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Bonding Properties of Cyclopropane and Their Chemical Consequences.

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Volume 18 . Number 1 1
November 1979
Pages 809-886
International Edition in English
Bonding Properties of Cyclopropane
and Their Chemical Consequences
By Armin de Meijere'''
Dedicated to Professor Wolfgang Liittke on the occasion of his 60th birthday
Among the cyclic compounds of carbon, cyclopropane and its derivatives are outstanding by
virtue of their unusual structural, spectroscopic, and chemical properties. The cyclopropane
ring more closely resembles the C=C double bond than the cyclobutane ring: it is a small ring
with "double bond character". Cyclopropyl and vinyl groups interact with neighboring T-electron systems and p-electron centers; both cyclopropane derivatives and olefins form metal
complexes, and add strong acids, halogens, and ozone; they both undergo catalytic hydrogenation and cycloadditions. While distinct differences in reactivity do exist-the double bond
usually being more reactive than the three-membered ring-there are no fundamental differences in behavior.-Although cyclopropane derivatives have been known for more than 90
years, intensive studies have been limited to the past 25 years. The development of carbene
chemistry has rendered cyclopropane derivatives far more readily accessible. In recent years,
the synthetic potential of the small-ring function has been increasingly exploited. A considerable number of newly developed methods utilizing this approach clearly demonstrates that the
reactivity of the cyclopropene ring, like that of the C-C double bond, qualify it as a "functional carbon group". This development is in full swing; we may therefore justifiably devote
considerable effort to the study of cyclopropane chemistry.
1. The Chemical Bond in the Cyclopropane Ring
Olefins and cyclopropane derivatives are related in many
ways"'. The reason for this lies in the similarity of bonding in
the C-C double bond and in the three-membered carbon
ring. There are two equivalent descriptions for each system.
According to the MO model of Walsh[2](see Fig. I),
three occupied molecular orbitals (MOs) determine the nature of the
C-C bonds of the three-membered ring. Of these, the orbit['I
Prof. Dr. A. de Meijere
Institut fur Organische Chemie und Biochemie der Universitat
Martin-Luther-King-Platz 6, D-2000 Hamburg 13 (Germany)
Angew. Chem. Int. Ed. Engl. 18,809-826 (1979)
Fig. 1. Molecular orbital (MO) description of bonding in cyclopropane and ethylene.
D Verlag Chemie, CmbH, 6940 Weinheim, 1979
0570-0833/79/11Il-OS09 $ 02.50/0
a1 of lowest energy (cr) is a linear combination of three sp2hybrid atomic orbitals (AOs), while the other two (es and e,)
are equal-energy linear combinations of three p-AOs differing only in their symmetry properties. This picture is strongly
reminiscent of the commonest description of a C-=C double
bond by two occupied MOs, one linear combination each of
two sp2 AOs (a-MO) and two p AOs (a-MO) (see Fig. 1). By
analogy with the latter MOs, the Walsh es and eAorbitals are
also called n or "quasi T" orbitals of the three-membered
The second kind of theoretical description is the valence
bond (VB) model of cyclopropane, due originally to Forsterf3I and refined by C o u l ~ o n [The
~ ~ . C -C bonds are described as resulting from the overlapping of two sps-hybrid
orbitals at each C atom (see Fig. 2). Since the directions of
Fig. 2. Valence bond (VB) model of cyclopropane and ethylene.
the orbitals cannot coincide with the directions of bonding,
but are directed outwards relative to the latter, the bonds
create the impression of being bent. However, this merely expresses the experimentally established factl'l that the density
of the bonding electrons is greatest off the C C connecting
line. In the more common MO model this fact is reflected by
the e, and eA orbitals in which the overlap region of the p
AOs also lies off the C--C connecting lines (see Fig. 3)161.
Fig. 3. Electron density distribution in the occupied molecular orbitals of cyclopropane responsible for the C C bonds (according to 161).
Another common feature of the two models is the participation of sp2 hybrid orbitals of the C atoms in C- -H bond
formation. This is substantiated by experimental facts: for instance, the cyclopropyl C-H bonds (like vinylic C -H
bonds) are shorter than normal aliphatic C --H bonds^'], and
the I3C-H coupling constants found for cyclopropane dcrivatives indicate 32% s character of the C-H bonding orbitals[*]].
Furthermore, the C=C double bond can also be described, according to Pauling, by bent bonds[']. As in the
three-membered ring, the so-called "T bonds" arise by overlapping of sp5 hybrid orbitals of the C atoms off the C-C
connecting line (see Fig. 2). For cyclopropane and ethylene,
we have two completely equivalent models which can be
transformed mathematically into each other["'. The physical
and chemical consequences can be explained equally well in
principle by either model. However, the a,n description of
the double bond and the three-membered ring is more convenient for quantum mechanical calculations.
These analogies in bonding properties help us to understand similarities in chemical behavior; the regions of high
electron density off the C -C connecting lines determine
their reactivity towards electrophilic reagents['.". ['I. This is
also the reason why both of the bond systems can undergo
electronic interaction with n or p-electron centers. It leads to
an effect usually designated as conjugation, which is generally manifested in the physical and chemical properties of the
corresponding compound. In the case of the C=C double
bond, conjugation effects are known for systems containing
in its immediate vicinity
a double bond or, more generally,
a CX multiple bond,
a cyclopropane ring,
a carbanion center,
a radical center, or
a carbenium ion center.
In principle, an interaction effect should be expected for
combinations of each of these five groups with a cyclopropane ring. It is the intention of this article to describe model
compounds with characteristic properties and thereby show
how far this prediction is fulfilled.
It should first be mentioned that the extent of interaction
in conjugated systems with a double bond and with a threemembered ring is highly dependent upon their conformation. In general, the interaction energy, and hence also the
effect of conjugation on physical and chemical properties, is
greatest when the axes of the mutually interacting orbitals
are parallel to each other because the overlap between the
orbitals is then at a maximum. Open-chain conjugated systems therefore preferentially adopt a conformation permitting such maximum interaction. Thus over 95% of the molecules of 1,3-butadiene exist in the antiperiplanar (s-trans)
conformation having a planar carbon ~ k e l e t o n ~ ' ~the
. ' ~allyl
anion, the allyl radical, and the allyl catiodiS1are planar.
Owing to the special kind of anisotropic electron distribution in the cyclopropane ring (vide supra), its interaction with
a suitable neighboring group is at a maximum when the porbital axis of the neighboring group is arranged parallel to
the plane of the three-membered ring. For vinylcyclopropane, for instance, this is the case in the antiperiplanar con-
* = 90.
Fig. 4. Conformations of vinylcyclopropane:a) synclinal (gauche);b) antiperiplanar (s-trans). Conformations of the cyclopropylmethyl cation: c ) perpendicular;
d) bisected.
formation (see Fig. 4) and for the cyclopropylmethyl cation
in the o-called bisected conformation.
The interaction energy in a system with a three-membered
ring and a double bond is apparently lower than in one with
Angew. Chem. Int. Ed. Engl. 18, 809-826 (1979)
two conjugated double bonds because the more stable antiperiplanar conformation of vinylcyclopropane predominates
only to the extent of 75% in the liquid and gaseous phase,
corresponding to an energy difference of 4.6 kJ/mol relative
to the less stable synclinal (gauche) form["I. The maximum
stabilization energy of a system with conjugated double bond
and three-membered ring would correspond to the energy
difference between the antiperiplanar form and a 90" conformation; this energy difference is somewhat greater than 4.6
kJ/mol (vide infra). In contrast, the energy difference between the lowest-energy bisected conformation of the cyclopropylmethyl cation and the energetically least favorable
perpendicular conformation is much greater at 60-70 kJ/
The gain in energy experienced by such a cation in
an optimum geometry is of the same order of magnitude as
the stabilization energy of an allyl or benzyl cation['91relative to a primary alkyl carbenium ion. Thus the ability of the
cyclopropyl group to stabilize a center of positive charge is
comparable with, or even greater than, that of the vinyl and
the phenyl group["].
On comparing the vinyl and the phenyl group on the one
hand with the cyclopropyl group on the other, it is essential
to bear in mind a difference in geometry, which can play an
important role primarily in conformationally rigid systems:
as a rule, the four substituents attached to the two carbon
atoms of a double bond are located in a plane (S) including
the carbon atoms and oriented perpendicular to the plane
(0)of the .rr-orbital axes (interplanar angle a = 90"; cf. Fig.
5); however, four substituents attached to two C atoms of a
cyclopropane ring define, together with the C atoms, two distinct planes (S' and S2) enclosing an angle of ca. 120" and
forming angles of ca. 60" with the plane of the three-membered ring, and thus also with that of the p-orbital axes (0)
(a=60", cf. Fig. 5).
Fig. 5 . Geometrical differences in the allyl and the cyclopropylmethyl cation at
maximum orbital overlap [ m = interplanar angle].
The modern description of the bonding properties of cyclopropane provides a theoretical basis for the classical concept of ring strain["', which has been invoked to explain various typical reactions of small ring compounds: according to
present-day ideas, ring strain is an expression of the sum of
all bond energies in a molecule. The experimental value can
be obtained for any cycloalkane from the difference between
its heat of combustion and that of a long-chain unstrained nwith the same number of CH, groups (see Table i).
This definition is less misleading and yet more comprehensive that the original one proposed by A. uon Baeyerr2'l,
which assumed that only the C valence angles deviating from
tetrahedral angles give rise to a strain in small rings which
increases with decreasing ring size. In fact, we nowadays distinguish three causes of ring strain and thus three components contributing to the total strain: deformation of bond
angles gives rise to angular strain (von Baeyer strain) and an
Angew. Chem. Inf. Ed Engl. IS, 809-826 (1979}
eclipsed or at least imperfectly staggered arrangement of
CH, groups causes torsional strain (Pitzer strain); the third
contribution is due to transannular van der Waals interaction
of nonbonded atoms.
Table 1. Strain energy of lower cycloalkanes (CH2). and ethylene
Bond angle
per CH2 group
Heat of combustion
per CH, group
AH,,, /n
Strain energy
per molecule
19.5" [a]
1.5" [a]
[a] Calculated for a planar ring, as assumed by A. uon Baeyer [21]
The values of the strain energy (Table 1) show that the
thermodynamic stability of a cyclopropane ring is lower than
that of a C-C double bond; accordingly, cyclopropane derivatives are often observed to rearrange to more stable olefins on acid
or thermally at sufficiently high
"I. Nevertheless, three-membered rings show
a pronounced tendency of formation; for example, certain
eliminations leading to olefins can be applied with comparable success to the synthesis of cyclopropane derivatives from
homologous substrates (y-elimination)[261.The numerous
methods for generating ~arbenes['~land their additions to
C=C double bonds have greatly increased the possible preparations of three-membered rings['*]. The recently developed generation of dichlorocarbene from chloroform and concentrated aqueous sodium hydroxide under phase transfer
has reduced the expenditure of effort and financial resources to such an extent that two of the principle obstacles on the way to an industrial utilization of cyclopropane chemistry have been removed.
2. Effects of Conjugation between Cyclopropane and
Multiple Bonds
StaIey has estimated from the position of the equilibrium
which is established in the presence of strong bases between
spiro[2.5]oct-5-ene (1) and spiro[2.5]oct-4-ene (2) at room
temperature that conjugation between the C=C double
bond and the cyclopropane ring effects a stabilization of ca.
5.0 k J / m ~ l ~ ~Dispiro[]dec-8-ene
(3) can accordingly
undergo more than 80% rearrangement to the more stable
conjugated isomer (4)[)13'l.
Conjugation in compounds of types (2) and (4) is manifested not only in their greater thermodynamic stability but
also in their UV, NMR, IR, and PE spectra. The bathochromic shift of the longest wavelength UV absorption band
of a 1,3-diene chromophore is ca. 15 nm per three-membered
ring, given optimum conformation of the system, as is almost
accomplished in dispiro[]deca-7,9-diene(5)[31,321.
spiro[2.4]hepta-4,6-diene(6), having the vinylcyclopropane
units fixed in the antiperiplanar conformation in the planar
five-membered ring[331,Clark and Fiato have deduced partial
delocalization of the cyclopropyl bond electrons into the
five-membered ring [as in (6a)l from the exceptional downfield position of the NMR signals due to the cyclopropyl protonsL3'].However, this assumption could not be confirmed by
way of the bond lengths of (6). In the five-membered ring
they correspond to those of cyclopentadiene and in the three~ ~ ~electron-do~.
membered ring to those of c y c l ~ p r o p a n e The
nating capacity of the cyclopropyl group apparently becomes
effective only when stimulated by electron withdrawal by a
n-acceptor substituent, such as a polar CX multiple
Thus a significant lengthening of the C1- C2 bond, and a
corresponding shortening of the C2-C3 bond have been determined experimentally for cyclopropanecarbonitrile (7),
just as predicted theoretically on the basis of the Walsh MO
(The C-C bond length in cyclopropane is 1.510
Table 2. Selected UV and IR data of some cyclopropyl-conjugated cyclohexanediones and reference systems.
UV. n-n* (EtOH)
Amax lnml
IR (KBr)
u c -0
271 (57)
280 (47)
281 (29)
373 (27)
360 (90)
1712, 1686
1701, 1578
380 (11)
271 (135)
279 (169)
[a] Not measured
tant; the data collected for compounds (10)-(18) are impressive illustrations (see Tables 2).
The particularly facile reductive cleavage of the cyclopropyl C-C bond in 1,4-dicarbonyl compounds of types (19)
and (21) may be regarded as a chemical consequence of cyclopropyl-carbonyl conjugation and of the low C-C bond
energy. This mode of reaction, which leads to 1,5-dicarbonyl
compounds (20) and (22)[471,
can be used to advantage, e.g.,
for ring
Thus it appears reasonable that the 'H-NMR and UV data
of spiro[2.5]octa-4,7-dien-6-one
and its benzo derivative (9)["] are best interpreted in terms of a significant contribution of the zwitterionic resonance structures (8a) and
The magnitude of the bathochromic shift of the n-v* band
in the UV spe~trum[~'l
and the shift of the vC=O band to
lower wave numbers in the IR spectrum[401of cyclopropyl
ketones as an expression of the conjugation between the cyclopropyl and the carbonyl group is critically dependent
upon the geometry of the
In cyclopropyl-conjugated diketones, the effect of through-space and throughbond interaction between the carbonyl groups is also impor-
Reductive ring cleavage of conjugated cyclopropyl monoketones can also be accomplished with lithium in liquid amm0nia[~~1.
In monocyclic conformationally mobile systems
such as (23), the type of substitution will determine which of
the cyclopropyl bonds overlaps with the TT orbital of the
C=O group in the energetically most favorable conformation and is thus preferentially opened (see Scheme l)['Ol. In
annelated bicyclic systems the fixed geometry leads to a stereoselective ring opening, which has been successfully utilized to reduce (+)-caran-2-one (26) to (-)-carvomenthane
(27)'"l and to produce the intermediate (29) from (28) in a
total synthesis of the spirosesquiterpene ( + )-a-chamigrene
(a), R ' = R2= CH,
(b), R'=CHS, R 2 = H
(c), R ' T H , RZ=CH3
Scheme I. Ring opening of cyclopropyl methyl ketones (23J depending upon
type of substitution [SO].
In protonated cyclopropyl ketones (31), the electron-donating capacity of the cyclopropyl group is exploited by a
neighboring carbenium ion center. In keeping with their cyclopropylmethyl cation structure (see Section 6), compounds
Angew. Chem. Inr. Ed. Engl. 18, 809-826 (1979)
Scheme 2. Methods of lusing cyclopentane lo cyclic ketones (40). R=(CH,)&.
(31) form homoallyl systems (32) by ring opening; this mode
of reaction is the basis of a synthetic method for 1,4-diketones (34) which result from trapping of (32) with water and
Being stereocontrolled, the alternative method via the phenylthio-substituted systems (47) and (48) also developed by
Trost et al.[”] may be advantageous. The trimethylsiloxy and
phenylthio groups in (42) and (47), respectively, facilitate
thermal rearrangement as compared to the parent system.
A comparable effect is observed with a methoxy
(E, = 161.9 kJ/mol) or a dimethylamino group (E, = 130.5
kJ/mol) in position 2 of the vinylcyclopropane [see (51) and
Conjugation of C=C double bonds with cyclopropyl
groups also affects chemical properties. The simplest compound of this kind, vinylcyclopropane (35), undergoes a relatively facile and uniform thermal rearrangement (Arrhenius
activation energy E, = 207.9 kJ/mol) to cyclopentene (36)[s41;
numerous substituted vinylcycl~propanes[~~~
251 behave analogously [e.g. (37)+(38)+(39)] provided they are not fixed in
On catalytic hydrogenation, vinyl-conjugated cyclopropyl
groups are generally more readily cleaved than isolated
moreover, vinyl as well as carbonyl and phenyl
groups lead to regioselective opening of the C’-Cz bond,
while it is mainly the Cz-C3 bond which is opened in the
case of alkyl-substituted cyclopropanes[601.
- 20.C
an antiperiplanar or anticlinal conformation that is unfavorable for this ring closure. This kind of rearrangement serves
as the principle underlying techniques of fusing cyclopentane rings onto cyclic ketones (40) (see Scheme 2)[55,561.
decisive intermediates are 1-vinylcyclopropyl trimethylsilyl
ethers (42), obtained according to Conia et al.[55]
by Simmons-Smith cyclopropanation of 2-trimethylsilyloxy-1,3dienes (41) or according to Trost et al.[561via the oxaspiropentanes (44).
Angew. Chem. Int. Ed. Engl. 18, 809-826 (1979)
Vinylcyclopropane (35) is hydrogenated to n-pentane (5s)
over palladium in methanol at 2-20 “C and at normal presin contrast, the trishomobarrelene derivatives (56)
undergo hydrogenation to the stereochemically interesting
2,6,7-trimethylbicyclo[2.2.2]octylderivatives (5 7) (R = ethyl,
1-methylcyclopropyl, methoxy) only at elevated hydrogen
pressure ( 25 bar) in the presence of platinum dioxide/glacia1 acetic acid[621.In oligocyclic systems having essentially
rigid geometry, however, non-conjugated C=C double
bonds may also affect the regioselectivity and ease of cyclopropyl ring opening. The unsaturated pentacycle (58) takes
up hydrogen far more rapidly than the corresponding saturated pentacycle (61), and gives a much higher proportion of
the fully ~ n e x p e c t e d [ ~product
~ . ~ ~ l (60)[631than does (61).
Compound (3) completely fails to give the e x p e ~ t e d [ ’ ~ . ~ ~ ~
1,1,2,2-tetramethylcyclohexane,but instead affords cis- (62)
and trans-l,2-diethylcyclohexane(63), as well as 1,2-diethylbenzene (64) alongside a small amount of saturated dispir0[]decane[~~].
+ others
759) ti
I 7%
-20 “C: the major product (52% yield) is 11,12-benzo-1,4dioxa-l1-cyclotetradecene-7,7,8,8-tetracarbonitrile(72)I7O1.
I 0%
(5) +TCNE
Thus in molecules such as (58) and (3) the olefinic group is
the better “ligand” for the catalyst surface, and therefore
plays a major role in determining how the overall molecule is
adsorbed on the catalyst surface and which cyclopropyl bond
subsequently undergoes preferential cleavage.
The interaction between the bonding orbitals of a cyclopropyl group and the 7~ orbitals of neighboring C=C double
bonds raises the energy of the highest occupied MO
(HOMO) of such a conjugated system. This corresponds to a
lowering of the .rr-ionization potential, as has been established by photoelectron spectroscopy for the compounds (2),
(4), (5)[”1, (6)[651,(65)[661,
and other examples[671.The ionization potential of dispirodecadiene (5) is especially low at 7.74
eV. This is apparently responsible for the unusual mode of
reaction of (5) with tetracyanoethylene (TCNE).
In contrast, the strain-free cyclic ether dioxane does not
participate in the reaction; as a polar solvent it instead prolongs the lifetime of the zwitterion (66) and permits its cyclization to the benzocyclooctene derivative (73) (73% yield)[701.
The bicyclo[2.2.2]octene derivative (74) is formed merely as
a by-product (2%) by normal Diels-Alder addition to the 1,3diene unit in (5). In contrast, this “normal” type of adduct is
formed exclusively with all dienophiles[” -73J which are not
also sufficiently strong oxidizing agents for (S), like TCNE or
certain substituted p-benzoq~inones[’~~.
Compound (73) is
formally a [s2 + ,2 + ,2]cycloadduct of TCNE and the synperiplanar-fixed bicyclopropyl unit. Analogous additions of
TCNE to synperiplanar-fixed vinylcyclopropane systems
have also been r e p ~ r t e d [ ’ ~ . ~ ~ l .
The major product (38%) of a reaction in tetrahydrofuran
(THF) at room temperature is the 1:1:2 cycloadduct (68) of
(5), TCNE, and THF[681.Since TCNE readily takes up an
electron to form the radical anion[691,electron transfer from
(5) to TCNE is probably the initial step of this reaction. After
recombination of the pair of radical ions from (5) and TCNE
the zwitterion (66) is formed, which ultimately cyclizes to the
18-membered ring (68) after incorporation of two molecules
of THF via (67) and a further intermediate. Careful work-up
of the reaction mixture afforded a further product (6%)[”’
shown by its ‘H-NMR spectrum to have the structure (69)
with a 13-membered ring, which must have arisen by cyclization of (67). This reaction can be extended to the preparation
of further macrocyclic ethers. In the presence of an excess of
oxetane, (5) and TCNE give a mixture of (70) (13%) and (71)
(12%) having a 16- and a 20-membered ring, respectively, in
addition to polymeric material[701.
Similarly, the more highly
strained oxirane is cyclooligomerized by (66) even at
ba, &::
TCNE, 20.C
(80) tN
Unlike (5), however, the spirovinylcyclopropanes (75),
n = l or 2, initially react by way of a [2+2]cycloaddition to
give isolable cyclobutane derivatives (76), which rearrange to
cycloheptene derivatives (77) only at elevated temperat ~ r e [ ~Prior
~ ] . electron transfer is not essential in this case because chlorosulfonyl isocyanate reacts analogously with (75)
to give the seven-membered ring (78)[761whereas this cyclophile gives a normal Diels-Alder adduct of type (74) with
(5)[771.Instead it is the conformation of the vinylcyclopropane system which is of prime importance. The adducts (80)
and (82) of the sterically undefined cyclopropylethylenes
Angew. Chem. Int. Ed. Engl. 18, 809-826 (1979)
(79) and (81)[781
undergo exclusive cycloreversion to (79) and
(83) on heating[75’.
(99)[”l, because the distance between the two cyclopropyl
groups in this compound is smaller than in all other systems
owing to the linkage via a double bond.
The proximity of two cyclopropyl groups is surely a determining factor in the cycloaddition of TCNE to a three-memhowever, bicyclopropyl (98)
bered ring of (89) to give (90)[*’];
does not react under comparable conditions. The same unusual type of cycloaddition as that of TCNE to the bicyclopropyl unit of (5) to give (66) has so far been found for only one
other class of compounds: quadricyclane (lOO)[”’ and quadricyclane derivatives[901react with dicyanoacetylene, azodicarboxylate, or other reactive dienophiles to form cycloadducts of the type (101)[x9a1
and (102)[89b1,
respectively. A photochemical [,4 + -2 + ,2]cycloaddition of anthracene (103) to
(100) giving (104) has also been reported[’‘].
Cyclopropylethylenes having a sufficiently low ionization
potential, such as (84), R = cyclopropyl or phenyl, react like
(5) in the initial steps; however, the zwitterion (85) preferentially cyclizes to the cyclopentane derivative (86) r7’I. As
shown by the examples (88)[’01 and (90)[”],TCNE also undergoes cycloaddition to phenyl- and cyclopropyl-conjugated cyclopropanes such as (87) and (89), probably without
intermediate formation of radical ions.
Further transformation of such tetracarbonitriles, formed
by TCNE addition to olefins and cyclopropanes, has hardly
been utilized so far in spite of the potential they offer. Thus
under alkaline conditions, (72) can readily be hydrolyzed to
the tetracarboxylic
in the absence of acid-labile
groups, acid-catalyzed hydrolysis with simultaneous decarboxylation is possible[”].
3. Cyclopropyl-Cyclopropyl Interaction
Although the electronic interaction between neighboring
cyclopropyl groups does not appear to exert any substantial
effect on the UV/VIS spectrum of corresponding compo~n&[31.83.841
, it is manifested in the PE spectra in accord
with theoretical concepts. Of particular value for such studies
were compounds such as (3), (4), (5), (89)13‘],the tris-a-homobenzenes (91)[851,(92)LR6],and [nlrotanes (94)-(97)[871
containing bicyclopropyl groups in uniformly defined conformations. However, comparable information was also provided by the PE spectrum of bicyclopropyl (98) which exists
in two equilibrium conformations[881.The resonance integrals serving as a measure for the interaction between neighboring 2 p atomic orbitals of conjugated cyclopropyl groups
vary from p = - 1.50 eV for (95) through p = - 1.73 eV for
(91), (92), (93), (98) up to p= -2.05 for (94). The highest
value, p = - 2.14 eV, was found for bicyclopropylidene
Angew. Chem. Int. Ed. Engl. 18,809-826 (1979)
Uncatalyzed and catalyzed thermal rearrangements of (5)
and (91)-(93) are also determined by the proximity of cyclopropyl groups in various ways. While the purely thermal
reaction of (5)-probably via intermediate diradicals-yields
87% o-ethylstyrene and only 13% tetralin[711,the gold-catalyzed reaction[921
gives more that 90% tetralin, the product of
a bicyclopropyl group cyclization. The same kind of rearrangement is catalyzed by gold and gold(1) complexes in the
case of diademane (91); in the presence of dicyclopentadienegold(1) chloride, (91) isomerizes even a room temperature to snoutene (105)[921from which it is in turn formed by
photochemical interamolecular [,2 + ,,2]~ycloaddition[~~~.~~1.
In the absence of catalyst, however, (91) rearranges above
80 “ C with cleavage of all its three-membered rings to triquinacene (106)[R3b,941.
This type of cycloreversion, which has an
activation energy of only 132.2 kJ/mol[’51in the case of (91), is
common to all cis-tris-u-homobenzene derivatives[961.
All experimental evidence indicates a concerted [,2, + ,2, + ,2,]cy-
cloreversion. If the three cyclically conjugated cyclopropyl
groups of a cis-tris-u-homobenzene are better oriented for
overlap of the Walsh orbitals than in (91), as is the case in
1,6-homodiademane (107)[93*971,
the isomerization proceeds
even more readily (E,=118.4 kJ/mol). Thence it could be
estimated that the hitherto unknown parent hydrocarbon
(109) should just be stable at room temperat~re[~'I.
Although the overlap between neighboring p orbitals in
two out of three bicyclopropyl groups is very small in transtris-a-homobenzene (931, it rearranges formally according to
the same scheme; however, this reaction requires an activation energy of 175.7 kJ/rn01[~~].
Thus, under the conditions
employed, the initial product, viz. the highly strained
cis,trans,trans-1,4,7-cyclononatriene(1 10)19xb1,
could not be
~ ' 2 C / ' 3 C = 9089/ 1.11
a consequence of an initial silica gel-catalyzed isomerization
to an 01efin['~~];
rather the ozone directly attacks a cyclopropyl C-C bond, possibly with cycloaddition to give a rather
unstable 1,2,3-tnoxane of type (122), as has been proved for
highly strained u bonds['M].
Because of the double bond-like properties of the cyclopropane ring (see Section I),
methylenecyclopropane (123)
and bicyclopropylidene (99) sometimes react like cumulenes.
The ready dimerization of (123)['05]and (99)['06]are pertinent
examples. Cycloadditions of the more reactive compound
(99)['061to double bonds of other reactants provide an entry
'kl'3C i 999510.05
isolated but detected only by the isotopic labeling pattern in
the final product ( I l l b ) from (93b)[9xa1.
Only when an additional bridge is present, as in (92) does the system avoid the
excessive strain energy in the bridged intermediates of type
(110) and instead undergoes [v2+ ,2]cycloreversion probably
proceeding via diradicals at higher temperatures, giving the
isomeric bishomobarrelenes (112) and (113)[991,
from which it
was in turn generated phot~chemically'~~~
and thermally1'0O1.
Although the [nlrotanes (94)-(97) would appear predestined for a number of interesting chemical transformations,
hardly anything of this kind is known about them. This is
partly due to the tedious synthetic pathways leading to them
before more convenient alternative approaches were develThe [4]rotane (95) obtainable by dimerization of
the bicyclopropylidene (99), which is now readily accessible['ozl, undergoes oxidative degradation to trispiro[]decan-lO-one(114) by ozone on silica gel[lo3].It
is not the ring strain of a spiro[2.3]hexane system which plays
a crucial role, but instead the activation of a spirocyclopropyl
group by at least one neighboring cyclopropyl group, for the
hydrocarbons (115), (118), and (120) are degraded analogously to the ketones (116) [alongside (117)], (119), and
(121), re~pectively["~~.
Moreover, this mode of reaction is not
n = 2 78%
n = ~~
n = 2 22°/o
to compounds having spirobicyclopropyl groups. Reaction
with conjugated dienes such as 1,3-butadiene (124) and 1,3cyclohexadiene (127) give mainly the cyclobutane derivatives (125) and (128), respectively, together with the
[2 + 4]cycloadducts (3) and (130)['071.Only cyclopentadiene
(126) reacts with (99) to give exclusively the formal [2+4]adduct (129)['07].Compound (99) does not add to electron-rich
but very readily to some double bond systems
bearing strong electron acceptors as substituents. Thus (99)
reacts with acrylonitrile to give the cyclobutanecarbonitrile
derivative (131), and with fumaronitnle to give a mixture of
the isomers (132) and (133); dichloroketene forms the "normal" [2 + 21adduct (134)[10R1.
In contrast, chlorosulfonyl iso-
& HCN&'
(1 14)
cyanate affords, alongside a small amount of (136), mainly
(137), possibly by cyclopropylallyl rearrangement of the intermediate zwitterion (135). N-Phenyltriazolinedione behaves differently: the intermediate (139) apparently undergoes cyclopropylmethyl-cyclobutyl ring expansion and subAngew.
Chem. Int. Ed. Engl. 18, 809-826 (1979)
sequent cyclization to the four-membered ring derivatives
(140). TCNE experiences all three kinds of addition, as
shown by the products (141), (142) (major product), and
(143)['OX1.Simple methylenecyclopropanes also undergo a
formally analogous reaction" O9I.
change process (152a)=(152b) is subject to a barrier of only
< 12.5 kJ/m~l["~I.This is much smaller than in the case of
4. Stabilization of Carbanions by Cyclopropyl
Owing to its bonding properties, a cyclopropyl group
should, in principle, have a mesomeric and an inductive stabilizing effect on a carbanionl""l. However, Perkins et al.
have deduced from measurements of hydrogen/deuterium
exchange rates for benzylcyclopropane (144), 3,4-benzobicyclo[4.1.O]heptene (145), 2,3-benzobicyclo[3.1.O]hexene (146),
and reference compounds that the benzyl anions obtained
from (144), (145), and (146) are, at best, only slightly more
stable than the corresponding anions having no a-cyclopropyl groups['I 'I. This conclusion, i. e. that cyclopropyl substituents have hardly any effect on the stability of carbanions
was confirmed by Streitwieser["21on the basis of the kinetic
acidities of (147) and (148).
The widely differing stabilities of the spiro[2.5]octadienyl
(149) and spiro[2.7]decatrienyl anion (151) reported by Staley et al. [I131 also convincingly demonstrate the cyclopropyl
group to be a poor 7r-electron acceptor but a very good TT donor: the anion (149) in which the cyclopropyl group is spirolinked to a 6 rn system and in which it can only act as an ac-
(15I )
the cyclopropylmethyl cation''', Is] indicating that a radical is
stabilized less by an a-cyclopropyl substituent than a carbenium ion.
Kinetic studies on the decomposition of azoalkanes
(153)-(157) led Martin and Timberfake to essentially the
same concIusion['l6'. Any replacement of a methyl by a cy-
clopropyl group in (153) increases the rate of thermolysis, on
average by a factor of 14. The steric influence due to the difference in sizes of these groups plays a subordinate role, as
shown by comparison of the values obtained for (156) and
(157). However, in the case of (15.51, (156), and (157), apparently not all the cyclopropyl groups can simultaneously adopt an optimum conformation for interaction with the incipient radical center in the transition state.
This difficulty is largely avoided in the bicyclo[2.2.0]hexane derivatives (1.58), (160), and (162): their thermolysis
leads initially to conformationally uniform 1,4-cyclohexanediyls (158a), (160a), and (162a), respectively['"I. It was estimated from the differences in activation energy for the over-
@-[@]- 3$
ceptor undergoes fast rearrangement at as low a temperature
as -65 "C to the aromatic phenethyl anion (150). In contrast, (151) in which the spirocyclopropyl group acts as a TT
donor, as in spiro[2.4]heptadiene (6), is itself already "aromatic" according to the ring current ~riterionl"~~l
and therefore stable up to - 30 "C.
5. Relative Stabilities of Cyclopropylmethyl Radicals
Although studies on the generation and transformation of
cyclopropylmethyl radicals and their relative stabilities are
not very numerous["41,they are far better represented than
those on cyclopropylcarbanions. This would indicate that cyclopropyl-substituted radicals have a greater potential.
ESR studies have shown that cyclopropylmethyl radicals
prefer the bisected conformation (152) with optimum overlap between the radical p orbital and the cyclopropyl Walsh
orbitaFI5l; however, the CH2 rotation responsible for the exAngew. Chem. Inr. Ed. Engl. 18, 809-826 (1979)
all reactions leading to (159), (161), and (163) that the stabilization energy of a cyclopropylmethyl radical with an optimum conformation is ca. 12 kJ/moI['"].
Simple cyclopropylmethyl radicals (164)-generated from
methylcyclopropanes by hydrogen abstraction with tert-butoxy radicals-undergo very fast rearrangement to homoallyl
radicals (165),in some cases even at ca. - 100OC[llxl.
In contrast, the bicyclo[3.l.0]hexeny1 radical (167) generated in the
(1 78)
same way from (166) is stable up to at least + 70 "C; it isomerizes to the cyclohexadienyl radical (168) only at
+ 150 0C[1191.
The facile ring cleavage of cyclopropylmethyl radicals is
the basis of a method for the chemospecific reductive ring
opening of vinylcyclopropanes (169). Photochemically initiated hydrostannylation leads via 1,4-addition to trialkylal-
lylstannanes (170) which are transformed by hydrogen
bromide into the alkenes (171) in more than 80% yield[1201.
Dispiro[]deca-4,9-diene(65) is an interesting special
case. The second step of its double ring cleavage via (1 72) to
the diradical (1 73), which is fast above 160 "C, belongs to the
class of cyclopropylmethyl to homoallyl rearrangements; the
yield of the (8lparacyclophane derivatives (1 74) (30-84%)
on cycloaddition of (1 73) or (1 72) to conjugated dienes are
surprisingly high['''].
(1 79)
2 relative to bicyclo[2.2.2]octane (1 78a);it becomes more and
more dominant as the number of a-annelated cyclopropane
rings increases, and is practically the only reaction in trishomobarrelene (182~).This is due not only to the weak yet definite radical stabilization by a-cyclopropyl groups; the strong
electron donating effect of the cyclopropane ring on electron-deficient centers (see Section 6) also plays a role since
the transition state of hydrogen abstraction by rert-butoxy radicals (and by electronegative radicals in general) exhibits
partial charge ~eparation['~'I.
This combined effect also becomes operative on attack of
C-H bonds by ozone; it is responsible for the selective oxid a t i ~ n [ ' ~ ~of
~ ~sites
' ' ] adjacent to a cyclopropane ring on dry
ozonationf1261,for ozone behaves as a dipolar 1,3-diradica1[128].
This new method for the synthesis of cyclopropyl ketones from cyclopropyl hydrocarbons (see Scheme 3) is a
Scheme 3. Relative yields of a-ketones on ozonation of cyclopropyl hydrocarbons as percentages (without considering unreacted starting material).
In spite of the pronounced tendency of a-cyclopropyl-substituted radicals to undergo ring opening, cyclopropyl hydrocarbons can be selectively derivatized by free radical attack.
For instance, comparatively mild chlorination can be accomplished with tert-butyl hypochlorite on irradiation, especially
at low temperat~res~''~-'*~~.
Thus, at 70-85 "C, bicyclo[3.1.0]hexane (175) gives a mixture of 78% of (176) and
22% of (1 77) in 34% yield['22a1.
Low temperature photochlorination (-40 "C) of the hydrocarbons (179a)-(182a) gave
good yields of the bridgehead chlorides (1 79b)-(182b) completely free of secondary products due to rearrangement of
the radical intermediate~'8~1231.
(176) mv.
convenient addition to the list of previous reactions["]. The
method also provides an entry to compounds which are
otherwise inaccessible or accessible only with difficulty. Ex-
The same applies to the preparation of the trichloride
(183b) from ( 1 8 3 ~ ) [ ~ ' ~
1 . in tricycl0['~~]nonane
(1 7 9 4 bridgehead attack is favored by a factor of more than
Angew. Chem. Int. Ed. Engl. 18, 809-826 (1979)
amples of such compounds are exo- (185) and endo-tricy-
(187) from (184) and (186), respectively, and the monoketone (189) and the diketone (15) as
convenient precursors of [5]- (96)11291 and [6]rotane
(9 7)1127b'.
The new one-step preparation of cis-caran-5-one (192)
from cis-carane (191))11301
is faster and gives better yields than
other multistep procedure^^'^'^. Further applications of this
oxidation in the field of terpenes are conceivable and would
appear promising.
6. Electron-Donating Effect of the Cyclopropyl
Undoubtedly the most versatile and hence most interesting
"cyclopropyl function" results on combination of the threemembered carbocycle with a neighboring electron-deficient
center. Several reviewsr1.'32-1351
witness to the wealth of publications about such systems. The basis of a directed synthetic application of this function is, inter alia, a detailed knowledge of structure/stability and structure/reactivity relationships of cationic cyclopropylmethyl systems.
Studies by several research groups, especially those on systems of uniform, defined conformation, have revealed the relationship between the stability of a cyclopropylmethyl cation and its c~nforrnation~~'~
In the didehydroadamantyl derivative (193) we see a system of this kind in the bisected conformation (see Fig. 4)
with a parallel arrangement of the interacting orbitals.
Therefore, (93) solvolyzes 2.5 x lo8 times faster than 2-adamantyl tosylate (194)1136al
under the same conditions. For a
perpendicular orientation of the cyclopropane Walsh orbital
and the carbenium ion p orbital, such as encountered in the
adamantane-2-spirocyclopropanesystem (195), the solvolysis
rate is reduced by a factor of 365 relative to the reference system (196), i. e. the cyclopropyl group has an inductive electron-attracting effect in this case and destabilizes the intermediate carbenium ionll'l. The overall range of rate ratios of
M 10" between (193)/(194)and (195)/(196) corresponds to a
in an a position relative to the bridgehead118.13xl.
Owing to
the cumulative effect of three such groups, the ratios of
(182b) to (178b) and of (198b) to (197b) are particularly large
at 2.8 x 10' and 3.9 x lo6,respectively. Although it is a bridgehead chloride, (198b) is some 1.6 x l o 5 times more reactive
than tert-butyl chloride: (198) thus exhibits the greatest
bridgehead reactivity found so far for any system[139].
Detailed analysis of the solvolysis rates of (1 786)-(182b),
paying due attention to all relevant structural factors, has
shown that the dependence of the relative stabilization energy E, of a cyclopropylmethyl cation upon the torsional angle
Q is reproduced very well by the cos2Q function
E,= E,=~cos' p
where E , = 75 kJ/rnol1"l. Apart from the value for maximum
stabilization (E,=,) the function exactly corresponds to the
curve calculated for this angular dependence by the CNDO
(see Fig. 6).
9Fig. 6. Change in energy of a cyclopropylmethyl cation with conformation calculated by the CNDO method (p=torsional angle, see Fig. 4) (according to
As a logical consequence of the enhanced bridgehead
reactivity of (1 79b)-(182b) and (198b), the corresponding
"free" bridgehead cations can be readily generatedI"1 by
Table 3. Examples of known bridgehead derivatives of trishomobarrelene (182)
and trishomobullvalene (198). Isolated yields given.
Trishomobarrelene (182), bridgehead substiltrent:
k,,, IK'CI
2.2 .lo5
. 10"
difference in free energy of AG298M 68 kJ/mol between the
bisected (Q= OD) and the perpendicular (Q= 90') conformation of the cyclopropylmethyl cation.
Essentially rigid intermediate conformations (Q = 5 k 6 0 ° )
are found in the bridgehead cations of the polycyclic systems
(179)-(182) and (198). The SN1 solvolysis rates of all the
bridgehead chlorides (1 79b)-(182b) and (198b) are acwrdingly much higher that those of the reference compounds
(1 78b) and (197b) which do not contain cyclopropyl groups
Angew. Chem. Int. Ed. Engl. 18, 809-826 (1979)
/ Si 0
SOCl,/Polym. base [b]
1 ) t-BuLi, 2) C 0 2
A 1(CH31 3
Imidazole (Im-H)
Trishomobullvalene(1 98), bridgehead substituent:
[a] N-Methylpyrrolidone. [b] (Diethy1aminomethyl)polystyrene.[c] Bistrishomobarrelenyl ether.
present-day technique~['~'].
Their 'H- and "C-NMR spectroscopic data suggest considerable delocalization of the positive charge into the cyclopropyl groups, as has been demonstrated for cyclopropylmethyl cations in other conformation~['~'].
The cations can generally be efficiently trapped by
nucleophilic reagents, regenerating bridgehead derivatives.
In no case was skeletal rearrangement observed. Thus, on
use of suitable reagents, nucleophilic substitution reactions
provide access to almost any bridgehead derivative, especially of the trishomobarrelene (182) and the trishomobullvalene
system (198) (see Table 3).
Unlike trishomobullvalene (198a), trishomobarrelene
(182a) has two equivalent reactive bridgehead sites; it therefore preferentially forms 1,5-dichlorotrishomobarrelene
(199a) on treatment with an excess of tert-butyl hypochlorite["']. Owing to the inductive effect of the second chlorine
substituent, (1994 is significantly less reactive than the
monochloride (182b)['231.
The logarithms of the solvolysis
rates of a series of 5-substituted 1 -chlorotrishomobarrelenes
correlate well with the inductive substit-
the known bicyclo[2.2.2]octyl dication (204)[1541
should be
the same as that for the monocation (205) relative to the kinetically unstable (206)[1551.
Cationic cyclopropylmethyl systems in general are
k n ~ w n [ ' ~ ' - ' to
~ ~ rearrange
to homoallyl systems via ring
opening or to cyclobutyl systems via ring expansion['561.
Neither of these types of rearrangement occurs in the bridgehead cyclopropylmethyl systems mentioned above, apparently because of extensive ring strain in the potential products. The dihydro-exo,exo-bishomobullvalene system
is an exception, since the reaction of the alcohol
(207b) with thionyl chloride in the presence of diethylaminomethyl-polystyrene even at room temperature yields a
rearranged chloride shown by its 'H- and "C-NMR spectra[1581
to have the structure (209~).
uent constants uCHI
of the Taft equation['481,and even bet~ ~ ]slope
ter with the u: constants introduced by G r ~ b [ ' The
the regression line, i. e. the reaction constant p; (at 25 "C), is
ca. 50% greater than that for 4-substituted 1-bicyclo[2.2.2]0~tyl p-nitrobenzenesulfonates (200)['501.
Hence the ability to
transmit inductive substituent effects must be considerably
greater for cyclopropane C-C u bonds that for normal
C-C u bonds, as would be expected from their greater p
character["]. In contrast, transmission of mesomeric effects
by the cyclopropane ring is much poorer than by a C-C
double bond[15'1.
With regard to the results obtained for (199a)-(199i), the
substantially stronger electron withdrawal of a carbenium
ion center should also be efficiently transmitted through the
cyclopropyl C -C bonds in this system. This may be the reason why it has been impossible so far to generate the trishomobarrelene dication (203) from any of the dihalides (201).
In all cases only the monohalomonocations (202) were dete~table['~']although, according to MIND0/3 calculat i o n ~ " ~the
~ ] ,extent of stabilization for (203) with respect to
I c l X =Br
; I b l X = O H ; (c1X;CI
Apparently the intermediate carbenium ion behaves, like
(208), as a bridged trishomocycloheptatrienyl cation which is
attacked by the nucleophile preferentially in positions 2 and
10, respectively.
Therefore (209) is the result of a threefold cyclopropylmethylhomoallyl rearrangement. This type of reaction plays a
major role in the synthetic utilization of the cyclopropyl ring
function (see above). Julia's olefin
is a classical
example of these methods; it has found wide application in
the preparation of isoprenoids['60-'621.
la1 RI :Alkyl.R2 = H
90- 95.1.
5 -I@/.
IblR' = AkyI,R2= CH3
R1 = CH3, C&
96 -97%
3 4%
R2 = Atkyl, Alkeryl
According to the original p r o c e d ~ r e [ ' ~ ~a "cyclopropyl.~]
methanol (210) is treated with 48% hydrobromic acid secondary alcohols (2104 give the (4-configurated olefins
(2114 with 90 to 95% stereoselectivity.Treatment of tertiary
alcohols (210b) with magnesium halides in ether also give the
(@-olefins (211b) in excellent yields['601.On the other hand,
the modified procedure of Johnson et aZ.['6'1leads to trisubstituted (E)-olefins (214) stereoselectively upon treatment of
the secondary cyclopropylmethyl bromides (213) with zinc
bromide in ether. Stereoselectivity is also observed if one of
the two alkyl groups in (210) carries a phenylsulfonyl
Interesting variants of the Julia method are the stereoselective production of conjugated enynes (218) as precursors for
conjugated E,Z-dienes from alkynylcyclopropylmethanols
via their dicobaltcarbonyl complexes (216) as intermeAngew. Chem. Inl. Ed. Engl. 18, 809-826 (1979)
d i a t e ~ [ ' ~as
~ ]well
as the acid-catalyzed rearrangement of
(phenylthiocyclopropy1)vinylmethanols (219) to functionalized conjugated dienes (220), which are versatile intermediates in
The "homologous Michael reaction", i. e. the ring opening
of cyclopropylcarbonyl compounds by nucleophiles, which
has been developed extensively in recent year^['^^^'^^], is derived from the same reaction principle. If sufficiently activated by two electron-withdrawing groups (especially as in
(221)), such compounds can add various nucleophilic reag e n t ~ [ ' ~The
~ ] . primary adducts of primary amines (e.g.
(222)) or water (223) readily cyclize to the five-membered
heterocycles (224) and (226) respectively, which, like the adducts of carbanions [e.g. (225)], can serve as intermediates in
the synthesis of natural prod~cts['~'I.
Monoactivated cyclopropanes do not react the same way
except in special cases11651.
Nucleophilic additions to such
systems do, however, occur smoothly with the assistance of
an ele~trophile~'~*-'~'1
(see Section 2[53J).In this way, cyclo-
X = 1,ClQ.
These are a few examples only for the various possibilities
of the cyclopropylmethyl homoallyl ring opening reaction.
Nonetheless the second type of cyclopropylmethyl rearrangement, i. e. the ring expansion to cyclobutane derivatives, was essential for a number of new synthetic react i o n ~ [ ' ~ ~All
- ' ~the
~ ~(I-hydroxycyclopropy1)methyl
derivatives (230) yield cyclobutanone (231) under appropriate cond i t i o n ~ [ ~A
~ *p-lactam
synthesis developed by Wasserman et
al. [e.g. (232) + (233)] is based on the same reaction princiI-Vinylcyclopropanol (234) reacts with electrophilic
reagents to yield derivatives of 2-methylcyclobutanone, e. g.
(235)[1741.1-Vinylcyclopropanols (236) can also be rearranged thermally to cyclobutanones (237)[1721.The greatest
flexibility is offered by the oxaspiropentanes (238)-readily
from aldehydes
available according to Trost et aZ.[56*57.175]
and ketones-because of their rearrangements to cyclobutanones (239), which can be utilized in the synthesis of a variety of compounds such as (240) and (241)1'751.
The wide spectrum of possible applications of electron-deficient cyclopropylmethyl groups has only been suggested by
these examples. Finally, it should be pointed out how the
electron-donating ability of the cyclopropyl group can be utilized in mechanistic problems. TidweN et al. have carefully
investigated electrophilic additions to alkenes and observed
that the rate enhancement by a cyclopropyl substituent is
proportional to the amount of positive charge localized on
the a-carbon atom in the transition state['761.In a reversed
sense, the cyclopropyl substituent can therefore be used as a
sensitive probe into the transition state structure of an electrophilic
7. Heterocyclic Analogues of Cyclopropane
propyl ketones are cleaved under mild conditions by trimethylsilyliodide (TMSI) to y-iodoketones [e.g. (228) --t
or by acetylmethanesulfonate (AcOMs) together
with nucleophiles to give &substituted enol acetates [e.g.
(228) + (229)]["'].
Angew. Chem. Pt. Ed. Engl. 18, 809-826 (1979)
While discussing the characteristics of the cyclopropane
ring one is automatically tempted to compare them with
those of simple heterocyclic three-membered rings, especially since their bonding properties can be described by the
same model as that used for the cyclopropane
far as the chemistry of aziridines and oxiranes is concerned,
reference is made to the relevant handbook^^'^^]. In this context, only the interesting question about the electron-donating ability of aziridyl and oxiryl groups, which has remained
unanswered for a long time in spite of elaborate studies[ l79/lKl], will be discussed briefly.
Previous kinetic and mechanistic investigations on aziridylmethyl[179.’ and oxirylmethyl
did not
give a clear-cut picture, because in all cases so far ring opening reactions and neighboring group participation of the heteroatom played an important role. In contrast to this, the 1chloro-3-methyl-3-azatrishomobarrelene(242b) and the 1chloro-3-oxatrishomobarrelene (243b) solvolyze exclusively
to unrearranged bridgehead derivatives (242c, d} and (243c,
respectively. Their solvolysis rates therefore yield
reliable information pertaining to the question of how an
intact three-membered heterocycle influences the relative
stability of an adjacent carbenium ion center.
Taking into account all the structural details, the exact
analysis of the rate data (see Table 4) shows that in these systems with their rigid conformations the electron-donating
ability of an unsubstituted aziridyl group is about 13 times
weaker than that of a cyclopropyl group, whereas the oxiryl
group even exhibits a strong electron-withdrawing effect.
The decreasing donating ability of the hetero-three-membered rings correlates with the increasing electronegativity of
the heteroatoms, which lowers the energy of its highest occupied Walsh molecular orbital[’841.Electron-withdrawing substituents at the cyclopropyl group as in (244b) act in the same
way (see Table 4)11821.
Ia)X=H ;
(244 )
Table 4. Rate constants and free energies of activation of heterologous l-chlorotrishomobarrelenes and reference compounds [I 821.
k25 [SKI]
hypothet. [a]
R = H [b]
- 15.9
- 3.7
- 6.9
- 1.2
[a] Calculated for a hypothetical model showing the same degree of skeletal
twisting in its transition state as found for (1826) (see (181). [b] Calculated from
the value for the N-methyl compound with a factor of l o - ’ to account for the
methyl group [183].
8. Outlook
It is obvious that the aspects of small ring chemistry presented here cannot be discussed extensively, and they have
not even been completely investigated yet. New polycyclic
small ring compounds which have already been prepared or
only trapped as short-lived intermediates will help to delineate the limits of the carbon atom’s bonding ability and the
possibilities of reactivity enhancement by ring strain. This is
exemplified by the molecules (245)-(249). In the so-called
small ring propellanes (245)-(247) the p character of the
central C-C single bond must be unusually high because all
four bonds on the two quaternary carbons are arranged as in
an “inverted” t e t r a h e d r ~ n [ ’ ~ ~Like
* ‘ ~ ~the
’ . n bonds in ole-
fins, these central bonds therefore easily add a variety of reagents. However, the most important factor determining the
reactivity of these propellanes is the high total strain energy,
which is largely liberated upon opening the central bond. In
this way, the [3.2.l]propellane (245}1‘87Jwith a strain energy
(SE) of about 250 kJ/mo11‘881
rapidly adds halogens, acids,
and even atmospheric oxygen. So far the [2.2.l]propellane
(246)[’891and the [2.2.2] parent system[’901
(SE about 330 kJ/
r n ~ l ~in
‘ ~each
’ ~ case) have only been postulated as intermediates based on the isolation of their addition products.
However, one cannot generally relate a high total strain
energy of a molecule to its thermal instability and draw conclusions about its ability to exist at room temperature. For
instance, (245) is thermally quite stable although it adds electrophiles quite easily. This difference is even more pronounced in the case of barettane (248) with S E 2 4 4 9 kJ/
in the presence of a catalyst (248) adds hydrogen extremely rapidly to the most highly strained u bonds of its two
bicyclo[2.1.O]pentane units; yet, on the other hand, it is completely stable up to 200°C[1921.In contrast to the isomeric
diademane (91) ( S E about 427 kJ/mol)[‘”l, (248) does not
have a low energy reaction path to a thermodynamically
more stable rearrangement product at its disposal.
The still hypothetical propellane (249) seems to approach
the limits of what is conceivable on the basis of current
bonding theory. Its three bicyclopentane units which all
share the same central bond contribute to a total strain energy of at least 670 kJ/m01[’~’1,the portion of about 328 kJ/
mol which would be released upon opening the central bond
very closely resembles the energy of a normal C-C single
bond. It remains questionable, therefore, whether (249) can
exist at all with a central “bond”, even if one takes into account that a certain stabilizing interaction may occur between the bridgehead p orbitals and the cyclopropyl Walsh
Nevertheless, there are experimental findings which suggest an intermediacy of (249) or its diradical or zwitterionic
The 1-tert-butyl derivative (250)
is formed at - 110 “C from 1,s-diiodotrishomobarrelene
(201d) and tert-butyllithium after aqueous work-up. Since a
direct tert-butylation of (201d) can be excluded-though the
more reactive I-iodotrishomobarrelene is smoothly metalated under the same conditions it does not yield a trace of
(252)-it is more probable that in fact (249) is formed via
An addition of tert-butyllithium to the central bond in
(249), which would be reasonable in view of its high strain
energy, leads to (252), the intermediacy of which was proved
by its carboxylation to (253). Final proof for the intermediate
formation of the symmetrical (249), which would be possible,
for instance, by use of a trishomobarrelene derivative (201e)
Angew. Chem. Int. Ed. Engl. f8, SOY-826 (19791
(261) constitutes a useful method for the annelation of cycloheptane ring~[‘~*I.
Wenkert et al. demonstrated an elegant utilization of the
methoxycyclopropyl function in important steps of the total
synthesis of ( + )-grandis01 [(265)+ (266)],of ( - )-valeranone
[(265)-+ (268)],and of other se~quiterpenes[’~~’.
with two different leaving groups in optically active
is still pending.
Better chances for a direct spectroscopic proof should exist
for the radical cation (255) which is closely related to (249),
because the substantial cation-stabilizing effect of the cyclopropyl group (vide supra) comes into play and the conceivable “bond” between the two bridgehead~[’~~I
would be a
one-electron bond and thereby longer than that in (249). It is
an open question what the lifetime of (255) may be, if it occurs as an intermediate in the sequence (254) + (257)11931.
this case, the use of optically active starting material[’961
would again be of help.
Thus more and more new model compounds can be conceived which will provide ever more detailed knowledge
about the “bonding properties of the cyclopropane ring and
their chemical consequences”. The development of new synthons, which utilize these properties, will build upon that
knowledge. Even nowadays, synthetic applications of the
small ring functions are beginning to play a major role.
Systems of type (257) can be constructed by standard
methods, e. g. from a$-unsaturated carbonyl compounds.
Their fragmentation, accompanied by a strain energy release
of about 230 kJ/mol, proceed under mild conditions and stereospecifically to give 1,6- and 1,7-difunctionalized molecules such as (259) and (260), which can serve as starting materials for the syntheses of acyclic terpene~[’~’I.
The thermal rearrangement of the adducts (263) of 2-vinylcyclopropyllithium (262) to 3-alkoxy-2-cycloalkenones
Angew. Chem. Int. Ed. Engl. IS,809-826 (1979)
These and many other examples1200~165~1631
point the way
for the directed utilization of three-membered ring synthons.
The authors’ own work cited in this article was only made
possible by the dedication and ingenuity of a group of enthusiastic co-workers. Their namens are given in the relevant references. Particular thanks go to Professor W. Liittke, Gotlingen,
for provision of excellent working conditions during the decisive initial phase. Financial support by the Deutsche Forschungsgemeinschaft,the Fonds der Chemischen Industrie, the
State of Lower Saxony, and Hoechst AG, FrankfurtlMain,
and BASF A G, Ludwigshafen, is gratefully acknowledged.
Received: August 23, 1979 [A 293 IE]
Supplemented: September 26, 1979
German version: Angew. Chem. 91, 867 (1979)
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11531 Doz. Dr. P. BischoJ Heidelberg, personal communication.
11541 G. A. Olah, G. Liang, P. uon R. Schleyer, E. M. Engler, M. J. S. Dewar, R.
C. Bingham, J. Am. Chem. SOC.95, 6829 (1973).
11551 G. A . Olah, G. Liang, J . Am. Chem. SOC.93, 6872 (1971).
11561 Cf. M . Geisel. C. A. Grob, W Santi, W. Tschudi, Helv. Chim. Acta 56,
1046,1055 (1973),and references cited therein.
[157]Systematic name: penlacyclo['o]dodecane.
[1 581 E. Proksch, A. de Meijere, unpublished cf. E. Proksch, Dissertation, Universitat Gottingen t 977.
11591 a) M . .Julia, S. Julia, R. Guegan, Bull. SOC.Chim. Fr. 1960, 1072;b) M. Julia, S. Julia, S:Y. Tchen, ibid. f961, 1849;c) M. Julia, S. Julia, B. StallaBourdillon, C. Descains, ibid. 1964, 2533;d) M. Julia, C. Descoins, C. Risse,
Tetrahedron Suppl. 8, 443 (1966); e) M. Julia, J. M. Paris, Tetrahedron
Lett. 1974, 3445.
(1601 J. P. McCormick, D. L. Barton, J . Chem. Soc. Chem. Commun. 1975,
11611 S. F. Brady, M. A. Ilton, W S. Johnson, J . Am. Chem. SOC.90, 2882
11621 See, e.g., a) B. H. Braun, M. Jacobson, M . Schwarz, P. E. Sonnet, N. Wakabayashi, R. M. Waters, J . Econ. Entomol. 61, 866 (1968);b) W. S. Johnson, T. Li, D. J. Faulkner, S. F. Campbell, J . Am. Chem. SOC.90, 6225
(1968);c) K. A. Parker, W. S. Johnson, Tetrahedron Lett. 1969,1329; d) H.
WaK U. Matzel, E:J. Brunke, E. Klein, ibid. 1979, 2339.
11631 C.Descoins, D. Samain, Tetrahedron Lett. 1976, 745.
(1641 R. D. Miller, D. R. McKean, D. Kaufmann, Tetrahedron Lett. 1979, 587.
11651 S. Danishefsky, Acc. Chem. Res. 12, 66 (1979).
11661 R. V. Stevens, Pure Appl. Chem. 51, 1317 (1979).
I1671 a) S. Danishefsky, R. K. Singh, J . Am. Chem. SOC.97,3239(1975);b) R. K.
Singh, S. Danishefsky, J . Org. Chem. 41, 1668 (1976).
[1681 a) G. Stork, P. Grieco, J . Am. Chem. SOC.91, 2407 (1969);b) G. Stork, M.
Marx, ibid. 91, 2371 (1969); c) G. Stork, M . Gregson, ibid. 91, 2373
11691 E. J. Corey, R D. Balanson, Tetrahedron Lett. 1973, 3153.
[I701 R. D. Miller, D. R. McKean, Tetrahedron Lett. 1979, 2305.
[I711 M. Demuth, P. R. Raghavan, Helv. Chim. Acta 62, in press (1979).
[I721 J. Salaun, B. Gamier, J. M. Conia, Tetrahedron 30, 1413 (1974),and further references cited therein.
11731 H. H. Wasserman, E. A. Glazer, M. J. Hearn, Tetrahedron Lett. 1973,4855;
H. H. Wasserman, E. Glazer, J. Org. Chem. 40, 1505 (1975).
[174] H. H. Wasserman, R. E. Cochoy, M. S. Baird, J . Am. Chem. SOC.91, 2375
(1969); H. H. Wasserman, H. W. Adickes, 0. Espejo de Ochoa, ibid. 93,
5586 (1971).
11751 B. M. Trost, Acc. Chem. Res. 7, 85 (1974);B. M. Trost, M. Preckel, L. M.
Leichter, J . Am. Chem. SOC.97, 2224 (1975);B. M . Trost, D. E. Keeley, H.
C. Arndt, M. J. Bogdanowicz, ibid. 99, 3088 (1977),and further references
cited therein.
11761 D. G. Garrat, A. Modro, K. Oyama, C. H. Schmid, T. T. Tidwell, K. Yules,
J . Am. Chem. Soc. 96, 5295 (1974);K. Oyama, T. T. Tidwell, ibid. 98, 947
(1976); I. C. Ambidge, S. K. Dwight, C. M. Rynard, T. T. Tidwell, Can. J .
Chem. 55, 3086 (1977),and references cited therein,
[I771 C. A. Coulson, T. H. Goodwin, J . Chem. SOC. 1962, 2851 and earlier work;
cf. D. T. Clark, Theor. Chem. Acta 10, 1 1 1 (1968).
11781 0. C. Dermer, G. E. Ham: Ethylenimine and Other Aziridines. Academic
Press, New York 1969; S. Winstein, R. B. Henderson in R. C. Elderfield:
Heterocyclic Chemistry, Vol. I. Wiley, New York 1950; R. E. Parker, N. S.
Isaacs, Chem. Rev. 59, 737 (1959).
11791 J. A. Deynrp, C. L. Moyer, Tetrahedron Lett. 1968, 6179; J. A . Deyrup, C.
L. Moyer, P. S. Dreyfus, J. 0 % . Chem. 35,3428 (1970); V. R. Gaertner, Tetrahedron Lett. 1968, 5919; 1. Org. Chem. 35, 3952 (1970).
[180] a) G. Szeimies, Chem. Ber. 106, 3695 (1973);b) G. Szeimies, K. Mannhardt,
M. Junius, ibid. 110, 1792 (1977).
11811 Cf. a) D. L. Whalen, J . Am. Chem. Soc. 92, 7619 (1970); h) W C. Danen,
ibid. 94, 4835 (1972), and references cited therein.
[1 821 C. Weitemeyer, A. de Meijere, unpublished; cf. C. Weitemeyer, Dissertation,
Universitat Gottingen 1976.
[t 831 Cf. P. uon R. Schleyer, G. W Van Dine, J. Am. Chem. SOC.88,2321 (1 966);
R. S. Brown, T. G. Traylor, ibid. 95, 8025 (1973).
[184] Cf. H. Basch, M. B. Robin, N. A. Kuebler, C. Baker, D. W . Turner, J.
Chem. Phys. 51, 52 (1969); M. Rohmer, B. Roos, J. Am. Chem. SOC.97,
2025 (1975).
[lS5] Cf. D. Ginsburg: Propellanes, Structure and Reactions. Verlag Chemie,
Weinheim 1975, and references published therein.
[I861 a) W. D. Stohrer, R. Hofmann, J. Am. Chem. SOC.94,739 (1972); b) M . L.
Herr, Tetrahedron 33, 1897 (1977).
[I871 K. B. Wiberg, G. J. Burgmaier, Tetrahedron Lett. 1969, 317; J. Am. Chem.
SOC.94, 7396 (1972); P. G. Gassman, A . Topp, J. W. Keller, Tetrahedron
Lett. 1969, 1093.
(1881 K B. Wberg, E. D. Lupton, Jr., G. J. Burgmaier, 1. Am. Chem. Soc. 91,
3372 (1969).
[189] K. B. Wiberg, W F. Bailey, M. E. Jason, J. Org. Chem. 41, 2711 (1976); P.
E. Wood, W. F. Bailey, K. B. Wiberg, J. Am. Chem. SOC.99, 268 (1977).
[190] K. B. Wiberg, G. A . Epling, M. Jason, J. Am. Chem. SOC.96, 912 (1974); J.
J. Dannenberg, T. M. Prouic, C. Huff,ibid. 96, 914 (1974); K. B. Wiberg, U.:
E. Pratt, W. F. Bailey, ibid. 99, 2297 (1977).
[191] Estimated with the usual assumption ofadditivity of strain contributions of
the subunits. Cf. L.N. Fergusont Highlights of Alicyclic Chemistry. Franklin Publ. Co., Palisade, N. J. 1973.
[I921 D. Bosse, A . de Meijere, Chem. Ber. 111, 2223 (1978).
11931 P. Giilirz, A . de Meijere, unpublished; P. G6litz, Dissertation, Universitat
Gottingen 1978.
[194] In the optically active derivatives of type (201e) [147] prepared so far, X
and Y were not good enough leaving groups.
[1951 ESR studies on the question of delocalization of the radical electron in
(255) are being conducted in collaboration with M. McBride and M. Saunders (Yale University, New Haven, Conn. (USA)).
[I961 Cf. W. Spielmann, A . de Meijere, Angew. Chem. 88, 446 (1976); Angew.
Chem. Int. Ed. Engl. IS, 429 (1976).
1197) B. M. Trost, W.J. Frame, J. Am. Chem. SOC.99, 6124 (1977).
11981 P. A . Wender, M. P. Filosa, J. Org. Chem. 41, 3490 (1976).
[I991 E. Wenkert, D. A . Bergers, N. F. Golab, J . Am. Chem. SOC.100, 1263
(1978): E. Wenkert, B. L. Buckwalier, A. A. Craueiro, E. L. Sanchez, S. S.
Sathe, ibid. 100, 1267 (1978); cf. also Y. Ito, T. Saegusa, J. Org. Chem. 42,
2326 (1977); Y. Ira, T. Sugaya, M. Nakatsuka, T. Saegusa, J. Am. Chem.
Soc.99, 8366 (1977).
[200] See, e.g. a) J. W ApSimon: The Total Synthesis of Natural Products. Vol.
1-3. Wiley-lnterscience, New York 1973, 1977; b) K Nakanishi, 7: Gofo,
S. Ifo, S. Narori, S. Nozoe: Natural Products Chemistry. Kodansha Ltd.,
Tokyo/Academic Press, New York 1975; c) D. Seebach, Angew. Chem. 91,
259 (1979); Angew. Chem. Int. Ed. Engl. f8,239 (1979).
Conformational Analysis by Photoelectron Spectroscopy
By Martin Klessinger and Paul Rademacher“]
Dedicated to Professor Wolfgang Liittke on the occasion of his 60th birthday
The conformation of organic molecules may be determined by means of photoelectron (PE)
spectroscopy if there are orbital interactions present which depend on a dihedral angle.
Straightforward application of the method requires that all ionization bands of interest can be
assigned unambiguously and that inductive effects and secondary orbital interactions do not
occur or can be accounted for appropriately. In many cases, this method complements conventional methods of conformational analysis. PE conformational analysis is particularly suited to
compounds containing vicinal lone pairs or 7~ systems.
1. Introduction
In order to completely describe the structure of an organic
molecule one has to specify not only the constitution and the
configuration, but also the conformation. While the constitution merely indicates which atoms are connected, different
spatial arrangements of the bonds with respect to a given
atom or group of atoms (e.g. a C=C double bond, a ring,
etc.) lead to different configurations which may be converted
into each other only by breaking and reforming one or several bonds.
According to Barton[’]the conformations of a molecule of
given constitution and configuration “are those arrangements in space of the atoms of the molecule which are not
superposable upon each other”. A molecule can therefore as[ * ] Prof. Dr. M. Klessinger
Organisch-Chemisches Institut der Universitat
Orleansring 23, D-4400Miinster (Germany)
Prof. Dr. P. Rademacher
Fachbereich Chemie der Universitat
Universitatsstrasse 5-7, D-4300 Essen (Germany)
0 Verlag Chemie, GmbH, 6940 Weinheim, 1979
sume an infinite number of conformations by varying its
bond lengths and bond angles. In practice, however, only
those arrangements of atoms are usually considered as different conformations which are obtained by rotation about single bonds. Different conformations are populated according
to their energy contents. While the few “stable” conformations of a molecule are of principal interest, energy rich
forms may be of special importance in connection with
chemical reactivity.
As the various stable conformers of a molecule can be interconverted by means of relatively low-energy processes (rotation about single bonds, inversion of nonplanar groups),
they may be isolated at room temperature only in exceptional cases. The borderline between conformational and configurational isomerism is not rigid a value of 80 kJ/mol may be
assumed for practical purposes.
Conformational analysis as a branch of stereochemistry is
concerned with physical and chemical properties of different
conformers of a given molecule. The principles of conformational
the historical de~elopment[~.~],
as well as
and the~retical[~,~l
methods have been dealt
LF 02.50/0
Angew. Chem. Inf. Ed. Engl. 18, 826-837 (1979)
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bonding, thein, properties, chemical, cyclopropane, consequences
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