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Diels-Alder-Reactions Part I New Preparative Aspects.

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Diels-Alder-Reactions
Part I: New Preparative Aspects[*]
BY PR1V.-DOZ. DR. J. SAUER
INSTITUT FUR ORGANISCHE CHEMIE DER UNIVERSITAT MUNCHEN (GERMANY)
Cycloadditions of conjugated dienes, named after their discoverers, have claimed preparative and mechanistic interest for nearly 40 years. The almost inexhaustible variability of
the components of these one-stage reactions ofers entry to important classes of compounds.
The systematization of the preparative uses of these reactions which is offered in this paper
relates predominantly to recent results. The mechanistic aspects of the Diels-Alder reactions
will be discussed later in the secondpart of this contribution.
A. Definition and History
B. The Diene Components
1. Acyclic Dienes
2. Acyclic Dienes with Heteroatoms
3. Polyenes
4. 1,2-Dimethylenecycloalkanes
5. Alicyclic Dienes
6 . Cyclopentadienones
7. o-Quinones and o-Quinonoid Systems
8. Aromatic Compounds
A. Definition and History
The combination of conjugated dienes with olefins is
only a special case of the more general reaction of cycloaddition 111; in the formation of the six-membered ring
( I ) , two new o-bonds are formed at the expense of two
x-bonds.
9. Heterocyclic Compounds
10. Olefins and Non-Conjugated Dienes
C. The Dienophilic Components
1 . Acyclic Alkenes and Alkynes
2. Allenes
3. Cyclic Dienophiles
4. Cyclic Azo Compounds
5 . Other Dienophiles with Heteroatoms
D. Retro-Diels-Alder Reactions
E. Future Prospects
structures proposed earlier by Stuudinger (with a cyclobutane ring) and Albrecht proved to require revision.
r
1
Other examples of cycloadditions are epoxidations and
carbene additions, dimerizations of olefins to cyclobutane derivatives, and 1,3-dipolar addition reactions [1,21.
Individual examples of diene additions according to the
Diels-Alder scheme are found in the literature as early
as the turn of the century. Although Zincke[31 correctly
explained the dimerization to perchloroindenone (2)
of the tetrachlorocyclopentadienone occurring as an
intermediate in the pyrolysis of l-hydroxyperchlorocyclopent-3-enecarboxylicacid, an elucidation of the
structure of the 1:1 adduct (3) of p-benzoquinone and
cyclopentadiene was first given by Diels and Alder[41;
[*I Part I1 will appear shortly in this Journal.
[ I ] R. Huisgen, R. Grashey, and J. Sauer in S. Patai: The Chemistry of Alkenes. Interscience, London 1964,p. 739.
[2]R. Huisgen, Angew. Chem. 75,604,742(1963);Angew. Cheni.
internat. Edit. 2, 565,633 (1963).
[3]T. Zincke and H. Giinther, Liebigs Ann. Chern. 272, 243
(1893); T. Zincke, ibid. 296, 135 (1897); T. Zincke and K. H.
Meyer, ibid. 367, 1 (1909).
Angew. Cliem. iilternot. Edit. ,! Vol. 5 (1966) J N o . 2
(3)
HO
The structure of the 1: 1 addition compound (4) from
cyclopentadiene and diethyl azodicarboxylate 151 first indicated that these addition reactions of dienes were cases
(41
[4a] 0. Dieis and K. Alder, Liebigs Ann. Chem. 460,98 (1928).
21 1
of a more general reaction principle. The classical paper
of Diels and Alder [4al provided the mental breakthrough
and introduced the fruitful preparative and mechanistic
investigations of these authors.
Complete treatment of the extensive experimental material is possible only within the scope of a monograph.
In this survey, the reviews that appeared before
1955 [6-13bl and a recent article 111 will be supplemented by newer examples from the literature.
1 -Substituted butadienes can be used
almost without
exception provided the substituent R is in the transarrangement (9), while the cis-form (10) generally
undergoes a Diels-Alder reaction only with poor yield.
B. The Diene Components
H
1. Acyclic Dienes
(10)
Owing to the possibility of rotation about the single
bond between the two conjugated double bonds, openchain dienes can occur in two conformations. With butadiene and its simple alkyl derivatives, the trunsoid form
( 5 ) frequently predominates in the conformer equilibrium [141. However, only the cisoid conformer (6) is capable of taking part in the Diels-Alder reaction.
transoid (5)
c i s o i d (6)
Substituents in butadiene influence the rate of cycloaddition to form six-membered rings, both through their
electronic nature and by displacing the conformational
equilibrium.
The extremely acid-sensitive 1-diethylaminobutadiene
(9), R = N(C2H5)2, adds to ethyl acrylate in benzene at 20 "C to form the 1 : 1 cis-adduct ( I I ) , which
changes readily into 2,3-dihydrobenzoic acid 1171. In the
analogous reactions of 1,4-bis(dialkylamino)butadiene
the two-fold elimination of amine from the Diels-Alder
adduct yields the aromatic system [181.
(11) 94%
1,4-Dihydroarornatic compounds, e.g. (12), are obtained in excellent yields when butadienes react with
dienophiles containing triple bonds 1191 (at about 150 "C
in toluene in the example illustrated).
By combining butadiene with dimethyl maleate or
fumarate in toluene at 155 "C the cis- (7) and the transform (8), respectively, of the cyclohexene-4,5-dicarboxylic ester are readily accessible via a stereospecific cisaddition [151.
[4b] 0. Diels,K . Alder, G . Stein, P . Pries, and H . Winckler, Ber.
dtsch. chem. Ges. 62, 2337 (1929).
[5] 0. Diels, J. H . Blom, and W. Koll, Liebigs Ann. Chem. 443,
242 (1925).
[6] K . Alder in W. Foerst: Neuere Methoden der Praparativen
Organischen Chemie. Verlag Chemie, Berlin 1943, Part I, p. 251.
[7] K . Alder in K . Ziegler: Praparative Organische Chemie. Verlag Chemie, Weinheim 1953, Part 11, p. 125.
[8] K . Alder and M . Schumacher in L. Zechmeister: Fortschritte
der Chemie Organischer Naturstoffe. Springer-Verlag, Vienna
1953, Vol. X, p. 1.
[91 K . Alder in Experientia Supplementum 11, 86 (1955).
[lo] J . A . Norton, Chem. Reviews 31, 319 (1942).
[ I l l M . C . Kloetzel, Org. Reactions 4, 1 (1948).
[I21 H . L. Holmes, Org. Reactions 4 , 60 (1948).
[I31 L . W . Butz and A . W . Rytina, Org. Reactions 5 , 136 (1949).
[13a] A . S . Onishchenko: Dime Synthesis. Translation from the
Russian by the Israel Program for Scientific Translations, Jerusalem, 1964; obtainable through Oldbourne Press, London.
[ 13bl A . Wassermann: Diels-Alder Reactions. Elsevier, New York
1965.
[I41 J. Gresser, A . Rajbenbach, and M . Szwarc, J. Amer.
chem. SOC.82, 5820 (1960); D. Craig, J. J . Shipman, and R . B.
Fowler, ibid. 83, 2885 (1961); W . B. Smith and J. L . Massingill,
ibid. 83, 4301 (1961).
[I51 A . A . Pefrov and N. P . Sopov, Sb. Statei Obshch. Khim. 2,
853 (1953); Chem. Abstr. 49, 5329 (1955).
212
112) 81%
l-Hydroxybuta-1,3-dienes can be regarded a s tautomers of
the a,$-unsaturated aldehydes a n d ketones. As a n example,
we select a reaction of 2-methylpent-2-enal (2-ethyl-1-methylacrolein) [71; here the primary adduct (13) can be isolated [201.
[I61 Review of the reactions of I-substituted butadienes: I. I .
Gurseinov and G . S. Vnsil'ev, Russ. chem. Rev. 32, 20 (1963).
(English transl. of Usp. Khim.).
[I71 S . Hiinig and H. Kahanek, Chem. Ber. 90, 238 (1957).
[ 181 M . F. Fegley, N . M . Bortnick, and C . H . McKeever, J. Amer.
chem. SOC.79, 4736 (1957).
[I91 See, e.g., N . P. Sopov and V . S . Miklashevskaya, Zh. obshch.
Khim. 26, 1914 (1956); Chem. Abstr. 51, 4968 (1957).
[20] H . Meerwein, Ber. dtsch. chem. Ges. 77, 227 (1944).
Angew. Chem. internat. Edit.
/ Vol. 5
(1966)
/ No. 2
T h e mechanistic relationship of this sequence of reactions t o
the Diels-Alder scheme has not, however, been shown. Recently, anthrone has been m ad e t o react with ethylene in the
presence of bases according t o th e sam e scheme t o give (14)
in 60 76 yieldr211.
OAc
(18)
OAc
COzCH3
~ll,O,C-C=C-CO,CR,
i - . Q
49%
OAc COzCH3
Tetraalkylbutadienes are eminently suitable for diene
additions provided they do not exhibit the structural element (10) of cis-1-substituted butadienes; 1,l'-bicyclopentenyl and 1 ,l'-bicyclohexenyl (19) ~ 8 lead
1
to polycyclic compounds 1291, as illustrated here for nitroethylene as the dienophile.
T h e adducts (15) of 2-alkoxybutadienes with maleic anhydride a nd its derivatives, which a r e obtained in high
yields, can, a s enol ethers, easily be hydrolysed t o cyclohexanone derivatives [221. I n th e case of 2-methylene-l,4pentadiene (2-vinylbutadiene), th e reaction with maleic anhydride does not s t o p at th e stage of th e 1 :1 adduct (16) ; t h e
new diene system ad d s on a second molecule of th e dienophile t o give the 1 :2 adduct [231.
Hexacyanobutadiene (20) 1301 acts not as a diene but as
a dierophile with respect to butadiene, i. e. it behaves as
a derivative of the very reactive tetracyanoethylene (see
Disubstituted dienes have been used very frequently;
Section
2,3-diphenylbutadiene, for example, gives o-terphenyl
derivatives 1241. The reaction of fruns,tvuns-l,4-diacetoxybutadiene (18) with methyl acrylate forms the first step
of a total synthesis of shikimic acid (17) [*51; a second
').
HC&H~
HC' Y H 2
NC,@N
+
IiCOkjjOcN
NC
'CN
- qN
N
(20)
OAc
2. Acyclic Dienes with Heteroatoms
?Ac
route to this compound begins with the Diels-Alder reaction between butadiene and propiolic acid (yield
85 "/o) 1261. Diacetoxybutadiene (f8) has very recently
been recognized as a suitable diene component for the
synthesis of benzene derivatives without isolation of intermediate products [271.
[21] J. S . Meek, W. Brice, V . Evans Godefroi, W. R . Benson,
M . F. Wilcox, W . G . Clark, and T . Tiedeman, J. org. Chemistry
26, 4281 (1960).
[22] M . S. Newmnri and H. A . Lloyd, J . org. Chemistry 17. 577
(1952).
[23] A . T. Blornquist and J. A . Verdol, J . Amer. chcrn. Soc. 77, 8 I
(1955).
[24] K . Alder and J . Haydn, Liebigs Ann. Chem. 570, 201 (1950).
[25] E. E. Stnissman, J. T . Sah, M . Oxman, and R . Daniels,
J . Arner. chern. Soc. 84, 1040 (1962).
[26] R . Grewe and I. Hinrich, Chem. Ber. 97, 443 (1964).
[27] R . K. Hill and R . M . Carlson, Tetrahedron Letters 1964,
1157; J . org. Chemistry 30, 2414 (1965).
Angew. Chem. internat. Edit.
/ Vul. 5
(1966)
No. 2
Whereas one or both carbon atoms in the dienophile
component can be replaced by heteroatoms (see Sections C. 4 and C. 5), there are fewer analogous examples
in the case of the dienes1311. Replacement of carbon
atom 1 in 1,3-dienes by oxygen yields cr$-unsaturated
aldehydes and ketones which combine preferentially
with electron-rich double bonds, enol ethers, olefins 1321,
enamines [331, N-vinylcarbamic esters, and N-vinylureas 1341 to form 1 :1-adducts; these addition compounds arise formally from a Diels-Alder reaction.
Hydrolysis of the enamine adducts (21) and the enol
ether adducts yield 1,5-dicarbonyl compounds, which
are valuable starting compounds for syntheses of alkaloids 1351. With acrolein (22) as the diene component,
[28] For example: E. D. Bergmann, H . Davies, and R . Pappo,
J. org. Chemistry 17, 1331 (1952).
[29] N. L . Drake and C . M . Kraebel, J. org. Chemistry 26, 41
(1961).
[30] 0.W. Websrer, J . Amer. chern. SOC.86, 2898 (1964).
[3 I ] A review of heterodienes and heterodienophiles is given by
S.B. Needleinan and M. C . Chang Kuo, Chern. Reviews 62, 405
(1962).
[32] C . W . Smith, D. C . Norton, and S . A . Ballard, J. Amer. chem.
SOC.73, 5267. 5273 (1951).
[33] G . Opitz and I. Luschnzanri, Angew. Chem. 72, 523 (1960).
[34] R . C . Schnlz and H . Hartmann, Chem. Ber. 95, 2735 (1962).
[35] K. Alder, H . Betzing, R. Kuth, and H. A . Dorrmann, Liebigs
Ann. Chem. 620, 73 (1959).
213
n > 1 are capable of adding dienes; with large values of
(21) 7970
(22)
n, Alder and Schamacher observed a relationship between the chain length and the position of addition of
the dienophile 1401.
c6Ht
C =CH- ( CH=CH)n-CH=
6Hg
the use for less reactive dienophiles is limited by the competing dimerization of the unsaturated aldehyde, which
formally is also a Diels-Alder reaction [361.
The reaction of compound (23), prepared in situ
from methanesulfonyl chloride and triethylamine, with
vinylogous amides can also be regarded as a DielsAlder reaction [371.
4. 1,2-Dimethylenecycloalkanes
1,2-Dimethylenecycloalkanes(26), in which the cisoid
conformation (6) necessary for reaction is fixed by the
linkage of the 2,3-positions of the diene through a ring,
are characterized by high reactivity 1411. This, and the
ready accessibility of this class of compounds by the
pyrolysis of esters or the Hofman elimination of suitable
bifunctional quaternary ammonium salts 1421, make the
1,2-dimethylenecycloalkanes (26) the favorite dienes
for the synthesis of polycyclic compounds, e.g. (27) ;the
reaction of 1,2-dimethylenecyclohexane[(26), n = 41
may serve as an example [431.
(27) 8570
(23)
R = CH,, R ’ = H, 80%
3. Polyenes
The mode of reaction of conjugated polyenes in diene
addition can be understood by regarding them as substituted butadienes. The case of 2-vinylbutadiene has already been mentioned in Section B. l. trans-Hexa-1,3,5triene reacts as 1-vinylbutadiene; the hydrogenation
product (24) of the Diels-Alder adduct with maleic anhydride can also be obtained from trans-hexa-1,3diene [381.
With (28), t h e Diels-Alder addition goes as far as t h e 1 :2adduct 1441; with (29) only two o f the three diene systems a r e
(28J
used for t h e addition of t h e dienophiIe[451. T h e dioxolane
derivatives (30) react only with t h e “record” dienophile tetracyanoethylene [461.
cis-Hexa-l,3,5-triene, as a cis-I-substituted butadiene
( l o ) , R = CH=CHz, does not react with dienophiles, so
that it can be separated from the trans isomer by the
Diels-Alder reaction 1391. Of the trans-w,w,w’w’-tetraphenylpolyenes (25), only the representatives with
1361 K. Alder and E. Ruden, Ber. dtsch. chem. Ges. 74,920 (1941);
K. Alder, H. Offermanns, and E. Riiden, ibid. 74, 905 (1941).
[37] G. Opitz and E. Tempel, Angew. Chem. 76, 921 (1964); Angew. Chem. internat. Edit. 3, 754 (1964).
[38] K. Alder and H . von Brachel, Liebigs Ann. Chem. 608, 195
(1957).
[39] J. C. H . Hwa, P . L. De Benneville, and H . J . Sims, J. Amer.
chem. SOC.82, 2537 (1960).
214
The four-membered cyclic diene (26), n = 2, adds to one
equivalent of maleic anhydride at 20-80 OC; for the formation of the 1:2-adduct an opening of the four-mem[40]K . Alder and M. Schumacher, Liebigs Ann. Chem. 570, 178
(1950). For further examples of polyene addition, see 181.
1411 Kinetic measurements: J. Sauer, D. Lang, and A . Mielerf,
Angew. Chem. 74, 352 (1962); Angew. Chem. internat. Edit. 1,
268 (1962); D. Lang, Dissertation. Universitat Miinchen 1963.
1421 Review: Y . A. Titov, Russ. chem. Rev. (Engl. transl. of Usp.
Khim.) 30, 327 (1961).
[43] W. J. Bailey and H . R. Golden, J. Amer. chem. SOC. 79, 6516
(1957).
[44] W . J. Bailey, E. J. Feffer,and J. Economy, J. org. Chemistry
27, 3479 (1962).
[45] H. Hopffand G. Kormany, Helv. chim. Acta 46, 2533 (1963).
1461 J. B. Miller, J. org. Chemistry 25, 1279 (1960).
Angew. Chem. internot. Edit. 1 Vol. 5 (1966)
No. 2
bered ring of the 1 : 1-addition compound (31) has been
discussed 1471. In the reactions of benzocyclobutene derivatives (32) with dienophiles (see Table l), a primary
solution with maleicanhydride, N-phenylmaleimide, oracrylonitrile [51,521. The “in siru” occurrence of 2,3-dihydronaphthalene and 2,2-dimethyl-2H-indene has been shown similarly
by means of trapping reactions [53,511. Both compounds, like
(36), were obtained by dehalogenation of dibromo compounds.
An intermediate (39) with the dihydronaphthalene unit
occurs also in the two-stage valence isomerization of the
benzocyclobutadiene dimer (37) to dibenzocyclooctatetraene (38). Compound (39) can be detected by a Diels-Alder
reaction with N-phenylmaleimide 1541.
ring opening to the 1,Zdimethylene derivative (33),
which here has an o-quinonoid structure, is also assumed [4*,491. The diiodo compound (32) ( X = I) reacts
similarly with N-phenylmaleimide [491 to give 35 % of the
naphthalenedicarboxylic derivative.
The expectation that the Diels-Alder reaction of (40)
with tetracyanoethylene would lead to a derivative of
cyclobutadiene proved incorrect; instead an adduct
with spiro structure 1551 is formed.
H5ct.,-
- moo
€
+
(35)
0
5. Alicyclic Dienes
Table 1. Reaction of benzocyclobutene derivatives (32) with maleic
anhydride.
(32), X
I TrT 1
Yield of (34)
[%I
I
Yield of (3.51
[%I
Huisgen and SeidI[5ol have recently shown that a valence-tautomeric equilibrium (32) + (33), in which
the four-membered ring opens stereospecifically, precedes the Diels-Alder reactions of cis- and truns-2,3-diphenylbenzocyclobutenes [(32), x = C ~ H S ] .
“0-Quinonoid” I ,2-dimethylenecycloalkeneshave been postulated as intermediates in other reaction sequences. Thus the
highly reactive 5,6-dimethylenecyclohexa-l,3-diene(o-quinodimethane) (36), which cannot be isolated, can be trapped in
1471 A. T . Blornquist and J. A . Verdol, J. Amer. chem. SOC. 77,
1806 (1955); 78, 109 (1956); K . Alder and 0. Ackermann, Chem.
Ber. 87, 1567 (1954).
[48] F. R . Jensen, W. E. Coleman, and A . J. Berlin, Tetrahedron
Letters 1962, 15.
[49] M . P. Cava and M . J. Mitchell, J. Amer. chem. SOC.81,5409
(1959); M . P. Cava, A . A . Deana, and K . Muth, ibid. 81, 6458
(1959); M . P. Cava, R . L. Shirlty, and B. W. Erickson, J. org.
Chemistry 27, 755 (1962).
[SO] R . Huisgen and H. Seidf, Tetrahedron Letters 1964, 3381;
cf. also G. Quinkert, K . Opitz, W . W. Wiersdorff,and M . Finke,
Tetrahedron Letters 1965,3009; G. Quinkert, Pure appl. Chem. 9,
607 (1964).
Angew. Chem. internat. Edit.
/
Vol. 5 (1966)
No. 2
The Diels-Alder reactions of alicyclic dienes claim both
historic and preparative interest. Diels and Alder recognized the general validity of the reaction scheme with
cyclopentadiene [41. For example, with maleic anhydride,
the 1 : 1-adduct (41) arises stereospecifically in quantitative yield.
d
The preferred endo-orientation in the addition is observed with many reactions of cyclic dienes, and is a
characteristic of this type of reaction [561. Thus endo-di[51] K . Alder and M . Fremery, Tetrahedron 14, 190 (1961).
[52] M . P. Cava, A . A . Deana, and K . Muth, J. Amer. chem. SOC.
81, 6458 (1959).
[53] I. G. Dinulescu, M . Avram, and C . D . Nenitzescu, Chem.
Ber. 93, 1795 (1960); M . Avram, I . G. Dinulescu, D . Dinu, and
C . D . Nenitzescu, Chem. and Ind. 1962, 555.
[54] M . Avram, I. G. Dinuslescu, D . Dinu, G. Mateescu, and
C . D . Nenitzescu, Tetrahedron 19, 309 (1963).
[ 5 5 ] A . T . BIomquist and Y. C. Meinwald, J. Amer. chem. SOC. 81,
667 (1959); the reaction of the corresponding dimethyl compound
is described by R . Criegee, Angew. Chem. 74, 703 (1962); Angew.
Chem. internat. Edit. I , 519 (1962).
[56] Review of the stereochemistry of Diels-Alder reactions:
J. G. Martin and R . K . Hill,Chem. Reviews 61, 537 (1961).
215
cyclopentadiene (42) is formed in high purity from the
monomer; in this reaction, cyclopentadiene acts both as
a diene and as a dienophile. This phenomenon, already
observed with acrolein, will be encountered again with
cyclopentadienones (see Section B.6), o-quinones (see
Section B.7), and thiophene 1,l-dioxide (see Section
B.9). Compound (42) serves as a source of cyclopentadiene, which can be obiained from it at 180 “C in a
retro-Diels-Alder reaction.
meric equilibrium between the monocyclic and the bicyclic compound can be detected in the eight-membered
cyclic triene [6*1(15 % of the bicyclic tautomer is present
in the equilibrium mixture at lOO”C), the existence of
such an equilibrium for the seven-membered cyclic triene
is still uncertain; it seems likely, however, from the recent investigations of Vogel et al. 1631 on oxepin [(48),
R = HI and its dimethyl derivative [(48), R = CH31.
(44)
(46) 77%
T he combination o f cyclopentadiene with alkenes an d alkynes
leads in single-stage syntheses and in high yields t o derivatives
of the angularly strained bicyclo[2.2.l]hept-2-ene and bicyclo[2.2.l]hepta-2,5-diene. Substituted cyclopentadienes
yield camphor derivatives in a few reaction steps [El, BicycloCLCl
(45)
(431
(430)
heptadiene itself is m ad e industrially f r o m cyclopentadiene
a nd acetylene in 60 to 65 % yieldr571; with hexachlorocyclopentadiene [581 it gives quantitatively compound (43), which
has become known a s a n insecticide under th e n am e Aldrin;
many other insecticides an d heat-resistant polymers a r e derived from the Diels-Alder adducts of hexachlorocyclopentadiene.
Like cyclopentadiene itself, hexafluorocyclopentadiene
(43a), which has been synthesized only very recently,
tends to undergo dimerization [58al, while hexachlorocyclopentadiene is stable as a monomer. The reactions
of (430) with dienophiles such as ethylene, maleic anhydride, or bicyclo[2.2.l]hepta-2,5-diene take place
smoothly; on the other hand, no reaction is obtained
with tetrafluoroethylene or tetracyanoethylene. With
respect to dienes (e.g. cyclopentadiene or anthracene),
(43a) behaves sometimes as a diene and sometimes as a
dienophile.
The reactivity decreases on passing to higher monocyclic conjugated dienes ; cyclooctadiene has almost no
ability for additionl91; dienes with 14- and 15-membered rings again react with dienophiles, although under
relatively severe conditions.
The Diels-Alder adducts of cycloheptatriene and cyclooctatriene are derived from the valence-bond tautomers
(44) and (45), respectively [59-621. Whereas the tauto[57] US.-Pat. 2875256 (Feb. 24th, 1959), J. Hyman, E. Freireich,
and R . E. Lidov; Chem. Abstr. 53, 13082 (1959).
[58] Reviews of the reactions of hexachlorocyclopentadiene:
H . E. Ungnade and E. T. McBee, Chem. Reviews 58, 249 (1958);
C. W . Roberts, Chem. and Ind. 1958, 110.
[%a] R . E. Banks, A . C . Harrison, R. N . Hasreldine, and K . G.
Orrell, Chem. Commun. (London) 1965, 41.
[59] K . Alder and G. Jacobs, Chem. Ber. 86, 1528 (1953).
[60] R. Huisgen and W . D. Wirth, unpublished work.
[61] W . Reppe, 0. Schlichting, K . Klager, and T. Toepel, Liebigs
Ann. Chem. 560, 1 (1948).
[62] A . C . Cope, A . C . Haven, F. L . Ramp, and E. R . Trumbull,
J. Amer. chem. SOC.74, 4867 (1952).
216
f49)
(50) R = CH3: 100%
The Diels-Alder adducts are again derived from the bicyclic compound (49) ; spectroscopic investigations have
shown a valence-tautomeric equilibrium (48) $ (49)
(in each case R = H), which is established very rapidly.
However, spectroscopic detection fails with bicyclo[4.2.0]octa-2,5,7-triene,
a valence-bond isomer of cyclooctatetraene. Nevertheless, Huisgen and Mietzsch demonstrated a small equilibrium concentration (ca.
0.01 %) by kinetic studies [641. At 165-170 OC, a product
analogous to (47) but poorer by 2 H is formed in 87
yield with maleic anhydride.
Heating of cyclooctatetraene gives several dimers [651.
G . Schriider recently revised the structure proposed for
one of them, and assigned to it the constitution (51) M I ;
he used this compound for his elegant synthesis of bullvalene (52) 1671. The typical Diels-Alder additions of the
___
[63] E. Vogel, R . Schubart, and W . A . Boll, Angew. Chem. 76,
535 (1964); Angew. Chem. internat. Edit. 3, 510 (1964); E. Vogel,
W . A . Boll, and H. Giinther, Tetrahedron Letters 1965, 609.
[64] R. Huisgen and F. Mietzsch, Angew. Chem. 76, 36 (1964);
Angew. Chem. Internat. Edit. 3, 83 (1964).
[65] W . 0.Jones, Chem. and Ind. 1955, 16.
[66] G. Schroder, Chem. Ber. 97, 3131 (1964).
[67] G. Schroder, Chem. Ber. 97, 3140 (1964).
Angew. Chem. internot. Edit. 1 Vol. 5 ( I 9 6 6 )
No. 2
cyclohexadiene system in (51) with dienophiles have
facilitated the elucidation of the structure of the dimer
(51).
monomers (58) or dimers (59) [74J. Like cyclopentadiene, cyclopentadienones may act as diene and dienophile components.
It may be recalled that cycloheptatriene reacts with nitrosobenzene [681 or azodicarboxylic ester 1691 to give l : 1adducts (53) and (54)respectively, which are not derived
from the valence tautomer (44). Compound (54) opens
up a productive route to tropylium salts L691.
(58)
I
Reaction 2 (58)
Table 2.
Fulvenes can be regarded as derivatives of the alicyclic
cyclopentadiene; dienophiles add onto the cisoid
diene system of the ring[70J*J. The splitting into the
starting materials, which takes place with the DielsAlder adducts of the fulvenes even under mild conditions, makes it difficult in many cases to elucidate the
configuration of the products; a critical study by Woodward and Baer has clarified the situation with the pentamethylenefulvene (55) maleic anhydride system 1721. The
reaction leading to the endo-adduct (56) at low temperatures is reversible; this enables the formation of the
thermodynamically more stable exo-adduct (57) at 80°C.
Q
R'
I
(58), R'
R2
I
R3
+ (59) as a function of
I
R4
I
the substituents.
Forms
present
2 (58)
\+ (59)
The tendency towards dimerization is particularly pronounced with the unsubstituted compound (58a). All
attempts to prepare this compound - e.g. by a retroDiels-Alder reaction - gave only the dimer [751. However,
the brief occurrence of cyclopentadienone (58a) - i. e.
a finite lifetime for this compound - is suggested by a
trapping experiment [76,77J; ( M a ) again exhibits diene
and dienophile properties, in this case in the reaction
with cyclopentadiene. The N,N-dimethylhydrazone of
+
The position of the adduct
components equilibrium
and the rate of the Diels-Alder addition have been
measured in the diarylfulvene-tetracyanoethylene and
diarylfulvene-acetylenedicarboxylicester systems 1731.
6. Cyclopentadienones
The diene activity of cyclopentadiene is retained in cyclopentadienone and its derivatives (58). Depending on the
substituents (see Table 2), cyclopentadienones exist as
[68] G. Kresze and G . Schulz, Tetrahedron J2, 7 (1961).
[69] J . M . Cinnamon and K. Weiss, J . org. Chemistry 26, 2644
(1961).
[70] Review on fulvenes: J. H. Day, Chem. Reviews 53, 167
(1953).
[71] Examples: K. Alder and R . Riihmann, Liebigs Ann. Chem.
566, 1 (1950); D . Craig, J . J. Shipman, J. Kiehl, F. Widmer, R .
Fowler, and A . Hawthorne, J. Amer. chem. SOC.76, 4573 (1954);
C . H . DePuy and P . R . Story, ibid. 82, 627 (1960).
1721 R . B. Woodwardand H . Baer, J. Amer. chem. Soc. 66, 645
(1944).
[73] G. Kresze, S . Rau, G . Sabelus, and H . Goetr, Liebigs A n n .
Chem. 648, 57 (1961).
Aiigcw. Cheni. internut. Edit.
1 Vol. 5
(1966)
!
No. 2
(58a), on the other hand, exists in the monomeric
forrn[781. The tendency of (58a) to dimerize can be deduced from its electron distribution 1791. Tetrachlorocyclopentadienone could be trapped as a monomer with
cyclopentadiene and norbornadiene L79al.
All cyclopentadienone derivatives existing in the monomeric form and the dimers which dissociate can take part
...
~
[74] C . F. H . Allen and J. A . van Allan, J. Amer. chern. SOC.72,
5 165 (1950); review of reactions of cyclopentadienones: C. F. H .
Allen, Chem. Reviews 37, 209 (1945); 62, 653 (1962).
[75] K . Alder and F. H . Flock, Chem. Ber. 87, 1916 (1954); C. H .
DePny and C. E. Lyons, J. Amer. chem. SOC. 82, 631 (1960).
[76] K . Hafner and K. Goliasch, Chem. Ber. 94, 2909 (1961).
[77] C . H . DePuv, M . Isaks, and K . L. Eilers, Chem. and Ind.
J961, 429; C . H . DePuy, M . Isaks, K. L. Eilers, and G . F. Morris,
J. org. Chemistry 29, 3503 (1964).
[78] K . Hafner and K. Wugner, Angew. Chem. 75, 1104 (1963);
Angew. Chem. internat. Edit. 2, 740 (1963).
[79] R . D . Brown, J . chem. SOC.(London) 1951,2670; E. D . Bergmann, G . Berthier, D . Ginsburg, Y. Hirshberg, D . Lavie, S . Pinrhas, P . Pullman, and A . Pullman, Bull. Soc. chim. France (5) 18,
661 (1951).
[79a] W . H . Dietsche, Tetrahedron Letters 1966, 201.
217
in Diefs-Alder reactions as diene components. With
double-bond dienophiles as co-reactants, the 1:1-adducts
occurring as primary products can as a rule be isolated;
when the temperature is raised, the CO bridges break [741.
The primary adducts with alkynes can be isolated only
in exceptional cases; the tendency towards aromatization possibly brings about the spontaneous elimination of C 0 [ 7 4 , 8 0 1 . Even the highly strained 1,2,4,5tetra-t-butylbenzene can be obtained in good yield in
this way from (60) [811.
An interesting complication occurs in the reaction of
tetraphenylcyclopentadienone with bicyclo[2.2.l]heptadiene (in CHC13 under reflux) [821. The angulary strained
1 :1-adduct (61) undergoes a retro-Diels-Alder reaction
under astonishingly mild conditions; here the tendency towards aromatization is an additional driving
force.
adducts in good yields. The rate of dimerization of corn
pounds (62) depends on the group R ; (62d) dimerizes
about 1100 times faster than (62a), and (626) almost
500 times faster than cyclopentadiene.
7. o-Quinones and o-Quinonoid Systems
The dimerization observed with many o-quinones shows
that these compounds are in principle capable of reacting
as dienes and dienophiles, e.g. to give (63) [83,841; however, as a rule, their capacity for acting as dienes predominates 1851. Thus the structure (64) of the 1:1-adduct
(63) 30-5070
from cyclopentadiene and tetramethyl-o-benzoquinone [861 proved to require revision : cyclopentadiene
takes part in the reaction as the dienophile and (65) is
formed [871.
o-Quinones contain two diene systems - the carbocyclic
system of the six-membered ring and that of the 1,2diketo grouping with two heteroatoms. Horner and
Merz [881 observed an interesting competition of these two
0+ co
92%
3 2%
2 3%
64%
It is not only cyclopentadienone (58a) that is characterized by an extraordinary tendency to undergo dimerization, but also the ketals (62) derived from it. Earlier
attempts to obtain the monomers (62d) gave only the
dimers [8%l.
c1
(62)
RO
OR
a R = CHI
b R = CzH5
c R-R
a R-R
=
=
-(CH2)3-(cH~)~-
Eaton and Hudson [82bl recently showed that the ketals
(62a) -(62d) have finite lifetimes. Trapping experiments
with some dienophiles gave the expected Diels-Alder
1958, 1718.
[80] J. J. Dudkowski and E. I. Becker, J. org. Chemistry 17, 201
(1 952).
[81] C. Hoogzand and W. Hubel, Tetrahedron Letters 1961, 637.
[82] K. Mackenzie, J. chem. SOC.(London) 1960, 473.
[82a] E. Vogel and E. G . Wyes, Angew. Chem. 74, 489 (1962);
Angew. Chem. internat. Edit. I, 404 (1962); C. H . DePuy, B. W.
Ponder, and J. D . Fitzpatrick, J. org. Chemistry 29, 3508 (1964).
[82b] P. E. Eaton and R. A . Hudson, J. Amer. chem. SOC.87,
2769 (1965).
[84] L. Horner and K . Sturm, Liebigs Ann. Chem. 597, 1 (1955);
L . Horner and W. Diirckheimer, Chem. Ber. 95, 1219 (1962).
[85] L. W. Butzand A . W. Rytina, Org. Reactions 5, 136 (1949);
J . A . Barltrop and J. A . D. Jeffreys, S. chem. SOC.(London) 1954,
154.
[86] L. I. Smith and L . R. Hac, J. Amer. chem. SOC. 58, 229
(1936).
[87] L . Horner and W. Spietschka, Liebigs Ann. Chem. 579, 159
(1953).
[88] L . Horner and H. Merz, Liebigs Ann. Chem. 570, 89 (1950).
218
[83] J. Harley-Mason and A. H . Laird, J. chem. SOC. (London)
Angew. Chem. internat.
Edit. I Vol. 5 (1966) J No. 2
diene systems in tetrachloro-o-benzoquinone (66). Addition to the cyclohexadiene system or to the heterodiene system takes place depending on the nature of the
dienophile (styrene, 1 ,I -diphenylethylene); with cyclopentadiene as the dienophile (all reactions at 80°C in
benzene) both reactions occur to comparable extents.
Tetrachloro-o-benzoquinoneis, however, inert to typical
dienophiles such as acrylonitrile and maleic anhydride.
On the basis of the addition reactions with cyclopentadiene and maleic anhydride as dienophiles, it has
been found that the chlorination products of phenol and
some methylphenols possess the o-quinonoid structure
(67) and not the hypohalite structure (68) (R1-R4 = C1
or CH3) 1891.
The tendency of the o-quinones to dimerize is retained
even in 6,6-disubstituted cyclohexadienones [90,911, as
can be seen from the example of methyl-o-quinol acetate
(69) 1921.
with dienophiles 1931. The reaction again takes place
preferentially with electron-rich dienophiles such as
butadiene, styrene (55 %), isobutylene (45 %), and
1,l-diphenylethylene (87 %). The intermediate (70)
is also accessible in situ by intramolecular elimination of
water from (71).
Analogous reactions are possible in the benzene series
with o-dialkyl(aryl)aminomethylphenols or o-hydroxymethylphenol as sources of dienes, although the yields
are only moderate 1931.
8. Aromatic Compounds
In the adducts from aromatic compounds and dienophiles, the low-energy state of cyclic conjugation is completely destroyed. Since the loss of aromatic resonance
may already be quite considerable in the transition
state of cycloaddition, high activation energies, i. e. low
reactivities, are to be expected for the Diels-Alder
additions of this class of compounds. In agreement
with theoretical considerations [941, the diene properties
increase in the sequence benzene < naphthalene <
anthracene. As expected, benzene itself takes part in
Diels-Alder reactions only very sluggishly, and no 1 : 1adducts have yet been isolated; the formation of 1,2bis(trifluoromethy1)benzene in the reaction of benzene
with hexafluorobut-2-yne can, however, be rationalized
as a normal diene addition with subsequent elimination
of acetylene 1951. With durene (72) as the diene component, the 1: 1-adduct (73) is obtained; this is a derivative
of the interesting bicyclic compound barrelene [95,961.
R
6870
It is also reasonable to assume an o-quinonoid intermediate (70) for reactions of certain Mannich bases
The reactions of naphthalene with dienophiles, e.g.
maleic anhydride, still require drastic reaction conditions (100 “C)[97,981; with maleic anhydride a total yield
of 5 % of the adducts (74) and (75), approximately in a
1: 1 ratio, is obtained. 1,2,3,4-TetramethylnaphthaIene
18ooc
70)
50-65%
[89] 5’. Kumamoto, J. chern. SOC.Japan, ind. Chem. Sect. (Kogyo
Kagaku Zasshi) 64, 188 (1961); Chem. Abstr. 58, 2391f (1963).
1901 D. Y. Curtin and R . R . Fraser, J. Amer. chem. SOC.81, 662
(1959).
[91] K . Alder, F. H . Flock, and H . Lessenich, Chem. Ber. 90,
1709 (1957).
[92] W . Metlesics and F. Wessely, Mh. Chem. 88, 108 (1957);
W. Metlesics, F. Wessely, and H . Budzikiewicz, ibid. 89, 102
(1958); F. Wessely and H . Budzikiewicz, ibid. 90, 62 (1959).
Angew. Chem. internat. Edit.
1 Vol. 5 (1966) / No. 2
[93] J. Brugidou and H . Cristol, C. R. hebd. Seances Acad. Sci.
256, 3149, 3326 (1963).
[94] R. D. Brown, J. chem. SOC. (London) 1950,691,2730; 1951,
1612. A. Streitwieser: Molecular Orbital Theory for Organic
Chemists. John Wiley, New York 1961, p. 432.
[95] C . G. Krespan, B. C . McKusick, and T. L. Cairns, J. Arner.
chern. SOC.83, 3428 (1961).
[96] C. D . Weis, J. org. Chemistry 28, 74 (1963).
[97] M . C. Kloetzel and H . L. Herzog, J. Amer. chem. SOC.72,
1991 (1950).
[98] K . Takeda, K . Kitahonoki, M . Sugiura, and Y.Takano, Chem.
Ber. 95, 2344 (1962).
219
reacts substantially faster than naphthalene. Surprisingly
an excess of the dienophile is said to slow down the
reaction with naphthalene [981. In contrast to other
examples[99al, the reaction is not accelerated by the
action of light [99bl.
Similarly to naphthalene, the 1,6-methanocyclodecapentaene (76) recently synthesized by VogeI and
Roth [loo] has a cyclic conjugated 10 x-electron system
with aromatic character. Diene addition with maleic anhydride sets in only at about 150 “C and stops at the 1: 1adduct; here the reaction involves the valence tautomer
(77) (two cyclohexadiene systems). The I :1-addition
compound (77a) from (76) and dimethyl acetylenedicarboxylate readily undergo thermolysis to give dimethyl phthalate and benzocyclopropene (see Section D).
As with other additions (e.g. halogenations to 9,lO-dihalogeno-9,10-dihydroanthracenes), with anthracene
and its derivatives the dienophile usually adds in positions 9 and 10. With 1,l-dicyanoethylene, 9,lO-dimethylanthracene yields 95 % of (83) even at room temperature, while reaction with the angularly strained norbornene to yield 88 % of (84) requires heating to 140 “C [1041.
P
R
H
H
On the basis of the structure of the resulting 1 :1-adducts,
Alder, Pascher, and Vagt [lo11 postulated for the addition
reactions of indene (78) a preliminary transition into
2H-indene (79), which adds dienophiles in the positions
I 78)
0
0
(79)
indicated. The fact that such an isomerization with a
hydrogen shift is possible in the temperature range of
diene additions (200 “C) has recently been shown by Roth
in an elegant NMR study on deuterated indene[102].
Berson and Aspelin[lo*al have come to the same conclusion concerning the reaction mechanism. The formation of (82) in small amount in the reaction of benzyne (80) with 1,l-dimethylcyclopropenecan also be explained readily by a 2H-indene intermediate (81) [1031.
[99a] G. 0. Schenck, Angew. Chem. 74,81 (1962); G. 0. Schenck,
S. P . Mannsfeld, G. Schomburg, and C. H. Krauch, Z . Naturforsch. 196, 18 (1964); D. Valentine, N. J. Turro, and G. S . Hammond, J . Amer. chem. SOC.86, 5202 (1964).
[99b] G. 0. Schenck, J. Kuhls, S . P. Mannsfeld, and C. H.
Krauch, Chem. Ber. 96, 813 (1963).
[I001 E. Vogel and H. D. Roth, Angew. Chem. 76, 145 (1964);
Angew. Chem. internat. Edit. 3, 228 (1964); E. Vogel, personal
communication.
[loll K . Alder, F. Pascher, and H . Vagt, Ber. dtsch. chem. Ges.
75, 1501 (1942).
[I021 W. R. Roth, Tetrahedron Letters 1964, 1009; G. Eergson,
Acta. chem. scand. 18, 2003 (1964).
[102a] J. A. Berson and G. E . Aspelin, Tetrahedron 20, 2697
(1964).
[I031 J. A . Berson and M. Pomerantr, J. Amer. chem. SOC.86,
3896 (1964).
220
The addition in dioxane of the compound c 6 0 6 (8.5), a
bis-anhydride of ethylenetetracarboxylic acid, to 9,lOdialkoxyanthracenes in the 9,lO-positions is reversible
at 20°C; at 100°C the dienophile adds irreversibly in
the 1,4-positions of the anthracene system[losl. This reaction resembles that of 9,lO-diphenylanthracene
with maleic anhydride; here a Diels-Alder addition
takes place only in the melt, again in the 1,4-position [106!.
In this case of the naphthacene derivative (86), as with
9,10-diphenylanthracene,steric factors are probably responsible for the fact that the dienophiles add to the
“external” diene systems in the positions indicated [1071.
[I041 J. Sauer, H . Wiest, and A . Mitlert, Chem. Ber. 97, 3183
(1 964).
[I051 J. Sauer, B. Schroder, and A . Mielerr, unpublished work;
J. Sauer, Angew. Chem. 75, 1123 (1963); Angew. Chem. internat.
Edit. 3, 150 (1964).
[I061 J. W . Cook and L. Hunter, J. chem. SOC.(London) 1953,
4109. In some disubstituted anthracenes, competing 9,lO- and
1,4-addition occurs with benzyne; E. H. Klanderman, J. Amer.
chem. SOC.87, 4649 (1965).
[I071 J. Rigaudy and N. K . Cuong, C. R. hebd. Seances Acad. Sci.
254, 4184 (1962). Other anthracene derivatives preferring 1,4addition are described by J. Rigaudy and N. K. Cuong, ibid. 260,
1705 (1965); J . Rigaudy and K. V. Thong, ibid. 260, 2527 (1965).
Angew. Client. iiirci,nat. Edit. 1 Vol. 5 (1966) f No. 2
The red-orange naphthothiadiazole (87) is less reactive
than anthracene, but, like the latter, adds e.g. maleic
anhydride to the central ring [1081.
T h e reactions of styrene a n d its derivatives, in which
only one double bond of t h e diene system belongs to the aromatic ring, sometimes give yields t o o low for preparative purposes because of t h e tendency of styrene t o undergo polymerization or copolymerization. As a rule, the 1 : I-adduct first
produced is n o t isolated; this c a n either a d d a second molecule of t h e dienophile [e.g. t o give (@)] or c a n undergo aromatization with a hydrogen shift [e.g. t o (89)1[109.1101.
meric keto forms of the phenols, as in the case of
2,5-dirnethylhydroquinone and rnaleic anhydride: at
200°C, 21 % of (91) is obtained and not the primary
adduct [1121.
Of the pseudoaromatic compounds azulene and tropolone, only some derivatives of the latter are suitable for
the Diels-Alder reaction [1151.2-Chlorotropolonefll6land
y-tropolone methyl ether [I171 react with maleicanhydride
to give respectively (92) and (93).
9. Heterocyclic Compounds
Since the discovery of the Diels-Alder reaction, the
heterocycles furan, pyrrole, and thiophen have been
thoroughly investigated with respect to their suitability
as diene components ; their reactivity decreases in the
above sequence.
HCH3
- H2c33-&
Furan adds rnaleic acid derivatives even at room temperature [118, 1191; oxabicycloheptene derivatives are
readily accessible in this way [e.g. (94) by reaction with
maleimide in ether at 20 "C].The tendency of the adducts
to redissociate is as pronounced as with the fulvene ad-
0
o o
(89) 40-5070
In contrast, 2-vinylnaphthalene and tetracyanoethylene
give 95 % of the 1: 1-adduct (90) at room temperature 1 11
ducts (cf. Section B.5). Like the alkyl derivatives, the
derivatives of cyanofuran [1201 and chlorofuran [1211, are
capable of undergoing cycloaddition.
Some intramolecular diene additions of furan derivatives take place particularly readily ; thus the nonactivated olefinic part of (95) adds to the furan nucleus
even at room temperature; dissociation takes place on
Phenols react with dienophiles only under drastic conditions [11*-1141; the adducts are derived from the tauto-
.CH2
H ~ =CHC '
[I081 M . P. C a w and R . H . Schlessinger, Tetrahedron Letters
1964, 3815.
[I091 K . Alder and R. Schmitz-Josten, Liebigs Ann. Chem. 595, 1
(1955); K. Alder and H . Niklas, ibid. 585, 97 (1954).
[I101 B. J. F. Hudson and R. Robinson, J. chem. SOC.(London)
1941, 715.
[ I 1 I ] W . J. Middleton, R . E. Heckert, E. L. Little, and C. G . Krespan, J. Amer. chem. SOC.80, 2783 (1958).
[ 1121 K . Takeda and K . Kitahonoki, Liebigs Ann. Chem. 606, 153
(1957).
[ I 131 R . C. Cookson and N . S . Wariyar, J. chem. SOC.(London)
1957, 327.
[ I 141 K . Takeda and K. Kitahonoki, J. pharmac. SOC.(Yakugakuzasshi) 73, 280 (1953); Chem. Abstr. 48, 2019 (1954); K . Takeda, S . Nagakura, and K. Kitahonoki, Pharmac. Bull. (Tokyo) I ,
135 (1953); Chem. Abstr. 49, 3103 (1955).
Angew. Cliem. iiiternnt. Edit.
.'
Vol. 5 (1966) / No. 2
[I 151 T. Nozoe in D. Ginsburg: Non-benzenoid Aromatic Compounds. Interscience Publishers, New York 1959, p. 396; K . Hafner and K . L. Morrtz, Liebigs Ann. Chem. 650, 92 (1961); W.
Treibs, Naturwissenschaften 47, 156 (1960).
[116] T. Nozoe and Y. Toyooka, Bull. Chem. SOC.Japan 34, 623
(1961); Chem. Abstr. 56, 12767b (1962).
[I171 0. L. Cltupinun and D. J. Pasto, J. Amer. chem. Sor. 81,
3696 (1959).
[118] With maleic anhydride: R . B. Woodward and H . Baer,
J. Amer. chem. SOC. 70, 1161 (1948). With maleimide: H.
Kwart and I. Burchuk, J. Amer. chem. SOC.74, 3094 (1952).
[I191 With maleic acid: J. A . Berson and R . Swidler, J. Amer.
chem. SOC.75, 1721 (1953).
[I201 C . D . Weis, J. org. Chemistry 27, 3514, 3520 (1962).
[I211 H. Krzikalla and H. Linge, Chem. Ber. 96, 1751 (1963).
22 1
vacuum distillation 11221. Furan itself combines with
acetylenedicarboxylic ester to give a 2 : 1-adduct (96) [1231.
R = COzCH,
0
Diphenylisobenzofuran (97), which itself is easy to obtain by a sequence including a Diels-Alder reaction [1241,
is a valuable diene component ;the benzocyclobutadiene
(98) appearing as an intermediate has recently been
ester. In the reaction of N-methoxycarbonylpyrrole [(loo),
R = HI, the primary adduct (101) cannot be isolated because
it eliminates acetylene at the high temperature.
It has so far been impossible to cause thiophene to react with
dienophiles; in fact, with hexachlorocyclopentadiene the
heterocycle acts as a dienophile with the formation of a bisadduct (1331. 2- and 3-vinylthiophenes, in which only one
double bond belongs t o the diene system of the heterocycle,
react in a manner similar to that of styrene “341. Of a number of
benzo[c]thiophenes [1351, the diphenyl derivative (104) may be
selected as an example [1361.
f104j
b
1105) 79%
5
(99)
trapped in the form of its diene adduct (99) with the aid
of this substance 1125-1271. The addition of (98) to furan
itself is possible, but gives a yield of only 5 % [1281.
Pyrrole and its derivatives have for many years had the reputation of being unsuitable for Diels-Alder additions; the electrophilic substitution readily occurring in the a-position of
the base substance gave rise t o side reactions: with maleic anhydride cr-pyrrylsuccinic acid was obtained after hydrolysis.
Some examples appearing in the last few years show that
pyrrole derivatives also possess, in principle, the capacity for
taking part in Diels-Alder reactions : N-benzylpyrrole [L29,1301,
N-methoxycarbonylpyrrole
[1311,
N-triphenylmethylpyrrole,
and N-l-naphthylpyrrole[1321 can be converted into
Diels-Alder adducts, particularly with acetylenedicarboxylic
ll0l)
f l 0 2 ) R = H: 43%
(103) R = CH,: 51%
R ’ = COzCH,
[I221 D. Bilovic, 2. Stojanac, and V. Hahn, Tetrahedron Letters
1964, 2071.
[123] 0 . Diels and S. Olsen, J. prakt. Chem. (2) 156, 285 (1940).
The second stereoisomer (96a) possible has recently also been
isolated; D. Gagnaire, personal communication.
[I241 R. Adams and R . B. Wearn, J. Amer. chem. SOC.62, 1233
(1940).
[125] M . P. Cava and R . Pohlke, J. org. Chemistry 27, 1564
(1962).
[126] M . Avram, I. G . Dinulescu, D. Dinu, and C. D . Nenitzescu,
Chem. and Ind. 1962, 555.
[I271 M . P. Cava and M . J. Mitchell, J. Amer. chem. SOC.81,
5409 (1959); M . Avram, G. D. Mateescu, D. Dinu, I. G . Dinulescu,
and C. D. Nenitrescu, Acad. Rep. Populare Romine, Studii
Cercetzri stiint. 9, 435 (1961); Chem. Abstr. 57, 4605a (1962).
[I281 M . P . Cava and M . J. Mitchell, J. Amer. chem. SOC. 81,
5409 (1959).
[129] L. Mandell and W. A. Blanchard, J. Amer. chem. SOC.79,
6198 (1957).
[I301 R. M. Acheson and J . M . Vernon, J. chem. SOC.(London)
1962, 1148.
[131] R . M . Achrson and J. M . Vernon, J. chem. SOC.(London)
1961, 457; cf. also N. W . Gabel, J. org. Chemistry 27, 301 (1962).
[I321 L. Mandell, J. U.Piper, and C. E. Pesterfield, J. org. Chemistry 28, 574 (1963).
222
Thiophene 1,l-dioxide (108) can be prepared “in situ”
in several stages from the butadiene-sulfur dioxide adduct (107); all attempts to isolate or trap (108) have so
far failed 11371, since dimerization outweighs all compet-
1107)
f108)
ing reactions. In the case of the stable 3,4-dichloro derivative (109), on the other hand, additions are successful, (109) taking part in the reaction sometimes as a
diene and sometimes as a dienophile. For example, the
adducts (l09a) and (1096) are formed in exothermic
reactions in 61 and 16 % yields, respectively, based on
(109). Dimerization occurs only at a relatively high
temperature 11381.
[I331 H. Hamadait and M . Neentan, Israel. Pat. 9749; Chem.
Abstr. 52, 1263 (1958).
[I341 W. Davies and Q . N. Porter, J. chem. SOC.(London) 1957,
4958, 4961; J. F. Scully and E. V . Brown, J. Amer. chem. SOC.75,
6329 (1953); J. Szmuszkovicz and E. J . Modest, J. Amer. chem.
SOC.72, 571 (1950).
[I351 0. Dann, M. Kokorudz, and R. Gropper, Chem. Ber. 87, 140
(1954).
[I361 G. Wittig, E. Knauss, and K . Niethammer, Liebigs Ann.
Chem. 630, 10 (1960).
[137] W . J. Bailey and E. W. Cummins, J. Amer. chem. SOC.76,
1936 (1954). An account of the relative rates of addition of SO2
and maleic anhydride to dienes is given by 0. Grummitt and
A. L. Endrey, J. Amer. chern. SOC.82, 3614 (1960).
[I381 H. Bluestone, R. M . Bimber, R . Berkey, and Z . Mnndel,
J. org. Chemistry 26, 346 (1961); US.-Pat. 3 I10739 (Nov. 12th,
1963), Diamond Alkali Comp., inventor: R . M . Bimber; Chem.
Abstr. 60, 2870b (1964).
Angew. Chem. internat. Edit.
1 Vol. 5 (1966) 1 No. 2
The reaction of arylphospholes with acetylenedicarboxylic ester can be formulated by means of a diene synthesis as the initial reaction step [139J; for example, the
pentaphenyl derivative ( I 10) forms tetraphenylphthalic
ester in 88 % yield; the fate of the P-containing fragment
has not been elucidated [1401.
1110)
R ‘ = COZCH,
-
(109b)
(l09a)
1109)
CsH5
H5c,,
The diene activity is retained in perchloro-a-pyrone “481. Like
anthracene, acridinium bromide adds dienophiles to the central ring[1491. The fact that the addition compounds from 2,3dimethylquinoxaline and alkenes are not true Diels-Alder
adducts has been shown only recently[I*ol.
The reactions of symmetrical tetrazines with simple olefins, discovered by Carboni and Lindsey [1513, deserve
interest; Avram, Dinulescu, Marica, and Nenitzescu “521
have studied some conversions of the very reactive
1,2,4,5-tetrazine-3,6-dicarboxylate.
Nitrogen is evolved
in an exothermic reaction under surprisingly mild conditions, sometimes at room temperature. 1,6Dihydropyridazines, whose structures have been established by
NMR spectroscopy [153,1541, are produced in high yields.
The reaction sequence formulated with a primary dienophile addition in the 3,6-positions of the tetrazines to give
H5C6
6%
1-Ethoxyphosphole 1-oxide, like thiophene 1,l-dioxide
(108) and cyclopentadienone ( M a ) , has a pronounced
tendency to dimerize and can be trapped in the form of
its 1 : 1-adduct (111) only’with
a 50- to 100-fold excess
3
of cyclopentadiene [1411.
P
(Ill)
1
R
012)
Of the five-membered heterocycles with several heteroatoms,
only oxazoles [142-1451 can be used successfully in Diels-Alder
additions, while pyrazoles, thiazoles, imidazoles, and isoxazoles fail [146J. Pyridine derivatives can be obtained in good
yields by hydrolytic treatment of the adducts of the oxazoles
with dienophiles.
Of the six-membered heterocycles, the a-pyrones (112) deserve t o be mentioned; they react with olefins t o give 1 : l-adducts, while the Diels-Alder adducts from (112) and acetylenes spontaneously lose C 0 2 and undergo aromatization [1471.
[I391 I. G. M . Campbell, R. C . Cookson, and M . B. Hocking,
Chem. and Ind. 1962, 359.
[I401 E. H . Braye, W. Hubel, and I. Caplier, J. Amer. chem. Soc.
83, 4406 (1961).
[I411 D . A . Usher and F. H . Westheimer, J. Amer. chem. SOC.86,
4732 (1964).
[I421 G. Y. Kondrat’eva, Izv. Akad. Nauk S.S.S.R., Ser. khim.
Nauk 1959, 484; Chem. Abstr. 53, 21 940 (1959).
[1431 C . D . Nenitzescu, E. Cioranescu, and L. Birladeanu, Commun. Acad. Rep. Populare Romine 8, 775 (1958); Chem. Abstr.
53, 18003 (1959).
[I441 An elegant pyridoxine synthesis via the diene addition of an
oxazole derivative is described by E. E. Harris, R. A . Firestone,
K . Pfster, R . R. Boettcher, F. J. Cross, R. B. Currie, M . Monaco,
E. R. Peterson, and W . Reuter, J. org. Chemistry 27, 2705 (1962).
[I451 G. Y. Kondrat’eva and C . H . Huang, Dokl. Akad. Nauk
S . S . S . R . 142, 593 (1962); Chem. Abstr. 57, 2204g (1962).
[I461 I. I. Grandberg and A . N. Kosr, Zh. obshch. Khim. 29, 1099
(1959); Chem. Abstr. 54, 1500g (1960).
[I471 J . D . Bu’Lock and H . G . Smith, J. chem. S O C . (London)
1960, 502.
Angew. Chem. internat. Edit. VoI. 5 (1966)
1 No. 2
(113) was elucidated on the basis of mechanistic investigations [1551. When enamines, enol ethers, or esters
and ketene acetal are used, substituted pyridazines such
as (116) and (117) are obtained directly by single-stage
syntheses in excellent yields [1541.
$ OC2H,
H~Cs<
N, R
1116)
OCZHS
OCzH,
J,
N’
I
N\
N
I1
N
Y
R
y5c6H5
r
o
H,C=C, .NJ
CbH,
N\
R
1117)
R = C6H5,
100%
R = C02CH3, 100%
[I481 G. Murkl, Chem. Ber. 96, 1441 (1963).
“491 C. K . Bradsherand T. W. G. Solomons, J . Amer. chem. SOC.
80, 933 (1958).
[150] C . W . Bird and G. W . H . Cheeseman, J . chem. SOC.(London) 1962, 3037; E. C . Taylor and E. Smakula-Hand, J . org.
Chemistry 27, 3734 (1962); Tetrahedron Letters 1962, 1225.
[151] R. A . Carboni and R. V. Lindsey, J. Amer. chem. SOC.81,
4342 (1959).
[I521 M . Avram, 1. G . Dinulescu, E. Marica, and C . D . Nenitzescu,
Chem. Ber. 95, 2248 (1962).
[I531 M . Avrain G . R. Bedford, and A . R. Katritzky, RecueilTrav.
chim. Pays-Bas 82, 1053 (1963).
223
10. Olefins and Non-Conjugated Dienes
also take part in ene syntheses; however, ketones and
thioketones sometimes undergo a change in orientation.
Some particularly reactive dienophiles also take part in
reactions with simple olefins and non-conjugated dienes,
giving 1 : 1-adducts. The mechanistic relation to DielsAlder diene additions [I] justifies a brief discussion.
The reaction of 1-hexene with dimethyl acetylenedicarboxylate “561, as an example, includes all the characteristics of this type of reaction which Alder, in analogy
with “diene synthesis” has called the “ene synthesis”, or
“indirect substitution addition” [*I : the product of ally1
substitution always arises with double displacement in a
stereospecific cis-addition. The experimental results, together with an elegant study of the asymmetric induction
Th e definition of Diels-Alder additions given in Section A
(two x-bonds changing into two o-bonds) does not apply t o
the reactions of dienophiles with homodienes, in which the two
double bonds ar e separated by a tetrahedral center. In the
homo-Diels-Alder additions of bicyclohep?adiene, three new
a-bonds ar e formed at the expense of th:ee ;c-bonds in a 1,5addition. Th e addition of maleic anhydride, t h e first example
of this type of reaction, takes place in low yield “651. A sub-
,& &
C,H,, 80%)
1
(NC)&=C(CN)z
(NC)z
(CN)z
(120) 100%
80%
in “ene syntheses” [1571, suggest a multi-center mechanism.
“Indirect substitution addition” also takes place with
azodicarboxylic ester, as Hiiisgen and Pohl[15*1 have
shown with 1,3-diarylpropenes and 1,2- and 1,4-dihydronaphthalenes, as the olefinic components; radical
and ionic modes of reaction were excluded. The reaction
of the azo ester with simple olefins (1-hexene, 1-pentene,
cyclopentene, and cyclohexene) also is an “ene synthesis” 11591.
The C=O and C-S functions in chloral [1601, carbonyl
cyanide [1611, pyruvic acid “621, perfluorocyclobutanone
( I IS) [1631, and hexafluorothioacetone (119) [I641 can
stantially higher yield is given by reaction with t h e “record
dienophiles” tetracyanoethylene[J661,4-phenyl-l,2,4-triazoline-3,5-dione [1671, a n d t h e bis-anhydride (85) [1’351, the products being respectively (120), (121), an d (122). Acrylonitrilerl681, azodicarboxylic ester [1691,dicyanoacetylene [961, an d
some other highly reactive cyanoethylenes “69al react similarly.
Th e combination of barrelene (bicyclo[2.2.2]octa-2,5,7-triene),
which has one more double bond, with alkynes also leads to
t h e formation of homo-Diels-Alder adducts [17’31.
Th e 1,7-addition of tetracyanoethylene t o 1,3,5,7-tetramethylenecyclooctane (124) in tetrahydrofuran takes place
in accordance with the same structural principle: 3 n-bonds
-f 3 a-bonds 11711.
11541 D . Lang, Dissertation, Universitat Miinchen 1963 ; J. Sauer,
A . Mielert, D . Lang, and D . Peter, Chem. Ber. 98, 1435 (1965).
[I551 J. Suuer and D . Long, Angew. Chem. 76, 603 (1964).
[I561 K . Alder and H . von Brachel, Liebigs Ann. Chem. 651, 141
(1962);cf. also J . C . Suuer and G . N . Snusen, J. org. Chemistry 27,
2730 (1962).
[157] R . K . Hill and M . Rnbinovitz, J. Amer. chem. SOC.86, 965
(1964);J . A . Berson, R . G . Wall, and H . D . Perlmtrtter, ibid. 88,187
(1966).
[158] R. Hiiisgen and H . Poltl, Chem. Ber. 93, 527 (1960).
[I591 0.Achmatowicz and 0 . Achmutowicz, Roczniki Chem. 36,
1791 (1962);-?7,317(1963);Chem. Abstr.59,8610b, 12655e (1963).
[160] M . Vilkas, G. Dupont, and R. Dulou, Bull. Soc. chim.
France 1955, 799.
[161] G. I. Birnbaum, Chem. and Ind. 1961, 1 1 16.
[I621 R . T . Arnold and P . Veeravngu, J. Amer. chem. SOC.82,
5411 (1960).
[I631 D . C.Euglnud, J. Amer. chem. SOC.83,2205 (1961).
[I641 W. J. Middleton, E. G . Howard, and W . H . Sharkey,
J . Amer. chem. SOC.8.7, 2589 (1961);J. org. Chemistry 30, 1375
( 1965) ; W . J . Middletoit and W. H . Sharkey, ibid. 30, I384 ( I 965);
W.J . Middleton, ibid. 30, 1390, I395 ( I 965).
224
1124)
[I651 E. F. Ulltnan, Chem. and Ind. 1958, 1173
[166] A . T . Blomyuist and Y. C . Meinwald, J. Amer. chem. SGC.
81, 667 (1959).
[167] R . C . Cookson, S. S . H . Gilani, and I. D . R . Stevens, Tetrahedron Letters 1962, 615.
[I681 H . K . Hull, J. org. Chemistry 25,42 (1960). In the presence
of the bisacrylonitrile-Ni(0) complex the yield is quantitative:
G. N . Schrnuzer and S. Eichler, Chem. Ber. 95, 2764 (1962).
[I691 S.J. Cristol, E. L. Allred, and D . L. Wetzel, J. org. Chemistry 27, 4058 (1962); R . M . Moriarty, ibid. 28, 2385 (1963).
[169a] W. J . Middleton, J. org. Chemistry 30, 1402 (1965).
[I701 H . E. Zimmermnn and G. L. Grunewald, J. Amer. chem.
SOC.86, 1434 (1964).
[I711 J . K . Willionis and R. E. Benson, J. Amer. chem. SOC.84,
1257 (1962).
Angew. Chcm. ititerntit. Edit.
Vol. 5 ( 1 9 6 6 ) / N o . 2
C . The Dienophilic Components
The enormous preparative importance of Diels-Alder
additions is based on the great variability of both the
reactants; the discussion above has given a small insight
into the variability of the dienes. A short systematization
of the dienophiles will now follow. Without going into
mechanistic details at this point, it may be mentioned
that the reactivity of the dienophiles is a function of the
diene component: with electron-rich dienes (e.g. cyclopentadiene or 9,10-dimethylanthracene), electron-attracting groups X on the double bond accelerate the reaction '1041 ; with electron-deficient dienes (e.g. hexachlorocyclopentadieneand 1,2,4,5-tetrazines),electron-donating substituents in the dienophile have a promoting
effeCt[154,155,1721.
1. Acyclic Alkenes and Alkynes
The low reactivity of ethylene and of allylic compounds
with respect to electron-rich dienes limits the use of these
dienophiles ; the necessity of working in autoclaves at
high temperatures is also troublesome in the laboratory.
Of the monosubstituted ethylenes, acrolein, methyl
acrylate and acrylonitrile, styrene derivatives, and nitroolefins [I731 enjoy greater favor. 1,l-Disubstituted olefins (e.g. dimethyl methylenemalonate and 1,l-dicyanoethylene) are more reactive than their 1,2-disubstituted
isomers (dimethyl fumarate and fumaronitrile) L1041. Triand tetrasubstituted olefins with several activating substituents increase the preparative possibilities to a considerable extent. The interesting reactions of tri- and
tetracyanoethylene, in particular, may be recalled at this
point 1174,1751.
Acetylene itself reacts with electron-rich dienes only
under severe conditions; working with relatively large
amounts of acetylene under pressure in the laboratory is
not without danger. The reaction of dienes with vinyl
bromide and the subsequent elimination of HBr from
the Diels-Alder adduct, however, leads to the same
product as the direct addition of acetylene. Among the
dienophiles derived from mono- and disubstituted alkynes propiolic acid, phenylpropiolic acid, and acetylenedicarboxylic ester may be mentioned in particular. Dicyanoacetylene and hexafluorobut-2-yne have been discussed above in Sections B. 10 and B. 8 [95,961.
2. Allenes
Allene itself exhibits sufficient activity only with respect
to electron-deficient dienes - e. g. hexachlorocyclopentadiene 11761. Reference may be made to the addition
[I721 J. Sauer and H. Wiest, Angew. Chern. 74, 353 (1962); Angew. Chern. internat. Edit. /, 269 (1962); H. Wiest, Dissertation,
Universitat Miichen 1963.
[I731 Review of diene syntheses with nitro compounds: S. S .
Novikov, G. A. Shvekhgeimer, and A. A. Dudinskaya, Russ. chern.
Reviews (Engl. transl.) 29, 79 (1960).
[ 1741 C. L. Diekinsort, D. W. Wiley, and B. C. McKusick, J. Amer.
chcrn. Soc. 82, 6132 (1960).
[I751 T.L. Cairnsand B.C. McKusick, Angew. Chem. 73,520(1961).
[I761 H . Pledger, J. org. Chemistry 25, 278 (1960).
Aiigew. Cltetn. interiittt. Edit.
/ Vol. 5 (1966) 1 No. 2
of ally1 bromide with subsequent elimination of HBr,
which was used in the example below for establishing
the structure of the allene adduct (125) [1771.
c1
clQClz
c1
c1
(125)
Cyclopentadiene combines with allenecarboxylic acid
(126) to give a 1: 1-adduct in 84 % yield; in this process
the dienophile reacts as a derivative of acrylic acid at the
double bond indicated [1781.
The absolute configuration of allenedicarboxylic acid
(127) was determined by Agosta[1791; a diene addition
to cyclopentadiene formed the introductory step of the
sequence of reactions.
Extensive investigations by Staudinger [1801 have shown
that for ketenes the four-center cycloaddition to
form cyclobutane derivatives is preferred to the formation of a six-membered ring. Buvtlett et d.pointed
out an artifice for the preparation of the Diels-Alder adducts of ketene itself [1811. The diene is treated with 1cyanovinyl acetate (128) to give an adduct which on alkaline hydrolysis yields the desired ketone (129).
128)
82% 1/29)
62%
3. Cyclic Dienophiles
Among the cross-conjugated dienophiles, the greatest
importance is attached to the derivatives of p-benzoquinone 1131. Quinones substituted with electron-attracting groups prove to be particularly reactive with respect
[177] R. Riemschneidtr, F. Herzel, and H. J . Koetstlt, Mh. Chern.
92, 1070 (1961).
[I781 E. R. H. Jones, G . H . Mansfield, and M . C . Whiting,
J. chern. SOC.(London) 1956, 4073.
[I791 W. C. Agosta, J. Amer. chern. SOC.84, I10 (1962); 86. 2638
(1964).
[I801 H. Staudinger: Die Ketene. F. Enke, Stuttgart 1912; see
also H. L . Drvclen, J. Amer. chern. SOC.76, 2841 (1954); A . T .
Blomqtrist and J . Kwiatrk, ibid. 73, 2098 (1951); IV. Rrllenstnanu
and K . Ha/tier, Chern. Ber. 95, 2579 (1962); see also [ I ] .
[I811 P . D . Bnrtlett and B. E. Tote, J . Amer. chern. Soc. 78, 2473
(1956); C . H . DePuj and P . R. Story, ibid. 82, 627 (1960).
225
to electron-rich dienes. The dicyanoquinone (129) reacts more slowly than tetracyanoethylene, whereas
quinonedicarboxylic anhydride (130) does so considerably faster [1821.
0
Diphenylcyclopropenone and 1-diethylaminobutadiene
in boiling benzene give 2,7-diphenylcyclohepta-2,4,6-trienone (136) in a single-stage reaction with a yield of almost 70 % [189al; the adduct (136a) probably occurring
as an intermediate undergoes elimination and valence-isomerization to (136).
0
f 132)
(1311
methylcyclopropene, probably for steric reasons, does
notre act [1881. Triphenylcyclopropene and tetraphenylcyclopentadienone give heptaphenylcycloheptatriene by
the elimination of CO from the primary 1 : I-adduct [1891.
In (129), (130), a n d 1,4,5,8-naphthodiquinone(131) [18*1, as
expected, cyclopentadiene, 2,3-dimethylbutadiene[l8zJ,an d
1,2-dimethylenecyclobutadiene11831 ad d t o th e more highly
activated double bond [in th e 2,3-position in (129) an d (130)
a n d the 9,lO-position in (131)] t o form th e monoadduct. A n
interesting difference is found with butadiene: (129) forms
two monoadducts by th e reaction of the 5,6- a n d th e 2,3positions (yields 16 an d 62 %, respectively) [1841, whereas
(131) gives a 2: I-adduct (addition in th e 2,3- an d 6,7-positions) a nd a 1:l-adduct (reaction of th e 9,lO-double bond)
with comparable yields[1821. On th e other hand, (130) adds
butadiene in the 2,3-position with a yield of ab o u t 75 0/0[18*J.
There is still n o satisfactory explanation for this phenomenon.
The dienophilic activity of p-benzoquinones is even retained
in N,N'-disulfonylquinonedi-imines [e.g. (132)]"851.
In cyclobutene derivatives, as well, the angular strain
has a reaction-promoting effect; 3,3,4,4-tetrafluorocyclobutene reacts with dienes under remarkably mild
conditions [1901, as do unsaturated four-membered cyclic
sulfones [190al. Trapping reactions with the benzocyclobutadiene probably appearing "in situ" (cf. Section B. 9)
Through its diene additions, cyclopent-l-ene-3,5-dione take place at room temperature. The isolable cyclobuta(133), which exists completely in the diketo form, makes
diene derivative (137) also proves to be a very reactive
enolized 1,3-dioxocyclopentanes readily accessible [1861.
dienophile [1911. The corresponding monobromonaphthocyclobutadiene and the dibromo compound are too
short-lived, and could only be detected by trapping 1191-4.
f133)
100%
A fairly large number of cyclic olefins and acetylenes
with pronounced angular strain have found application
as dienophiles in the last few years. Already in the transition state, adduct formation is associated with a reduction in angular deformation; this acts as a driving
force in the Diels-Alder addition.
Cyclopropene [(134), R = HI combines with cyclopentadiene even at 0 "C rapidly and stereospecifically to give
the endo adduct [(135), R = HI [1871. Methylcyclopropene
reacts similarly to give (135) [R = CH3][1881, but di[I821 J. Sausr and B. Schroder, unpublished work; B. Schroder,
Dissertation, Universitat Miinchen, 1965.
11831 H . D . Hartzler and R. E. Benson, J . org. Chemistry 26, 3507
(1961).
[184] M . F. Ansell, B. W . Nash, and D . A . Wilson, J. chem. SOC.
(London) 1963, 3006, 3012.
[I851 Review: R. Adams and W . Reijschneider, Bull. SOC.chim.
France 1958, 23.
[I861 C. H . DePuy and E. F. Zaweski, J. Amer. chern. Soc. 81,
4920 (1959); C. H . DePuy and C. E. Lyons, ibid. 82, 631 (1960),
11871 K . E . Wiberg and W. J. Eartley, J. Amer. chem. SOC. 82,
6375 (1960).
[I881 G. L. Closs, L. E. Closs, and W . A. Bull, J. Amer. chem. SOC.
85, 3796 (1963); see also M . A . Buttiste, Tetrahedron Letters
1964, 3795.
226
The sp-hybridization determines the linear structure of
acetylene and permits the strain-free incorporation of
a triple bond only in rings with nine or more members.
The increase in the angular deformation with decreasing
ring size in the sequence cyclooctyne
cyclopentyne is
shown in an increasing tendency to undergo additions;
cyclooctyne exhi bits pronounced dienophilic properties.
Lower cycloalkynes have not been isolated, but their
existence has been proved by trapping reactions [19*1; for
--f
[I891 M . A. Buttiste, Chem. and Ind. 1961, 550.
[189a] J. Cicibattoni and G . A . Eerchtold, J. Amer. chem. SOC.
87, 1404 (1965).
[I901 R. J . Shozda and R. E. Putnam, J . org. Chemistry 27, 1557
(1962).
[190a] For example, L. A . Paquette, J. org. Chemistry 30, 629
(1965); D . C. Dittmer and N . Takashina, Tetrahedron Letters
1964, 3809.
[I911 M . P. Cavn, B. Hwang, and J. P. van Meter, J. Amer. chem.
SOC.85, 4032 (1963).
[191a] M . P.Cnvn and M . Hwang,Tetrahedron Letters 1965,2297.
[I921 G. Wittig and A. Krebs, Chem. Ber. 94, 3260 (1961);
G. Wirtig and R. Pohlke, ibid. 94, 3276 (1961); further studies o n
cyclic alkynes: G. Wirrig and J. Weinlich, ibid. 98, 471 (1965).
Angew. Chem. internat. Edit.
1 VoI. 5
(1966)
1 No.2
*
example, cyclopentyne gives the bis-adduct (138) with
diphenylisobenzofuran.
1138)
The cyclic compounds (142) [2001 and (143) [1671, on the
other hand, can be isolated. Compound (142) adds to
cyclopentadienc reversibly ; slightly above room temperature (142) offers a high-yield route to dehydrobenzene (80).
/
Arynes, e.g. dehydrobenzene (80) (see also Section B. 8),
represent cyclic acetylenes in one resonance form. In
brilliant investigations, Wittig and his school [I931 have
demonstrated the Diels-Alder additions of the “dehydroaromatic” intermediates. Cyclopentadiene ‘1931,
cyclohexadiene [1941, and even benzene and naphthalene [I951 add to the highly reactive species C 6 H 4 (80).
The dienophilic activity is also retained in the “dehydroaromatics” of the pyridine series and in quinoline derivatives [1961.
I
- N,, - S O ,
(80)
4-Phenyl-l,2,4-triazoline-3,5-dione(143) was found
in kinetic experiments to be a dienophile with extremely
good addition properties, many times better than tetracyanoethylene [1821; it combines with cycloheptatriene
even at -50°C to give (144) [1671. The Diels-Alder adducts with 9,lO-dialkoxyanthracenesundergo an acidcatalysed rearrangement at room temperature to give
(146) [1821.
4. Cyclic Azo Compounds
Some cyclic azo compounds, which have been synthesized only recently, possess high dienophilic activity;
however, only some of them are stable. Thus
indazol-3-one (139) [1971, 2,3-diaza-p-benzoquinone
(140) 11981, and 2,3-diaza-1,4-naphthoquinonehave
been detected by their reactions with dienes at low temperatures; in all cases the azo compounds were prepared by oxidation of the corresponding cyclic hydrazo
compounds. The dienes add to the -N=N- bond system of (139) and (140). In the dehalogenation of the
m
0
6
N
1144)
H ,o@
RO
0
1I 45)
1146)
’O
5 . Other Dienophiles with Heteroatoms
1140)
n
pyrazolinone (141), it is reasonable to postulate an
intermediate with a cyclic azo grouping [1991.
1/41)
1143)
‘70-90qo
[I931 G . Wittig, Angew. Chem. 69, 245 (1957); 74, 479 (1962);
Angew. Chem. internat. Edit. I, 415 (1962); G. Wittig, W. Uhlenbrock, and P. Weinhold, Chem. Ber. 95, 1692 (1962).
[I941 H . E. Simmons, J. Amer. chem. SOC.83, 1657 (1961).
(1951 R. G. Miller and M . Stiles, J. Amer. chem. SOC.85, 1798
(1963).
[196] T. Kauffmannand F. P. Boettcher, Chem. Ber. 95, 949, 1528
(1962); R. J. Martens and H . J. den Hertog, Tetrahedron Letters
1962, 643.
[I971 E. F. UIIman and E. A . Bartkus, Chem. and Ind. 1962, 93.
11981 T. J. Kealy, J. Amer. chem. SOC. 84, 966 (1962); R. A.
Clement, J. org. Chemistry 25, 1724 (1960); 27, 1115 (1962).
I1991 L. A. Carpino, P . H. Terry, and S. D . Thatte, Tetrahedron
Letters 1964, 3329.
Angew. Chem. internat. Edit. / VoI. 5 (1966) 1 No. 2
The replacement of carbon in the diene chain by heteroatoms is possible only in individual cases, as shown by
the examples of the u,P-unsaturated aldehydes and ketones and the 1,2,4,5-tetrazines (cf. Sections B. 2 and
B. 9). In contrast, in the dienophiles one or both C atoms
of the dienophilic multiple bond can frequently be replaced by heteroatoms without loss of activity. This has
already been illustrated by the cyclic azo compounds
described in Section C. 4.
Carbonyl functions in aldehydes and ketones add to
dienes particularly well if the C=O double bond is deprived of electrons by means of suitable substituents.
Formaldehyde reacts slowly [2011; the reactivity increases on passing to chloral [2021 and mesoxalic ester or
[200] G. Wittig and R . W. Hoffmann,Chem. Ber. 95,2718 (1962).
[201] D . G. Kubler, J. org. Chemistry 27, 1435 (1962); T. L. Gresham and T. R . Steadman, J. Amer. chem. SOC. 71, 737 (1949).
[202] W. J. Da/e and A . J. Sisti, J. Amer. chem. SOC. 76,81 (1954).
227
mesoxalonitrile [2031, and reaches a maximum with perfluorinated cyclobutanone (118) [204,1041; other fluoroketones (147) also react readily [2051. Glyoxylic ester and
Br'
92%
100% (148)
1118)
tely formed 12093. cc-Ketonitriles and cyanopyridines react at temperatures as low as about 250 "C [*lo].
R
RFNR
its semiacetals also react with dienes to give partially
hydrogenated pyrans [*061.
(153)
, 531
~
While the C=S bond system has proved to be a highly
dipolarophilic grouping [21, only a few examples of a
dienophilic activity are known ; the dienophilic systems
(119), (149), and (150) again bear electron-attracting groups
I-
Some of the longest-known addition reactions are those
azodicarboxylic ester 151. Tetrahydropyridazines such
as (154) call be isolated, usually in excellent
Of
B
F"Y2
F3
H F - c 0 2 c 2 H 5 ---t
"C02CzH5
More recent investigations [164,206a] have shown that
simple thioketones - for example, thiofluorenone - react with dienes to give Diels-Alder adducts even at room
temperature. Obviously the dienophilic nature of compounds with the C=S double bond has been overlooked,
not least because of their unpleasant odor. Here is presumably a wide field of preparative application.
Among Schiff bases [2071, immonium salts [2081, and nitriles [2091 (the latter react only at high temperatures)
C=N or CE N heterodienophiles are occasionally
found. (151) generally combines with dienes to give
Diels-Alder adducts in high yields (> 90 %)[2071. The
immonium salts that may be formed as intermediates from cc-halogenoamines such as (152) make spirocyclic ammonium compounds accessible 12081. Simple nitriles, such as benzonitrile, acetonitrile, and dicyanogen,
add to dienes only at about 400°C; the products of a
subsequent dehydrogenation, e.g. (153), are immedia[203] 0. Achnzatowicz and A . Zamojski, Bull. Acad. polon. Sci.,
CI. 111, 5, 927 (1957); Chem. Abstr. 52, 6333 (1958).
12041 D . C. England, J. Amer. chem. SOC.83, 2205 (1961); US.Pat. 3036091 (May 22nd, 1962); Chem. Abstr. 57, 16567e (1962).
[205] W . J. Linn, J. org. Chemistry 29, 3111 (1964).
[206] Y. A . Arbuzov, E. M . Klirnor, and E. I. Kliinova, Dokl.
Akad. Nauk S . S . S . R . 142, 341 (1962); Chem. Abstr. 57, 765,
(1962).
[206a] A. Sclionberg and B. Konig, Tetrahedron Letters 1965,
3361.
[207] G. Kresze and R. Albrecht, Chem. Ber. 97, 490 (1964); see
also R. Albrecht and G. Kresze, ibid. 98, 1431 (1965).
[208] H . Bohme, K. Hartke, and A. Miller, Chem. Ber. 96, 601
(1963).
228
H3C H
NH
H3C H
yields[211,2121, and they can be converted into cyclic
hydrazine derivatives. The Diels-Alder adducts, e.g. ( 4 ) ,
lead in many cases to new azo compounds, such as (155)
which, in turn, are capable of undergoing interesting reactions and make new compounds accessible [213,2141.
(4)
' 155)
94%
[209] G. J, Janz and A . G . Keenan, Canad. J. Chem. 25 B, 283
(1947); G . J. Janz and W. J. H . McCulloch, J. Amer. chem. SOC.
77, 3143 (1955); G . J. Janz and A . R. Monahan, J. org. Chemistry
29, 569 (1964).
[210] Examples: W . Polaczkowa and J . Wolinski, Roczniki Chem.
26, 407 (1952); Chem. Abstr. 48, 11359 (1954); W . Polaczkown,
T. Jaworski, and J. Wolinski, ibid. 27, 468 (1953); Chem. Abstr.
49, 3181 (1955); T. Jaworski and W . Polaczkowa, ibid. 34, 887
(1960); Chem. Abstr. 55, 8407d (1961); T . Jaworski, ibid. 35,
1309 (1961); Chem. Abstr. 57, 58881 (1962).
[21 I ] P. Baranger and J. Levisalles, Bull. SOC.chim. France 1957,
704; P . Baranger, J. Levisalles, and M . Vuidart, C. R. hebd.
Seances Acad. Sci. 236, 1365 (1953).
[212] K . Alder and H. Niklas, Liebigs Ann. Chem. 585, 81, 97
(1954); J. C. J. McKenzie, A. Rodginan, and G . F. Wright, J. org.
Chemistry 17, 1666 (1952); A . Rodgman and G . F. Wright, ibid.
18, 465 (1953); Y. S . Shabarov, N . I. Vasil'ev, and R. Y. Levina,
Dokl. Akad. Nauk S . S . S . R . 229, 600 (1959); Chem. Abstr. 54,
14259 (1960).
[213] R. Criegee and A. Rirnmelin, Chem. Ber. 90, 414 (1957).
[214] Experiments with hexachlorocyclopentadiene and azo
compounds: J. G. Kuderna, J . W . Sims, J. F. Wikstroin, and
S . B. Soloway, J. Amer. chem. SOC.81, 382 (1959).
Aiigew. Chem. internot. Edit. , Vol. 5 (1966)
No. 2
T h e possibility, mentioned in Section B. 10, of a radical ally1
substitution[2151 o r a multi-center reaction with a shift of t h e
double bond i n the reaction of azodicarboxylic ester with olefins also exists in principle with dienes, an d sometimes makes
it difficult t o establish the constitution of th e Diels-Alder 1 : Iadducts. Apparently slight changes in th e reaction conditions
lead t o the formation of different products [2161. T h u s azodicarboxylic ester a n d cyclohexa-1,3-diene a t 2OoC i n cyclohexane give the compounds (156) a n d (157) in a n exothermic
reaction (total yield 89 %). Without a solvent, between 20 an d
YO O C , only (158) is formed.
I
A
Possibly the influence of light, recently discovered by Askani [216al,offers a n explanation of th e apparent discrepancy:
on irradiation with a high-pressure mercury lamp, cyclohexad i e m a nd azodicarboxylic ester form only t h e adduct (1.56)
in 87 "/o yield.
radiation [2191, can be regarded formally in some cases
as Diels-Alder adducts. These reactions will not be
discusssed in this review.
D. Retro-Diels-Alder Reactions
The diene additions are reversible, often under surprisingly mild conditions; for the fulvenes and furans
(Sections B. 5 and B. 9) we have already demonstrated
this capacity for undergoing the retro-Diels-Alder reaction. Many adducts can be modified chemically and
yet still undergo cleavage in a retro-Diels-Alder reaction.
In this way a modified diene and/or dienophile are obtained. The fact that the retro-Diels-Alder reactions frequently claim preparative interest may be illustrated by
the following example.
The alkali-lability of the simple p-benzoquinones interferes with their epoxidation with alkaline H202. On the
other hand, the benzoquinone adducts (162) with cyclopentadiene can be easily epoxidized ; pyrolysis at
420 "C/10 mm smoothly yields the desired quinone
epoxides [2201.
Finally, there is also a possibility of replacing the two C
atoms of the double bond in the dienophile by two
different heteroatoms : nitroso compounds (159) and
N-sulfinyl compounds (160), on addition to dienes,
form six-membered heterocycles 131,2171. The adducts of the nitrosoaromatic compounds can easily be
converted by hydrogenolysis into cis-l,4-aminoalcohols [2181, and the diene adducts of N-sulfinyl compounds such as (161) give rise to a wealth of new reactions 12171, two of which are illustrated here.
R-N=O
(159)
R-N=S=O
(160)
The 1 : 1-addition compounds from dienes and molecular oxygen, which frequently are formed on ir[215] R . Huisgen, F. Jacob, W. Siegel, and A . Cadus, Liebigs Ann.
Chem. 590, 1 (1954); R . Huisgen and F. Jacob, ibid. 590, 3 1 (1954).
[216] S. G. Cohen and R . Zand, J. Amer. chem. SOC.84, 586
(1962); B. T. Gillis and 5 . E. Beck, J. org. Chemistry 27, 1947
(1962); 5 . Franzus and J. H . Surridge, ibid. 27, 1951 (1962); see
also M . Cais in S. Patai: The Chemistry of Alkenes. Interscience
Publishers, New York 1964, p. 739.
[216a] R . Askani, Chem. Ber. 98, 2551 (1965). cis-Azodicarbotylate: G. 0. Schenck et al., Z . Naturforsch. 206, 637 (1965).
[217] G. Kresze, A. Maschke, R . Albrecht, K . Bederke, H. P .
Patzschke, H. Stnalla, and A . Trede, Angew. Chem. 74, 135 (196%);
Angew. Chem. internat. Edit. I, 89 (1962); G. Kresze and J. Firl,
Angew. Chem. 76, 439 (1964); Angew. Chem. internat. Edit. 3,
382 (1964). E. S. Levchenko, J. G. Baron, and A . V. Kirsanov,
J. gen. Chem. U.S.S.R. (Engl. trans]. of Zh. obshch. Khim.) 33,
1546 (1963).
[218] G. Kresze and G. Schrilz, Tetrahedron 12, 7 (1961); Chem.
Ber. 96, 2165 (1963).
Angew. Chem. internat. Edit. f Vol. 5 (1966)
No. 2
R = H, CHs
n
4
0
+
@
'O
H
80-95%
R
0
As further examples may be mentioned: the preparation
of 6,6-disubstituted cyclohexadienones from dimeric fulvene epoxides 1911, the preparations of o-quinodimethane 148,491, and of acetylenedicarbonyl dichloride from
the anthracene adduct of the free acid 12211, and the conversion of 1-vinylcyclohexene into vinylcyclohexane via
the anthracene adduct 12221. The determination of the
position of groups in the cycloheptatriene ring has been
carried out through the addition of acetylenedicarboxylic ester and pyrolysis of the adduct to substituted
phthalic esters 12231. The transient existence of isobenzo[219] G. 0. Schenck, Naturwissenschaften 35, 28 (1948); Angew.
Chem. 64, 12 (1952); A . Schonberg: Priparative Organische
Photochemie. Springer-Verlag, Berlin 1958; see also [8]; K . Gullnick and C. 0 . Schenck in: Organic Photochemistry. Internat.
IUPAC Symposium, Strasbourg 1964; Butterworths, London
1965.
[220] K . Alder, F. H . Flock, and H . Benmling, Chem. Ber. 93,
1896 (1960).
[221] 0. Diels and W. E. Thiele, Ber. dtsch. chem. Ges. 71, 1173
(1 938).
[222] L . H. Slaugh and E. F. Magoon, J. org. Chemistry 27, 1037
(1962).
[2%3] K . Alder, R . Muders, W. Krane, and P . Wirfz,Liebigs Ann.
Chem. 627, 59 (1959); K . Alder, H . Jungen, and K . Rust, ibid. 602,
94 (1957); W. von E. Doering, G. Laber, R . von der Wahl, N . F.
Chamberlain, and R . 5. Williams, J. Amer. chem. SOC.78, 5448
(1956).
229
furan [(163), R = HI and its dimethyl derivative was
also shown for the first time by the retro-Diels-Alder reaction with trapping experiments 12241.
R
R
R
A
urably fast 12271; the preparation of the compound C6O6
(85) in solution (Section B. 8) in a similar manner may
be recalled. In warm ethanol, the hydrolysis product
(167) of the adduct from azodicarboxylic ester and
anthracene gives the diimide; which is capable of stereospecific cis-addition [2281.
95%
R = H, CH3
(167)
L
J
1163) R = H:
>
92%
It is not always the bonds formed in the addition that
are split on pyrolysis, as can be seen from an example
due to Criegee[2251. The adduct (164) decomposes at
about 2OO0C/18 mm into dimethyl phthalate and diacetoxybutadiene. Tetramethoxyethylene (166) was first
obtained by Hofmann and Hauser [2261 by a retro-diene
F0ZCH3
A
c
Ac 0
;
b
+
F
FC02CH3
-
H
COzCH3
Ac$$-jJ
COzCH3
Ac 0
fl64j
Compounds (168) and (169), which were isolated as the
only products, probably arise from many addition and
splitting steps: the reversibility of the addition step possibly ensures the establishment of thermodynamic equilibrium 12291.
(1681 30%
(169) 35%
A particularly fine example of a retro-Diels-Alder reaction has recently been contributed by Vogel et al. [2301.
The adduct (77a) (see Section B. 8) decomposes at
100 "C/1 mm to give a 45 % yield of benzocyclopropene,
which is very interesting in relation to bond theory, and
phthalic ester.
E. Future Prospects
synthesis from the easily accessible adduct (165) of 5,5dimethoxytetrachlorocyclopentadiene and phenylacetylene.
(165)
CCH3
oc
cH3q C=
c H,O'
H3
1166)
The adducts of tri- and tetracyanoethylene, dicyano-pbenzoquinone, and dicyanomaleimide with 9,lO-dialkoxyanthracenes decompose into the components in
solution, even at room temperature, sometimes immeas12241 L. F. Fieser and M. J. Huddadin, J. Amer. chem. SOC. 86,
2081 (1964).
12251 R. Criegee, W. HorauL and W. D . Schellenberg, Chem. Ber.
86, 126 (1953).
12261 R. W. Hoffmann and H . Hauser, Tetrahedron Letters 1964,
197.
230
Any short account of the Diels-Alder reaction must
necessarily be incomplete. However, the discussion of
the modes of reaction of diene and dienophile, possible
here only in a sketchy fashion, shows that the preparative
possibilities of diene additions are still not exhausted.
It has not been possible to discuss Diels-Alder reactions
initiated by irradiation.
In addition to preparative investigations, since the discovery of this cycloaddition to form six-membered rings
attempts have been made to clarify the reaction mechanism. A n account of systematic mechanistic studies
with the inclusion of stereochemical and kinetic results
and of orientation and catalysis phenomena will be given
in the second part of this paper.
Received: March 2nd, 1965
[A 486/279 IE]
German version: Angew. Chem. 78, 233 (1966)
Translated by. Express
Translation Service, London
.
[227] J. Sauer, R. Wiemer, and A . Mielert, unpublished work.
[228] E. J. Corey and W . L. Mock, J. Amer. chem. SOC. 84, 685
(1962); see also J. K. Stille and T.Anyos, J. org. Chemistry 27,
3352
12291 C. D . Weis, J. org. Chemistry 27, 3693 (1962).
[230] E. Vogel, W. Grimme, and S. Korte, Tetrahedron Letters
1965, 3625.
Angew. Chem. internut. Edit.
1 Vol. 5 (1966) No. 2
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