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Intramolecular Ene Reactions in Organic Synthesis.

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[35] A . Kornberg: DNA Synthesis, Freeman Comp., San Francisco 1974.
1361 C . C. Price: Synthesis of Life. Dowden, Hutchinson and Ross, Stroudsburg 1974.
[37] R. E. Ireland: Organic Synthesis. Prentice-Hall, Englewood Cliffs 1969.
[38] I . Fleming: Selected Organic Synthesis-A Guidebook for Organic
Chemists. Wiley, London 1973.
1391 S. lhrner: The Design of Organic Syntheses. Elsevier, Amsterdam 1976.
[40] S. Warren: Designing Organic Syntheses. Wiley, Chichester 1978.
[41] E. J . Corey, Pure Appl. Chern. 14, 19 (1967).
[42] E. J . Corey, W 7: Wipke, Science 166, 178 (1969).
[43] E. J . Corey, Q . Rev. Chem. SOC.25,455(1971).
[44] W 7: Wipke in W 7: Wipke, S. R. Heller, R. J . Feldmann, E. Hyde:
Computer Representation and Manipulation of Chemical Information.
Wiley, New York 1974, p. 147.
[45] J . Blair, J . Gasteiger, C . Gillespie, P . D. Gillespie, I. U g i in W 7:
Wipke, S. R. Heller, R. J . Fe/diuunn, E . Hyde: Computer Representation
and Manipulation of Chemical Information. Wiley, New York 1974,
p. 129.
[46] H. L. Gelernter, A . F. Sanders, D. L. Larsen, K . K . Agarwal, R. M .
Boirie, G . A . Spritzer, J . E. Searleman, Science 197, 1041 (1977).
[47] J . B. Hendrickson, Fortschr. Chem. Forsch. 62,49 (1976).
[48] G . J . Powers, R. L. Jones, G. A . Randall, M . H . Caruthers, J . H.
van de Sande, H. G. Khorana, J. Am. Chem. SOC.97, 875 (1975).
[49] S. R. Heller, G. W A. Milne, R . J . Feldmann, Science 195, 253 (1977).
[50] M.Bersohn, A . Esack, Chem. Rev. 76,269 (1976).
[51] K . Hetdsler, Science 189, 609 (1975).
[52] H . Bruns, Nachr. Chem. Tech. Lab. 25, 304 (1977).
[53] J . Thesing: Industrielle Arzneimittelforschung. Medizinisch Pharmazeutische Studienges., Frankfurt am Main 1977.
[54] J. Thesing, Naturwissenschaften 64,601 (1977).
[55] K . Alder, XIVth Int. Congr. Pure Appl. Chem., Experientia Suppl.
2. Birkhauser, Basel 1955, p. 86.
[56] A. Fischli, Chimia 30, 4 (1976).
[57] D.Seebach, H.-0. Kalinowski, Nachr. Chern. Tech. 24,415 (1976).
[58] A. Fischli, Nachr. Chem. Tech. Lab. 25, 390 (1977).
[59] D. H. R. Barton, Pure Appl. Chem. 49, 1241 (1977).
Intramolecular Ene Reactions in Organic Synthesis
New synthetic
methods (22)
By Wolfgang Oppolzer and Victor Snieckus [*I
Thermal cyclizations of appropriate dienes, enynes, enones and related unsaturated systems,
some of them carried out on an industrial scale, demonstrate increasingly the preparative
power of the intramolecular ene reaction. A variety of substituted, fused and bridged ring
systems, including natural products, are thus easily accessible in a regio- and stereo-selective
manner. Numerous examples are discussed systematicallyillustrating the possibilities. 11 initations,
and common features of this cyclization reaction and its reverse ring-opening procw
1. Introduction
The ene reaction, first recognized and systematically investigated nearly 35 years ago by Alder['], usually involves the
thermal reaction of an olefin containing an allylic hydrogen
(ene) with an electron-deficient multiple bond (enophile) to
form a 1 : 1 adduct as illustrated in Scheme 1. Experimental
evidence[*]and orbital symmetry consideration~[~]
are consistent with a concerted pathway involving a supra-suprafacial
endo- or exo-oriented interaction (see A). It thus resembles
the Diels-Alder reactionr4] and [1,5] sigmatropic shiftsr4,'I,
which are also considered to involve a cyclic 6e transition
state. Recent calculations concerning the ene
suggest
that in the transition state A the C-X bond is more developed
than the H-Y bond. (For related discussions regarding an
unsymmetrical transition state in the Diels-Alder reaction
seeC6].)
Mechanistic and preparative aspects of the ene reaction
were comprehensively reviewed by Hofmann in 1969['] (see
also [*I).
[*I
Prof. Dr. W. Oppolrer
DCpartement de Chimie Organique, UniversitC de Gen6ve
CH-1211, Geneve 4 (Switzerland)
Prof. Dr. V. Snieckus
Guelph-Waterloo Center for Graduate Work in Chemistry
University of Waterloo
Waterloo, Ontario N2L 3Gl (Canada)
476
Scheme 1 . The intermolecular ene reaction.
Early examples of the intramolecular ene reaction (Scheme
2) date back to the 1 9 3 0 ~ ~ ~ - "however,
1;
its synthetic utility
has become recognized only recently parallel to the general
interest in intramolecular [4 + 21"
41 and [3 21" 4* ' I cycloadditions. Similar to the cycloadditions, the intramolecular ene process profits from entropic advantage and exhibits
preparatively useful regio- and stereoselectivity. This applies to
three different modes of thermally-induced cyclizations (and
cycloreversions) (Scheme 2 ) in which the enophile is linked
by an appropriate bridge, either to the olefinic terminal
(Type I), the central atom (Type II), or the allylic terminal
(Type 111) of the ene unit.
'-
+
Angew. Chem. Int. Ed. Engl. 17,476-486 (1978)
Scheme 2. Variants of the intramolecular ene reaction (Type I, Type I1
and Type 111).
The aim of this review-in continuation of a review on
intramolecular cycloadditions[141-is to delineate the common
characteristic features of the intramolecular ene reaction and
to show, by selected examples, its scope, limitations, and utility
in organic synthesis.
(2)["] and also ring closure of ( I b ) gave (3) and (4) in
the ratio 14:1[161.
The analogous thermolysis of linalool(5) to give the plinols
( 6 ) - ( 9 ) was first carried out by Zkeda in 1936"" and more
carefully investigated by Ohloff 30 years later" *I. Flash
pyrolysis of ( 5 ) at 650°C under reduced pressure gave a
9 : 15 :50: 26 mixture of all four possible diasteriomeric plinols
(6) to ( 9 ) in high yield, again indicating high regioselectivity
but considerable loss of stereochemical control. In fact, a
recent careful study has shown['9] that thermolysis of ( 5 )
under kinetically controlled conditions at lower temperature
affords almost exclusively (8) and ( 9 ) . Thus, vapor phase
pyrolysis (240 to 290°C) of the silylether of ( 5 ) (so as to
avoid the partial dehydration occurring with ( 5 ) ) showed the
kinetic parameters AS*= -18.7 to -19.4 cal K-' mol-',
AH*=31.2 to 31.8 kcal mol-' and AG*=32.3 to 32.9 kcal
mol-' for the formation of (8) and ( 9 ) which is favored
over the formation of (6) and (7) by a difference
AAG* =2.2 to 3.1 kcal mol-'. Therefore the earlier observed
formation of the products ( 6 ) and ( 7 ) at 650"Cf'81 may
be attributed to the reversibility of the reaction at the higher
temperature. The synthetic utility of such cyclizations is
demonstrated["] by the conversion of the main product (8)
into the fungal sesquiterpene cyclonerodiol (1 0).
2. Type I Additions
2.1. 1,bDienes
2.1.1. Acyclic 1,6-Dienes
The majority of intramolecular ene reactions are concerned
with the thermolysis of 1,6-dienes. In the first systematic study,
Huntsman showed[161that 1,6-dienes undergo cyclization to
vinyl cyclopentanes, e . g . (1 a)+ (2). This demonstrated the
effective participation of nonactivated double bonds in the
intramolecular ene process in contrast to the necessity for
activated enophiles in the bimolecular counterpart. That this
effect may be due to entropic factors is evident from the
less negative entropy of activation (AS* = - 18 cal K- ' mol- ')
for the reaction ( 1 a)+(2) compared with that for intermolecular cases (AS* = - 30 to -45 cal K- ' mol- 'Izh, 'I). Furthermore, this example illustrates the regioselectivity observed
for numerous intramolecular ene reactions of 1,6-dienes in
that predominant C-C bond formation occurs between the
c/osest olefinic termini leading to five-membered rings. In
addition, stereochemical selectivity was displayed in that cyclization of ( 1 a ) yielded a 4:l mixture of the C(3)-epimers
(Ib),
I
Y
Thermolysis of the structurally similar dienes (11 a ) and
(1 1b ) likewise results in almost exclusive formation of cyclopentanes (13) and (14) with cis oriented adjacent isopropenyl
and methyl groups at C-4 and C-3["'. On the other hand,
loss of regioselectivity was observed in the pyrolysis of the
dienones ( 1 5 ) , leading to the cyclopentanones ( 1 6 a ) and
( 1 6 6 ) together with the cyclohexanone ( 1 7) in the ratio
2: 3 :
At 570°C, partial interconversion of ( 1 7 ) and ( 1 6 )
was observed, again indicating the operation of a retro ene-process.
R=H
422 "C
Angew. Chem. Int. E d . Engl. 17,476-486 (1978)
477
provided the cis-substituted cyclopentane ( 2 4 ) at the
same rate thus indicating no preference for an endooriented methoxycarbonyl group in the transition ~ t a t e ' ' ~ ] .
r
3009:/14 h
The first systematic stereochemical investigation[231of the
intramolecular ene reaction dealt with the regioselective thermal cyclization of the N-allyl-N-(2-butenyl)amides ( 1 8 ) and
( 19 ) to afford the cis-substituted pyrrolidine derivatives ( 2 0 a )
in high yields. The cis dienes ( 1 8 ) reacted under kinetic control
with 100% stereoselectivity whereas the trans dienes ( 1 9 )
furnished, in addition to (20a), minor amounts of the trans
isomers (20b). Model considerations (Scheme 3) show that
the observed stereochemical results are consistent with a suprasuprafacial process. In the cyclization of the cis diene (18),
the endo transition state C appears to be highly strained
thus favoring the exclusive formation of the cis-substituted
pyrrolidine ( 2 0 a ) via the relatively unstrained exo transition
state B.
JF$P'
R3
!
23@-2809:
(18)
R ' = M e , OMe
R 2 = H, M e
R3 = Me, P h
(191
xR3=;;oMe
R'
=
H
f
In the analogous cyclization of the trans diene (19), preference of the endo transition state D over the exo transition
state E is indicated. From these studies, it also appeared
that not only the stereochemical outcome but also the rate
of the intramolecular ene reaction of 1,6-dienes may be largely
independent of the ene geometry.
COOM e
COOM e
(22)
1
A
HR.H
(24)
(23)
In an attempt to synthesize the natural anthelminthics,
u-kainic acid (28) and a-allokainic acid (29), cyclization
of the readily available fumaric ester amide ( 2 5 ) was examAt 150"C, the cis-pyrrolidone (26) was the exclusive
product; on the other hand, thermolysis of the diene (25)
or (26) at higher temperature furnished predominantly the
thermodynamically more stable trans isomer (27). This finding
demonstrates the possibility of selectively synthesizing both
cis- and trans-substituted five-membered rings under conditions of kinetic or thermodynamic control. The conversions
(26)+ ( 2 8 ) and ( 2 7 ) - +( 2 9 ) have not yet been realized; however, the natural amino acid ( 2 9 ) has been prepared in good
yield from the simple precursor ( 3 0 ) in two synthetic operations12']. The key step (30)+(31) proceeds in quantitative
yield at surprisingly low temperatures (8OoC/16h or 25"C/3
months). Whether or not the exclusive formation of the transsubstituted pyrrolidine (31 ) is due to the reversibility of the
reaction remains to be clarified.
'COOH
q : O M e
COOH
(281
l"P
1
> 250°C
\ 1 6300°C
h
t
COCF,
80°C
COOEt
D
69%
CHCOOEt
Scheme 3. Transition states for the thermal cyclizations of the dienes ( 1 8 )
and (19).
Similarly, at 300 "C, both the terminally carbonyl-conjugated trans,trans diene (22) and its cis,trans isomer ( 2 3 )
478
The analogous cyclizations of the diene amides, esters, and
ketones ( 3 2 ) with carbonyl-conjugated ene units provide stereo
Angew. Chem. I n t . Ed. Engl. 17, 476-486 ( 1 9 7 8 )
and double bond isomers ( 3 3 ) and ( 3 4 ) in good yields and
thus indicate preference for Ha over Hh hydrogen transferF2@.
(An alternative explanation for this preference involves hydrogen transfer uin a dienol intermediate by a Type I1 ene reaction.)
Tlx 8
+
290-370s'
A
the C-I epimeric endo products ( 4 5 ) . Their base-induced interconversion provides easy access to either 1,4-trans or 1,Ccissubstituted natural spir0[4,5]decanes[*~~]
such as j3-acorenol
( 4 6 ) [ 2 7 a 1acorenone-B
,
( 4 7 ) [ 2 7 b 1and acorenone (48)[27'1.
Similar stereoselective formation of spiro-lactams, -lactones,
and -ketones (50) is observed on heating compounds ( 4 9 )
at high temperaturesrz61.
70-90 %
Ha
Hb
Ha
(32)
Ha
(33)
(01, x = NH, NR; ( b j , X
= 0;
(34)
( c j , X = CH2
(44 j
OH
DL - ( 4 6 )
2.1.2. Cyclic 1,6-Dienes
Cyclic dienes in which one double bond is situated in the
ring and the other in a side chain can likewise undergo intramolecular ene reactions. In contrast to the reaction
( 3 2 ) + ( 3 3 ) + ( 3 4 ) essentially no discrimination in the
transfer of Ha and Hb was observed in the thermolysis of
the cyclopentenylamide ( 3 5 ) to give the structural isomers
( 3 6 ) and (37)Iz3].However, 1,6-dienes containing an endocyclic ene component and a terminal olefin as enophile unit,
cyclize efficiently to single bicyclic products. Thus the highly
stereoselective transformations ( 3 8 ) + ( 3 9 ) , ( 4 0 ) + (41 ), and
( 4 2 ) + ( 4 3 ) illustrate nicely a simple route to fused or spiro
bicyclic systems containing cis-related methyl- and vinyl sub~tituents[~'J.
H,u~iNCOCF3
270"c/7h,
74 %
DL
- (47)
n
0
Activation of the enophile component by three carbonyl
groups as in ( 5 1 ) promotes smooth cyclization even at room
temperature to give a single spirolactone ( 5 2 ) , the stereochemistry of which has not yet been elucidated[281.The formation of three C-C bonds in a single synthetic operation
is demonstrated[2g1by the thermal addition of the triene ( 5 3 )
at 180°C to maleic anhydride involving an ene reaction of
the intermediate Diels-Alder adduct ( 5 4 ) . This simple
approach to the cage compound ( 5 5 ) illustrates the general
potential of combining pericyclic reactions in the synthesis
of complex molecules.
H b J
(35)
NCOCF3
Yi
(36)
qcoph
w
~ ~ - ( 4 8 j
28O"ciS h
84 %
,.-NCOM
COOM e
e
290 "C/13 h
0
___)
0
COOM e
75 %
0 - r C O M e
qo-%
-
MeOCN
250s'/3 h
___)
no I
(42)
MeB
(43)
0
0
These stereochemical features, which are also observed in
the thermal cyclization of open chain dienes (see Section 2.1.1),
have been exploited in a flexible and stereoselective approach
to spir~sesquiterpenes[~~].
Thus the readily available cyclohexenyl derivative ( 4 4 ) cyclizes at 280 to 290°C exclusively to
Angew. Chem. Int. Ed. Engl. 17,476-486 ( 1 9 7 8 )
4
(53)
Intramolecular ene reactions involving the transfer of atoms
other than hydrogen have rarely been observed. An interesting
o b s e r ~ a t i o n [ is
~ ~the
" ~cyclization
~~
of the Grignard reagent
479
( 5 6 ) which is readily a v d a b l e in one synthetic operation from
butadiene. Even at temperatures between 0 and 70"C, highly
selective cyclization to the cis-substituted cyclopentane (57 a )
is observed. At llO"C, ( 5 7 a ) as well as ( 5 6 ) isomerize to
the more stable trans product (57 b ) , indicating the reversibility
of the reaction (56)+ (57) at higher temperatures. Reaction
of the cyclic Grignard products ( 5 7 ) with a series of electrop h i l e ~ [ ~provides
~ " ] access to variously functionalized 1,2-disubstituted cyclopentane derivatives in a stereoselective manner.
MgBr
Analogous lithium transfer seems to occur in the cyclization of
3,7-dimethylocta-1,6-dienewith nBuLi/TMEDA to give the
allylic carbanion of 1,2-dimethyl-3-isopropenylcyclopent a d 3O '1.
2.2. 1,7-Dienes
tions. Thus, even on brief heating at 400"C, the enyne ( 6 4 a )
gives the cyclic 1,4-diene ( 6 5 a ) in good
Cyclization
of the enynes (64b)[231 and ( 6 4 ~ ) ~ also
~ ~ 'proceeds
'
easily
at about 200°C to the pyrrolidine derivatives (65 b ) and (65 c),
respectively, thus demonstrating smooth cyclization of an acetylenic enophile. Alternatively, an acetylenic ene component
is involved in the thermal conversion of (66) under similar
conditions into the allene (67)[231.The quantitative transformation of dehydrolinalool (68) into (69)[33a1 proceeds at
200°C with AS*=-13.7 cal K-' mol-' and AH*=28.7
kcal mol-'['91 (showing a significantly lower free energy of
activation than the analogous reaction of linalool ( 5 ) ) . The
reaction (68)+ (69) has recently been
in the
synthesis of the spirosesquiterpene, 0-acoratriene ( 7 2 ) . The
allylic alcohol in (69) serves as the reactive site for the introduction ofthe remaining carbon atoms of ( 7 2 ) via the intermediates ( 7 0 ) and (71). Similar Claisen rearrangement t.ia
reaction of ( 6 9 ) with 1-ethoxy-1-propene provides easy
access to the industrially important perfume ingredient
(82)r33
R
1,7-Dienes undergo the intramolecular ene reaction less
readily than the corresponding 1,6-dienes. Thus the transformations (%a)+ ( 5 9 ~ ) [ ~ ' ] , ( 6 0 a ) - (61
and
(62)- (63)[26a1require higher temperatures and proceed in
lower yields. Nevertheless, preparatively useful yields of sixmembered ring products such as ( 5 9 b ) or ( 6 1 b ) may be
obtained from 1,7-dienes containing carbonyl-activated enophile or ene components.
47
A
$
J
(64)
X
(65)
Y
( a ) , CH2
( b ) , NTs
Hz
Hz
(c). NMe 0
R
H
400'C;
seconds;
65%
H
180°C;
5h;
50%
Me
220°C;
2h;
80%
17NcocFv
210T12 h
H2
A
4
R2
@R1
I H
(66)
A
A
(67)
-
(59)
(58)
( a ) , R'
(b), R'
NCOCF3
43 56
= R' = H;
= COOMe,
R 2 = Me;
R2
49OOC;
25%
400 "C;
82%
200 "C
@OH
100 %
R2
Similarly, cyclization of the multifunctionalized enyne ( 7 3 )
to ( 7 4 ) represents the key step in a total synthesis of prosta-
& OSiM e3
2.3. 1,GEnynes and 1,2,GTrienes
NC
In contrast to dienes acetylenes generally participate in
intramolecular ene reactions under considerably milder condi480
OSiMeB
25OTl 27 min
\
OSiM e3
(73)
C5Hll
60%
OSi(t -Bu) Me2
NC&
- C~€€~I
OSiMe3
OSi(t-Bu)Mez
(74)
Anyew. Chem. Int. Ed. Engl. 17, 4 7 6 4 8 6 f 1978)
g l a n d i n ~ i ~In~ an
! exceedingly elegant synthesis of chiral acetic
the supra-supra character of the ene reaction is utilized
in the thermal cyclization of the enyne ( 7 5 ) to control the
configuration of the exocyclic double bond in the transient
product (76). Intramolecular chirality transfer by a subsequent
retro-ene reaction, (76)+( 771, generates the desired asymmetric center. Thus ( 7 7 ) , obtained from ( 7 5 ) in one synthetic
operation, provides after Kuhn-Roth oxidation (R)-['H, 3H]acetic acid in high optical purity.
2.4. Enones
Intramolecular ene reactions of enones have been widely
used in the synthesis of five- and six-membered ring systems.
The carbonyl group serves either as the enophile or, via its
en01 tautomer, as the ene unit.
2.4.1. Hydrogen Transfer from Carbon to Oxygen (Carbonyl
as Enophile)
Although the acid-induced cyclization of citronella1 (83),
observed as long ago as 189d3", probably proceeds
via cationic intermediates, the thermal transformation
(83)- (84) at 350°C, first reported 31 years later['], may
be described by an intramolecular ene mechanism. This
mechanism is also implicated in the reverse process, which
proceeds at 500°C and reflects the delicate energy balance
between (83) and (84). Both the forwardig1and reversei'']
reactions were observed before the ene reaction was formulated
as a general reaction principle.
An interesting selectivity is displayed by the thermal cyclizations of the propargyl ethers of nerol (78a) and geraniol
(78b) to ( 7 9 a ) and (79h ), respectively; in both cases transfer
of H, predominates over H,-tran~fer[~~"I.
that the sulfoxide (80a),
Recently, it has been
containing an allenic enophile unit, cyclizes quantitatively
to the doubly functionalized cyclopentene derivative (81 a ) .
Striking rate enhancement of this reaction can be achieved
by Lewis acid catalysis. An industrial process, actually carried
out on a scale of several 100 kg, involves efficient thermolysis
of the allene (80b) (also readily prepared from (68)) to give
(81 b), which is then converted into the odorant (82) (also
accessible from (69), vide
(83)
(8401
p-OH
(846)
a-OH
180 C / 3 Oh
49%
16%
ZnBr2/5-1OoC/15 min
66%
4 70
(84c)
P-OH
(84dj
a-OH
4%
124
traces
Because of its industrial importance the pyrolytic cyclization
ofcitronellal(83) has beenrestudied inm~redetail[~*"'I. Heating of (83) at 180°C leads to all possible stereoisomeric
isopulegols (84), the major isomer ( M a ) exhibiting transrelated hydroxyl and isopropenyl groups. This isomer is formed even more selectively from (83) at low temperature in the
presence of 1 equiv. of ZnBr,[38d1.On the other hand, when
the reaction is catalyzed by tris(tripheny1phosphane)rhodium
chloride, ( 8 4 ) is formed as the predominant isomer at 25 0C[391.
Theanalogouscyclization of the benzylimine derived from (83)
in the presence of SnCI, at - 25 0C[401yields a similar product
pattern as the uncatalyzed process of (83). A related example
is the synthesis of the eudesmane sesquiterpenes: the aldehyde
( 8 5 ) , readily available via reductive alkylation of rn-toluic acid,
smoothly isomerizes in the presence of zinc iodide catalyst to a
1 :3 mixture of the bicyclic dienols ( 8 6 a ) and (86b)C4'1.
2.4.2. Hydrogen Transfer from Oxygen to Carbon (Enol as
Ene-Component)
Monocyclizatian: By far the largest number of intramolecular enone cyclizations described to date involve hydrogen
Angew. Chem. lnt. Ed. Engl. 17,476-486 ( 1 9 7 8 )
481
transfer from an enol intermediate to an olefinic enophile.
As developed by Conia et al., this method leads to an enormous
variety of monocyclic, bicyclic, and bridged systems. A few
selected examples will suffice here in order to discuss this
principle within the framework of the intramolecular ene reaction (for a major review see r421). Thus &,<-unsaturatedketones
(87), on heating at 350-270°C on a Pyrex surface, furnish
substituted cyclopentanes (89) in high yield[431.In general,
these reactions proceed by two successive steps: rate-determining tautomerization, (87)- (881, followed by the actual cyclization process, (88)- (89). The high temperatures and surface catalysis required for the first step somewhat limit the
general applicability of this reaction. Subsequent enolization
determines also the trans configuration of the products (89a)
and (89 b ) containing available a-hydrogens. However, in
analogy to cyclizations of 1,6-dienes, kinetic control favors
a cis relationship between the hydrogen donor and hydrogen
acceptor units in the product, as in (89c).
tions, the ‘‘trans’’ enol intermediate (91) derived from (90)
affords[441a mixture of the stereoisomers (92a) and (92b),
whereas the cis en01 (94) resulting from ( 9 3 ) provides145J
exclusively the spiro product ( 9 5 ) with cis-related methyl
and carbonyl groups. Furthermore, bridged ring systems are
easily accessible,as exemplified by the efficient thermal conversion of (96) into (98)[461.
Double cyclizations:Elegant examples exploiting successive
pericyclic reactions include the thermal conversions
(99)-+ (101)[471, (102)and (105)- (107)[481.
Thus a single synthetic operation involving two sequential
ene reactions provides fused, spiro, and propellane systems.
P
oJo..
--_
(99)
( a ) , R’ = R~ = H;
( b ) . R’ = H;
(C),
R’ = Me;
R‘/H: trans; 84%
R’ = COOMe; R’/H:
trans; 90%
R‘IH: cis; 90%
R 2 = H;
In the kinetically controlled pyrolysis of cyclic ketones the
stereochemical outcome depends on whether the enol intermediate is fixed in the trans or cis configuration with respect
to the enophilic bridge. Thus, in accord with model considera-
2.5. Retro-Ene Reactions
*
Ring strain effects clearly shift the equilibrium between
( 1 08) and ( 1 09) highly in favor of the diene (retro-ene proces~)[~’].
In agreement with a concerted retro-ene mechanism
(transition state F), cyclopropanes with cis-related hydrogen
0
(92a) 17%
(92b) 58%
donor (Y) and acceptor (X) units cleave at significantly lower
temperatures than the corresponding trans isomers.
2.5.1. Hydrogen Transfer from Carbon to Carbon
(93)
(94)
r - 7
(97)
(95)
n
(98)
The suprafacial character of the retro-ene reaction is further
demonstrated by the highly specific chirality transfer
observed[s0]in the conversion of the carene derivative (110)
into the menthadiene ( f If). The related ring enlargement
’I
reaction of the annelated cycl~propanes[~and epoxidesC5
(112) into dienes ( I 13) implies transannular hydrogen
transfer and concomitant cleavage of the C-C bond common
to the two rings.
Angew. Chem. Int. Ed. Engl. 17,476-486 ( I 978)
K
(1231
(a), X = CHCH,OH; n = 2; 34OoC; seconds
( b ) , X = 0; n = 2; 195OC; 2 d a y s
(c),
(124)
R' = H, Me; R2 = H, Me, Et; n = 3, 10
X = CH,; n = 1; 180-3OO0C; ?
The earlier observations concerning the selective formation
of (2)-olefins (109) in the ring opening of the cis-alkylvinyl
cyclopropanes ( 1 08)[491have been elegantly exploited[531in
the stereoselective synthesis of the trisubstituted olefin (1 16).
This building block for the synthesis of Cecropia juvenile
hormone was obtained by pyrolysis of the cis-cyclopropane
( 1 1 5 ) which was readily available from the dienol (114).
OH
OH
2.5.3. Hydrogen Transfer from Carbon to Oxygen
cis-Methylcyclopropane carbaldehydes, ketones, and esters
( 128) also undergo thermal ring opening to provide y$-unsaturated carbonyl compounds (130) in good yield^[^^".^^'. 581.
This conversion, proceeding via enol (129), as well as the
related transformation ( 132) -+ (133)[591,
correspond to the
retro-ene equivalent of the reaction (87)-+(88)+(89) mentioned in Section 2.4.2. The analogous examples ( 1 35) + ( 136)
The synthesis of a jasmone precursor via the sequence
(117)-+(118)-+(119) also illustrates the highly stereoselective (Z)-olefin formation in the retro-ene step
( 1 18)+ ( 1 19)[541.
2.5.2. Hydrogen Transfer from Oxygen to Carbon
R = H. M e
As mentioned earlier (Section 2.4), the equilibrium
( 8 3 ) p ( 8 4 ) is shifted to the side of the acyclic enone ( 8 3 )
at higher temperatures. Likewise, unsaturated aldehydes ( 1 2 2 )
with different chain lengths can be obtained by heating the
55al. For example, transP-hydroxyolefins (121) to 500"C[38a,
2-vinylcyclohexanols,prepared by acid treatment of 7-hydroxymethylbicyclo[4.l.0.]heptanes, on heating to 440°C for 2 min
afforded stereoselectively (E)-&,<-unsaturatedcarbonyl compound~'~~
.
At~ 'considerable
lower temperature, the unsaturated glycols ( 1 24) cleave readily to the energetically more
favorable diketoaes ( 125)[561.Loss of cyclobutane ring strain
facilitates the related cleavage of ( I 26) to the y,&unsaturated
aldehydes (127)c5'].
Angew. Chem. I n t . Ed. Engl. 17,476-486 ( 1 978)
483
and ( 1 3 8 ) - ( 1 3 9 ) represent interesting thermal ring enlargements[601;thus, the annelated cycloheptane ( 1 3 9 ) is a potential
precursor for the synthesis of hydroazulene sesquiterpenes.
3. Type I1 Additions
3.1. 1,dDienes
The Type I1 addition of dienes has hitherto received relatively little attention. This reaction occurs less readily than
the corresponding Type I addition, as seen by the low conversion of ( 1 4 0 ) into f f 4 1 ) [ 6 1 1 .Likewise, the thermolysis of
3.2.2. Hydrogen Transfer from Oxygen to Carbon (Enol as
Ene Unit)
&,&-Unsaturatedketones with available a'-protons form cyclohexanones (Type 11) rather than cyclobutyl ketones (Type
I) because of ring strain. In fact, retro-ene reaction of ( 1 4 7 )
gives ( 1 4 8 ) which cyclizes via its n'-enol directly to ( 1 4 9 )
at higher temperatures[641.Complicated bridged ring systems
are accessible in an analogous manner by thermolysis of 6 , ~ and y,&-unsaturatedcyclic ketones, as shown by the conversions of ( 1 5 0 ) and (1 5 3 ) into the bicyclo[2.2.2]octanone (1 52)
j
-*
0
[d,J
4
( 1 9 ) , R' =R3=Me, RZ= H, which offers internal competition
betweenTypeI[ -t(20)]and Type I1 [+(21)] modes also shows
high preference for the former process.
3.2. Enones
(150)
The preparative utility of the Type I1 additions of enones
can be illustrated with the aid of a few examples.
3.2.1. Hydrogen Transfer from Carbon to Oxygen (Carbonyl
as Enophile)
Hydroazulene derivatives are formed in high yield by silica
gel catalyzed cyclizations of enones ( 1 4 2 a ) and (142b)162!
The operation of an ene process appears to be responsible
for the exclusive formation of exo-methylene products and
for the high stereoselectivity; in both cases major isomers
are formed, to which structures ( 1 4 3 ) and (144), respectively,
have been assigned[62a.62b1. This approach to hydroazulenes
has been exploited in the synthesis of the sesquiterpene
(152)
1151)
R = H, Me
[:A]
.
,
6&--.
&
O
(153)
and camphor ( 1 5 5 ) respectively at 400°C[651.The relative
configuration of ( 1 5 2 ) results from the endo transition state
requirement in Type I1 additions.
3.3.3. Sulfinyl Cations and Nitroso Groups as Enophiles
Although groups with hetero multiple bonds such as azo
and nitroso groups may serve as effective enophiles in intermolecular ene reactions[7],their participation in intramolecular
(143)
(142)
( a ) , R' = M e , R 2 = H;
( b ) , R'
(144)
=
H,
R2 = M e
180°C/1.5 h
86 %
or
AlCI,, O"Cll0 rnm
54 96
6N+
,C02R
X = C1, OH, S-i-Pr, NHPh, N.
'NH-CO~R
( + )-kessanol[62dl.Recently, the analogous stereoselectivecyclization of a G,&-unsaturatedaldehyde to produce a methylenedecanol was also
In the thermolytic
or Lewis acid-catalyzed cyclization of the ten-membered ring
enone ( 1 4 5 ) to the decalin (146)[631,conformational factors
appear to favor transfer of Ha (Type I1 addition) over transfer
of 9 or H, (Type I addition).
484
COOR
(158)
ene processes have rarely been tested. One of the few reports[661
describes the transformation of ( 1 5 6 ) derived from penicillin
sulfoxide into the cepham (158), presumably via the transient
sulfinium ion (157). An analogous cyclization of an unisolable
aliphatic nitroso compound into a cyclic hydroxylamine has
been described[671.
Angew. Chem. Int. Ed. Engl. 17,476-486 11978)
4. Type 111 Additions
The few cases of Type 111 reactions so far reported deal
with the thermal equilibrium between medium-sized cycloalkenes and acyclic @,coo-dienes,
the latter being favored at higher
temperature^[^.^'". 681. For example, 1,7-octadiene ( 1 6 0 ) is
obtained on heating trans- ( 1 5 9 ) or cis-cyclooctene (161),
observed in the formation of five-, six- and seven-membered
rings using nonpolarized enophiles may be ascribed to entropic
factors consistent with an “unsymmetrical” transition state[3J.
Thus, the development of the C-C-bond being more advanced
in the transition state than H-transfer concords well with
the regioselectivity which is also observed for other biradicaloid intramolecular processes. Steric repulsion probably favors
C-C bond formation between terminal olefinic centers in
Type I11 additions of ct,o-dienes to give medium-sized rings.
5.3. Stereochemistry
\
Hb,
the more strained trans-isomer opening at lower temperature.
In contrast, exclusive cyclization, ( 1 6 2 ) - ( 1 6 3 ) (164), was
observed at 350”C[691.
+
In systems where the ene and the enophile units are linked
by three or four atoms, the highly ordered transition state
may induce useful endo-exo discrimination avoiding nonbonding interactions between the bridge and substituents
and/or bond angle deformation. For example, the Type I
additions of systems containing the hydrogen donor site Z
cis with respect to the enophilic chain (Scheme 4) exclusively
lead to rings where the H-donor and H-acceptor sites Z and
Y appear in a cis relationship, e. g . (18)-+ ( 2 0 a ) , ( 2 3 ) - ( 2 4 ) ,
( 3 8 ) - ( 3 9 ) , ( 9 4 ) - ( 9 5 ) . Model considerations clearly show
this selectivity to be derived from a strong preference for
the endo over the exo transition state which would exhibit
considerable angle strain (see also Scheme 3).
5. Discussion
The available evidence allows the following generalizations.
5.1. Entropic Assistance
Since the intermolecular ene process shows a high negative
entropy of activation[2b,71 it clearly should profit from intramolecularity, as is well known for other pericyclic reactions[’4!
Accordingly, kinetic measurements of the transformations
( 1 ) - ( 2 ) and ( 5 ) - ( 8 ) ( 9 ) show an activation enthalpy
AH*=31.2 to 31.8 kcal mol-’ and an activation entropy
AS* = - 18.0 to - 19.4 cal K- mol- whereas the intermolecular ene reactions of alkenes with maleic anhydride exhibit
activation parameters AH+= 18.0 to 21.5 kcal/mol and
AS* = -36 to -45 cal K-’ mol-’[2b1. It thus appears that
the effective participation of nonactivated enophiles in the
intramolecular ene process is due to the less negative AS*
which compensates for the higher AH * values. Intramolecularity also facilitates the ene reactions of activated enophiles
as exemplified by the reactions (30)- ( 3 1 ) and (51)+ ( 5 2 ) .
+
’,
5.2. Direction of Addition
In 1,6- and 1,7-dienes and -enynes and the corresponding
enones and dienols containing several allylic or propargylic
hydrogens, preference for hydrogen transfer follows the order
Type I > Type I1 > Type I11 [for an exception see the
reaction ( 1 4 5 ) - ( 1 4 6 ) l . When the linking chain is shorter
than three atoms, formation of three- to four-membered rings
by the Type I pathway is thermodynamically disfavored thereby promoting the less strained Type I1 products, as illustrated
by the transformations ( 1 4 7 ) - ( 1 4 8 ) - (149), ( 1 5 0 ) - ( 1 5 2 )
and ( 1 5 3 ) - ( 1 5 5 ) . In most reactions of Type I and Type
11, carbon-carbon bond formation occurs preferentially
between the closest unsaturated centers. This preference,
Angew. Chem. I n t . Ed. Engl. 17,476-486 (1978)
Scheme 4. Stereochemistry of Type I reactions involving “cis” enophiles.
For the same reason, Type I1 reactions can occur only
in an endo manner when leading to five-, six- or seven-memberedrings [see e.g. (150)-+ ( 1 5 1 ) - ( 1 5 2 ) l . The counterplay
of kinetic versus thermodynamic control may influence the
stereochemical outcome as seen in the thermolysis of ( 5 ) ,
( 2 5 ) and ( 5 6 ) .
6. Concluding Remarks
Accumulating evidence points to the synthetic potential
of the intramolecular ene reaction. Based on the given examples
a set of rules have been derived, similar to those obtained
for intramolecular cycloaddition reactions[’41.Particular mention should be made of the stereoselective construction of
five-membered carbo- and heterocyclic systems including substituted, annelated, spiro-fused and bridged systems. The
smooth intramolecular ene reaction involving magnesium
transfer merits further application and suggests the use of
other organometallic ene components. More attention could
also be given to the Type I1 process using activated enophiles.
Combination of an intramolecular ene process either with
itself or with other pericyclic reactions offers additional fascinating possibilities.It appears possible that further mechanistic details of the ene reaction may be revealed through work
on the intramolecular variant. In view of the continuing need
for high yield and selective carbon-carbon bond forming cyclizations in the synthesis of natural products and other complex
485
molecules, further exploitation of this reaction is expected
in the near future.
Some of our own work mentioned in this article was carried
out at Sandoz Ltd., Basle, and some at the University of Geneva.
The latter investigations were kindly supported by the Fonds
National Suisse de la Recherche Scientifique, Sandoz Ltd., Basle,
and Givaudan SA, Vernier. We are indebted to Hendrik Andres,
Kumar Mahalanabis, Emil Pfenninger and Tarun Sarkar for
their valuable contribution. One of us ( K S.) thanks the National
Research Council of Canada and the Department of External
Affairs, Ottawa for Travel Grants as well as the University
of Geneva in aid of a Visiting Professorship in Geneva (19761977).
Received: September 13,1977 [A 221 IE]
German version: Angew. Chem. 90,506(1978)
_______
K. Alder, F. Pascher, A. Schmitz, Ber. Dtsch. Chem. Ges. 76,27 (1943).
a) L. M . Stephenson, D. L. Mattern, J. Org. Chem. 41, 3614 (1976);
b) F . R . Benn, J . Diq‘er, I . Chappell, J. Chem. SOC. Perkin Trans.
2,1977,533.
S. Znagaki, H . Fujimoto, K. Fukui, J. Am. Chem. SOC.98,4693 (1976).
Reviews: R. B. Woodward, R . Hofmann, Angew. Chem. 81,797 (1969);
Angew. Chem. Int. Ed. Engl. 8, 781 (1969); K. N . Houk, Acc. Chem.
Res. 8, 361 (1975).
R. C. Bingham, M. J . S. Dewar, J. Am. Chem. SOC. 94,9107 (1972).
Review: J . W Mcluer, Jr., Acc. Chem. Res. 7,72 (1974);P. Caramella,
K . N . Houk, L . N . Domelsmith, J. Am. Chem. SOC.99,4511 (1977).
Review: H. M. R. Hofmann, Angew. Chem. 81, 597 (1969); Angew.
Chem. Int. Ed. Engl. 8,566 (1969).
Review: E. C . Keung, H . Alper, J . Cbem. Educ. 49,97 (1972).
W Treibs, H. Schmidt, Ber. Dtsch. Chem. Ges. 60,2335 (1927).
V Grignard, J. Doeuure, C. R. Acad. Sci. 190,1164(1930).
7: Ikeda, K . Wakatsuki, J. Chem. SOC.Jpn. 57,425(1936);Chem. Abstr.
30, 5937 (1936).
Review: R. G. Carlson, Annu. Rep. Med. Chem. 9,270 (1974).
Review: G. Mehta, J. Chem. Educ. 53,551 (1976).
Review: W Oppolzer, Angew. Chem. 89,10 (1977);Angew. Chem. Int.
Ed. Engl. 16,10 (1977).
Review: A. Padwa, Angew. Chem. 88,131 (1976);Angew. Chem. Int.
Ed. Engl. 15, 123 (1976).
a) W D. Huntsman, 7: H. Curry, J. Am. Chem. SOC. 80, 2252 (1958);
b) W D. Huntsman, V C. Solomon, D. Eros, ibid. 80, 5455 (1958);c)
W D. Huntsman, Intra-Sci. Chem. Rep 6,151 (1972).
J . Tanaka, ‘7: Katagiri, K . Ozawa, Bull. Chem. SOC. Jpn. 44,130 (1971);
F. J . McQuillin, D.G. Parker, J. Chem. SOC.Perkin I, 1974,809.
H . Strickler, G. Ohlof, E. Kouats, Helv. Chim. Acta 50, 759 (1967).
W Pickenhagen, G. Ohlof, R . K. Russel, W R. Roth, unpublished work.
S. Nozoe, M. Goi, N . Morisaki, Tetrahedron Lett. 1971,3701.
K . H . Schulte-Elte, M . Gadola, G. Ohloff, Helv. Chim. Acta 54, 1813
(1971).
C. F . Mayer, J . K . Crandall, J. Org. Chem. 35,2688 (1970).
W Oppolzer, E. Pfenninger, K . Keller, Helv. Chim. Acta 56,1807(1973).
W Oppolzer, 7: Sarkar, unpublished results.
W Oppolzer, H. Andres, unpublished results.
a) M . Bortolussi, R. Bloch, J. M . Conia, Bull. SOC.Chim. Fr. 1975,
2722;b) ibid. 1975,2727;c) ibid. 1975,2731.
a) W O p p o l x r . Helv. Chim. Acta 56, 1812 (1973);b) W Oppolzer,
K. K . Muhulanabis, Tetrahedron Lett. 1975,3411;c) W Oppolzer, Prelog
Symposium, Zurich, November 1976;d) W Oppolzer, K. K . Mahular~ubis,
K . Bitrig, Helv. Chim. Acta 60, 2388 (1977).
I:R. KelIy, Tetrahedron Lett. 1973,437.
W Mauer, W. Grimme, Tetrahedron Lett. 1976,1835.
a) H. Felkin, J . D. Umpleby, E. Hagaman, E. Wenkert, Tetrahedron
Lett. 1972, 2285; b) H . Felkin, L. D. Kwart, G. Swiercrewski, J. D.
Umpleby, J . Chem. SOC.Chem. Commun. 1975,242.c) J. H . Edwards,
F. J . McQuillin, J. Chem. SOC.Chem. Commun. 1977,838.
486
[31] W D. Huntsman, P. C . Lang, N . L. Madison, D. A. Uhrick, J. Org.
Chem. 27,1983 (1962).
[32] W D. Huntsman, R. P. Hall, J . Org. Chem. 27,1988 (1962).
[33] a) W Hofmann, H. Pasedach, H. Pommer, W Re$ Justus Liebigs Ann.
Chem. 747,60(1971);b) P. Naegeli, R. Kaiser, Tetrahedron Lett. 1972,
2013;c) K . H . Schulte-Elte, DOS 2405568 (1974).
[34] G. Stork, G. Klaus, J. Am. Chem. SOC.98,6747(1976).
[35] C . A. Townsend, T Scholl, D. Arigoni, J . Chem. SOC.Chem. Commun.
1975,921.
[36] a) R. C. Cookson, E. Dufl; R. D. G. Rigby, unpublished work; b) R.
C. Cookson, P. J . Parsons, 5th Int. Symp. “Synthesis in Organic
Chemistry”, Oxford, July 1977;c) V Rautenstrauch, DOS 2657903
(1977).
1371 F. Tiemann, R. Schmidt, Ber. Dtsch. Chem. Ges. 29,903 (1896).
[38] a) G. Ohloff,Tetrahedron Lett. 1960,No. 11, p. 10; b) K. H . Schulte-Elte,
G. Ohlof, Helv. Chim. Acta 50, 153 (1967);c) 7: C. Chang, S. Washio,
H . Ueda,Agric. BioLChem.34,1734(1970);d)I: Nakatani, K . Kawashima,
Synthesis 1978,147.
[39] K . Sakai, 0.Oda, Tetrahedron Lett. 1972,4375.
[40] G. Demailly, G. Solladie, Tetrahedron Lett. 1977,1885.
[41] J . A. Marshall, P. G . M . Wuts, J. Org. Chem. 42,1794 (1977).
[42] Review: 1. M. Conia, P. Le Perchec, Synthesis 1975,1.
[43] F. Rouessac, P. Le Perchec, J . M . Conia, Bull. SOC.Chim. Fr. 1967,
818.
[44] J . M . Conia, G. Moinet, Bull. SOC.Chim. Fr. 1969,500.
[45] F . Rouessac, P. Beslin, J . M . Conia, Tetrahedron Lett. 1965, 3319.
[46] F. Leyendecker, G. Manduille, J . M . Conia, Bull. SOC.Chim. Fr. 1970,
556.
[47] F . Leyendecker, J . Drouin, J . M . Conia, Tetrahedron Lett. 1974,2931.
[48] J . Drouin, F . Leyendecker, J. M . Conia, Tetrahedron Lett. 1975,4053;
[49]
[SO]
[5i]
[52]
[53]
[54]
[55]
[56]
[57]
[SS]
7: Prange, J . Drouin, F. Leyendecker, J . M . Conia, J . Chem. SOC.Chem.
Commun. 1977,430.
For reviews see: a) W R. Roth, Chimia 20,229 (1966);b) D. S. Glass
R. S. Boikess, S. Winstein, Tetrahedron Lett. 1966,999;c) H. M . Frey,
R. Walsh, Chem. Rev. 69, 103 (1969);d) see also M . J . Jorgenson,
A . F. Thacher, Tetrahedron Lett. 1969,4651.
G. Ohloff, Chem. Ber. 93,2673 (1960).
a) W Grimme, Chem. Ber. 98,756 (1965); b) D. L. Garin, J. Am. Chem.
SOC.92,5254 (1970).
J . K. Crandall, R. J . Watkins, Tetrahedron Lett. 1967,1717.
E. J . Corey, H . Yamamoto, D. K. Herron, K. Achiwa, J . Am. Chem.
SOC.92,6635 (1970);E. J . Corey, H . Yamamoto, ibid. 92,6636 (1970).
I: Bahurel, L. Cottier, G . Descotes, Synthesis 1974,118.
a) R . 7: Arnold, G. Smolinsky, J. Am. Chem. SOC.82,4918 (1960);b)
E . N . Maruell, R. Rusay, J. Org. Chem. 42,3336(1977).
J. M . Conia, J. P. Barnier, Tetrahedron Lett. 1969,2679.
a) D. Joulain, F. Rouessac, J. Chem. SOC.Cbem. Commun. 1972,314;
b) G. Ohlof, Angew. Chem. 82, 777 (1970); Angew. Chem. Int. Ed.
Engl. 9,743 (1970).
a) G. Ohloff, Tetrahedron Lett. 1965,3795;b) D. E. McGreer, N . W
K . Chiu, Can. J. Chem. 46,2217 (1968);c) W Ando, Tetrahedron Lett.
1969,929;d) J . M . Watson, J. L. Iruine, R. M . Roberts, J . Am. Chem.
SOC.95,3348 (1973),and references cited therein; d) P. Dowd, K . Kang,
J. Chem. SOC.Chem. Commun. 1974,258;c) I: L . Ho, Synth. Commun.
7,351 (1977).
[59] X . Creary, F. Hudock, M . Keller, J. F. Kerwin, Jr., J . P. Dinnocenzo,
J. Org. Chem. 42,409 (1977).
[60] S . A. Monti, 7: W McAninch, Tetrahedron Lett. 1974,3239.
[61] W Oppolzer, unpublished results.
1621 a) J . A. Marshall, N . H . Andersen, P. C. Johnson, J. Org. Chem. 35,
186 (1970);b) N . H. Andersen, H. S. Uh, S . E. Smith, P. G. M . Wuts,
J. Chem. SOC.Chem. Commun. 1972,956;c) see also J . A. Marshall,
N . H . Andersen, J . W Schlicher, J . Org. Chem. 35,858 (1970);d) N. H.
Andersen, F. A. Golec Jr., Tetrahedron Lett. 1977,3783;e) N . H. Andersen, D. W Ladner, Synth. Commun., in press.
[63] M . Niwa, M . Iguchi, S. Yamamura, Bull. Chem. SOC. Jpn. 49, 3148
(1 976).
[64] J . Brocard, G. Moinet, J . M . Conia, Bull. SOC.Chim. Fr. 1973,1711.
[65] G. L. Lunge, J . M. Conia, Nouveau J . Chim. 1, 189 (1977).
[66] S. Kuko(ia, S. R. Lammert, M . R. B. Gleissner, A. 1. Ellis, J . Am.
Chem. SOC.98, 5040 (1976).
[67] W B. Motherwell, J. S. Roberts, J . Cbem. SOC.Chem. Commun. 1972,
329.
[68] A . I: Blomquist, P. R . Taussig, J . Am. Chem. SOC. 79, 3505 (1957).
[69] J. B. Lambert, J . J. Napoli, J. Am. Chem. SOC.95, 294 (1973).
Angew. Chem. Int. Ed. Engl. 17,476-486 (1978)
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