- Email: [email protected]
Effects of Lewis acids on higher order, mixed cuprate couplings
Tetrahedron Letters,Vo1.25,No.52,pp Printed in Great Britain
0040-4039/84 $3.00 + .OO 91984 Pergamon Press Ltd.
5959-5962,1984
OF LRWIS ACIDS ON
BFFEcrS
RIGBER ORDRR, RIKRD CDI’RATR COUPLINGS
Bruce
H. Lipshntz,*l
David A. Parker, Sam L. Nguyen Department of of California Santa Barbara,
Dniversity
Joseph
Chemistry at Santa CA 93106
A. Kozlonski.
Barbara
-SUMMARY: The p~ti~ce 06 BF3-Et20 in ~~eactitti~6 R2Cu(CN)Li and R (Z-~h&xy~JCu(CNJL~ u&h epotidti and a,%-utiahtcLted keRonu Lea& to dm_m&c whhncmeti in mactioi haten andlat pmduct y&L& ~~?_ecLtiweto Rhone abnemed in tithe abbewe CJ~ tkin Lewd Acid. In bean
tracing
placed
on
potentially
1.4
developing
During
chemistry
of the
As influence conditions.
of
is
a study
of
I,
Acid
acids
need
the
more for
such
to to
be
higher highly
recently
been
of Lewis
enone),
to
compatible
with
the
5959
only
invested
mired
in
was however,
emphasis
species
a
reagent
monitored TiC14,
of
homocuprates R2Cu(CN)Li2,
RTRRCu(CNjLi2, this
lithio
i&Cl2,
the
report.
wo
cuprates.
ligand, under
a
formation.2
to
In
vinyl
has
equivalent
cyanocuprates.
on C&N-derived
of
one
relative
described.5
addition
isophorone cuprate,
that
order
Acids
conjugate
tremendous
some degree
more
vs
(1 equiv
were
of
robust
the
has
effects
extent
need
sacrificed
the
chemistry,
RTRRCuLi,
RTLi,
usually
on the
organocaprate
reagents
RR = 2-thienyl)
Table
a Lewis
of
species,
corresponding
(with
in
Most
Gilman
investigations
the
results
of
mixed
reactivity
our
which
shown
course
organolithium
cuprate
we recognized
present
evolutionary
valuable
Unfortunately, R2CuLi.3
the
under
a given
set
and SnCl4
the of all
5960
formed
insoluble
m3*Et20 also
g-s
afforded
of
addition
UpOIl
the
desired
no consequence,
to
oyclohexanone
as was
its
use
Effects
Table I.
RT(2-thienyl)Ca(CN)Li2, to
any
essentially
RT = vinyl,
significant
as
of Various
2,
at
-7goC.
&lY
Trimethylborate
degree.
was
co-solvent.6
Lewis
Acids
on the
Reaction:
(1.4 equivle
Lewis
Entry
0
i h, Lewis Acid
-78q
THF/Et20,
96 Product
Acid
Ovb
<5
1
none
2
EtAIC12
12
3
Et2AICI
8
4
LiC104
0
5
LiBr
4
‘6
TiCI,
0
7
Ti(O-(14
0
8
ZnCIz
0
9
SnCI,
0 90
10
BF,
ii
B (OCH&
1
12
AIF,
0
Bv quantitative
Et20
b
VPC analysis.
In all
cases,
(entry
10)
the remaining mass
was starting material.
Considering (entry
the
its
1).
potential
following
observations:
52% yield
of
(2)
the
impact
reaction of
following been
of
this
BF3*Et20
1,4-addition, unsuccessful.
effect an
full while
in
Bp3*~t20 was
0.26
eqniv
attempts
no
to
be
not of
trap
greater
the
alter
the
this
type;
the
at
couplings (presumably)
to
detail. as
ketone
excellent in
compared
required,
gave
advantage to
in
is
on reactions
appears
provides
probed
equivalent
100% TEF does
solvent
all
of
additive
one
addnct,
ZJBF3*EtZO combination
utilization
far
the
as (1)
conjugate
performing
well-known
dramntic
use to
of
the
reaction 7.8
the which
has
0.52
equiv
extent
(3)
the
2
boron
with
in
thermal below
secondary
enolate
reaction
lead
with
to
the
afforded
of 28k
outcome,
temperatures of
control
(by
spite
a
VPC); of
stability
the of
-25’C;’
(4)
halides;
(5)
Et1
have
thus
5961
SCHEME
I.
0
0 &
(2-Thienyl)Cu(CN)Li2 EteO / THF t-78’,
1 h)
(-78o-O:
i h)
BF3. Et,0
:
98
% (57%f
No additive
:
49
%
BF3. Et,0
: >95
%
No additive
:
:
87
% (58?‘0)~
:
77
%
0 Ph2Cu(CN)Li2 II Et,0
/ THF, -5O0.75 h
15O-
n-Bu(2-Thienyl)Cu(CN)Li2
Ph
b
-
Et,0
/ THF
( -78q
1h 1
BF,.
(
9h)
No additive
rt,
0 %
Et,0
OH i-
Et20,
a
Yield
reaction
from
n-Bu ,\” -
Bu(2-Thienyl)Cu(CN)Li2
reaction
-78O,
2h
of &Cu(CN)Li
using g-BuCu(CN)Li
+ BF3*
+ BF EtiO.
3
BF3. Et,0
:
86
NO additive
:
0
-
Et20;
b
From
% %
displacement
5962
In light and
of
2/BF3*Et20
illustrates phenyl material
is
&-2-batene noted
for In
reactions noted
by
to
cyclohexene
of
these
in
due
which
a general order
others.12.13
study11
via
Most
in
of
in
its
activation
in organomctallio
assistance
of
is
reaction
the
is
(i.e., to
natural
products
I
of
a
found
the
desired
the
case
findings
cnprate
Acids,
for and
In
Similar
been
compensate oxiranes
of
11
Scheme
1,4-addition
recovered.
Lewis
has
of both
Acid.
none
toward
of It
for
a Lewis
remarkable.
influence
to
reactions
essentially
well-behaved
ability
the
successful
being
conducted.
chemistry
the
BF3*Et20,
not
been
contrast
1.2-adduct
oftentimes
has
alone
substrate
and
rates
and
noteworthy
Without
concerning
cuprates
stands
the
material
is
compare
of were
reagents.7a.10
in
particular,
that
on
BF3*Et20,
somewhat
reduced
enones).
The
synthesis14
will
as mixed
appl ica t ions be
reported
course.
Acknowlednment. and
difference
oxide,
higher
advances
starting
to
without
isophorone.
only the
enones
out
examples.
BF3-activated
formed,
reactivity
and
representative
summary,
we set
information,
epoxides
oxide,
of
cuprate
on
four group
this
the
Petroleum
Financial Research
support Fund,
provided
by
administered
the by
National the
American
Science
Foundation
Chemical
Society,
(CRE 83-02421) is
gratefully
acknowledged. References 1. 2. 3. 4. 5. 6. 7. 8. 9.
10. 11. 12.
13.
14.
and Notes
Fellow of the Alfred P. Sloan Foundation, 1984-1986. “An Introduction to Synthesis Using Organocopper Reagents,” J. Wiley and G.E. Posner, Sons, New York, 1980. W.H. Mandeville, G.M. Whitesides, J. Org. Chem.. ae. 400 (1974). B.E. Lipshutx, R.S. Wilhelm, J.A. Koxlowski, Tetrahedron Reports, in press. J.A. Koalowski, D.A. Parker, K.E. McCarthy, S.L. Nguyen. J. Organomet. B.H. Lipshutz, Chem., submitted. M.W. Rathke, A. Lindert, J. Org. Chem., 35. 3966 (1970). C.R. Johnson, R.W. Herr, D.M. Wieland, J. Org. Chem.. 38, 4263 (1973): (b) H-0. (a) 43, 2443 (1978); (c) G.H. Posner, Org. React., 19. 1 (1972). House. J.M. Wilkins, &@., that the initial color changes accompanying introduction of the We have noted, however, substrate in Et2OjTBF do not occur in the absence of Et20. the reagent begins to darken and significantly loses its efficacy Above this temperature, (Table I) was formed after adding after warming over 30 min to OoC. 15% ketone [e.g., isophorone 1. G. Dabbagh, J. Org. Chem., 49, 1119 (1984); S.R. Bertz. G. Dabbagh, G-k S.H. lbrtz, Villacotta, J. Am. Chem. Sot., &.Q& 5824 (1982). Y. Ito, H. Imai, T. Matsuura. T. Saegusa, Tat. Lett.. 25. 3091 (1984). A.B. Smith, P.J. Jerris, J. Am. Chem. Sot., 103. 194 (1981); (b) t4.J. Eiss J.E. (a) 106, 3693 (1984); (c) M. Wada, X. Sakurai, K. Akiba, Tet. Lett., Wrobel, B. Ganem. ibid.. 25, 1079 (1984); (d) C. Mioskowski, S. Manna, J.R. Falck, ibA., 24, 5521 (1983): (e) Y. S. Yamamoto, 8. Yatagai, Y. Ishihara, K. Maruyama. J. Org. Chem.0 % 119 Yamamoto, (1982). While this manuscript was in preparation, Ghribi, A., Alexakis, A.,and Normant. J0F.p reported similar findings on epoxides, acetals, and ethers: of. Tet. Lett., 22. 3075, 3079. 3083 (1984). B.B. Lipshuts, J.A. Koxlowski, J. Org. Chem., 29, 1147 (1984). (Received
in
USA
14
August
1984)
0040-4039/84 $3.00 + .OO 91984 Pergamon Press Ltd.
5959-5962,1984
OF LRWIS ACIDS ON
BFFEcrS
RIGBER ORDRR, RIKRD CDI’RATR COUPLINGS
Bruce
H. Lipshntz,*l
David A. Parker, Sam L. Nguyen Department of of California Santa Barbara,
Dniversity
Joseph
Chemistry at Santa CA 93106
A. Kozlonski.
Barbara
-SUMMARY: The p~ti~ce 06 BF3-Et20 in ~~eactitti~6 R2Cu(CN)Li and R (Z-~h&xy~JCu(CNJL~ u&h epotidti and a,%-utiahtcLted keRonu Lea& to dm_m&c whhncmeti in mactioi haten andlat pmduct y&L& ~~?_ecLtiweto Rhone abnemed in tithe abbewe CJ~ tkin Lewd Acid. In bean
tracing
placed
on
potentially
1.4
developing
During
chemistry
of the
As influence conditions.
of
is
a study
of
I,
Acid
acids
need
the
more for
such
to to
be
higher highly
recently
been
of Lewis
enone),
to
compatible
with
the
5959
only
invested
mired
in
was however,
emphasis
species
a
reagent
monitored TiC14,
of
homocuprates R2Cu(CN)Li2,
RTRRCu(CNjLi2, this
lithio
i&Cl2,
the
report.
wo
cuprates.
ligand, under
a
formation.2
to
In
vinyl
has
equivalent
cyanocuprates.
on C&N-derived
of
one
relative
described.5
addition
isophorone cuprate,
that
order
Acids
conjugate
tremendous
some degree
more
vs
(1 equiv
were
of
robust
the
has
effects
extent
need
sacrificed
the
chemistry,
RTRRCuLi,
RTLi,
usually
on the
organocaprate
reagents
RR = 2-thienyl)
Table
a Lewis
of
species,
corresponding
(with
in
Most
Gilman
investigations
the
results
of
mixed
reactivity
our
which
shown
course
organolithium
cuprate
we recognized
present
evolutionary
valuable
Unfortunately, R2CuLi.3
the
under
a given
set
and SnCl4
the of all
5960
formed
insoluble
m3*Et20 also
g-s
afforded
of
addition
UpOIl
the
desired
no consequence,
to
oyclohexanone
as was
its
use
Effects
Table I.
RT(2-thienyl)Ca(CN)Li2, to
any
essentially
RT = vinyl,
significant
as
of Various
2,
at
-7goC.
&lY
Trimethylborate
degree.
was
co-solvent.6
Lewis
Acids
on the
Reaction:
(1.4 equivle
Lewis
Entry
0
i h, Lewis Acid
-78q
THF/Et20,
96 Product
Acid
Ovb
<5
1
none
2
EtAIC12
12
3
Et2AICI
8
4
LiC104
0
5
LiBr
4
‘6
TiCI,
0
7
Ti(O-(14
0
8
ZnCIz
0
9
SnCI,
0 90
10
BF,
ii
B (OCH&
1
12
AIF,
0
Bv quantitative
Et20
b
VPC analysis.
In all
cases,
(entry
10)
the remaining mass
was starting material.
Considering (entry
the
its
1).
potential
following
observations:
52% yield
of
(2)
the
impact
reaction of
following been
of
this
BF3*Et20
1,4-addition, unsuccessful.
effect an
full while
in
Bp3*~t20 was
0.26
eqniv
attempts
no
to
be
not of
trap
greater
the
alter
the
this
type;
the
at
couplings (presumably)
to
detail. as
ketone
excellent in
compared
required,
gave
advantage to
in
is
on reactions
appears
provides
probed
equivalent
100% TEF does
solvent
all
of
additive
one
addnct,
ZJBF3*EtZO combination
utilization
far
the
as (1)
conjugate
performing
well-known
dramntic
use to
of
the
reaction 7.8
the which
has
0.52
equiv
extent
(3)
the
2
boron
with
in
thermal below
secondary
enolate
reaction
lead
with
to
the
afforded
of 28k
outcome,
temperatures of
control
(by
spite
a
VPC); of
stability
the of
-25’C;’
(4)
halides;
(5)
Et1
have
thus
5961
SCHEME
I.
0
0 &
(2-Thienyl)Cu(CN)Li2 EteO / THF t-78’,
1 h)
(-78o-O:
i h)
BF3. Et,0
:
98
% (57%f
No additive
:
49
%
BF3. Et,0
: >95
%
No additive
:
:
87
% (58?‘0)~
:
77
%
0 Ph2Cu(CN)Li2 II Et,0
/ THF, -5O0.75 h
15O-
n-Bu(2-Thienyl)Cu(CN)Li2
Ph
b
-
Et,0
/ THF
( -78q
1h 1
BF,.
(
9h)
No additive
rt,
0 %
Et,0
OH i-
Et20,
a
Yield
reaction
from
n-Bu ,\” -
Bu(2-Thienyl)Cu(CN)Li2
reaction
-78O,
2h
of &Cu(CN)Li
using g-BuCu(CN)Li
+ BF3*
+ BF EtiO.
3
BF3. Et,0
:
86
NO additive
:
0
-
Et20;
b
From
% %
displacement
5962
In light and
of
2/BF3*Et20
illustrates phenyl material
is
&-2-batene noted
for In
reactions noted
by
to
cyclohexene
of
these
in
due
which
a general order
others.12.13
study11
via
Most
in
of
in
its
activation
in organomctallio
assistance
of
is
reaction
the
is
(i.e., to
natural
products
I
of
a
found
the
desired
the
case
findings
cnprate
Acids,
for and
In
Similar
been
compensate oxiranes
of
11
Scheme
1,4-addition
recovered.
Lewis
has
of both
Acid.
none
toward
of It
for
a Lewis
remarkable.
influence
to
reactions
essentially
well-behaved
ability
the
successful
being
conducted.
chemistry
the
BF3*Et20,
not
been
contrast
1.2-adduct
oftentimes
has
alone
substrate
and
rates
and
noteworthy
Without
concerning
cuprates
stands
the
material
is
compare
of were
reagents.7a.10
in
particular,
that
on
BF3*Et20,
somewhat
reduced
enones).
The
synthesis14
will
as mixed
appl ica t ions be
reported
course.
Acknowlednment. and
difference
oxide,
higher
advances
starting
to
without
isophorone.
only the
enones
out
examples.
BF3-activated
formed,
reactivity
and
representative
summary,
we set
information,
epoxides
oxide,
of
cuprate
on
four group
this
the
Petroleum
Financial Research
support Fund,
provided
by
administered
the by
National the
American
Science
Foundation
Chemical
Society,
(CRE 83-02421) is
gratefully
acknowledged. References 1. 2. 3. 4. 5. 6. 7. 8. 9.
10. 11. 12.
13.
14.
and Notes
Fellow of the Alfred P. Sloan Foundation, 1984-1986. “An Introduction to Synthesis Using Organocopper Reagents,” J. Wiley and G.E. Posner, Sons, New York, 1980. W.H. Mandeville, G.M. Whitesides, J. Org. Chem.. ae. 400 (1974). B.E. Lipshutx, R.S. Wilhelm, J.A. Koxlowski, Tetrahedron Reports, in press. J.A. Koalowski, D.A. Parker, K.E. McCarthy, S.L. Nguyen. J. Organomet. B.H. Lipshutz, Chem., submitted. M.W. Rathke, A. Lindert, J. Org. Chem., 35. 3966 (1970). C.R. Johnson, R.W. Herr, D.M. Wieland, J. Org. Chem.. 38, 4263 (1973): (b) H-0. (a) 43, 2443 (1978); (c) G.H. Posner, Org. React., 19. 1 (1972). House. J.M. Wilkins, &@., that the initial color changes accompanying introduction of the We have noted, however, substrate in Et2OjTBF do not occur in the absence of Et20. the reagent begins to darken and significantly loses its efficacy Above this temperature, (Table I) was formed after adding after warming over 30 min to OoC. 15% ketone [e.g., isophorone 1. G. Dabbagh, J. Org. Chem., 49, 1119 (1984); S.R. Bertz. G. Dabbagh, G-k S.H. lbrtz, Villacotta, J. Am. Chem. Sot., &.Q& 5824 (1982). Y. Ito, H. Imai, T. Matsuura. T. Saegusa, Tat. Lett.. 25. 3091 (1984). A.B. Smith, P.J. Jerris, J. Am. Chem. Sot., 103. 194 (1981); (b) t4.J. Eiss J.E. (a) 106, 3693 (1984); (c) M. Wada, X. Sakurai, K. Akiba, Tet. Lett., Wrobel, B. Ganem. ibid.. 25, 1079 (1984); (d) C. Mioskowski, S. Manna, J.R. Falck, ibA., 24, 5521 (1983): (e) Y. S. Yamamoto, 8. Yatagai, Y. Ishihara, K. Maruyama. J. Org. Chem.0 % 119 Yamamoto, (1982). While this manuscript was in preparation, Ghribi, A., Alexakis, A.,and Normant. J0F.p reported similar findings on epoxides, acetals, and ethers: of. Tet. Lett., 22. 3075, 3079. 3083 (1984). B.B. Lipshuts, J.A. Koxlowski, J. Org. Chem., 29, 1147 (1984). (Received
in
USA
14
August
1984)