Alkylation reactions at the benzo moiety of 2,4-Dimethoxy-3- (phenylsulfonyl)benzo[a]heptalenes - Model compounds of colchicinoids

Article abstract of DOI:10.1002/hlca.201000191

Alkylation reactions of 3-(X-sulfonyl)benzo[a]heptalene-2,4-diols (X=Ph, morpholin-4-yl) and their dimethyl ethers were studied. The diols form with K₂CO₃/MeI in aqueous media the 1-methylated benzoheptalenes, but in yields not surpassing 20% (Table1). On the other hand, 2,4-dimethoxybenzo[a]heptalenes can easily be lithiated at C(3) with BuLi and then treated with alkyl iodides to give the 3-alkylated forms in good yield (Table2). Surprising is the reaction with two equiv. or more of t-BuLi since the alkylation at C(4) is accompanied by the reductive elimination of the X-sulfonyl group at C(3) (Table3). Most exciting is also the course of 2,4-dimethoxy-3-(phenylsulfonyl)benzo[a]heptalenes in the presence of an excess of MeLi. After the expected exchange of MeO against Me at C(4) (Scheme6), rearrangement takes place under formation of 4-benzyl-2-methoxybenzo[a] heptalenes and concomitant loss of the sulfonyl group at C(3) (Table4). In the case of X=morpholin-4-yl, rearrangement cannot occur. However, the intermediate benzyl anions of Type E (Scheme8) react easily with O₂ of the air to build up corresponding benzo[a]heptalene-4-methanols (Table6).

Full text of DOI:10.1002/hlca.201000191

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Helvetica Chimica Acta – Vol. 93 (2010)
Alkylation Reactions at the Benzo Moiety of 2,4-Dimethoxy-3-
(phenylsulfonyl)benzo[a]heptalenes – Model Compounds of Colchicinoids
by Samir El Rayesa), Anthony Lindenb), Khaled Abou-Hadeed*b), and Hans-Jꢀrgen Hansen*b)
a) Faculty of Science, University of Suez Canal, Ismailia, Egypt
b) Organisch-chemisches Institut der Universitꢀt Zꢁrich, Winterthurerstr. 190, CH-8057 Zꢁrich
(phone: þ 41-44-6354231; fax: þ 41-44-6356833; e-mail: h.j.hansen@oci.uzh.ch)
Dedicated to Albert Eschenmoser on the occasion of his 85th birthday
The times change, along with fashions,
ways of being and of trust change;
all the worldꢀs made up of change,
consistent only in alteration.
Everything we see seems novel
and altered from all we ever dreamed;
evil endures as grief remembered,
good, if one finds it, as fond recall.
˜
Luꢂs de Camoes [1]
Alkylation reactions of 3-(X-sulfonyl)benzo[a]heptalene-2,4-diols (X ¼ Ph, morpholin-4-yl) and
their dimethyl ethers were studied. The diols form with K2CO3/MeI in aqueous media the 1-methylated
benzoheptalenes, but in yields not surpassing 20% (Table 1). On the other hand, 2,4-dimethoxyben-
zo[a]heptalenes can easily be lithiated at C(3) with BuLi and then treated with alkyl iodides to give the 3-
alkylated forms in good yield (Table 2). Surprising is the reaction with two equiv. or more of t-BuLi since
the alkylation at C(4) is accompanied by the reductive elimination of the X-sulfonyl group at C(3)
(Table 3). Most exciting is also the course of 2,4-dimethoxy-3-(phenylsulfonyl)benzo[a]heptalenes in the
presence of an excess of MeLi. After the expected exchange of MeO against Me at C(4) (Scheme 6),
rearrangement takes place under formation of 4-benzyl-2-methoxybenzo[a]heptalenes and concomitant
loss of the sulfonyl group at C(3) (Table 4). In the case of X ¼ morpholin-4-yl, rearrangement cannot
occur. However, the intermediate benzyl anions of Type E (Scheme 8) react easily with O2 of the air to
build up corresponding benzo[a]heptalene-4-methanols (Table 6).
1. Introduction. – Just 15 years ago, on the occasion of Albert Eschenmoserꢃs 70th
birthday, we reported in this journal on the transformation of colchicine and some of its
4-alkyl analogs into their underlying heptalene structure, i.e., 1,2,3,9,10-pentamethoxy-
benzo[a]heptalenes [2]. About two years later, we found by chance a new benzo-fusion
reaction of dimethylheptalene-4,5- and -1,2-dicarboxylates with (sulfonylmethyl)lithi-
ums as C1 carrier in the presence of an excess of BuLi to yield 3-(X-sulfonyl)benzo[a]-
heptalene-2,4-diols [3]. We have improved this new ꢄone-pot accessꢃ to benzo[a]hep-
talenes in the meantime continuously (see [4] and lit. cit. therein), so that colchicine-
like compounds of type 2 and 3 – with the non-natural position of the O-functionalities
as compared with colchicine – became available in yields of > 80% (Scheme 1). A
ꢅ 2010 Verlag Helvetica Chimica Acta AG, Zꢁrich

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slight modification of our procedure gave also access to 4-methyl-2-(X-sulfonyl)ben-
zo[a]heptalenes with the MeO groups in the natural 1,3-position [5]. The sulfonyl
groups of these compounds can be removed reductively [5][6] and the missing third
MeO group thus introduced by lithiation and catalyzed air oxidation and then
methylation of the formed OH group (see 3 ! 4 ! 5 in Scheme 2) [7].
Scheme 1
Scheme 2
The ease of the availability of compounds of type 2 – 4 inspired us to study in more
detail alkylation reactions with these heptaleno-fused resorcinols and their methyl
ether – what in some cases led to astonishing results.
2. C-Alkylation Reactions. – 2.1. Methylation of C(1) of 3-(Phenylsulfonyl)ben-
zo[a]heptalene-2,4-diol 2a. The benzo-fusion products 2 can be O-methylated almost
quantitavely with MeI under Claisenꢃs standard conditions of methyl ether formation of
phenols (Scheme 1). On the other hand, a sluggish methylation of C(1) is observed in
protic media such as acetone/H2O, EtOH/H2O, or H2O alone, in general agreement
with O- vs. C-alkylation of phenols (see, e.g., [8]). But, the yields of 1-methylben-
zo[a]heptalene-2,4-diol 6a, resulting from 2a as model compound, did not exceed 20%
(Table 1), possibly due to a steric screening effect by MeꢀC(12) on the methylation of
C(1) (see [5] for the X-ray crystal structure of 6a). Fortunately, the one-pot step-by-
step benzo-fusion of 8-isopropyl-3,3-dimethoxy-6,11-dimethylheptaleno[1,2-c]furan-

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Table 1. Methylation of C(1) of 3-(Phenylsulfonyl)benzo[a]heptalene-2,4-diol 2aa)
Aqueous systemb)
Yield [%]
Acetone (5)/H2O (20)
EtOH (5)/H2O (30)
H2O (15)
7
20c)
3
c
a) For details, see Exper. Part. b) In parentheses ml, applied for 0.22 mmol of 2a. ) The reaction in pure
EtOH gave the O- and C-methylated product in 5% yield.
1(3H)-one (7a), one of the two possible pseudoesters of 1’a (R ¼ 5-Me, 7-iPr) [9], at
first with [1-(phenylsulfonyl)ethyl]lithium and then with [(phenylsulfonyl)methyl]-
lithium and BuLi gives 6a in a yield of 72% besides 17% of 2a (Scheme 3) [5].
Scheme 3a)
2.2. Alkylation of C(3) of 2,4-Dimethoxybenzo[a]heptalenes. These compounds can
easily and in good yields be alkylated with MeI and EtI after lithiation with BuLi
(Table 2). The yield of the 3-Me products 8aa, 8ba, and 8ca is in all cases higher (65 –
81%) than that of the corresponding 3-Et analogues 8ab, 8bb, and 8cb (46 – 70%).
We performed X-ray crystal-structure analyses of 8ca and 8bb. The stereo-
projection of the crystal structure of 3-ethyl-2,4-dimethoxy-7,8,10,12-tetramethylben-
zo[a]heptalene (8bb) is displayed in Fig. 1. It is of interest to note that the three-
dimensional arrangement of the 2,3,4-substituents is the same as for all colchicinoids of
this type, and it corresponds with that of the 1,2,3-pattern of colchicine-like compounds
(cf. [2][5] and lit. cit. therein). These spatial arrangements are not influenced – at best
accentuated – by further substituents at the heptalene part. Fig. 2, which shows the
stereoprojection of the AM1-calculated and energetically relaxed structure of the four

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Table 2. Alkylation of 2,4-Dimethoxybenzo[a]heptalenes 4a)
Reactant
R
R’
Product
Time [h]
Yield [%]
4a
4a
4b
4b
4c
4c
7-Me, 9-iPr
Me
Et
Me
Et
Me
Et
8aa
8ab
8ba
8bb
8ca
8cb
2
6
5
20
5
12
81
70
65
46
73
54
7,8,10-Me3
8,10-Me2
a) See Exper. Part for details.
possible (P)-configured benzo[a]heptalenes, carrying three MeO groups at the benzo
moiety and alternatively at C(4) or C(1), respectively, a Me group, illustrates the steric
constrains that determine the spatial arrangements at the benzo moiety (the steric
substituent interactions are quite similar to those of 1,2,3-trimethoxynaphthalenes).
Fig. 1. Stereoscopic view of the X-ray crystal structure of 3-ethyl-2,4-dimethoxy-7,8,10,12-tetramethyl-
benzo[a]heptalene (8bb) (50% probability ellipsoids)
Fig. 2,a, demonstrates that the heptalene fragment C(12a)¼C(12)ꢀH forces the
MeO group at C(1) in an out-of-plane anti-position with respect to the fragment. As a
consequence, MeOꢀC(2) takes the out-of-plane anti-position with respect to
MeOꢀC(1). Only MeOꢀC(3) lies in an in-plane orientation with respect to the
benzo moiety. An additional Me group at C(4) drives also MeOꢀC(3) in the out-of-
plane position with respect to its MeO neighbor at C(2) (Fig. 2,b). The spatial
arrangement is quite similar for the 2,3,4-substitution pattern (Fig. 2,c). Here, it is
MeOꢀC(4) that takes an out-of-plane anti-position with respect to the heptalene

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Fig. 2. Stereoscopic view of AM1-calculated structures of benzo[a]heptalenes with three MeO and one Me
substituent at the benzo moiety
fragment HꢀC(5)¼C(6). And, again, as a consequence, MeOꢀC(3) occupies the out-
of-plane anti-site with respect to MeOꢀC(4). The nonoccupied C(1) allows
MeOꢀC(2) to be in-plane with the benzo moiety. An additional Me group at C(1)

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changes the spatial arrangement in that MeOꢀC(2) is now in an out-of-plane position
with respect to MeOꢀC(3) (Fig. 2,d). In other words, it is the fused heptalene part that
determines the ꢄup and downꢃ of two-atom chains at the benzo moiety of
benzo[a]heptalenes, a situation, which is also verified in the X-ray crystal structure
of 8bb (Fig. 1) and 8ca and which may also be of biological relevance (see [2] and lit.
cited therein).
2.3. Reaction of 2,4-Dimethoxy-3-(X-sulfonyl)benzo[a]heptalenes with t-BuLi. The
ortho-position of the two MeO groups in relation to the electron-attracting X-sulfonyl
group of compounds 3 should facilitate principally their nucleophilic exchange by metal
alkanides. Therefore, we investigated the behavior of 3 in the presence of an excess of t-
BuLi in THF. The result was surprising in that indeed the MeO group at C(4) was
exchanged by a t-Bu group; however, the X-sulfonyl group at C(3) was eliminated also
(Table 3 and Fig. 3). The yield of the products 9 was good as long as at least two equiv.
of t-BuLi were applied. We also observed that the yields of 9, starting with the
corresponding 3-(phenylsulfonyl)benzo[a]heptalenes, were in all cases higher than
those from the 3-(morpholinosulfonyl)benzo[a]heptalenes. Moreover, in the case of
the reaction of 3e with t-BuLi, we performed a careful chromatographic separation of
the crude product. By this way, we found the 2-methoxy-4-morpholinobenzo[a]hepta-
lene 10a as a second product (Scheme 4). The position of the substituents at the benzo
moiety was secured by an X-ray crystal-structure determination (see Exper. Part).
We performed a number of control experiments to understand mechanistically the
reductive elimination of the X-sulfonyl group, which accompanies the substitution
reaction of compounds 3 with t-BuLi. We envisaged two principal possibilities, which
are displayed in Scheme 5, thereby taking into account that an H-atom (or in an
alternative view, a hydride ion) had to be transferred to C(3) of the benzo moiety
carrying the X-sulfonyl group, so that this group could be eliminated as X-sulfinate.
Table 3. 4-(tert-Butyl)-2-methoxybenzo[a]heptalenes 9 from 2,4-Dimethoxy-3-X-sulfonylbenzo[a]hep-
talenes 3 and t-BuLi
Entry
Reactant
R
Xa)
Product
Yield [%]b)
1
2
3
4
5
6
3a
3e
3b
3d
3c
3f
7-Me, 9-iPr
Ph
Mor
Ph
Mor
Ph
Mor
9a
9a
9b
9b
9c
9c
94
79c)
72
7,8,10-Me3
8,10-Me2
66
65
59
a) Mor¼ morpholino. b) Yield of crystallized products. c) See text and Scheme 4.

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Fig. 3. Stereoscopic view of the X-ray crystal structure of 4-(tert-butyl)-9-isopropyl-2-methoxy-7,12-
dimethylbenzo[a]heptalene (9a) (50% probability ellipsoids)
Scheme 4
There is little doubt that nucleophiles enter compounds 3 first at C(4) due to the
reduction of peri-strain (C(4)ꢀOMe $ HꢀC(5)) in the intermediates A (Scheme 5).
The elimination of MeOꢀ leads thus to the primary products 11. Indeed, the reaction of
3a with t-BuLi gave small isolable amounts of 11a (R ¼ 7-Me, 9-iPr, X ¼ Ph). On the
other hand, when we used BuLi instead of t-BuLi the corresponding 4-butyl-2-
methoxy-3-(phenylsulfonyl)benzo[a]heptalene 12a was found in a yield of 82% (see
Exper. Part), but no possible follow-up products comparable with 9a. In addition, we
found that quenching the reaction of 3a and t-BuLi with D2O did not lead to any D-
incorporation at C(3) of 9a according to its 2H-NMR analysis. This means that
compounds 9, lithiated at C(3), are not intermediates of the elimination of the X-
sulfonyl group in the course of the discussed reaction.
The intermediates A would have principally the structural prerequisite for a
pericyclic H-shift by elimination of formaldehyde and formation of intermediate B – in
analogy to the thermal retro-ene reaction of allyl methyl ethers (Scheme 5, Path a).
Intermediates B would be ideally disposed for the elimination of X-sulfinate under
formation of compounds 9. The second molecule of alkyllithium would then be
necessary for the trapping of formaldehyde as primary lithium alkoxide. In someway
more realistic seems to be, however, the uptake of a second molecule of t-BuLi at C(2)
of the primary products 11. This will result in the formation of intermediates C, which
also can undergo an anionic retro-ene fragmentation under formation of intermediates
D and 2-methylprop-1-ene (Scheme 5, Path b). Now, elimination of X-sulfinate can
take place under formation of the final products 9. This second pathway would also

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Scheme 5
explain the appearance of by-product 10a in case of the reaction of the 3-
(morpholinosulfonyl)benzo[a]heptalene 3e with t-BuLi – we suppose that similar by-
products were also present in the product mixtures obtained from 3d and 3f (cf.
Table 3), but we looked not specifically for them. Lithium morpholinosulfinate, formed
in the elimination reaction of the corresponding intermediate D, seems to decompose
under the reaction conditions into morpholinolithium and SO2. The morpholinolithi-
um, on the other hand, seems to act as competitor for t-BuLi in the substitution reaction
at C(4) of 3e. Indeed, the reaction of 3a with piperidinolithium in THF at ꢀ 58 gives
smoothly the corresponding 2,4-dipiperidino-3-(phenylsulfonyl)benzo[a]heptalene in
a yield of 89% [10]. The further steps of intermediate 11 (R ¼ 7-Me, 9-iPr, Rꢃ ¼ X ¼
morpholino) to 10a would then follow the path of reduction by t-BuLi as sketched in
Scheme 5, Path b.
A last point, worth to be investigated, was the question whether Path a in Scheme 5
contributes to the global reductive elimination of the X-sulfonyl group at C(3) or not or
to what extent. To clarify this point, we synthesized 3a with [2H3]MeOꢀC(4), following
an established pathway [6], and treated it in the usual manner with t-BuLi. The result of
2
this experiment was unequivocal. We found neither by H-NMR spectroscopy nor by
2
mass spectrometry any H incorporation in product 9a. This result means that Path a
(Scheme 5) has no relevance for the formation of the products 9.

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2.4. Reaction of 2,4-Dimethoxy-3-(phenylsulfonyl)benzo[a]heptalenes with MeLi.
The reaction of the model compound 3a with three equiv. of MeLi in THF at ꢀ 58
offered no surprise. We isolated the expected 2-methoxy-4-methyl-3-(phenylsulfonyl)-
benzo[a]heptalene 13a after crystallization from AcOEt/hexane in 94% yield
(Scheme 6).
Scheme 6
However, the chemical scene changed completely when we applied 7 equiv. of MeLi
on 3a and its analogs 3b and 3c (Table 4). We isolated from the product mixtures in
good to excellent yields the 4-benzyl-2-methoxybenzo[a]heptalenes 14a – 14c. In the
case of the reaction of 3b, we isolated by column chromatography a second unusable
product 15b (Scheme 7). Its structure was solved by an X-ray crystal-structure
determination (Fig. 4). It revealed the relation of 15b to other dibenzothiophene
derivatives, which we had found after treatment of 3a with lithium diisopropylamide
(LDA) [10].
Treatment of 13a with MeLi or other alkyllithiums gave 14a in high yields (Table 5).
The formal elimination of SO2 in the course of the rearrangement 13 to 14 must
therefore follow a quite different path as compared with the transformation 3 to 9
caused specifically by t-BuLi, despite the fact that the products look quite similar.
Table 4. Reaction of 2,4-Dimethoxy-3-(phenylsulfonyl)benzo[a]heptalenes 3 with an Excess of MeLia)
Reactant
R
Time [h]
Product
Yield [%]b)
3a
3b
3c
7-Me, 9-iPr
7,8,10-Me3
8,10-Me2
1.5
6
2.5
14a
14b
14c
91
76c)
84
c
a) For details, see Exper. Part. b) Yield of purified product. ) A second product, 15b, was isolated in this
case; see text.

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Scheme 7
Fig. 4. Stereoscopic view of the X-ray crystal structure of the heptaleno-fused dibenzothiophene 15b (50%
probability ellipsoids)
Table 5. Rearrangement of 2-Methoxy-4-methyl-3-(phenylsulfonyl)benzo[a]heptalene 13a
Base
Time [min]a)
Yield [%]
MeLi
BuLi
t-BuLi
90
10
30
83
65
68
a) Time at r.t., after addition of RLi and 15 min at ꢀ 58.

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A possible mechanism of the surprising rearrangement 13a ! 14a, driven by MeLi
or other alkyllithiums and accompanied by the formal loss of SO2, is shown in
Scheme 8. It starts with the deprotonation (lithiation) of MeꢀC(4) by MeLi to give
intermediate E. The cyclization of E to intermediate F profits by the better stabilization
of the negative charge as cyclohexadienyl anion. The latter shifts the negative charge by
ring opening to the sulfinate structure G. The sulfinate substituent of G takes up MeLi
(in general, RLi; see Table 5) in the same way as carboxylates react with RLi to form
finally ketones. In the present case, fragmentation to methanesulfinate and the
corresponding phenyl anion takes place, followed by protonation in the course of
workup.
Scheme 8
A last point of concern was the question how 2,4-dimethoxy-3-(morpholinosulfo-
nyl)benzo[a]heptalenes 3 would behave in the presence of an excess of MeLi. The
expected benzyl anion of type E (cf. Scheme 8; morpholinoSO2 instead of PhSO2)
showed as expected no further reactions. However, traces of air led to the formation of
the corresponding benzyl alcohols 16 in good yield (Table 6). The necessity of air for
the formation of 16 excludes the possibility that MeLi deprotonates (lithiates)
MeOꢀC(4) of 3 (X ¼ morpholino), so that the formed anion undergoes a three-atom
Smiles rearrangement to the corresponding benzyl oxides of 16.
The most interesting spectroscopic feature of the new compounds 16 is that the
benzylic H-atoms of the primary alcohol function at C(4) are diastereotopic. Their
1H-NMR signals (CDCl3) appear as AB system, for 16e for example, at d(H) 5.09 and
4.83, with JAB ¼ 12.7 Hz, whereby both signals are further split by a vicinal coupling
(J ¼ 9.7 and 5.9 Hz, resp.) with the H-atom of the OH group. These findings, together
with the observation of a strong reciprocal NOE effect between one of the CH2ꢀC(4)
proton (d(H) 4.83, 3J ¼ 9.7 Hz) and HꢀC(5) speaks for a relatively fixed arrangement
of the CH2OH group in 16e due to H-bonding of the H-atom of the OH group and one

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Table 6. Reaction of 2,4-Dimethoxy-3-(morpholinosulfonyl)benzo[a]heptalene 3 with an Excess of MeLi
in the Presence of Air
Reactant
R
Time [h]
Product
Yield [%]a)
3e
3d
3f
7-Me, 9-iPr
7,8,10-Me3
8,10-Me2
4
8
5
16e
16d
16f
78
63
69
a) Yield of purified and recrystallized product.
of the O-atoms of the SO2 group. The same is true for 16d and 16f. The structure of 16e
was finally established by an X-ray crystal-structure determination, which revealed an
intramolecular H-bond with a distance of 206 pm between the H-atom of the OH
group and one of the O-atoms of the SO2 group (Fig. 5).
Fig. 5. Stereoscopic view of the X-ray crystal structure of 9-isopropyl-2-methoxy-7,12-dimethyl-3-
(morpholinosulfonyl)benzo[a]heptalene-4-methanol (16e) (50% probability ellipsoids)
In conclusion, we can say that the synthesis of benzo[a]heptalenes, starting with
heptalene-1,2- or -4,5-dicarboxylates or their derivatives, allows the entrance to
colchicinoids with substituents at the benzo moiety, which can be changed at will to
optimize possible biological activities.
We thank our NMR department for specific NMR measurements, our MS laboratory for recording
mass spectra, and our micro-analytical laboratory for elemental analyses. Financial support by the Swiss
National Science Foundation is gratefully acknowledged.

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Experimental Part
General. For the synthesis of the benzo[a]heptalene derivatives as starting material, see [4] and ref.
cit. therein. All solvents (Et2O, THF) were purified by refluxing over Na benzophenone. They were
distilled just before use. All reactions with carbanions were performed under Ar. Melting points: Bꢁchi-
FP5 melting-point apparatus; uncorrected. Column chromatography (CC): silica gel 60 (SiO2 ; 40 –
63 mm; Chemie Uetikon AG). TLC: aluminium sheets coated with SiO2 60 F254 (Merck). 1H- and
13C-NMR Spectra: Bruker-ARX300, -AMX-500, or -AMX-600 spectrometers; in CDCl3; d in ppm rel. to
internal SiMe4 (¼0 ppm) at 300 K and internally adjusted to the solvent signals d(H) 7.26 and d(C)
77.00), J in Hz; assignment by additional DEPT 90, DEPT 135, COSY, NOESY, NOE, HSQC, HMBC,
TOCSY, and 2H-NMR measurements; for most of the benzo[a]heptalenes, only the signals for the benzo
moiety (C(1)ꢀC(4)) are given since the position of the signals of the heptalene part and its substituents
do not vary very much (see, e.g., [3][5][9][11]). Mass spectra: CI: Finnigan-MAT-95 mass spectrometer;
at 70 eV and 2508, with NH3; EI: at 70 eV ionization energy on a GC/MS Carlo-Erba instrument (GC-
8000-Top gas chromatograph; OV-5 capillary column (15 m ꢁ 0.25 mm), coated with 95% dimethyl- and
5% diphenylpolysiloxane); oily compounds showed correct MS; in m/z (rel. %). Elemental analyses: all
crystalline compounds gave correct elemental analyses.
1. Alkylation Reactions. 1.1. Methylation of 9-Isopropyl-7,12-dimethyl-3-(phenylsulfonyl)benzo[a]-
heptalene-2,4-diol (2a). 1.1.1. General Procedure. To a soln. of K2CO3 (0.5 g, 3.6 mmol) in H2O (30 ml), a
soln. of 2a (0.100 g, 0.22 mmol) in EtOH (5 ml) was added, and the mixture was stirred for 1 h at ꢀ 58.
Then, MeI (1 ml, 7 mmol) was added. The mixture was stirred for 24 h at r.t. The mixture was treated with
HCl/ice, and the product was extracted with Et2O. The org. phase was washed with brine and dried
(Na2SO4). The residue of the org. phase was purified by CC (hexane/AcOEt 8 :1) to give, after
crystallization from CH2Cl2, 0.021 g (20%) of 9-isopropyl-1,7,12-trimethyl-3-(phenylsulfonyl)benzo[a]-
heptalene-2,4-diol (6a). Yellow plates. M.p. 207.1 – 208.38 ([5]: 208.6 – 209.58 (CH2Cl2/hexane)). Spectra:
identical with those reported in [5].
1.1.2. C- and O-Methylation of 2a. Heptalene 2a (0.100 g, 0.22 mmol) was added to a suspention of
K2CO3 (0.5 g, 3.6 mmol) in EtOH (20 ml). The mixture was stirred for 1 h at ꢀ 58. MeI (1 ml, 7 mmol)
was added, and stirring was continued for 24 h at r.t. After addition of H2O, the product was extracted
with Et2O, the Et2O phase dried (Na2SO4), the solvent evaporated, and the product purified by CC
(hexane/AcOEt 8 :1). The product was crystallized from Et2O with a drop of CH2Cl2 to give 5.4 mg (5%)
of 9-isopropyl-2,4-dimethoxy-1,7,12-trimethyl-3-(phenylsulfonyl)benzo[a]heptalene. Yellow crystals.
M.p. 179.9 – 180.48. Rf (hexane/AcOEt 3 :1) 0.49. 1H(13C)-NMR: 3.92 (63.42) (MeOꢀC(4)); 3.86
(62.46) (MeOꢀC(2)); 1.98 (12.86) (MeꢀC(1)).
1.2. Alkylation of 2,4-Dimethoxybenzo[a]heptalenes 4: General Procedure. To a soln. of 2,4-
dimethoxybenzo[a]heptalene 4 (0.50 g) in dry THF (10 ml), 2.5m BuLi (2.5 equiv. per equiv. of 4) was
slowly added at ꢀ 58. The mixture was stirred for 2 h, then MeI or EtI (20 equiv. per equiv. of 4) was
slowly added, and stirring was continued for the time indicated in Table 2. The mixture was treated with
ice/4n HCl and then extracted with AcOEt. The org. phase was washed with brine and dried (Na2SO4).
The yellow products were purified by CC (hexane/AcOEt 10 :1), followed by crystallization from a Et2O/
hexane mixture. For yields, see Table 2.
9-Isopropyl-2,4-dimethoxy-3,7,12-trimethylbenzo[a]heptalene (8aa): M.p. 118.0 – 121.68. Rf (hexane/
AcOEt 4 :1) 0.74. 1H(13C)-NMR: 6.30 (106.35) (HꢀC(1)); 3.80 (55.73) (MeOꢀC(2)); 3.74 (60.71)
(MeOꢀC(4)); 2.17 (8.89) (MeꢀC(3)).
2,4-Dimethoxy-3,7,8,10,12-pentamethylbenzo[a]heptalene (8ba): M.p. 106.0 – 108.38. Rf (hexane/
AcOEt 4 :1) 0.70. 1H(13C)-NMR: 6.28 (105.54) (HꢀC(1)); 3.78 (55.71) (MeOꢀC(2)); 3.77 (60.74)
(MeOꢀC(4)); 2.19 (8.92) (MeꢀC(3)).
2,4-Dimethoxy-3,8,10,12-tetramethylbenzo[a]heptalene (8ca): M.p. 129.2 – 130.88. Rf (hexane/AcOEt
4 :1) 0.78. 1H(13C)-NMR: 6.31 (106.46) (HꢀC(1)); 3.79 (55.73) (MeOꢀC(2)); 3.75 (60.67)
(MeOꢀC(4)); 2.19 (8.92) (MeꢀC(3)). For the X-ray crystal structure of 8ca, see Table 7.
3-Ethyl-9-isopropyl-2,4-dimethoxy-7,12-dimethylbenzo[a]heptalene (8ab): Yellow oil. Rf (hexane/
AcOEt 4 :1) 0.77. 1H(13C)-NMR: 6.32 (106.70) (HꢀC(1)); 3.81 (55.63) (MeOꢀC(2)); 3.78 (61.67)

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Helvetica Chimica Acta – Vol. 93 (2010)
(MeOꢀC(4)); 2.74, 2.67 (17.21) (AB of ABX3, 2JAB ¼ 12.9, MeCH2ꢀC(3)); 1.18 (14.42) (3JAX ¼ 3JBX ¼ 7.1,
MeCH2ꢀC(3)).
3-Ethyl-2,4-dimethoxy-7,8,10,12-tetramethylbenzo[a]heptalene (8bb): M.p. 154.0 – 158.58. Rf (hexane/
AcOEt 4 :1) 0.74. 1H(13C)-NMR: 6.29 (105.94) (HꢀC(1)); 3.77 (55.66) (MeOꢀC(2)); 3.80 (61.70)
(MeOꢀC(4)); 2.73, 2.69 (17.27) (AB of ABX3, 2JAB ¼ 12.9, MeCH2ꢀC(3)); 1.19 (14.43) (3JAX ¼ 3JBX ¼ 7.5,
MeCH2ꢀC(3)). For the X-ray crystal structure of 8bb, see Fig. 1 and Table 7.
3-Ethyl-2,4-dimethoxy-8,10,12-trimethylbenzo[a]heptalene (8cb): Yellow oil. Rf (hexane/AcOEt
4 :1) 0.81. 1H(13C)-NMR: 6.31 (106.88) (HꢀC(1)); 3.78 (55.66) (MeOꢀC(2)); 3.77 (61.70)
2
(MeOꢀC(4)); 2.73, 2.67 (17.29) (AB of ABX3, JAB ¼ 12.9, MeCH2ꢀC(3)); 1.18 (14.41) (3JAX ¼ 3JBX
¼
7.5, MeCH2ꢀC(3)).
1.3. Reaction of 2,4-Dimethoxy-3-(X-sulfonyl)benzo[a]heptalenes 3 with t-BuLi: General Procedure.
To a soln. of heptalene 3 (0.50 g) in dry THF (10 ml) was added slowly at ꢀ 58 1.6m t-BuLi (4 equiv. per
equiv. of 3). The mixture was stirred at ꢀ 58 for 15 min. Then, the mixture was treated with ice/4n HCl,
followed by extraction with AcOEt. The org. phase was washed with brine and dried (Na2SO4), the
solvent evaporated, and the residue subjected to CC (hexane/AcOEt 5 :1). Finally, the products were
crystallized from hexane/petroleum ether. See Table 3 and Scheme 4 for yields.
4-(tert-Butyl)-9-isopropyl-2-methoxy-7,12-dimethylbenzo[a]heptalene (9a): M.p. 89.9 – 91.08. Rf
(hexane/AcOEt 4 :1) 0.74. 1H(13C)-NMR: 159.90 (C(2)); 149.06 (C(4)); 7.03 (113.08) (Jm ¼ 2.7,
HꢀC(3)); 6.40 (109.98) (Jm ¼ 2.9, HꢀC(1)); 3.80 (55.19) (MeOꢀC(2)); 1.51 (35.95, 31.39)
(Me3CꢀC(4)). For the X-ray crystal structure of 9a, see Fig. 3 and Table 7.
4-(tert-Butyl)-9-isopropyl-2-methoxy-7,12-dimethyl-3-(phenylsulfonyl)benzo[a]heptalene (11a): Rf
1
(hexane/AcOEt 3 :1) 0.59. H-NMR (300 MHz): 7.54 (m, Ho of Ph); 7.42 (m, Hp of Ph); 7.33 (m, Hm
of Ph; d, 3J(5,6) ¼ 12.1, HꢀC(5)); 6.44 (AB, HꢀC(10), HꢀC(11)); 6.26 (d, 3J(6,5) ¼ 12.1, HꢀC(6)); 6.12
(s, HꢀC(1)); 5.81 (s, HꢀC(8)); 3.00 (s, MeOꢀC(2)); 2.53 (sept., Me2CHꢀC(9)); 1.80 (s, Me3CꢀC(4));
3
1.71 (s, MeꢀC(7)); 1.49 (s, MeꢀC(12)); 1.14, 1.13 (2d, J ¼ 6.9, 6.8, Me2CHꢀC(9)).
9-Isopropyl-7,12-dimethyl-4-(morpholin-4-yl)benzo[a]heptalene (10a): Yellow crystals. M.p. 199.9 –
1
202.08 (Et2O/hexane). Rf (hexane/AcOEt 3 :1) 0.56. H(13C)-NMR: 161.06 (C(2)); 151.88 (C(4)); 6.58
(105.11) (Jm ¼ 2.5, HꢀC(3)); 6.28 (107.80) (Jm ¼ 2.4, HꢀC(1)); 3.89, 3.82, 3.18, 2.77 (67.34, 52.60)
(O(CH2CH2)2NꢀC(4)); 3.79 (55.40) (MeOꢀC(2)). EI-MS (C26H31NO2; 389.20): 390.2 (75, [M þ 1]þ),
.
.
389.2 (100, Mþ ), 374.1 (84, [M ꢀ Me]þ), 349.1 (50, [M ꢀ MeC ꢂ CH]þ ). For the X-ray crystal structure
of 10a, see Table 7.
4-(tert-Butyl)-2-methoxy-7,8,10,12-tetramethylbenzo[a]heptalene (9b): M.p. 127.3 – 129.88. Rf (hex-
ane/AcOEt 4 :1) 0.77. 1H(13C)-NMR: 159.78 (C(2)); 149.10 (C(4)); 7.00 (108.88) (Jm ¼ 2.7, HꢀC(3)); 6.34
(112.99) (Jm ¼ 2.6, HꢀC(1)); 3.76 (55.24) (MeOꢀC(2)); 1.50 (35.97, 31.44) (Me3CꢀC(4)).
4-(tert-Butyl)-2-methoxy-8,10,12-trimethylbenzo[a]heptalene (9c): M.p. 68.9 – 70.88. Rf (hexane/
1
AcOEt 4 :1) 0.75. H(13C)-NMR: 160.22 (C(2)); 149.14 (C(4)); 7.01 (113.31) (Jm ¼ 2.7, HꢀC(3)); 6.36
(109.81) (Jm ¼ 2.7, HꢀC(1)); 3.77 (55.27) (MeOꢀC(2)); 1.48 (35.98, 31.48) (Me3CꢀC(4)).
1.4. Reaction of 9-Isopropyl-2,4-dimethoxy-7,12-dimethyl-3-(phenylsulfonyl)benzo[a]heptalene (3a)
with BuLi. To a soln. of 3a (0.5 g, 1.05 mmol) in dry THF (15 ml), 2.5m BuLi (0.55 ml, 1.37 mmol) was
added slowly at ꢀ 408. The mixture was stirred for 10 min. Then, the mixture was treated with ice/4n HCl
and extracted with AcOEt. The org. phase was washed with brine and dried (Na2SO4). The residue of the
extract was purified by CC (hexane/AcOEt 8 :1). The product was crystallized from Et2O/hexane to give
0.43 g (82%) of pure 4-butyl-9-isopropyl-2-methoxy-7,12-dimethyl-3-(phenylsulfonyl)benzo[a]heptalene
(12a): Yellow crystals. M.p. 92.1 – 94.08. Rf (hexane/AcOEt 4 :1) 0.42. 1H-NMR (600 MHz): 7.89 (dd, Jo ¼
7.3, Jm ¼ 1.3, Ho of Ph); 7.51 (m, Hp of Ph); 7.46 (m, Hm of Ph); 7.05 (d, 3J(5,6) ¼ 12.1, HꢀC(5)); 6.40 (d,
3
4
3J(11,10) ¼ 11.9, HꢀC(11)); 6.36 (dd, J(10,11) ¼ 11.9, J(10,8) ¼ 1.1, HꢀC(10)); 6.32 (s, HꢀC(1)); 6.30
(d, 3J(6,5) ¼ 12.2, HꢀC(6)); 5.74 (s, HꢀC(8)); 3.50, 3.34 (2m, MeCH2CH2CH2ꢀC(4)); 3.47 (s,
MeOꢀC(2)); 2.53 (sept., Me2CHꢀC(9)); 1.82, 1.74 (2m MeCH2CH2CH2ꢀC(4)); 1.71 (s, MeꢀC(7));
1.62 (s, MeꢀC(12)); 1.57 (m, MeCH2CH2CH2ꢀC(4)); 1.14, 1.13 (2d, 3J ¼ 6.8, 6.7, Me2CHꢀC(9)); 1.02 (t,
3J ¼ 7.4, MeCH2CH2CH2ꢀC(4)). 13C-NMR (150 MHz): 158.39 (s, C(2)); 147.18 (s, C(9)); 144.79 (s, Cipso
of Ph); 144.56 (s, C(12b)); 144.13 (s, C(4)); 135.44 (d, C(11)); 135.08 (s, C(12a)); 134.15 (s, C(7a)); 132.97
(d, C(6)); 132.06 (d, Cp of Ph); 131.60 (d, C(10)); 131.05 (s, C(12)); 130.11 (s, C(4a)); 128.37 (d, C(5));
128.16 (s, C(7)); 128.13 (d, Cm of Ph); 126.99 (s, C(3)); 126.87 (d, Co of Ph); 121.96 (d, C(8)); 110.88 (d,

Helvetica Chimica Acta – Vol. 93 (2010)
1909
C(1)); 55.85 (q, MeOꢀC(2)); 34.45 (d, Me2CHꢀC(9)); 29.14 (t, MeCH2CH2CH2ꢀC(4)); 33.70 (t,
MeCH2CH2CH2ꢀC(4)); 23.29 (t, MeCH2CH2CH2ꢀC(4)); 22.69, 22.78 (2q, Me2CHꢀC(9)); 19.65 (q,
MeꢀC(12)); 16.57 (q, MeꢀC(7)); 13.85 (q, MeCH2CH2CH2ꢀC(4)). EI-MS (C12H36O3S; 500.71): 501.2
.
.
(33, [M þ 1]þ), 500.1 (100, [M]þ ), 485.06 (30, [M ꢀ Me]þ), 460.1 (12, [M ꢀ MeC ꢂ CH]þ ).
1.5. Reaction of 2,4-Dimethoxy-3-(X-sulfonyl)benzo[a]heptalenes 3 with MeLi. 1.5.1. 2,4-Dimethoxy-
3-(phenylsulfonyl)benzo[a]heptalenes 3a – 3c: General Procedure. To a soln. of 0.50 g of the 3-
(phenylsulfonyl)benzo[a]heptalene 3 in dry THF (10 ml) was added slowly at ꢀ 58 a soln. of 1.6m
MeLi (7 equiv. per equiv. of 3) in portions of 2 equiv. of MeLi. The mixture was stirred at ꢀ 58 for
15 min, and then stirring was continued at r.t. for the time indicated in Table 4. Ice/4n HCl was added, and
the product was extracted with AcOEt. The org. phase was washed with brine and dried (Na2SO4). The
yellow oily products were purified by CC (hexane/AcOEt 4 :1).
4-Benzyl-9-isopropyl-2-methoxy-7,12-dimethylbenzo[a]heptalene (14a): Rf (hexane/AcOEt 4 :1)
0.76. 1H(13C)-NMR: 160.62 (C(2)); 140.15 (C(4)); 6.66 (115.82) (Jm ¼ 2.6, HꢀC(3)); 6.44 (111.39)
(Jm ¼ 2.8, HꢀC(1)); 4.12, 4.07 (39.75) (AB, 2JAB ¼ 15.9, PhCH2ꢀC(4)); 3.75 (55.27) (MeOꢀC(2)).
9-Isopropyl-2-methoxy-4,7,12-trimethyl-3-(phenylsulfonyl)benzo[a]heptalene (13a): Yellow crystals.
M.p. 216.7 – 218.28 (hexane/AcOEt). Rf (hexane/AcOEt 1:1) 0.70. 1H(13C)-NMR: 158.48 (C(2)); 139.21
(C(4)); 127.80 (C(3)); 6.33 (110.81) (HꢀC(1)); 2.92 (16.59) (MeꢀC(4)). EI-MS (C29H30O3S; 458.62):
.
.
459.1 (31, [M þ 1]þ), 458.0 (100, Mþ ), 423.0 (39, [M ꢀ Me]þ), 418.0 (35, [M ꢀ MeC ꢂ CH]þ ).
Rearrangement of 13a with Alkyl Lithium (RLi) Bases: To a soln. of 13a (0.50 g, 1.09 mmol) in dry
THF (10 ml), kept under stirring at ꢀ 58, were added slowly in portions 3.27 mmol of the corresponding
RLi soln. (R ¼ Me, Bu, and t-Bu). Stirring was continued at ꢀ 58 for additional 15 min and then at r.t. for
the time indicated in Table 5 to give 14a.
4-Benzyl-2-methoxy-7,8,10,12-tetramethylbenzo[a]heptalene (14b): Rf (hexane/AcOEt 4 :1) 0.81.
1H(13C)-NMR: 160.53 (C(2)); 139.53 (C(4)); 6.49 (115.74) (Jm ¼ 2.7, HꢀC(3)); 6.40 (110.32) (Jm ¼ 2.7,
HꢀC(1)); 4.15, 4.05 (39.83) (AB, 2JAB ¼ 15.9, PhCH2ꢀC(4)); 3.73 (55.26) (MeOꢀC(2)).
1,3,5,6-Tetramethylbenzo[b]heptaleno[2’,1’:4,5]benzo[1,2-d]thiophen-9-ol 10,10-Dioxide (15b): Yel-
low needles. M.p. 304.9 – 307.38 (AcOEt/Et2O). Rf (hexane/AcOEt 2 :1) 0.48. 1H-NMR (600 MHz): 7.80
(d, Jo ¼ 7.6, HꢀC(11)); 7.69 (d, Jo ¼ 7.5, HꢀC(14)); 7.61 (td, Jo ¼ 7.4, Jm ¼ 1.1, HꢀC(13)); 7.50 (td, Jo ¼ 7.6,
Jm ¼ 1.1, HꢀC(12)); 7.07 (d, 3J(8,7) ¼ 11.9, HꢀC(8)); 6.93 (s, HꢀC(15)); 6.33 (br. s, HOꢀC(9); 6.45 (d,
3J(7,8) ¼11.9, HꢀC(7)); 6.21 (struct. s, HꢀC(2)); 6.08 (struct. s, HꢀC(4)); 2.05 (d, 4J(Me,HꢀC(2)) ¼ 1.1,
MeꢀC(3)); 1.95 (d, 4J(Me,HꢀC(4)) ¼ 1.1, MeꢀC(5)); 1.75 (s, MeꢀC(6)); 1.69 (s, MeꢀC(1)). 13C-NMR
(125 MHz): 149.74 (C(9)); 145.33 (C(15a)); 139.27 (C(3)); 138.12 (C(10a)); 137.75 (C(5a)); 135.96
(C(7)); 133.86 (C(13)); 133.33 (C(14b)); 131.81 (C(14a)); 131.17 (C(1)); 130.45 (C(2)); 130.14 (C(5),
C(12)); 113.88 (C(15)); 120.70 (C(9a)); 121.95 (C(11)); 121.79 (C(14)); 129.16 (C(15b)); 128.85 (C(4));
128.35 (C(8a)); 127.86 (C(6)); 123.25 (C(8)); 25.09 (MeꢀC(3)); 22.97 (MeꢀC(5)); 19.07 (MeꢀC(1));
17.82 (MeꢀC(6)). CI-MS (C26H22O3S; 414.52): 434.3 (21), 433.3 (32), 432.3 (100, [M þ NH4]þ), 414 (5,
.
Mþ ). For the X-ray crystal structure of 15b, see Fig. 4 and Table 7.
4-Benzyl-2-methoxy-8,10,12-trimethylbenzo[a]heptalene (14c): Rf (hexane/AcOEt 4 :1) 0.83.
1H(13C)-NMR: 160.94 (C(2)); 139.52 (C(4)); 6.69 (116.11) (Jm ¼ 2.7, HꢀC(3)); 6.45 (111.29) (Jm ¼ 2.7,
HꢀC(1)); 4.14, 4.08 (39.83) (AB, 2JAB ¼ 15.9, PhCH2ꢀC(4)); 3.75 (55.26) (MeOꢀC(2)).
1.5.2. 2,4-Dimethoxy-3-(morpholin-4-ylsulfonyl)benzo[a]heptalenes 3d – 3f: General Procedure. To a
soln. of 3-(morpholin-4-ylsulfonyl)benzo[a]heptalene 3 (0.50 g) in dry THF (10 ml) at ꢀ 58 was added
slowly at ꢀ 58 a soln. of 1.6m MeLi (10 equiv. per equiv. of 3) in portions of 2 equiv. After 15 min of each
addition of MeLi, the flask was opened and the mixture exposed to air for 30 s. After the last exposure to
air, stirring was continued at r.t. for the time indicated in Table 6. Ice and 4n HCl were added. The yellow
products were extracted with AcOEt, purified by CC (hexane/AcOEt 3 :1), and finally recrystallized
from hexane/Et2O.
9-Isopropyl-2-methoxy-7,12-dimethyl-3-(morpholin-4-ylsulfonyl)benzo[a]heptalene-4-methanol
(16e): Yellow prisms. M.p. 194.0 – 197.78. Rf (hexane/AcOEt 1:1) 0.59. 1H(13C)-NMR: 157.51 (C(2));
2
3
139.97 (C(4)); 127.24 (C(3)); 6.58 (112.64) (HꢀC(1)); 5.09 (A of ABX, JAB ¼ 12.7, JAX ¼ 5.9,
2
3
HOCH2ꢀC(4)); 4.83 (B of ABX, JAB ¼ 12.6, JBX ¼ 9.7, HOCH2ꢀC(4)); 3.90 (56.72) (MeOꢀC(2));
3.35 (OH, partially covered by O(CH2CH2)2NSO2ꢀC(3)). For the X-ray crystal structure of 16e, see
Fig. 5 and Table 7.

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Helvetica Chimica Acta – Vol. 93 (2010)
2-Methoxy-7,8,10,12-tetramethyl-3-(morpholin-4-ylsulfonyl)benzo[a]heptalene-4-methanol (16d):
1
Yellow prisms. M.p. 215.2 – 216.78. Rf (hexane/AcOEt 1:1) 0.44. H(13C)-NMR: 157.42 (C(2)); 140.12
(C(4)); 127.20 (C(3)); 6.56 (111.69) (HꢀC(1)); 5.12 (A of ABX, 2JAB ¼ 12.7, 3JAX ¼ 5.7, HOCH2ꢀC(4));
2
3
4.84 (B of ABX, JAB ¼ 12.8, JBX ¼ 9.7, HOCH2ꢀC(4)); 3.87 (56.73) (MeOꢀC(2)); 3.41 (OH, partially
covered by O(CH2CH2)2NSO2ꢀC(3)).
2-Methoxy-8,10,12-trimethyl-3-(morpholin-4-ylsulfonyl)benzo[a]heptalene-4-methanol (16f): Yel-
low prisms. M.p. 225.1 – 226.38. Rf (hexane/AcOEt 1:1) 0.42. 1H(13C)-NMR: 157.64 (C(2)); 140.05
(C(4)); 127.52 (C(3)); 6.58 (112.66) (HꢀC(1)); 5.11 (A of ABX, 2JAB ¼ 12.8, 3JAX ¼ 5.7, HOCH2ꢀC(4));
2
3
4.82 (B of ABX, JAB ¼ 12.7, JBX ¼ 9.5, HOCH2ꢀC(4)); 3.88 (56.72) (MeOꢀC(2)); 3.36 (OH, partially
covered by O(CH2CH2)2NSO2ꢀC(3)).
2. Crystal-Structure Determination of 8bb, 9a, 15b, 16e, 10a, and 8ca (Table 7 and Figs. 1 and 3 – 5)1).
All measurements were conducted on a Nonius KappaCCD area detector diffractometer [12][13] by
using graphite-monochromated MoKa radiation (l 0.71073 ꢆ) and an Oxford-Cryosystems-Cryostream-
700 cooler. The data collection and refinement parameters are given in Table 7, while views of the
molecules of 8bb, 9a, 15b, and 16e are shown in Figs. 1 and 3 – 5. The intensities were corrected for
Lorentz and polarization effects but not for absorption. Each structure was solved by direct methods with
either SIR92 [14] or SHELXS97 [15], which revealed the positions of all non-H-atoms. The non-H-atoms
were refined anisotropically. The OH H-atom of 15b was placed in the position indicated by a difference-
electron-density map, and its position was allowed to refine together with an isotropic displacement
parameter. All of the remaining H-atoms were placed in geometrically calculated positions, and each H-
atom 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 groups of 9a). The orientation of the hydroxy OꢀH vector in 16e was based on
the position of a peak located in a difference-electron-density map. The refinement of each structure was
carried out on F (F2 for 9a) by using full-matrix least-squares procedures. A correction for secondary
extinction was applied in the cases of 8bb, 9a, 10a, and 8ca.
The asymmetric unit of 9a contains one molecule of the heptalene plus one half of a hexane
molecule. The hexane molecule sits across a crystallographic center of inversion and is disordered. Two
positions were defined for the central two C-atoms of the hexane molecule. The site-occupation factors of
the two conformations were held fixed at a ratio of 0.8/0.2. Bond-length restraints were applied to the
bonds of the hexane molecule so as to maintain reasonable geometry. Compound 8ca crystallized in a
noncentrosymmetric polar space group with two symmetry-independent molecules in the asymmetric
unit. These molecules are almost perfectly related to one another by a local center of inversion; however,
no additional crystallographic symmetry could be found. The absolute direction of the polar axis was
chosen arbitrarily.
Neutral-atom scattering factors for non-H-atoms were taken from [16a], and the scattering factors
for H-atoms were taken from [17]. Anomalous dispersion effects were included in Fc [18]; the values for
f’ and f’’ were those of [16b]. The values of the mass-attenuation coefficients are those of [16c]. All
calculations were performed with the teXsan crystallographic software package [19] (SHELXL97 [14]
for 9a). The crystallographic diagrams were drawn with ORTEPII [20].
REFERENCES
˜
[1] ꢄThe Collected Lyric Poems of Luꢂs de Camoesꢃ, translated by Landeg White, Princetown University
Press, Princetown, 2008, p. 226.
[2] P. Kouroupis, H.-J. Hansen, Helv. Chim. Acta 1995, 78, 1247.
[3] K. Abou-Hadeed, H.-J. Hansen, Helv. Chim. Acta 1997, 80, 2535.
[4] K. Abou-Hadeed, H.-J. Hansen, in ꢄScience of Synthesisꢃ, Georg Thieme Verlag KG, Stuttgart – New
York, 2010, Vol. 45b, p. 1043.
1
)
CCDC-775914 – 77599 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.

Helvetica Chimica Acta – Vol. 93 (2010)
1911
[5] K. Abou-Hadeed, H.-J. Hansen, Helv. Chim. Acta 2003, 86, 4018.
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Received May 12, 2010