Hyperconjugation involving strained carbon-carbon bonds. Application of the variable oxygen probe to ester and ether derivatives of cubylmethanol

Article abstract of DOI:10.1039/c3ob40288f

Application of the variable oxygen probe to derivatives of (4-methoxycarbonyl)cubylmethanol 11 demonstrated a strong response of C-OR bond distance to the electron demand of the OR substituent, consistent with an enhanced σ-donor ability of the strained C-C bonds of cubane. The extent of cubane donor ability was found to be superior to an unstrained donor 13, comparing data extracted from the Cambridge Structural Database (T. W. Cole, Ph.D. Dissertation, University of Chicago, 1966), but weaker than the previously studied cyclopropane donors. Structural evidence is also found for σ_CC-π*_CO interactions in these structures. The Royal Society of Chemistry 2013.

Full text of DOI:10.1039/c3ob40288f

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Hyperconjugation involving strained carbon–carbon
bonds. Application of the variable oxygen probe to
ester and ether derivatives of cubylmethanol†
Cite this: DOI: 10.1039/c3ob40288f
Benjamin Harris,a G. Paul Savageb and Jonathan M. White*a
Application of the variable oxygen probe to derivatives of (4-methoxycarbonyl)cubylmethanol 11 demon-
strated a strong response of C–OR bond distance to the electron demand of the OR substituent, consistent
with an enhanced σ-donor ability of the strained C–C bonds of cubane. The extent of cubane donor ability
was found to be superior to an unstrained donor 13, comparing data extracted from the Cambridge Struc-
tural Database (T. W. Cole, Ph.D. Dissertation, University of Chicago, 1966), but weaker than the previously
studied cyclopropane donors. Structural evidence is also found for σCC–π*CO interactions in these structures.
Received 8th February 2013,
Accepted 14th March 2013
DOI: 10.1039/c3ob40288f
www.rsc.org/obc
substrate 2. The basis of this huge rate enhancement is stabil-
isation of the intermediate carbenium ion 3 by strong σC–Si–p
Introduction
Donation of electron density from σ-bonds, into electron poor hyperconjugation.
acceptor orbitals, impacts to varying extents the properties of
all organic compounds.1 The simplest form of this is the inter-
action between a filled σ bonding orbital (σC–X) and a carbo-
cation p orbital, represented by the double bond–no bond
resonance form (Fig. 1), known as hyperconjugation this inter-
actions impacts not only on ground state properties but also
on transition state energies.2
Compared with the group 4 metals, C–C and C–H bonds are
Good σ-donors are high energy orbitals with readily polariz-
able electrons. The best characterised of these are the σ-bonds
between carbon and the lower group 4 elements Si, Ge, Sn and
Pb, which are donors involved in the well-known group
4 metal β-effects.3–5 An example of this effect is provided by
the enhanced unimolecular solvolysis of the antiperiplanar
β-trimethylsilyl-substituted trifluoroacetate 1, which occurs
at a rate of 1012 relative to the corresponding silicon-free
relatively weak σ-donors. However, introduction of strain into
an organic molecular framework can significantly increase the
energy of C–C σ-bonding orbitals, thereby improving the
energy match with electron deficient orbitals.6 The impacts of
strain enhanced hyperconjugation have been demonstrated in
several studies.7–11
In cyclopropyl rings, the enhancement of carbon–carbon
bond donor ability has been demonstrated by their ability to
stabilise carbenium ion intermediates during solvolysis.
Enhanced donation from the cyclopropyl-substituent of the
ester 4 allows unimolecular solvolysis to occur at a rate of
503 000 : 1 relative to the unstrained analogue 5.12,13 Partici-
pation by the strained 4-membered ring has been found in the
rearrangements of the α and β-nopinol derivatives 6 and 7
during solvolysis.14,15
Fig. 1 Hyperconjugation between σCX and a carbocation p-orbital.
aSchool of Chemistry and the Bio21 Institute, The University of Melbourne, Australia.
E-mail: whitejm@unimelb.edu.au
bCSIRO Materials Science and Engineering, Private Bag 10, Clayton South, VIC 3169,
Australia
†Electronic supplementary information (ESI) available: A full listing of geome-
Information on the relative donor abilities of C–X bonds can
be obtained from a number of sources, both experimental16–19
and computational.20 The variable oxygen probe, first
tries and energies (Gaussian archive entries) for ground state structures and 1H
13C NMR, and MS data for 11a–11f. CCDC 923685–923691. For ESI and crystallo-
graphic data in CIF or other electronic format see DOI: 10.1039/c3ob40288f
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introduced by Kirby and Jones, is a method for obtaining such
information using X-ray crystallography.21,22
This approach is based on the linear relationship that has
been established between a C–OR bond distance and the elec-
tron demand of the OR group, quantified by the pKa value of
the parent acid (ROH). In a series of derivatives with varied OR
groups, the compounds with greater electron demand display
increased bond distances. This reflects a greater contribution
of the fragmented C+ −OR no-bond resonance form to the
ground state structure.
Results and discussion
The parent alcohol 11a was prepared by partial hydrolysis and
borane reduction of 1,4-bis(methoxycarbonyl)cubane 12. This
was then converted to crystalline ester and ether derivatives
11b–f using standard methods.
The slope of this relationship has been shown to be sensi-
tive to the interactions of donor orbitals with the C–OR anti-
bonding orbital and thus the steepness can be taken as a
measure of the combined donor abilities of these orbitals.
This technique has been successfully applied to determine
the donor abilities of oxygen non-bonded electrons,19 σC–H and
20,23
24
25
σC–C
,
σC–Si
,
σC–S, σC–Se and σC–Te bonding orbitals,
remote πCvC functionalities,26,27 and the strained σC–C of both
cyclopropane and cyclobutane rings.28,29 In this work we report
the results of the application of the variable oxygen probe to
establish the donor ability of the strained cubane σC–C bonds.
The strong σ-donor ability of cubanes is suggested by the
enhanced unimolecular solvolysis rates of cubylmethyl p-nitro-
benzoate 8 compared to tert-butyl p-nitrobenzoate, analogous
to the cyclopropyl and cyclobutyl examples above.30 Partici-
pation of the vicinal cubane C–C bond during solvolysis is also
proposed to be responsible for the susceptibility of cubyl-
methanol 9 to Wagmer Meerwein ring expansion in the pres-
ence of acid, or upon conversion to reactive ester derivatives.31
Attempts to prepare the more electron demanding p-nitro-
benzene sulphonate, resulted in quantitative conversion to the
corresponding homocubane analogue, 14, by Wagner Meer-
wein ring expansion. The structure of 14 was verified by single
crystal X-ray analysis, and is presented in Fig. 2.
The X-ray structures of 11a–f were collected at 130 K to
minimise the unwanted effects of thermal motion, the
thermal ellipsoid plot of the methane sulphonate 11f is pre-
sented in Fig. 3 with atom numbering scheme representative
of all derivatives.
The methoxycarbonyl group of the compounds 11a–f
adopted two types of conformation (Fig. 4). In type 1, which is
adopted by 11b, the carbonyl group is essentially orthogonal
to one of the cubane C–C bonds and is therefore ideally
positioned to maximise σCC–π* hyperconjugation between the
Computational modelling of this rearrangement suggests that
participation by the antiperiplanar cubane C–C bond induces
rearrangement in concert with the loss of the leaving group,
and that the cubylmethyl carbocation 10 is not involved as an
intermediate (Scheme 1).32
The ester-substituted cubylmethanol derivatives 11 investigated
in this study were chosen as they were expected to be crystalline
and readily prepared from readily available cubane diester 12.
The experimental results have been compared to structural
data for compounds with a single unstrained carbon–carbon
σ-bond donor 13 retrieved from the Cambridge Structural
Database.33,34
Fig. 2 Thermal ellipsoid plot of rearrangement product 14. Ellipsoids are at the
Scheme 1 Modelled rearrangement of cubylmethanol to homocubanol.
30% probability level.
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Application of the variable oxygen probe
In all the cubane derivatives, the –CH2OR substituent adopted
a conformation, which was antiperiplanar to one of the
cubane C–C bonds (labelled C1–C2 for all structures, see
Fig. 3). This bond was therefore optimally positioned to inter-
act with the electron deficient σ*C9–OR antibonding orbital and
its donor ability could therefore be determined by the variable
oxygen probe approach.19,20
Selected bond distances, angles and dihedral angles are
presented in Table 2. A clear relationship between the C9–OR
bond distance and the electron demand of the oxygen substi-
tuent (estimated by the pKa of ROH) was observed, with the
bond distance increasing with increased electron demand
(Table 2). This is consistent with increasing strength of the
Fig. 3 Thermal ellipsoid plot for 11f. Ellipsoids are at the 30% probability level.
σ
CC–σ*C–OR interaction as the σ*C–OR orbital decreases in
energy, also consistent is the steady decrease of the C1–C9
bond distance which gains some double bond character as a
result of this interaction. As has been noted in previous
studies, the σCC–σ*C–OR interaction does not have observable
impact on the σCC donor bond distance (C1–C2),24 this reflects
the fact that the antiperiplanar C–C bond is not the only
donor orbital interacting with the σ*C–OR orbital.
Fig. 4 The two conformation types adopted by the methoxycarbonyl substitu-
ent. The cubane C–C bonds, which can interact significantly with the carbonyl
π-system are indicated in bold.
Table 1 The two conformational types of the methoxycarbonyl group, with
This data is shown in Fig. 5 and gives rise to the following
relationship between C9–OR bond distance and pKa:
selected bond lengths (Å)
Methoxycarbonyl
dihedral with:
Bond distances of:
r
C–O=Å ¼ 1:47–2:85 ꢀ 10ꢁ3 pKaðROHÞ R2 ¼ 0:88
Non-interacting Interacting Non-interacting Interacting
The slope of this plot provides a measure of the donor
ability of a single cubane C–C bond.‡ To best assess the contri-
bution of strain to this value, this was compared to data for a
system with a single unstrained C–C bond antiperiplanar to
the C–OR bond.
bonds (°)
bonds (°)
82.55
bonds (Å)
bonds (Å)
1.580 (2)
Type 2
11b
−33.65
−158.4
1.564 (2)
1.562 (2)
Type 1
11a
−0.37
−8.22
13.85
171.66
−6.37
14.04
121.97
−120.94
111.14
−130.76
136.46
−104.43
−71.03
43.15
1.562 (2)
1.560 (2)
1.559 (2)
1.558 (2)
1.553 (5)
1.561 (2)
1.575 (2)
1.577 (2)
1.567 (2)
1.584 (2)
1.568 (2)
1.587 (2)
1.575 (2)
1.566 (2)
1.569 (5)
1.571 (5)
1.567 (2)
1.574 (2)
The donor ability of a single unstrained carbon–carbon
bond was estimated in an early paper establishing the linear
relationship between C–OR bond distance and electron
demand. In that work, the Cambridge Structural Database31
was searched for structures containing the R–O–CH2R′ and by
roughly assigning the electron demand of OR to three pKa
groups (alkyls = 16, aryls = 10 and esters = 4) a slope of 2.19 ×
10−3 was determined for an unstrained C–C bond donor.37
Since then the total number of structures in the Cambridge
Structural Database has risen dramatically and an improved
value can be derived. A search was therefore conducted for the
sub-structure 13 containing –OR groups of known electron
demand with the O–C–C–C dihedral angle constrained to 180
( 20)° (Table 3).
11aa
11c
11d
11e
11f
114.22
−126.71
138.39
−102.67
a For molecule 2.
cubane C–C bond and the carbonyl π-system. Consistent with
this is significant lengthening of this bond (1.580(2) Å) com-
pared to the other two non-interacting C–C bonds, which were
1.564(2) and 1.562(2) Å respectively. In type 2, which is adopted
by the remaining derivatives, the carbonyl system is aligned
close to synperiplanar with one of the cubane C–C bonds and
synclinal to the other two C–C bonds. In this conformation,
both the synclinal C–C bonds can participate in σCC–π* inter-
action with the carbonyl π-system, but to a lesser extent than
11b, while the periplanar bond cannot (Fig. 4). Consistent with
this is a general lengthening of the synclinal C–C bonds com-
pared to the synperiplanar C–C bond, see Table 1.
This data is shown in Fig. 6, and gives rise to the following
relationship between C9–O1 bond distance and pKa:
r
C–O=Å ¼ 1:456–2:42 ꢀ 10ꢁ3 pKaðROHÞ R2 ¼ 0:96
‡A referee has commented that the slopes of correlations between r(C–O) and
pKa (ROH) reflect the first derivative of the donor ability rather than donor
ability per se.
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Table 2 Selected bond distances and angles for the derivatives of 11
C9–OR
(Å)
C1–C9
(Å)
C1–C2
(Å)
C9–C1–C2 C2–C1–C9–O
(°) (°)
pKa
11aa 15.7
1.428 (2) 1.497 (2) 1.569 (2) 124.69 (1) 176.83
1.424 (2) 1.493 (2) 1.575 (2) 124.05 (1) 177.69
15.7
11b
11c
11d
11e
7.1535 1.437 (2) 1.491 (2) 1.567 (2) 124.95 (1) 175.46
3.4633 1.462 (2) 1.489 (2) 1.571 (2) 124.02 (1) 177.33
2.1733 1.451 (2) 1.487 (2) 1.563 (2) 123.36 (1) 175.11
0.6633 1.473 (3) 1.483 (3) 1.567 (3) 123.17 (2) 177.65
11f −1.936 1.478 (2) 1.483 (2) 1.565 (2) 124.25 (1) 175.40
a Two sets of values are shown for 11a as two molecules were
contained in the asymmetric unit.
Fig. 6 r(C–O) vs. pKa(ROH) relationship for the derivatives of 13 obtained from
the Cambridge Crystallographic database.
C–OR bond. A variable oxygen probe study of these derivatives
gave the following relationships:
rC–OR (Å) = 1.482 − (3.20 × 10−3)pKa (ROH) R2 = 0.975.
Taking into consideration the contribution of the
additional unstrained carbon–carbon bond donor in α-nopinol
15, this suggests that cyclobutane and cubane bonds likely
have similar σ-donor abilities.
Fig. 5 r(C–O) vs. pKa(ROH) relationship for the derivatives 11a–f.
Variable oxygen probe investigation of a single strained
cyclopropane bond and a combination of two cyclopropane
bonds in cyclopropylmethanol 16 and dicyclopropylmethanol
17 gave the relationships below. These indicated that
compared to cyclopropane, cubane C–C bond is a significantly
weaker σ-bond donor.
Table 3 Structural data for a single C–C bond donor obtained from the CSD36
R =
Structures
pKa
Av. C–O bond length (Å)
H–
Me–
Ph–
p-NO2–Ph–
Me–CO–
1150
57
10
1
263
38
23
11
33
1
15.7
1.423
1.414
1.426
1.440
1.443
1.448
1.451
1.463
1.461
1.463
15.538
9.9839
7.1533
4.7640
4.238
Ph–CO–
p-NO2–Ph–CO–
Me–SO2–
p-Me–Ph–SO2–
p-NO2–Ph–SO2–
3.4333
−1.934
−2.734
−3.834
16: rC–OR (Å) = 1.48 − (4.60 × 10−3) pKa (ROH) R2 = 0.940.
17: rC–OR (Å) = 1.50 − (7.70 × 10−3) pKa (ROH) R2 = 0.980.
A measurement of donor ability was attempted from deriva-
tives of the mono-substituted cubylmethanol 18, but the
number of reliable X-ray structures obtained of these less crys-
talline cubanes was insufficient to carry out a variable oxygen
probe analysis.
The effect of strain on the donor ability of a cubane C–C
bond is illustrated by comparison of the measured slope of
−2.85 × 10−3 for 11a–11f with that found for a single
unstrained C–C bond, −2.42 × 10−3
.
The donor ability of cubane can also be compared to the
results of previous variable oxygen probe studies on other
strained bonds. The derivatives of α-nopinol 15 position a
strained cyclobutyl bond, in addition to an unstrained C–C
donor orbitals from the unstrained ring, antiperiplanar to the
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However 18 was included in the computational modelling,
In comparison with the cubyl donor 18, the presence of the
below in order to assess the effect, if any, of the methoxycarbo- additional methoxycarbonyl substituent in 11 was predicted to
nyl substitute on the cubane σC–C donor ability.
have little effect on the donor ability of the C1–C2 bond.
The strained donors 11, 16, 18 and 19 were all found to
have significant higher energy donor orbital energies, εi, than
the unstrained n-propyl donors 13 (R′ = H). This is the major
effect of strain on donor ability, and their improved inter-
actions with the C–OR antibonding orbital were consistent
with the variable oxygen probe results.
Between the similarly highest energy donors, the cubyl
donors 11 and 18 compared to cyclopropyl 16, the difference
in donor ability appeared to be a result of orbital overlap,
reflected by the higher off-diagonal NBO Fock matrix element
(F(i,j)), which could be attributed to the bent bonds of cyclo-
propyl. While cubane bonds also have a centre of density that
lies outside the bond vector,42 this appeared to be to a lesser
extent.
Computational studies
The donor σC–C orbitals and their interactions with the σ*C–O
acceptor orbitals were characterised using NBO analysis.41
These calculations translate an N-electron wavefunction into
N/2 localised filled orbitals that are reminiscent of Lewis struc-
ture descriptions. The local orbitals include nearly doubly
occupied core, lone pair and bonding orbitals, and to describe
delocalisation, weakly occupied antibonding and Rydberg orbi-
tals. Interactions between orbitals, such as the σC–C–σ*C–O of
present interest, are identified and can be quantitatively esti-
mated by deletion analysis, or as used in this work, second-
order perturbation analysis.
The σCC donor orbitals modelled were the strained meth-
oxylcarbonyl cubyl 11, cubyl 18, cyclopropyl 16, cyclobutyl 19,
and the unstrained donor 13.
Conclusion
Application of the variable oxygen probe to derivatives of
(4-methoxycarbonyl)cubylmethanol 11 demonstrated a strong
response of C–OR bond distance to the electron demand of
the OR substituent, consistent with an enhanced σ-donor
ability of strained C–C bonds. The extent of cubane donor
ability was found to be superior to an unstrained donor 13,
comparing data extracted from the Cambridge Structural Data-
base,31 but weaker than the previously studied cyclopropane
donor.26
NBO analysis found the expected difference between
strained and unstrained donor orbital energies. The predicted
difference between the strained cubane and cyclopropyl
donors was not donor bond energy, which was very similar,
but rather orbital overlap. This reinforces the importance of
bond hybridisation in addition to relative positioning to the
strength of these orbital interactions.
The order of stabilisation energies, predicted by second-order
perturbation, for these interactions was consistent with the
results from the variable oxygen probe described above: cyclo-
propane > cubane > cyclobutyl > unstrained bond systems. The
origin was sought of the factors that determine the extent of
this interaction: donor population (qi), the energy difference
between donor and acceptor orbitals (εj − εi), and off-diagonal
NBO Fock matrix element (F(i,j)) which reflects the amount of
orbital overlap (Table 4).
Table 4 Interaction energies E(2), donor orbital energies εi, and off-diagonal
NBO Fock matrix elements (F(i,j))
2
Fði;jÞ
Eð2Þ ¼ ꢁqi
εj ꢁεi
pKa
E(2) (kJ mol−1
)
qi (a.u.) εi (a.u.) εj (a.u.) F(i,j)
Experimental
Crystallography
Cyclopropyl
16a
16c
16f
15.7
3.46 15.1
−1.9
14.1
1.950
1.946
1.944
−0.538
−0.551
−0.550
0.284
0.229
0.217
0.048
0.048
Intensity data for were collected on a CCD diffractometer
0.048 using either Cu-Kα radiation (graphite crystal monochromator
λ = 1.54184), or with Mo-Kα radiation (graphite crystal mono-
chromator λ = 0.71073). The temperature during data collec-
0.046 tions was maintained at 130.0(1).
15.4
Methoxycarbonyl cubyl
11a
11c
15.7
3.46 14.1
11.4
1.967
1.962
1.960
−0.543
−0.551
−0.548
0.279
0.227
0.216
0.043
0.046
11f
Cubyl
−1.9
14.2
11.7
Crystal data for 11a. C11H12O3, M = 192.21, T = 130.0(2) K,
18a
18c
15.7
3.46 14.2
1.966
1.959
1.961
−0.534
−0.537
−0.542
0.278
0.230
0.219
0.043
0.046
λ = 1.54184 Å, monoclinic, space group P21/c, a = 8.6179(3), b =
18f
Cyclobutyl
−1.9
13.5
10.5
0.044 7.0392(3), c = 30.2576(10) Å, β = 91.859(3)°, V = 1834.55(12) Å3,
Z = 8, Dc = 1.392 Mg M−3, μ(Cu-Kα) 0.832 mm−1, F(000) = 816,
19a
19c
15.7
3.46 12.6
1.974
1.972
1.970
−0.556
−0.572
−0.569
0.280
0.233
0.221
0.041
0.044
crystal size 0.40 × 0.25 × 0.10 mm. 7121 reflections measured,
19f
n-Propyl
−1.9
12.9
0.044 3586 independent reflections (Rint = 0.0216) the final R was
0.0444 [I > 2σ(I)] and wR(F2) was 0.1491 (all data).
13a
13c
13f
15.7
3.46 11.5
−1.9
9.9
1.987
1.985
1.984
−0.604
−0.621
−0.618
0.282
0.236
0.224
0.041
0.043
Crystal data for 11b. C17H15NO5, M = 313.30, T = 130.0(2) K,
0.044 λ = 0.71073 Å, triclinic, space group P1, a = 6.9852(10), b =
ˉ
11.8
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10.5113(15), c = 10.8498(11) Å, α = 68.415(11), β = 91.859(3)°, r.t. The mixture was stirred overnight and then evaporated
γ = 80.137(12)°, V = 721.99(16) Å3, Z = 2, Dc = 1.441 Mg M−3
,
under vacuum with minimal heating. The residue was diluted
μ(Mo-Kα) 0.107 mm−1, F(000) = 328, crystal size 0.33 × 0.26 × with H2O (100 mL) and extracted with CHCL3 (3 × 50 mL).
0.17 mm. 5867 reflections measured, 3374 independent reflec- Evaporation of the extract under vacuum afforded 0.371 g (6%)
tions (Rint = 0.0196) the final R was 0.0425 [I > 2σ(I)] and wR(F2) of unreacted diester. The aqueous layer was acidified to
was 0.1167 (all data).
pH ∼ 3 with conc. HCl, then extracted with CHCl3 (3 × 50 mL)
Crystal data for 11c. C18H15NO6, M = 341.31, T = 130.0(2) K, and the combined extracts dried (MgSO4). Removal of the
λ = 1.54184 Å, triclinic, space group P1, a = 8.1260(6), b = solvent under vacuum left 5.147 g (MW 206.19 g mol−1
,
ˉ
8.7446(5), c = 12.5714(7) Å, α = 89.867(5), β = 76.801(5)°, γ = 24.96 mmol, 89%) of 20 as a colourless crystalline solid; mp
62.719(7)°, V = 767.54(8) Å3, Z = 2, Dc = 1.477 Mg M−3, μ(Cu-Kα) 181–182 °C, Lit. 182–183 °C.50,51 1H NMR: δ 3.72 (3H, s), 4.27
0.945 mm−1, F(000) = 356, crystal size 0.45 × 0.26 × 0.11 mm. (6H, m). 13C NMR: δ 47.0, 47.1, 51.7, 55.5, 55.8, 171.8, 177.2.
4671 reflections measured, 2935 independent reflections (Rint
= 0.0165) the final R was 0.0431 [I > 2σ(I)] and wR(F2) was oxycarbonylcubane carboxylic acid 20 (5.001 g, 24.25 mmol)
0.1196 (all data). in anhydrous THF (150 mL) was cooled to 0 °C and treated
(4-Methoxycarbonyl)cubylmethanol 11a. A solution of 4-meth-
Crystal data for 11d. C18H15NO6, M = 341.31, T = 130.0(2) K, dropwise with BH3·SMe2 (3.70 mL, 39.0 mmol). The reaction
ˉ
λ = 0.71073 Å, triclinic, space group P1, a = 7.5474(4), b = mixture was stirred at 0 °C for 30 min and then at room temp-
8.4100(5), c = 13.9152(8) Å, α = 102.757(5), β = 90.682(4)°, γ = erature for a further 30 min before quenching with H2O
115.310(5)°, V = 773.07(8) Å3, Z = 2, Dc = 1.466 Mg M−3, μ(Mo- (10 mL). The mixture was diluted with Et2O (150 mL) and the
Kα) 0.111 mm−1, F(000) = 356, crystal size 0.45 × 0.40 × organic layer was washed successively with H2O (150 mL),
0.20 mm. 7502 reflections measured, 3639 independent reflec- brine (50 mL) and saturated aqueous NaHCO3 solution
tions (Rint = 0.0217) the final R was 0.0426 [I > 2σ(I)] and wR(F2) (50 mL). The ethereal solution was dried (MgSO4), filtered, and
was 0.1093 (all data).
concentrated to afford (4-methoxycarbonyl)cubylmethanol 11a
Crystal data for 11e. C13H11Cl3O4 M = 341.31, T = 130.0(2) K, as a colourless crystalline solid (4.061 g, 1.13 mmol, 87%), mp
λ = 1.54184 Å, triclinic, space group P1, a = 5.7385(4), b = 85–87 °C (lit. 86–90 °C);52 1H NMR: δ 3.71, 3.78 (2H, s), 3.89
ˉ
10.3221(7), c = 13.5698(9) Å, α = 111.374(6), β = 92.266(5)°, γ = (3H, m), 4.15 (3H, m); 13C NMR: δ 44.5, 46.3, 51.5, 56.3, 58.8,
102.902(6)°, V = 723.10(9) Å3, Z = 2, Dc = 1.550 Mg M−3, μ(Cu- 63.1, 172.7.
Kα) 5.839 mm−1, F(000) = 356, crystal size 0.45 × 0.40 ×
(4-Methoxycarbonyl)cubylmethyl p-nitrophenoxide (11b).
0.20 mm. 4069 reflections measured, 2563 independent reflec- (4-Methoxycarbonyl)cubylmethanol (50 mg, 0.26 mmol) 11a
tions (Rint = 0.0265) the final R was 0.0522 [I > 2σ(I)] and wR(F2) was added to a suspension of NaH (62 mg, 2.6 mmol) in anhy-
was 0.1479 (all data).
drous ether (20 mL). The solution was stirred for 30 min at r.t.
Crystal data for 11f. C12H14O5S M = 270.29, T = 130.0(2) K, then cooled to 0 °C before a solution of 1-fluoro-4-nitroben-
ˉ
λ = 0.71073 Å, triclinic, space group P1, a = 5.8663(3), b = zene (53 mg, 0.38 mmol) in anhydrous ether (20 mL) was
8.9585(6), c = 12.2036(7) Å, α = 95.715(5), β = 103.005(5)°, γ = added and the reaction was stirred at r.t. The reaction was
104.096(5)°, V = 597.93(6) Å3, Z = 2, Dc = 1.501 Mg M−3, μ(Mo- quenched with H2O (10 mL), washed with H2O (30 mL). The
Kα) 0.281 mm−1, F(000) = 284, crystal size 0.60 × 0.47 × organic layer was dried (MgSO4), filtered, and concentrated to
0.34 mm. 4741 reflections measured, 2777 independent reflec- afford 11b (70 mg, 0.21 mmol, 79%), which was recrystallized
tions (Rint = 0.0185) the final R was 0.0372 [I > 2σ(I)] and wR(F2) from MeOH to give colourless blocks, mp = 109–113 °C; 1H
was 0.0957 (all data).
NMR: δ 3.72 (3H, s), 3.99 (3H, m), 4.20 (3H, m), 4.23 (2H, s),
Crystal data for 15. C17H15NO7S, M = 377.36, T = 130.0(2) K, 6.98 (2H, m), 8.20 (2H, m); 13C NMR: δ 45.1, 46.7, 51.6, 56.1
λ = 0.71073 Å, monoclinic, space group P21, a = 7.3222(2), b = 56.4, 69.0, 114.5, 125.9, 141.6, 164.2, 172.3; IR νmax: 2986,
8.3972(3), c = 13.2244(4) Å, β = 92.244(3)°, V = 812.49(4) Å3, Z = 1590 cm−1; HRMS (ESI): Calculated for C17H16NO5 [M + H]+
+
2, Dc = 1.542 Mg M−3, μ(Mo-Kα) 0.242 mm−1, F(000) = 392, 314.1023, found 314.1022.
crystal size 0.64 × 0.49 × 0.11 mm. 5025 reflections measured,
General procedure for ester synthesis
3062 independent reflections (Rint = 0.0234) the final R was
0.0375 [I > 2σ(I)] and wR(F2) was 0.0936 (all data), Flack par- To
a solution of (4-methoxycarbonyl)cubylmethanol 11a
ameter 0.06(8).
(50 mg, 0.26 mmol) in CH2Cl2 (20 mL) was added pyridine
(2 ml) and the mixture stirred for 30 min before the acid chlor-
ide (1.5 eq.) was added at 0 °C and the reaction stirred for
Computational
Optimization calculations were performed using the Gaussian 12 h. The mixture was then diluted with Et2O (30 mL), and
03 software package43 employing the B3LYP hybrid func- washed with saturated aqueous CuSO4 (20 mL), saturated
tional44 with the 6-311++G** basis set,45–48 and natural bond aqueous NaHCO3 (20 mL) solution and water (20 mL). The
analysis was conducted with NBO 3.1.49
4-Methoxycarbonylcubane carboxylic acid (20). A solution of afford.
organic layer was dried (MgSO4), filtered, and concentrated to
methanolic NaOH (11.0 mL, 2.50 M, 27.5 mmol) was added
(4-Methoxycarbonyl)cubylmethyl 3-nitrobenzoate (11c).
dropwise to a solution of 1,4-bis(methoxycarbonyl)cubane 12 Yield 79%; mp = 109–113 °C; 1H NMR: δ 3.70 (3H, s), 3.97 (3H,
(6.198 g, MW 220.22 g mol−1, 28.15 mmol) in THF (70 mL) at m), 4.20 (3H, m), 4.56 (2H, s), 7.66 (1H, m), 8.34 (1H, m), 8.40
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(1H, m), 8.82 (1H, m); 13C NMR: δ 45.1, 46.5, 51.5, 56.1, 56.4, 10 H. Hassall, S. Lobachevsky, C. H. Schiesser and
65.8, 124.6, 127.4, 129.6, 131.9, 135.2, 148.3, 164.6, 172.3; IR J. M. White, Organometallics, 2007, 26, 1361.
νmax: 2970, 2851, 1740, 1532 cm−1; HRMS (ESI): Calculated for 11 (a) B. Gold, N. Shevchenko, N. Bonus, G. B. Dudley and
C18H16NO6+ [M + H]+ 342.0972, found 342.0973.
(4-Methoxycarbonyl)cubylmethyl 2-nitrobenzoate (11d).
Yield 83%; mp = 131–133 °C; 1H NMR: δ 3.72 (3H, s), 3.89 (3H,
I. V. Alabugin, J. Org. Chem., 2012, 77, 75; (b) B. Gold,
G. B. Dudley and I. V. Alabugin, J. Am. Chem. Soc., 2013,
135, 1558.
m), 4.21 (3H, m), 4.57 (2H, s), 7.67 (1H, m), 8.35 (1H, m), 8.42 12 A. de Meijere, Angew. Chem., Int. Ed., 1979, 18, 809.
(1H, m), 8.84 (1H, m); 13C NMR: δ 45.1, 46.3, 51.6, 56.1, 56.5, 13 H. C. Brown and E. N. Peters, J. Am. Chem. Soc., 1973, 95,
65.8, 124.6, 127.4, 129.7, 132.0, 135.3, 148.3, 164.6, 172.4; IR
νmax: 2971, 2870, 1729, 1534 cm−1; HRMS (ESI): Calculated for 14 P. v. R. Schleyer, W. E. Watts and C. Cupas, J. Am. Chem.
C18H16NO6+ [M + H]+ 342.0972, found 342.0972.
Soc., 1964, 86, 2722.
(4-Methoxycarbonyl)cubylmethyl 2,2,2-trichloroacetate (11e). 15 S. Winstein and N. J. Holness, J. Am. Chem. Soc., 1955, 77,
2400.
Yield 63%; mp = 103–106 °C; 1H NMR: δ 3.70 (3H, s), 3.97 (3H,
3054.
m), 4.19 (3H, m). 4.56 (2H, s); 13C NMR: δ 45.1, 46.6, 51.6, 16 D. D. Davis, J. Organomet. Chem., 1981, 206, 21.
55.8, 56.4, 68.9, 162.4, 172.2; IR νmax: 2997, 2831, 1721 (CvO); 17 M. A. Cook, C. Eaborn and D. R. M. Walton, J. Organomet.
+
HRMS (ESI): Calculated for C13H11Cl3O4 [M + H]+ 336.9796,
Chem., 1970, 24, 293.
found 336.9793.
18 W. Hanstein, H. J. Berwin and T. G. Traylor, J. Am. Chem.
Soc., 1970, 92, 829.
(4-Methoxycarbonyl)cubylmethyl methanesulphonate (11f).
Yield 65%; mp = 160–162 °C; 1H NMR: δ 2.27 (3H, s), 3.10 (3H, 19 W. Adcock, D. P. Cox and W. Kitching, J. Organomet. Chem.,
s), 3.36 (2H, m), 3.63–3.75 (6H, m); 13C NMR: δ 38.2, 39.5, 43.3,
1977, 133, 393.
44.6, 45.2, 48.8, 96.4 177.3; IR νmax: 3008, 2618, 1330; HRMS 20 I. V. Alabugin and M. Manoharan, J. Org. Chem., 2004, 69,
(ESI): Calculated for C12H15O5S+ [M + H]+ 271.0635, found
271.0635.
9011.
21 A. J. Briggs, R. Glenn, P. G. Jones, A. J. Kirby and
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J. K. Parker, J. M. Percy and M. Der Su, J. Chem. Soc., Perkin
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