Reductive elimination of phenylsulfonyl groups in the 3-position of benzo[a]heptalene-2,4-diols

Article abstract of DOI:10.1002/hlca.200590080

3-(Phenylsulfonyl)benzo[a]heptalene-2,4-diols 1 can be desulfonylated with an excess of LiAlH₄/MeLi · LiBr in boiling THF in good yields (Scheme 6). When the reaction is run with LiAlH₄/MeLi, mainly the 3,3′-disulfides 6 of the corresponding 2,4-dihydroxybenzo[a]heptalene-3- thiols are formed after workup (Scheme T). However, the best yields of desulfonylated products are obtained when the 2,4-dimethoxy-substituted benzo[a]heptalenes 2 are reduced with an excess of LiAlH₄/TiCl ₄ at - 78 → 20° in THF (Scheme 10). Attempts to substitute the PhSO₂ group of 2 with freshly prepared MeONa in boiling THF led to a highly selective ether cleavage of the 4-MeO group, rather than to desulfonylation (Scheme 13).

Full text of DOI:10.1002/hlca.200590080

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Reductive Elimination of Phenylsulfonyl Groups in the 3-Position of
Benzo[a]heptalene-2,4-diols
by Mohy eldin Abdel Fattaha), Samir El Rayesa)1), El Sayed Ahmed Solimanb), Anthony Lindenc),
Khaled Abou-Hadeed*c), and Hans-Jürgen Hansen*c)
a) Faculty of Science, University of Suez Canal, Ismailia, Egypt
b) Faculty of Science, University of Ain Shams, Cairo, Egypt
c) Organisch-chemisches Institut der Universität Zürich, Winterthurerstrasse 190, CH-8057 Zürich
3-(Phenylsulfonyl)benzo[a]heptalene-2,4-diols 1 can be desulfonylated with an excess of LiAlH4/MeLi ´
LiBr in boiling THF in good yields (Scheme 6). When the reaction is run with LiAlH4/MeLi, mainly the 3,3'-
disulfides 6 of the corresponding 2,4-dihydroxybenzo[a]heptalene-3-thiols are formed after workup (Scheme 7).
However, the best yields of desulfonylated products are obtained when the 2,4-dimethoxy-substituted
benzo[a]heptalenes 2 are reduced with an excess of LiAlH4/TiCl4 at À 78 ! 208 in THF (Scheme 10). Attempts
to substitute the PhSO2 group of 2 with freshly prepared MeONa in boiling THF led to a highly selective ether
cleavage of the 4-MeOgroup, rather than to desulfonylation ( Scheme 13).
Introduction. ± Dimethyl heptalene-4,5-dicarboxylates, when reacted at À 78 to 208
with an excess of lithiomethyl sulfones in the presence of alkyl lithium (BuLi, MeLi ´
LiBr), yield in a one-pot procedure 3-(X-sulfonyl)benzo[a]heptalene-2,4-diols (X ˆ
Ph, NR2) [1 ± 3] (see also [4]), thus opening a new access to colchicinoids. However, for
the synthesis of colchicinoids, it is necessary to exchange the target X-sulfonyl group by
a MeOor other ether group. Since all attempts to replace the sulfonyl group in a
nucleophilic substitution reaction by MeOÀ failed (see below), we decided to remove
the X-sulfonyl group reductively and to add an O-functionality in a second step
(Scheme 1)2). We now report a new, highly selective cleavage reaction of diaryl
sulfones (X ˆ Ph) and aryl sulfonamides (X ˆ NR2), as present in the envisaged 3-(X-
sulfonyl)benzo[a]heptalene-2,4-diols.
Scheme 1
1
)
Part of the Ph.D. thesis of S. E. R., Suez Canal University, 2003; scholar at the University of Zurich 2000 ±
2002, with a scholarship of the Egyptian Channel Programme.
We reported on this procedure already during the autumn meeting of the Swiss Chemical Society, Zurich,
October 12, 2001 [5].
2
)
ꢀ 2005 Verlag Helvetica Chimica Acta AG, Zürich

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Results and Discussion. ± The reductive cleavage of aryl alkyl and diaryl sulfones by
alkali amalgams in the presence of protic solvents [6 ± 8], or under Birch conditions by
Na/NH3 or Li/MeNH2 [9], or electrochemically at different cathodes [10 ± 13] is a well-
established reaction known for more than 50 years3). It has been characterized as a
two-electron process, whereby, after the uptake of the first electron, CÀS fission takes
place to yield the corresponding arenesulfinate and a C-radical, which is reduced by the
second electron to the carbanion (Scheme 2). The carbanion is then protonated or
captured by other electrophiles. It is of interest to note that sulfones unsymmetrically
substituted by s- and p-donor groups are cleaved highly selectively at the sterically
more-congested CÀS bond, which rationalizes why the fission rate (kf) is rate-
determining. Two examples of this fission selectivity of diaryl ethers are shown in
Scheme 2. Despite these favorable aspects, we were not interested to do electro-
chemistry or to work with alkali amalgams in a preparative way.
Scheme 2
A first hint that under favorable circumstances complex hydrides may also induce
CÀS bond cleavage of diaryl sulfones came from an investigation of Brown et al. who
found that the reaction of LiEt3BH (and other ꢁsuper-hydridesꢂ of this type) and
diphenyl sulfone in boiling THF gave ethylbenzene (or the corresponding alkylben-
zenes) and lithium phenylsulfinate as cleavage products (Scheme 3) [15].
Scheme 3
Since an Et group is biochemically isosteric with a MeOgroup, we tried to react 3-
(phenylsulfonyl)benzo[a]heptalene-2,4-diol (1a), without further protection, with
LiEt3BH (10 equiv.; to account for the free OH groups), as shown in Scheme 4.
However, 1a was recovered almost quantitatively. When we performed the reaction
3
)
The reductive cleavage of Ph2SO2 was first realized with Raney-Ni in boiling EtOH more than 60 years ago
[14]. However, it can be assumed that the reduction starts, in this case, at the S-atom (see below).

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with the dimethoxy derivative 2a, we were surprised to observe an excellent
demethylation reaction of the ether functions, but no desulfonylation at all. The
situation did not change when 1a was first deprotonated with NaH in THF, and then
treated with LiEt3BH. When we used the same procedure as before, but added at the
end BuLi (10 mol-equiv.) in two portions, this being a strong base and promoter for
alkanide or hydride transfer, the desulfonylated product 3a was formed in acceptable
yield (45%), together with a small quantity of the envisaged 3-ethylated benzo[a]-
heptalene-2,4-diol 4a (Scheme 5).
Scheme 4
Scheme 5
Since the presence of LiEt3BH did not lead to a significant yield of 4a, we
4
substituted the reagent by a large excess of LiAlH4 ) and used the MeLi ´ LiBr complex
‡
as the promoting agent for reduction, and to keep the Li concentration, a weak Lewis
acid, as high as possible. These conditions, indeed, led to good yields of the
corresponding desulfonylated products. In the case of the substrate 1a, these products
were accompanied by a small amount of deoxygenated 5a (Scheme 6). Neither LiAlH4
nor MeLi ´ LiBr alone in refluxing THF gave the results of their combined action. In the
first case, 1a was recovered unchanged, and in the second one, it was destroyed.
However, when we used a mixture of LiAlH4 and MeLi alone, the product pattern
changed substantially (Scheme 7). After workup, we found mainly the disulfides 6 of
the corresponding 3-(sulfanyl)benzo[a]heptalene-2,4-diols, accompanied, in the case of
1a, by small amounts of 3a and 5a.
4
)
It is known that LiAlH4 does not react with diphenyl sulfone [16]. However, it has been demonstrated that
cyclic four- and five-membered sulfones can be reduced with LiAlH4 in Et2Oto the corresponding thia
cycles [17].

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Scheme 6
The reduction of N,N-dialkylsulfonamides by LiAlH4 to the corresponding thiols is
well-established [18]. The formation of 6a from 1d, therefore, offers no new aspects. It
has also been reported that complex hydrides such as DIBAL (diisobutylaluminum
hydride) are able to reduce alkyl aryl sulfones or diaryl sulfones at temperatures > 1008
in toluene/hexane to the corresponding sulfides [19]. It seems reasonable, therefore, to
assume that under our conditions the phenyl sulfones 6a and 6b are first deoxygenated
to the phenyl thioethers, as witnessed by the presence of 5a in the reaction mixtures of
1a (Scheme 6 and 7). In the next step, the PhÀS bond is cleaved reductively to yield the
corresponding benzo[a]heptalene-3-thiolates, which are present, after workup, as the
corresponding disulfides 6, because oxygen has not been excluded during workup.
Finally, the C(3)ÀS bond of the 2,4-dioxidobenzo[a]heptalene-3-thiolates must be
cleaved reductively. We suppose that the alkyl lithium reagents (BuLi, MeLi) are
necessary for the formation of alkyl aluminum hydrides, which reduce the phenyl
sulfones to the corresponding sulfides (see above). The formed 3-(phenylsulfanyl)-
benzo[a]heptalene-2,4-diolates should be suitable bidentate ligands for the formation
of cyclic five-membered aluminum hydrido complexes. Since the phenyl ring should be
oriented parallel to the AlÀH bonds in such complexes according to an AM1
calculation of a model structure (Fig. 1,a), an intramolecular hydride transfer to Cip of
the phenyl ring can occur, following the ꢁprinciple of least motionꢂ, thus leading at the
end to the thiolates and benzene. The 2,4-oxidobenzo[a]heptalene-3-thiolates should
again be excellent ligands for the formation of cyclic five-membered aluminum hydrido
complexes (Fig. 1,b). However, an intramolecular hydride transfer to C(3) is now
much more difficult due to the high electron density on the benzene ring. The reaction
stops, therefore, in the presence of a LiAlH4/MeLi mixture, and, after air oxidation, the
corresponding disulfides 6a and 6b, respectively, are isolated.
The situation changes in the presence of BrÀ ions, which are imported by the use of
MeLi ´ LiBr. It seems that BrÀ is necessary to induce, by nucleophilic attack on the
tetrahedral Al-atom, the intramolecular hydride transfer under formation of the
desulfonylated products 3 and sulfide ions (Scheme 6)5). The discussed mechanism of
the reduction process of 3-(phenylsulfonyl)benzo[a]heptalene-2,4-diols is summarized
in Scheme 8.
5
)
The smell of H2S was recognized after acidification of the reaction mixtures.

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Fig. 1. DFT-Calculated structures of binary aluminum hydrido complexes of a) 2-(phenylthio)benzene-1,3-
diolate and b) 1,3-dioxidobenzene-2-thiolate as model compounds for the reduction of 2 with LiAlH4
Scheme 8
Several years ago, Akgün et al. reported that the inertness of diphenyl sulfone
against LiAlH4 can be overcome in the presence of TiCl4 [20]. At low temperature, it is
reduced by a preformed 2 :1 mixture of LiAlH4/TiCl4 to the diphenyl sulfide in
excellent yield (Scheme 9). The formation of diphenyl sulfide under these conditions
encouraged us to run the reduction with the dimethyl ethers 2 of our sulfonylated
substrates 1, but using a LiAlH4/TiCl4 ratio of 3 :1, and a 10-fold molar excess with

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respect to 2 (Scheme 10)6). The yields of the expected products 7 were good-to-
excellent for the (phenylsulfonyl)-substituted dimethoxy derivatives 2a ± 2c. Also, the
sulfonamide 2d still gave an acceptable yield of 7a (51%) on reduction with LiAlH4/
7
TiCl4 ). The procedure has been successfully applied to other 1,3- and 1,2-dimethox-
ybenzo[a]heptalenes bearing a phenylsulfonyl group in 2- and 3-position, respectively
[4][21].
Scheme 9
Scheme 10
We have not undertaken any mechanistically oriented experiments or searched for
the other cleavage products, since we concentrated on the benzo[a]heptalenes 7, which
could easily be identified by chromatographic separation on silica gel due to their
intense yellow color. Nevertheless, it is known that LiAlH4 reduces TiCl4 at low
temperature in THF to low-valent Ti species such as TiH2 (see literature cited in [20]),
and that these species, due to their oxophilicity, reduce sulfones [20] and sulfoxides [22]
at the S-atom to sulfides. Diaryl sulfides are cleaved by alkali metals ± in liquid NH3 or
MeNH2 [8][23], or in etheral solvents [24] ± to yield the corresponding aryl thiolates
and arenes, just as discussed for diaryl sulfones (cf. Scheme 2)8). Therefore, it is
reasonable to assume that our sulfonyl compounds 2, under the conditions applied here,
are first deoxygenated to the sulfides, which are then cleaved reductively to the
6
)
)
Lower molar ratios of the reducing system and 2 gave lower yields of the desulfonylated products 7.
The structure of 7a was secured by X-ray analysis (see Table 4 in the Exper. Part). Moreover, all
compounds of this type exhibited J(1,3) values of 2.4 Hz in their H-NMR spectra (CDCl3; cf. Table 2 in
7
1
the Exper. Part).
8
)
The reductive cleavage of diaryl sulfides can also be induced by anions via charge-transfer (CT) complex
formation in the excited state [25].

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desulfonylated compounds 79). We suppose that a similar sequence of complexes of
bicyclic aluminum hydrido species, as discussed before (Scheme 8), are responsible for
the smooth desulfonylation of 2 with LiAlH4/TiCl4, whereby, in this case, ClÀ ions
induce the intramolecular hydride transfer (Scheme 11). A totally different mechanism
is followed when diaryl sulfones are cleaved by strong bases such as lithium
triphenylsilanide [27] or sodium piperidinide [28].
Scheme 11
In the search for the corresponding sulfides, we stopped the reduction before
completion of the reaction (Scheme 12). However, we found no sulfides in the reaction
mixtures. Instead, we isolated small amounts of the 2-demethoxy sulfones 8a and 8d,
Scheme 12
9
)
A single-electron-transfer (SET) reaction, as discussed above, can be excluded due to the reduction
potential Ti2‡/Ti3‡ of À 0.368 V [26], which is too small for an electron transfer to a diaryl sulfide. For
diphenyl sulfone, a reduction potential of À 2.16 V is listed [26].

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respectively, in addition to 7a. The structures of 8a and 8d were established
spectroscopically (1H-NMR: J(1,2) ˆ 8.2 Hz) and by an X-ray crystal-structure analysis
of 8d (Fig. 2).
Fig. 2. Stereoscopic view of the X-ray crystal structure of 8d
The structures of the by-products speak for a nucleophilic substitution of the MeO
group at C(2) by hydride ions, possibly delivered by intramolecular complexes of Al or
Ti hydrides with the two O-atoms of the sulfonyl group and the two adjacent MeO
groups at C(2) and C(4). Indeed, the X-ray crystal structures of 3-(X-sulfonyl)ben-
zo[a]heptalenes of type 1 typically show quite short O´´´ Odistances between the 2-O-
as well as the 4-O-atoms and their adjacent 3-sulfonyl O-atom neighbors (Table 1) [4].
It is, therefore, possible that cyclic, six-membered Al or Ti complexes can also be
formed with the dimethyl ethers 2, in which hydride transfer can take place to
substitute, in a side-process, the 2-MeOgroup. Additional experiments would be
necessary to clarify this situation.
Table 1. Shortest Intramolecular CÀO ´´´ OˆS Distances (in pm) in 1c, 8d, and 9c
1c
8d
9c
C(2)ÀO´´´ OS(O) ÀC(3)
C(4)ÀO´´´ OS(O) ÀC(3)
295.4(2)
259.0(2)
±
297.0(2)
258.3(2)
293.2(2)
We mentioned in the introduction that the 3-sulfonyl group of the dimethyl ethers
of 1 could not directly be substituted by MeOÀ in a nucleophilic-displacement reaction.
Indeed, the reaction in boiling THF takes another path. When 2a or 2c was heated
under anhydrous conditions with MeONa (8 mol-equiv.) in THF, a regioselective
demethylation of the 4-MeOgroup took place ( Scheme 13)10). The structure of 9c was
unequivocally established by X-ray crystal-structure determination (Fig. 3). It showed,
as expected, a short intramolecular H-bond between the 4-OH group and one of the O-
atoms of the adjacent sulfonyl group. This H-bond was also present in solution, as
10
)
The selective demethylation of 2a could also be realized with a mixture of MeONa/TiCl4 at À 78 to 208 in
THF (for details, see Exper. Part).

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Scheme 13
Fig. 3. Stereoscopic view of the X-ray crystal structure of 9c
deduced from the corresponding 1H-NMR (CDCl3) chemical shift (d(H) 11.01 (OH);
for other examples, see [4]).
We thank the NMR laboratory, University of Zurich, for specific NMR measurements, the MS laboratory
for recording mass spectra, and the micro-analytical laboratory for elemental analyses. Financial support of this
work by the Swiss National Science Foundation is gratefully acknowledged.
Experimental Part
General. See [1 ± 3].
1. Formation of 3-(X-sulfonyl)benzo[a]heptalene-2,4-diols 1. 1.1. Improved General Procedure (GP 1, cf.
[3]). To a soln. of methyl phenyl sulfone (4.00 g, 25.64 mmol) or methyl morpholino sulfone (3.83 g,
25.64 mmol) in THF (15 ml), a 2.5m soln. of BuLi in hexane (10.75 ml, 25.96 mmol) was added at À 58. After
stirring for 20 min, a yellow precipitate was formed. The suspension was cooled to À 788, and a soln. of the
corresponding 3,3-dimethoxyheptaleno[1,2-c]furan-1-one (6.40 mmol) in THF (3 ml) was added. Stirring was
continued for 3 h at À 788. Then, the mixture was allowed to warm to À 58, and a second portion of a 2.5m BuLi
soln. in hexane (10.75 ml, 25.96 mmol) was added slowly. The color of the mixture changed immediately to a
dark reddish-brown. Stirring was continued for 12 h at r.t. The mixture was treated with ice/HCl, and the product
was extracted with AcOEt. The org. phase was washed with brine, and dried (Na2SO4). The solvent was distilled
off, and the product was purified by CC (SiO2; hexane/AcOEt 3 :1). The products were crystallized from Et2O.
Yield: 82% of 1a [3], 94% of 1b [1], 76% of 1c [2], and 58% of 1d [3]. Compound 1c was re-crystallized from
Et2O/CH2Cl2. The crystals contained Et2O, but were suitable for an X-ray crystal-structure analysis (see
Table 4).

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1.2. O-Methylation of Compounds 1. General Procedure (GP 2): The diol 1 and K2CO3 (13 mol-equiv.) were
stirred in acetone at À 58 for 20 min. MeI (13 mol-equiv.) was added, and stirring was continued for 12 h at r.t.
The product was extracted with AcOEt, and the org. phase was dried (MgSO4). The solvent was distilled off, and
the product was purified by CC (hexane/AcOEt 3 :1). The yellow products were crystallized from Et2O/CH2Cl2.
Yield (m.p.): 97% (190.9 ± 191.88) for 2a; 98% (184.7 ± 186.38) for 2b; 92% (169.1 ± 171.38) for 2c, and 95%
(201.0 ± 202.08) [1] for 2d. The MeO 1H-NMR signals are characteristic, appearing, in CDCl3, at d(H) 3.64 ± 3.68
(2-MeO) and 3.98 ± 4.00 (4-MeO) for 2a ± 2c, and at 3.86 (2-MeO) and 3.89 (4-MeO) [1] for 2d.
1.3. O-Demethylation of 9-Isopropyl-2,4-dimethoxy-7,12-dimethyl-3-(phenylsulfonyl)benzo[a]heptalene
(2a). To a soln. of 2a (0.25 g, 0.53 mmol) in THF (10 ml), a 1.0m soln. of LiEt3BH in hexane (5.3 ml,
5.3 mmol) was added. The mixture was heated at reflux during 4 h, until all 2a had been transformed into a salt
(TLC). The mixture was carefully added to ice/HCl. After extraction with AcOEt, washing with brine, drying
(MgSO4), and evaporation of the solvent, the residue was purified by CC (SiO2; hexane/AcOEt 2 :1), which
gave pure 1a (0.22 g, 93%).
2. Reductive Cleavage of 3-(Phenylsulfonyl)benzo[a]heptalene-2,4-diols 1. 2.1. With NaH/LiEt3BH/BuLi.
2.1.1. A soln. of 1a (0.50 g, 1.12 mmol) in THF (10 ml) was heated at reflux with NaH (0.06 g, 2.50 mmol) for 1 h.
Then, a 1.0m soln. of LiEt3BH in hexane (11.2 ml, 11.2 mmol) was added. The mixture was refluxed for 7 h, and a
2.5m soln. of BuLi in hexane (2.24 ml, 5.6 mmol) was added. After 8 h at reflux, another portion of a 2.5m BuLi
soln. (2.24 ml, 5.6 mmol) was added, and heating was continued for a further 8 h. After cooling, the mixture was
carefully added to ice/HCl, and the products were extracted with AcOEt. The org. phase was washed with brine
and dried (MgSO4). The solvent was distilled off, followed by separation of the products 3a and 4a by CC (SiO2;
hexane/AcOEt 2 :1).
Data of 9-Isopropyl-7,12-dimethylbenzo[a]heptalene-2,4-diol (3a). Yield: 0.15 g (45%). Yellow oil. Rf
(hexane/AcOEt 1 :1) 0.71. 1H-NMR (300 MHz, CDCl3): 6.93 (d, 3J ˆ 11.8, HÀC(5)); 6.40 (d, 3J ˆ 11.8,
HÀC(11)); 6.36 (dd, 3J ˆ 12.3, 4J ˆ 0.8, HÀC(10)); 6.32 (d, 4J ˆ 2.4, HÀC(3)); 6.23 (d, 3J ˆ 11.8, HÀC(6)); 6.10
(d, 4J ˆ 2.3, HÀC(1)); 5.70 (s, HÀC(8)); 5.08 (s, HOÀC(4)); 4.88 (s, HOÀC(2)); 2.54 (sept., Me2CHÀC(9));
1.69 (s, MeÀC(7,12)); 1.14, 1.13 (2d, 3J ˆ 6.9 and 6.8, Me2CHÀC(9)). 1H-NMR (300 MHz, (D6)acetone): 8.45
(br. s, HOÀC(4)); 8.19 (br. s, HOÀC(2)); 7.06 (d, 3J ˆ 11.9, HÀC(5)); 6.42 (d, 4J ˆ 2.3, HÀC(3)); 6.37 (m,
HÀC(10,11)); 6.03 (d, 3J ˆ 11.9 HÀC(6)); 6.02 (d, 4J ˆ 2.2, HÀC(1)); 5.70 (s, HÀC(8)); 2.56 (sept.,
Me2CHÀC(9)); 1.65 (s, MeÀC(7)); 1.64 (s, MeÀC(12)); 1.14, 1.13 (2d, 3J ˆ 6.9 and 6.8, Me2CHÀC(9)).
13C-NMR (75 MHz, (D6)acetone): 160.43 (s, C(2)); 156.32 (s, C(4)); 147.67 (s, C(9)); 140.97 (s, C(12b)); 137.07
(s, C(12)); 136.59 (d, C(11)); 132.98 (s, C(7a)); 131.52 (d, C(10)); 130.40 (s, C(12a)); 130.17 (d, C(6)); 128.49 (s,
C(7)); 127.32 (d, C(5)); 122.92 (d, C(8)); 117.93 (s, C(4a)); 107.52 (d, C(1)); 101.86 (d, C(3)); 35.13 (d,
Me2CHÀC(9)); 23.09, 23.13 (2q, Me2CHÀC(9)); 19.90 (q , MeÀC(12)); 17.23 (q, MeÀC(7)). EI-MS (C21H22O2;
‡
‡
‡
‡
306.41): 307.1 (25, [M ‡ 1] ); 306.1 (100, M ); 291.1 (26, [M À Me] ); 266.9 (56, [M À MeÀCꢀCH] ); 251.0
‡
(39); 238.0 (27, [M À Me2CHÀCꢀCH] ); 189.0 (48); 165.0 (51).
Data of 3-Ethyl-9-isopropyl-7,12-dimethylbenzo[a]heptalene-2,4-diol (4a). Yield: 4 mg (1%). Yellow oil. Rf
(hexane/AcOEt 1 :1) 0.82. 1H-NMR (300 MHz; CDCl3): 7.03 (d, 3J ˆ 11.8, HÀC(5)); 6.75 (s, HOÀC(4)); 6.40
(d, 3J ˆ 11.9, HÀC(11)); 6.36 (m, HÀC(10)); 6.34 (s, HÀC(1)); 6.29 (s, HOÀC(2)); 6.21 (d, 3J ˆ 11.8,
HÀC(6)); 5.70 (s, HÀC(8)); 2.66 (q, 3J ˆ 7.4, MeCH2ÀC(3)); 2.54 (sept., Me2CHÀC(9)); 1.70 (s, MeÀC(7));
1.69 (s, MeÀC(12)); 1.26 (t, 3J ˆ 7.4, MeCH2ÀC(3)); 1.14, 1.13 (2d, 3J ˆ 6.8 and 6.9, Me2CHÀC(9)).
2.2. With LiAlH4/MeLi ´ MeBr. General Procedure (GP 3): Compound 1 and LiAlH4 (30 mol-equiv.) were
heated at reflux in THF for 2 h. Then, a 1.6m soln. of MeLi ´ LiBr in hexane (2 mol-equiv.) was added. After 24 h
of heating, a second portion of MeLi ´ LiBr (2 mol-equiv.) was added, and heating was continued for a further
24 h. The cooled mixture was carefully added to ice/HCl and the products were extracted with AcOEt. The org.
phase was washed with brine and dried (Na2SO4). After evaporation of the solvent, the residue was subjected to
CC (SiO2; hexane/AcOEt 5 :1).
2.2.1. 9-Isopropyl-7,12-dimethylbenzo[a]heptalene-2,4-diol (3a). Compound 1a (1.00 g, 2.25 mmol) and
LiAlH4 (2.60 g, 68.4 mmol) in THF (20 ml) were reacted with MeLi ´ LiBr according to GP 3. After CC, pure 3a
(0.49 g, 71%) and a small amount of 9-isopropyl-7,12-dimethyl-3-(phenylsulfanyl)benzo[a]heptalene-2,4-diol
(5a; 46 mg, 5%) were obtained.
Data of 3a. See Sect. 2.1.1.
Data of 5a. Yellow oil. Rf (hexane/AcOEt 2 :1) 0.83. 1H-NMR (300 MHz, CDCl3): 7.57 (m, Ho of PhS); 7.38
(m, Hp and Hm of PhS); 6.95 (d, 3J ˆ 11.9, HÀC(5)); 6.39 (d, 3J ˆ 11.9, HÀC(11)); 6.37 (dd, 3J ˆ 11.9, 5J ˆ 1.2,
HÀC(10)); 6.27 (s, HOÀC(4)); 6.21 (s, HOÀC(2)); 6.19 (d, 3J ˆ 11.9, HÀC(6)); 5.74 (s, HÀC(1)); 5.59 (s,
HÀC(8)); 2.54 (sept., Me2CHÀC(9)); 1.7 (br. s, MeÀC(7,12)); 1.14, 1.13 (2d, 3J ˆ 6.9 and 6.8, Me2CHÀC(9)).
1H-NMR (600 MHz, (D6)acetone): 8.61 (br. s, HOÀC(4)); 7.96 (br. s, HOÀC(2)); 7.66 (m, Ho of PhS); 7.34 (m,

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Helvetica Chimica Acta ± Vol. 88 (2005)
Hm of PhS); 7.31 (m, Hp of PhS); 7.00 (d, 3J ˆ 11.9, HÀC(5)); 6.39 (br. s, HÀC(10,11)); 6.15 (s, HÀC(1)); 6.10
(d, 3J ˆ 11.9, HÀC(6)); 5.72 (s, HÀC(8)); 2.56 (sept., Me2CHÀC(9)); 1.64 (s, MeÀC(7,12)); 1.13, 1.12 (2d, 3J ˆ
6.9 and 6.8, Me2CHÀC(9)). 13C-NMR (150 MHz, (D6)acetone): 160.84 (s, C(2)); 156.92 (s, C(4)); 148.28 (s,
C(9)); 142.88 (s, C(12b)); 138.03 (s, Cip of PhS); 136.41 (d, C(11)); 136.09 (s, C(12a)); 133.20 (s, C(7a)); 132.08
(d, C(10)); 131.46 (d, C(6)); 131.13 (s, C(12)); 130.65 (d, Co of PhS); 129.88 (d, Cm of PhS); 128.88 (s, C(7));
128.65 (d, Cp of PhS); 127.02 (s, C(5)); 123.07 (d, C(8)); 118.03 (s, C(4a)); 107.74 (d, C(1)); 107.65 (s, C(3)); 35.15
(d, Me2CHÀC(9)); 23.03/23.07 (2q, Me2CHÀC(9)); 19.83 (q, MeÀC(12)); 17.13 (q, MeÀC(7)).
2.2.2. 8,10,12-Trimethylbenzo[a]heptalene-2,4-diol (3b). Compound 1b (1.00 g, 2.39 mmol) and LiAlH4
(2.72 g, 71.7 mmol) in THF (20 ml) were reacted with MeLi ´ LiBr according to GP 3. CC afforded pure 3b
(0.45 g, 68%). Yellow oil. Rf (hexane/AcOEt 1:1) 0.61. 1H-NMR (500 MHz, (D6)acetone): 8.50 (s, HOÀC(4));
4
8.31 (s, HOÀC(2)); 7.11 (d, 3J ˆ 11.7, HÀC(5)); 6.44 (d, J ˆ 2.4, HÀC(3)); 6.13 (dd, 3J ˆ 11.7, 5.8, HÀC(6));
4
3
4
6.11 (s, HÀC(11)); 6.02 (d, J ˆ 2.4, HÀC(1)); 5.93 (s, HÀC(9)); 5.67 (d, J ˆ 5.8, HÀC(7)); 1.98 (d, J ˆ 1.2,
MeÀC(8)); 1.94 (d, J ˆ 1.2, MeÀC(10)); 1.60 (s, MeÀC(12)). 13C-NMR (125 MHz, (D6)acetone): 160.82 (s,
4
C(2)); 156.47 (s, C(4)); 142.54 (s, C(7a)); 141.19 (s, C(12b)); 136.91 (s, C(8)); 135.39 (s, C(10)); 132.23 (d,
C(11)); 131.62 (s, C(12a)); 131.59 (s, C(12)); 129.03 (d, C(9)); 128.02 (d, C(5)); 125.43 (d, C(6)); 122.73 (d,
C(7)); 118.71 (s, C(4a)); 107.55 (d, C(1)); 102.10 (d, (C(3)); 25.30 (q, MeÀC(10)); 24.96 (q, MeÀC(8)); 20.3 (q,
‡
‡
‡
MeÀC(12)). EI-MS (C19H18O2, 278.35): 279.1 (22, [M ‡ 1] ); 278.1 (100, M ); 263.1 (51, [M À Me] ); 238.1 (64,
‡
[M À MeÀCꢀCH] ); 223.0 (33); 207.0 (46); 189.0 (23); 165.0 (29).
2.3. With LiAlH4/MeLi. General Procedure (GP 4): The benzo[a]heptalene-2,4-diol and LiAlH4 (30 mol-
equiv.) in THF were heated at reflux for 2 h. Then, a 1.6m soln. of MeLi in hexane (5 mol-equiv.) was added.
After 24 h at reflux, a second portion of 1.6m MeLi in hexane (5 mol-equiv.) was added. Heating was continued
for a further 24 h. The cooled mixture was carefully added to ice/HCl. The products were extracted with AcOEt.
The org. phase was washed with brine, and dried (Na2SO4). After evaporation of the solvent, the residue was
subjected to CC (SiO2; hexane/AcOEt 5 :1).
2.3.1. 3,3'-Dithiobis(9-isopropyl-7,12-dimethylbenzo[a]heptalene-2,4-diol) (6a). Compound 1a (1.00 g,
2.25 mmol) and LiAlH4 (2.60 g, 68.4 mmol) in THF (20 ml) were reacted with MeLi according to GP 4. CC
afforded 6a (0.50 g, 40%; 1:1 mixture of meso- and rac-forms), 3a (0.048 g, 7.0%), and 5a (0.040 g, 4.3%). When
the reaction was performed with 1d (1.00 g, 2.20 mmol), a 1:1 mixture of meso- and rac-6a (0.53 g, 71%) was
obtained exclusively.
Data of 6a. Yellow oil. Rf (hexane/AcOEt 2 :1) 0.75. 1H-NMR (300 MHz, CDCl3): 6.90, 6.89 (2d, 3J ˆ 11.9
each, HÀC(5,5')); 6.45, 6.43 (2s, HOÀC(4,4')); 6.40 (d, 3J ˆ 11.9, HÀC(11,11')); 6.37 (d, 3J ˆ 11.9,
HÀC(10,10')); 6.24, 6.22 (2s, HÀC(1,1')); 6.19, 6.17 (2d, 3J ˆ 11.9 each, HÀC(6,6')), 5.98 (2s, HOÀC(2,2'));
5.70 (s, HÀC(8,8')); 2.53 (sept., Me2CHÀC(9,9')); 1.714, 1.711 (2s, MeÀC(12,12')); 1.696, 1.692 (2s,
MeÀC(7,7')); 1.14, 1.13 (2d, 3J ˆ 6.9, 6.8, Me2CHÀC(9,9')). 13C-NMR (75 MHz, CDCl3): 158.26 (s, C(2,2'));
154.84 (s, C(4,4')); 147.16 (s, C(9,9')); 144.86 (s, C(12b,12b')); 135.50 (d, C(11,11')); 134.37 (s, C(12a,12a')); 132.86
(s, C(7a,7a')); 131.90 (d, C(6,6')); 131.69 (d, C(10,10')); 131.31 (s, C(12,12')); 128.44 (s, C(7,7'); 125.19 (d,
C(5,5')); 122.41 (d, C(8,8')); 117.92 (s, C(4a,4a')); 107.52 (d, C(1,1')); 104.21 (s, C(3,3')); 34.49 (d,
Me2CHÀC(9,9')); 22.76 (q, Me2CHÀC(9,9')); 19.67 (q, MeÀC(12,12')); 17.07 (q, MeÀC(7,7')).
2.3.2. 3,3'-Dithiobis(7,12-dimethylbenzo[a]heptalene-2,4-diol) (6c). Compound 1c (1.00 g, 2.31 mmol) and
LiAlH4 (2.63 g, 69.3 mmol) in THF (20 ml) were reacted with MeLi according to GP 4. CC afforded 6c (0.49 g,
36%) as a 1:1 mixture of the meso- and rac-forms. Yellow oil. Rf (hexane/AcOEt 2 :1) 0.66. 1H-NMR (600 MHz,
CDCl3): 6.927, 6.903 (2d, 3J ˆ 11.9 each, HÀC(5,5')); 6.48, 6.43 (2 br. s, HOÀC(4,4')); 6.190, 6.175 (2s,
HÀC(1,1')); 6.173, 6.154 (2d, 3J ˆ 11.7 each, HÀC(6,6')); 6.157 (br. s, HÀC(11,11')); 6.05, 5.98 (2 br. s,
HOÀC(2,2')); 6.006 (br. s, HÀC(9,9')); 2.017 (s, MeÀC(10,10')); 1.918, 1.909 (2s, MeÀC(8,8')); 1.714, 1.708 (2s,
MeÀC(7,7')); 1.696, 1.690 (2s, MeÀC(12,12')). 13C-NMR (150 MHz, CDCl3): 158.21, 158.11 (2s, C(2,2')); 154.98,
154.84 (2s, C(4,4')); 144.98, 144.90 (2s, C(12b,12b')); 138.68, 138.65 (2s, C(10,10')); 136.11, 136.03 (2s, C(7a,7a'));
134.19, 134.16 (2s, C(8,8')); 131.72, 131.64 (2d, C(6,6')); 130.54 (d, C(11,11')); 130.37 (s, C(12,12')); 129.96 (s,
C(12a,12a')); 128.41 (d, C(9,9')); 127.49, 127.48 (2s, C(7,7')); 125.44, 124.42 (2d, C(5,5')); 117.79, 117.77 (2s,
C(4a,4a')); 106.76, 106.72 (2d, C(1,1')); 103.67, 103.60 (2s, C(3,3')); 25.04 (q, MeÀC(10,10')); 22.81 (q,
MeÀC(8,8')); 19.34, 19.31 (2q, MeÀC(12,12')); 17.93, 17.92 (2q, MeÀC(7,7')). ESI-MS: 650.2/649.3/648.3/647.2
‡
‡
‡
(2/8/17/33, [M ‡ 1] ); 326.2/325.2/324.2/323.2 (8/48/100/88, [1ꢃ2M ‡ 2] ). CI-MS ([M ‡ 1] not obs.): 363.2 (51,
‡
‡
[C23H22O2S ‡ 1] ); 325.2 (100, [1ꢃ2M ‡ 2] ); 293.2 (21).
3. Reductive Cleavage of 2,4-Dimethoxy-3-(X-sulfonyl)benzo[a]heptalenes 2. General Procedure (GP 5):
At À 788, fresh TiCl4 (10 mol-equiv.) was dissolved in THF under Ar gas, and LiAlH4 (30 mol-equiv.) in THF
was added slowly through a dropping funnel. The mixture was allowed to warm to À 108, so that a vigorous
reaction accompanied by the development of a yellow vapor took place, turning the mixture into a dark-blue

Helvetica Chimica Acta ± Vol. 88 (2005)
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suspension. The mixture was cooled again to À 788, and a soln. of 2 (1 mol-equiv.) in THF was slowly added,
whereby effervescence of the mixture was observed. The mixture was allowed to warm slowly to r.t., and stirring
was continued for 1.5 ± 10 h. The mixture was added to an aq. sat. soln. of NH4Cl, and stirred for 1 h. Then, the
products were extracted with AcOEt (3Â), and the org. phase was dried (Na2SO4). After evaporation of the
solvent, the residue was subjected to CC (hexane/AcOEt 3 :1). The desulfonylated products 7a ± 7d were
crystallized from hexane/Et2O.
3.1. 9-Isopropyl-2,4-dimethoxy-7,12-dimethylbenzo[a]heptalene (7a) and 9-Isopropyl-4-methoxy-7,12-di-
methyl-3-(phenylsulfonyl)benzo[a]heptalene (8a). According to GP 5, TiCl4 (8.0 ml, 42.1 mmol) in THF
(10 ml) and LiAlH4 (4.80 g, 126.3 mmol) in THF (5 ml) were combined, and then reacted with 2a (2.00 g,
4.21 mmol) in THF (5 ml) for 1.5 h at r.t. Yield of crystallized 7a: 1.30 g (91%). Its structure was secured by an
X-ray crystal-structure analysis (cf. Table 4). When the reduction of 2a was interrupted after 45 min, the mixture
contained 7a and a small amount of 8a.
Data of 7a. Yellow crystals. M.p. 163.0 ± 163.68. Rf (hexane AcOEt 4 :1) 0.57. 1H- and 13C-NMR: see
‡
‡
‡
Tables 2 and 3, resp. EI-MS: 335.0 (25, [M ‡ 1] ); 334.0 (100, M ); 319.0 (32, [M À Me] ); 294.0 (55, [M À
‡
‡
i
‡
MeÀCꢀCH] ); 279.0 (49, [M À (Me ‡ MeÀCꢀCH)] ); 266 (33, [M À PrÀCꢀCH] ); 261.0 (16); 202.0 (26);
189 (21). Anal. calc. for C23H26O2 (334.46): C 82.60, H 7.84; found: C 82.49, H 7.67.
Data of 8a. Yellow crystals. M.p. 212.7 ± 213.68 (hexane/AcOEt). 1H-NMR (300 MHz, CDCl3): 8.11 (d,
3J ˆ 8.3 HÀC(2)); 8.00 (m, Ho of Ph); 7.56 (m, Hp of Ph); 7.50 (m, Hm of Ph); 6.94 (d, 3J ˆ 7.8, HÀC(1)); 6.89 (d,
3J ˆ 12.1, HÀC(5)); 6.40 (AB, HÀC(10,11)); 6.34 (d, 3J ˆ 11.9, HÀC(6)); 5.72 (s, HÀC(8)); 3.87 (s,
MeOÀC(4)); 2.55 (sept., Me2CHÀC(9)); 1.61 (s, MeÀC(7,12)); 1.16, 1.14 (2d, 3J ˆ 6.9, 6.8, Me2CHÀC(9)). EI-
‡
‡
‡
MS (C28H28O3S; 444.60): 445.1 (62, [M ‡ 1] ); 444.1 (100, M ); 429.01 (76, [M À Me] ); 404.0 (71, [M À
‡
i
‡
MeÀCꢀCH] ); 376.0 (23, [M À PrÀCꢀCH] ); 288.0 (17); 256.0 (29); 245.0 (30); 229.0 (25); 214.9 (40);
201.9 (45); 188.9 (30); 76.8 (37).
Table 2. 1H-NMR Data for Compounds 7a ± 7c. At 500 or 600 MHz in CDCl3; d in ppm, J in Hz.
7a
7b
7c
4
HÀC(1)
6.14 (d, J ˆ 2.4)
6.14 (d, 4J ˆ 2.4)
6.12 (d, 4J ˆ 2.4)
2-MeO3.79 (
HÀC(3)
s)
3.78 (s)
3.78 (s)
4
6.42 (d, J ˆ 2.4)
6.43 (d, 4J ˆ 2.4)
3.85 (s)
6.43 (d, 4J ˆ 2.4)
3.87 (s)
4-MeO3.85 (
HÀC(5)
s)
3
7.08 (d, J ˆ 11.9)
7.15 (d, 3J ˆ 11.8)
6.30 (dd, 3J ˆ 11.8, 5.8)
5.73 (d, 3J ˆ 5.8)
2.04 (d, 4J ˆ 0.9)
5.95 (s)
7.13 (d, 3J ˆ 11.9)
6.21 (d, 3J ˆ 12.0)
1.73 (s)
3
HÀC(6)
6.20 (d, J ˆ 11.9)
7-Mea)
1.70 (d, 4J ˆ 0.9)
HÀC(8)b)
HÀC(9)c)
HÀC(10)d)
HÀC(11)
12-Me
5.70 (s)
1.94 (d, J ˆ 1.2)
4
2.56 (sept.); 1.16, 1.15 (2d, 3J ˆ 6.9 and 6.8)
6.05 (s)
6.36 (dd, 3J ˆ 11.9, J ˆ 1.3)
2.00 (d, 4J ˆ 1.0)
2.04 (d, 4J ˆ 1.1)
4
3
6.41 (d, J ˆ 11.7)
6.18 (s)
6.19 (s)
1.67 (s)
1.65 (s)
1.67 (s)
a) HÀC(7) for 7b. b) 8-Me for 7b and 7c. c) 9-(i-Pr) for 7a. d) 10-Me for 7b and 7c.
3.2. 2,4-Dimethoxy-8,10,12-trimethylbenzo[a]heptalene (7b). According to GP 5, TiCl4 (8.55 ml,
44.8 mmol) in THF (10 ml) and LiAlH4 (5.11 g, 134.4 mmol) in THF (5 ml) were combined and then reacted
with 2b (2.00 g, 4.48 mmol) in THF (5 ml) for 2.5 h at r.t. Yield of crystallized 7b: 1.15 g (84%). Yellow crystals.
M.p. 172.0 ± 173.18. Rf (hexane/AcOEt 4 :1) 0.70. IR (KBr): 2965m, 2935m, 2907m, 1599vs, 1561s, 1543m, 1476m,
1462s, 1437vs, 1344m, 1318vs, 1258m, 1219m, 1196vs, 1161vs, 1115s, 1025vs, 810s. 1H- and 13C-NMR: see Tables 2
‡
‡
‡
and 3, resp. EI-MS: 307.0 (22, [M ‡ 1] ); 306.0 (100, M ); 291.0 (52, [M À Me] ); 266.0 (69, [M À
‡
MeÀCꢀCH] ); 252.0 (26); 250.9 (33); 201.9 (27); 188.9 (32). Anal. calc. for C21H22O2 (306.41): C 82.32, H
7.24; found: C 82.20, H 7.37.
3.3. 2,4-Dimethoxy-7,8,10,12-tetramethylbenzo[a]heptalene (7c). According to GP 5, TiCl4 (8.29 ml,
42.1 mmol) in THF (10 ml) and LiAlH4 (4.95 g, 129.3 mmol) in THF (5 ml) were reacted with 2c (2.00 g,
4.34 mmol) in THF (5 ml) for 6 h at r.t. Yield of crystallized 7c: 1.06 g (76%). Yellow crystals. M.p. 151.5 ±
‡
153.18. Rf (hexane/AcOEt 3 :1) 0.73. 1H- and 13C-NMR: see Tables 2 and 3, resp. EI-MS: 321.00 (24, [M ‡ 1] ),

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Helvetica Chimica Acta ± Vol. 88 (2005)
Table 3. 13C-NMR Data of Compounds 7a ± 7c. At 125 or 150 MHz in CDCl3; d in ppm.
7a
7b
7c
C(1)
C(2)
C(3)
104.29
161.86
97.27
104.25
162.16
97.40
103.40
161.76
97.07
C(4)
C(4a)
C(5)
C(6)
C(7)
C(7a)
C(8)
C(9)
C(10)
C(11)
C(12)
C(12a)
C(12b)
2-MeO55.46
4-MeO55.60
7-Me
157.55
119.68
25.79
157.60
120.35
126.80
126.10
121.94
142.33
136.61
128.45
138.19
131.62
131.81
130.47
139.88
157.59
119.51
125.98
130.71
127.09
136.10
134.20
128.26
138.10
130.76
131.46
129.55
140.41
131.04
128.19
132.85
122.17
146.99
131.25
135.69
130.51
135.66
139.69
55.47
55.57
17.01
55.45
55.51
±
19.40
22.89
±
8-Me
9-(i-Pr)
±
±
24.88
34.43, 22.89, 22.77
10-Me
12-Me
±
25.38
20.16
25.02
19.86
19.74
‡
‡
‡
‡
320.0 (100, M ); 305.0 (87, [M À Me] ); 290.0 (29, [M À CH2O] ); 280.0 (38, [M À MeÀCꢀCH] ); 266.0 (42);
265.0 (21); 201.9 (12); 188.9 (12); 144.4 (19); 100.9 (10). Anal. calc. for C22H24O2 (320.44): C 82.46, H 7.55;
found: C 82.28, H 7.47.
3.4. 9-Isopropyl-2,4-dimethoxy-7,12-dimethylbenzo[a]heptalene (7a) and 9-Isopropyl-4-methoxy-7,12-di-
methyl-3-(morpholinosulfonyl)benzo[a]heptalene (8d). Following GP 5, TiCl4 (7.90 ml, 41.4 mmol) in THF
(10 ml) and LiAlH4 (4.72 g, 124.2 mmol) in THF (5 ml) were reacted with 2d (2.00 g, 4.14 mmol) in THF (5 ml).
The mixture was finally stirred for 6 h at r.t. Yield of crystallized 7a: 0.73 g (51%). When the reduction of 2d was
interrupted after 5 h, the mixture contained 7a and a small amount of 8d, which was isolated by CC.
Data of 7a. See Sect. 3.1.
Data of 8d. Yellow crystals. M.p. 219.4 ± 222.18 (Et2O/hexane). Rf (hexane/AcOEt 1:1) 0.59. 1H-NMR
3
3
3
(300 MHz, CDCl3): 7.83 (d, J ˆ 8.3, HÀC(2)); 7.03, (d, J ˆ 12.0, HÀC(5)); 6.85 (d, J ˆ 8.2, HÀC(1)); 6.42
(m, HÀC(6,10,11)); 5.74 (s, HÀC(8)); 3.91 (s, MeOÀC(4)); 3.73, 3.21 (2m, 8 morpholino H); 2.56 (sept.,
Me2CHÀC(9)); 1.73 (s, MeÀC(7)); 1.63 (s, MeÀC(12)); 1.16, 1.15 (2d, 3J ˆ 6.9, 6.8, Me2CHÀC(9)). EI-MS
‡
‡
‡
‡
(C26H31NO4S; 453.61): 455.1 (26, [M ‡ 2] ); 454.1 (29, [M ‡ 1] ); 453.1 (100, M ); 438.1 (30, [M À Me] ) 413.0
‡
i
‡
(33, [M À MeÀCꢀCH] ); 412.0 (24); 385.0 (10, [M À PrÀCꢀCH] ); 271.0 (19): 245.0 (25); 215.0 (33); 201.0
(35); 189.0 (21); 86.0 (52); 56.0 (84).
4. Selective Demethylation of Compounds 2. General Procedure (GP 6): Compound 2 (1.10 mmol) and anh.
MeONa (8.7 mmol; freshly prepared from Na and MeOH) were heated at reflux for 24 h in THF (20 ml). After
usual workup, the products were purified by CC (SiO2; hexane/AcOEt 5 :1) and crystallized from Et2O/hexane.
4.1. Data of 9-Isopropyl-2-methoxy-7,12-dimethyl-3-(phenylsulfonyl)benzo[a]heptalen-4-ol (9a). Yield:
1
70%. Yellow crystals. M.p. 217.3 ± 218.28. Rf (hexane/AcOEt 3 :1) 0.42. H-NMR (600 MHz, CDCl3): 10.98 (s,
HOÀC(4)); 7.98 (m, Ho of Ph); 7.59 (m, Hp of Ph); 7.17 (t, 3J ˆ 7.6, Hm of Ph); 7.13 (d, 3J ˆ 11.9, HÀC(5)); 7.11
(d, 3J ˆ 11.9, HÀC(11)); 6.37 (dd, 3J ˆ 11.9, 4J ˆ 1.0, HÀC(10)); 6.29 (d, 3J ˆ 12.0, HÀC(6)); 5.96 (s, HÀC(1));
5.69 (s, HÀC(8)); 3.63 (s, MeOÀC(2)); 2.52 (sept., Me2CHÀC(9)); 1.70 (s, MeÀC(7)); 1.63 (s, MeÀC(12));
1.14/1.13 (2d, 3J ˆ 6.5 each, Me2CHÀC(9)). 13C-NMR (150 MHz, CDCl3): 158.68 (s, C(2)); 155.66 (s, C(4));
147.48 (s, C(9)); 144.37 (s, C(12b)); 142.01 (s, Cip of Ph); 135.51 (d, C(11)); 134.44 (s, C(12a)); 133.34 (d, Cp of

Helvetica Chimica Acta ± Vol. 88 (2005)
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Ph); 132.44 (s, C(7a)); 132.34 (d, C(6)); 132.06 (d, C(10)); 131.42 (s, C(12)); 128.98 (s, C(7)); 128.51 (d, Cm of
Ph); 127.84 (d, Co of Ph); 125.14 (d, C(5)); 122.27 (d, C(8)); 120.45 (s, C(4a)); 109.97 (s, C(3)); 102.71 (d, C(1));
56.03 (q, MeOÀC(2)); 34.41 (d, Me2CHÀC(9)); 22.68, 22.78 (2q, Me2CHÀC(9)); 19.61 (q, MeÀC(12)); 16.97
‡
‡
‡
(q, MeÀC(7)). EI-MS: 461.0 (33, [M ‡ 1] ); 460.0 (100, M ); 445.0 (27, [M À Me] ); 420.0 (49, [M À
‡
i
‡
MeÀCꢀCH] ); 405.0 (33); 392.0 (11, [M À PrÀCꢀCH] ); 281.0 (22); 191.0 (17); 96.0 (33); 77.0 (78); 73.0
(42). Anal. calc. for C28H28O4S (460.60): C 73.02, H 6.13, S 6.96; found: C 73.01, H 6.16, S 6.76.
4.2. Data of 2-Methoxy-7,8,10,12-tetramethyl-3-(phenylsulfonyl)benzo[a]heptalen-4-ol (9c). Yield: 58%.
Yellow crystals. M.p. 206.6 ± 208.88. Rf (hexane/AcOEt 2 :1) 0.74. 1H-NMR (600 MHz, CDCl3): 11.01 (s,
HOÀC(4)); 8.00 (m, Ho of Ph); 7.60 (m, Hp of Ph); 7.47 (m, Hm of Ph); 7.36 (d, 3J ˆ 11.9, HÀC(5)); 6.28 (d, 3J ˆ
12.0, HÀC(6)); 6.15 (s, HÀC(11)); 6.01 (s, HÀC(9)); 5.94 (s, HÀC(1)); 3.60 (s, MeOÀC(2)); 2.01 (s,
MeÀC(10)); 1.90 (s, MeÀC(8)); 1.73 (s, MeÀC(7)); 1.62 (s, MeÀC(12)). 13C-NMR (150 MHz, CDCl3): 158.62
(s, C(2)); 155.91 (s, C(4)); 145.23 (s, C(12b)); 142.15 (s, Cip of Ph); 139.07 (s, C(10)); 135.73 (s, C(7a)); 134.48 (s,
C(8)); 133.35 (d, Cp of Ph); 132.19 (d, C(6)); 130.49 (d, C(11)); 130.47 (s, C(12)); 130.18 (s, C(12a)); 128.63 (d,
C(9)); 128.53 (d, Cm of Ph); 128.03 (s, C(7)); 127.89 (d, Co of Ph); 125.41 (d, C(5)); 120.28 (s, C(4a)); 109.82 (s,
C(3)); 102.06 (d, C(1)); 56.10 (q, MeOÀC(2)); 25.06 (q, MeÀC(10)); 22.82 (q, MeÀC(8)); 19.33 (q,
‡
‡
MeÀC(12)); 17.89 (q, MeÀC(7)). EI-MS (C27H26O4S; 446.57): 447.0 (32, [M ‡ 1] ); 446.0 (100, M ); 431.0 (81,
‡
‡
[M À Me] ); 406.0 (36, [M À MeÀCꢀCH] ); 290.0 (18); 275.0 (16); 215.0 (18); 202.0 (29); 189.0 (21); 78.0 (21);
77.0 (67).
4.3. Alternative Procedure for the Selective Demethylation of 2a. At À 788, TiCl4 (0.21 ml, 1.1 mmol) was
added to THF (5 ml). Then, solid anh. MeONa, freshly prepared from Na (0.20 g, 8.7 mmol) and MeOH (3 ml),
was added under Ar gas, whereby a yellow suspension was formed. A soln. of 2a (50 mg, 0.105 mmol) in THF
(15 ml) was slowly added, and the mixture was allowed to warm to r.t. Stirring was continued for 3 h. The
mixture was added to a sat. aq. soln. of NH4Cl, and stirred for 1 h. Usual workup afforded 9a in 94% yield.
5. X-Ray Crystal-Structures of Compounds 1c, 7a, 8d, and 9c (see Table 4, and Figs. 2 and 3)11). All
measurements were conducted at low temperature using graphite-monochromated MoKa radiation (l ˆ
0.71073 Š). A Rigaku AFC5R diffractometer on a 12-kW rotating anode generator was used for 7a, and a
Nonius KappaCCD diffractometer [29][30] fitted with a Cryostream-700 cooler (Oxford Cryosystems) was used
for 1c, 8d, and 9c. The data collection and refinement parameters are given in Table 4, and views of the
molecules of 8d and 9c are shown in Figs. 2 and 3. The intensities were corrected for Lorentz and polarization
effects, and equivalent reflections were merged. An absorption correction was applied only in the case of 1c
based on the multi-scan method [31]. Each structure was solved by direct methods using either SHELXS97 [32]
or SIR92 [33], which revealed the positions of all non-H-atoms. The asymmetric unit of 1c contains one
molecule of the heptalene derivative plus one disordered Et2Omolecule. Two positions were defined for each
atom of the solvent molecule, and refinement of constrained site occupation factors for the two orientations
yielded a value of 0.785(9) for the major conformation.
Similarity restraints were applied to the chemically equivalent bond lengths and angles involving all
disordered atoms, while neighboring atoms within and between the disordered conformations were restrained to
have similar atomic displacement parameters.
The non-H-atoms of each structure were refined anisotropically. The OH H-atom in 9c was placed in the
position indicated by a difference Fourier map, and its position was allowed to refine together with an isotropic
displacement parameter. The positions of the OH H-atoms of 1c were initially located in a difference Fourier
map, then their positions were geometrically optimized, while retaining the direction of the OÀH vector in line
with that given by the peak in the map. All remaining H-atoms were fixed in geometrically optimized positions,
and each was assigned a fixed isotropic displacement parameter with a value equal to 1.2 Ueq of its parent atom
(1.5 Ueq for the Me and OH groups of 1c). The structures of 7a, 8d, and 9c were refined on F, using full-matrix
least-squares procedures, which minimized the function Sw(j Fo j ± j Fc j )2. For 1c, the refinement was carried out
on F2 by minimizing the corresponding function based on F2. A correction for secondary extinction was applied
in the case of 1c, 7a, and 8d. For 1c, 8d, and 9c, one, four, and eight reflections, resp., whose intensities were
considered to be extreme outliers, were omitted from the final refinement. Neutral-atom-scattering factors for
non-H-atoms were taken from [34], and the scattering factors for H-atoms were taken from [35]. The values of
11
)
CCDC-263001-263003 (for 7a, 8d and 9c, resp.) and -263983 (for 1c) contain the supplementary
crystallographic data for this paper. These data can be obtained, free of charge, via www.ccdc.cam.ac.uk/
data_request/cif, or from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge
CB21EZ, UK; fax: ‡ 44-1223-336033; e-mail: deposit@ccdc.cam.ac.uk).

1100
Helvetica Chimica Acta ± Vol. 88 (2005)
Table 4. Crystallographic Data for Compounds 1c, 7a, 8d, and 9c
1c
7a
8d
9c
Crystallized from
Empirical formula
Formula weight [g/mol]
Crystal color, habit
Crystal dimensions [mm]
Temperature [K]
Crystal system
Space group
Z
CH2Cl2/Et2Ohexane/Et
C26H24O4S ´ C4H10O C23H26O2
2Ohexane/Et
2Ohexane/Et
2O
C26H31NO4S
453.59
colorless, plate yellow, tablet
C27H26O4S
446.56
506.65
334.46
yellow, prism
yellow, prism
0.20 Â 0.22 Â 0.25 0.33 Â 0.33 Â 0.40 0.03 Â 0.14 Â 0.14 0.12 Â 0.30 Â 0.30
160(1)
173(1)
orthorhombic
Pbca
160(1)
monoclinic
P21/n
160(1)
monoclinic
P21/c
triclinic
Å
P1
2
8
4
4
Refl. for cell determination
2q Range [8]
Unit-cell parameters: a [Š]
b [Š]
22904
4 ± 60
25
5659
2 ± 55
5403
20 ± 37
15.813(1)
23.724(6)
10.116(4)
90
90
90
3795(1)
1440
1.171
0.0728
w/2q
55
5639
4357
4 ± 55
8.6395(1)
15.9392(2)
16.5413(3)
90
94.1305(6)
90
2271.93(6)
944
1.305
0.174
f and w
55
59600
5205
11.1409(2)
12.0702(2)
12.4394(3)
61.2531(9)
76.7103(9)
68.663(1)
1362.98 (5)
540
1.234
0.156
f and w
60
40871
16.9868(2)
7.0230(1)
19.3143(3)
90
95.9446(8)
90
2291.77(6)
968
1.315
0.174
f and w
55
47163
4999
0.077
c [Š]
a [8]
b [8]
g [8]
V [Š3]
F(000)
Dx [g/cm3]
m(MoKa) [mmÀ1
Scan type
]
2q (max) [8]
Total refl.
Symmetry-independent refl.
Rint
7909
0.105
0.099
0.060
Refl. with I > 2s(I)
Parameters refined
Restraints
3893
382
137
2169
227
0
3427
290
0
3772
293
0
Refl. for refinement
Final R(F)
7908
2169
3427
3772
0.0596
0.0629
0.0542
0.005
0.0494
0.0421
0.005
0.0538
0.0604
0.005
wR(F)
0.1777 (on F2)
a
Weights: p in w ˆ [s2(Fo) ‡ (pFo)2]À1
)
Goodness-of-fit
0.977
2.062
1.940
3.283
Secondary extinction coefficient
0.011(3)
0.001
0.35; À 0.54
1.8(3) Â 10À7
0.0002
0.29; À 0.28
5.6(8) Â 10À7
0.0003
0.67; À 0.45
±
Final Dmax/s
D1 (max; min) [e Š
0.0003
0.62; À 0.32
À3
]
a) wÀ1 ˆ s2(F2o ) ‡ (0.0903P)2, where P ˆ (Fo2 ‡ 2F2o )/3.
the mass-attenuation coefficients were those of [36]. The calculations for 1c were performed with the
SHELXL97 program [37], while those for 7a, 8d and 9c employed the teXsan crystallographic-software package
[38]. The crystallographic diagrams were drawn with ORTEPII [39].
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Received February 21, 2005