Electronic substituent effects for the fine-tuning of the regioselectivity in the diastereoselective rearrangement of 1,3- cyclopentanediyl radical cations generated from tricyclo[3.3.0.02,4]octanes (housanes) by chemical electron transfer

Article abstract of DOI:10.1021/ja982329e

1,3-Cyclopentanediyl radical cations 5·⁺ were generated from tricyclo[3.3.0.0^2,4]octanes (housanes) 5 through chemical oxidation with tris(4-bromophenyl)aminium hexachloroantimonate (TBA·⁺SbCl₆^-) and

Full text of DOI:10.1021/ja982329e

11858
J. Am. Chem. Soc. 1998, 120, 11858-11863
Electronic Substituent Effects for the Fine-Tuning of the
Regioselectivity in the Diastereoselective Rearrangement of
1,3-Cyclopentanediyl Radical Cations Generated from
Tricyclo[3.3.0.02,4]octanes (Housanes) by Chemical Electron Transfer
Waldemar Adam and Thomas Heidenfelder*
Contribution from the Institut fu¨r Organische Chemie, UniVersita¨t Wu¨rzburg, Am Hubland,
D-97074 Wu¨rzburg, Germany
ReceiVed July 3, 1998
Abstract: 1,3-Cyclopentanediyl radical cations 5•+ were generated from tricyclo[3.3.0.02,4]octanes (housanes)
5 through chemical oxidation with tris(4-bromophenyl)aminium hexachloroantimonate (TBA•+SbCl6-) and
shown to afford the regioisomeric olefinic products 6 and 7 on methyl 1,2 migration. A complete reversal in
the regioselectivity of the 1,2 shift was observed, which reflects the electronic character of the X substituent
at the migration terminus in the radical cation 5•+. The regioselectivity is rationalized in terms of a simple
MO interaction diagram by considering the ꢀSOMO orbital energies (AM1 method) of the X-substituted radical
fragments in the intermediary 1,3 radical cations 5•+ relative to that of the cumyl radical fragment. The excellent
correlation between the calculated orbital energy differences (∆ꢀ) and the experimentally observed regioisomeric
ratios allows a quantitative assessment of the electronic substituent effects. The diastereoselectivity of the 1,2
shift is controlled by the steric factors in the intermediary 1,3 radical cations 5•+.
Introduction
substantial electronic substituent effects on the rate and regio-
chemistry.4 These transformations may be understood as
nucleophilic displacements on one-electron σ bonds and occur
stereoselectively with inversion of configuration. Ab initio
calculations by Borden have dealt with the ring opening of the
cyclopropane radical cation to the propene radical cation and
display no chemically significant stability for the trimethylene
radical cation.2b Bicyclic derivatives of cyclopropanes are the
much more strained bicyclo[2.1.0]pentanes (housanes), whose
electron-transfer chemistry has in recent years been extensively
explored. Mechanistic studies have demonstrated that the
intermediary 1,3-cyclopentanediyl radical cations exhibit a high
propensity to rearrange by 1,2 shift to the corresponding 1,2
radical cations, which after electron back-transfer (BET) yield
substituted cyclopentenes.5 EPR spectroscopy under matrix
isolation conditions5f,g and pulse radiolysis studies5c proved
helpful in detecting and characterizing the transient radical
cations for the elucidation of the rearrangement. The bicyclo-
[3.2.0]hept-6-ene-2,4-diyl radical cation, generated from the
corresponding housane, is intramolecularly trapped by the
juxtaposed cyclobutenyl double bond to afford quadricyclane
radical cations.5d
The intermediary 1,3 radical cations are generated either
photochemically (PET) or chemically (CET), the latter by using
one-electron oxidants such as the readily available aryl aminium
salts.6 Since in the catalytic CET mode no radical ion pairs
are formed as intermediates, electron back-transfer is minimized
and excellent yields of rearrangement products have been
obtained.5b,e Therefore, this oxidative rearrangement methodol-
ogy may serve as a useful synthetic tool for tailor-made target
molecules.5e Such electron-transfer oxidations, which engage
the well-known and highly exothermic cyclopropane-propene
Electron-transfer oxidations are of current interest and numer-
ous studies have been employed not only for mechanistic but
also for synthetic purposes.1,2 Particularly, radical cations with
strained rings have attracted considerable attention.2a,b,3-5 For
example, the electron-transfer photochemistry of vinylcyclo-
propane derivatives has been well examined by Roth and was
found to proceed in a high degree of regio- and stereoselectivity.3
For instance, the products of the [1,3]-sigmatropic hydrogen
shift of the (1R,5R)-(+)-sabinene radical cation preserved their
optical activity. Dinnocenzo studied the reaction of substituted
arylcyclopropane cation radicals with nucleophiles and found
* Corresponding author: (fax) +49(0)931/888-4756; (e-mail) adam@
chemie.uni-wuerzburg.de.
(1) For a recent review, see: Schmittel, M.; Burghart, A. Angew. Chem.
1997, 109, 2658.
(2) (a) Shaik, S. S.; Dinnocenzo, J. P. J. Org. Chem. 1990, 55, 3434. (b)
Du, P.; Hrovat, D. A.; Borden, W. T. J. Am. Chem. Soc. 1988, 110, 3405.
(c) Maslak, P.; Chapman, W. H., Jr.; Vallombroso, T. M., Jr.; Watson, B.
A. J. Am. Chem. Soc. 1995, 117, 12380. (d) Bauld, N. L.; Yueh, W. J. Am.
Chem. Soc. 1994, 116, 8845.
(3) (a) Weng, H.; Sethuraman, V.; Roth, H. D. J. Am. Chem. Soc. 1994,
116, 7021. (b) Weng, H.; Sheik, Q.; Roth, H. D. J. Am. Chem. Soc. 1995,
117, 10655. (c) Herbertz, T.; Roth, H. D. J. Am. Chem. Soc. 1996, 118,
10954. (d) Herbertz, T.; Roth, H. D. J. Am. Chem. Soc. 1997, 119, 9574.
(4) (a) Dinnocenzo, J. P.; Lieberman, D. R.; Simpson, T. R. J. Am. Chem.
Soc. 1993, 115, 366. (b) Dinnocenzo, J. P.; Simpson, T. R.; Zuilhof, H.;
Todd, W. P.; Heinrich, T. J. Am. Chem. Soc. 1997, 119, 987. (c) Dinnocenzo,
J. P.; Zuilhof, H.; Lieberman, D. R.; Simpson, T. R.; McKechney, M. W.
J. Am. Chem. Soc. 1997, 119, 994.
(5) (a) Adam, W.; Handmann, V.-I.; Kita, F.; Heidenfelder, T. J. Am.
Chem. Soc. 1998, 120, 831. (b) Adam, W.; Corma, A.; Miranda, M. A.;
Sabater-Picot, M.-J.; Sahin, C. J. Am. Chem. Soc. 1996, 118, 2380. (c)
Adam, W.; Kammel, T.; Toubartz, M.; Steenken, S. J. Am. Chem. Soc.
1997, 119, 10673. (d) Adam, W.; Heidenfelder, T.; Sahin, C. J. Am. Chem.
Soc. 1995, 117, 9693. (e) Adam, W.; Heidenfelder, T.; Sahin, C. Synthesis
1995, 1163. (f) Adam, W.; Sahin, C.; Sendelbach, J.; Walter, H.; Chen,
G.-F.; Williams, F. J. Am. Chem. Soc. 1994, 116, 2576. (g) Adam, W.;
Walter, H.; Chen, G.-F.; Williams, F. J. Am. Chem. Soc. 1992, 114, 3007.
(6) Schmidt, W.; Steckhan, E. Chem. Ber. 1980, 113, 577.
10.1021/ja982329e CCC: $15.00 © 1998 American Chemical Society
Published on Web 11/06/1998

Radical Cations Generated from Tricyclo[3.3.0.02,4]octanes
J. Am. Chem. Soc., Vol. 120, No. 46, 1998 11859
Scheme 1a
rearrangement,7 proceed not only catalytically but also diastereo-
and regioselectively. For the symmetrical, stereolabeled anti-
and syn-5-methylbicyclo[2.1.0]pentanes, a remarkable stereo-
chemical memory effect was disclosed (eq 1).5g
The anti stereoisomer furnished only 1-methylcyclopentene
as the rearrangement product, while the syn one afforded
predominantly 3-methylcyclopentene. These product studies,
combined with the direct observation of the transient radical
cations by EPR spectroscopy under matrix isolation, demanded
a persistent conformation as precursor, whose stereochemical
arrangement is dictated by the configuration of the starting
housane. In the case of unsymmetrical derivatives of bicyclo-
[2.1.0]pentane, a reversal in the regioselectivity of the 1,2
migration was observed (eq 2).5b Thus, 1-methylbicylopentane
a Conditions: (i) N2H4‚H2O; (ii) CF3COOH, cyclopentadiene; (iii)
H2, Pd/C, EtOAc; (iV) hν (333-364 nm), n-pentane.
The 1,3-cyclopentanediyl radical cations 5•+ were chosen for
the present study, since in a preliminary study their suitability
was demonstrated.5a The methyl-substituted (a-g) and the
yielded exclusively 3-methylcyclopentene, while 1-phenylbi-
cyclopentane gave 1-phenylcyclopentene as the major product.
These remarkable regioselectivities were rationalized in terms
of preferred positive-charge localization at the migration
terminus in these Wagner-Meerwein-type rearrangements.
Thus, the site that stabilizes the positive charge in the 1,3-diyl
radical cation better than the unpaired electron promotes
migration in that direction.
carbonyl (h, i) derivatives were selected to probe electronic
substituent effects. Such fine-tuning should disclose what
electronic factors operate in the relative stabilization of the cation
versus the radical center in the 1,3 radical-cation intermediate.
To elucidate possible steric perturbations, the aryl (j-n)
derivatives were employed, in which the para substituent should
act only electronically. For comparison, the acid-catalyzed
rearrangement of the housanes 5 was examined in order to
establish the chemical behavior of the carbocations 5(H)+ versus
the radical cations 5•+. Our novel results confirm that pro-
nounced electronic effects operate on the regioselectivity of the
rearrangement for the radical cations 5•+, while the diastereo-
selectivity is governed by steric features at the diyl sites.
Although the chemistry of 1,3-cyclopentanediyl radical
cations has been extensively studied and the mechanistic features
are reasonably well understood,5 the fundamental question of
the relative stabilization of their cation and radical sites is still
largely open-ended. Thus, mechanistic information is essential
in rationalizing the chemical behavior of these elusive inter-
mediates, which intervene in most thermal and photochemical
electron-transfer processes. Unquestionably, the radical cations
derived from housanes are ideally suited to aquire such data,
since from the aforementioned (eq 2) it should be evident that
the rearrangement regioselectivities offer the unique opportunity
to assess what electronic factors control the relative stabilization
of the cation versus radical centers. For this purpose, a wide
range of bridgehead-substituted housanes would be necessary,
a rather formidable synthetic chore for the parent bicyclo[2.1.0]-
pentane system. Fortunately, the Hu¨nig azoalkane route8
(Scheme 1) provides a general and convenient method, in which
the substitution pattern in the 1,3-dione 1 becomes the desired
structural feature in the housane derivative 5. The additional
advantage of the tricyclic skeleton of 5, besides the large variety
of X substituents, is that the cyclopentane-annelated ring serves
as stereochemical label to monitor the diastereoselectivity of
the rearrangement process.
Results
Synthesis of the Azoalkanes and Tricyclooctanes. The
preparation of the known azoalkanes 4a,j-m and housanes
5a,j-m has already been published.5e,9 The hitherto unknown
azoalkanes 4b-i were prepared according to Hu¨nig’s isopyra-
zole cycloaddition method (Supporting Information) and from
them the housanes 5 by photodenitrogenation (Scheme 1).
Electron-Transfer Reactions of the Tricyclooctanes. The
product data are summarized in Table 1 (Scheme 2). The
configurations of the diquinanes 6 and 7 were assigned by means
of a prominent (∼8%) NOE effect between the 4R substituent
at the C-4 position and the bridgehead hydrogen at C-1 but none
(7) (a) Boche, G.; Walborsky, H. M. In Updates from the Chemistry of
Functional Groups: Cyclopropane-deriVed ReactiVe Intermediates; Patai,
S., Rappaport, Z., Eds.; Wiley & Sons: Chichester, U.K., 1990; p 207. (b)
Qin, X.-Z.; Snow, L. D.; Williams, F. Chem. Phys. Lett. 1985, 117, 383.
(c) Qin, X.-Z.; Williams, F. Chem. Phys. Lett. 1984, 112, 79.
(9) Adam, W.; Kita, F.; Harrer, H. M.; Nau, W. M.; Zipf, R. J. Org.
Chem. 1996, 61, 7056.
(8) Beck, K.; Hu¨nig, S. Chem. Ber. 1987, 120, 477.

11860 J. Am. Chem. Soc., Vol. 120, No. 46, 1998
Adam and Heidenfelder
Table 1. Product Data of the Chemical Electron-Transfer and Acid-Induced Rearrangements of Housanes 5
product distributionc
entry
substrate
X
solvent
modea
time
baseb
0.1
convn (%)
6(exo-Me)
6(endo-Me)
7(exo-Me)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
5ad
5a
5c
5c
5d
5d
5e
5e
5f
CH3
CH3
CH2Cl2
CH3CN
CH2Cl2
CDCl3
CH2Cl2
acetone-d6
CH2Cl2
acetone-d6
CH2Cl2
CDCl3
CH2Cl2
CD3CN
CH2Cl2
CDCl3
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CDCl3
TBA•+ (0.1)
HClO4
5 min
24 h
24 h
20 min
5 min
6 h
10 min
10 min
12 h
10 min
19 h
24 h
30 min
15 min
30 min
1 d
95
100
95e
100
49
100
21
0
0
0
79
CH2OAc
CH2OAc
CH2OH
CH2OH
CH2OMe
CH2OMe
CH2F
TBA•+ (0.3)
HClO4
1.5
1.3
1.5
1.5
0
86
0
85
0
57
0
30
0
0
0
0
67
21
0
0
14
0
15
0
12
0
8
0
0
0
0
100
0
TBA•+ (0.3)
HClO4
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100f
0
TBA•+ (0.3)
HClO4
100
31
TBA•+ (0.3)
HClO4
5f
CH2F
100f
62
5g
5h
5h
5i
5i
5j
5k
5l
5m
CH2CN
CHO
TBA•+ (0.3)
TBA•+ (0.5)
HClO4
1.5
1.2
100
100
100
100
33
79
100
100
CHO
COMe
COMe
TBA•+ (0.5)
HClO4
C6H4-p-Me
C6H4-p-Cl
C6H4-p-CO2Me
C6H4-p-CN
TBA•+ (0.1)
TBA•+ (0.1)
TBA•+ (0.1)
TBA•+ (0.1)
0
0
0
0
2 h
30 min
3 d
0
a TBA•+ is tris(4-bromophenyl)aminium hexachloroantimonate, molar equivalents (in parentheses) are given relative to the housane; 70% HClO4;
1
at 20 °C, except entry 11 at reflux. b 2,6-Di-tert-butylpyridine, molar equivalents are given relative to the housane. c Determined by H NMR
spectroscopy (error ∼5% of the stated values) on the crude product mixture; mass balances >90%, except entry 3 (<5%). d See ref 5e. e Undefined
complex product mixture. f Cyclopentene exo-7n was formed.
Scheme 2
formyl- and acetyl-substituted tricyclo[3.3.0.02,4]octanes 5h,i
(entries 12 and 14), only the cyclopentenes 7h,i(exo-Me) were
observed, i.e., migration of the endo substituent exclusively to
the phenyl terminus.
A similar trend of electronic substituent effects on the
regioselectivity was observed in the CET oxidation for the aryl-
substituted housanes 5j-m (Table 1). The p-CN- and p-CO2-
Me-substituted derivatives 5l,m (entries 18 and 19) afforded
exclusively the diquinanes 7l,m(exo-Me) by 1,2-methyl migra-
tion to the phenyl-bearing terminus. In contrast, the p-Me- and
p-Cl-substituted derivatives 5j,k (entries 16 and 17) gave both
regioisomeric oxidation products 6j,k(exo-Me) and 7j,k(exo-
Me). The 6j(exo-Me) regioisomer is preferred for the methyl
case 5j, while the 7k(exo-Me) one dominates for the p-Cl
derivative 5k. For all these aryl substrates, only the exo
diastereomers were formed.
Acid-Catalyzed Rearrangement of the Housanes 5. For
all acid-catalyzed reactions (Table 1), 70% HClO4 was used as
the proton source (Scheme 2). Only the conditions under which
the highest mass balances (>90%) were achieved are given.
Contrary to the CET reactions, the acid-induced rearrangement
of the housanes 5a,c,e,h,i yielded in all cases the 7(exo-Me)
cyclopentenes as the major (entry 2) or as the exclusive (entries
4, 8, 13, and 15) rearrangement product. The housanes 5d,f
(entries 6 and 10), instead of the expected rearrangement
products 7d,f(exo-Me), gave the ether 7n(exo-Me), which is the
for the methylene hydrogens at C-6,7. Furthermore, the high-
field displacement of the 6-H protons (δ ) 0.8) in the diquinanes
6j,k and 7 derives from shielding by the proximate aryl group,
which signifies that the original syn-methyl group in the housane
has migrated. The cis arrangement of the two fused cyclo-
pentenes was established by an appreciable (∼7%) reciprocal
NOE effect for the hydrogen atoms at the C-1,5 positions.
Additionally, the structure of the diquinanes 6 and 7 was
determined by 2D-INADEQUATE NMR experiments for 6 and
7j,k.
The desired 1,3 radical cations 5•+ were generated by
chemical electron transfer with tris(4-bromophenyl)aminium
hexachloroantimonate (TBA•+SbCl6-) as one-electron oxidant.6
The reactions were carried out in either CH2Cl2 or CH3CN as
solvents for all substrates. Since no solvent dependence was
found in the CET reactions, only one example for each housane
is given in Table 1. Treatment of the tricyclooctanes 5 with
catalytic amounts of TBA•+ afforded exclusively the rearranged
olefins 6 and 7 in high yields. The CET reactions of the acid-
sensitive housanes 5a-f,h,i were carried out in the presence of
an excess of the hindered base 2,6-di-tert-butylpyridine to
prevent undesirable acid-catalyzed rearrangements.
For the methyl-, hydroxymethyl-, and methoxymethyl-
substituted housanes 5a,d,e (entries 1, 5, and 7), only migration
to the methyl-bearing site occurred. The housanes 5d,e (entries
5 and 7) yielded the diastereomeric cyclopentenes 6d,e(exo,
endo-Me) through migration of both methyl groups in the
starting housanes. The CET oxidation of the acetoxy-substituted
housane 5c (entry 3) afforded an undefined product mixture.
The fluoromethyl- and cyanomethyl-substituted housanes 5f,g
(entries 9 and 11) led to a mixture of regioisomeric cyclo-
pentenes 6f,g(exo, endo-Me) and 7f,g(exo-Me) due to 1,2-methyl
shift to both the methyl- and phenyl-bearing sites. For the
result of the acid-catalyzed condensation of the diquinanes
7d,f(exo-Me). Suprisingly, the cyanomethyl-substituted housane
5g and the aryl-substituted housanes 5j-m persisted acid
treatment. For the latter, presumably the steric bulk of the two
bridgehead phenyl groups prevents protonation of these hou-
sanes.

Radical Cations Generated from Tricyclo[3.3.0.02,4]octanes
J. Am. Chem. Soc., Vol. 120, No. 46, 1998 11861
Scheme 3
Figure 1. Schematic orbital interaction diagram of the radical fragments
in the 1,3 radical cations 5a•+ (left) and 5h•+ (right).
In CH3CN, the housanes 5c-f afforded the Ritter product
7o(exo-Me) on acid treatment. By monitoring the product
distribution of these acid-catalyzed reactions as a function of
time, it was established that the cyclopentene 7c(exo-Me) is
converted significantly slower to the Ritter product than the
corresponding housane 5c. Thus, this control experiment reveals
that the Ritter product 7o(exo-Me) is formed directly from the
housane 5c rather than subsequently from the cyclopentene
7c(exo-Me).
CN (5g), CHO (5h), COCH3 (5i), C6H4-p-Cl (5k), C6H4-p-CO2-
CH3 (5l), and C6H4-p-CN (5m) cases, the 7 regioisomer is
favored.
How can these regioselective substituent effects be mecha-
nistically rationalized? The rearrangement of a 1,3 radical cation
is of the Wagner-Meerwein type and, thus, a cationic process.2a,5
Accordingly, the regioselectivity in the CET-induced rearrange-
ment of the housanes 5 is governed by the orbital interaction
of the LUMO(σ*) orbital of the 1,3-cyclopentanediyl radical
cations 5•+ with the HOMO(σ) of the migrating C-Me σ bond.
Consequently, the orbital coefficients at the 1,3 termini in the
LUMO(σ*) of the radical cations are required to rationalize the
experimental regioselectivities of the rearrangement. The
desired SOMO(σ) and LUMO(σ*) orbitals may be assembled
in a qualitative manner through the interaction of the orbitals
for the fragments R-CMe2 and Ph-CMe2 in the 1,3 radical
cation, as shown in Figure 1 for the two extreme cases 5a•+
(complete methyl migration to the X terminus) and 5h•+
(complete methyl migration to the Ph terminus).
Discussion
Reaction Mechanism. The results presented in Table 1 show
that the oxidative rearrangement of the tricyclooctanes 5
proceeds cleanly to the corresponding diquinanes 6 and 7
(Scheme 2). Since in all cases catalytic amounts of oxidant
were enough to achieve complete conversion, we propose that
the catalytic cycle in Scheme 3 operates. Electron transfer from
the housane 5 to Ar3N•+ initiates the cycle, the subsequent
Wagner-Meerwein 1,2 rearrangement of the radical cation 5•+
leads to the regioisomeric cyclopentene radical cations 6•+ and/
or 7•+. Electron back-transfer from Ar3N to 6•+ or 7•+ forms
the diquinanes 6 and/or 7 and completes thereby the catalytic
cycle. Alternatively, BET could also occur directly from the
housane 5 to the radical cations 6•+ and/or 7•+ to yield the
diquinanes 6 and/or 7 and a new housane radical cation 5•+.
Energy considerations, however, speak against this alternative
pathway. From cyclovoltammetric measurements for the refer-
ence system, the reported5b oxidation potentials are 1.42 V
(SCE) for housane 5a, 1.58 V (SCE) for cyclopentene 6a, and
1.06 V (SCE) for TBA•+. Thus, the BET step 6a•+ + 5a f 6a
+ 5a•+ is only by ∼0.16 V exothermic, while for 6a•+ + Ar3N
f 6a + Ar3N•+ it is ∼0.5 V, and the latter process is favored.
Note that the overall reaction proceeds although the aminium
salt possesses a lower oxidation potential than the housane 5.
This is attributed to the highly exergonic rearrangement step,
which follows the initial electron-transfer process.
The relative ordering of the orbital fragments is given by the
corresponding ꢀSOMO orbital energies, which are readily acces-
sible through AM1 calculations (Table 2).10 The experimental
Eox data11 for the CH3, C6H5, and C6H4-p-CN cases confirm
the relative order of the ꢀSOMO values; unfortunately, no Eox
data is available for the remaining radicals. For convenience,
we define the ∆ꢀ quantity, for which positive values (∆ꢀ > 0)
apply when the ꢀSOMO of the X-substituted fragment lies above
the cumyl one (the phenyl substituent is taken as reference
point), while negative values (∆ꢀ < 0) are observed when the
ꢀSOMO of the X-substituted fragment lies below the cumyl one.
As a consequence, for ∆ꢀ > 0, the LUMO in the radical cation
5
•+ will be in energy more similar to the X-substituted fragment
and also carry the larger coefficient on this site (Figure 1).
Hence, the 1,2 shift will take place preferentially to the X site
to yield the 6 regioisomer, as observed for the radical cation
5a•+ (X ) CH3). Analogously, for ∆ꢀ < 0, the LUMO of the
radical cation 5•+ lies in energy closer to the cumyl fragment;
now the phenyl terminus (Figure 1) bears the larger coefficient
Regioselectivity of the 1,2 Migration in the Radical
Cations. The regioselectivity of the CET-mediated housane 5
rearrangement expresses the competition between the X (re-
gioisomer 6) and the Ph terminus (regioisomer 7) for the
migrating methyl group (Scheme 3). Indeed, reversal in the
regioselectivity of the 1,2 migration was observed: For the CH3
(5a), CH2OH (5d), CH2OCH3 (5e), CH2F (5f), and C6H4-p-Me
(5j) derivatives, the 6 regioisomer is preferred, but for the CH2-
(10) The AM1 method was used; cf.: Dewar, M. J. S.; Zoebisch, E. G.;
Healy, E. F.; Stewart, J. J. P. J. Am. Chem. Soc. 1985, 107, 3902 (VAMP
program on a Silicon Graphics Iris Indigo workstation: Rauhut, G.; Alex,
A.; Chandrasekhar, J.; Steinke, T.; Clark, T. VAMP 5.0; Universita¨t
Erlangen; Erlangen, FRG, 1993).
(11) (a) Wayner, D. D. M.; McPhee, D. J.; Griller, D. J. Am. Chem.
Soc. 1988, 110, 132. (b) Sim, B. A.; Milne, P. H.; Griller, D.; Wayner, D.
D. M. J. Am. Chem. Soc. 1990, 112, 6635.

11862 J. Am. Chem. Soc., Vol. 120, No. 46, 1998
Adam and Heidenfelder
Table 2. SOMO Energies and Orbital Energy Differences of the
Radical Fragments in the 1,3 Radical Cations 5•+ and the
Regioselectivities of the Rearrangement
Scheme 4
for the rearrangement of unsymmetrically substituted radical
cation 5•+ if the two ꢀSOMO orbital energies of the corresponding
radical fragments are known, provided the orbital energy
differences fall in the range of - 0.42 eV < ∆ꢀ < + 0.36 eV
(Table 2). For ∆ꢀ values of g0.36 eV, exclusively migration
to the X site (regioisomer 6) is observed, e.g., CH3, CH2OMe
and CH2OH, whereas the opposite (regioisomer 7) is obtained
for ∆ꢀ values of e-0.42 eV, e.g., CHO, COMe, C6H4-p-CO2-
Me, and C6H4-p-CN.
Diastereoselectivity of the 1,2 Migration. While housanes
5h-m yielded exclusively 6(exo-Me), the housanes 5d-g gave
additionally small amounts (8-15%) of the 6(endo-Me) dias-
tereomer (Table 1). Thus, some migration of the endo sub-
stituent is observed only when the rearrangement terminus bears
alkyl groups, i.e., CH2OH (5d), CH2OMe (5e), CH2F (5f), and
CH2CN (5g), whereas exclusively the exo-methyl group migrates
when this site carries aryl substituents. The formation of both
the exo-Me and endo-Me diastereomers suggests a planar
radical-cation geometry in the rearrangement step (Scheme 4),
since for a persistent puckered conformation only one diaste-
reomer would be expected.5g The preference for the exo-Me
diastereomer is presumably due to the larger steric interaction
during the transposition of the endo-methyl group at the 2
position with the annelated cyclopentane ring. Also, steric
effects appear to be responsible for why aryl substitution at the
rearrangement terminus suppresses endo-methyl migration
completely. Inspection of molecular models reveals that severe
steric interactions between the aryl group and the annelated
cyclopentane ring in the radical cation obliges the phenyl ring
to align conformationally in a skewed orientation with respect
to the planar cyclopentane-1,3-diyl ring, as displayed in the
transition-state structure TS-5•+. As a consequence, the endo-
a In parentheses is given the corresponding radical cation 5•+ to which
the radical fragment belongs. b AM1 method;10 in parentheses experi-
mental Eox (eV) values.11 c Relative to the cumyl radical. d 6(exo/endo-
Me) represents migration to the X and 7(exo-Me) to the Ph terminus.
e Phenyl taken as reference system.
Figure 2. Orbital energy differences ∆ꢀ versus the regioisomeric ratios
ln(6/7).
and the 7 regioisomer is preferred, as is the case for the radical
cation 5h•+ (X ) CHO). That these regioselectivities are
governed by electronic and not steric effects of the X substituent
should be evident from the aryl-substituted derivatives 5j-m,
because the para substituent in the aryl group is too remote
to cause steric perturbations relative to the phenyl reference
case.
This simple MO approach also allows one to rationalize the
regioselectivities for the intermediate cases, namely, CH2F (5f),
CH2CN (5g), C6H4-p-Me (5j), and C6H4-p-Cl (5k), for which
both regiosiomers 6 and 7 are formed (Table 2). The plot in
Figure 2 of the semiempirical orbital energy differences (∆ꢀ)
versus the logarithm of the experimentally observed regioiso-
meric ratios [ln(6/7)] of the radical cations 5f,g,j,k•+ displays
an excellent linear correlation (r2 ) 0.989). This linear
correlation substantiates once more that electronic and not steric
properties of the substituent decide the observed regioselectivi-
ties. Thus, it is now possible to predict the regioisomeric ratio
methyl group is sterically blocked by the skew aryl substituent
and only the exo-methyl group migrates to give exclusively the
exo-Me diastereomer of the regioisomer 7.
Acid-Catalyzed 1,2 Migration. The acid-catalyzed rear-
rangement of the housanes 5 (Table 1, entries 2, 4, 6, 8, 10, 13,
and 15) affords preferrably the 7(exo-Me) over the 6(exo-Me)
cyclopentenes (Scheme 2). Such regio- and stereoselective
electrophilic carbon-carbon bond cleavages of cyclopropane
derivatives have been the subject of considerable investigation.12
For example, it has been documented that corner attack on
cyclopropanes by protons is generally favored over edge attack.13
Furthermore, Wiberg reported that the acid-catalyzed addition
(12) Coxon, J. M.; Battiste, M. A. In The Chemistry of the Cyclopropyl
Group; Rappoport, Z., Ed.; J. Wiley & Sons: Chichester, 1987; Chapter 6.
(13) (a) Lehn, J.-M.; Wipff, G. J. Chem. Soc., Chem. Commun. 1973,
747. (b) Coxon, J. M.; Steel, P. J.; Whittington, B. I.; Battiste, M. A. J.
Am. Chem. Soc. 1988, 110, 2988. (c) Coxon, J. M.; Steel, P. J.; Whittington,
B. I. J. Org. Chem. 1990, 55, 4136.

Radical Cations Generated from Tricyclo[3.3.0.02,4]octanes
J. Am. Chem. Soc., Vol. 120, No. 46, 1998 11863
Scheme 5
offered for the exo-methyl diastereoselectivity of the radical
cations TS-5•+ (Scheme 4) also applies for the 1,2 shift in a
open, planar carbocation 5(H)+.
Conclusions
The housanes 5 have offered the unique opportunity to
explore electronic and steric substituent effects on the regio-
and diasteroselectivity of the CET-induced rearrangement of
1,3 radical cations. The regioselectivity of the migration may
be tuned through the electronic character of the substituents on
the diyl sites, which is rationalized in terms of a simple MO
interaction diagram by considering the SOMO orbital energies
of the corresponding radical fragments. Indeed, the excellent
correlation between the calculated orbital energy differences
(∆ꢀ) and the experimentally observed regioisomeric ratios allows
a quantitative assessment of the electronic substituent effects.
The diastereoselectivity of the 1,2 shift is controlled by the steric
factors in the intermediary 1,3 radical cation.
to housane generates the most stable carbocation on rate-
determining protonation.14 The rearrangement products have
been proposed to be formed directly from the protonated
housane before the latter has become a genuine carbocation, to
account for stereoselective capture by nucleophiles, migration,
or proton loss. Presumably, the same mechanism also applies
for the housanes 5 in that initial corner attack of the proton
leads to the protonated housane 5(H)+ (Scheme 5). The
carbocation 5(H)+ is expected to be preferred, since the positive
charge is better stabilized at the phenyl-substituted site (cumyl
type).15 Hence, the charge-stabilizing ability of the aryl
substituent at the cationic site is responsible for the regioselec-
tivity in the 1,2 migration for this Wagner-Meerwein rear-
rangement. As for the diastereoselectivity, the subsequent 1,2
shift of the endo-methyl group to the developing C-4 carbocation
occurs before a planar bona fide carbocation is attained, which
thereby accounts for the stereoselective formation of the 7(exo-
Me) isomers (Scheme 5). However, the stereoselective genera-
tion of the 7(exo-Me) cyclopentenes is also consistent with the
intermediacy of a cyclopentyl cation 5(H)+, since the rationale
Acknowledgment. We express our gratitude to the Fonds
der Chemischen Industrie and the Volkswagen-Stiftung for
generous financial support of this work. We thank Birgit Beck
for technical assistance.
Supporting Information Available: Text describing ex-
perimental data (30 pages, print/PDF). This material is con-
tained in many libraries on microfiche, immediately follows this
article in the microfilm version of the journal, can be ordered
from the ACS, and can be downloaded from the Internet. See
any current masthead page for ordering information and Internet
access instructions.
(14) Wiberg, K. B.; Kass, S. R.; Bishop, K. C., III J. Am. Chem. Soc.
1985, 107, 996.
(15) Arnett, E. M.; Hafelich, T. C. J. Am. Chem. Soc. 1983, 105, 2889.
JA982329E