 46,
Academic
Press,
1971
4591
3373
724 J.
P. 2615;
Org.
Chem.
Blckvall,
Comm. (1980)
Nordberg,
Org.
Palladium”,
(1983)
Warwick,
J.
1287 Chem.
Tetrahedron
43,
(1977)
Chem.
3179
J.
of D.
(1978)
28,
G.
Chemistry
Chem.
Learn,
International
C.N.R.,
Organic
Ruth,
C.
Backvall,
SIR-CAOS,
S.;
Tetrahedron
Hutchins,
Camalli,
(1987)
Comm. (1984)
Tetrahedron
Moberg,
Org.
4236
Chem.
Lett.
G.
D.E.;
48,
Organomet.
Chem.
Palmieri,
13)
16)
Sot.
Misiti,
B.M.
J.
Organomet.
F.;
J.
Academic R.F.
Compounds”,
(1983)
S.
La Torre, K.
Birmingham
J.
Czernecki,
14) 15)
Chem.
Heck,
575
Chem.
R.;
1-t) Bergstrom, 12) Trost,
G.
Syntheses”,
2415;
Palladium
Cacchi,
Tetrahedron
P.M.
10) Yamamura,
Org.
F.;
Palmieri,
Organic 40,
with
J.
A.
in
(1984)
Synthesis
3)
La Torre,
Reagents
Tetrahedron
L.S.
Chem.
R.E. (1982)
J.-E.;
1432
Nordberg,
R.E.
;
Bjorkman,
943
J.
Org.
47,
4380
Crystallography,
Vol.
Chem. IV,
(1984) pp.
49,
4619
99-149,
Kynoch
Press,
(1974) M.;
Capitani,
Italian C.P.
n.
Patent 10,
00016
D.; n.
Cascarano, 35403c/86:
Monterotondo
G.; User
Cerrini, Guide
Stazione,
S.; (Istituto
Roma,
Italy)
Giacovazzo, di
C.;
Strutturistica
Spagna, Chimica,
R.
Terrakdron Printed
in Great
OO4&4020/89
CONJUGATE ADDITION
VS.
VINYLIC
OF ARYL HALIDES
A.
Istituto
Amoresea,
b)
di
A.
Stazione
Dipartimento
di
c)
di
Dip.
PALLADIUM-CATALYSED
Chimica
G.
S.
G.
REACTION
AND -ENALS
Bernocchic,
W. Fedelib,
Press plc
Cacchic*,
Ortard
Giacomello,
C.N.R.,
CP 10,
00016
Roma (Italy) Ingegneria
Chimica
e Materiali,
via
Assergi
4,
(Italy)
Studi
Attive,
Cerrinia,
Chimica,
L’Aquila
E.
Arcadib,
,
IN
R-SUBSTITUTED-a,&ENDNES
Strutturistica
Monterotondo 67100
SUBSTITUTION
WITH
S.
a)
$3.00+.00
Pergamon
Britain.
di
Chimica
Universita
degli
e
Tecnologia
Studi
“La
delle
Sapienza”,
Sostanze P.le
A.
Biologicamente
Moro
5,
00185
Roma
(Italy) d)
di
Dip. A.
Studi
Moro
5,
Universita
Farmaceutici,
00185
degli
Studi
“La
Sapienza”,
P.le
Roma (Italy)
(Received in UK 11 November 1988) Abstract aryl
-
The
reaction
investigated. dependent favour
on
the
the
The
outcome
the or
better
than
use those
reaction
the
yield
the
and
palladium
added
base.
that acetate with
of
halides
found
results
acetate
tend
to
sodium
products. comparable
bicarbonate.
or
Furthermore, strongly
afforded
been
greatly
while
substitution
containing
substitution
be
amines
products
vinylic
with
has
to
Tertiary
produced
sodium
-enals
catalyst
was
addition-type
acetate
sodium
vinylic
a
reaction
sodium aryl
groups, of
the
conjugate
obtained
of
-withdrawing the
of
of
of of
of
sodium
the
B-substituted-o,&enones
presence
nature
formation
bicarbonate Usually,
of
in
halides
in
electron-
a dramatic
increase
in
products.
Introduction It
is
complexes
well
to
give
syn-B-elimination however, our
this
hands,
amines.
Poor
Table
on
the
a
vinylic
has
not
been
extended
variety
intermediates
1.
This
nature failure
of
when
of
reacted of
the
aryl
can
be
in
the
from
with
species substitution to
with
accounted
acyclic
presence
and
halides,
Some for
by
of
a,B-unsaturated
813
a
rapid,
products.’
-enals
the tertiary
observations amines carbonyl
our
and
-enals to
catalyst
products
representative
spontaneous
To
failed
palladium
addition-type
halide).
carbon(sp’)-palladium
undergo
l3-substituted-u,O-enones
aryl
conjugate
a-bonded
which
R-substituted-a,R-enones
yields
decomposition derived
react
a-alkylpalladium form
moderate
on the
systems
to
reaction
to
olefinic
HPdX
products
(depending the
that
unstable of
indeed,
substitution
known
were
results
give and
instead are
we
reported
of
the
compounds.
knowledge, (I)‘. vinylic tertiary obtained
summarized previousl$
o-alkylpalladium The
In
competition
in
A. AMORESE et
814
between
Co-Pd
Scheme
1,a)
and
rationalyzed the
bond
and
basic
species
while
stop
quickly amounts
vinylic
substitution
confirmed to
the
triethylamine
as
a,%unsaturated
is
used
presence
the
R$H
to
(for
of
the
bond
to
(conjugate
path;
the
addition
Scheme
nature
of
electron-withdrawing
tertiary
has
type
in
the
the
1,b)
path; has
been
substituents
power
are
of
the
organic
catalytic
of (3)
cycle.
the
on
carbonyl
to
some is
reduce extent.
not
(from
suggested
high.
palladium-catalysed
to
of
yield)
previously
palladium
and and
2
intermediates efficiency the
Recently,
Michael
reaction
production poor
their
a
unless
the
after
However,
as
Therefore,
traces
o-alkyl
very
framework
formate),2*3
palladium
As
products). able
to
the
trialkylammonium
derivatives
compounds
system
leaves
amounts
(minor
amines
been
maintain
example
products
reducing
atom
catalytic
(4)
carbonyl
lactones
Co-H
substitution
palladium
addition
addition-type
a,R-unsaturated
acyclic
the
a,
derivatives
conjugate
the
related
to
necessary
conjugate
I),
(vinylic
effects
related
is
system
now (Table
give
steric
pathway
Pd(0)
of
HPdX
of
medium.
the
in
variable
of
effects
reducing
by formation of
terms
reaction to
an efficient will
in
electronic
According Pd(II)
followed
syn-R-elimination
mainly
S-carbon,
group,
breaking
al.
arylation
of
with use
of
cyclic
reported.’
X-
ArX R;N
I H-Pd-X
I
I Ar-Pd-X
I
R
0
Ar &k
R’
(4) -i
HASOR, X
=
Br,
R = alkyl, R’
= H
R2=E;,Su
J
(2)
R YU I
Ar
aryl aryl
alkyl
’
H Scheme
I
~l~adiurn-cattish
reaction of aryl halides
815
Table I - The Palladium-Catalysed Reaction of Benzalacetone with Aryl Halides in the Presence of Tributy1amine.a Vinylic substitution product f% yieldjb
Benzalacetone Conjugate addition type product recovered (X yield)b f% yieldjb
Aryl halide
Pd-catalyst
Phi
Pd(OAc)2(PPhS)2
74
14
4-MeO-C6H4-I
Pd(OAc)2(PPh3)2
47
34
4-MeO-C6H4-I
Pd(OAc12
-7c
40
22
5=
4-MeO-C6H4-I
Pd(OAc)2[Pto-To~)3]2 57
17
15=
4-HO-C6H4-I
Pd(OAc)2(PPh3)2
46
40
13c
4-MeCO-C6H4-Br
Pd(OAcf2fPPh312
84
__
__
4-MeCO-C6H4-8r
PdfOAc)2[P(o-To113]2 97
_-
__
a) Reactions were carried out at 60 OC (6 hf in DMF by using the following molar ratios: benzalacetone:ArX:n-8u3N:Pd-catalyst= 1:1.5:2.5:0.03. b) Yields refer to single, non optimized runs. c) As E/Z mixture.
Since
the
extension of the vinylic substitution reaction to 8-substituted-a,R-enones
and -enals would provide a significative widening of the scope of this methodology in organic synthesis, it seemed to us of interest to expend efforts in seeking methods to control the reactivity of (2) in order to favour
the formation of vinylic substitution
products. The results of this study are reported hereafter. Discussion Selecting benzalacetone and phenyl iodide as different yield
conditions*, by
using
NaHC03
we as
have the
succeded base
and
to
obtain
n-Bu4NCl
as
model
systems
and
after
screening
in
4,4-diphenyl-3-buten-2-one phase-transfer
catalyst
as
reported
70% by
Jeffery:**’ *
by reacting benzalacetone with phenyl iodide in the presence of palladium example, catalyst,' an excess of NaHC03, and n-Bu4FHS04 only traces (Z-4%) of the vinylic substitution product were isolated (benzalacetonewas recovered in 80 % yield; 8 h, 60 OCf suggesting a dependence of the reaction course on the nature of the anion of the ammonium salt. However, the use of LiCl instead of n-3u4NC1 afforded the vinyl& substitution derivative in 71% yield (benzalacetonewas recovered in 78 % yield; 8 h, 60 OCf showing the need for a more lipophilic cation. This result, unsatisfactory from a synthetic point of view, may be of interest if compared to the almost complete absence of products observed when the reaction was carried out in the presenee of NaHC03 alone. It merits a For
note
**
that
n-8u4WS04
reaction
of
phenyl
isolated
in
40% and
Benzalacetone obtained
only
was iodide
found with
59% yield,
to
be
less
efficient the
than
3-buten-Z-one
in
presence
respectively;
3-buten-2-one:PhI
n-8u4NCl of
NaHC03 = 1:2,
in
the
Pd-catalysed
(benzalacetone WF,
was recovered in 84% yield and the vinylic substitution in traces by substituting Pd(OAc)2(PPh3)2for Pd(OAcf2.
24
h,
was
3OV).
product
was
A.
816
.&ORESE
et al.
Pd(OAc12 n-Bu4NC1, ,h&‘Me
+
NaHC03 >
Phi DMF,
Ph
60°C
Me Scheme
These bromides
conditions
(Table
derivatives
2,
in
have entries
b,e)
in
or
by
anion
was
(Table
2,
substituting found
i,m,u).
Interestingly
the
of
n-Bu4NC1.
conditions
of
It
The
of
those -
with
amines
MeS03H with
an efficiency
type
using
with -
AcOH,
a
product
tertiary was
entry
CF3COCH or
comparable
to
entry
c).
with
other
yield
The
that
amine always also
c).
MeS03H observed
in
20% yield
in
reacted
to
be
in
the
reduction tertiary
3,
Ph
R3N, Me
+
usual
in
case
the
recovered
iodide
one -
the
and
the
a,d,g,l),
(results
Table
palladium
amines
in
entries
major
reaction, of
under
the
(benzalacetone
phenyl
CF3CODH
this
in
obtained
this
(Table
with
well
traces.
with
base
in
as
even
AcONa
that
Pd-catalyst 0
groups
than
found
with
acetate
better
the
allows
the
and
as
least
of
iodide
obtained At
entries
reaction
was
a dramatic 2,
functional
only
strongly
(Table
presence
the
and
substitution
we observed
mixture
of
iodides
containing
phenyl
was formed was
aryl
vinylic
cases,
(benzalacetone
benzalacetone
3,
obtain
reaction
with
of
halides
these
the
NaHC03
AcOH were
Table
to aryl
significantly
or
product
obtained
or
1)
when
addition-type
b,e,f,h,i,m tertiary
by
yield
increased
result
addition
acid
2,
variety
4,4-diphenyl-3-buten-2-one
a
that,
above
benzalacetone
produced
(Table
conjugate
acetic
conjugate to
of
of
the
the
a
failed
In
(Table
of
reaction
we
a,d). to
NaHC03
anion
yield),
noteworthy
acid
increase
for
preserce
entries
acetate
tributylamine
is
presence
68%
2,
for
an
n-Bu4NC1
in
unchanged).
similar
The
without
recovered
presence
the
cause
the
acetic
AcONa
to
in
(Table
by adding
entries
absence
was
yield
satisfactory However,
yield
groups
the
found
h,l,n,q,s).
satisfactory
electron-withdrawing increase
been
II
3,
very entries
combination
species
to
of occur
HCOOH.
Ph
0
J-AMe
HB
Phi
Ph
DMF, 60-80°C
56-85% R = Et,
n-Bu;
BH = A&H,
The
CF3COOH,
question of
reactivity addition
and
MeS03H
thus
arises
o-alkylpalladium
vinylic
substitution.
on
how
amines,
intermediates
acids (2)
and
and control
NaHC03 the
or
AcONa
balance
can
between
Scheme
III
affect
the
conjugate
Palladium-catalysed
Table
2 -
Vinylic Aryl
Substitution Halides
Aryl
Entry
Derivatives
and
Obtained
Reaction
Time
Vinylic
(h)
product
Ae
6
15
(70)
97:3
(--)
98:2
11
Ce
6
87
(10)
97:3
4-OHC-C6H4-Br
Ae
24
_-
(--)
11
Be
24
64
(25)
96:4
Af
24
39
(58)
91:9
Bf
24
42
(56)
94:6
Ae
6
52
(37)
91:9
Be
*
74
(12)
97:3
Af
4.5
64
(30)
98:2
Cf
3.5
78
(18)
g8:2
Phi
Af
8
73
(21)
--
II
0f
8
70
(23)
Cf
8
74
(21)
--
4-MeO-C6H4-I
Af
3.5
82
(13)
82:18
*,
Cf
3.5
84
(12)
85:15
4-HO-C6H4-I
Af
3
96
(--)
56:44
3-MeOCO-C6H4-I
Af
7
36
(56)
98:2
Bf
8
47
(48)
98:2
0
I*
(9
##
11
Reactions
,,
were
carried
out
by using
the
following
A = benzalacetone:ArX:n-Bu4NC1:Pd(OAc)2:NaHC03 B = benzalacetone:ArX:n-Bu4NCl:Pd(OAc) refer in
to
single
determined
by
reasonable amines
‘H-NMR
coordination
of
the
be
involved
anionic
in
moiety
the the of
state7
formation
carbonyl
of group
decomposition this
loose
runs,
with
based
of
= 1:1.5:1::0.03:4:1.7;
a
(2)
reaction on
the
to
high
the
anionic
addition-type
stabilize
a-alkylpalladium
are
starting
amine
conjugate to
and
recovered worked-up
be
the
of
of
may
strongly ability
analysis
ratios:
= 1:1.5:1:0.03:1.7.
the
explanation
transition
favours
to
-_
1:1.5:1:0.03:4;
2:NaHC03:AcOH
optimized
refer
pentacoordinated
the
non
parentheses
molar
=
C = benzalacetone:ArX:n-8u4NCl:Pd(OAc)2:AcONa
tertiary
relative
84
,I
of
percentagesd
6
11
A
E/Z
(% yield)b’c
Be
4-MeCONH-C6H4-I
were
substitution (4)
(1
I,
Figures
Reaction
1,
3-MeCO-C6H4-Br
Yields
Palladium-Catalysed
1,
I,
b)
the
conditions
halide
4-MeOCO-C6H4-I
c)
in
817
Benzalacetone.a
4-MeCO-C6H4-Br
a)
reaction of aryl halides
as
a the
negative proton
species.
given
for
pure
material. mixtures.
e)
assumption
source
products.
on
in
the
and on for
percentages f)
can
products charge
80°C.
that
palladium’ character
isolated
d)Relative
60°C.
the
presence
produce Co.
can
This
a
late
behaviour
be facilitated
the
Co.
The
the
protonation
of
by
acid
could of
the
818
Table
A. AMOB
3 -
Catalysts, Phenyl
Entry
Amines,
Tertiary
and
et al.
Acids,
in
the
Reaction
of
Senralacetone
with
Iodide.a
Base
Acid
Pd catalyst (5
Time
mol X)
Total
(h)
yield,
,
Products %
yield
%
Starting
Conjugate
Vinylie
material
addition
substitution 20 :7
a
EQN
ACOH
PdlC
5%
4
87
10.3
69
b
Et3N
CF3CDOtl
Pd/C
5%
4
89
24.7
67.4
7.9
C
Et3N
MeS03H
Pd/C
5%
4
07
16.7
70.7
12.6
d
n-Bu3N
ACOH
Pd/C
5%
4
65
10.8
86.2
3
e
n-Bu3N
CF3COGH
Pd/C
5%
4
55
3.1
90.8
6.1
fC
n-Bu3N
CF3CODH
PdlC
5%
4
69
5.8
94.2
Qc,d
n-Eu3N
ACDii
Pd/C
5%
15
80
8.7
91.3
herd
n-8u3N
CF3CODH
?d/C
5%
15
79
7.6
92.4
ic,e
n-Bu3N
CF3COOH
Pd~OA~~2{PPh3~2
7
90
17.1
88.9
lc,e
n-Bu3N
AcOH
Pd(OAc)2(PPh3)2f
7
76
700
mc,e
n-Su3N
CF$OOH
Pd(OAc)2(PPh3)2f
7
05
100
a)
Unless
mmal
of
otherwise phenyl
catalyst
in
DMF (Imlf
of 0.34 mmof of
The rotation
d)
(2)
under
At
allows
carried
out
tertiary
an
60°C.
the
of
argon
e> At
Ca-Pd
fl
breaking
ho-C~bond~syn-~-h~dridopa~ladium
has
already in
the
IO
been
suggested
palladium
catalysed
3.42
8.98
mmol of mm01
b)
atmosphere.
7O*C,
bond
with
amine,
the
products with
were
mmol
80aC
n-Bu4NI.
intermediates
could
at
around
compounds
15.23
protonation
addition-type
reactions
noted,
iodide,
of
benzalacetone, acid,
GLC yield.
mmol
of
cb In the presence
mol %.
to
occur
faster
than
elimination. to
8.16
0.017
allow
reaction
the
the
sequence:
Protonation
formation
of
arylmercury
amines,
the
of
8,Q
of
conjugate
and
8
aryltin
a,&-enones.
When NaHC03
and
AcONa
are
be favoured
by a reduced
substituted extent
of
for &a-W
tertiary bond
cleavage
in
the
B-elimination transition
of state
HPdX
and/or
Palladium-catalysed
a minor
availability
of
protons
HPdX
the
presence
of
these
with
phenyl
in
benzalacetone conditions
a
mixture
substitution 39-40X
yield.
conjugate-addition product
was The
observed
vinylic
vinylic
variable
shift
shifted
the
ruled
in
ring.
with Table
the
presence
Decomposition
major
palladium
promote
mixture
of for of
or
the
and
tha
and
was as
these vinylic
recovered
the
in
base,
vinylic
the
substitution
Eu(fodb that
olefinic
are
E/Z
of
of
the
in (4d)
donor
in
the
to
an
ratio
Presence
of
6 Values
(ppm;
CDC13ITMS)
6.65
6.73
-0.08
6.73
6.76
-0.03
0.4
10.83
10.83
0.00
0.8
10.63
10.47
0.16
acetate
in
medium,
however,
o-alkylpalladium acetic
be
range invariably
of
the
closer
the
of
group to
the
conformation
(products the
from results
Variable
A6 = 6E-6Z
0.0
protic
of
Eu(dpm)g
0.2
the
presence the
example,
Z isomer
a
the
4.
E isomer
of
main to
was
isomers
As Table
in
of
major
the
the
power
found
irrespective
to
in
proton
the
were
assigned.
summarized
Mixture
the
revealed
Eu(dpm)g
olefinic
protons
E-configuration
(4d)
or
the
E-isomers,
conceivably
of
species
products
independently
in
analyses
arylpalladium
substitution
showed
isomers,
anti-
stereochemistry
X-ray
of
precedented”
less
HPdX.
reagents
ratio
a
and
acid
has
does
not
intermediate been
reported
appear derived
to
occur
HPdOAc .I0
to from through
play
a
chalcone
dominant and
role. phenyl-
syn-R-elimination
of
OAc Ph
Ph&‘Ph
of
Under
yield)
Et3 N
of
reaction
AcONa.
material
observed
syn-addition
was
the
the
‘H-NMR
vinylic
ring
of
of
models,
thus
4 -&Values
of
could
fact,
shift
aromatic
Eu(dpm)3/substrate
The
71% yield
B-elimination
in
(22-24%
using
in
the
NaHC03
starting
but
ground
from
of
Dreiding
Amounts
*
derive
molar the
From
E/Z
In
mixtures
molecule;
the
the
syn-R-elimination
syn-addition/syn-B-elimination) obtained
isolated
on
paramagnetic
all
on
the
obtained.
AcONa
out
to
and E/Z
the
greater
by
The
derivatives.
of
of
site
was
give
obtained
and
derivative
was
reagent/substrate
coordination adopted
was
bond
spectra
aromatic
result
n-Bu4NCl
conditions,
NaHC03 and
products
double
0.2-1.0
on the
that
HPdX
amounts
HCODH,
the
to
only in traces.2
substitution
‘H-NMR
by
819
tendency
addition-type
related
substitution
carbon-carbon
yield)
derivative
hypothesis of
The
confirmed
conjugate
closely type
-8-elimination main
the
is
medium*.
Pd(OAcI2,
(26-29%
Under
the
bases
iodide,
of
derivative
from
reaction of aryl halides
o
- HPdOAc
+ PhH Ph
H
PhJ&
Ph 75%
A. Amom.%
820
Results The low
yield.
(5)
was
the
of
isomeric Only
observed
Whatever
the
E/Z
the
2,
of
entry
of
this
4-hydroxy
and
most
s),
the
likely
reported
were
the
result
a
of
an
vinylic
next in
E/Z
amount
phenolic
methyl
substitution
very of
isomerization
free
the
section. only
significant
the of
the
obtained
of
by
substitution
the
in
usually
favoured
may be,
affords
are
formation
as
product,
q,r)
(41) (5)
group
behaviour
entries
2,
(4a)
derivatives
syn-S-elimination
reason
(Table
compounds
substitution
(Table
real
of
presence
formed
proton
usual
analyses
vinylic in
initially
labile
X-ray
al.
et
of group.
group
derivative
for
the
in
the
ratio. 0
Ar
(5) As concerns based
on
the
containing
a).
~-al~ylpalladium 1 ,3-dienes13
have
induced
ally1
of a the
acetates
acetate
acetate
mechanisms been acetate
IV,
the
anion
o-alkylpalladium
complexes12
(Scheme of
of
Related
palladium monoxide
reduction
of
attack
IV,
carbon
effect
formation
intramolecular (Scheme
the
b), to
acetate
moiety
on
involving
a
suggested
to
migration and
of
and
for
terminal
on
reaction
and
its
the
palladium
to
palladium-catalysed the
is
seven-membered for
an
regio-
through
and
IV,
basic proposed
transition
state
stereochemistry
an unsaturated 1,4-functionaly~ation
(Scheme
explanation
tentatively
cyclic
palladium-catalysed
alkenes14
course,
decomposition
S-hydrogen
the
account
from
the
regioselective
carbon
of
ligand of
in
cyclic formate
c).
Me
a Ar
H
*&tR1+.
MeCCCti
+
Pd(O)
Me
I 0-o
3 J gi
I
oAo
b
-A-
+ +
Pd(O)
co:!
+
Pd(O)
Scheme
IV
Palladium-catalysed
R-Hydrogen agreement
abstraction
with
electronic
both
effects
(greatest
in
groups;
4-acetylphenyl entries
b and In
various
the
in
Table
2).
Table
noting
the
5 the
B-carbon
atom
aryl
halides
main
products
arising
that
the
the
to
be
and
readdition-elimination
+
of
rings
is
NaHCOS
halides
as
compounds
obtained
with
(Table
mixtures
of
5,
or
bearing and
vinylic
Ar
bases
group
acetate
m,
n).
derivatives
and
summarized.
alkyl
without
entries
with (compare
the
are an
In (6),
It
on
even
with
these most
the
cases likely
HPdX species:
ArX
W (4)
R = Et;
as
susbtrates
more
reacted anion
AcONa
in
strongly
conceivably
when
trifluoroacetate
either
is
and
containing
elimination
basic
groups
E/Z
aromatic
species
syn-S-elimination)
less
aryl
were
from
unchanged
carbonyl
results
the
derive
recovered
using
electron-withdrawing
found
R’
of
-enals
same
o-alkylpalladium
hydridopalladium
obtained or
the
with
was
a,f3-unsaturated
essentially containing
from
cases
to
products
observed
presence
results
with
were
are
these
R-substituted-a,R-enones
worth
(main
benzalacetone
bromide c,
complexed
results
effects
Furthermore,
difficult).
acetate
stereochemical
electron-withdrawing
is
by the
821
reaction of aryl halides
(6)
n-Pr
= 4-MeCO-C&H4 Scheme
In
conclusion,
palladium with
intermediates
aryl
simple
halides
and
materials
The
through
The
are
reported
derived
from
be effectively tool
subtle
stereochemistry established of
these
coordinates
listed
results
to
the
this
the
of
by
different in
paper
reaction
controlled
select
changes
in
the
show that
reactivity
of
S-substituted-a,R-enones nature
synthetic
reaction
the
of
pathways
the for
and
base the
o-alkyl-
thus
-enals
providing
a
same starting
medium.
Structure
unambiguously structures
can
efficient
Crystal
atomic
the
V
in
Table
of
by X-ray
compounds and 6.
the
thermal
vinylic crystal
exhibiting parameters
substitution structure the of
products analysis.
E configuration the
non-hydrogen
(4a)
Figure of
the atoms
and
(41)
1 shows vinylic of
the
double the
two
has
been
molecular bond. structures
The
A. AMORESE et al.
822
Table 5 - Vinylic Aryl
Substitution
Halides
and
a,&Unsaturated
Entry
carbonyl
Derivatives
Obtained
R-Substituted-a,R-Enones Aryl
halide
in
the
and
Reaction
compounds
Palladium-Catalysed
Vinylic
conditions
Reaction
of
Enals.a
substitution
product
(4)
E/Z
(% yield)b’c
relative
percentagesd
0 a
Phi
Ae
43
(55)
b
Phi
Ce
57
(39)
C
4-HO-C6H4-I
Ae
67
(30)
63:37
d
4-MeCONH-C6H4-I
Ae
84
(14)
83:17
e
4-MeCO-C6H4-Sr
Cf
46
(38)
87:13
f
Phi
Ae
81
g
3-HOCH2-C6H4-I
Ae
60
(20)
g1:g
h
4-M&O-C6H4-Sr
Af
36
(60)
8g:ll
Cf
66
(30)
gg:i
4-HO-C6H4-I
Agye
74
(20jh
5g:41
4-MeCO-C6H4-Br
Ag,f
16
(51jh
g2:8
CS,f
15
(60jh
g8:2
cg,f
17
(52jh
g6:4
,I
,,
4-MeCO-C6H4-Sr
a)
Reactions
were
carried
out
(8
h)
by using
the
following
A = benzalacetone:ArX:n-BuqNC1:Pd(OAc)2:NaHCO3 Yields
refer
c)
Unless
otherwise
d)
Relative
e)
60°C.
(41),
single
80°C.
bond
Unusual -and they
non
stated,
percentages f)
The values.
to
g)
were 24
h.
distances values can
h)
and are
Yield
the
by
of
the
valence observed
to
the
and
are
parentheses
determined
only
be ascribed
runs,
in
ratios:
= 1:1.5:1:0.03:1.7.
optimized
figures
molar
-
= 1:1.5:1:0.03:4;
C = benzalacetone:ArX:n-BuqNCl:Pd(OAc)2:AcONa b)
-
‘H-NMR E/Z
given
refer of
angles
generally
in
extreme
bad
pure
isolated
products.
the
for
recovered
starting
material.
of
worked-up
reaction
mixtures.
analysis
mixture
the
to
location
of
vinylic
fall part
the
derivative
within of
atoms,
(6).
the
the
range
of
accepted
ring
of
compound
benzene
due
to
their
large
thermal
factors. In
the
the
aromatic
the
planes
corresponding
of
solid
state,
rings
and
the
rings
values
for
of
the
molecules
the
vinylic
A and
S and
compound
(41)
of
the
moiety. that are
two In
of 58
the and
compounds
compound double 37’.
show
(4a), bond
These
a
the C(4)=C(5)
structural
similar dihedral are
arrangement angles 59
and
parameters
of
between 20”. lead
The to
a
823
PalIadium~a~alysed reaction of aryi halides
Fig.
1 -
Molecular
structures of (4a) and (41).
nearly perpendicular orientation of the two aromatic systems, being 7Q" the angle between their best planes in both the molecules.Jhe groups -COMe and -NHCOMe, substituents of the B ring of the two molecules, are almost coplanar with this ring, being 12 and 15" the angle between their planes in compound (4a) and 1411, respectively. A major
difference between the structures is found in the conformation of the -COMe
group at C(4) with respect to the rest of the molecule. The carbonyl C(21=0(3) is anti-periplanar, in f4af, and syn-periplanar, in (411, to the double bond C(4t=C(5). This conformationalvariation may be attributable to a higher efficiency of the crystal packing, which in both cases is mainly governed by Van der Waals forces. In the crystal of compound (411, molecules
related
by two-fold screw axes are also linked by intermolecular hydrogen
bonds involving N(18) and O(201, with the following geometrical parameters:N(18)....0(20)= 3.05 A, H(N(l8))....Of20) = 2.09 il,N(16)-H....0(20) = 172.6O and C(l9)=O(ZO)....H(Nfl8)~= 150.40. EXPERIMENTAL M.ps were determined with a Bijchi510 apparatus and are uncorrected. All starting materials, catalysts and solvents are commercially available and were used without further purification.
4-Acetylaminophenyl
iodide,
as
well
as
3-carbomethoxy-
and
4-carbomethoxy-
and 3-iodo and was prepared from 4-iodobenroic acids according to standard methods. I-Phenyl-I-penten-3-one commercially available l-penten-3-oneand phenyl iodide according to Jeffery.' Reactions were carried out on a 0.62-4.0 mmol scale. phenyl
iodides
were
prepared
from
commercially
available
4-aminophenyl
iodide
A. AMORESE et al.
824
Table 6 - Atomic coordinates
and isotropic
thermal parameters
with their e.s.d.'s
in parentheses.
x
Compound
Compound
(4a)
(41)
z
C(1)
-0.0905(3)
C(2) O(3) C(4) C(5) C(6) C(7) C(8) C(9) C(10) (x11) C(12) C(13) C(14) C(15) C(16) C(17) C(18) O(19) C(20)
-0.0580(3) -0.1372(2) 0.0732(2) 0.1581(2) 0.1239(2) 0.1887(3) 0.1561(3) 0.0578(3) -0.0070(3) 0.0263(3) 0.2894(2) 0.3425(3) 0.4631(3) 0.5384(2) 0.4876(2)0.3644(2) 0.6708(3) 0.7038(2) 0.7622(3)
0.0083(3) 0.0275(2) 0.0134(2) 0.0524(2) 0.1196(2) 0.1942(2) 0.1885(2) 0.2600(2) 0.3366(2) 0.3424(2) 0.2724(2) 0.1285(2) 0.0417(2) 0.0510(2) 0.1444(2) 0.2313(2) 0.2231(2) 0.1472(2) 0.0778(2) 0.2332(3)
0.1345(3) 0.2729(3) 0.3141(2) 0.3635(2) 0.3470(2) 0.2338(2) 0.1561(2) 0:0518(2) 0.0236(3) 0.0990(3) 0.2042(3) 0.4467(2) 0.5363(2) 0.6292(2) 0.6368(2) 0.5485(2) 0.4554(2) 0.7369(2) 0.8225(2) 0.7327(3)
C(1) C(2) O(3) C(4) C(5) C(6) C(7) C(8) C(9) (x10) C(ll) C(l2) C(13) C(14) CC151 C(16) C(l7) N18) C(19) O(20) cc211
0.4023(S) 0.3575(4) 0.2644(4) 0.4279(4) 0.4245(3) 0.3572(4) 0.2340(S) 0.1695(6) 0.2399(8) 0.3605(7) 0.4181(S) 0.4944(4) 0.4758(4) 0.5406(4) 0.6294(3) 0.6492(4) 0.5825(4) 0.6999(3) 0.7288(4) 0.6946(3) 0.8091(5)
-0.4406(4) -0.3036(3) -0.2341(3) -0.2626(3) -0.1402(3) -0.0188(3) 0.0552(4) 0.1719(4) 0.2016(4) 0.1331(S) 0.0218(4) -0.1211(3) -0.2176(3) -0.2005(3) -0.0857(3) 0.0119(3) -0.0049(3) -0.0591(2) -0.1474(3) -0.2668(2) -0.0873(3)
0.4124(2) 0.3880(2) 0.4199(l) 0.3222(l) 0.2921(l) 0.3250(2) 0.2892(2) 0.3239(3) 0.3914(4) 0.4239(3) 0.3920(2) 0.2235(l) 0.1710(l) 0.1067(l) 0.0934(l) 0.1454(l) 0.2087(l) 0.0294(l) -0.0225(l) -0.0199(l) -0.0832(2)
a) B(eq) = (413) Eijaiajbij.
B(eqja 6.2(l) 4.5(l) 6.4(l) 4.2(l) 3.7(l) 3.6(l) 4.4(l) 4.8(l) 5.1(l) .5.1(l) 4.5(l) 3*9(l) 4.4(l) 4.6(l) 4.0(l) 4.2(l) 4.2(l) 4.6(l) 6.5(l) 6.7(l)
7.6(l) 5*4(l) 7.8(l) 5.4(l) 4.8(l) 5.6(l) 7.9(l) 10.4(2) 10.9(2) 10.4(2) 7.5(l) 4.7(l) 5.1(l) 5.0(l) 4.6(l) 5.4(l) 5.5(l) 4.9(l) 4.0(l) 6.2(l) 6.4(l)
Palladium-catalysed
The equipped -
products with
from
Waters
eluting
‘H-NMR
spectra
IR
the
A -
iodide phenyl
of
This
(Table
5,
iodide
(0.587
mmol)
in
mmol)
in
nitrogen
DMF (1
ml).
residue
was
The
compound
(4f)
Procedure
g, is
bromide
(Table
2,
entry
bromide
(0.517
g,
2.60
AcCH
(0.166
(0.012 80
ml, 0.051
g,
“C under
purified (4b)
a
by
Procedure
C -
mmol) in
in
ml). for
HPLC eluting Reaction
with
diethyl
ether
and IR
ml)
3.47
(s,
Reaction
0.8 of
of
mixture were
with was added,
aryl
Co.)
internal
halides g,
and
phenyl mmol), g,
(0.0129
stirred
added,
with 1.92
(0.645
NaHCg
Pd(OAc12
at
the
g,
60
at
a 9515
n-hexane/AcOEt
reduced
7.68 0.0576
“C
organic
concentrated
with
of
g,
benzalacetone (0.250
1.70
under
layer
a was The
pressure. mixture
up
NaHC03 to
to
give
with
before
afforded
4-acetylphenyl
mmol),
4-acetylphenyl
(0.544
g,
a
purged
as
a 80120
with
1.70
stirring
was
Work
g,
mmol),
with
mixture
6.80
solution
nitrogen
n-hexane/AcOEt
H);
a
were
a 75125
of and
a
to
mmol), Pd(OAcj2
stirred
residue
mixture
benzalacetone
stirred the
at
at
which
give
was
compound
with
phenyl
benzalacetone
g,
1.70 of and at organic
60
5H);
iodide, g,
formic
acid
under
layer
(0.012
g, g,
(0.109 a
was
ml,
nitrogen separated,
was
; ’
H-NMR: Hz,
and
in
mmol)
atmosphere washed
for with
was 8
(4
h;
water,
16% yield) (m,
3.65
(s,
(m,
(1
g,
ml)
ml).
added h;
The 24
preparative
8.12-7.88 H);
(0.530
DMF
DMF
ml).
2H);
1.2
H);
3H).
bicarbonate
iodide in
was
51 %; mp = oil;
1.1-0.73
sodium
g,
ml)
with g,
g,
6
(0.591
for
by
(0.076
0.4
2H);
phenyl mmol)
purified
(4m) (0.246
(m,
78% yield).
DMF (0.5
residue
mmol)
2.90
in
washed
J = 6.7
nitrogen
DMF (1
separated,
acid
0.051
in
was
1.78-1.77
6.80
g,
atmosphere
cm-l
a
by preparative
bromide
mmol)
purified
mmol),
under
(0.371
mmol)
compound
(t,
formic 1.70
a
2.90 mmol)
m)
7.92
0.059
further
5.7
“C
g,
0.051
nitrogen
give
843
H);
(m,
g,
The
(4m)
entry
g,
layer to
958;
0.6
5,
g,
purified
4-acetylphenyl
OC under
not
NaHC03(0.571
Pd(OAcj2 “C
was
(0.250
mmol),
80
pressure.
1269;
2.38-1.85
(0.0133
mixture
Hz,
3H);
of
(0.665
organic
which
1606;
J = 6.7
NaHC03 at
the
(Table
60
was
4-acetyl-
(0.238
(0.012
at
which
mmol),
AcONa
Pd(OAc)2
compound
mmol),
4-acetylaminophenyl
1.70
mmol),
stirred
give
1.98
Pd(OAc)2
reduced
(6m)
to
g,
1.70
of
and
bromide
stirred
added,
1680;
solution
of
g,
a residue
g,
mmol),
and
compound
(s,
nitrogen
with
(0.250
a solution
mixture
(0.250 1.98
benzalacetone
(0.472
afforded
n-hexane/AcOEt
(t,
to
with
before
solution
water
2.55
n-8u4NC1
stirring
purged
g,
concentrated
nitrogen
mmol),
of
benzalacetone
4-acetylphenyl
nitrogen
6.13
reaction of
n-hexane/AcOEt
with
1712;
A solution
purged
to
2H);
a
and
added
h.
by the
up as
(0.550
film)
to
6 with
with
and
of
stirring
The
for
3-octen-2-one
mixture
(0.472
and
mmol), of
were
reaction
was
solution
was
Work
a 50150
and
n-Bu4NC1
)
(0.472
ml).
2.60
added
mixture h.
and
(m,
(TMS
(0.307
nitrogen water
benzalacetone
ml)
eluting
A
g,
was
The
with
(liquid
7.58-7.25
HPLC
(0.678
3.5
(MgSO4) an E/Z
DMF (1
m).
purged
HPLC eluting
spectrometer
1.92
solution
with
the of
DMF (3
exemplified
stirring
was
p(Amicon
1-phenyl-1-penten-3-one
g,
a
and
(MgS04
by
atmosphere
n-Bu4NCl
mixture dried
in
3-octen-2-one
mmol),
added
in
is
A solution 2.97
mmol)
entry
with
of
20-45
Yvon
detector
spectrometer.
compounds
of
(0.534
HPLC eluting
n-8u4NC1
2,
DMF (3
DMF (I
Jobin
index
microanalyses.
to
purged
A solution
This
iodide
atmosphere
gel
from
84% yield).
(Table
aminophenyl
silica
1-phenyl-1-penten-3-one
ether
dried
mmol),
nitrogen
g,
was
FT/IR
carbonyl
stirring
exemplified b).
mmol)
10
refractive
81% yield).
preparative
(0.377
iodide
2.90
Prep
and
EM-390
50X
reaction
of
diethyl
h;
water,
This
the
n-8u4NCl
with
by preparative
(0.453
B -
mmol),
mixture 8
with
purified
with
Varian
a,B-unsaturated
solution
added
a
satisfactory
by
A
2.88
for
washed
separated,
system
packed
a Nicolet
gave
of
f).
was
atmosphere
columns
with
exemplified g,
ml)
(Chromatospac
delivery
with
recorded
reaction
entry
DMF (4
compressed
products
is
HPLC
solvent
recorded
were
isolated
procedures
Procedure
preparative -
mixtures.
were
spectra
of
by 500A
on axially
n-hexane/AcOEt
standard).
General
purified
LC/System
Ass.)
with
All
were
a Prep
825
reaction of aryl halides
all dried
mmol),
added
The
diethyl
water,
2.60
was
mixture at
ether
once. and
(MgS04)
with was The water and
A. AMORESE et al.
826
Table
7 -
Characterization Reaction
Compound
of
of
Vinylic
Benzalacetone
M.p.
(4)
4-MeCD-C6H4
83-84
(E
Isomers)
229-230
b
the
6 ( ppm) CDCl3
1655,
1696,
from
1 H-NMR
777,
1606, 703a
1655,
826,
Derived
Halides
(cm-‘)
1680, 843,
4-CtiC-C6H4
Aryl
I.R.
V
( OC)
Ar
Products
Substitution
with
777,
1606,
7.95
(d,
7H)
6.61
10.07
703’
J=8.2
Hz,
(s,lH),
(s,
IH),
7.62-7.15
2H),
7.57-7.16
2.56
(s,3H),
7.88
(m,
(d,
J
(m, 1.87
= 8.2
7H)
(s,3H)
Hz,
2H),
7H),
6.65
(s,
IH),
1.90
(s,
9H),
6.62
(s,
IH),
2.28
(s,
3H) 4-MeDCD-C6H4
63-64
1721,
1655,
1606,
7.63-7.07
1286,859,769,703a 3-MeCD-C6H4
222-223b
1688,
1655,
802, 4-MeCONH-C6H4
121-122
777,
3312, 1589, 777,
Ph
99-l
oob
1589,
6.62
1688,
1663,
8.47
1179,
835,
(s,
4-HO-C6H4
1663,
1606,
1688,
1655,
761, 3-MeOCD-C6H4
183-184b
b)
KBr.
E/Z
As
the
(bs,
2H),
lH),
7.61-6.94
2.53 IH),
(s,
(s,
3H),
(m,
IOH
,
7.76-6.78
(m,
9H)
3H),
(s,
3H)
(m,
3H),
1.88
7.73-7.10
2.14
7.58-7.08
1589, 777,
(m, 1.88
(s,
7H),
(s,
3H)
9H),
6.60
3H)
1729,
1.86
1.85
1688,
1663,
(m,
(s,
1.68
8.25-7.92 (s,
2,4_dinitrophenylhydrazone.
c)
6.58
(s,
IH),
1.81
3H)
7.58-6.52
695’
1606,1294,761,703c
a)
(m, (s,lH),
(s,
1253,835,769,703’ 3410, 835,
oil
3H)
703a
1688,
179-180b
(s,
8.07-7.81
695’
1589,777,761,703’ 4-MeD-C6H4
(m,
3H),1.88
(s,
Ill-l),
IH),
3.82
(s,
(s,
1.32
H),
1.93
H)
(m,2H),
IH),
Liquid
6.62
3.87
7.62-7.12
(s,
film.
d)
3H),
(m,7H),
1.87
Isolated
(s,
and
6.62
3H)
analyzed
as
mixture.
concentrated eluting
at
substitution yield
reduced a
with
residue
n-hexanelethyl conjugate
product,
88 %) whose
The
pressure.
80120 relative
was
acetate
addition-type
percentages
filtered
product,
(29.5
on
mixture
%,
to and
25 %,
a
short
give
a
starting
45.5
%,
silica
gel
mixture
vinylic
benzalacetone
respectively)
column
of
(overall
were
determined
by ‘H-NMR. Reaction
of
benzalacetone
A solution n-8u4NCl (4
ml)
(0.472
g,
was added
(1
ml).
The
all
at
once.
as
before
mixture The
and 43
Crystal
%,
n-hexane
1.70
mmol),
with
stirring
was
;
was
a
starting
and
plate
NaHC03 with
measured MO-Ka unit-cell
with
radiation,
a Syntex
in e-28 were
yield
crystals
space
yellow
groups
Weissenberg
mode;
derived
(0.012
acid
a
2.91
0.051
ml,
2.90
whose
mmol),
mm011
for
conjugate relative
2.60 mmol)
mmol)
atmosphere
product, %)
g,
g,
9,
(0.109
nitrogen
93
(0.530
AcOH (0.174
Pd(OAcl2
formic
acetate
iodide
8
in
DMF
in
DMF
was added h.
Work
up
addition-type
percentages
(31
%,
by ‘H-NMR.
pale
quality,
automatic
scan
mmol),
of
sodium
determinations
and P2,
and phenyl
substitution
(overall
The
oscillation
8.55
OC under
determined
prismatic
poor
g,
acid
mmol),
and
60
vinylic
structure
colourless
dimensions
at
of
formic 1.70
solution
nitrogen
benzalacetone
shaped,
from
a
stirred
were
g, (0.923
to
dichloromethane/n-hexane.
determined
iodide,
(0.250
mixture
crystal
shaped
phenyl
purged
mixture
respectively)
data Well
with
benzalacetone
afforded
product, 26 %,
from
of
of
(4a)
and
by
compound
least-squares
of The
equipped (411
grown
Cu-K, calculations
from
compound
approximated
photographs.
diffractometer for
were
crystals
unit-cell
data
graphite
radiation of
were
was the
obtained
parameters
intensity with
dichloromethane/
(41)
were
(4a)
were
monochromator
and
used.
angular
of
The
refined
settings
of
Palladium-catalysed
Table
8 -
Characterization Reaction
Compound
of
Ph
Ph
Vinylic
and
v (cm -’
(OC) 191-192a
H
-fnals
(E
with
Isomers)
Aryl
from
the
’ H-NMR
6
)
2844,1663,1589, 1122,
Derived
Halides
I.R.
M.p. R’
Products
Substitution
l3-Substituted-o,O-Enones
(4) R
Ar
of
827
reaction of aryl halides
769,
695b
9.60
(d,
(m,
IOH),
(ppm)
J=8.2
WC13
Hz,
6.62
lH),
(d,
7.64-7.18
J
= 8.25
Hz,
0.63
H),
H),
7.63-6.50
1H) Ph
4-HO-C6H4
H
3181,1663,1639,
oil’
1606,1286, 777, 4-MeCONH-C6H4
Ph
H
248-24ga
744,
835, 703bvc
9.60
(d,
J=8.2
Hz,
(d,
J=8.2
Hz,
0.37
(m,
11H)’
3312,1663,1598,
9.56
(d,J=8.2
835,
lH),
7.82-7.18
744,
703b
J = 6.2 4-MeCO-C6H4
Ph
H
91-93
1680,1655,1598,
9.65
835,
J = 8.2
761,
695d
lH), = 9.2
(s,
Hz,
lH),
Hz,
(d,
3H) 8.02
7.64-7.22
J =8.2
(bs,
6.56
2.16
Hz,2H),
(d,
8.67
(m ,SH),
Hz,
(d,J
6.64
Hz,lH),
9.47
(d,
(m,7H),
IH),
2.60
(s,
3H) Ph
Ph
131-132a
Et
1688,1663,1589,
7.62-7.12
769,
2.25
695b
(m,
(q,
J = 6.7 3-HOCH2-C6H4
Ph
Ph
177-l
78a
1220, 777, 4-MeCO-C6H4
Ph
n-C5Hl
I
101-102a
859,
Hz,
13H),
794,
Hz,
6.62
(s,
2H),
0.93
lH), (t,
3H)
8.05-7.82
3443,1655,1598,
lOHI,
J =6.7 (m,
4.67
2H),
(s,
7.62-7.08
(m,
2.17
1H)
2H),
(bs,
703b
1688,1606,1269,
7.97
826,
(m,7H),
777,
703b
(d,
J = 8.7Hz,2H), 6.65
2.25
(t,
(m,
6H),
7.58-7.12
(s,lH),
J=6.7
2.56
Hz,
0.82
(s,3H),
2H),
1.72-0.98
J
(t,
= 6.7
Hz,
3H) 4-HO-C6H4
n-C3H7
oil’
H
3443,1663,1605,
10.17
1220,
(d,
J=8.2
8.2
Hz,0.82
835b*C
(d,
1.18
J=8.2 Hz, H),
n-C3H7
Me
19%197a
6.94
6.36
(d,
J = 8.2
(d,
J=8.2
7.5
Hz,
Hz,
1.18
1680,1598,1269,
8.05
958,
J = 8.2
826b
0.82
Et
Me
194-195a
1680,1598,1269,
8.10
958,
8.2
826b
(m,
Hz,2H), (m,
(m,
Hz,2H),
J=
2H),
7.64
6.52
(d,
(s,
2.6
lH1,
(s,
3H),
(m,
4H),
3 H) Hz,2H),
6.52
-1.18
6.15 (t,
J = 7.5
1.57-1.07
(m,
J=8.2
(t,
2H),
(d,J=8.2 Hz,2H),
2H),
H), 3.00
2.57
2H),
3H),
1.00-0.67 4-MeCO-C6H4
H),
Hz,
Hz,
3HjC
J=8.2
(s,
9.53 (d,J=
(d,J=8.2
J =8.2
1.77-1.32
(m, Hz,
H), 7.48
Hz,0.59
H),
H),
3.19-2.90 2.28
(d,
Hz,0.41
(d,
0.41 H),
7.21
H),
1.05-0.78 4-MeCO-C6H4
Hz, 0.59
2.62
2H),
7.64
(s,lH), 0.92
(d, 3.07
(s,3H), (d,
J= (t,
1.68-
J=8.2
Hz,
3H) a)
As the
mixture.
2,4_dinitrophenylhydrazone. d)
KBr.
b)
Liquid
film.
c)
Isolated
and
characterized
as
E/Z
A. AMORESEet al.
828 15 selected
reflections.
Crystal
data
b = 11.80(i), g/cm3,
k(Mo-Kc)
= 0.8
Crystal
data
b = 9.978(2),
compound i,
cm-‘,
of
sine
The
intensity
reveal
cm-‘,
sin s /X < 0.61
multisolution block-diagonal last
few
(Rw
= 0.073)
and
for
the
cycles
of
and
R =
to
dimensions
0.4x0.5x0.5
2543
for
three
data
(41).
those
the
density,
their
calculations.
(Rw
=
0.117)
atomic
for
I>20
the
= 8.042(2), DC =
1.21
which
did
the
1804
were
crystal
were
by
refined
by
located
on
kept
converged
structure
of
2327
solved
were
atoms
unique and
were
parameters
refinements
2975
(I),
parameters
hydrogen
The
a = 4,
reflections,
structures
atomic
11.65(l), DC = 1.21
mm.
Of
having The
The
calculations;
least-squares
standard
=
mm.
0.7x0.4x0.07
collections.
elucidation.
SIR-CAOS”.
electron
0.082
dimensions
using the
structure with
of
crystal
monitored
least-squares
syntheses
i-‘,
during
methods
(9x9) Fourier
the
(4a),
used
direct
difference
were
variations for
were
crystal
Mw = 279.339, monoclinic, C18H-l?ND2* 8 = 94.61, U = 1531 i3, space group P 21/a, 2
measurements
measured
respectively,
k’,
a
2 = 4,
(41):
i,
significant
reflections
/X
compound
= 6.4
monoclinic, Cl aH16OZ 1 Mw = 264.324, U = 1450 i3,space group P 21/a,
(4a):
I3 = 114.5(l),
c = 19.143(3)
g/cm 3, ~(CU-Ko) not
of
c = 11.60(2)
to (4a)
fixed
in
R =
0.047
and
(41),
respectively. All
the
calculations
crystallographic Full bond
were
software lists
distances
of
atomic
and
valence
Crystallographic
Data
Acknowledgements Istruzione
-
performed
SIR-CAOS15;
on
Data
General
scattering
and
anisotropic
coordinates angles,
a
atomic with
MV 8000
factors thermal
e.s.d.‘s,
have
II
were
computer,
taken
from
coefficients
been
deposited
at
using
the 16
literature. and
tables
the
Cambridge
of
della
Pubblica
Centre.
The
was
research
by a
supported
grant
from
Minister0
(Italy).
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