Regio- and stereoselectivity in halomethoxylation of 7-phenyl-1- phenylsulfonyltricyclo[4.1.0.02,7]heptane

Article abstract of DOI:10.1134/S1070428010020077

The reaction of 7-phenyl-1-phenylsulfonyltricyclo[4.1.0.0 ^2,7]heptane with N-halo(chloro, bromo, iodo)succinimide in methanol led to the formation of a single product of conjugate syn-addition to the central C¹-C⁷ bond of the norpinane structure with a halogen atom in the geminal position to the sulfonyl substituent. The stereochemical result of the addition originates from the features of the reaction intermediate structure, a norpinanyl cation of a benzyl type where the reaction site is shielded from the nucleophile attack from the anti-direction by the sulfonyl group whose oxygen atom is approached to the reaction site to a distance of ～1.45 A according to the nonempirical calculations by the 6-31G method; this distance is nearly by half less than the sum of van der Waals radii of C...O.

Full text of DOI:10.1134/S1070428010020077

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 2, pp. 186−190. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © V.A. Vasin, P.S. Petrov, S.G. Kostryukov, V.V. Razin, 2009, published in Zhurnal Organicheskoi Khimii, 2010, Vol. 46, No. 2,
pp. 193−197.
Regio- and Stereoselectivity in Halomethoxylation
of 7-Phenyl-1-phenylsulfonyltricyclo[4.1.0.02,7]heptane
V. A. Vasina, P. S. Petrova, S. G. Kostryukova, and V. V. Razinb
aOgarev Mordovian State University, Saransk, 430005 Russia
e-mail: vasin@mrsu.ru
bSt. Petersburg State University, St. Petersburg, Russia
Received December 19, 2008
Abstract—The reaction of 7-phenyl-1-phenylsulfonyltricyclo[4.1.0.02,7]heptane with N-halo(chloro, bromo,
iodo)succinimide in methanol led to the formation of a single product of conjugate syn-addition to the central C1–
C7 bond of the norpinane structure with a halogen atom in the geminal position to the sulfonyl substituent. The
stereochemical result of the addition originates from the features of the reaction intermediate structure, a norpinanyl
cation of a benzyl type where the reaction site is shielded from the nucleophile attack from the anti-direction by
the sulfonyl group whose oxygen atom is approached to the reaction site to a distance of ~1.45 according to the
nonempirical calculations by the 6-31G method; this distance is nearly by half less than the sum of van der Waals
radii of C···O.
DOI: 10.1134/S1070428010020077
It was established experimentally that 1-phenyl-
tricyclo[4.1.0.02,7]heptane (I) and its 7-X-substituted
derivatives II–V were involved into the electrophilic
addition: hydromethoxylation[1, 2], hydration [2, 3], ionic
hydrogenation [4], methoxymercuration [1], halogenation
[3], halomethoxylation [1, 3, 5, 6], haloamination [6], and
other reactions of conjugate halogenation [3, 7] and
exhibited strict chemo- and regioselectivity. In these
reactions the C1–C7 bond opened at an electrophilic attack
on the position 7, as a result of the benzyl stabilization of
intermediate norpinanyl cation A [8, 9]. From this rule in
this series only the hydration and the hydromethoxylation
of tricycloheptane I are excluded, where the
chemoselectivity of the addition is broken: alongside the
norpinane adduct (4 and 18% respectively) formed
predominantly a norcarane adduct (54 and 56%)
corresponding to the opening of the C2–C7 bond also at
the electrophilic attack on the position 7 [2]. As to the
stereochemistry of the addition to the C1–C7 bond, here
its certain dependence is observed on the nature of the
reagent and the character of the substituent X in the
position 7. Yet this dependence corresponds only to the
stage of the transfer of the nucleophilic coreagent to
carbocation A, since the stage of the electrophilic attack
on the central bicyclobutane bond C1–C7 is considered
to be strictly endo-directed [8, 9]. As a result the
_
Nu
E+
+
E
Ph
Nu
E
E
Ph
X
Ph
X
Nu
anti-adduct
X
Ph
syn-adduct
X
I_V
A
X = H (I), CO2Me (II), SO2Ph (III), Br (IV), Cl (V); E = H, Cl, Br, I, HgOAc; Nu = H, OH, OMe, OCOR, Cl, Br, I, NHCN, SCN,
N(COCH2)2
186

REGIO- AND STEREOSELECTIVITY IN HALOMETHOXYLATION
187
formation of only two, and not all four diastereomers of
the final substituted norpinane becomes possible: syn-
and/or anti-adducts. For instance, in the reaction of
methoxymercuration of tricycloheptane I a strict syn-
stereoselectivity was observed, whereas the halo-
methoxylation of the same substrate gave both diastereo-
mers with a strong prevalence of the anti-adduct
demonstrating the role of the reagent character [1, 3].
The found strict syn-hydromethoxylation of tricyclo-
heptanes III and IV in contrast to the nonselectivity of
the methanol addition to tricycloheptane II demonstrates
the importance of the nature of substituent X in the
tricycloheptane substrate [10].
Table 1. Stereoselectivity of halomethoxylation and
hydroxylation of tricycloheptanes II and III (fraction of syn-
adduct is indicated, %)
from the signals of atoms H3 in the upfield region of the
1H NMR spectrum, ~1.5 ppm, whereas at the opposite
orientation these signals would occur in the shielding
region of the syn-oriented phenyl ring and would appear
at ~0.6 ppm [3, 7, 11]. The configuration at the atom C6
follows from the known endo-directed electrophilic attack
on the bicyclobutane system. This configuration
assignment was confirmed by a chemical reaction:
bromide VIb by a stereospecific hydrodebromination with
triphenyltin hydride was transformed into a known [10]
norpinane VII (cf. [12]).
Although in reviews [8, 9] and in the other publications
cited above useful rules are formulated regarding the
effect of substituents on the direction and stereochemistry
of the opening of the bicyclobutane system in the
reactions of electrophilic addition to hydrocarbon I and
related structure, obviously additional research is required
for confirmation and refining of these rules.
With the goal of obtaining new experimental data on
the chemo-regio-, and stereoselectivity of the electrophilic
addition to 7-substituted derivatives of 1-phenyltricyclo-
[4.1.0.02,7]heptane we report here on the study of the
halomethoxylation of sulfone III and on the comparison
of the results obtained with the known findings [5] on
the halomethoxylation of ester II. Note that both com-
pounds are similar in possessing beside a phenyl group
also strong electron-acceptor substituents at the
bridgehead.
Ph3SnH
VIb
MeO
Ph
VII
SO2Ph
Comparing the results on the composition of the
halomethoxylation products of tricyclic sulfone III with
the products of the same reactions of ester II, and also
with the results of the acid-catalyzed hydromethoxylation
of the same compounds [10], we find a considerable
difference in the stereoselectivity of the addition: In ester
II the stereoselectivity obviously depends on the nature
of the electrophile, whereas sulfone III in all cases reacts
strictly syn-stereoselectively (Table 1).
The reactions of tricycloheptane III were performed
at 20°C in an anhydrous methanol using equimolar amount
of N-halo(chloro, bromo, iodo)succinimide as the source
of a halogen cation. The reactions were completed
approximately in three days furnishing in 80–87% yield
a single product of the syn-addition to the C1–C7 bond,
norpinane VIa–VIc isolated in an individual state by the
column chromatography on Al2O3.
It is presumable that the noted difference in two
reaction series is due to the difference in the electronic
and spatial structure of the corresponding reaction
intermediates, carbocations AII and AIII. We suggested
that the phenylsulfonyl group in cations AIII creates
considerable steric hindrances to the approach of the
external nucleophile, methanol, to the atom C6 from the
anti-side not only due to its large bulk, but also because
of a donor-acceptor interaction between its oxygen atom
and the cation center. In the limiting case an isomerization
of cation AIII into cation BIII can be presumed as a result
of a nucleophilic attack of the sulfonyl oxygen on the
cation center. Such precedents of isomerization involving
3
4
2
Hlg+
5
1
III
MeO
Hlg
MeOH
7
6
Ph
VIа_VIc
SO2Ph
The structure of compounds VIa–VIc was established
from 1H and 13C NMR spectra. The configuration at the
atom C7 of the norpinanes under study was determined
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 2 2010

VASIN et al.
188
significantly less than 180°.
The other and really the most important difference
between cations AII and AIII revealed by the calculations
was the difference in the distances between the atom C6
and the oxygen atom of the carbonyl or the sulfonyl group.
In each case this distance l1 is less than the sum of the
van der Waals radii C···O (3.00 Å [15])indicating the
existence of the shortened intramolecular contacts and
nonzero bond order between these atoms. However in
cations AIII the donor-acceptor interaction is so large that
it is possible to regard them as practically completely
isomerized into cations BIII. Yet analogous isomerization
AII → BII is less probable because of the essentially
shorter bonde at the carbonyl carbon atom than the bonds
at the sulfur atom; therefore the tricyclic cation BII should
be notably more strained than cation BIII. Therefore the
direct precursor of the products of halo(hydro) methoxyla-
tion of sulfone III turn out to be intermediate BIII, where
the approach to the reaction site of the nucleophilic
coreagent is possible only from the syn-direction. For
ester II the reaction intermediates are carbocations AII
with a flat reaction site with permissible approach of the
nucleophilic coreagent from both sides explaining the
simultaneous formation of syn- and anti-adducts in its
reactions of halomethoxylation [5, 11] and hydro-
methoxylation [10].
Hlg
Ph
Hlg
Ph
Ph
O
S
O
O
OMe
BIII
BII
a sulfonyl substituents are known in the series of endo-
6-phenylsulfonyl-2-bicyclo[2.2.1]heptyl cations [13]. It
seems, that analogous isomerization is admissible also for
carbocation AIII with the formation of cation BIII.
Hoping to get some confirmation of the suggested
hypothesis we carried out nonempirical quantum-chemical
calculation of cations AII and AIII using the program PC
GAMESS 7.1 [14]. The main calculation results sig-
nificant for the discussion are presented in Table 2. It
was established that the most stable conformers of cations
in each case were those where one of the oxygens of
the sulfo group or oxygen atom of the carbonyl group is
located in the plane C3C6C7, and the fragment C3H2 is
inclined to the atom C6, and it is characterized by angle
α (angle between planes C1C2C4C5/C2C3C4) of less than
180°, see the figure.
Phenyl ring in each cation is oriented practically normal
to the plane C3C6C7. therewith one of the distinctions of
cations AII from cations AIII is the location of the phenyl
ring in the former in the C1C5C6 plane, whereas in the
latter it deviates from this plane in the direction of the
C3H2 fragment, as show the values of angles β (between
the plane of the phenyl ring and the plane C1C5C6)
The calculation provided also the other useful
information. Thus, the bond lengths C1–C6 (C5–C6) (l2) in
each of the cations under consideration are notably shorter
than the bonds C1–C7 (C5–C7) (l3). The interatomic
distances C6···C7 (l4) are somewhat less than the sum of
the carbon van der Waals radii (3.42 [15]). The positive
(a)
(b)
Spatial arrangement of 7-methoxycarbonyl- (a) and 7-sulfonyl-substituted (b) cations AII and AIII, according to quantum-chemical
calculations.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 2 2010

REGIO- AND STEREOSELECTIVITY IN HALOMETHOXYLATION
189
Table 2. Selected geometric parameters, bond orders, and atomic charges on the atoms of cations A according to the ab initio
quantum-chemical calculation by the method 6-31G a
aFor iodine atom into the standard basis were included the functions from the basis STO-6G.
charge is concentrated not only on the atom C6, but mainly
on the sulfur atom (in cations AIII), on the carbonyl C-
atom (in cations AII), and partially on the halogen atom in
each of the cations. Therewith the positive charge on the
halogen atom increased in the series from chlorine to
bromine and further to iodine. The latter fact indicates the
probable additional stabilization of benzyl cations A and B
by anchimeric assistance of the halogen atom, especially,
iodine, providing an extra contribution in favor of the syn-
stereoselectivity of the addition and appearing, in particular,
as we believe, in the observed stereochemical result of
the iodomethoxylation of ester II, cf. [4].
a mixture of low-boiling petroleum ether and ethyl ether,
4:1. Nonempirical calculations were performed by the
restricted Hartree–Fock method in the basis 6-31G (for
iodine atom into the standard basis were included the
functions from the basis STO-6G) at preliminary
parametrization by PM3 method using the program PC
GAMESS 7.1 [14]. Tricycloheptane III was obtained as
described in [16].
Halomethoxylation of tricycloheptane III.
General procedure. To a solution of 1.55 g (5 mmol)
of sulfone III in 15 ml of anhydrous methanol was slowly
added at 20°C 5 mmol of N-halosuccinimide. The mixture
was stirred at the same temperature for 70–80 h (TLC
monitoring by the consumption of the initial
tricycloheptane). Methanol was removed in a vacuum of
a water-jet pump. The residue was dissolved in 25 ml of
CHCl3, washed in succession with 5 ml of 10% Na2SO3
solution, 5 ml of 5% Na2CO3 solution, and 2 × 12.5 ml of
water for succinimide removal, and dried with CaCl2.
On evaporating the solvent the reaction product was
analyzed by 1H NMR, and then it was subjected to column
chromatography.
Hence it should be stated that the regioselectivity of
reactions of the conjugate electrophilic addition to
tricycloheptane compounds II and III is governed by a
concerted orientation effect of the phenyl ring and
substituent X at the bridgehead, and their stereoselectivity
depends both on the character of the substituent X and
on the nature of the electrophilic reagent, and one of these
factors can prevail in certain cases.
EXPERIMENTAL
7-syn-Methoxy-7-anti-phenyl-6-exo-phenyl-
sulfonyl-6-endo-chlorobicyclo[3.1.1]heptane (VIa):
yield 80%, mp 98–99°C. H NMR spectrum, δ, ppm:
Elemental analyses were performed on a CHN-
1
analyzer HP-185Β. H and 13C NMR spectra were
1
1.53–1.68 m (1H) and 1.82–1.98 m (1H), H3; 2.26–2.41
m (2H) and 2.46–2.59 m (2H), H2,4; 2.86 s (3H, OCH3),
3.84 br.s (2H, C1,5); 7.34–7.41 m (1H), 7.42–7.52 m (6H),
7.55–7.62 m (1H) and 7.71–7.77 m (2H), Ph. 13C NMR
spectrum, 15.63 (C3), 28.74 (2C, C2,4), 50.57 (2C, C1,5),
51.98 (OCH3), 79.76 (C7), 90.60 (C6); 127.56 (2C),
registered on a spectrometer Bruker DPX-300 (300.130
and 75.468 MHz respectively) from samples dissolved in
CDCl3.Analytic TLC was carried out on Silufol UV-254
plates; eluent ether–hexane, 1:1, development in iodine
vapor. The reaction products were purified by column
chromatography on silica gel L 40/100 μ, elution with
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 2 2010

VASIN et al.
190
REFERENCES
127.65, 128.27(2C), 128.38(2C), 129.42 (2C), 133.32,
138.09 and 139.18, Carom. Found, %: C 63.66, H 5.71.
C20H21ClO3S. Calculated, %: C 63.74, H 5.62.
1. Razin, V.V., Zadonskaya, N.Yu., and Shamurzaev, Kh.T.,
Zh. Org. Khim., 1991, vol. 27, p. 1253.
6-endo-Bromo-7-syn-methoxy-7-anti-phenyl-6-
exo-phenylsulfonylbicyclo[3.1.1]heptane (VIb). Yield
83%, mp 115–116°C. 1H NMR spectrum, δ, ppm: 1.58–
1.73 m (1H) and 1.77–1.98 m (1H), H3; 2.30–2.43 m
(2H) and 2.59–2.71 m (2H), H2,4; 2.85 s (3H, OCH3),
3.86 br.s (2H, C1,5); 7.32–7.39 m (1H), 7.41–7.51 m (6H),
7.53–7.61 m (1H) and 7.73–7.76 m (2H), Ph. 13C NMR
spectrum, δ, ppm: 15.59 (C3), 31.30 (2C, C2,4), 50.95 (2C,
C1,5), 51.90 (OCH3), 80.13 (C7), 88.67 (C6); 127.52 (2C),
127.59, 128.23 (4C), 129.37 (2C), 133.24, 138.13 and
2. Christl, M., Gerstner, E., Kemmer, R., Llewellyn, G., and
Bently, T.W., Chem. Ber., 1994, vol. 127, p. 367.
3. Gerstner, E., Kemmer, R., and Christl, M., Chem. Ber., 1994,
vol. 127, p. 381.
4. Vasin, V.A., Kostryukov, S.G., Vovod, S.Yu., Petrov, P.S.,
and Razin, V.V., Zh. Org. Khim., 2008, vol. 44, p. 333.
5. Razin, V.V., Makarychev,Yu.A., Zolotarev, R.N., Vasin, V.A.,
Hennig, L., and Baldamus, J., Zh. Org. Khim., 2007, vol. 43,
p. 822.
6. Vasin, V.A., Semenov, andA.V., Razin, V.V., Izv. Akad. Nauk,
Ser. Khim., 2005, vol. 54, p. 457.
7. Vasin, V.A., Semenov,A.V., and Razin, V.V., Zh. Org. Khim.,
2004, vol. 40, p. 1647.
8. Christl, M., Adv. Strain, Org. Chem., 1995, vol. 4, p. 163.
9. Razin, V.V., Sovr. Problemy Org. Khimii, Mezhvuz. Sb.
(Contemporary Problems of Organic Chemistry: Collection
of Papers), St. Petersburg: Izd. SPb Univ., 1996, no. 11,
p. 54.
10. Razin, V.V., Zolotarev, R.N., Yakovlev, M.E., Kostryu-
kov, S.G., and Vasin, V.A., Zh. Org. Khim., 1996, vol. 32,
p. 1697.
11. Razin, V.V., Zadonskaya, N.Yu., Alekseev, A.G., and
Makarychev, Yu.A., Zh. Org. Khim., 1992, vol. 28, p. 972.
12. Razin, V.V. and Makarychev, Yu.A., Zh. Org. Khim., 1996,
vol. 32, p. 1692.
13. Cossu, S., De, Lucchi, O., and Dilillo, F., Gazz. Chim. Ital.,
1989, vol. 10, 519; Lucchini, V., Modena, G., Pasquato, L.
Chem. Commun., 1992, p. 293.
140.45 Carom
.
6-endo-Iodo-7-syn-methoxy-7-anti-phenyl-6-exo-
phenylsulfonylbicyclo[3.1.1]heptane (VIc). Yield
1
87%, mp 119–120°C. H NMR spectrum, δ, ppm: 1.65–
1.90 m (2H, H3), 2.23–2.37 m (2H) and 2.79–2.92 m
(2H), H2,4; 2.82 s (3H, OCH3), 3.81 br.s (2H, C1,5), 7.31–
7.38 m (1H), 7.40–7.51 m (6H), 7.53–7.60 m (1H) and
7.73–7.76 m (2H), Ph. 13C NMR spectrum, δ, ppm:
15.21 (C3), 35.60 (2C, C2,4), 51.67 (2C, C1,5), 51.71
(OCH3), 72.61 (C6), 78.84 (C7); 127.44 (2C), 127.49,
128.08 (2C), 128.22 (2C), 129.40 (2C), 133.22, 138.28
and 142.12 Carom. Found, %: C 51.33, H 4.56. C20H21IO3S.
Calculated, %: C 51.29, H 4.52.
Reaction of bromosulfone VIb with triphenyltin
hydride. Into a round-bottom flask was charged 0.46 g
(1.1 mmol) of bromosulfone VIb, 0.29 g (1.0 mmol)of
Ph3SnH, 5 mg of azobisisobutyronitrilr, and 15 ml of
anhydrous benzene. The mixture was boiled in an
argon atmosphere for 4 h and evaporated in a vacuum
of a water-jet pump. From the solid residue by column
chromatography was isolated 0.15 g (41%) of sulfone
14. Schmidt, M.W., Baldridge, K.K., Boatz, J.A., Elbert, S.T.,
Gor-don, M.S., Jensen, J.J., Koseki, S., Matsunaga, N.,
Nguyen, K.A., Su, S., Windus, T.L., Dupuis, M., and
Montgomery, J.A., J. Comput. Chem., 1993, vol. 14, p. 1347;
Nemukhin, A.V., Grigorenko, B.L., and Granovsky, A.A.,
Moscow University Chem. Bull., 2004, vol. 45, p. 75.
15. Zefirov, Yu.V. and Zorkii, P.M., Usp. Khim., 1989, vol. 58,
p. 713.
1
VII, mp 124–125°C [10]. H and 13C NMR spectra
16. Vasin, V.A., Kostryukov, S.G., and Razin, V.V., Zh. Org. Khim.,
1996, vol. 32,p. 59.
of compound VII are identical to those published in
[10].
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 2 2010