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EPR evidence for a single electron transfer mechanism in reactions of aromatic ketones with lithium amides
Tetrahedron Letters, V01.22, No.44, Pp 4355 - 4358, 1981 Printed in Great Britain
0040-4019-/81/444355-04$02.00/O @1981 Pergamon Press Ltd.
EPR EVIDENCE FOR A SINGLE ELECTRON TRANSFER bECHANI.SM IN REACTIONSOF
AROMATICKETONESWITH LIIHIUMAMIDES E. C. Ashby,*A. B. Goel and R. N. DePriest Schoolof Chemistry,GeorgiaInstituteof Technology, Atlanta,Georgia 30332USA SUMMARY:
Nsrn
Directspectroscopic evidence(EPR)supportinga singleelectrontransfer in the reactionof lithiumamideswith aromaticketonesis presented.
We have recentlyprovidedconvincingevidencein supportof a singleelectrontransfer (SET)mechanismin reactionsof stericallyhinderedaromaticketoneswith reagentsof main group elements(metalalkylsand metal hydrides)(eq. 1) by providingdirectspectroscopic evidence(EPR 1-6 By using a sterically and W/visible) as well as indirectevidence(productformationstudies). .
kl R2c=o + M-Y-
[ (Rzc-0) 0-M) +1
-
k2 R2$-GM
(1)
(WhereY = H or R) hinderedketone,such as dimesitylketone,we have been able to detect the radicalintermediate(A) by EPR spectroscopy since k2 shouldbe rate determining when couplingof stericallyhinderedradicals are involved.576However,when benzophenone was employed,no stableintermediate was detected. Since k2 is dependenton the stericrequirementof both the ketone and the reagent(M-Y),we decided to study the reactionsof benzophenone with more stericallyhinderedreagentssuch as lithiumamides. We have recentlyreportedthat lithiumamidesreactwith polynuclearhydrocarbons and alkyl halidesvia a SET mechanism.7 In addition,there are two reportsin the literatureconcerning 899 One reportdescribedthe mechanismof reactionsof lithiumdi-isopropylamide with benzophenone. this reactionto be of a polar nature involvingreductionof benzophenoneto behzhydrolvia a sixcenter transitionstate8and the secondreportdescribedthe formationof benzhydroland tetraphenylethyleneoxide (no quantitative results)when the reactionwas carriedout in 20% HMPA/THF(60°C, 24 Hr).' Formationof tetraphenylethylene oxidewas suggestedto proceedvia a SET mechanism. It is importantto note that no such productcould be observedwhen this reactionwas carriedout at lower temperature.Furthermore,in reactionsof Grignardreagentswith benzophenone, we have shown that althoughthe pinacolproductPh2C(cH)C(@I)Ph2, (precursorof tetraphenylethylene oxide) is an indirectindicationof an electrontransferprocess,it certainlydoes not provideinformationabout the degreeto which electrontransfertakesplace in the main productformingstep. This is'because of the fact that the pinacolis merely a minor by-productwhich can be formednot only as a result of ketyl escape from the solventcage containingthe radicalanion-cation intermediate, but also as 4355
4356
the result
of an independent
concenring
the reactions
strates
Here we wish to report
of benzophenone and dimesityl
thium di-isopropylamide,
information amides e.g.,
li-
pathway. when aromatic ketones
found to be paramagnetic intermediate
increased
of a particular
(benzophenone or dimesityl
in nature,
exhibiting
the rate of electron
transfer
to be dependent on the nature of the amide reagent.
diphenylamide
nal decreased dimesityl
as the product
ketone,
was observed
on reaction
which contain
at a much faster
once the maximumEPR signal
In a typical zophenone solution
experiment,
intermediate
rapidly
was calculated
throughout
the course
Figure 1:
EPR spectrum
intermediate di-n_-butylamide
no decrease
( -35% dior
of benzophenone with those
the intensity
However, in the reaction
when lithium
di-isopropylamide
in ‘IHF at O’C, a deep blue color
increased
of the radica
In the reaction
of the EPR sig-
of those same amides with in the EPR signal
with time
product was found on hydrolysis.
showed a complex EPR spectrum which consisted of the signal
lithium
In the reaction
was observed,
with li-
It was found that lithium
(such as LiNPri and LiNB$),
(Ph,QIcm) formed.
and indeed no reacticm
The concentration
rate than either
with the same ketone.
B-hydrogens
to react
formed which were
and the amount of radical
transfers
an electron
solutions
reached a maxirmrmconcentration.
ispropylamide amide reagents
were allowed
strong EPR signals.
with time and eventually
ketone,
ketone)
Bun and Ph) in ‘IHF, blue colored
were observed
dical
lithium
di-n-butylamide and lithium diphenylamide, which clearly demonof a single electron transfer mechanism in these reactions as the major
thium amides (LiIT$ where R = Pri,
lithium
spectroscopic
ketone with various
lithium
the involvement
reaction
secondary process.
of several
with time and after to be ~35%.
of the reaction.
well-defined
Reduction product
to react with a benThis solution
a few minutes. lines
8 hours the estimated
Complete conversion
of the intermediate benzophenone in ‘IW at 8oC.
was allowed
developed within
(Ph$HM)
(Fig.
1).
The intensit
concentration
of benzophenone to benzhydrol
formed in the reaction
of the ra-
was formed slowly
of lithim
was ob-
di-ispropylamide
and
served after
4 days at which time the EPR signal
duct formation were carried
was proceeding
out at temperatures
(e.g. , tetraphenylethylene probably anion,
directly
the consequence
completely
from the radical
disappeared,
intermediate.
ranging from O°C to R.T.
oxide)
was observed.
(24’C)
The reduction
of B-hydrogen atom abstraction
thus indicating Seve,al
similar
that proexperiments
and in every case no other product
product
formed in this
from the amide radical
cation
reaction
is
by the radical
(Scheme 1) . SCHEME1 Ph2C=0 +
LiNPri
THF
B
Ph2C=0.
. LiNPri
1 [Ph2&)
Ph2CHOLi +
(LiNPr$+]---+
(Solvent
i-PrN=C
Cage)
m3
(A)
LiO OLi
-Li20
Ph C/l\ 2
2d
It was previously a-hydrogen It also
of the isopropyl
(B) shown8 that the hydrogen involved group and the by-product
appears that the formation
reactions
at highter
proportionation ly the reduction the reagents
temperatures
of the radical
does not take place
‘i’ Ph21’-OLi
Ph2;-dPh2 L-,,
CPh
is probably
and the reaction
product.
it is unlikely
of the reduction
of tetraphenylethylene
intermediate proceeds
Since lithium
the result (A).
benzophenone by LDA is the
is N-isopropyl
oxide observed by Scott, of a minor side reaction,
At lower temperature,
this
via a B-hydrogen atom transfer
benzophenone ketyl
that reduction
in reducing
product
is stable
acetone et.
al.,
i.e.,
imine. in
the dis-
disproportionation step to give exclusive-
in ‘IHF and in the presence
is formed as a result
of
of hydrogen atom transfer
by (B). Acknowledgements: We grately
acknowledge support of this work by the National
Science
Foundation
CHE 78-00757). References: 1.
E.C. Ashby, Pure Appl.
Chem., 52,
Bowers, Jr.,
545 (1980);
and references
2.
E.C. Ashby and J.S.
3.
E.C. Ashby and T.L. Wiesmann, J. Amer. Chem. Sot.,
J. Amer. Chem. Sot.,
4.
E.C. Ashby, J. Bowers and R.N. DePriest,
Tetrahedron
5.
E.C. Ashby, A.B. Goel and R.N. &Priest,
J. Amer. Chem. Sot.,
6.
E.C. Ashby and A.B. Goel,
J. Amer. Chem. Sot.,
I&
therein.
99, 8504 (1977). 3101 (1978). Lett.,
(Submitted).
2,
3541 (1980). l&,
7779 (1980).
(Grant No.
7.
E.C. Ashby,A.B. Goel and R.N. &Priest, J. Org. Chem., (In F?-ess)
8.
C. Kowalski,X. Creary,A.J. Rollinand M. Burke,J. Org. Chem.,43, 3101 (1978)
9.
L.T. Scott,K.J. Carlinand T.H. Schultz,TetrahedronLett.,4637 (1978).
(Receivedin USA 6 June 1981)
0040-4019-/81/444355-04$02.00/O @1981 Pergamon Press Ltd.
EPR EVIDENCE FOR A SINGLE ELECTRON TRANSFER bECHANI.SM IN REACTIONSOF
AROMATICKETONESWITH LIIHIUMAMIDES E. C. Ashby,*A. B. Goel and R. N. DePriest Schoolof Chemistry,GeorgiaInstituteof Technology, Atlanta,Georgia 30332USA SUMMARY:
Nsrn
Directspectroscopic evidence(EPR)supportinga singleelectrontransfer in the reactionof lithiumamideswith aromaticketonesis presented.
We have recentlyprovidedconvincingevidencein supportof a singleelectrontransfer (SET)mechanismin reactionsof stericallyhinderedaromaticketoneswith reagentsof main group elements(metalalkylsand metal hydrides)(eq. 1) by providingdirectspectroscopic evidence(EPR 1-6 By using a sterically and W/visible) as well as indirectevidence(productformationstudies). .
kl R2c=o + M-Y-
[ (Rzc-0) 0-M) +1
-
k2 R2$-GM
(1)
(WhereY = H or R) hinderedketone,such as dimesitylketone,we have been able to detect the radicalintermediate(A) by EPR spectroscopy since k2 shouldbe rate determining when couplingof stericallyhinderedradicals are involved.576However,when benzophenone was employed,no stableintermediate was detected. Since k2 is dependenton the stericrequirementof both the ketone and the reagent(M-Y),we decided to study the reactionsof benzophenone with more stericallyhinderedreagentssuch as lithiumamides. We have recentlyreportedthat lithiumamidesreactwith polynuclearhydrocarbons and alkyl halidesvia a SET mechanism.7 In addition,there are two reportsin the literatureconcerning 899 One reportdescribedthe mechanismof reactionsof lithiumdi-isopropylamide with benzophenone. this reactionto be of a polar nature involvingreductionof benzophenoneto behzhydrolvia a sixcenter transitionstate8and the secondreportdescribedthe formationof benzhydroland tetraphenylethyleneoxide (no quantitative results)when the reactionwas carriedout in 20% HMPA/THF(60°C, 24 Hr).' Formationof tetraphenylethylene oxidewas suggestedto proceedvia a SET mechanism. It is importantto note that no such productcould be observedwhen this reactionwas carriedout at lower temperature.Furthermore,in reactionsof Grignardreagentswith benzophenone, we have shown that althoughthe pinacolproductPh2C(cH)C(@I)Ph2, (precursorof tetraphenylethylene oxide) is an indirectindicationof an electrontransferprocess,it certainlydoes not provideinformationabout the degreeto which electrontransfertakesplace in the main productformingstep. This is'because of the fact that the pinacolis merely a minor by-productwhich can be formednot only as a result of ketyl escape from the solventcage containingthe radicalanion-cation intermediate, but also as 4355
4356
the result
of an independent
concenring
the reactions
strates
Here we wish to report
of benzophenone and dimesityl
thium di-isopropylamide,
information amides e.g.,
li-
pathway. when aromatic ketones
found to be paramagnetic intermediate
increased
of a particular
(benzophenone or dimesityl
in nature,
exhibiting
the rate of electron
transfer
to be dependent on the nature of the amide reagent.
diphenylamide
nal decreased dimesityl
as the product
ketone,
was observed
on reaction
which contain
at a much faster
once the maximumEPR signal
In a typical zophenone solution
experiment,
intermediate
rapidly
was calculated
throughout
the course
Figure 1:
EPR spectrum
intermediate di-n_-butylamide
no decrease
( -35% dior
of benzophenone with those
the intensity
However, in the reaction
when lithium
di-isopropylamide
in ‘IHF at O’C, a deep blue color
increased
of the radica
In the reaction
of the EPR sig-
of those same amides with in the EPR signal
with time
product was found on hydrolysis.
showed a complex EPR spectrum which consisted of the signal
lithium
In the reaction
was observed,
with li-
It was found that lithium
(such as LiNPri and LiNB$),
(Ph,QIcm) formed.
and indeed no reacticm
The concentration
rate than either
with the same ketone.
B-hydrogens
to react
formed which were
and the amount of radical
transfers
an electron
solutions
reached a maxirmrmconcentration.
ispropylamide amide reagents
were allowed
strong EPR signals.
with time and eventually
ketone,
ketone)
Bun and Ph) in ‘IHF, blue colored
were observed
dical
lithium
di-n-butylamide and lithium diphenylamide, which clearly demonof a single electron transfer mechanism in these reactions as the major
thium amides (LiIT$ where R = Pri,
lithium
spectroscopic
ketone with various
lithium
the involvement
reaction
secondary process.
of several
with time and after to be ~35%.
of the reaction.
well-defined
Reduction product
to react with a benThis solution
a few minutes. lines
8 hours the estimated
Complete conversion
of the intermediate benzophenone in ‘IW at 8oC.
was allowed
developed within
(Ph$HM)
(Fig.
1).
The intensit
concentration
of benzophenone to benzhydrol
formed in the reaction
of the ra-
was formed slowly
of lithim
was ob-
di-ispropylamide
and
served after
4 days at which time the EPR signal
duct formation were carried
was proceeding
out at temperatures
(e.g. , tetraphenylethylene probably anion,
directly
the consequence
completely
from the radical
disappeared,
intermediate.
ranging from O°C to R.T.
oxide)
was observed.
(24’C)
The reduction
of B-hydrogen atom abstraction
thus indicating Seve,al
similar
that proexperiments
and in every case no other product
product
formed in this
from the amide radical
cation
reaction
is
by the radical
(Scheme 1) . SCHEME1 Ph2C=0 +
LiNPri
THF
B
Ph2C=0.
. LiNPri
1 [Ph2&)
Ph2CHOLi +
(LiNPr$+]---+
(Solvent
i-PrN=C
Cage)
m3
(A)
LiO OLi
-Li20
Ph C/l\ 2
2d
It was previously a-hydrogen It also
of the isopropyl
(B) shown8 that the hydrogen involved group and the by-product
appears that the formation
reactions
at highter
proportionation ly the reduction the reagents
temperatures
of the radical
does not take place
‘i’ Ph21’-OLi
Ph2;-dPh2 L-,,
CPh
is probably
and the reaction
product.
it is unlikely
of the reduction
of tetraphenylethylene
intermediate proceeds
Since lithium
the result (A).
benzophenone by LDA is the
is N-isopropyl
oxide observed by Scott, of a minor side reaction,
At lower temperature,
this
via a B-hydrogen atom transfer
benzophenone ketyl
that reduction
in reducing
product
is stable
acetone et.
al.,
i.e.,
imine. in
the dis-
disproportionation step to give exclusive-
in ‘IHF and in the presence
is formed as a result
of
of hydrogen atom transfer
by (B). Acknowledgements: We grately
acknowledge support of this work by the National
Science
Foundation
CHE 78-00757). References: 1.
E.C. Ashby, Pure Appl.
Chem., 52,
Bowers, Jr.,
545 (1980);
and references
2.
E.C. Ashby and J.S.
3.
E.C. Ashby and T.L. Wiesmann, J. Amer. Chem. Sot.,
J. Amer. Chem. Sot.,
4.
E.C. Ashby, J. Bowers and R.N. DePriest,
Tetrahedron
5.
E.C. Ashby, A.B. Goel and R.N. &Priest,
J. Amer. Chem. Sot.,
6.
E.C. Ashby and A.B. Goel,
J. Amer. Chem. Sot.,
I&
therein.
99, 8504 (1977). 3101 (1978). Lett.,
(Submitted).
2,
3541 (1980). l&,
7779 (1980).
(Grant No.
7.
E.C. Ashby,A.B. Goel and R.N. &Priest, J. Org. Chem., (In F?-ess)
8.
C. Kowalski,X. Creary,A.J. Rollinand M. Burke,J. Org. Chem.,43, 3101 (1978)
9.
L.T. Scott,K.J. Carlinand T.H. Schultz,TetrahedronLett.,4637 (1978).
(Receivedin USA 6 June 1981)