Formation of 2-(phenylsulfonyl)resorcinols (=2-(phenylsulfonyl)benzene-1,3- diols) from symmetrically substituted maleic anhydrides (=furan-2,5-diones)

Article abstract of DOI:10.1002/hlca.201300225

Treatment of symmetrically substituted maleic anhydrides (=furan-2,5-diones) 6 with lithium (phenylsulfonyl)methanide, followed by methylation of the adduct with MeI/K₂CO₃ in acetone, give the corresponding 4,5-disubstituted 2-methyl-2-(phenylsulfonyl)cyclopent-4-ene- 1,3-diones 8 (Scheme 3). Reaction of the latter with lithium (phenylsulfonyl)methanide in THF (-78°) and then with 4 mol-equiv. BuLi (-5° to r.t.) leads to 5,6-disubstituted 4-methyl-2-(phenylsulfonyl)benzene- 1,3-diols 9 (Scheme 4). Copyright

Full text of DOI:10.1002/hlca.201300225

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Helvetica Chimica Acta – Vol. 96 (2013)
Formation of 2-(Phenylsulfonyl)resorcinols (¼2-(Phenylsulfonyl)benzene-
1,3-diols) from Symmetrically Substituted Maleic Anhydrides
(¼ Furan-2,5-diones)
by Khaled Abou-Hadeed and Hans-Jꢀrgen Hansen*
Organisch-chemisches Institut der Universitꢀt Zꢁrich, Winterthurerstr. 190, CH-8057 Zꢁrich
(phone: þ 41-44-6354231; fax: þ 41-44-6356833; e-mail: hjhansen@oci.uzh.ch)
Dedicated to John Anthony Robinson on the occasion of his 60th birthday
Treatment of symmetrically substituted maleic anhydrides (¼ furan-2,5-diones) 6 with lithium
(phenylsulfonyl)methanide, followed by methylation of the adduct with MeI/K2CO3 in acetone, give the
corresponding 4,5-disubstituted 2-methyl-2-(phenylsulfonyl)cyclopent-4-ene-1,3-diones 8 (Scheme 3).
Reaction of the latter with lithium (phenylsulfonyl)methanide in THF (ꢀ 788) and then with 4 mol-equiv.
BuLi (ꢀ 58 to r.t.) leads to 5,6-disubstituted 4-methyl-2-(phenylsulfonyl)benzene-1,3-diols 9 (Scheme 4).
Introduction. – More than 15 years ago, we reported on a ꢂOne-Pot Anellation
Method for the Transformation of Heptalene-4,5-dicarboxylates into Benzo[a]hepta-
lenesꢃ (see 1 ! 2 in Scheme 1) [1], which allowed us to envisage and probe a new
entrance into the field of colchicinoids starting with azulenes and acetylenedicarbox-
ylates (see, e.g., [2]). At the beginning, we had no clear insight into the mechanism of
this new anellation reaction, apart from the experimental facts, which showed that at
least two mol-equiv. of the (X-sulfonyl)methanides (X ¼ N(CH2CH2)2O, Ph) were
necessary, whereby one served as C1-carrier and the other one obviously as (X-
sulfonyl)methine building block. Moreover, we observed that a minimum of 4 mol-
equiv. of BuLi or an other alkyllithium reagent were needed for good yields of the
benzo[a]heptalenediols. Finally, we learnt more about the anellation mechanism when
we treated the tetramethylheptalene-1,2-dicarboxylate 3 with 4 mol-equiv. of lithium
(phenylsulfonyl)methanide in THF at ꢀ 788, followed by slow warming to ꢀ 108 and
then by addition of 4 mol-equiv. of BuLi and stirring for 15 h at room temperature
(Scheme 2) [3]. Beside the expected benzo[a]heptalene-2,4-diol 4, we found the highly
polar 5,11b-dihydro-3-hydroxy-2-(phenylsulfonyl)-11b-[(phenylsulfonyl)methyl]-1H-
cyclopenta[a]heptalen-1-one (5), the structure of which was secured by an X-ray
crystal-structure analysis. Its treatment with an excess of BuLi in THF led to 4 showing
that it was the crucial intermediate in the described benzo-anellation process, which by
loss of benzenesulfinate under the strongly basic conditions induced the 5 ! 6-ring
enlargement.
The C¼C bond arrangement of 3 with its 1,2-dicarboxylate partial structure
remembered us that simple 2,3-disubstituted maleic acid (¼(2Z)-but-2-enedioic acid)
derivatives may behave similarly to the vicinal heptalenediester and yield 2-(phenyl-
ꢄ 2013 Verlag Helvetica Chimica Acta AG, Zꢁrich

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Scheme 1
Scheme 2
a) 1. 4 mol-equiv. of LiCH2SO2Ph/THF, ꢀ 788 (1 h) to ꢀ 108 (1.5 h); 2. 4 mol-equiv. of BuLi (15 h). b)
6 mol-equiv. of BuLi/THF, ꢀ 108 (20 min) to r.t. (30 min); 61% of cryst. 4.
sulfonyl)resorcinols (¼2-(phenylsulfonyl)benzene-1,3-diols) under the above descri-
bed treatment. We give in the following part a detailed report on our experiments to
verify this idea (see [4] for a preliminary report).
Results and Discussion. – We focused our experiments on symmetrically 2,3-
disubstituted maleic acid anhydrides (¼ 3,4-substituted furan-2,5-diones) 6 (Scheme 3),
which gave with lithium (phenylsulfonyl)methanide in THFat ꢀ 788 the corresponding
adducts, i.e., 5-hydroxy-5-[(phenylsulfonyl)methyl]furan-2(5H)ones 7. Treatment of
Scheme 3
a) 2 mol-equiv. of PhSO2CH2Li/THF, ꢀ 788 (1 h); 7a and 7b 77%; 7c (74%; with 1,5 mol-equiv. of
PhSO2CH2Li/THF). b) MeI, K2CO3, acetone, r.t., 8 h; 8a 89%, 8b 87%, 8c 91%.

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Helvetica Chimica Acta – Vol. 96 (2013)
the latter with MeI and K2CO3 in acetone at room temperature led to the symmetrically
4,5-disubstituted 2-methyl-2-(phenylsulfonyl)cyclopent-4-ene-1,3-diones 8 in good
yields. The 1,3-diones 8 contained all the necessary structural ingredients for a possible
rearrangement into corresponding benzene-1,3-diols by reaction with lithium (phenyl-
sulfonyl)methanide and then with an excess of BuLi as initiator for the 5 ! 6-ring
enlargement. Indeed, all three 1,3-diones 8 gave under these conditions the 2-
(phenylsulfonyl)benzene-1,3-diols 9 (Scheme 4).
Scheme 4
a) 1. 4 mol-equiv. of PhSO2CH2Li/THF, ꢀ 788 to ꢀ 58 (3 h); 2. 4 mol-equiv. of BuLi, ꢀ 58 to r.t. (0.5 h),
r.t. (15 h); 9a (R ¼ Me) 11%, 9b (R ¼ Ph) 71%. b) 1. 5 mol-equiv. of PhSO2CH2Li/THF, ꢀ 788 to ꢀ 58
(3 h); 2. 4 mol-equiv. of BuLi/THF, ꢀ 58 to r.t. (0.5 h), r.t. (3 h); 9c (RꢀR ¼ꢀ(CH2)4) 15%, endo-10c/
exo-10c 35% (cf. Scheme 5).
The structure of the products was evident according to their spectra, in particular,
1
their H-NMR spectra in CDCl3. Since 1,3-diol 9a (R ¼ Me) possesses Cs symmetry,
one finds, indeed, for the Me groups two sharp s at d(H) 2.09 and 2.17 in a ratio of 2 :1.
Moreover, the OH group appear as one sharp s at d(H) 8.85 indicating intramolecular
H-bonding with one of the O-atoms of the two sulfonyl groups. The other two
resorcinols, 9 (R ¼ Ph) and 9 (R ꢀ R ¼ ꢀ(CH2)4 ꢀ ), show both two sharp s for their
OH groups, whereby those of 9b appear at d(H) 9.75 and 7.681) and those of 9c at d(H)
8.88 and 8.71. The structures of 9a and 9b were finally established by an X-ray
diffraction analysis of suitable crystals. The found OꢀH ··· OS distances in the crystals
are listed in Table 1. In addition, one OH group in molecule A of 9a forms an
intermolecular H-bond with one of the sulfonyl O-atoms of a neighboring molecule B,
thereby linking the A and B molecules of 9a into dimer pairs. Similarly in 9b, where one
OH group forms a weak intermolecular H-bond with a sulfonyl O-atom of a
neighboring molecule, thus linking the molecules of 9b into centrosymmetric dimers.
The formation of 5,6,7,8-tetrahydro-4-methyl-2-(phenylsulfonyl)naphthalene-1,3-
diol (9c) by the established treatment of 4,5,6,7-tetrahydro-2-methyl-2-(phenylsul-
fonyl)-1H-indene-1,3(2H)-dione (8c) was accompanied to an appreciable amount by a
pair of diastereoisomers (Schemes 4 and 5). The main isomer could be purified and
crystallized, so that its structure could be characterized as rel-(3aR,7aS,8R)-4,5,6,7-
tetrahydro-8-methyl-2-(phenylsulfonyl)-3-[(phenylsulfonyl)methyl]-3a,7a-methano-
1H-inden-1-one (endo-10c) by an X-ray diffraction analysis (Fig.). It is of interest to
note that the cyclohexane ring is disordered in that CH2(5) and CH2(6) each occupy
two positions (Fig., a and b) representing alternate twist forms of the cyclohexane ring.
1
)
Responsible for the observed shift difference of the OH signals is without doubt the Ph group in o-
and p-position to the OH groups of 9b, which shields the signal of o-OH and deshields that of p-OH.

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Table 1. H-Bonding in the Crystals of 9a and 9ba)
H Bonding (d [pm])
9a
9b
O(1)ꢀH ··· O(1)S
O(1)ꢀH ··· O(1)S’
O(3)ꢀH ··· O(2)S
O(1)ꢀH ··· O(1)S’
O’(1)ꢀH ··· O(1)S’
O’(3)ꢀH ··· O(2)S’
202(3)
198(3)
248(3)
186(3)
180(3)
225(3)
196(3)
169(4)
a) Primed atoms refer to the molecule in the following symmetry related position.
The approximate relative site occupation factors of the two conformations are
0.75 :0.252).
The reaction of 8c with lithium (phenylsulfonyl)methanide under varying
conditions gave some further new products, which cast some light on the reactivity of
the reactant (Scheme 5). Without the addition of BuLi, we found as sole product the
ring-opened form 12c. Much more interesting was the result of the reaction of 8c with a
minimum excess of the lithium methanide, followed by a reduced amount of BuLi. In
this case, we isolated rel-(3aR,7aR)-3a,4,5,6,7,7a-hexahydro-3-hydroxy-2-(phenylsul-
fonyl)-3a-[(1S)-1-(phenylsulfonyl)ethyl]- 1H-inden-1-one (11c) in a yield of 86%. The
structure of 11c was assigned on the basis of its analytical data (1H- and 13C-NMR, and
MS). The weak point is the assignment of the relative configuration of the 1-
(phenylsulfonyl)ethyl group at C(3a). However, AM1 calculations showed the
indicated rel-(1S)-configuration to be by 0.9 kcal molꢀ1 more stable in comparison to
the rel-(1R)-configuration3). Therefore, we believe that the side chain at C(3a) is rel-
(1S)-configured. The similarity of 11c with the intermediate 5, which we found in the
benzo-anellation reaction of heptalene-1,2-dicarboxylate 3 (Scheme 2), gave us the
certainty that compounds of type 11c are the crucial intermediates for the formation of
resorcinols 9 from cyclopent-4-ene-1,3-diones 8 on treatment with PhSO2CH2Li/BuLi
(Scheme 4). Indeed, the reaction of 11c with BuLi gave the corresponding tetrahy-
2
)
AM1 Calculations of the basic structure of endo-10c, i.e., of ((3aS,7aR,8S)-4,5,6,7-tetrahydro-8-
methyl-3a,7a-methano-1H-inden-1-one, show that the (ꢀ)-sc conformation at C(5)ꢀC(6) is slightly
more stable (ꢀ0.10 kcal molꢀ1) than the (þ)-sc conformation in contrast to the X-ray crystal
structures with the reverse observation (cf. Fig., a and b).
We found no relevant indication for the presence of the tautomeric form of 11c, i.e., of rel-
(3aR,7aR)-3a,4,5,6,7,7a-hexahydro-3-hydroxy-2-(phenylsulfonyl)-7a-[(1S)-1-(phenylsulfonyl)ethyl]-
1H-inden-1-one. AM1 Calculations showed this tautomer to be 3.5 kcal molꢀ1 above the DHf0 value
of 11c.
3
)

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Scheme 5
a) See Scheme 4. b) 1. 3 Mol-equiv. of PhSO2CH2Li/THF, ꢀ 788 to ꢀ 58 (2 h); 2. 3 mol-equiv. of BuLi,
ꢀ 58 to r.t. (2 h). c) 4 mol-equiv. of BuLi/THF, 08 to 408 (1 h). d) 3 mol-equiv. of PhSO2CH2Li/THF,
ꢀ 788 to 08 (3 h).
dronaphthalene-1,3-diol 9c (Scheme 5), however, in a yield less satisfying as in the case
of 5 ! 44).
Taking all results together, it can be said that in the first step of the resorcinol
formation, the 1,3-diones 8 are (phenylsulfonyl)methylated at one of their C¼O
groups (demonstrated by 8c ! A in Scheme 6). The next step needs BuLi as a strong
base for the deprotonation of the introduced (phenylsulfonyl)methyl substituent,
which induces ring opening and a new ring closure under formation of B. The thus
formed 5,5-disubstituted cyclopentadiene substructure undergoes a charge-driven
suprafacial [1,5]-C shift of the 1-(phenylsulfonyl)ethyl substituent under formation
of dilithium 3a,5,6,7-tetrahydro-2-(phenylsulfonyl)-3a-[1-(phenylsulfonyl)ethyl]-4aH-
indene-1,3-diolate (C). Under the electronic ꢂpressureꢃ of two olate groups at the
cyclopentadiene part, a 5 ! 6-ring enlargement takes place under extrusion of
benzenesulfinate5). The primarily formed cyclohexa-2,5-dien-1-one structure, i.e.,
lithium 1,4,5,6,7,8-hexahydro-1-methyl-4-oxo-3-(phenylsulfonyl)naphthalen-2-olate, is
stabilized by deprotonation to yield the dilithium dianion of 9c and finally 9c itself by
neutralization (Scheme 6).
4
)
)
None of the described reactions in this work has systematically been optimized.
To the utmost, the [1,2]-C shift could be the result of a forgoing carbene formation by loss of
benzenesulfinate.
5

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Figure. a) Stereoscopic view of the X-ray crystal structure of the main conformer (75%) of rel-
(3aR,7aS,8R)-4,5,6,7-tetrahydro-8-methyl-2-(phenylsulfonyl)-3-[(phenylsulfonyl)methyl]-3a,7a-methan-
1H-inden-1-one (endo-10c; 50% probability ellipsoids). b) Stereoscopic view of the X-ray crystal structure
of the minor conformer (25%) of endo-10c (50% probability ellipsoids)
Most interesting is the formation of endo- and exo-10c. There is little doubt that
their source is the bis[(phenylsulfonyl)methyl]ated intermediate D, which rearranges
in the presence of BuLi in analogy to B ! C to lithium 3a,5,6,7-tetrahydro-2-
(phenylsulfonyl)-3a-(1-(phenylsulfonyl)ethyl)-3-((phenylsulfonyl)methyl)-4aH-inden-
1-olate (E)). In contrast to its analog C, E carries only one enolate group, but just at the
right position to induce the indicated intramolecular nucleophilic three-center
substitution reaction yielding endo- and exo-10c. The appearance of both stereoisomers
in the reaction mixture indicates that intermediate E must also be built in rel-(R,R)-
and rel-(R,S)-form.
We demonstrated that the benzo-anellation procedure of heptalenedicarboxylates
can in a variation also be applied to 2,3-disubstituted maleic anhydrides for the
synthesis of correspondingly substituted resorcinols. On the other hand, this new
procedure cannot be applied to the cyclic anhydrides of heptalene-1,2- or -4,5-

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Scheme 6
dicarboxylic acids, since they exist under thermal conditions as heptaleno[4,5-c]furan-
1,3-diones, i.e., with a twisted C(4)ꢀC(5) bond [5]. This fact leads to the situation that
C(3)¼O can indeed preferentially be phenylsulfonylmethylated, however, the further
methylation step (MeI/K2CO3) causes ring-opening to corresponding methyl 4-[2-
(phenylsulfonyl)acetyl]heptalene-5-carboxylates.
We are thankful to Dr. A. Linden for the crystal-structure determinations, to our NMR laboratory
for NMR measurements, and to our MS laboratory for mass spectra. Financial support of this work by the
Swiss National Science Foundation is gratefully acknowledged.
Experimental Part
General. See [1][6].
1. Formation of the 4,5-Disubstituted 2-Methyl-2-(phenylsulfonyl)cyclopent-4-ene-1,3-diones 8. 1.1. 5-
Hydroxy-3,4-dimethyl-5-[(phenylsulfonyl)methyl]furan-2(5H)-one (7a). To a soln. of (methylsulfonyl)-
benzene (3.472 g, 22.22 mmol) in THF (40 ml) at 08, 2.5m BuLi in hexane (8.90 ml, 22.22 mmol) was
added dropwise, whereby a colorless precipitate of PhSO2CH2Li was formed. After 30 min stirring at 08,
the mixture was cooled to ꢀ 788, and a soln. of 6a (1.528 g, 12.12 mmol) in THF (5 ml) was added

Helvetica Chimica Acta – Vol. 96 (2013)
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dropwise. After some time at ꢀ 788 to ꢀ 608, nearly all precipitate of PhSO2CH2Li had been dissolved.
Then, ice was added, and the org. matter extracted with AcOEt, and the combined AcOEt extract
washed once with aq. 2n HCl (100 ml) and then several times with brine, dried (Na2SO4), and
concentrated. The colorless crystalline residue was washed with Et2O to remove residual (methylsulfo-
nyl)benzene to yield 1.75 g (77%) of 7a. Colorless, microcrystalline powder. M.p. 148.0 – 148.58. Rf
1
2
(AcOEt/hexane 3 :2) 0.34. H-NMR (CHCl3 at d(H) 7.26): 8.0 – 7.6 (m, PhSO2); 3.74, 3.42 (AB, JAB
¼
5
5
14.85, CH2ꢀC(5)); 1.965 (d-like, J(MeꢀC(3),MeꢀC(4)) ¼ 1.18, MeꢀC(3)); 1.762 (d-like, J(MeꢀC(4),
MeꢀC(3)) ¼ 1.18, MeꢀC(4)). 13C-NMR (CDCl3 at d(C) 76.92): 155.52 (C(2)); 139.10 (C(4)); 134.47,
129.21, 128.43 (Cp, Cm, Co of PhSO2; Cipso not recognizable); 126.54 (C(3)); 101.72 (C(5)); 60.03
(CH2ꢀC(5)); 10.52 (MeꢀC(4)); 8.45 (MeꢀC(3)).
1.2. 5-Hydroxy-3,4-diphenyl-5-[(phenylsulfonyl)methyl]furan-2(5H)-one (7b). As described in 1.1,
with 6b (2.00 g, 8.00 mmol), (methylsulfonyl)benzene (2.50 g, 16.0 mmol), and 2.5m BuLi (6.4 ml,
16.0 mmol): 2.50 g (77%) 7b. Colorless powder. M.p. 183 – 1848. Rf (AcOEt/hexane 3 :2) 0.59. 1H-NMR
(CHCl3 at d(H) 7.25): 8.1 – 7.6 (m, PhSO2) ; 7.5 – 7.2 ( m, PhꢀC(3), PhꢀC(4)); 6.54 (br. s, OHꢀC(5)); 3.66,
3.52 (AB, 2JAB ¼ 15.9, CH2ꢀC(5)). 13C-NMR (CDCl3 at d(C) 76.90): 168.24 (C(2)); 155.03 (C(4)); 139.21,
134.52, 130.38 (Cipso, Cp, Cm of PhSO2; Co not recognizable); 129.50 (C(3)); 129.34 – 128.37 (PhꢀC(3),
PhꢀC(4)); 101.54 (C(5)); 60.70 (CH2ꢀC(5)).
1.3. 4,5,6,7-Tetrahydro-3-hydroxy-3-[(phenylsulfonyl)methyl]isobenzofuran-1(3H)-one (7c). As
described in 1.1, with 6c (0.517 g, 3.40 mmol), 1.5 mol-equiv. of (methylsulfonyl)benzene, and 2.5m
BuLi: 0.77 g (74%) of 7c. Colorless powder. Rf (AcOEt/hexane 3 :2) 0.36. IR (KBr): 3354s (br.,
1
OH), 1754s (C¼O), 1688 (C¼C). H-NMR (CHCl3 at d(H) 7.26): 8.05 – 7.55 (m, PhSO2); 5.98 (br. s,
2
OHꢀC(3)); 3.73, 3.46 (AB, JAB ¼ 14.88, CH2ꢀC(3)); 2.50 – 1.55 (m, 8 H, CH2(4) to CH2(7)).
Treatment of 7c with HCl/MeOH at r.t. gave the MeOꢀC(3) derivative of 7c as colorless powder
(89%). Rf (AcOEt/hexane 3 :2) 0.58. 1H-NMR (CHCl3 at d(H) 7.27): 7.9 – 7.5 (m, PhSO2); 3.89, 3.67 (AB,
2JAB ¼ 14.98, CH2ꢀC(3)); 3.04 (s, MeOꢀC(3)); 2.5 – 1.7 (m, 8 H, CH2(4) to CH2(7)). 13C-NMR (CDCl3 at
d(C) 76.95): 168.88 (C(1)); 158.05 (C(3a)); 139.28, 134.03, 129.22, 127.99 (Cipso, Cp, Cm, Co of PhSO2);
132.38 (C(7a)); 104.60 (C(3)); 59.44 (CH2ꢀC(3)); 49.62 (MeOꢀC(3)); 22.39 (C(7)); 21.19 (C(4)); 21.05
(C(5)); 19.93 (C(6)).
1.4. 2,4,5-Trimethyl-2-(phenylsulfonyl)cyclopent-4-ene-1,3-dione (8a). To a soln. of 7a (0.200 g,
0.708 mmol) in dry acetone (10 ml), K2CO3 (1.0 g, 7.24 mmol) was added. The mixture was stirred for
30 min at 08, and MeI (1.0 ml, 16.0 mmol) was added. After 2 h, the mixture was replenished with further
MeI (1.5 ml, 24.0 mmol) and stirring continued at r.t. for 4 h. Workup as described in 1.1 and
crystallization from CH2Cl2/Et2O gave 0.88 g (89%) of 8a. Colorless crystals.
M.p. 192 – 1938. Rf (AcOEt/hexane 3 :2) 0.60. 1H-NMR (CHCl3 at d(H) 7.27): 7.77 – 7.54 (m, PhSO2);
2.05 (s, MeꢀC(4), MeꢀC(5)); 1.53 (s, MeꢀC(2)). 13C-NMR (CDCl3 at d(C) 76.92): 194.73 (C(1),C(3));
156.85 (C(4),C(5)); 135.13, 134.65, 130.25, 128.88 (Cipso, Cp, Cm, Co of PhSO2)); 70.23 (C(2)); 13.57
.
.
(MeꢀC(2)); 9.69 (MeꢀC(4), MeꢀC(5)). EI-MS: 278 (13, Mþ ), 141 (54, [M ꢀ PhSO2]þ), 77 (100, Phþ ).
1.5. 2-Methyl-4,5-diphenyl-2-(phenylsulfonyl)cyclopent-4-ene-1,3-dione (8b). As described in 1.4,
with 7b (0.60 g, 1.48 mmol), acetone (40 ml), K2CO3 (4.0 g, 29 mmol), and MeI (5.0 ml, 0.08 mol): 8b
1
(0.514 g, 87%). Colorless powder. Rf (AcOEt/hexane 1:1) 0.60. H-NMR (CHCl3 at d(H) 7.26): 7.85 –
7.60 (m, PhSO2); 7.42 – 7.25 (m, PhꢀC(4), PhꢀC(5)); 1.74 (s, MeꢀC(2)). 13C-NMR (CDCl3 at d(C)
76.90): 193.66 (C(1), C(3)); 153.38 (C(4), C(5)); 135.35 (Cipso of PhSO2); 134.68 (Cp of PhSO2); 130.47,
130.19, 129.79, 129.13, 128.43 (PhꢀC(4), PhꢀC(5), Cm and Co of PhSO2); 128.11 (Cipso of PhꢀC(4),
PhꢀC(5)); 71.97 (C(2)); 13.38 (MeꢀC(2)).
1.6. 4,5,6,7-Tetrahydro-2-methyl-2-(phenylsulfonyl)-1H-indene-1,3(2H)-dione (8c). As described in
1.4, with 7c (0.100 g, 0.324 mmol), acetone (5 ml) K2CO3 (0.300 g, 2.17 mmol), and MeI (1.0 ml,
16.0 mmol): to yield 8c (0.90 g, 91%) Colorless crystals. M.p. 201 – 2028 (CH2Cl2/Et2O). Rf (AcOEt/
hexane 1:1) 0.47. 1H-NMR (CHCl3 at d(H) 7.26): 7.8 – 7.55 (m, PhSO2); 2.39 (sym. m, CH2(4),CH2(7));
1.70 (sym. m, CH2(5), CH2(6))); 1.56 (s, MeꢀC(2)). 13C-NMR (CDCl3 at d(C) 76.92): 193.81 (C(1),C(3));
159.67 (C(3a), C(7a)); 135.38, 134.57, 130.18, 128.91 (Cipso, Cp, Cm, Co of PhSO2); 71.65 (C(2)); 21.04
.
(C(4), C(7)); 20.67 (C(5), C(6)); 13.11 (MeꢀC(2)). EI-MS: 304 (11, Mþ ), 179 (21), 163 (23), 141 (53,
.
[M ꢀ PhSO2]þ), 77 (100, Phþ ).

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2. Formation of the 2-(Phenylsulfonyl)resorcinols (¼2-(Phenylsulfonyl)benzene-1,3-diols) 9. 2.1.
4,5,6-Trimethyl-2-(phenylsulfonyl)benzene-1,3-diol (9a). As described in 1.1, PhSO2CH2Li was prepared
from (methylsulfonyl)benzene (0.180 g, 1.15 mmol) at ꢀ 58 in THF (4 ml). At ꢀ 788, 8a (0.080 g,
0.287 mmol) was added, followed by 2m BuLi (0.574 ml, 1.435 mmol). The temp. was raised to r.t., and
stirring was continued for 12 h. After usual workup, the residue of the AcOEt extracts was subjected to
CC (silica gel, AcOEt/hexane 3 :2): 9a (9 mg, 11%). Colorless powder. M.p. 168 – 171.38 (after CC
without recryst.). Rf (AcOEt/hexane 1:1) 0.79. 1H-NMR (300 MHz, CDCl3; CHCl3 at d(H) 7.26): 8.85 (s,
OHꢀC(1), OHꢀ(3)); 7.94 (d-like, Jo ¼ 8, Ho of PhSO2); 7.62 (t-like, Jo ꢁ 7.5, Hp of PhSO2); 7.53 (t-like, Jo ¼
8, Hm of PhSO2); 2.17 (s, MeꢀC(5)); 2.09 (s, MeꢀC(4), Meꢀ(6)).
The structure of 9a was finally established by an X-ray crystal-structure analysis of a suitable crystal
obtained from Et2O (Tables 1 and 2).
2.2. 4-Methyl-5,6-diphenyl-2-(phenylsulfonyl)benzene-1,3-diol (¼6’-Methyl-4’-(phenylsulfonyl)-
[1,1’:2’,1’’-terphenyl]-3’,5’-diol; 9b). As described in 2.1 (same molar amounts): 9b (0.074 g, 71%) after
crystallization from CH2Cl2/Et2O. Colorless crystals. M.p. 173.5 – 174.28. Rf (AcOEt/hexane 1:1) 0.68.
1H-NMR (300 MHz, CDCl3; CHCl3 at d(H) 7.25): 9.75, 7.68 (2s, OHꢀC(3’), OHꢀC(5’)); 8.05 (d-like, Jo ¼
8, Ho of PhSO2); 7.67 (t-like, Jo ¼ 7, Hp of PhSO2); 7.56 (t-like, Jo ¼ 7, Hm of PhSO2); 7.17 – 7.06 (m, 6 H,
PhꢀC(1’), PhꢀC(2’)); 6.95 – 6.87 (m, 4 H, PhꢀC(1’), PhꢀC(2’)); 1.93 (s, MeꢀC(6’)); most probable: 6.93
(d with f.s., Jo ¼ 7.8, Ho of PhꢀC(1’)); 6.89 (d with f.s., Jo ¼ 7.8, PhꢀC(2’)). 13C-NMR (CDCl3; CDCl3 at
d(C) 76.90): 153.61 (C(5’)); 150.02 (C(3’)); 141.55 (Cipso of PhSO2); 138.70 (Cipso of PhꢀC(1’)); 134.73
(Cipso of PhꢀC(2’’)); 133.90 (Cp of PhSO2); 131.02 – 126.72 (CH of PhSO2, PhꢀC(1’), PhꢀC(2’)); 121.92
(C(2’)); 117.58 (C(6’)); 108.42 (C(4’)); 13.17 MeꢀC(6’)).
The structure of 9b was finally established by an X-ray crystal-structure analysis (Tables 1 and 2).
2.3. 5,6,7,8-Tetrahydro-4-methyl-2-(phenylsulfonyl)naphthalene-1,3-diol (9c). As described in 2.1,
with 8c (0.076 g, 0.25 mmol) and PhSO2CH2Li (generated from (methylsulfonyl)benzene (0.156 g,
1.0 mmol) at ꢀ 788 and 2m Buli (0.375 ml, 1.0 mmol)) in THF (15 ml) at ꢀ58 to r.t. then, additional 2m
BuLi (0.375 ml, 1.0 mmol) was added and the temp. finally brought to r.t. After 15 h stirring and usual
workup, CC (silica gel, AcOEt/hexane 3 :2) gave 9c as colorless powder (12 mg, 15%) and endo-10c/exo-
10c 4 :1, from which pure endo-10c (0.031g, 28%) was obtained by crystallization (CH2Cl2/Et2O).
1
Data of 9c: M.p. 183 – 186.58 (after CC without recryst.). Rf (AcOEt/hexane 1:1) 0.78. H-NMR
(300 MHz, CDCl3; CHCl3 at d(H) 7.26): 8.88, 8.71 (2s, OHꢀC(1), OHꢀC(3)); 7.93 (d-like, Jo ¼ 7.2, Ho of
PhSO2); 7.52 (t-like, Hm of PhSO2); 7.44 (t-like, Hp of PhSO2); 2.57 (t-like, CH2(5), CH2(8)); 2.01 (s,
MeꢀC(4)); 1.72 (q-like, CH2(6),CH2(7)).
Data of rel-(3aR,7aS,8R)-4,5,6,7-Tetrahydro-8-methyl-2-(phenylsulfonyl)-3-[(phenylsulfonyl)-
1
methyl]-3a,7a-methano-1H-inden-1-one (endo-10c): H-NMR (300 MHz, CDCl3; CHCl3 at d(H) 7.27):
8.15 – 7.50 (m, H of 2 PhSO2); 5.90, 4.25 (AB, 2JAB ¼ 12.3, PhSO2CH2ꢀC(1)); 2.4 – 2.2 (m, 3 H); 1.69 (q,
3J ¼ 6.6, HꢀC(8)); 1.65 – 1.20 (m, 5 H); 1.16 (d, 3J ¼ 6.5, MeꢀC(8)).
The structure of endo-10c was finally established by an X-ray crystal-structure analysis (Fig., Table 2).
Data of rel-(3aR,7aS,8S)-4,5,6,7-Tetrahydro-8-methyl-2-(phenylsulfonyl)-3-[(phenylsulfonyl)-
methyl]-3a,7a-methano-1H-inden-1-one (exo-10c): 1H-NMR (300 MHz, CDCl3; in the presence of
80% endo-10c; recognizable signals): 8.25 (d-like, Jo ¼ 7.2, Ho of PhSO2ꢀC(2)); 5.88, 4.22 (AB, 2JAB ¼ 12.0,
3
PhSO2CH2ꢀC(1)); 0.94 (d, J ¼ 6.5, MeꢀC(8)).
3. Experiments with 4,5,6,7-Tetrahydro-2-methyl-2-(phenylsulfonyl)-1H-indene-1,3(2H)-dione (8c).
3.1. 1-{2-[(1Z)-1-Hydroxy-2-(phenylsulfonyl)ethenyl])cyclohex-1-en-1-yl}-2-(phenylsulfonyl)propan-1-
one (12c). A soln. of 8c (0.130 g, 0.43 mmol) in THF (15 ml), cooled to ꢀ 788, was treated with
PhSO2CH2Li (generated from (methylsulfonyl)benzene (0.200 g, 1.28 mmol) and 2.5m BuLi (0.70 ml,
1.67 mmol) in the usual manner (cf. 1.1)). The mixture was warmed to 08 and stirred for 3 h.
The formed white precipitate was filtered off and washed with Et2O (20 ml). Evaporation of the
Et2O filtrate delivered 12c (0.055g, 41%). Colorless powder. Rf (AcOEt/hexane 3 :2) 0.43. 1H-NMR
(CHCl3 at d(H) 7.26): 8.0 – 7.5 (2 PhSO2); 4.75 (s, HꢀC(2’’)); 4.56 (s, OHꢀC(1’’)); 3.62 (q,
3J(HꢀC(2’),MeꢀC(2’)) ¼ 7.0, HꢀC(2’)); 2.50 (qt-like, CH2(3)); 2.14 (sym. m, CH2(6)); 1.80 – 1.57 (m,
CH2(4), CH2(5)); 1.47 (d, 3J(MeꢀC(2’),HꢀC(2’)) ¼ 7.0, MeꢀC(2’)). 13C-NMR (CDCl3 at d(C) 76.90):
191.77 (C(1’)); 171.99 (C(1’’)); 141.08 (C(2)); 138.16, 138.04 (Cipso of PhSO2ꢀC(2’,2’’)); 134.21, 134.07 (Cp
of PhSO2ꢀC(2’), PhSO2ꢀC(2’’)); 129.39, 129.29 (Cm of PhSO2ꢀC(2’), PhSO2(2’’)); 128.84, 128.38 (Co of

Helvetica Chimica Acta – Vol. 96 (2013)
1927
PhSO2ꢀC(2’) and PhSO2(2’’)); 80.42 (C(1)); 70.87 (C(2’)); 63.14 (C(2’’)); 23.32, 21.51, 20.58, 20.00 (C(3)
.
.
to C(6)); 11.89 (MeꢀC(2’)). EI-MS: 460 (21, Mþ ), 443 (32, [M ꢀ OH]þ), 442 (18, [M ꢀ H2O]þ ), 396
.
.
.
(100, [M ꢀ SO2]þ ), 332 (30, [M ꢀ 2 SO2]þ ). CI-MS: 478 (100, [M þ NH4]þ), 460 (8, Mþ ).
3.2. rel-(3aR,7aR)-3a,4,5,6,7,7a-Hexahydro-3-hydroxy-2-(phenylsulfonyl)-3a-((1S)-1-(phenylsulfo-
nyl)ethyl)-1H-inden-1-one (11c). PhSO2CH2Li was formed at 08 from (methylsulfonyl)benzene
(0.308 g, 1.98 mmol) in THF (15 ml) with 2.5m BuLi (1.05 ml, 2.65 mmol). After cooling to ꢀ 788, a
soln. of 8c (0.200 g, 0.66 mmol) in THF (15 ml) was added dropwise. Stirring of the mixture was
continued for 3 h, and the temp. increased again to 08. Then 2.5m BuLi (0.79 ml, 1.98 mmol) was added
dropwise, (yellow mixture ! dark orange). After 1 h stirring, the mixture became turbid and a white
precipitation was formed. Ice was added, followed by the usual workup procedure with CH2Cl2 for the
extraction. The thus obtained residue was crystallized from CH2Cl2/Et2O: Colorless crystals. 11c (0.261 g,
86%). M.p. 174.3 – 175.28. Rf (AcOEt/hexane 3 :2) 0.0. 1H-NMR (300 MHz, CDCl3; CHCl3 at d(H) 7.26):
11.25 (OHꢀC(3)); 8.01 (d-like, Jo ¼ 8.1, Ho of PhSO2ꢀC(2)); 7.81 (d-like, Jo ¼ 7.9, Ho of PhSO2CH-
(Me)ꢀC(3a)); 7.68 – 7.63 (m, Hp of both PhSO2)); 7.58 – 7.51 (m, Hm of both PhSO2)); 3.75 (t-like, 3J ¼ 4.6
and 3.3, HꢀC(7a)); 3.35 (q, 3J(H, Me) ¼ 7.0, PhSO2CH(Me)ꢀC(3a)); 2.65 (td, 3J(HaxꢀC(7), Hax
ꢀ
2
C(6)) ꢁ J(Heq ꢀ C(7),HaxꢀC(7)) ¼ 13.8, 3J(HaxꢀC(7),HꢀC(7a)) ¼ 4.6, HaxꢀC(7)); 2.3 – 2.1 (m, 2 H);
1.73 – 1.40 (m, 3 H)); 1.40 – 1.20 (m, 1 H); 0.98 – 0.80 (m, 1 H); 0.72 (d, 3J((Me, H) ¼ 7.0, PhSO2CH-
(Me)ꢀC(3a)). 13C-NMR (75 MHz, CDCl3; CDCl3 at d(C) 76.91): 198.89 (C(1)); 195.37 (C(3)); 139.45
(Cipso of PhSO2ꢀC(2)); 139.10 (Cipso of PhSO2CH(Me)ꢀC(3a)); 134.18 (Cp of PhSO2ꢀC(2)); 133.73 (Cp of
PhSO2CH(Me)ꢀC(3a)); 129.16, 129.10 (Cm of both PhSO2); 128.16 (Co of PhSO2ꢀC(2)); 127.45 (Co of
PhSO2CH(Me)ꢀC(3a)); 115.36 (C(2)); 62.68 (PhSO2CH(Me)ꢀC(3a)); 53.14 (C(3a)); 41.38 (C(7));
24.48 (C(4)); 20.37 (C(7)); 16.80 (C(5)); 16.33 (C(6)); 11.47 (PhSO2CH(Me)ꢀC(3a)). EI-MS: 460 (1.8,
Mþ), 396 (6.6, [M ꢀ SO2]þ), 319 (64, [M ꢀ PhSO2]þ), 291 (12, [M ꢀ PhSO2CH(Me)]þ), 246 (10), 231
.
(5.0), 177 (9.6); (100, Phþ ).
3.2.1. Rearrangement of 11c. A soln. of 11c (0.030 g, 0.065 mmol) in THF (5 ml) was cooled to 08.
2.5m BuLi (0.13 ml, 0.325 mmol) was added. Under stirring, the temp. was increased within 1h to 408. The
usual workup delivered 9c (5 mg, 24%).
4. Crystal-Structure Determinations of 9a, 9b, and endo-10c (Tables 1 and 2, Fig., a and b)6). All
measurements were made with a Rigaku AFC5R diffractometer with graphite-monochromated MoKa
radiation (l 0.71069 ꢅ) and a rotating anode generator. All three structures were solved and refined
successfully with no unusual features.
Benzene-1,3-diol 9a: There are two symmetry-independent molecules in the asymmetric unit,
however, there are no significant conformational differences between the molecules. Each OH group in
each symmetry-independent molecule forms an intramolecular H-bond with an adjacent sulfonyl O-
atom. In addition, one OH group in molecule A forms an intermolecular H-bond with one of the sulfonyl
O-atoms of a neighboring molecule B, thereby linking the A and B molecules into dimeric pairs
(Table 1).
Benzene-1,3-diol 9b: Similar by to 9a, each OH group forms an intramolecular H-bond with one of
the adjacent sulfonyl O-atoms. Additionally, one OH group forms a weak intermolecular H-bond with a
sulfonyl O-atom of a neighboring molecule, thus linking molecules into centrosymmetric dimers
(Table 1).
Tricyclic endo-10c: Since the space group is centrosymmetric, the crystals are racemic. The
cyclopropane ring is fused to the common bond between the cyclohexane and cyclopentene rings. The
cyclohexane ring is disordered in that two adjacent methylene C-atoms each occupy two positions
representing alternate twist forms of the ring (Fig., a and b). The disordered sites were successfully
resolved and refined satisfactorily. The approximate relative site occupation factors of the two
conformations are 0.75 :0.252). Due to the relative small amount of the minor conformer, the geometry of
the minor conformation is less than ideal, and the corresponding geometric parameters have large
standards uncertainties.
6
)
CCDC-941510 – 941512 contain the supplementary crystallographic data for this article. These data
can be obtained free of charge from the Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data request/cif.

1928
Helvetica Chimica Acta – Vol. 96 (2013)
Table 2. Crystallographic Data for Compounds 9a, 9b, and endo-10c
9a
9b
endo-10c
Crystallized from
Empirical formula
Mr
Et2O
C15H16O4S
292.35
Et2O
C25H20O4S
416.49
CH2Cl2/Et2O
C24H24O5S2
456.57
Crystal color, habit
Crystal dimensions [mm]
Temperature [K]
colorless, prism
0.20 ꢂ 0.20 ꢂ 0.55
173(1)
colorless, prism
0.18 ꢂ 0.32 ꢂ 0.38
173(1)
pale yellow, prism
0.40 ꢂ 0.43 ꢂ 0.60
173(1)
Crystal system
Space group
Z
triclinic
P1 (#2)
4a)
monoclinic
P21/n (#14)
4
monoclinic
P21/n (#14)
4
¯
Reflections for cell determination
25
25
25
2q Range for cell determination [8]
24 – 26
24 – 26
24 – 26
Unit cell parameters:
a [ꢅ]
b [ꢅ]
c [ꢅ]
a [8]
b [8]
10.559(2)
16.713(2)
7.679(2)
93.65(1)
66.44(2)
89.39(1)
1343.9(4)
616
11.953(3)
9.411(4)
18.058(4)
90
97.52(2)
90
2014(1)
872
1.373
0.191
w/2q
11.219(2)
10.158(2)
19.178(3)
90
98.10(2)
90
2163.7(7)
960
1.401
0.280
w/2q
g [8]
V [ꢅ3]
F(000)
Dx [g/cmꢀ3
]
1.445
0.251
w/2q
m(MoKa) [mmꢀ1
Scan type
]
2q(max) [8]
55
50
50
Total reflections measured
Symmetry-indepedent reflections
Rint
Reflections used (I > 2s(I))
Parameters refined
Reflection/parameter ratio
Final R
wR
Weightsb)
Goodness of fit
6499
6166
0.022
4819
378
12.7
0.0527
0.0560
0.005
3969
3538
0.038
2683
279
4262
3807
0.028
3188
298
9.62
10.7
0.0418
0.0420
0.005
1.991
0.0454
0.0478
0.005
2.699
2.601
Secondary extinction coefficient
Final Dmax/s
3.0(7) · 10ꢀ7
0.0002
0.63; ꢀ 0.47
0.003 – 0.005
0.0003
0.0003
D1 (max; min) [e ꢅꢀ3
s(d(CꢀC)) [ꢅ]
]
0.24; ꢀ 0.31
0.70; ꢀ 0.38
0.003 – 0.004
0.004 – 0.03
b
a) Two formula units per asymmetric unit. ) p in w ¼ [s2(Fo) þ (pFo)2]ꢀ1
.
REFERENCES
[1] K. Abou-Hadeed, H.-J. Hansen, Helv. Chim. Acta 1997, 80, 2535.
[2] K. Abou-Hadeed, H.-J. Hansen, in ꢂScience of Synthesisꢃ, Georg Thieme Verlag KG, StuttgartꢀNew
York, 2010, Vol. 45b, p. 1043.
[3] M. Lutz, A. Linden, K. Abou-Hadeed, H.-J. Hansen, Helv. Chim. Acta 1999, 82, 372.
[4] K. Abou-Hadeed, Chimia 2000, 54, 760.

Helvetica Chimica Acta – Vol. 96 (2013)
1929
[5] R. H. Weber, P. Brꢁgger, T. A. Jenny, H.-J. Hansen, Helv. Chim. Acta 1987, 70, 742.
[6] K. Abou-Hadeed, H.-J. Hansen, Helv. Chim. Acta 2003, 86, 4018.
Received May 31, 2013