578 J . Org. Chem., Vol. 67, No. 2, 2002
Adam and Librera
Ta ble 2. P r od u ct Distr ibu tion of th e Electr on -Tr a n sfer
a n d Acid -In d u ced Rea r r a n gem en ts of th e Hou sa n es 4
differentiation is not possible because migration of the
endo-methyl and exo-methyl groups to the methyl-bearing
terminal affords the same rearrangement product, namely
the regioisomer 2.
A similar scenario is observed for the acid-catalyzed
rearrangement of the annelated housane 4a (Table 2,
entry 3) and the reference housane 1 (Table 1, second
entry). Although the product distributions are nearly the
same for the acid catalysis of these two housanes, they
are quite different from the electron-transfer case. Specif-
ically, housane 1 gives both regioisomers 2 and 2′, the
latter as a mixture of endo-2′ (major) and exo-2′ (minor)
diastereomers. Thus, both the exo-methyl and endo-
methyl groups migrate to the phenyl-substituted as well
as the methyl-substituted terminal, but in the 2 regio-
isomer the exo and endo migrations are not distinguish-
able. Nearly the same regioisomeric ratio (endo-5a +6a /
endo-7a ) is obtained for the housane 4a , with preferred
migration to the phenyl-substituted site to afford the
regioisomer endo-7 (Table 2, entry 3). Since migration of
the methylene group in the annelated six-membered ring
would result in a highly strained olefin as rearrangement
product, only the endo-7 diastereomer is formed along
the rearrangement path to the phenyl-bearing C-8 ter-
minal.
The methyl-substituted housane 4b displays quite
different rearrangement behavior compared to the phen-
yl-substituted derivative 4a , both for the electron-transfer
and the acid-catalyzed reactions (Table 2, entries 2 and
4). In contrast to the phenyl case 4a , the methyl deriva-
tive 4b is neither regioselective nor stereoselective. Thus,
for the electron-transfer rearrangement (entry 2), the
ratio of the regioisomers (endo-5b + 6b/endo-7b) is about
equal within the experimental error, so that the methyl
shift to the respective positions C-2 and C-8 takes place
with nearly equal facility. For the migration to the C-2
position, both the endo-methyl substituent (product endo-
5b) and the exo-methylene group in the annelated six-
membered ring (product 6b) transpose also in about the
same amounts within the experimental error. Clearly,
replacement of the phenyl (4a ) by the methyl (4b) group
erases the regioselective control displayed by the former,
whereas the stereoselectivity is for both similarly low
(Table 2, entries 1 and 2). Remarkable is the acid-
catalyzed rearrangement of the methyl derivative 4b
(Table 2, entry 4), which affords exclusively the endo-5b
product, that is, only endo-methyl migration to the
position C-2 is found.
product distributiona
entry substrate
R
modeb
endo-5
6
endo-7
-
1
2
3
4
4a
4b
4a
4b
Ph TBA•+SbCl6- 55 ( 4 45 ( 4
-
Me TBA•+SbCl6
Ph HClO4
Me HClO4
37 ( 6 25 ( 6 43 ( 6
24 ( 2 9 ( 2
> 95
67 ( 2
-
-
Determined on the crude product mixture by 1H NMR
a
spectroscopy, except entry 2 (quantitative 13C NMR spectroscopy),
conversion >95%, except entry 2 (77%), and mass balances >90%.
TBA•+SbCl6 is tris(4-bromophenyl)aminium hexachloroanti-
b
-
monate, 70% aqueous HClO4 was used.
The acid-catalyzed rearrangement of the phenyl-
substituted housane 4a (entry 3) gave the endo-7a as
major product (67%), along with appreciable (24%)
amounts of endo-5a and a small (9%) quantity of 6a . The
methyl-substituted housane 4b (entry 4) yielded exclu-
sively (>95%) the rearrangement product endo-5b.
The configurations of the rearrangement products 5-7
were assigned by means of NOE effects, combined with
HH and CH correlations, and by spectral comparison
with already known diquinane derivatives.5 Additionally,
the connectivity in the diquinanes endo-5a , 5b, and 6a
was determined by 2D-INADEQUATE NMR experi-
ments.
Discu ssion
The product distributions for the phenyl-substituted
annelated housane 4a (Table 2) and the reference hou-
sane 1 (Table 1) display similar regiochemical and
stereochemical features for the electron-transfer and acid-
catalyzed rearrangements. Thus, in regard to the regio-
selectivity, the housane 1 affords on electron transfer
(Table 1, first entry) exclusively the diquinane regioiso-
mer 2 by methyl migration to the methyl-bearing site;
methyl migration to the phenyl-substituted terminal to
generate the regioisomer 2′ is not observed. Analogously,
electron transfer with the housane 4a leads only to the
rearrangement products endo-5a and 6a (these cor-
respond to the regioisomer 2 derived from housane 1),
and endo-7a (this one corresponds to the regioisomer
endo-2′) is not formed (Table 2, entry 1). Again, absolute
regiochemical control applies in that exclusive migration
to the alkyl-substituted terminal (C-2 position) occurs.
The triquinane-like product endo-5a results from migra-
tion of the endo-methyl substituent, whereas the spiro-
cyclic diquinane 6a is generated by the shift of the exo-
methylene group in the annelated six-membered ring,
both at the C-7 position. The advantage of the annelated
housane 4a is the fact that the two migrating substitu-
ents (methyl and methylene) are structurally distinct
and, thus, provide stereochemical information on the
rearrangement process. Mechanistically significant, both
rearrangement products endo-5a (endo-methyl migration)
and 6a (exo-methylene migration) are formed in about
equal amounts (Table 2, entry 1). It should be evident
that for the reference housane 1 such stereochemical
The observed regio- and stereoselectivities for the
housane 1 (Table 1) and 4a (Table 2) are mechanistically
rationalized in Schemes 4 and 5. Analogous to the
carbocations, the rearrangement of the 1,3 radical cat-
ions, generated by electron transfer, is of the Wagner-
Meerwein type;1,8 consequently, the preferred site of
positive charge localization in the corresponding 1,3
radical cations determines the regioselectivity. As elabo-
rated for the reference housane 1 (Scheme 4), the
regioselectivity may be accounted for by comparison of
the SOMO energies of the corresponding radical frag-
ments.1 For the radical cation A, the Me(CH3)2C• radical
fragment lies in energy above Ph(CH3)2C•, and thus the
positive charge will be localized at the Me terminus and
the 1,2 shift will occur preferentially to the methyl-
(8) Shaik, S. S.; Dinnocenzo, J . P. J . Org. Chem. 1990, 55, 3434-
3436.