Origin of stereofacial selectivity in electrophilic additions to methylenecyclohexanes and methylenedioxanes. A theoretical and experimental study

Article abstract of DOI:10.1039/a800999f

Addition reaction studies and ab initio calculations on methylenecyclohexane and 5-methylene-1,3-dioxane systems suggest that two electronic factors contribute to the stereoselectivity of epoxidation and diimide reduction. These are respectively the spatial anisotropy of the HOMO with respect to the two faces of the double bond, common to both molecules, which is likely to be responsible for the overall axial stereofacial selectivity exhibited, and a similar anisotropy in the electrostatic potential field of the methylenedioxane caused by the oxygens; which also favours attack from an axial direction by polarisable electrophilic species. The anisotropy of the HOMO arises from the important topological difference between the contributions made to the HOMO by the periplanar β C-H σ bonds and opposing β C-O or C-C σ bonds. Catalytic reduction proceeds with equatorial face selectivity for both the cyclohexane and the dioxane systems and appears to be governed largely by steric effects.

Full text of DOI:10.1039/a800999f

View Article Online / Journal Homepage / Table of Contents for this issue
Origin of stereofacial selectivity in electrophilic additions to
methylenecyclohexanes and methylenedioxanes. A theoretical and
experimental study
(The late) John Hudec,a Jerry Hukeb and John W. Liebeschuetzc
a Department of Chemistry, University of Southampton, Southampton, UK SO17 1BJ
b Department of Chemistry, Victoria University of Manchester, Manchester, UK M13 9PL
c Proteus Molecular Design Ltd., Beechfield House, Lyme Green Business Park, Macclesfield,
UK SK11 0JL
Addition reaction studies and ab initio calculations on methylenecyclohexane and 5-methylene-1,3-
dioxane systems suggest that two electronic factors contribute to the stereoselectivity of epoxidation and
diimide reduction. These are respectively the spatial anisotropy of the HOMO with respect to the two
faces of the double bond, common to both molecules, which is likely to be responsible for the overall
axial stereofacial selectivity exhibited, and a similar anisotropy in the electrostatic potential field of the
methylenedioxane caused by the oxygens; which also favours attack from an axial direction by polarisable
electrophilic species. The anisotropy of the HOMO arises from the important topological difference
between the contributions made to the HOMO by the periplanar â C᎐H ó bonds and opposing â C᎐O or
C᎐C ó bonds. Catalytic reduction proceeds with equatorial face selectivity for both the cyclohexane and
the dioxane systems and appears to be governed largely by steric effects.
Prediction of the stereochemistry of reaction of a simple func-
tional group, such as a double bond or carbonyl group, with a
given reagent is still an inexact science. Where such a reaction is
kinetically controlled, apart from steric effects, a number of
factors which may be loosely described as stereoelectronic in
nature have previously been invoked to account for the
observed stereochemistry. For example, an anisotropy in the
electron distribution about the double bond in 7-methylene-
norbornane compounds 1 and 2 has been used to rationalise
electrophiles to the exocyclic double bond of 9-isopropyl-
idenebenzonorbornenes 4.9,10 However, in 1,2,3,4-tetrafluoro-9-
isopropylidenebenzonorbornene, syn addition is observed for a
number of neutral electrophiles and this is thought to be due to
a strong electropositive region syn to the double bond, which
promotes charge separation in the electrophile and the more
common anti addition is promoted by homo-aromatic partici-
pation by the benzene ring.11,12 More recently, Houk and his
colleagues13 have also calculated electrostatic potentials for the
system 4 and have concluded that weak electrophiles, such as
m-chloroperbenzoic acid (m-CPBA) and tert-butyl hypo-
chlorite, which have lone pair electrons, are effectively ‘negative’
in their ground states and as such add to the less electron rich
face of the alkene, i.e. they give anti addition with 4, because
they are repelled by the high electron density of the syn face due
to the electron rich aromatic ring. Positive electrophiles favour
syn addition because they are attracted by this highly negative
region.†
O
O
163.5°
O
1
2
3
4
their stereoreactivity.1,2 For the case of norbornene itself, Fukui
and co-workers3 have predicted this anisotropy by theoretical
calculation. The exo selectivity of these systems has been
rationalised on the basis of the predicted increased exo exten-
sion of the highest occupied molecular orbital (HOMO). Both
the early and more recent calculations show that here this
anisotropy is due to the interaction of the C᎐C᎐C methylene
bridge σ orbitals with the π system, which differs from that of
the ethano bridge as a result of the different torsion angle.3,4
Alternatively, structural perturbations, arising out of the
electronic structure of the molecule (rather than steric effects),
have been invoked. Thus, in syn sesquinorbornene 3 the double
bond is bent in the endo direction by 14.4Њ, although there are
no obvious steric interactions that could cause this perturb-
ation.5 Additions to sesquinorbornenes show a high degree of
exo selectivity which it has been suggested arises from this bend-
ing. Calculations by Houk and his colleagues6–8 have predicted
a similar displacement of the hydrogens bound to the double
bond in norbornene by 3.4Њ in an endo direction. This has been
used to explain the pronounced exo reactivity of these systems.
A third factor that has been considered is the electrostatic
potential field on either face of the functional group. Thus anti
stereoselectivity is generally observed in additions of neutral
A further issue is the importance of destabilising interactions
between a developing bond and adjacent eclipsing bonds which
have long been suggested as a major factor in determining
stereofacial selectivity in additions to ketones and is the basis of
the torsional strain model proposed by Felkin and co-workers.14
In the stereofacial selectivity of additions to carbonyl com-
pounds, the role of substituents in a fixed conformation has
been examined previously by a number of workers. Klein15
studied the sodium borohydride reduction of cyclohexanones
and concluded that the interaction of the σ and σ* orbitals of
the β C᎐C bonds with the π and π* orbitals of the carbonyl
group was responsible for the preferred axial addition of H to
the C᎐O group. His view and that of Felkin have been chal-
᎐
lenged by the conclusions of Cieplak et al.16 as a result of his
group’s comprehensive study on stereofacial selectivity in the
reactions of 3-substituted cyclohexanones and 3-substituted
† There is some confusion here between the calculations of the
Paquette group and those of Houk. Paquette speaks of a positively
charged region, but talks of a charged electrophile being ‘guided in’ by
the electron density, whereas Houk indicates that the predominant
factor is a high electron density region, i.e. a negatively charged space
on this side of the molecule.11–13
J. Chem. Soc., Perkin Trans. 2, 1998
1129

View Article Online
methylenecyclohexanes. The influence of the distant substituent
was large and could be directly related to its relative electro-
negativity. The authors concluded that their results strongly
supported Cieplak’s previously proposed hypothesis that back-
donation from the eclipsing β C᎐C and C᎐H σ bonds into the
σ* orbital of the new bond being formed is the major factor
that controls stereofacial selectivity.17
double bond is protected by cyclopentadiene, the rest of the
molecule is constructed and the cyclopentadiene cleaved off in a
retro Diels–Alder reaction by flash pyrolysis as the final step. A
similar strategy, using anthracene as the protecting group, has
been employed by Ripoll to prepare 2,3-bis(hydroxymethyl)but-
2-ene-1,4-diol (ethylenetetramethanol) 9.21 We have adapted his
method to synthesise the previously unknown compound 7.
Anthracene protected tetrol 10, prepared by Ripoll’s method,
was condensed with pivalaldehyde under acid catalysis. Two
isomeric products were obtained, easily separated by crystal-
lisation. The sparingly soluble isomer, with mp 322 ЊC, was
shown to contain two planes of symmetry by NMR spectro-
scopy and was assigned structure 11. (The alternative sym-
To summarise, many hypotheses have been put forward to
rationalise the stereochemistry of reaction of different systems.
In a number of cases different hypotheses can be used to
explain the same data and there is often debate about which
rationalisation is most useful. Molecular orbital calculations,
whether ab initio or semi-empirical, often provide valuable
information in this regard. The challenge comes in interpreting
the calculations in a manner that is not only applicable to the
system in hand, but which may also provide simple yet powerful
insights into the reactivity of many other systems as well. The
best known example where this has been achieved resulted in
the Woodward–Hoffmann rules for pericyclic reactions.
Although a great deal of work has been carried out on the
addition of nucleophilic reagents to carbonyl groups and carb-
onyl conjugated alkenes, there has been relatively little attention
paid to electrophilic additions to C᎐C double bonds and in
particular to unsymmetrically di-substituted alkenes. The most
significant amongst the studies are the work of Srivasta and
le Noble on additions to 5-substituted-2-methyleneadaman-
tanes18 and that of Berti and co-workers19 on the stereoselective
epoxidation of cyclohexenes β-substituted with alkyl, methoxy
and acetoxy groups. These in particular confirm the fact that
stereoelectronic control of π face diastereoselection by sub-
stituents, often quite distant, is a powerful but not fully under-
stood factor.
HO
HO
OH
OH
9
But
But
O
O
O
O
ButCHO
H+
11
OH
OH
HO
OH
10
But
O
O
O
O
13
But
Our interest has been in examining how the stereoselectivity
of addition to a double bond is influenced by a β-substituent in
a conformation fixed with respect to the double bond. In par-
ticular we have been interested in isolating the electronic factors
that determine this stereoselectivity. Hence we wished to carry
out reactivity studies on suitable model compounds and
accompany them with appropriate theoretical calculations. The
aim was to work towards developing a consistent theory that
could be applied to a wide range of systems and a wide range of
neutral and electrophilic addition reagents.
O
O
O
O
But
But
12
metrical product 12 is unlikely to form due to the large steric
effects.) The other isomer, readily soluble in chloroform, with
mp 207 ЊC, had an NMR spectrum which showed it to contain
only a single plane of symmetry and was assigned structure 13.
Sublimation of 11 under vacuum through a scrupulously clean
We have chosen to examine the 5-methylene-1,3-dioxane
system, as represented by the model compounds 5, 6 and 7,
together with the methylenecyclohexane system as 8. The two
450 °C
O
O
O
O
O
O
But
Ph
But
O
O
O
O
But
O
O
O
O
O
O
But
But
7
But
But
5
6
7
11
quartz column heated to 450 ЊC resulted in clean pyrolysis. No
epimerisation occurred at the acetal carbons and stereoisomeric-
ally pure 7 could be separated from anthracene by flash chrom-
atography. Similar pyrolysis of 13 cleanly afforded the trans
isomer 14.
But
8
systems have been studied both theoretically, using ab initio
molecular orbital calculations, and experimentally by physico-
chemical means using photoelectron spectroscopy and by
establishing their stereoreactivity in some common addition
reactions. The phenyl and tert-butyl groups in the models are
present for their ability to conformationally stabilise the six-
membered rings and make ring inversion highly unlikely during
reaction. One would expect that these substituents would be too
remote to have any primary influence on the double bond.
But
O
O
But
450 °C
O
O
O
O
O
But
14
O
But
13
Fully geometry optimised ab initio restricted Hartree–Fock
calculations using the 6-31G basis set were carried out on both
models 2-tert-butyl-5-methylene-1,3-dioxane 5 and 1-tert-butyl-
4-methylenecyclohexane 8. They were performed using the
Results
The model compounds 5 and 6 were prepared using the elegant
synthesis previously described by Weiss et al.20 In this route the
1130
J. Chem. Soc., Perkin Trans. 2, 1998

View Article Online
Table 1 Atomic coordinates for 2-tert-butyl-5-methylene-1,3-dioxane
5 (Å)
Table 3 Atomic coordinates for 1-tert-butyl-4-methylenecyclohexane
8 (Å)
C4
C4
C2 C1
C2 C1
O6
O
C6
C3
C7
C3
C7
O
C8
C9
C8
C9
O5
C11
C5
C11
C10
C10
5
8
x
y
z
x
y
z
C1
C2
C3
C4
C5
C6
C7
H11
H12
H31
H32
H41
H42
H71
C8
3.561
2.381
1.640
1.639
0.263
0.262
Ϫ0.427
4.067
4.066
1.676
0.000
0.001
Ϫ1.253
1.257
Ϫ1.161
1.162
0.002
Ϫ0.913
0.911
Ϫ1.400
Ϫ2.127
1.411
2.129
0.005
Ϫ0.554
0.042
0.426
C1
C2
C3
C4
C5
C6
C7
H11
H12
H31
H32
H41
H42
H51
H52
H61
H62
H71
C8
3.708
2.526
1.780
1.782
0.351
0.352
Ϫ0.436
4.214
4.215
1.719
2.317
1.721
2.320
0.414
Ϫ0.155
0.413
Ϫ0.151
Ϫ0.461
Ϫ1.937
Ϫ2.658
Ϫ3.722
Ϫ2.302
Ϫ2.524
Ϫ2.647
Ϫ3.714
Ϫ2.498
Ϫ2.295
Ϫ2.095
Ϫ3.148
Ϫ1.632
Ϫ1.662
Ϫ0.004
0.000
Ϫ1.259
1.264
Ϫ1.253
1.256
0.004
Ϫ0.918
0.907
Ϫ1.333
Ϫ2.134
1.351
2.135
1.299
Ϫ2.153
1.293
2.159
0.010
0.001
Ϫ1.226
Ϫ1.167
Ϫ2.157
Ϫ1.270
1.261
1.194
1.366
Ϫ0.470
0.130
0.498
0.418
0.483
Ϫ0.019
Ϫ0.011
0.450
Ϫ0.808
Ϫ0.813
1.503
Ϫ0.059
1.495
Ϫ0.071
1.540
Ϫ0.112
0.392
0.038
1.478
0.038
0.399
0.049
1.484
0.045
Ϫ1.648
Ϫ2.017
Ϫ2.041
Ϫ2.022
Ϫ0.078
Ϫ0.091
0.346
Ϫ0.720
Ϫ0.730
1.583
0.150
1.567
0.127
Ϫ1.161
0.249
Ϫ1.175
0.230
Ϫ1.438
Ϫ0.104
0.495
0.296
0.072
1.572
0.436
0.256
1.507
2.040
1.674
2.038
Ϫ0.446
Ϫ1.848
Ϫ2.575
Ϫ3.600
Ϫ2.600
Ϫ2.087
Ϫ2.574
Ϫ2.086
Ϫ2.600
Ϫ3.600
Ϫ1.808
Ϫ1.297
Ϫ2.820
Ϫ1.296
0.000
1.259
1.260
1.292
C9
H91
H92
H93
C10
H101
H102
H103
C11
H111
H112
H113
2.157
Ϫ1.256
Ϫ2.155
Ϫ1.282
Ϫ1.259
Ϫ0.004
Ϫ0.883
Ϫ0.005
0.872
C9
H91
H92
H93
C10
H101
H102
H103
C11
H111
H112
H113
2.166
Ϫ0.043
Ϫ1.636
Ϫ1.900
Ϫ2.109
Ϫ2.066
Ϫ0.034
Ϫ0.022
0.824
Table 2 Bond lengths and primary three-centre bond angles and
dihedral angles calculated for 2-tert-butyl-5-methylene-1,3-dioxane 5.
Symmetry unique values only are quoted.
Ϫ0.929
assumed as a starting conformation. No other constraints were
imposed. The first job was completed in 374 min, the second in
644 min.
The values of the electrostatic potentials and all contour
maps were calculated using the MOLDEN package.23 Each
contour plot is based on a grid of 61 × 61 values and plot width
12.5 Å.
Bond lengths/Å
Bond angles/Њ
Dihedral angles/Њ
H11᎐C1᎐C2᎐C3
C1᎐H11 1.074
H11᎐C1᎐C2 121.9
H11᎐C1᎐H12 116.2
Ϫ0.3
C1᎐C2
C2᎐C3
C3᎐O5
O5᎐C7
1.321
1.506
1.439
1.420
C1᎐C2᎐C3᎐O5 Ϫ133.3
C1᎐C2᎐C3
C3᎐C2᎐C4
C2᎐C3᎐O5
C3᎐O5᎐C7
O5᎐C7᎐O6
O5᎐C7᎐C8
C7᎐C8᎐C9
C7᎐C8᎐C10 109.4
C2᎐C3᎐H31 110.5
C2᎐C3᎐H32 123.0
123.4
113.1
110.3
114.8
111.5
107.5
109.5
C2᎐C3᎐O5᎐C7
C3᎐O5᎐C7᎐O6
C1᎐C2᎐C3᎐H31
C1᎐C2᎐C3᎐H32 Ϫ106.8
O5᎐C7᎐C8᎐C9 59.9
O5᎐C7᎐C8᎐C10 Ϫ60.1
Ϫ51.8
Ϫ56.2
15.0
C3᎐H31 1.088
C3᎐H32 1.077
C7᎐H71 1.090
Atomic coordinates of 5, after optimisation, are given in
Table 1. Key bond lengths and dihedral angles are given in
Table 2. The corresponding values for 8 are given in Tables 3
and 4. The energies of the lowest unoccupied molecular orbital
and the five highest occupied molecular orbitals are given in
atomic units in Table 5. Iso-contour surfaces for the HOMOs of
5 and 8, contoured at the 0.005 au level, are shown in Figs. 1(a)
and (b), and 2(a) and (b) respectively. Views of each surface are
displayed from both the axial and the equatorial perspectives
with respect to the double bond. Calculated cross sections of
the molecular electrostatic potential field, perpendicular to the
plane of the double bond, are given in Fig. 3 for 5 and in Fig. 4
for 8.
He(I) photoelectron spectra of 5 and 8 have been recorded
and the low energy regions of these spectra are presented in Fig.
5. The spectrum of 8 is essentially identical to that reported
previously.24 Neither spectrum shows interpretable structure for
ionisation energies (Ei) of greater than ca. 11 eV. In that of 8,
the first ionisation is clearly defined, with a vertical potential of
9.09 eV. It shows a vibrational progression with an interval of
about 1370 cmϪ1: a feature typical of ionisations from carbon–
carbon double bonds. The spectrum of 5 contains a broad band
stretching from 9.55 to 10.4 eV, showing evidence of fine struc-
ture, and which presumably comprises the ionisations from a
C7᎐C8
C8᎐C9
1.528
1.539
C9᎐H91 1.084
C9᎐H92 1.086
C9᎐H93 1.081
C8᎐C10
1.536
C10᎐H101 1.081
C10᎐H111 1.084
C10᎐H112 1.086
GAMESS program package22 implemented on an SGI Origin
2000 workstation (R10 000, 2 × 80 MHz IP27 processors, 256
Mbytes main memory). Convergence of the SCF iterations
was monitored using changes in the density matrix and the
calculations were considered converged when the density
change between two consecutive SCF iterations was less than
10Ϫ5. Geometry optimisations were performed with GAMESS
using analytic gradient techniques. Convergence was moni-
tored using the energy gradients and was considered to have
occurred when the maximum gradient was less than 1 × 10Ϫ4
hartree bohrϪ1 and the rms gradient was less than 3.3 × 10Ϫ5
hartree bohrϪ1. No symmetry constraints were imposed and a
chair conformation with tert-butyl equatorially substituted was
J. Chem. Soc., Perkin Trans. 2, 1998
1131

View Article Online
Table 4 Bond lengths and primary three-centre bond angles and dihedral angles calculated for 1-tert-butyl-4-methylenecyclohexane 8. Symmetry
unique values only are quoted.
Bond lengths/Å
Bond angles/Њ
Dihedral angles/Њ
C1᎐H11
C1᎐C2
C2᎐C3
C3᎐C5
C5᎐C7
C3᎐H31
C3᎐H32
C5᎐H51
C5᎐H52
C7᎐H71
C7᎐C8
1.074
H11᎐C1᎐C2
H11᎐C1᎐H12
C1᎐C2᎐C3
C3᎐C2᎐C4
C2᎐C3᎐C5
C3᎐C5᎐C7
C5᎐C7᎐C6
C5᎐C7᎐C8
C7᎐C8᎐C9
C7᎐C8᎐C10
C2᎐C3᎐H31
C2᎐C3᎐H32
121.8
116.4
123.0
114.1
111.1
111.3
111.4
110.0
109.5
109.5
109.1
110.5
H11᎐C1᎐C2᎐C3
C1᎐C2᎐C3᎐C5
C2᎐C3᎐C5᎐C7
C3᎐C5᎐C7᎐C6
C1᎐C2᎐C3᎐H31
C1᎐C2᎐C3᎐H32
C2᎐C3᎐C5᎐H51
C2᎐C3᎐C5᎐H52
C3᎐C5᎐C7᎐C8
C5᎐C7᎐C8᎐C9
C5᎐C7᎐C8᎐C10
Ϫ0.78
Ϫ125.4
Ϫ53.4
Ϫ55.2
Ϫ0.8
Ϫ114.8
67.4
Ϫ175.8
177.5
60.0
Ϫ60.0
1.326
1.509
1.541
1.543
1.089
1.084
1.086
1.083
1.091
1.566
1.544
1.084
1.082
1.086
1.544
C8᎐C9
C9᎐H91
C9᎐H92
C9᎐H93
C8᎐C10
C10᎐H101 1.085
C10᎐H111 1.086
C10᎐H112 1.083
Table 5 Energies of the lowest unoccupied and the five highest
occupied molecular orbitals for 5 and 8 (au)
E/au
Occupancy
5
8
0
2
2
2
2
2
0.159
Ϫ0.372
Ϫ0.420
Ϫ0.425
Ϫ0.450
Ϫ0.454
0.182
Ϫ0.338
Ϫ0.413
Ϫ0.421
Ϫ0.436
Ϫ0.452
Fig.
2
1-tert-Butyl-4-methylenecyclohexane (8: HOMO electron
density. Isocontour surface (a) from axial face (contoured at 0.005 au),
and (b) from equatorial face (contoured at 0.005 au).
reduction with diimide as a potentially frontier molecular orbital
(FMO) controlled reaction as it is known to transfer H2 by an
electrocyclic mechanism.25 However, calculations by Skancke26
have shown that the primary interaction in the transition state
involves donation from the pi orbitals of the double bond that
is being reduced into the antibonding sigma orbitals of the
N᎐H bonds of diimide, supporting the idea that this reagent
has significant electrophilic character and may also be classified
as electrophilic. The compounds were also reduced under
catalytic conditions (Pt and H2) as an example of an electro-
neutral addition process.
The stereochemistry of the products of the addition of
hydrogen were, in all cases, readily identifiable by interpretation
of the coupling pattern of the H5 in the 1H NMR spectra of the
isolated products 15a,b, 16a,b, 19 and 20. The stereochemistry
of the products of epoxidation were not so readily determined.
Each was isolated and separately reduced with LiAlH4. The
products of reduction of 17b and 18b were shown to be
5-hydroxy-5-methyl-1,3-dioxanes, 27 and 28, readily identifiable
Fig. 1 2-tert-Butyl-5-methylenedioxane (5): HOMO electron density.
Isocontour surface (a) from axial face (contoured at 0.005 au), and
(b) from equatorial face (contoured at 0.005 au).
number of the highest lying occupied molecular orbital
although these cannot be individually distinguished.
Addition studies were carried out on compounds 5, 6 and 7
under kinetic conditions. Epoxidation using m-CPBA was
selected as an example of an electrophilic addition reagent;
1132
J. Chem. Soc., Perkin Trans. 2, 1998

View Article Online
Fig. 4 Mid-plane cross section of molecular electrostatic potential
field for 1-tert-butyl-4-methylenecyclohexane (8)
Fig. 3 Mid-plane cross section of molecular electrostatic potential
field for 2-tert-butyl-5-methylenedioxane (5)
O
O
O
O
R
R
R
R
O
O
O
O
O
O
R = But
R = Ph
18 a R = But
a
b
R = But
R = Ph
15
16 a R = But
R = Ph
a
b
17
b
b
R = Ph
But
O
O
But
O
O
But
O
O
O
O
But
20
19
O
O
O
O
O
O
O
O
O
Fig. 5 He(I) photoelectron spectra for (a) 2-tert-butyl-5-methylene-
1,3-dioxane (5) and (b) 4-tert-butylmethylenecyclohexane (8)
O
But
But
But
But
21
22
stereochemistry of the product of reduction of 21, compound
29, was identified from the coupling pattern of the 4Ј-, 5Ј- and
6Ј-hydrogens and this was corroborated using the IR spectrum
as for 27 and 28.
But
But
But
But
The following control experiments largely rule out the possi-
bility that, during the epoxidation reaction, acid catalysed
epimerisation of the dioxane ring had occurred with con-
sequent formation of a thermodynamically controlled mixture
of products. Each of the epoxides 17a and 17b was separately
subjected to the identical reaction conditions as for epoxid-
ation. For 17a, no isomerisation was detectable even after the
addition of toluene-p-sulfonic acid. The phenyl compound 17b
was found to isomerise to a small extent (30%), but only after 7
days reaction. Epoxidation of the unsymmetric bi(dioxanyl-
idene) 14 under the same conditions as for 7 gave exclusively a
single unsymmetric epoxide 30 strongly suggesting that no
epimerisation occurred during the epoxidation of either 7 or 14.
Table 6 contains details of the product ratios obtained in
all the reactions, together with results of similar experiments
previously carried out on the methylenecyclohexane 8.28,29
O
O
26
23
24
25
But
O
O
O
Ph
HO
Ph
O
O
O
OH
O
O
OH
28
29
27
But
But
O
O
O
O
O
But
30
Discussion
by comparison of their spectral properties with those reported
by Eliel and Enanoza for analogous molecules.27 The use of
dilute solution IR spectra as well as the H NMR shifts of the
Both 5 and 8 retain a chair conformation when optimised.
This is flatter in 5 (C1᎐C2᎐C3᎐O5 = Ϫ133.5Њ) than it is in 8
(C1᎐C2᎐C3᎐C5 = Ϫ125.4Њ). As a consequence the equatorial
1
methyl groups allowed the stereochemical assignment. The
J. Chem. Soc., Perkin Trans. 2, 1998
1133

View Article Online
Table 6 Products formed in the reactions with peracid, diimide and Pt–hydrogen. Ratio of products from axial and equatorial attack. (Structures in
parentheses.)
Alkene
Orientation
Peracid
Diimide
Pt–hydrogen
Axial
Equatorial
56 (17a)
44 (18a)
95 (16a)
5 (15a)
9 (16a)a
91 (15a)
O
But
O
5
Axial
Equatorial
54 (17b)
46 (28b)
100 (16b)
0 (15b)
2 (16b)
98 (15b)
O
Ph
O
6
Axial
Equatorial
62 (21)
38 (22)
100 (19)
0 (20)
0 (19)
100 (20)
O
O
O
O
But
But
7
Axial
Equatorial
70 (25)b
30 (26)
51 (24)c
49 (23)
16 (24)d
84 (23)
But
8
a Data from ref. 36. b Data from ref. 37. c Data from ref. 26. d Data from ref. 27.
hydrogens on the α-carbons (H31 and H41) in 5 lie at an angle
of 15Њ above the plane of the double bond whereas in 8 they are
in the plane of the double bond. Only negligible deviations
from planarity are predicted for the double bonds in both 5 and
8, less than one degree in each case. These are too small to be
of any significance experimentally. For both molecules the tert-
butyl group maintains a conformation in which one methyl
group points upwards away from the double bond and lies in
the C1᎐C2᎐C7 plane.
The HOMO and LUMO for both 5 and 8 are largely consti-
tuted from the pz orbitals on C1 and C2 in phase and antiphase
respectively. The oxygen lone pairs appear to contribute little to
either the HOMO and LUMO of 5. They do contribute signifi-
cantly to each of the next three occupied orbitals although in
each case the contribution is not overwhelming and each of
these orbitals otherwise show similar features to respectively the
second, fourth and fifth highest occupied molecular orbitals of
8. The energies of the highest occupied orbitals of both 5 and 8
and the ionisation energies determined from the photoelectron
spectra are in good agreement assuming equivalence according
to Koopman’s theorem.
The eigenvectors of the HOMOs of both molecules were
examined for evidence of what has previously been described as
‘orbital twisting’.30,31 This would arise out of mixing of some
small s and px contributions in with the much larger pz orbital
contribution on atoms C1 and C2, and would lead to an
anisotropy in the HOMO in the close vicinity of the double
bond. Very little s and px contribution on C1 and C2 was found.
Therefore, although other workers have claimed it as an
important effect, we do not think that orbital twisting is signifi-
cant here.
Because there is no twisting of the π orbital there is no
anisotropy immediately above and below the double bond.
However, examination of Figs. 1 and 2 reveal there is a signifi-
cant anisotropy in the HOMOs of both of these molecules
further away from the π system. On the equatorial face there is
clearly a node between C1 and both C3 and C4. Such a node
also exists on the axial face. However, it is obscured by two
lobes extending beyond [C or O]5 and [C or O]6, which are in
phase with the lobe from the π system on that side. Because they
are in phase and because they are adjacent to the π system they
may be considered, in effect, to extend the π lobe of the HOMO
over a large region of the axial face. If this is so then it might be
expected that the attack of an electrophile sensitive to frontier
orbital effects might be biased towards axial rather than
equatorial attack, for both 5-methylenedioxanes and methylene-
cyclohexanes.
As well as exhibiting anisotropy in its HOMO, 5 also exhibits
an anisotropy in its molecular electrostatic potential. This has a
significant negative potential well on the axial face of the
double bond and therefore might be expected to again favour
axial attack of electrophiles on the dioxanes 5 and 6. No similar
anisotropy is present in the cyclohexane 8.
One further factor that needs to be considered is the relative
steric accessibility of the two faces of the double bond. On this
basis it would be anticipated that for all the molecules 5, 6, 7
and 8 and for all the reagents, there should be a bias towards
equatorial attack and that equatorial attack should be more
favoured for 8 than for 5 and 6 on account of both the add-
itional steric effect of the axial hydrogens at C3 and C5 and the
fact that the methylenedioxane ‘chair’ is noticeably flatter than
that of methylenecyclohexane.
The anisotropy of the HOMO described for both 5 and 8
deserves further consideration. Its existence has been demon-
strated using calculations employing a full MO representation.
However it is common to consider the HOMOs of systems such
as 5 and 8 as localised π-orbitals which are perturbed by inter-
action with a σ-framework. Such a description is useful as it can
be easily transferred to other similar systems. A close examin-
ation of the eigenvectors from the calculations on 5 and 8 reveal
that there is a large contribution to the HOMO from the
orbitals that make up respectively the two β C᎐Hax and the two
β C᎐O (in 5) or C᎐C (in 8) σ bonds. In terms of perturbational
interaction between localised orbitals, these contributions can
be described as arising out of two different types of four-
electron interactions. One is the interaction between the β
C᎐Hax σ bond and the πC᎐C [Fig. 6(a)] and one is the interaction
between the β C᎐C or C᎐O σ bond and the πC᎐C [Fig. 6(b)].
In both cases, the filled–filled interaction raises the HOMO
energy. The interaction between β C᎐Hax and the πC᎐C is com-
pletely out of phase and results in a node in the HOMO between
C2, and C3 and C4. This is not entirely the case for the inter-
action between β C/O᎐C σ and πC᎐C, however. Unlike the β
C᎐Hax σ orbital, the β C/O᎐C σ orbi᎐tal has p character at both
ends. Most of the orbital makes an out of phase contribution.
However the orbital lobes pointing away from the β C/O atom
1134
J. Chem. Soc., Perkin Trans. 2, 1998

View Article Online
preference is marginally less than that for addition to 8 and
(a)
π'
σ'
leads to the conclusion that the influence of the electrostatic
potential field on m-CPBA epoxidations of molecules such as 5,
6 and 7 is small. This is contrary to the case of peracid epoxid-
ation of allylic alcohols, where hydrogen bonding of the reagent
to the hydroxy group is the factor which controls the stereo-
chemistry.33 The reason for a smaller extent of axial epoxid-
ation on 5 and 6, as opposed to 8 is not entirely clear. However,
it could be a consequence of the conclusion by Houk and co-
workers that m-CPBA is a ‘nucleophilic’ electrophile with the
tendency to attack the less negative side of an alkene.13
X
X
π
H
σC-H
(b)
O
O
The addition reaction of diimide with 5, 6 and 7 proceeds
with striking axial face selectivity, in contrast with the equiv-
alent reaction for 8 and is also in total contrast to the catalytic
reduction of these compounds, which occurs almost exclusively
from the equatorial face. This difference in selectivity between
the two types of reduction is much more pronounced than that
observed for 8. Given the results from the epoxidation and the
calculations, this cannot be described to a frontier orbital effect.
It is more probable that it is caused by the electrostatic potential
field anisotropy in 5, 6 and 7 demonstrated by the calculations.
Unlike the epoxidation, the diimide reduction is carried out in a
polar solvent, which would tend to promote electrostatic effects.
Recent kinetic evidence from the diimide reduction of maleate
and fumarate anions supports the view that there is a large
electrostatic effect in its reduction reactions.34
π'
π'
σ'
π
σC-C
σC-O
σ'
(c)
X
X
H
Fig. 6
The greater equatorial selectivity observed in the catalytic
reduction of 5, 6 and 7 over that for 8 may most reasonably be
ascribed to an effect of product development control as previ-
ously proposed by Siegel and co-workers.28,35 In the course of
reduction of 8 from the equatorial face, the incipient methyl
group approaches an axial position and experiences unfavour-
able interactions with the axial hydrogens at C3 and C5. Such
interactions will not occur in the reduction of methylene-
dioxanes owing to the absence of these hydrogens. It is well
known that, unlike methylcyclohexane, 5-methyl-1,3-dioxanes
prefer a conformation with the methyl group axial.
into the axial face are in phase with the π contribution and, as a
result appear to extend the π lobe of the axial face HOMO. The
large scale anisotropy in the HOMO therefore can be thought
to arise out of the difference between these two types of σ–π
interaction. The effect is illustrated schematically in Fig. 6(c).
It is worth noting that there is a significant distinction
between the perturbational interactions in 5 and those in 8. The
C᎐O σ orbital is lower in energy than the C᎐C σ orbital and
should interact less strongly with the π system, resulting in a
smaller increase in the HOMO energy of 5 than in 8. The
photoelectron spectra of 5 and 8 support this. The latter shows
a band at 9.09 eV corresponding to the ionisation from the
occupied π orbital. This is higher in energy by at least 0.4 eV
than the corresponding band in the spectrum of 5, the precise
position of which is unclear as it is convoluted with the two
bands likely to be due to the p type lone pairs of the endocyclic
oxygens. These two bands, due to ionisation from the anti-
symmetric and symmetric combination orbitals of the lone
pairs, have been observed at 10.1 and 10.4 eV in the parent 1,3-
dioxane.32 Their position in the spectrum of 5 appears little
changed and indicates that in the methylenedioxane system
these lone pairs are not involved in interaction with the double
bond. The lack of any involvement by the lone pairs in the
HOMO of 5 and the higher energy for the HOMO of 8 with
respect to 5, determined by calculation, are consistent with
these observations.
Our theoretical study has adduced three factors that might
influence the kinetic stereoselectivity of electrophile addition
(i) the axial HOMO anisotropy, (ii) the electrostatic effect and
(iii) the preferred equatorial access. The experimental results
might therefore be expected to reflect an interplay between
these factors.
The addition reactions of m-CPBA (and diimide) with the
methylenecyclohexane 8 show a slight preference for axial
attack, despite the steric bias against this direction. This
suggests that the influence of the anisotropy of the HOMO
overrides the steric effect in these reactions. This conclusion is
bolstered by the observation that catalytic reduction, where
the steric accessibility to the catalyst surface should be most
significant and the influence of the HOMO liable to have less
importance, proceeds preferentially from the equatorial face.
The addition reaction of m-CPBA with the dioxanes 5, 6 and 7
also proceeds with a slight preponderance of axial attack. This
The Cieplak hypothesis16 suggests that axial selectivity in
additions to both cyclohexanones and methylenecyclohexanes
is caused by the more favourable back-donation from the β
C᎐H σ bond periplanar with the π bond into the σ* orbital of a
bond forming on the axial side compared with that from the
equivalently placed β C᎐C σ bonds to the σ* orbital of a bond
forming on the equatorial side. Consideration of the molecules
we have studied in the light of this postulate leads to the conclu-
sion that for the methylenedioxanes, 5, 6 and 7, the extent of
axial attack should be greater than is observed for the cyclo-
hexane case, due to the poorer hyperconjugating ability of the
C᎐O σ bond as compared with that of the C᎐C σ bond. Our
experimental results for epoxidation are completely at variance
with this expectation. While we do not rule out involvement of
the back-donation proposed by Cieplak, we suggest that the
HOMO anisotropy shown by the calculations can be used to
rationalise the results in a more straightforward manner.
Conclusions
The addition reaction studies on methylenecyclohexane and
5-methylene-1,3-dioxane have demonstrated a bias for axial
attack by electrophilic species, despite the axial face being
the more sterically hindered. The calculations suggest that two
electronic factors contribute to the stereoselectivity observed.
The first is the spatial anisotropy of the HOMO with respect
to the two faces of the double bond. This arises out of the
significant hyperconjugative interactions of the C᎐C, C᎐O and
C᎐H bonds positioned β to the π system. These interactions are
particularly strong in 8 and 5 because the β C᎐C, C᎐O and axial
C᎐H bonds are ideally oriented for interaction with the π
system. We believe that this anisotropy is responsible for the
overall axial stereofacial selectivity exhibited both by 8 and 5
J. Chem. Soc., Perkin Trans. 2, 1998
1135

View Article Online
towards electrophiles. Particularly noteworthy is the observ-
ation that because a C᎐H σ orbital (1 node) is topologically
distinct from a C᎐C or C᎐O σ orbital (2 nodes), a β C᎐H bond
aligned with a π system contributes to the stereofacial distribu-
tion of the HOMO in a fashion which is different from that of
the interaction of a periplanar β C᎐C or C᎐O bond with the
same π system.
The second effect is the electrostatic field potential which
results from the endocyclic oxygens in the dioxane ring. This
also favours attack from an axial direction by polarisable
electrophilic species and accounts for the greatly enhanced axial
selectivity exhibited by diimide for reaction with 5, 6 and 7 as
compared to 8.
(3.14 g). Purification of this material was carried out by con-
tinuous Soxhlet extraction with chloroform to give 11. The
crude original filtrate was washed (NaHCO3, 25 ml, 2 × H2O),
dried, filtered and the solvent evaporated under reduced pres-
sure. The combined solid residues were recrystallised from
ethanol–water to yield fine colourless needles of a second prod-
uct (2.07 g), 13. Reducing the quantity of solvent and increas-
ing reaction times increased the yield of the first product at the
expense of the second.
11, Mp 322–323 ЊC, ν(1.0 mm, CHCl3)/cmϪ1 2860, 1599,
1455, 1338, 1106, 969; δH(100 MHz, CDCl3) 1.03 (s, 18H) 3.12
(d, J 10, 4H), 3.54 (d, J 10, 4H), 4.05 (s, 2H), 4.97 (s, 2H), 7.25
(m, 8H).
Catalytic reduction, a non-electrophilic process, proceeds
with equatorial face selectivity for both the carbocyclic and the
dioxane systems and appears to be governed largely by steric
considerations.
13, Mp 207–208 ЊC (Found: C, 77.8; H, 8.10. C28H38O4
requires C, 77.8; H, 8.30%); ν/cmϪ1 2980, 2970, 1489, 1160,
1126, 1118, 1111, 1050; δH(100 MHz, CDCl3), 0.97 (s, 9H), 1.02
(s, 9H), 3.35 (d, J 11.5, 2H), 3.475 (s, 1H), 3.965 (s, 2H), 4.12 (d,
J 11.5, 2H), 5.02 (s, 1H), 7.08 (m, 6H), 7.4 (m, 2H); δC(25.18
MHz, CDCl3) 24.6, 34.8, 35.0, 40.8, 42.3, 48.3, 53.2, 71.1, 73.8,
107.4, 107.8, 124.4, 125.6, 126.2, 126.4, 139.8, 141.8.
Preparation of (Z)-2,2Ј-di-tert-butyl-5,5Ј-bi(1,3-dioxan-5-
ylidene) 7. Compound 11 (520 mg) was pyrolysed by sublimation
into and through a quartz pyrolysis tube [50 × 1.5 cm, packed
with quartz glass fragments and wound with nichrome resist-
ance wire (5 Ω mϪ1), with a pitch of 4 mm, on top of alumina
cement (3 mm thick)] heated to 450 ЊC, at a pressure of 1
mmHg. The condensate at the top of the column was collected
and chromatographed (silica, toluene) to remove anthracene.
Compound 7 was collected as colourless crystals (173 mg)
(ethanol–water), mp 121.5–122.5 ЊC (Found: C, 67.1; H, 10.25.
C16H28O4 requires C, 67.6, H, 9.90%); ν/cmϪ1 2985, 2965, 2835,
1484 1404, 1366, 1145, 1080; δH(100 MHz, CDCl3) 0.92 (s,
18H), 4.02 (br d, J 13, 4H), 4.19 (s, 2H), 4.733 (br d, J 13, 4H);
δC(25.18 MHz, CDCl3) 24.7, 35.0, 64.0, 107.6, 124.3.
(E)-2,2Ј-Di-tert-butyl-5,5Ј-bi(1,3-dioxan-5-ylidene) 14. Com-
pound 13 (360 mg) was pyrolysed under the same conditions as
for 11. After chromatography (silica, toluene), this gave colour-
less crystalline material (166 mg) mp 133–134 ЊC, recrystallised
from ethanol–water (Found: C, 67.1; H, 10.20. C16H28O4
requires C, 67.6; H, 9.90%); ν/cmϪ1 3021, 2841, 1485, 1406,
1366, 1145, 1081, 1050; δH(100 MHz, CDCl3) 0.90 (s, 18H), 4.20
(s, 2H), 4.23 (d, J 13.7, 4H), 4.64 (d, J 13.7, 4H); δC(25.18 MHz,
CDCl3) 24.7, 34.9, 66.1, 107.8, 124.3.
Catalytic hydrogenation of 5-methylene-2-phenyl-1,3-dioxane.
Reduction of 6 (0.850 g) in EtOH (6 ml) with PtO2ؒH2O (50 mg)
at 18 ЊC took 70 min. Some excess consumption of hydrogen
occurred due to hydrogenolysis of the benzylidene acetal.
Crude product (0.675 g) was obtained. Pure 5-methyl-2-phenyl-
1,3-dioxane as a mixture of cis and trans isomers (9:1 by NMR
spectroscopy) could be obtained by chromatography (silica,
toluene). The isomer ratio was identical to that in the crude
material.
Experimental
All solvents were dried and distilled before use. Flash column
chromatography was carried out on MN Kieselgel 60 (230–400
mesh). Melting points were determined on a Gallenkamp
solid block apparatus and are uncorrected. Elemental analyses
were performed at the Microanalytical laboratory, University
College, London. Infrared spectra were recorded on a Perkin-
Elmer 298 Infrared Spectrophotometer. All spectra were
recorded in chloroform solution. Unless otherwise stated the
cell thickness was 0.1 mm. All NMR spectra were recorded on a
Varian Associates XL-100-12 with internal lock in CDCl3 as
solvent. J values are given in Hz.
General procedures
Catalytic hydrogenation. A solution of the substrate, in abso-
lute ethanol, containing Adam’s catalyst (50 mg) was hydro-
genated at rt and atmospheric pressure in a standard apparatus
until one equiv. of hydrogen had been taken up. The catalyst
was filtered off and the solvent evaporated at reduced pressure
to yield the crude product.
Diimide reduction. The substrate was dissolved in distilled
tert-butyl alcohol and hydrazine hydrate (5 equiv.) added with
stirring. Diimide was generated by the addition of a mixture
of tert-butyl hydroperoxide and tert-butyl peroxide (70:30) (5
equivs. based on oxygen). When all the starting material had
been consumed (TLC), the solvent and excess reagents were
removed under reduced pressure to afford crude product.
Epoxidations. The substrate was dissolved in chloroform and
m-chloroperbenzoic acid (from 1.5 to 3 equivs.) added. The
solution was stirred at rt until the reaction was complete (TLC).
The mixture was washed (NaOH, 2 × H2O), dried, filtered
and solvent removed under reduced pressure to afford crude
product.
Diimide reduction of 5-methylene-2-phenyl-1,3-dioxane.
Reduction of 6 (0.51 g) in tert-butyl alcohol (20 ml) was complete
in 2 h. Chromatography (silica, toluene) afforded a colourless
volatile oil (130 mg) that was a mixture of cis and trans isomers,
5:95 by NMR spectroscopy, identical to that in the crude
material.
Syntheses‡
Preparation of (E,E) and (Z,E)2,2Љ-di-tert-butyldispiro[(1,3-
dioxane)-5,11Ј-(9,10-dihydro-9,10-ethanoanthrarene)-12Ј,5Љ-
(1,3-dioxane)], 11 and 13. 9,10-Dihydro-9,10-ethanoanthracene-
11,11,12,12-tetramethanol (prepared by Ripoll’s method)21
(4.39 g, 0.013 mol) and pivalaldehyde (2.49 g, 0.029 mol) were
refluxed in benzene (200 ml) under nitrogen in the presence of
toluene-p-sulfonic acid (30 mg) for 90 min. The cold reaction
mixture was diluted with chloroform (150 ml) and cooled to
4 ЊC. The colourless powder that precipitated was collected
(Z)-5-Methyl-2-phenyl-1,3-dioxane 15b. ν/cmϪ1 2945, 1600,
1450, 1385, 1270, 1110, 1065, 1020, 950; δH(100 MHz, CDCl3)
1.35 (d, J 6, 3H), 1.65 (m, 1H), 3.93 (br d, J 11, 2H), 4.11 (br d,
J 11, 2H), 5.48 (s, 1H), 7.4 (m, 5H) [Found (HRMS): 178.091.
Required for C11H14O2: 178.099].
(E)-5-Methyl-2-phenyl-1,3-dioxane 16b. ν/cmϪ1 2970, 1600,
1455, 1385, 1270, 1160, 1070, 1025, 970; δH(100 MHz, CDCl3)
0.73 (d, J 7, 3H), 2.3 (m, 1H), 3.2 (dd, J 11.5, 11.5, 2H), 4.17
(dd, J 11.5, 5, 2H), 5.4 (s, 1H), 7.4 (m, 5H).
Diimide reduction of 5-methylene-2-tert-butyl-1,3-dioxane.
Reduction of 5 (0.530 g) in tert-butyl alcohol (20 ml) was com-
plete in <24 h. Removal of solvent afforded a volatile oil (135
‡ The products have been named using E and Z terminology to
describe the positions of the two substituents relative to the plane of the
dioxane ring. Z indicates that the two substituents are located on the
same side of the ring, and E indicates that they are on opposite faces of
the ring. Where there are two substituents on a single ring carbon
normal priority rules are obeyed. In the case of 7 and 14, the stereo-
chemistry is assigned in relation to the entire bidioxanylidene unit.
1136
J. Chem. Soc., Perkin Trans. 2, 1998

View Article Online
1
mg). From the H NMR spectrum, this appeared to contain
reduced [LiAlH4 (30 mg) in THF (10 ml), reflux for 24 h] to
only the E isomer of 5-methyl-2-(tert-butyl)-1,3-dioxane 16a.
ν/cmϪ1 2960, 1482, 1460, 1163, 1111, 984; δH(100 MHz, CDCl3)
0.69 (d, J 7, 3H), 2.0 (m, 1H), 3.27 (dd, J 12, 11.5, 2H), 4.02
(s, 1H), 4.03 (dd, J 11.5, 4.5, 2H).
afford a single compound.
(Z,Z)-2,2Ј-Di-tert-butyl-5,5Ј-epoxy-5,5Ј-bi(1,3-dioxanyl) 21,
mp 215–215.5 ЊC (sublimes above 209 ЊC) (Found: C, 63.7; H,
9.25. C16H28O5 requires C, 63.9; H, 9.40%); ν(pathlength 1.0
mm)/cmϪ1 2845, 1361, 1139, 1081, 967; δH(100 MHz, CDCl3)
0.935 (s, 18H), 3.82 (d, J 13, 4H), 4.07 (d, J 13, 4H), 4.175
(s, 2H); δC(25.18 MHz, CDCl3) 24.5, 35.0, 59.1, 67.8, 107.2.
(Z,Z)-2,2Ј-tert-Butyl-5-hydroxy-5,5Ј-bi(1,3-dioxanyl) 29, mp
228.5–229.5 ЊC (sublimes above 209 ЊC) (Found: C, 63.4; H,
9.95. C16H30O5 requires C, 63.55; H, 10.00%); ν(pathlength
0.1 mm)/cmϪ1 3570, 2960, 1483, 1402, 1362, 1154, 1118, 968;
(pathlength 1.0 mm) 3560, 2965, 1360, 1150, 1118, 970; δH(100
MHz, CDCl3) 0.88 (s, 9H), 0.95 (s, 9H), 1.3 (m, 1H), 3.46
(s, disappears on D2O shake, 1H), 3.80 (dd, J 11.5, 4, 2H), 3.85
(d, J 11, 2H), 4.01 (d, J 11, 2H), 4.15 (s, 1H), 4.06 (s, 1H), 4.36
(br d, J 11.5, 2H); δC(25.18 MHz, CDCl3) 24.5, 24.8, 34.9,
37.5, 66.4, 73.5, 79.3, 107.8, 108.1.
(E,E)-2,2Ј-Di-tert-butyl-5,5Ј-epoxy-5,5Ј-bi(1,3-dioxanyl) 22,
mp 119–120 ЊC; ν/cmϪ1 2985, 2965, 1484, 1364, 1142, 1119,
1100; δH(100 MHz, CDCl3) 0.94 (s, 18H), 3.84 (d, J 12, 4H),
4.00 (d, J 12, 4H), 4.25 (s, 2H); δC(25.18 MHz, CDCl3) 24.6,
34.9, 60.3, 66.8, 107.2.
Epoxidation of (Z)-2,2Ј-di-tert-butyl-5,5Ј-bi(1,3-dioxan-5-
ylidene). Epoxidation of 14 (130 mg) with m-CPBA (240 mg) in
CDCl3 (15 ml) took 4 days and afforded a single crystalline
compound 30 (157 mg), mp 176.5–177 ЊC (ethanol–water)
(Found: C, 63.9; H, 9.70. C16H28O5 requires C, 64.0; H, 9.40%);
ν/cmϪ1 2965, 1484, 1364, 1154, 1097, 980; δH(100 MHz, CDCl3)
0.92 (s, 9H), 0.96 (s, 9H), 3.75 (d, J 11.5. 2H), 3.85 (d, J 11.5,
2H), 4.145 (s, 1H), 4.21 (s, 1H), 4.31 (d, J 12, 2H); δC(25.18
MHz, CDCl3) 24.6, 34.7, 34.9, 57.1, 61.4, 66.6, 69.2, 107.0,
107.7.
Catalytic reduction of (Z)-2,2Ј-di-tert-butyl-5,5Ј-bi(1,3-
dioxan-5-ylidene). Hydrogenation of 7 (200 mg) in EtOH (5 ml)
with PtO2ؒH2O (20 mg) took 20 min. A white solid (180 mg)
was obtained that appeared from the NMR spectrum to consist
solely of the Z,Z isomer (20) of 2,2Ј-di-tert-butyl-5,5Ј-bi(1,3-
dioxanyl). Recrystallisation (EtOH–H2O) afforded colourless
plates of (Z,Z)-2,2Ј-di-tert-butyl-5,5Ј-bi(1,3-dioxanyl) 20, mp
132–133 ЊC (Found: C, 66.8; H, 10.80. C16H30O4 requires
C, 67.1; H, 10.55%); ν/cmϪ1 2990, 2965, 2905, 1484, 1465,
1405, 1364, 1143, 1073; δH(100 MHz, CDCl3) 0.88 (s, 18H),
1.86 (br s, 2H), 3.86 (br d, J 11, 4H), 4.165 (s, 2H), 4.18 (br d,
J 11, 4H); δC(25.18 MHz, CDCl3) 24.6, 32.3, 35.1, 68.7, 108.2.
Diimide reduction of (Z)-2,2Ј-di-tert-butyl-5,5Ј-bi(1,3-dioxan-
5-ylidene). Reduction of 7 (0.200 g) in tert-butyl alcohol (35 ml)
at 53 ЊC took 4 days. A white solid (174 mg) was obtained that
appeared from the NMR spectrum to consist solely of the E,E
isomer (19) of 2,2Ј-di-tert-butyl-5,5Ј-bi(1,3-dioxanyl). Recrys-
tallisation (EtOH–H2O) afforded colorless plates of (E,E)-2,2Ј-
di-tert-butyl-5,5Ј-bi(1,3-dioxanyl) 19, mp 208–209 ЊC (Found:
C, 67.2; H, 10.50. C16H30O4 requires C, 67.1; H, 10.55%);
ν/cmϪ1 2980, 2970, 1484, 1403, 1145, 1076; δH(100 MHz,
CDCl3) 1.77 (m, 2H), 3.44 (dd, J 11, 9, 4H), 4.02 (s, 2H), 4.03
(dd, J 11, 4, 4H); δC(25.18 MHz, CDCl3) 24.7, 34.1, 34.8, 69.6,
107.9.
Epoxidation of 2-tert-butyl-5-methylene-1,3-dioxane. Epoxi-
dation of 5 (400 mg) with m-CPBA (1.0 g) in CHCl3 (15 ml)
took two days and afforded crude product (0.475 g). Chrom-
atography [silica, light petroleum (bp 40–60 ЊC)–CH2Cl2] gave
the two diastereoisomeric epoxides as oils.
(Z)-6-tert-Butyl-1,5,7-trioxaspiro[2.5]octane 17a, ν/cmϪ1 2980,
2955, 2857, 1481, 1353, 1110, 950; δH(100 MHz, CDCl3) 0.95
(s, 9H), 2.875 (s, 2H), 3.61 (d, J 11.5, 2H), 3.98 (d, J 11.5, 2H),
4.15 (s, 1H).
Acknowledgements
I (J. W. L.) am heavily indebted to Dr Ian D. R. Stevens of the
Department of Chemistry, The University of Southampton, for
the major part he played in the preparation of this manuscript
and for the helpful guidance he was able to give. This he did
gladly for the sake of the memory of my supervisor, his good
friend and greatly missed colleague Dr John Hudec. Very sadly
Ian died suddenly shortly before this manuscript went to press.
Thanks are also due to Professor I. H. Hillier for useful discus-
sions and Dr William Wylie for invaluable assistance with
redoing the calculations. We thank the SERC for the award of a
maintenance grant (J. W. L.).
(E)-6-tert-Butyl-1,5,7-trioxaspiro[2.5]octane 18a, ν/cmϪ1 2980,
2960, 1480, 1325, 1106, 947; δH(100 MHz, CDCl3) 0.97 (s, 9H),
2.69 (s, 2H), 3.57 (d, J 13, 2H), 4.24 (s, 1H), 4.26 (d, J 13, 2H).
Epoxidation of 5-methylene-2-phenyl-1,3-dioxane. Epoxid-
ation of 6 (0.948 g) with m-CPBA (1.43 g) in CHCl3 (20 ml)
took 7 days and gave a colourless solid (0.78 g). Chromato-
graphy (silica, CHCl3) separated this into the two diastereo-
meric epoxides. Reduction of each epoxide separately [LiAlH4
(1 equiv.) in diethyl ether, rt] afforded, in each case, a single
5-hydroxy-1,3-dioxane as reduction product.
(Z)-6-Phenyl-1,5,7-trioxaspiro[2.5]octane 17b, mp 85–86.5 ЊC
(pentane); ν/cmϪ1 2980, 2850, 1495, 1460, 1390; δH(100 MHz,
CDCl3) 2.915 (s, 2H), 3.77 (d, J 12, 2H), 4.24 (d, J 12, 2H), 5.63
(s, 1H), 7.5 (m, 5H).
(Z)-5-Methyl-2-phenyl-1,3-dioxan-5-ol 27. ν(pathlength 1.0
mm)/cmϪ1 3690, 3575, 2975, 2860, 1604, 1454; δH(100 MHz,
CDCl3) 1.04 (s, 3H), 3.52 (br s, disappears slowly on D2O shake,
1H), 3.785 (d, J 12, 2H), 3.875 (d, J 12, 2H), 5.41 (s, 1H), 7.44
(m, 5H).
(E)-6-Phenyl-1,5,7-trioxaspiro[2.5]octane 18b, mp 86–86.5 ЊC
(cyclohexane); ν/cmϪ1 2980, 2850, 1505, 1456, 1447, 1395, 1113;
δH(100 MHz, CDCl3) 2.71 (s, 2H), 3.72 (d, J 13, 2H), 4.48 (d
J 13, 2H), 5.57 (s, 1H), 7.45 (m, 5H).
(E)-5-Methyl-2-phenyl-1,3-dioxan-5-ol 28. ν(pathlength 1.0
mm)/cmϪ1 3690, 3605, 3575, 2860, 1604, 1454; δH(100 MHz,
CDCl3) 1.43 (s, 3H), 1.93 (s, 1H), 3.68 (d, J 10.2, 2H), 3.87
(d, J 10.2, 2H), 5.51 (s, 1H), 7.39 (m, 5H).
References
1 R. W. Hoffmann and N. Hauel, Tetrahedron Lett., 1979, 4959.
2 K. Okada and T. Mukui, J. Am. Chem. Soc., 1978, 100, 6509.
3 S. Inagaki, H. Fugimoto and K. Fukui, J. Am. Chem. Soc., 1976, 98,
4054.
4 T. Ohwada, Tetrahedron, 1993, 49, 7649.
5 W. H. Watson, J. Galby, P. D. Bartlett and A. A. M. Roof, J. Am.
Chem. Soc., 1981, 103, 2022.
6 P. H. Mazzochi, B. Stahly, J. Dodd, N. G. Rondan, L. N.
Domelsmith, M. D. Rozeboom, P. Caramella and K. N. Houk,
J. Am. Chem. Soc., 1980, 102, 6582.
7 N. G. Rondan, M. N. Paddon-Row, P. Caramella and K. N. Houk,
J. Am. Chem. Soc., 1981, 103, 2436.
8 N. G. Rondan, M. N. Paddon-Row, P. Caramella, P. H. Mueller,
J. Mareda and K. N. Houk, J. Am. Chem. Soc., 1982, 104, 4974.
9 L. A. Paquette, L. W. Hertel, R. Gleiter and M.C. Bohm, J. Am.
Chem. Soc., 1978, 100, 6510.
10 L. W. Hertel and L. A. Paquette, J. Am. Chem. Soc., 1979, 101, 7620.
11 L. A. Paquette, L. W. Hertel, R. Gleiter, M. C. Bohm, M. A. Beno
and G. G. Christoph, J. Am. Chem. Soc., 1981, 103, 7106.
12 L. A. Paquette, F. Klinger and F. W. Hertel, J. Org. Chem., 1981, 46,
4403.
Epoxidation of (Z)-2,2Ј-di-tert-butyl-5,5Ј-bi(1,3-dioxan-5-
ylidene). Epoxidation of 7 (202 mg) with m-CPBA (370 mg) in
CHCl3 (15 ml) took 5 days and afforded a colourless crystalline
material. Fractional recrystallisation (EtOH–H2O) separated
the two solid diastereoisomers. The major product (60 mg) was
13 Y.-D. Wu, Y. Li, J. Na and K. N. Houk, J. Org. Chem., 1993, 58,
4625.
J. Chem. Soc., Perkin Trans. 2, 1998
1137

View Article Online
14 M. Cherest, H. Felkin and N. Prudent, Tetrahedron Lett., 1968,
2199.
15 J. Klein, Tetrahedron, 1974, 30, 3349.
16 A. S. Cieplak, B. D. Tait and C. R. Johnson, J. Am. Chem. Soc.,
1989, 111, 8447.
17 A. S. Cieplak, J. Am. Chem. Soc., 1981, 103, 4540.
18 S. Srivasta and W. J. le Noble, J. Am. Chem. Soc., 1987, 109, 5873.
19 G. Bellucci, G. Berti, R. Bianchini, G. Ingrosso and E. Mastrorilli,
J. Org. Chem., 1978, 43, 422.
28 S. Siegel, G. M. Foreman and D. Johnson, J. Org. Chem., 1975, 40,
3589.
29 E. E. van Tamelen and R. J. Timmons, J. Am. Chem. Soc., 1962, 84,
1067.
30 L. A. Paquette, R. V. C. Carr, M. C. Bohm and R. Gleiter, J. Am.
Chem. Soc., 1980, 102, 1186.
31 M. R. Giddings and J. Hudec, Can. J. Chem., 1981, 59, 459.
32 D. A. Sweiger and D. W. Turner, J. Am. Chem. Soc., 1972, 94, 5599.
33 H. B. Henbest and R. A. L. Wilson, J. Chem. Soc. II, 1957, 1958.
34 H. R. Tang, M. L. McKee and D. M. Stanbury, J. Am. Chem. Soc.,
1995, 117, 8967.
20 F. Weiss, A. Isard and R. Bensa, Bull. Soc. Chim. Fr., 1965, 1355.
21 J. L. Ripoll, Bull. Soc. Chim. Fr., 1974, 2567.
22 M. W. Schmidt, K. K. Baldridge, J. A. Boatz, S. T. Elbert,
M. S. Gordon, J. H. Jensen, S. Koseki, N. Matsunaga, K. A. Nguyen,
S. J. Ju, T. L. Windus, M. Dupuis and J. A. Montgomery, J. Comput.
Chem., 1993, 14 1347.
23 G. Schaftenaar, Caos/Camm Center, Faculty of Science, University
of Nijmegen, PO Box 9010, 6500 GL Nijmegen, Netherlands.
24 R. S. Brown, R. W. Marcinko and A. Tse, J. Electron Spectrosc.
Relat. Phenom., 1979, 15, 75.
35 S. Siegel, M. Dunkel, G. V. Smith, W. Halpern and J. Cozort, J. Org.
Chem., 1966, 31, 2802.
36 J.-I. Ishiyama, Y. Senda and S. Imaizumi, J. Chem. Soc., Perkin
Trans. 2, 1982, 71,
37 A. Sevin and J.-M. Cense, Bull. Soc. Chim. Fr., 1974, 963.
Paper 8/00999F
Received 4th February 1998
Accepted 13th February 1998
25 D. J. Pasto, Org. React., 1991, 40, 91.
26 P. N. Skancke, Chem. Phys. Lett., 1977, 47, 259.
27 E. L. Eliel and R. M. Enanoza, J. Am. Chem. Soc., 1972, 94, 8072.
1138
J. Chem. Soc., Perkin Trans. 2, 1998