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Lithium norcaranylidenoids. Alkylation and epimerization
0040-4039/85 $3.00 + .OO 01985 Pergamon Press Ltd.
Tetrahedron Letters,Vo1.26,No.44,pp 5371-5374,1985 Printed in Great Britain
LITHIUM NORCARANYLIDENOIDS. ALKYLATION AND EPIMERIZATION’ Philip M. Warner,* Suae-Chen Chang and Nicholas J. Koszewski Chemistry Department, Iowa State University, Ames, IA 50011 The epimeric 7-bromo-7-lithionorcaranes have been stereospecifically Summary: exo-bromo isomer is stable at -78"C, while the endo- bromo isomer is reactive. stereochemistry of its reaction with nBuLi involves inversion.
The recent report'
of a partially
tBuLi prompts us to communicate in the stereospecifically of the Skattebol
similar
generated
results
carbenoids
of la and lb,
rearrangement'
of the latter was preceded
invertive
alkylation
in a cyclopropylidenoid
vinylidenoid system.
2a3-' and 2b3-5 was stimulated where
by its epimerization
of a lithium
it appeared
generated; The
reasonable
the
with
Our interest
by our studies6
that rearrangement
to the former.
2a
B
Br
1. -78"Cj 30 min. 2. MeOD/-95°C
1
2
X = Li, Y = Br
a,
b, X = Br, Y = Li
3-d
a, X = Li, Y = Br b, X = Br, Y = Li c, X = SnMe3,
Y = Br
d, X = Br, Y = SnMe3
Generation min.).
of carbenoid
When 2a was warmed
2a from stannane
2~ was effected at -95°C' in THF (5 eq. nBuLi, 5
to -78°C for 30 min., followed
with MeOD, only 3-d resulted.
by retooling
Thus, 2a was stable at -78°C.
Epimeric
sized from 2da at -95°C in THF (3 eq. nBuLi, 20 min.), ' behaved Now, quenching
of the retooled
time, up to 5 main products
2b
2b solution with Me00
(eqn. l)."*"
4
to -95°C
and quenching
carbenoid
2b, synthe-
quite differently
(-95°C) gave, depending
The overall yield of these products
4-d 5371
3-d
5-d
at -78°C.
upon reaction was 60-70%.
6
5372
The ratios of the products O-8 min. at -78°C.
were determined
Reasonable
pseudo-first-order
4-d) = (5.9 + 0.4) X 1O-3 Sd; From the ratios of 3-d:5-d:6, 12 fi; InBuLij = 0.05 M13): Scheme
by analytical
kobs (production their relative
gc for reaction
kinetics13
times varying
were observed:
kobs
from
(loss of
of 5-d and 6) = (5.8 + 0.4) x 10s3 set-l.
rates of formation
were calculated
(using [THFJ =
kl/k3 : 1.3 M; k2/k3 z 160.
I MeOD
/+Br
l
3-d
2a
Li k2CBuLi-i
MeOD
>
5-d
>
ti 2b
7
;;;” H
\
k3CTHFl
>
0
6
Mechanistically, pathways set -’
. l4
The important
relatively
can be interpreted
conclusions
slow at -78"C, although
la conversion;6 reevaluated undergoes
the results
for the demise of 2b (Scheme
I).
are:
to see whether
stereoselective
involves a nucleophilic
(1) epimerization
rapid enough
this means that previously
encountered
attackI
The higher temperature
insertion!' with
chemistry
3
2a -50°C:
18
-25°C:
0
:
apparent
2a is
with the aforementioned epimerizations
via bimolecular
should
exchange;8
alkylation;
lb to
be
and (2) 2b
alkylation
of configuration.
of carbenoid
to other products, 3a those shown in eqns.
kl= 3.5 x 10m4
of 2b to the more stable
and stereospecific
inversion
competitive
one can calculate
to be consistent
they might have proceeded solvent
in terms of three parallel
From such a scheme,
2a was investigated
(2) and (3) were found
briefly.
in the indicated
5
8
6
6
8
13
8
7
19
In addition ratios
for
(3)
5373
reactions
at -50°C and -25"C,
-5O"C,
and only nBu4Sn at -25°C.
random
at -50" to -25°C.
equilibrium
Also,
respectively.
nBu3SnMe
and nBu4Sn were both formed
It can be seen that carbenoid
In our view, these results
with its less stable, more reactive
butylation
are best explained
epimer,
is fairly
by assuming
at
stereo-
2a is in
2b, which is the source of 5 and 6
(eqn. 4).
8
< MeOH
BuLi
2a
/
7
2b
THF BuLi
>
6
+
7
MeOH
,
8
(4)
9 Further
studies
of the kinetic
behavior
of lithium carbenoids
will be reported
in due
course. References
and Notes
1.
We gratefully Foundation.
2.
Duraisamy,
3.
2019; (b) Skattebol, L. (a) Moore, W. R; Ward, H. R.; Merritt, R. F. ibid. 1961, E, Acta. Chem. Stand. 1963, 17, 1683; (c) Marquis,. T.; Gardner, P. 0. J. Chem. Sot., Chem. Commun. 1966, 726.
4.
Kobrich,
5.
acknowledge
M.; Walborsky,
G.; Goyert,
partial
support
of this work by the National
Science
H. M. J. Am. Chem. Sot. 1984, 106, 5035.
W. Tetrahedron
1968, 2,
4327.
(a) Moore, W. R.; Ward, H. R. J, Org. Chem. 1960, 3, 2073; (b) ibid. 1962, 27, 4179; (c) Jr., M.; Petrillo, Jr., E. W. Tetrahedron Lett. 1969, 3953; (d) Paquette, L. A.: Taylor, R. T. J. Am. Chem. Sot. 1977, 99, 5708.
Jones, 6.
Warner,
7.
Skattebol,
a.
Seyferth,
9.
The amount of nBuLi used was determined by what was required for complete disappearance of 2d in reasonable time (given the difficulty of maintaining the -95°C temperature bath for long times'). Thus 2d still remained after 40 min. with 2 eq. nBuLi, and after 10 min. with 3 eq. nBuLi.
10.
Almost all the 4 was produced in the initial exchange reaction at -95°C. Thus MeOD quenching of the 2d/nBuLi/-95°C reaction after 6 min. at -95°C gave the same deuterium incorporation result as after 20 min. at -95"C, namely a s. 55:45 ratio of 4-d:4; the amount of 4 remained approximately constant over time at -78"C, while 4-d decreased (in accord with it being the quench product from 2b). The production of 4, suggestive of electron transfer in the -95°C carbenoid formation step, is apparently related to the amount of n-BuLi used; further studies are in progress.
11.
In addition to these products, ~5% of the two binorcaranylidene dimers3a*'2 were formed (but not included in our analysis). Intramolecular insertion products3a do not arise from 2b.
12.
Fukuda,
13.
Formation
P. M.; Herold,
R. D. J. Or-q. Chem. 1983, 48, 5411.
L. Tetrahedron 0.; Lambert,
Y.; Yamamoto,
1967, 23,
1107.
Jr., R. L.; Massol,
Y.; Kimura,
M. J. Organomet.
K.; Odaira,
of 6 is pseudo-first-order,
Chem.
Y. Tetrahedron
while production
of 5-d
1975, 88, 255.
Lett. 1979, 877. is approximately
so under our
5374
conditions. We use an [nBuLiJi = 0.076 i. After formation of 2b, [nBuLi] = 0.05 M. This represents a ca. 8 fold excess over that amount of 2b which reacts with nBuLi to eventually give 5-d. However, the situation is complicated by the loss of some nBuLi via its to give nBu SnMe2. reaction with nBuSnMe In any event, we do not observe the fall-off in the production of s -d which wou fd be expected if the pseudo-first-order approximation were grossly incorrect. 14.
This represents an "overall" rate constant; we cannot yet address involving aggregation effects," ion pair behavior,L6~17 etc.
15.
Seebach,
16.
Kitatani,
17.
(a) Schleyer, P.; Clark, T.; Kos, A. J.; Spitznagel, G. W.; Rohde, C.; Arad, D.; Houk, K. N* Rondan, N. G. J. Am. Chem. Sot. 1984, 106, 6467; (b) Mareda, J.; Rondan, N. G.; Houk, K:'N.; Clark, T.; Schleyer, P. ibid. 1983, 105, 6997; (c) Luke, B. T.; Pople, J. A.; Schleyer, P.; Clark, T. Chem. Phys. Lett. 1983, 102, 148.
18.
Taylor,
19.
At times there appears to be some confusion regarding the overall mechanism of carbenoid it might nucleophilically attack RX alkylation. Because a carbenoid is ambiphilic," (itself generated via the initial metal-halogen exchange with RLi). While such a reaction Thus we have found that i is possible,21 it is not the source of alkylated cyclopropane. + CH3Li in CH31/Et20 (]CD3Il/]CH3Lil = 5.1) at room temperature gave iv (7% isolated) with only ca. 8% CD3 (92% CH3), with that amount having arisen from reaction of the CD3Li In the absence of MeI, the epimeric IO-bromo-IO-methylgenerated 6 the final step. [4.3.l]propellanes were formed in a 12:l ratio, with vi predominating. While vi was
0.; Hassig,
R.; Gabriel,
K.; Yamamoto,
K. G.; Chaney,
kinetic
questions
J. Helv. Chim. Acta 1983, 55, 308.
H.; Hiyama,
J.; Deck, J.
T.; Nozaki,
C. J.
H. Bull. Chem. Sot. Jpn. 1977, 3,
2158.
Am. Chem. Sot. 1976, 98, 4163.
CH3Li
rt, lh
,
s3w_ gH3+
CD3Li
...
111
ii
L
(JPJ
L
V
&+ii
vi
produced in -1% yield in the presence of MeI, a control experiment showed it did not give v was always the major product (63% iv under the reaction conditions. As reported," of iv and the on 2, it is clear that. the stereochemistry isolated). _ _ of . the work . . . In view reglochemistry of L-H insertion are due to the predominance of carbenoid ii, which is Lastly, for the carbenoid generation method thermodynamically preferred over its epimer. used herein, nucleophilic attack on RX is precluded by its absence. 20.
(a) Seebach, il.; Oammann, R.; Lindner, H. J.; Kitschke, B. Helv. Chim. Acta 1979, 62, 1143; (b) Kirmse, W. "Carbene Chemistry," 2nd edition, New York: Academic Press, 1971, p. 97; (c) Taylor, K. G. Tetrahedron 1982, 38, 2751.
21.
Siegel,
22.
(a) Paquette, L. A.; Chamot, W. R.; Hall, S. S.; Largman, Dissertation , Massachusetts
H. Top. Curr. Chem.
1982, 106, 55. E.; Browne, A. R. J. Am. Chem. Sot. 1980, 102, 637; (b) Moore, C. Tetrahedron Lett. 1969, 4353; (c) Boardway, N. L.. Ph.0. Institute of Technology, 1970.
(Received in USA 14 June 1985)
Tetrahedron Letters,Vo1.26,No.44,pp 5371-5374,1985 Printed in Great Britain
LITHIUM NORCARANYLIDENOIDS. ALKYLATION AND EPIMERIZATION’ Philip M. Warner,* Suae-Chen Chang and Nicholas J. Koszewski Chemistry Department, Iowa State University, Ames, IA 50011 The epimeric 7-bromo-7-lithionorcaranes have been stereospecifically Summary: exo-bromo isomer is stable at -78"C, while the endo- bromo isomer is reactive. stereochemistry of its reaction with nBuLi involves inversion.
The recent report'
of a partially
tBuLi prompts us to communicate in the stereospecifically of the Skattebol
similar
generated
results
carbenoids
of la and lb,
rearrangement'
of the latter was preceded
invertive
alkylation
in a cyclopropylidenoid
vinylidenoid system.
2a3-' and 2b3-5 was stimulated where
by its epimerization
of a lithium
it appeared
generated; The
reasonable
the
with
Our interest
by our studies6
that rearrangement
to the former.
2a
B
Br
1. -78"Cj 30 min. 2. MeOD/-95°C
1
2
X = Li, Y = Br
a,
b, X = Br, Y = Li
3-d
a, X = Li, Y = Br b, X = Br, Y = Li c, X = SnMe3,
Y = Br
d, X = Br, Y = SnMe3
Generation min.).
of carbenoid
When 2a was warmed
2a from stannane
2~ was effected at -95°C' in THF (5 eq. nBuLi, 5
to -78°C for 30 min., followed
with MeOD, only 3-d resulted.
by retooling
Thus, 2a was stable at -78°C.
Epimeric
sized from 2da at -95°C in THF (3 eq. nBuLi, 20 min.), ' behaved Now, quenching
of the retooled
time, up to 5 main products
2b
2b solution with Me00
(eqn. l)."*"
4
to -95°C
and quenching
carbenoid
2b, synthe-
quite differently
(-95°C) gave, depending
The overall yield of these products
4-d 5371
3-d
5-d
at -78°C.
upon reaction was 60-70%.
6
5372
The ratios of the products O-8 min. at -78°C.
were determined
Reasonable
pseudo-first-order
4-d) = (5.9 + 0.4) X 1O-3 Sd; From the ratios of 3-d:5-d:6, 12 fi; InBuLij = 0.05 M13): Scheme
by analytical
kobs (production their relative
gc for reaction
kinetics13
times varying
were observed:
kobs
from
(loss of
of 5-d and 6) = (5.8 + 0.4) x 10s3 set-l.
rates of formation
were calculated
(using [THFJ =
kl/k3 : 1.3 M; k2/k3 z 160.
I MeOD
/+Br
l
3-d
2a
Li k2CBuLi-i
MeOD
>
5-d
>
ti 2b
7
;;;” H
\
k3CTHFl
>
0
6
Mechanistically, pathways set -’
. l4
The important
relatively
can be interpreted
conclusions
slow at -78"C, although
la conversion;6 reevaluated undergoes
the results
for the demise of 2b (Scheme
I).
are:
to see whether
stereoselective
involves a nucleophilic
(1) epimerization
rapid enough
this means that previously
encountered
attackI
The higher temperature
insertion!' with
chemistry
3
2a -50°C:
18
-25°C:
0
:
apparent
2a is
with the aforementioned epimerizations
via bimolecular
should
exchange;8
alkylation;
lb to
be
and (2) 2b
alkylation
of configuration.
of carbenoid
to other products, 3a those shown in eqns.
kl= 3.5 x 10m4
of 2b to the more stable
and stereospecific
inversion
competitive
one can calculate
to be consistent
they might have proceeded solvent
in terms of three parallel
From such a scheme,
2a was investigated
(2) and (3) were found
briefly.
in the indicated
5
8
6
6
8
13
8
7
19
In addition ratios
for
(3)
5373
reactions
at -50°C and -25"C,
-5O"C,
and only nBu4Sn at -25°C.
random
at -50" to -25°C.
equilibrium
Also,
respectively.
nBu3SnMe
and nBu4Sn were both formed
It can be seen that carbenoid
In our view, these results
with its less stable, more reactive
butylation
are best explained
epimer,
is fairly
by assuming
at
stereo-
2a is in
2b, which is the source of 5 and 6
(eqn. 4).
8
< MeOH
BuLi
2a
/
7
2b
THF BuLi
>
6
+
7
MeOH
,
8
(4)
9 Further
studies
of the kinetic
behavior
of lithium carbenoids
will be reported
in due
course. References
and Notes
1.
We gratefully Foundation.
2.
Duraisamy,
3.
2019; (b) Skattebol, L. (a) Moore, W. R; Ward, H. R.; Merritt, R. F. ibid. 1961, E, Acta. Chem. Stand. 1963, 17, 1683; (c) Marquis,. T.; Gardner, P. 0. J. Chem. Sot., Chem. Commun. 1966, 726.
4.
Kobrich,
5.
acknowledge
M.; Walborsky,
G.; Goyert,
partial
support
of this work by the National
Science
H. M. J. Am. Chem. Sot. 1984, 106, 5035.
W. Tetrahedron
1968, 2,
4327.
(a) Moore, W. R.; Ward, H. R. J, Org. Chem. 1960, 3, 2073; (b) ibid. 1962, 27, 4179; (c) Jr., M.; Petrillo, Jr., E. W. Tetrahedron Lett. 1969, 3953; (d) Paquette, L. A.: Taylor, R. T. J. Am. Chem. Sot. 1977, 99, 5708.
Jones, 6.
Warner,
7.
Skattebol,
a.
Seyferth,
9.
The amount of nBuLi used was determined by what was required for complete disappearance of 2d in reasonable time (given the difficulty of maintaining the -95°C temperature bath for long times'). Thus 2d still remained after 40 min. with 2 eq. nBuLi, and after 10 min. with 3 eq. nBuLi.
10.
Almost all the 4 was produced in the initial exchange reaction at -95°C. Thus MeOD quenching of the 2d/nBuLi/-95°C reaction after 6 min. at -95°C gave the same deuterium incorporation result as after 20 min. at -95"C, namely a s. 55:45 ratio of 4-d:4; the amount of 4 remained approximately constant over time at -78"C, while 4-d decreased (in accord with it being the quench product from 2b). The production of 4, suggestive of electron transfer in the -95°C carbenoid formation step, is apparently related to the amount of n-BuLi used; further studies are in progress.
11.
In addition to these products, ~5% of the two binorcaranylidene dimers3a*'2 were formed (but not included in our analysis). Intramolecular insertion products3a do not arise from 2b.
12.
Fukuda,
13.
Formation
P. M.; Herold,
R. D. J. Or-q. Chem. 1983, 48, 5411.
L. Tetrahedron 0.; Lambert,
Y.; Yamamoto,
1967, 23,
1107.
Jr., R. L.; Massol,
Y.; Kimura,
M. J. Organomet.
K.; Odaira,
of 6 is pseudo-first-order,
Chem.
Y. Tetrahedron
while production
of 5-d
1975, 88, 255.
Lett. 1979, 877. is approximately
so under our
5374
conditions. We use an [nBuLiJi = 0.076 i. After formation of 2b, [nBuLi] = 0.05 M. This represents a ca. 8 fold excess over that amount of 2b which reacts with nBuLi to eventually give 5-d. However, the situation is complicated by the loss of some nBuLi via its to give nBu SnMe2. reaction with nBuSnMe In any event, we do not observe the fall-off in the production of s -d which wou fd be expected if the pseudo-first-order approximation were grossly incorrect. 14.
This represents an "overall" rate constant; we cannot yet address involving aggregation effects," ion pair behavior,L6~17 etc.
15.
Seebach,
16.
Kitatani,
17.
(a) Schleyer, P.; Clark, T.; Kos, A. J.; Spitznagel, G. W.; Rohde, C.; Arad, D.; Houk, K. N* Rondan, N. G. J. Am. Chem. Sot. 1984, 106, 6467; (b) Mareda, J.; Rondan, N. G.; Houk, K:'N.; Clark, T.; Schleyer, P. ibid. 1983, 105, 6997; (c) Luke, B. T.; Pople, J. A.; Schleyer, P.; Clark, T. Chem. Phys. Lett. 1983, 102, 148.
18.
Taylor,
19.
At times there appears to be some confusion regarding the overall mechanism of carbenoid it might nucleophilically attack RX alkylation. Because a carbenoid is ambiphilic," (itself generated via the initial metal-halogen exchange with RLi). While such a reaction Thus we have found that i is possible,21 it is not the source of alkylated cyclopropane. + CH3Li in CH31/Et20 (]CD3Il/]CH3Lil = 5.1) at room temperature gave iv (7% isolated) with only ca. 8% CD3 (92% CH3), with that amount having arisen from reaction of the CD3Li In the absence of MeI, the epimeric IO-bromo-IO-methylgenerated 6 the final step. [4.3.l]propellanes were formed in a 12:l ratio, with vi predominating. While vi was
0.; Hassig,
R.; Gabriel,
K.; Yamamoto,
K. G.; Chaney,
kinetic
questions
J. Helv. Chim. Acta 1983, 55, 308.
H.; Hiyama,
J.; Deck, J.
T.; Nozaki,
C. J.
H. Bull. Chem. Sot. Jpn. 1977, 3,
2158.
Am. Chem. Sot. 1976, 98, 4163.
CH3Li
rt, lh
,
s3w_ gH3+
CD3Li
...
111
ii
L
(JPJ
L
V
&+ii
vi
produced in -1% yield in the presence of MeI, a control experiment showed it did not give v was always the major product (63% iv under the reaction conditions. As reported," of iv and the on 2, it is clear that. the stereochemistry isolated). _ _ of . the work . . . In view reglochemistry of L-H insertion are due to the predominance of carbenoid ii, which is Lastly, for the carbenoid generation method thermodynamically preferred over its epimer. used herein, nucleophilic attack on RX is precluded by its absence. 20.
(a) Seebach, il.; Oammann, R.; Lindner, H. J.; Kitschke, B. Helv. Chim. Acta 1979, 62, 1143; (b) Kirmse, W. "Carbene Chemistry," 2nd edition, New York: Academic Press, 1971, p. 97; (c) Taylor, K. G. Tetrahedron 1982, 38, 2751.
21.
Siegel,
22.
(a) Paquette, L. A.; Chamot, W. R.; Hall, S. S.; Largman, Dissertation , Massachusetts
H. Top. Curr. Chem.
1982, 106, 55. E.; Browne, A. R. J. Am. Chem. Sot. 1980, 102, 637; (b) Moore, C. Tetrahedron Lett. 1969, 4353; (c) Boardway, N. L.. Ph.0. Institute of Technology, 1970.
(Received in USA 14 June 1985)