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On the homo Diels-Alder reaction of substituted norbornadienes as a possible route to longicyclene.
Tetrahedron Letten
Ho. 6, pp 437 - 440, 1973.
Per-n
ON THE HOMO DIELS-ALDBR NORBORNADIENBS
Printsdin keat
Press.
Britsin.
REACTION OF SUBSTITUTED
AS A POSSIBLE ROUTE TO LONGICYCIBNE.
AN IBTRAMOLBCULARENB
REACTION.
T. Ross Kelly Department of Chemistry, Boston College Chestnut Hill, Mass. 02167 (Fboeived
In USA 6 Deoember 1972; reoeivedia UK for publloation8 Jaauar~ 1973)
Nearly ten years ago Nayak and Dev reported1 identified tetracyclic tetracyclic
sesguiterpene,
sesquiterpenes
total synthesis
the structure
longicyclene
(A).
have been both characterized'
of longicyclene
has yet been achieved
of the first
More recently2
other
and synthesized but no3'2o
&spite
a number of at-
tempts? In our projected considered between
synthesis
of longicyclene
utilizes as the major constructive
a substituted
norbornadiene
the feasibility
reaction
(e.g. Equation
of this approach
6
1).
to the
of longicyclene. (2)7 which
2,3_Dimethylnorbornadiene from cyclopentadiene
can
be
up to 200° both with"
and without6
reactions,
tendency of norbornadiene
the lack of reactivity
a result of kinetic
intramolecular
observed
and not thermodynamic
felt that the chances of successfully be significantly
added
of dieno-
($3P)2Ni(CO)2.
tar.
In view of the well-known6 Diels-Alder
(in abysmal yield)
(e.g. 2) formed, the usual product
In no case was any of the desired cycloadduct being an intractable
prepared
and 2-butyneS at 300° was heated with a variety'
philes at temperatures
certainly
one of the routes we have
and a suitable dienophile
We wish to report our findings regarding
synthesis
u)
step the homo Diels-Alder
enhanced by modifying
homo Diels-Alder
effecting
factors.
the &sired
the basic synthetic
reaction.
437
itself to undergo homo
in the case of 2 is almost
a,% -Unsaturated
Consequently cycloaddition
we could
scheme to permit an esters of dienol 3
No.
430
seemed attractive of reasons
candidates
including
6
for this intramolecular
cycloaddition
for a number
(a) relative ease of synthesis,
(b) potential
for easy vari-
ation of the dienophilic
component,
and (c) abundance
of methods available
R& & 0
I
S,R=CHO
R
for
0
R 0
0 1, R=R'=H
6, R=R'=H
10, R=R'=COOCH3
8, R=H,R'=COOCH3 2, R=R'=COOCH3 the ultimate
conversion
of the -CH20- moiety to a methyl group.
Dienol s7'11 was prepared by LiAlH4reduction is formed from cyclopentadiene acrylyl chloride
and but-2-yna112
triethylamine
($3P)2Ni(C0)2 at temperatures polymer as judged by tic. devoid of absorptions
gives 5.
of aldehyde 2 which
at 100°.
Thermolysis
Reaction
of 6 with or without
up to 200° resulted primarily
Infrared
attributable
in turn
of 4 with
in the formation of
spectra of the crude reaction products were to a y-lactone
(e.g. 1).
The corresponding latter being
maleate 2 7'11 Was prepared by reaction of 4 with ll, the 13 formed by the action of oxalyl chloride on 12. Thermolysis of 2
again gave no isolable products but the observation.that trum of the crude product had a small but nevertheless provided
sufficient
in some runs the ir spec
definite band at 1780 cm -1
incentive to prepare the synthetically
less accessible
tri-
ester 2.
COOCH3
2,
R=COCl
2.
12, R=COO-K+
Condensation
14
R=OC(CH3)3
14, R=OH
(piperidine, refluxing benzene,
removal of H20) of dimethyl
and f-butyl glyoxylate l5 gives 13 7*11 (bp 87-95O/O.O5 mm, 70%) which is converted cleanly to the diester acid -147,Ll (mp 65-68O) upon treatment with tri-
malonate
fluoroacetic
acid.
enetricarboxylic
TO
our knowledge
acid has appeared
no other report of a partial ester of eth-
in the literature.
The diester acid -14 was
439
No. 6
converted to the mixed anhydride -157 upon refluxing in trifluoroacetic anhydride. When -15 was added at room temperature to a pyridine solution of dienol 4 tic indicated the immediate formation of a new compound whose tic characteristics (rf, color with detecting
agents) were entirely
quent tic's of the reaction mixture give a new compound, possesses
The new compound, which
a molecular
weight
nmr spectrum of "X", which several olefinic
methoxyls,
of the desired product
is devoid of peaks attributable resonances
layer or vapor
in addition
in the ir (1790, (l0).
But the
to a C-CH2 group and
to an expected
peak due to the
10. These spectral data are, 16ii (stereochemistry of lactone unassigned) and the nmr spectra of "X" and -17 5a,16 display a striking resemblance Structure -16 may be rationalized mechanistically as the in the olefinic region.
however,
is totally incompatible with
Subse-
reaction to
is almost the sole product of the
(M+ = 280) and absorption
1740 cm-l) consistent with the structure contains
that 2 quickly underwent
"X", which could be isolated by preparative
phase chromatography. reaction,
consistent with structure 2.
revealed
completely
consistent
structure
with structure
4c-f H
OOCH2
CCOCH2
CCCH
0
-16
0
-17
example of an ene reaction
17 The formation of -16 is the only involving a 1,8-transfer of hydrogen between carbon
atoms and is particularly
noteworthy
product of an intramolecular
which
it occurs.
ene
17
reaction.
for the exceptionally
mild conditions
under
of 2 into -16 is unaffected by the presence of (P(3P)3Ni(C0)2 in the reaction of -15 and 4. It is perhaps noteworthy that virtually all homo Diels-blder reactions are
observed
The conversion
in systems
(e.g. norbornadiene,
barrelene 18igwhere ene reactions
could
violation of Bredt's rule. The formation of -16 suggests that where both reaction pathways are available the ene reaction may well 19 In any event the foregoing results suggest be the one which is usually favored. occur only with concurrent
that the homo Diels-Alder
reaction will not be the cornerstone
realized
We are presently
synthesis
of 1.
Acknowledqements: Petroleum
by the American Chemical
Society,
The author is indebted to Cornel Pietruszewski.
Schmidt, and John Hagge_rty for assistance ials.
of our yet-to-be
other routes to longicyclene
The financial support of Research Corporation
Research Fund, administered
fully acknowledged.
exploring
in the preparation
and the is grate-
Thomas
of starting mater-
440
No. 6
Footnotes
and References
1.
U.R. Nayak and Sukh Dev, Tetrahedron 4099 (1968).
2.
See T.K. Devon and A.I. Scott, "Handbook of Naturally Occurring Volume 11,"Terpenes: Academic Press, London, 1972, p. 181.
3.
In view of the fact that Nayak and Dev demonstrated1 that (+)-longicyclene and (+)-longifolene ar interconverted by cupric acetate in acetic acid, the two recorded syntheses % of (+) longifolene also constitute, in a formal sense, syntheses of longicyclene.
4.
E.J. Corey, M. Ohno, R.B. Mitra, and P.A. Vatakencherry, J. Amer. Chem. Sot., 86, 478 (1964); J.E. McMurry and S.J. Isser, z., 94, 7132 (1972).
5.
E.g.see (a) W_dZ. Barnett and J.C. McKenna, Tetrahedron Letters, 227 (1971);. (b) Steven C. Welch, Ph.D. Thesis,University of Southern California, 1969; Diss. Abstr. B, -29,3685 (1969). For leading references see (a) R.C. Cookson, J. Dance and J. Hudec, J. Chem. sot., 5416 (1964); (b) P.K. Freeman, D.M. Balls and J.N. Blazevich, J. Amer. Chem. SOC.,~, 2051 (1970); (c) reference 12 in H.G. Kuivila and C.R. Warner, J. Org. Chem.,& 2845 (1964).
6.
Letters,
243 (1963); Tetrahedron,
Compounds~~,
7.
Ir and nmr spectra of this compound are completely assigned structure.
8.
Farchan Research Laboratories, Willoughby, Ohio. We are also grateful Professor Ernst Koerner von Gustorf for a generous gift of 2-butyne.
9.
Dienophiles examined include acrylonitrile, maleic anhydride, dimethyl acetylenedicarboxylate, fumaronitrile, and tetracyanoethylene. Ber.,z,
consistent
10.
G.N. Schrauzer and P. Glockner,
11.
The elemental
12.
J. C. Lunt and F. Sondheimer,
13.
J. Shields, J. Chem. Sot., 2,
14.
G. Jones, Org. Reactions, 15, 204 (1967).
15.
L.A. Carpino, J. Org. Chem.,B,
16.
We are grateful this compound.
17.
For a recent review see H.M.R. Hoffman, Angew. Chem. Internat. (1969).
analysis of this compound
24,
with the to
2451 (1964). supports the assigned
structure.
J. Chem. Sot., 3361 (1950). 736 (1891). 2820 (1964).
to Dr. James McKenna
and G.L. Grunewald,
for making available
an nmr
SpCtrUm
Edit.,&
J. Amer. Chem. Sot., 86. 1434
Of 556
18.
H.E. Zimmerman
19.
For an exception to this generalization 84, 1257 (1962). s.,
20.
After this manuscript had been completed Professor Steven Welch informed us of We thank him for comthe synthesis of (+)-longicyclene in his laboratory. municating his results prior to publication.
see
J.K.
Williams
(1964).
and R.E. BenSOn,
Ho. 6, pp 437 - 440, 1973.
Per-n
ON THE HOMO DIELS-ALDBR NORBORNADIENBS
Printsdin keat
Press.
Britsin.
REACTION OF SUBSTITUTED
AS A POSSIBLE ROUTE TO LONGICYCIBNE.
AN IBTRAMOLBCULARENB
REACTION.
T. Ross Kelly Department of Chemistry, Boston College Chestnut Hill, Mass. 02167 (Fboeived
In USA 6 Deoember 1972; reoeivedia UK for publloation8 Jaauar~ 1973)
Nearly ten years ago Nayak and Dev reported1 identified tetracyclic tetracyclic
sesguiterpene,
sesquiterpenes
total synthesis
the structure
longicyclene
(A).
have been both characterized'
of longicyclene
has yet been achieved
of the first
More recently2
other
and synthesized but no3'2o
&spite
a number of at-
tempts? In our projected considered between
synthesis
of longicyclene
utilizes as the major constructive
a substituted
norbornadiene
the feasibility
reaction
(e.g. Equation
of this approach
6
1).
to the
of longicyclene. (2)7 which
2,3_Dimethylnorbornadiene from cyclopentadiene
can
be
up to 200° both with"
and without6
reactions,
tendency of norbornadiene
the lack of reactivity
a result of kinetic
intramolecular
observed
and not thermodynamic
felt that the chances of successfully be significantly
added
of dieno-
($3P)2Ni(CO)2.
tar.
In view of the well-known6 Diels-Alder
(in abysmal yield)
(e.g. 2) formed, the usual product
In no case was any of the desired cycloadduct being an intractable
prepared
and 2-butyneS at 300° was heated with a variety'
philes at temperatures
certainly
one of the routes we have
and a suitable dienophile
We wish to report our findings regarding
synthesis
u)
step the homo Diels-Alder
enhanced by modifying
homo Diels-Alder
effecting
factors.
the &sired
the basic synthetic
reaction.
437
itself to undergo homo
in the case of 2 is almost
a,% -Unsaturated
Consequently cycloaddition
we could
scheme to permit an esters of dienol 3
No.
430
seemed attractive of reasons
candidates
including
6
for this intramolecular
cycloaddition
for a number
(a) relative ease of synthesis,
(b) potential
for easy vari-
ation of the dienophilic
component,
and (c) abundance
of methods available
R& & 0
I
S,R=CHO
R
for
0
R 0
0 1, R=R'=H
6, R=R'=H
10, R=R'=COOCH3
8, R=H,R'=COOCH3 2, R=R'=COOCH3 the ultimate
conversion
of the -CH20- moiety to a methyl group.
Dienol s7'11 was prepared by LiAlH4reduction is formed from cyclopentadiene acrylyl chloride
and but-2-yna112
triethylamine
($3P)2Ni(C0)2 at temperatures polymer as judged by tic. devoid of absorptions
gives 5.
of aldehyde 2 which
at 100°.
Thermolysis
Reaction
of 6 with or without
up to 200° resulted primarily
Infrared
attributable
in turn
of 4 with
in the formation of
spectra of the crude reaction products were to a y-lactone
(e.g. 1).
The corresponding latter being
maleate 2 7'11 Was prepared by reaction of 4 with ll, the 13 formed by the action of oxalyl chloride on 12. Thermolysis of 2
again gave no isolable products but the observation.that trum of the crude product had a small but nevertheless provided
sufficient
in some runs the ir spec
definite band at 1780 cm -1
incentive to prepare the synthetically
less accessible
tri-
ester 2.
COOCH3
2,
R=COCl
2.
12, R=COO-K+
Condensation
14
R=OC(CH3)3
14, R=OH
(piperidine, refluxing benzene,
removal of H20) of dimethyl
and f-butyl glyoxylate l5 gives 13 7*11 (bp 87-95O/O.O5 mm, 70%) which is converted cleanly to the diester acid -147,Ll (mp 65-68O) upon treatment with tri-
malonate
fluoroacetic
acid.
enetricarboxylic
TO
our knowledge
acid has appeared
no other report of a partial ester of eth-
in the literature.
The diester acid -14 was
439
No. 6
converted to the mixed anhydride -157 upon refluxing in trifluoroacetic anhydride. When -15 was added at room temperature to a pyridine solution of dienol 4 tic indicated the immediate formation of a new compound whose tic characteristics (rf, color with detecting
agents) were entirely
quent tic's of the reaction mixture give a new compound, possesses
The new compound, which
a molecular
weight
nmr spectrum of "X", which several olefinic
methoxyls,
of the desired product
is devoid of peaks attributable resonances
layer or vapor
in addition
in the ir (1790, (l0).
But the
to a C-CH2 group and
to an expected
peak due to the
10. These spectral data are, 16ii (stereochemistry of lactone unassigned) and the nmr spectra of "X" and -17 5a,16 display a striking resemblance Structure -16 may be rationalized mechanistically as the in the olefinic region.
however,
is totally incompatible with
Subse-
reaction to
is almost the sole product of the
(M+ = 280) and absorption
1740 cm-l) consistent with the structure contains
that 2 quickly underwent
"X", which could be isolated by preparative
phase chromatography. reaction,
consistent with structure 2.
revealed
completely
consistent
structure
with structure
4c-f H
OOCH2
CCOCH2
CCCH
0
-16
0
-17
example of an ene reaction
17 The formation of -16 is the only involving a 1,8-transfer of hydrogen between carbon
atoms and is particularly
noteworthy
product of an intramolecular
which
it occurs.
ene
17
reaction.
for the exceptionally
mild conditions
under
of 2 into -16 is unaffected by the presence of (P(3P)3Ni(C0)2 in the reaction of -15 and 4. It is perhaps noteworthy that virtually all homo Diels-blder reactions are
observed
The conversion
in systems
(e.g. norbornadiene,
barrelene 18igwhere ene reactions
could
violation of Bredt's rule. The formation of -16 suggests that where both reaction pathways are available the ene reaction may well 19 In any event the foregoing results suggest be the one which is usually favored. occur only with concurrent
that the homo Diels-Alder
reaction will not be the cornerstone
realized
We are presently
synthesis
of 1.
Acknowledqements: Petroleum
by the American Chemical
Society,
The author is indebted to Cornel Pietruszewski.
Schmidt, and John Hagge_rty for assistance ials.
of our yet-to-be
other routes to longicyclene
The financial support of Research Corporation
Research Fund, administered
fully acknowledged.
exploring
in the preparation
and the is grate-
Thomas
of starting mater-
440
No. 6
Footnotes
and References
1.
U.R. Nayak and Sukh Dev, Tetrahedron 4099 (1968).
2.
See T.K. Devon and A.I. Scott, "Handbook of Naturally Occurring Volume 11,"Terpenes: Academic Press, London, 1972, p. 181.
3.
In view of the fact that Nayak and Dev demonstrated1 that (+)-longicyclene and (+)-longifolene ar interconverted by cupric acetate in acetic acid, the two recorded syntheses % of (+) longifolene also constitute, in a formal sense, syntheses of longicyclene.
4.
E.J. Corey, M. Ohno, R.B. Mitra, and P.A. Vatakencherry, J. Amer. Chem. Sot., 86, 478 (1964); J.E. McMurry and S.J. Isser, z., 94, 7132 (1972).
5.
E.g.see (a) W_dZ. Barnett and J.C. McKenna, Tetrahedron Letters, 227 (1971);. (b) Steven C. Welch, Ph.D. Thesis,University of Southern California, 1969; Diss. Abstr. B, -29,3685 (1969). For leading references see (a) R.C. Cookson, J. Dance and J. Hudec, J. Chem. sot., 5416 (1964); (b) P.K. Freeman, D.M. Balls and J.N. Blazevich, J. Amer. Chem. SOC.,~, 2051 (1970); (c) reference 12 in H.G. Kuivila and C.R. Warner, J. Org. Chem.,& 2845 (1964).
6.
Letters,
243 (1963); Tetrahedron,
Compounds~~,
7.
Ir and nmr spectra of this compound are completely assigned structure.
8.
Farchan Research Laboratories, Willoughby, Ohio. We are also grateful Professor Ernst Koerner von Gustorf for a generous gift of 2-butyne.
9.
Dienophiles examined include acrylonitrile, maleic anhydride, dimethyl acetylenedicarboxylate, fumaronitrile, and tetracyanoethylene. Ber.,z,
consistent
10.
G.N. Schrauzer and P. Glockner,
11.
The elemental
12.
J. C. Lunt and F. Sondheimer,
13.
J. Shields, J. Chem. Sot., 2,
14.
G. Jones, Org. Reactions, 15, 204 (1967).
15.
L.A. Carpino, J. Org. Chem.,B,
16.
We are grateful this compound.
17.
For a recent review see H.M.R. Hoffman, Angew. Chem. Internat. (1969).
analysis of this compound
24,
with the to
2451 (1964). supports the assigned
structure.
J. Chem. Sot., 3361 (1950). 736 (1891). 2820 (1964).
to Dr. James McKenna
and G.L. Grunewald,
for making available
an nmr
SpCtrUm
Edit.,&
J. Amer. Chem. Sot., 86. 1434
Of 556
18.
H.E. Zimmerman
19.
For an exception to this generalization 84, 1257 (1962). s.,
20.
After this manuscript had been completed Professor Steven Welch informed us of We thank him for comthe synthesis of (+)-longicyclene in his laboratory. municating his results prior to publication.
see
J.K.
Williams
(1964).
and R.E. BenSOn,