- Email: [email protected]
alkylation: direct one-pot conversion of 1-alkynes to E-1,2-disubstituted alkenes
Tetrahedron Letters, Vo1.32, No.41. pp X47-5650. 1991
0040.4039/91
Printed in Great Britain
Pergamon Press plc
HYDROZIRCONATION
/ TRANSMETALATION
CONVERSION
OF l-ALKYNES
Bruce
University
Abstract.
Hydrozirconation
zirconate with a higher variety of electrophiles. In a recent report’ with higher mixed vinylic
order
cuprates
Department
of
California,
cyanocuprate
we disclosed
to a$-unsaturated
and
Kaneyoshi
the tendency
cyanocuprates
Barbara,
mixed vinylic
cuprates
CA
93106
These
to arrive at products
4. 3
of the intermediate
which
undergo
alkylations
1 to undergo ligand exchange
of vinylic zirconates2
(e.g., 2).
transmetalations
3, which can then be used to selectively
ketones
Kato#
Chemistry
Santa
affords
ONE-POT
ALKENES
of terminal acetylenes followed by transmetalation
order
(H.O.)
DIRECT
TO E-1,2-DISUBSTITUTED
H. Lipshutz”
of
/ ALKYLATION:
proceed
deliver the olefinic
While this new technology
rapidly
-
THF, rt
1.
cp’
15 mm
‘cp
MeLI, -75”
)
R*
Cu(CN)Li,
2. Me$u(CN)LI2 (2), -78’
residue in a Michael
works well for conjugate
sense add-
Me
’It is not applicable
to the other
main mode of cuprate
toupling;
of this type it is the al/ry/ group, e.g., in 3, which
Given the procedural
simplicity
arriving
at vinylic
cuprates
problem
(as shown in Scheme
of this process, we endeavered
capable
R 3 cl
1
with electrophiles
enone -
/
cl itions,”
processes
0 R*Zr,C’
CppZr(H)CI
H
vinyl with a
at -78” to afford
R II
$3.00 + .@I
of effecting
1) which thereby
alkylations. extends
transmetalations.6
2. (P-Th)Cu(CN)LI
5647
reactions,”
released
since
from copper.5
to find an equally simple yet related method for
the desired significantly
i.e., substitution
is preferentially
We now report a solution
the usefulness
to this
of H.O. cuprate-mediated
5648
Following
an early recipe from the NilssonlUllenius
2-thienyl
(2-Th)
nitrile group) inducing
moiety
in
in, e.g., 5.
transmetalation
work with vinvlic
R(2-Th)Cu(CN)Li2
Our
plan,
(Scheme
we previously
school,6
demonstrated
the attributes
or “dummy”
ligand
as a non-transferrable
therefore,
anticipated
the use of cuprate
of the
7 (as is the
Me(P_Th)Cu(CN)Li2,
6, for
, which looked promising in light of earlier
2), in place of Me2Cu(CN)Lip
stannanes.”
+ Cp,ZrMe,
7 cl Initial experiments streamline
on 1 using
the procedure
combination
of PMeLi
smoothly. iodide. olefin
in Table
1, reactions
Under our standard
MeMgCl
in place
which reacts
the need
pursued. lo
was
in either of MeLi,
with
however,
epoxides,
were
reaction conditions case. 12
halides,
examples
these substrates
a presumed
mixed
metal cuprate
with primary
triflates
CpsZr(H)CI 2MeMgCI, -78”
3.
ThCu(CN)LI -78 to -2O”, 30 mln
are fully consumed,
IScheme
triflate
results,
but
relatively
bromide
and
yet none of the alkylated
(vinyl)(2_Th)Cu(CN)LiMgBr, (Scheme
i.e., switching
to
8, is produced,’
3
3).14
rrC6H13
I-*
/ ?WI,oOBn (76%)
1
*
rrC6H13,+
AcO(CH&OTf
3)
to
alternative
occur
primary
modification;
*
=H
*CsH,s
the
it led to identical
and a vinyl
BnO(CHs)roOTf 1. 2.
However,
of 6,’
of an unactivated
In time, it was found that via a trivial
best at low temperatures
successful.
formation
1
available.’
activated
the simplest
were indeed
for prior
Not surprisingly,
that both reagents are commercially
Most surprising,
is obtained
by eliminating
+ (2-Th)Cu(CN)Li
with the added advantage As illustrated
(a) MeLi and (b) Me(2_Th)Cu(CN)Li2,
still further
KW,,OAc (72%)
In summary,
a new
method
for
converting
1-alkynes
developed.15
It relies on a three step sequence
single
The mildness
flask.
and rapidity
elements
associated
with
containing
electrophilic
centers. t6
Acknowledgement.
this
Financial
Fund, and Takeda Industries,
to
frans-1,2-disubstituted
utilizing commercially
of vinylzirconatelH.0.
chemistry,
and
have
permitted
available
cyanocuprate the
first
olefins
reagents
has
and is conducted
transmetalations preparation
been in a
are two key
of lithio
cuprates
These and related studies will be reported in due course.
support
provided
Ltd., is gratefully
by the National Science
acknowledged.
Foundation,
the Petroleum
Research
5649
Table 1. Hydrozirconation Epoxide
Acetylene
PhY 0
/ Transmetalation
/ Alkylation of 1-Alkynes
Conditions
Product(s)’
Yield(%)b
OH Ph _J.,,+/c6HWn
=C6H,~-n
-78 to 0’
---C6H,3-n
-78 to 0”
=C6H,3-n
-78 to 0’
95
-78 to 0”
71
-78toO”
52
-7O”, BF3=
71
-78 to rt
95
-78 to rt
75
-78 to -40”
75
88
78
PhAOyC,H,,-n OH
I OS+ I
/y
“-fJ OTMS
-0
Cl
I7
OTf COpEt II
*C7H15
\/X
lI
no product (starting halide consumed)d
(X = I, Br)
.__________ ~~~~~~~~~__~_~__~__~~~~~~~~~~~~~~_~~~~~~~_~~~~~~~~~~~~~~~~_~~~~~~~_~~~~~~~_~~~~~~~ ‘Fully
characterized
materials.
by IR, NMR, MS, and HRMS data.
‘One equlv vs. substrate.
dSee text.
blsolated,
chromatographlcally
pure
5650
References
#
On leave from Takeda Chemical Industries,
and
Notes
Ltd., Kyoto, Japan.
E.L., J. Am. Chem. Sot., 1990,112
1.
Lipshutz,
2.
Schwartz,
B.H., Ellsworth,
3.
Babiak, K.A., et al., J. Am. Chem. Sot., 1990, m,
4.
Lipshutz,
B.H., Sengupta,
S., Org. React., in press; Posner,
5.
Lipshutz,
B.H., Kozlowski,
J.A., Wilhelm,
6.
For related work using catalytic
7.
Lipshutz, 1985,
B.H.,
m,
Kozlowski,
Malmberg,
9.
Behling, JR,
H., Nilsson,
10.
Lipshutz,
11.
Cyanocuprate
Parker,
M., Parker,
(2-Th)Cu(CN)Li
The explanation
using
longer
coupling.
effect
transfer/reduction,
S.L.,
McCarthy,
J. Organomet. Chem.,
K.E.,
mixed
vinylic
elimination,
Aldrich
(cat.
in the desired fashion
3823.
945.
#32,417-5).
may lie in the incompatibility
Under the elevated
cuprates,
Halide
Letters, 1982, a,
2641.
from
Cp2ZrMe2.
temperatures
it is likely that 5 is altered
consumption
etc.) initiated
B.H., et al., Tetrahedron,
Lipshutz,
253.
3928.
R.E., Diss. ETH Nr. 8507, Zurich 1988.
Tetrahedron Letters, 1987,28,
D.A.,
is available
for the lack of coupling
displacements
A primary
G.H., ibid., 1972, I_$, 1; 1975,22,
D.A., J. Org. Chem., 1984,49,
Nguyen,
C., Tetrahedron
M., Ullenius,
5 and the Lewis acidic by-product,
14.
D.A.,
et al., J. Am. Chem. Sot., 1988,11p,
B.H., Koerner,
13.
R.S., Parker,
CuCN, see Lehmann,
J.A.,
333.
7441.
437.
8.
12.
7440.
J.A., Angew. Chem. IN. Ed. Engl., 1976,x,
J., Labinger,
may
reflect
required
for
in such a way that it can no
competing
processes
by either a Cu or Zr species,
1986, 42,
of cuprates
normally
(e.g.,
electron
or both.
2873.
iodide gave a low yield (ca. 27%) under these conditions,
while the corresponding
bromide
did not react. 15.
A typical
procedure
for the preparation
with a stir bar was charged evacuated by
the
stirred MeLi
addition
of
(0.95
(45
subsequently
mg,
was
to -78”
and
stirred
for
mg,
in saturated
washed
water,
hexane)
Cm-l
2935,
3.34
(2H,
2861, d, J=6.6
calcd for C,sH,sOSi Lipshutz,
THF
again
and stirring
with
in
being
cone NH40H
in
mmol)
and the suspension
After (40
thiophene
The solution
mg,
flask equipped The flask was
0.23
mmol)
aqueous
(46 mL, 48 mg, 0.57
mL)
which
was
via cannula
transferred min
and then
at
-78”,
kept
the
for
lh
for an additional
NHdCI, and was followed
in vacua.
NMR
(CDCIs) 6 0.59
3.63
(2H,
t, J=6.6
219.1191;
(Received in USA 19 June 1991)
results.
found:
Hz),
at -78”
(6H,
219.1198.
followed
3h. Quenching
Column
was
bath
was
the vinyl
treated
by warming
was carried
with ether.
(59
(2H,
The
containing
chromatography
s), 0.90
(0.25 mL,
to a suspension
-78”.
solution
by extraction
5.54-5.60
to
to the solution
and concentrated
1096;
in a
to obtain a clear orange solution
resulting
l-dimethyl-1-butylsilyloxy-6-phenyl-3-pentene
(M+-Bu):
was placed
via cannula
pre-cooled
gave
B.H., Keil, R., unpublished
mmol)
was
with ethereal
and purged with Argon as above and THF (1
dried,
Hz),
mixture
and treated
was cooled to -20” to which was added n-BuLi
(1
30
The
mmol).
to -78”
warmed to room temperature
at this temperature
1354,
0.51
was then stirred for 1 h at -20” and transferred
cooled
bromide
temperature
16.
0.51
removed
zirconate.
EtOAc
round-bottom
(126 mg, 0.48 mmol).
which was cooled
The flask was evacuated
via syringe.
The solution
(95
solution
Concurrently,
flask with a stir bar.
0.50 mmol). CuCN
a clear yellow
mL, 1.04 mmol).
mL) was introduced
benzyl
hydride
l-dimethyl-t-butylsilyloxy-3-butyne
for 15 min to yield
which
A 10 mL 2-necked
chloride
and purged with Argon, the process being repeated 3 times. THF (3 mL) was injected followed
round-bottom
of
of 9 follows.
with zirconocene
with
to room
out using 10%
The extracts were
with silica gel (10% mg,
(9H,
s), 2.24
m),
7.20-7.30
95%);
IR
(neat)
(2H, q, J=6.6 (5H,
m);
Hz)
HRMS
0040.4039/91
Printed in Great Britain
Pergamon Press plc
HYDROZIRCONATION
/ TRANSMETALATION
CONVERSION
OF l-ALKYNES
Bruce
University
Abstract.
Hydrozirconation
zirconate with a higher variety of electrophiles. In a recent report’ with higher mixed vinylic
order
cuprates
Department
of
California,
cyanocuprate
we disclosed
to a$-unsaturated
and
Kaneyoshi
the tendency
cyanocuprates
Barbara,
mixed vinylic
cuprates
CA
93106
These
to arrive at products
4. 3
of the intermediate
which
undergo
alkylations
1 to undergo ligand exchange
of vinylic zirconates2
(e.g., 2).
transmetalations
3, which can then be used to selectively
ketones
Kato#
Chemistry
Santa
affords
ONE-POT
ALKENES
of terminal acetylenes followed by transmetalation
order
(H.O.)
DIRECT
TO E-1,2-DISUBSTITUTED
H. Lipshutz”
of
/ ALKYLATION:
proceed
deliver the olefinic
While this new technology
rapidly
-
THF, rt
1.
cp’
15 mm
‘cp
MeLI, -75”
)
R*
Cu(CN)Li,
2. Me$u(CN)LI2 (2), -78’
residue in a Michael
works well for conjugate
sense add-
Me
’It is not applicable
to the other
main mode of cuprate
toupling;
of this type it is the al/ry/ group, e.g., in 3, which
Given the procedural
simplicity
arriving
at vinylic
cuprates
problem
(as shown in Scheme
of this process, we endeavered
capable
R 3 cl
1
with electrophiles
enone -
/
cl itions,”
processes
0 R*Zr,C’
CppZr(H)CI
H
vinyl with a
at -78” to afford
R II
$3.00 + .@I
of effecting
1) which thereby
alkylations. extends
transmetalations.6
2. (P-Th)Cu(CN)LI
5647
reactions,”
released
since
from copper.5
to find an equally simple yet related method for
the desired significantly
i.e., substitution
is preferentially
We now report a solution
the usefulness
to this
of H.O. cuprate-mediated
5648
Following
an early recipe from the NilssonlUllenius
2-thienyl
(2-Th)
nitrile group) inducing
moiety
in
in, e.g., 5.
transmetalation
work with vinvlic
R(2-Th)Cu(CN)Li2
Our
plan,
(Scheme
we previously
school,6
demonstrated
the attributes
or “dummy”
ligand
as a non-transferrable
therefore,
anticipated
the use of cuprate
of the
7 (as is the
Me(P_Th)Cu(CN)Li2,
6, for
, which looked promising in light of earlier
2), in place of Me2Cu(CN)Lip
stannanes.”
+ Cp,ZrMe,
7 cl Initial experiments streamline
on 1 using
the procedure
combination
of PMeLi
smoothly. iodide. olefin
in Table
1, reactions
Under our standard
MeMgCl
in place
which reacts
the need
pursued. lo
was
in either of MeLi,
with
however,
epoxides,
were
reaction conditions case. 12
halides,
examples
these substrates
a presumed
mixed
metal cuprate
with primary
triflates
CpsZr(H)CI 2MeMgCI, -78”
3.
ThCu(CN)LI -78 to -2O”, 30 mln
are fully consumed,
IScheme
triflate
results,
but
relatively
bromide
and
yet none of the alkylated
(vinyl)(2_Th)Cu(CN)LiMgBr, (Scheme
i.e., switching
to
8, is produced,’
3
3).14
rrC6H13
I-*
/ ?WI,oOBn (76%)
1
*
rrC6H13,+
AcO(CH&OTf
3)
to
alternative
occur
primary
modification;
*
=H
*CsH,s
the
it led to identical
and a vinyl
BnO(CHs)roOTf 1. 2.
However,
of 6,’
of an unactivated
In time, it was found that via a trivial
best at low temperatures
successful.
formation
1
available.’
activated
the simplest
were indeed
for prior
Not surprisingly,
that both reagents are commercially
Most surprising,
is obtained
by eliminating
+ (2-Th)Cu(CN)Li
with the added advantage As illustrated
(a) MeLi and (b) Me(2_Th)Cu(CN)Li2,
still further
KW,,OAc (72%)
In summary,
a new
method
for
converting
1-alkynes
developed.15
It relies on a three step sequence
single
The mildness
flask.
and rapidity
elements
associated
with
containing
electrophilic
centers. t6
Acknowledgement.
this
Financial
Fund, and Takeda Industries,
to
frans-1,2-disubstituted
utilizing commercially
of vinylzirconatelH.0.
chemistry,
and
have
permitted
available
cyanocuprate the
first
olefins
reagents
has
and is conducted
transmetalations preparation
been in a
are two key
of lithio
cuprates
These and related studies will be reported in due course.
support
provided
Ltd., is gratefully
by the National Science
acknowledged.
Foundation,
the Petroleum
Research
5649
Table 1. Hydrozirconation Epoxide
Acetylene
PhY 0
/ Transmetalation
/ Alkylation of 1-Alkynes
Conditions
Product(s)’
Yield(%)b
OH Ph _J.,,+/c6HWn
=C6H,~-n
-78 to 0’
---C6H,3-n
-78 to 0”
=C6H,3-n
-78 to 0’
95
-78 to 0”
71
-78toO”
52
-7O”, BF3=
71
-78 to rt
95
-78 to rt
75
-78 to -40”
75
88
78
PhAOyC,H,,-n OH
I OS+ I
/y
“-fJ OTMS
-0
Cl
I7
OTf COpEt II
*C7H15
\/X
lI
no product (starting halide consumed)d
(X = I, Br)
.__________ ~~~~~~~~~__~_~__~__~~~~~~~~~~~~~~_~~~~~~~_~~~~~~~~~~~~~~~~_~~~~~~~_~~~~~~~_~~~~~~~ ‘Fully
characterized
materials.
by IR, NMR, MS, and HRMS data.
‘One equlv vs. substrate.
dSee text.
blsolated,
chromatographlcally
pure
5650
References
#
On leave from Takeda Chemical Industries,
and
Notes
Ltd., Kyoto, Japan.
E.L., J. Am. Chem. Sot., 1990,112
1.
Lipshutz,
2.
Schwartz,
B.H., Ellsworth,
3.
Babiak, K.A., et al., J. Am. Chem. Sot., 1990, m,
4.
Lipshutz,
B.H., Sengupta,
S., Org. React., in press; Posner,
5.
Lipshutz,
B.H., Kozlowski,
J.A., Wilhelm,
6.
For related work using catalytic
7.
Lipshutz, 1985,
B.H.,
m,
Kozlowski,
Malmberg,
9.
Behling, JR,
H., Nilsson,
10.
Lipshutz,
11.
Cyanocuprate
Parker,
M., Parker,
(2-Th)Cu(CN)Li
The explanation
using
longer
coupling.
effect
transfer/reduction,
S.L.,
McCarthy,
J. Organomet. Chem.,
K.E.,
mixed
vinylic
elimination,
Aldrich
(cat.
in the desired fashion
3823.
945.
#32,417-5).
may lie in the incompatibility
Under the elevated
cuprates,
Halide
Letters, 1982, a,
2641.
from
Cp2ZrMe2.
temperatures
it is likely that 5 is altered
consumption
etc.) initiated
B.H., et al., Tetrahedron,
Lipshutz,
253.
3928.
R.E., Diss. ETH Nr. 8507, Zurich 1988.
Tetrahedron Letters, 1987,28,
D.A.,
is available
for the lack of coupling
displacements
A primary
G.H., ibid., 1972, I_$, 1; 1975,22,
D.A., J. Org. Chem., 1984,49,
Nguyen,
C., Tetrahedron
M., Ullenius,
5 and the Lewis acidic by-product,
14.
D.A.,
et al., J. Am. Chem. Sot., 1988,11p,
B.H., Koerner,
13.
R.S., Parker,
CuCN, see Lehmann,
J.A.,
333.
7441.
437.
8.
12.
7440.
J.A., Angew. Chem. IN. Ed. Engl., 1976,x,
J., Labinger,
may
reflect
required
for
in such a way that it can no
competing
processes
by either a Cu or Zr species,
1986, 42,
of cuprates
normally
(e.g.,
electron
or both.
2873.
iodide gave a low yield (ca. 27%) under these conditions,
while the corresponding
bromide
did not react. 15.
A typical
procedure
for the preparation
with a stir bar was charged evacuated by
the
stirred MeLi
addition
of
(0.95
(45
subsequently
mg,
was
to -78”
and
stirred
for
mg,
in saturated
washed
water,
hexane)
Cm-l
2935,
3.34
(2H,
2861, d, J=6.6
calcd for C,sH,sOSi Lipshutz,
THF
again
and stirring
with
in
being
cone NH40H
in
mmol)
and the suspension
After (40
thiophene
The solution
mg,
flask equipped The flask was
0.23
mmol)
aqueous
(46 mL, 48 mg, 0.57
mL)
which
was
via cannula
transferred min
and then
at
-78”,
kept
the
for
lh
for an additional
NHdCI, and was followed
in vacua.
NMR
(CDCIs) 6 0.59
3.63
(2H,
t, J=6.6
219.1191;
(Received in USA 19 June 1991)
results.
found:
Hz),
at -78”
(6H,
219.1198.
followed
3h. Quenching
Column
was
bath
was
the vinyl
treated
by warming
was carried
with ether.
(59
(2H,
The
containing
chromatography
s), 0.90
(0.25 mL,
to a suspension
-78”.
solution
by extraction
5.54-5.60
to
to the solution
and concentrated
1096;
in a
to obtain a clear orange solution
resulting
l-dimethyl-1-butylsilyloxy-6-phenyl-3-pentene
(M+-Bu):
was placed
via cannula
pre-cooled
gave
B.H., Keil, R., unpublished
mmol)
was
with ethereal
and purged with Argon as above and THF (1
dried,
Hz),
mixture
and treated
was cooled to -20” to which was added n-BuLi
(1
30
The
mmol).
to -78”
warmed to room temperature
at this temperature
1354,
0.51
was then stirred for 1 h at -20” and transferred
cooled
bromide
temperature
16.
0.51
removed
zirconate.
EtOAc
round-bottom
(126 mg, 0.48 mmol).
which was cooled
The flask was evacuated
via syringe.
The solution
(95
solution
Concurrently,
flask with a stir bar.
0.50 mmol). CuCN
a clear yellow
mL, 1.04 mmol).
mL) was introduced
benzyl
hydride
l-dimethyl-t-butylsilyloxy-3-butyne
for 15 min to yield
which
A 10 mL 2-necked
chloride
and purged with Argon, the process being repeated 3 times. THF (3 mL) was injected followed
round-bottom
of
of 9 follows.
with zirconocene
with
to room
out using 10%
The extracts were
with silica gel (10% mg,
(9H,
s), 2.24
m),
7.20-7.30
95%);
IR
(neat)
(2H, q, J=6.6 (5H,
m);
Hz)
HRMS