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The reactions of benzyne with α,β-unsaturated carbonyl compounds
Tetrahedron
Letters
No. 23,
pp 2043 - 2046, 1974.
Printed
Pergamon Press.
in Great Britain.
THE REACTIONSOF BENZYNEWITH a,B-UNSATURATED CARBONYLCOMPOUNDS Arlyce Department
T. Bowne and Ronald H. Levin* of Chemistry,
Cambridge, (Received
in USA 25 Fabruery
The cycloaddition has already
been reported
the carbon-carbon
a
of benzyne
double
in the
to
Harvard University
Massachusetts 1974;
received
conjugatively
literature.
bond to produce
02138,
U.S.A.
in Dg for
publication
unsaturated
esters’
In the former III-a
was reported.
case,
and aldehydes’
only
In the
2 May 1974)
cycloaddition
latter
to
example,
: X=OEt, b : X=H, c : X=CH3, d : X=C2HS, e : X=CoHS, f : X=SCH3
only
Type I products In order
derived
to elucidate
from initial the
factors
carbonyl responsible
2043
cycloaddition for
this
were detected.
selectivity,
we have inves-
No.
2044 tigated
the reactions
Generation
of
benzyne
the carbon-carbon
product,
(m, 4.5
4.59
(br
s,
2.7
in a 7:l
H);
6 (br
5
III-C.
However,
mass measurement:
double
change
is
also
7.28-6.86 2.30
of methyl
178.0456;
2.9 ir
Had the
H);
(neat)
vinyl
(II-c)
compounds.
ketone
(III-c),
I-acetylbenzocyclobutene5
ethyl
produced and the
[nmr (100 MHz, CC14) 7.16-6.60
of
48% as determined
an authentic
6
that
effects
an excess
6
produced
of
its
to -ca.
isomer
cycloaddition
4.7
of to
in 2-substituted vinyl
ketone,
was obtained.
thioester
product,
valence
now the ratio
of phenyl
bond cycloadduct,
by vpc analysis
and vpc comparison.
had decreased
substituent
146.07221,
an additional
sample6
except
found
from carbonyl
IV-e under our vpc conditions.
4.40
precise
the product
ketone,
with
thiolacrylate
stabilities
ClOHlOO; 146.0732,
at the expense
cycloadduct
double
to
vco
for
was -ca.
(I-c),
vinyl
to react
H),
calcd
be produced
with known steric
entirely
6 (m, 4.2
6 (s,
with
carbon-carbon
rearranged
the presence
could
by synthesis
was allowed
the rearranged
of methyl
Depending upon the vpc conditions,
bond to Diels-Alder
in accord
When benzyne
yield
4-methyl-2H-chromene
were obtained
carbon
absolute
(IV-c),
was shown to be absent results
excess
carbonyl
t, J=3.0 Hz, 0.9 H), 3.33 6 (br d, J=3.0 Hz, 1.8 H), 1.86 6
standard.
3-methylisochromene
of a,@unsaturated
of a large
bond cycloadduct,
The total
with an internal
a variety
2-methyl-4H-chromene
precise
ratio.
with
in the presence
double
Diels-Alder H),
of benzyne3
5 III-f
carbon-
1; such a butadienes. only
Authentic
Generation
Similar
IV-e, III-e
of benzyne
in
[nmr (100 MHz, CC14)
(t, J=4.0 Hz, 0.9 H), 3.48 6 (d, J=4.0 Hz, 2.0 H),
mass measurement:
1679 cm-l]
calcd
in approximately
of the presumed biradical
for
ClOHlOOS: 178.0452,
found:
45% yield. ally1
(V) and oxallyl
(VI)
inter-
VI
mediates
played
a controlling
have expected
to observe
adduct
substituent
are,
as the
however,
inconsistent
role
an increase
in directing
in the amount of
X became more electron with
the mode of
such a scheme,
cycloaddition,
we would
the Type I carbon-oxygen
withdrawing.
The observed
but are in accord
with
cyclo-
results
a mechanism
7
23
No. 23
whereby the reactivity ester)
is
of the
the determining
In seeming
initial
agreement
with
this
can be supressed
crotonaldehyde
reacts
product
rearranged late
and,
mixture
(E)-
of
to produce
been identified
of
55%. In contrast
> ketone
- thioester’
-
its
the
to produce
Type I products
of a-substituents.
For example,
two compounds in a 19:l
component
nmr spectrum,
of
we have found that
as 2-methyl-2H-chromene
The minor
by isomerization
with methacrolein
aldehyde
introduction
is
exceedingly
two products
identified
to the above reaction,
however,
ratio
the major
the to it
iso-
as a
a substance
ene product.
in a 19:l
The
difficult
[E- and (Z)-VIII],lo
8,y-unsaturated
ratio.
(VII),2a’g
we have tentatively
and (Z)-a-phenylcrotonaldehyde
sumably arising reacts
by the
cycloadduct.
on the basis
of
explanation,
with benzyne
has already
carbonyl
(i.e.,
factor.
from aldehydes
major
carbonyl
pre-
Benzyne also
with
an overall
yield
compound was now derived
VII
+
v
H
via -
the ene reaction
The minor product 6.80-6.50 3.0
product carbonyl both
changes
and an excess sented rate
of
H),
6.07
from initial
addition
had,
6 (br
of both
in the following
cycloaddition
s,
1.0 H),
calcd
for
4.60
6 (br s,
we performed
In order
’
H3
and methacrolein. indicate
upon a-substitution.
1.80
found:
6 (br
The relative a substantial Such an effect,
s,
146.07251,
to determine
experiment
(IX).12
[nmr (100 MHz, CC14)
2.2 H),
or the ene reaction
a competition
These results
(X)
ClOHlOO: 146.0732,
cycloaddition.
been retarded
crotonaldehyde table.
as 3-methyl-ZH-chromene
carbonyl
in fact,
were occurring,
carbonyl
X
pathway and was found to be a-methylene-hydrocinnamaldehyde
mass measurement:
derived
0
IX
has been identified
6 (m, 3.8
H); precise
ar,
c6,
H
H3
if
accelerated,
benzyne
data
decrease perhaps
the or if
involving rate
the
is prein the
steric
No. 23
2046
crotonaldehyde methacrolein
Kco rel
Kene rel
19.0
1.0
1.7
31.7
in origin, is consistentwith our explanations.It is also interestingto note that the ene reaction rate is also very sensitiveto the substitutionpattern. The source of this latter effect is currentlyunder investigation.
REFERENCES 1. T. Matsuda and T. Mitsuyasu,Bull. Chem. Sot. Japan, 32, 1342 (1966). 2. a) H. Heaney, J.M. Jablonskiand C.T. McCarthy,J.C.S. Perkin I, 2903 (1972). b) H. Heaney and C.T. McCarthy,Chem. Commun., 123 (1970). c) H. Heaney and J.M. Jablonski,ibid, 1139 (1968). 3. Our benzyne was generatedvia thermal decompositionof benzenediazonium-2-carboxylate hydrochlorideaccordingto the method of Friedman as describedby D.C. Dittmer, et.al.4 4. D.C. Dittmer and E.S. Whitman,J. Org. Chem., 24, 2004 (1969). 5. R. Hug, H.-J. Hansen and H. S&mid, Helv. Chem. Acta, _5_5, 10 (1972). 6. F. Baranton,G. Fontaineand P. Maitte, Bull. Sot. Chim. Fr.. 4203 (1968). 7. D. Craig, J.J. Shipman and R.B. Fowler, J. Amer. Chem. Sot., 83 __ 2885 (1961). 8. See p. 156 in R.B. Woodward,Pure Appl. Chem., 33, __ 145 (1973). 9. R. Hug, H.-J. Hansen and H. S&mid, Helv. Chem. Acta, 25, 1828 (1972). 10. Enough sample was obtainedto secure a PFT-NMR spectrum.As our acquisitiontime was much shorter than the expectedTl relaxationtimes for these protons, integralvalues were not recorded.The 100 MHz nmr spectrumof (E)- and (Z)-VIIIin Ccl4 was as follows:9.52 6 (s), 9.18 6 (s), 7.34-6.926 (m), 6.90-6.626 (m), 1.98 6 (d, J=6.9 Hz), 1.41 8 (d, J = 6.5 Hz). Compare these values to those for (Z)-a-phenylcro11 tononitrile. It should also be noted that even if our structuralassignmentis incorrect, it still serves to set an upper limit on the relativerate of the ene reaction. 11. G. Descotes and P. Laconche.Bull. Sot. Chim. Fr., 2149 (1968). 12. W. Sucrow and W. Richter,Chem. Ber., 103, 3771 (1970).
Letters
No. 23,
pp 2043 - 2046, 1974.
Printed
Pergamon Press.
in Great Britain.
THE REACTIONSOF BENZYNEWITH a,B-UNSATURATED CARBONYLCOMPOUNDS Arlyce Department
T. Bowne and Ronald H. Levin* of Chemistry,
Cambridge, (Received
in USA 25 Fabruery
The cycloaddition has already
been reported
the carbon-carbon
a
of benzyne
double
in the
to
Harvard University
Massachusetts 1974;
received
conjugatively
literature.
bond to produce
02138,
U.S.A.
in Dg for
publication
unsaturated
esters’
In the former III-a
was reported.
case,
and aldehydes’
only
In the
2 May 1974)
cycloaddition
latter
to
example,
: X=OEt, b : X=H, c : X=CH3, d : X=C2HS, e : X=CoHS, f : X=SCH3
only
Type I products In order
derived
to elucidate
from initial the
factors
carbonyl responsible
2043
cycloaddition for
this
were detected.
selectivity,
we have inves-
No.
2044 tigated
the reactions
Generation
of
benzyne
the carbon-carbon
product,
(m, 4.5
4.59
(br
s,
2.7
in a 7:l
H);
6 (br
5
III-C.
However,
mass measurement:
double
change
is
also
7.28-6.86 2.30
of methyl
178.0456;
2.9 ir
Had the
H);
(neat)
vinyl
(II-c)
compounds.
ketone
(III-c),
I-acetylbenzocyclobutene5
ethyl
produced and the
[nmr (100 MHz, CC14) 7.16-6.60
of
48% as determined
an authentic
6
that
effects
an excess
6
produced
of
its
to -ca.
isomer
cycloaddition
4.7
of to
in 2-substituted vinyl
ketone,
was obtained.
thioester
product,
valence
now the ratio
of phenyl
bond cycloadduct,
by vpc analysis
and vpc comparison.
had decreased
substituent
146.07221,
an additional
sample6
except
found
from carbonyl
IV-e under our vpc conditions.
4.40
precise
the product
ketone,
with
thiolacrylate
stabilities
ClOHlOO; 146.0732,
at the expense
cycloadduct
double
to
vco
for
was -ca.
(I-c),
vinyl
to react
H),
calcd
be produced
with known steric
entirely
6 (m, 4.2
6 (s,
with
carbon-carbon
rearranged
the presence
could
by synthesis
was allowed
the rearranged
of methyl
Depending upon the vpc conditions,
bond to Diels-Alder
in accord
When benzyne
yield
4-methyl-2H-chromene
were obtained
carbon
absolute
(IV-c),
was shown to be absent results
excess
carbonyl
t, J=3.0 Hz, 0.9 H), 3.33 6 (br d, J=3.0 Hz, 1.8 H), 1.86 6
standard.
3-methylisochromene
of a,@unsaturated
of a large
bond cycloadduct,
The total
with an internal
a variety
2-methyl-4H-chromene
precise
ratio.
with
in the presence
double
Diels-Alder H),
of benzyne3
5 III-f
carbon-
1; such a butadienes. only
Authentic
Generation
Similar
IV-e, III-e
of benzyne
in
[nmr (100 MHz, CC14)
(t, J=4.0 Hz, 0.9 H), 3.48 6 (d, J=4.0 Hz, 2.0 H),
mass measurement:
1679 cm-l]
calcd
in approximately
of the presumed biradical
for
ClOHlOOS: 178.0452,
found:
45% yield. ally1
(V) and oxallyl
(VI)
inter-
VI
mediates
played
a controlling
have expected
to observe
adduct
substituent
are,
as the
however,
inconsistent
role
an increase
in directing
in the amount of
X became more electron with
the mode of
such a scheme,
cycloaddition,
we would
the Type I carbon-oxygen
withdrawing.
The observed
but are in accord
with
cyclo-
results
a mechanism
7
23
No. 23
whereby the reactivity ester)
is
of the
the determining
In seeming
initial
agreement
with
this
can be supressed
crotonaldehyde
reacts
product
rearranged late
and,
mixture
(E)-
of
to produce
been identified
of
55%. In contrast
> ketone
- thioester’
-
its
the
to produce
Type I products
of a-substituents.
For example,
two compounds in a 19:l
component
nmr spectrum,
of
we have found that
as 2-methyl-2H-chromene
The minor
by isomerization
with methacrolein
aldehyde
introduction
is
exceedingly
two products
identified
to the above reaction,
however,
ratio
the major
the to it
iso-
as a
a substance
ene product.
in a 19:l
The
difficult
[E- and (Z)-VIII],lo
8,y-unsaturated
ratio.
(VII),2a’g
we have tentatively
and (Z)-a-phenylcrotonaldehyde
sumably arising reacts
by the
cycloadduct.
on the basis
of
explanation,
with benzyne
has already
carbonyl
(i.e.,
factor.
from aldehydes
major
carbonyl
pre-
Benzyne also
with
an overall
yield
compound was now derived
VII
+
v
H
via -
the ene reaction
The minor product 6.80-6.50 3.0
product carbonyl both
changes
and an excess sented rate
of
H),
6.07
from initial
addition
had,
6 (br
of both
in the following
cycloaddition
s,
1.0 H),
calcd
for
4.60
6 (br s,
we performed
In order
’
H3
and methacrolein. indicate
upon a-substitution.
1.80
found:
6 (br
The relative a substantial Such an effect,
s,
146.07251,
to determine
experiment
(IX).12
[nmr (100 MHz, CC14)
2.2 H),
or the ene reaction
a competition
These results
(X)
ClOHlOO: 146.0732,
cycloaddition.
been retarded
crotonaldehyde table.
as 3-methyl-ZH-chromene
carbonyl
in fact,
were occurring,
carbonyl
X
pathway and was found to be a-methylene-hydrocinnamaldehyde
mass measurement:
derived
0
IX
has been identified
6 (m, 3.8
H); precise
ar,
c6,
H
H3
if
accelerated,
benzyne
data
decrease perhaps
the or if
involving rate
the
is prein the
steric
No. 23
2046
crotonaldehyde methacrolein
Kco rel
Kene rel
19.0
1.0
1.7
31.7
in origin, is consistentwith our explanations.It is also interestingto note that the ene reaction rate is also very sensitiveto the substitutionpattern. The source of this latter effect is currentlyunder investigation.
REFERENCES 1. T. Matsuda and T. Mitsuyasu,Bull. Chem. Sot. Japan, 32, 1342 (1966). 2. a) H. Heaney, J.M. Jablonskiand C.T. McCarthy,J.C.S. Perkin I, 2903 (1972). b) H. Heaney and C.T. McCarthy,Chem. Commun., 123 (1970). c) H. Heaney and J.M. Jablonski,ibid, 1139 (1968). 3. Our benzyne was generatedvia thermal decompositionof benzenediazonium-2-carboxylate hydrochlorideaccordingto the method of Friedman as describedby D.C. Dittmer, et.al.4 4. D.C. Dittmer and E.S. Whitman,J. Org. Chem., 24, 2004 (1969). 5. R. Hug, H.-J. Hansen and H. S&mid, Helv. Chem. Acta, _5_5, 10 (1972). 6. F. Baranton,G. Fontaineand P. Maitte, Bull. Sot. Chim. Fr.. 4203 (1968). 7. D. Craig, J.J. Shipman and R.B. Fowler, J. Amer. Chem. Sot., 83 __ 2885 (1961). 8. See p. 156 in R.B. Woodward,Pure Appl. Chem., 33, __ 145 (1973). 9. R. Hug, H.-J. Hansen and H. S&mid, Helv. Chem. Acta, 25, 1828 (1972). 10. Enough sample was obtainedto secure a PFT-NMR spectrum.As our acquisitiontime was much shorter than the expectedTl relaxationtimes for these protons, integralvalues were not recorded.The 100 MHz nmr spectrumof (E)- and (Z)-VIIIin Ccl4 was as follows:9.52 6 (s), 9.18 6 (s), 7.34-6.926 (m), 6.90-6.626 (m), 1.98 6 (d, J=6.9 Hz), 1.41 8 (d, J = 6.5 Hz). Compare these values to those for (Z)-a-phenylcro11 tononitrile. It should also be noted that even if our structuralassignmentis incorrect, it still serves to set an upper limit on the relativerate of the ene reaction. 11. G. Descotes and P. Laconche.Bull. Sot. Chim. Fr., 2149 (1968). 12. W. Sucrow and W. Richter,Chem. Ber., 103, 3771 (1970).