A new alkylation method for heptalene-4,5-dicarboxylates their pseudoester forms

Article abstract of DOI:10.1002/hlca.201100510

Dimethyl heptalene-4,5-dicarboxylates³) undergo preferentially a Michael addition reaction at C(3) with α-lithiated alkyl phenyl sulfones at temperatures below -50°, leading to corresponding cis-configured 3,4-dihydroheptalene-4,5-dicarboxylates (cf. Table 1, Schemes 3 and 4). The corresponding heptalenofuran-1-one-type pseudoesters of dimethyl heptalene-4,5-dicarboxylates (Scheme 5) react with [(phenylsulfonyl)methyl] lithium almost exclusively at C(1) of the furanone group (Scheme 6). In contrast to this expected behavior, the uptake of 1-[phenylsulfonyl)ethyl]lithium occurs at C(5) of the heptalenofuran-1-ones as long as they carry a Me group at C(11) (Schemes 6 and 7). The 1,4- as well as the 1,6-addition products eliminate, on treatment with MeONa/MeOH in THF, benzenesulfinate, thus leading to 3- and 4-alkylated dimethyl heptalene-4,5-dicarboxylates, respectively (Schemes 8-13). The configuration of the addition reaction of the nucleophiles to the inherently chiral heptalenes is discussed in detail (cf. Schemes 14-19) on the basis of a number of X-ray crystal-structure determinations as well as by studies of the temperature-dependence of the ¹H-NMR spectra of the addition products.

Full text of DOI:10.1002/hlca.201100510

Helvetica Chimica Acta – Vol. 95 (2012)
885
A New Alkylation Method for Heptalene-4,5-dicarboxylates and of One of
Their Pseudoester Forms
by Khaled Abou-Hadeed*, Zolta`n A. Molnar1), Pinar Gçksaltık2), Roland W. Kunz, Anthony Linden,
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 Conrad Hans Eugster on the occasion of his 90th birthday
Dimethyl heptalene-4,5-dicarboxylates3) undergo preferentially a Michael addition reaction at C(3)
with a-lithiated alkyl phenyl sulfones at temperatures below ꢀ 508, leading to corresponding cis-
configured 3,4-dihydroheptalene-4,5-dicarboxylates (cf. Table 1, Schemes 3 and 4). The corresponding
heptalenofuran-1-one-type pseudoesters of dimethyl heptalene-4,5-dicarboxylates (Scheme 5) react with
[(phenylsulfonyl)methyl]lithium almost exclusively at C(1) of the furanone group (Scheme 6). In
contrast to this expected behavior, the uptake of 1-[phenylsulfonyl)ethyl]lithium occurs at C(5) of the
heptalenofuran-1-ones as long as they carry a Me group at C(11) (Schemes 6 and 7). The 1,4- as well as
the 1,6-addition products eliminate, on treatment with MeONa/MeOH in THF, benzenesulfinate, thus
leading to 3- and 4-alkylated dimethyl heptalene-4,5-dicarboxylates, respectively (Schemes 8 – 13). The
configuration of the addition reaction of the nucleophiles to the inherently chiral heptalenes is discussed
in detail (cf. Schemes 14 – 19) on the basis of a number of X-ray crystal-structure determinations as well as
by studies of the temperature-dependence of the 1H-NMR spectra of the addition products.
1. Introduction. – Substitution reactions at the 12p-electron annulene core of
heptalenes under spontaneous re-establishment of the 12p-electron skeleton, as it is
well known for aromatic substitution reactions due to the recovery of aromatization
energy, are unknown. The situation changes on the level of transition-metal complexes
of heptalenes. In this way, Vogel and co-workers [2] synthesized, e.g., heptalene-1,6-
dicarboxaldehyde by Vilsmeier formylation of the cis-configured bis(tricarbonyliron)
complex of heptalene. This type of electrophilic substitution reaction can also be
realized, however, with [Fe(CO)3] complexes of open-chain hexa-1,3,5-trienes (see,
e.g., [3]). We have recently realized an electrophilic acetoxylation reaction of a MeO-
substituted heptalene-4,5-dicarboxylate, taking advantage of a corresponding hepta-
lenone as a relay compound [1]. The principle is displayed in Scheme 1. It demonstrates
the procedure that generally has to be followed when we undertake substitution
reactions at C¼C bonds in aliphatic or alicyclic surroundings, where we mostly have to
deal with individual addition and elimination steps or, in rarer cases, the reverse steps,
respectively.
1
)
)
)
Part of the Ph.D. thesis of Z. A. M., University of Zurich, 2002.
Part of the M.S. thesis of P. G., University of Zurich, 2000.
The locants of heptalene itself are maintained throughout the whole work. See footnote 4 in [1] for
reasoning.
2
3
ꢂ 2012 Verlag Helvetica Chimica Acta AG, Zꢁrich

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Scheme 1
Here, we report on a new alkylation at C(3) or C(2) of heptalene-4,5-dicarboxylates
and one of their pseudoester forms, respectively. It is based on the afore-mentioned
two-step principle, involving the Michael-addition reaction of a-lithiated alkyl phenyl
sulfones in the first step and the base-catalyzed elimination reaction of benzenesulfi-
nate in the second ꢃre-establishmentꢄ step.
2. Results and Discussion. – 2.1. Alkylation of Heptalene-4,5-dicarboxylates at C(3).
We knew from our earlier alkylation experiments of dimethyl heptalene-4,5-
dicarboxylates with lithiomethyl phenyl sulfone (¼ [(phenylsulfonyl)methyl]lithium)
and other lithiomethyl sulfones that these nucleophiles did not react exclusively with
the sterically less hindered methoxycarbonyl group at C(4) but also to a varying extent
at C(3) of the heptalene skeleton in a Michael-type addition reaction [4][5]. We were
interested, therefore, to find the optimal conditions for the Michael-addition pathway
and the optimal base for the planned subsequent elimination reaction of the
corresponding sulfinates (Scheme 2).
Scheme 2
Dimethyl heptalene-4,5-dicarboxylate (1) itself reacted with [(phenylsulfonyl)me-
thyl]lithium in THF at ꢀ 788 exclusively at C(3) (!2), and so did a number of other
simply substituted heptalene-4,5-dicarboxylates, i.e., 3, 5, 7, and 9, leading thus in good
yields to the corresponding cis-configured 3,4-dihydro-3-[(phenylsulfonyl)methyl]-

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887
heptalene-4,5-dicarboxylates 4, 6, 8, and 10, respectively, as an almost 1:1 mixture of
epimers with respect to the axis (C(5a)ꢀC(10a)) of chirality (Table 1).
Table 1. Michael-Addition Reaction of [(Phenylsulfonyl)methyl]lithiuma) and Dimethyl Heptalene-4,5-
dicarboxylates 1, 3, 5, 7, and 9
Reactant
R
Michael Adductb)
Yield [%]
1
3
5
7
9
H
2
4
6
8
10
69 – 95
67
67
1-Me
6-Me
8-Me
1,6-Me2
76
62c)
a) 1.1 mol-equiv. of methyl phenyl sulfone were beforehand lithiated with BuLi at 108. Larger quantities
of the nucleophile led to increasing amounts of tricyclic bis-adducts [4]. b) For the structure assignment
of the cis-configured adducts, see below. c) Methyl 1,6-dimethyl-4-[(phenylsulfonyl)acetyl]heptalene-5-
carboxylate was formed in minor amount (3%).
However, the reaction of 9 with [(phenylsulfonyl)methyl]lithium gave as a by-
product small amounts of the alkylation product of MeOOCꢀC(4) as the sterically less
hindered ester group, a fact that we had observed already in our former experiments
with heptalene-4,5-dicarboxylates with a higher number of peri-substituents [4]. A
more detailed investigation with the heptalene-4,5-dicarboxylates 11 and 14, derived
from 1,4,8-trimethylazulene and guaiazulene, respectively, showed that the ratio of
Michael addition at C(3) and the alkylation reaction at MeOOCꢀC(4) is strongly
dependent on the applied reaction temperature (!12/13 and 15/16, resp.; Scheme 3).
The observation that the ratio Michael adduct/alkylation product changed substantially
in favor of the latter at ꢀ 208 speaks for the fact that the Michael addition at C(3) is
reversible, whereas the alkylation at MeOOCꢀC(4) is irreversible due to the rapid
elimination of methoxide and deprotonation of the formed (phenylsulfonyl)acetyl
group at C(4). The electronic nature of the [(sulfonyl)methyl]lithium nucleophile has
no great influence on the said ratio as experiments with N,N-diphenylmethanesulfon-
amide and 4-(methylsulfonyl)morpholine demonstrated (!17/18 and 19/20, resp.).
Much more effective in view of the ratio of Michael addition at C(3) vs. alkylation
at MeOOCꢀC(4) turned out to be the presence of an a-Me substituent in [(phenyl-
sulfonyl)methyl]lithium as experiments with [1-(phenylsulfonyl)ethyl]lithium showed
(!21/22 and 23/24; see Scheme 4 and below). The higher nucleophilicity and steric
encumbrance of the a-branched ethyllithium reactant favor distinctly its 1,4-addition in
comparison with the 1,2-addition.

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Scheme 3
Scheme 4

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889
2.2. Alkylations of Heptalene Pseudoesters at C(5). As we have reported already in
earlier publications, heptalene-4,5-dicarboxylates can be transformed via their half-
esters into the corresponding regioisomeric pseudoesters [6][7], which allow selective
reactions at their C¼O groups (Scheme 5) [5][8]. In the course of these investigations,
we were quite astonished to find that the furanone 25, derived from heptalenedicar-
boxylate 14, reacted with [(phenylsulfonyl)methyl]lithium in the expected manner
(!26) whereas its reaction with [1-(phenylsulfonyl)ethyl]lithium led to a completely
unexpected product, namely, as an X-ray crystal-structure determination (see below)
revealed, to the 1,6-addition product (P*)-27 (Scheme 6). Further experiments
disclosed that a Me group at C(11) of the heptaleno[1,2-c]furan-1-ones and at the a-
position of the [(phenylsulfonyl)alkyl]lithium reactants are decisive for the formation
of 1,6-adducts, whereas the presence or absence of a Me group at C(6) has no
significant influence on the addition of the alkyllithium nucleophile at C(5) of the
heptaleno[1,2-c]furanones (see 28 ! (P*)-30 and 29 ! (P*)-31; Scheme 7). The crystal
structure of the 1,6-adducts (P*)-30 and (P*)-31 was again determined by an X-ray
diffraction analysis (see below). The reaction of heptalenofuranone 32 with [1-
(phenylsulfonyl)ethyl]lithium gave mainly alkylation at C(1) resulting in the formation
of 33, and only small amounts of furanone 34 were identified spectroscopically.
Scheme 5
The AM1-calculated structure of heptalenofuranone 25 clearly revealed the reason
for its propensity to undergo a 1,6-addition reaction with [1-(phenylsulfonyl)ethyl]-
lithium (Fig. 1). The perspective view of (P)-25 with the dotted van der Waals surface
of the O-atom of the C¼O group and MeꢀC(11) plainly demonstrates that the re-face of
the C¼O group is perfectly shielded by MeꢀC(11) against a nucleophilic attack. On the
other hand, the si-face of the C¼O group cannot take up a nucleophile since the van der
Waals surfaces of the O-atom of the C¼O group and MeꢀC(11) are touching each
other, so that there is no free space for the necessary bending mode of the C¼O group
when changing from sp2 to sp3 hybridization on addition of a nucleophile. Moreover,
the torsion angles V(O¼C(1)ꢀC(11b)ꢀC(3a)) and V(C(11b)ꢀC(3a)ꢀC(4)ꢀC(5))
amount to 1788 and 258, respectively, ideal for the uptake of a nucleophile at C(5),
which exerts no influence on the packed spatial arrangement at the C¼O group since
the sp2 ! sp3 bending mode takes place at C(5). In the case of heptalenofuranones

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Scheme 6
Scheme 7

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891
without a Me group at C(11) (e.g., 32; see also [5]), the spatial interactions at the C¼O
group are strongly reduced, so that the 1,2-addition of a nucleophile at the C¼O group
is favored.
Fig. 1. Stereoscopic view of the AM1-calculated structure of (P*,5S*)-4,5-dihydro-8-isopropyl-3,3-
dimethoxy-6,11-dimethyl-5-[(1R*)-1-(phenylsulfonyl)ethyl]heptaleno[1,2-c]furan-1-one ((P*)-27) with
dotted van der Waals surfaces of O¼C(1) and MeꢀC(11)
2.3. Elimination Reactions with the 1,4- and 1,6-Adducts. After the failure of
elimination reactions of the 1,4-adduct 15 with DBU (1,3-diazabicyclo[5.4.0]undecane)
or LDA (lithium diisopropylamide) as a base in THF according to Scheme 2, we found
that MeONa in boiling MeOH/THF was the system of choice for the desired removal of
PhSOꢀ2 , followed by base-catalyzed tautomerization (Scheme 8). The formed hepta-
lenedicarboxylate was obtained as a thermal equilibrium mixture of 35 and its double-
bonds-shifted (DBS) isomer 35’, which we had obtained already earlier with a number
of other products by thermal reaction of 3-methylguaiazulene with dimethyl
acetylenedicarboxylate in decalin at 2008 (cf. [9]). Other leaving groups such as
Ph2NSOꢀ2 (16% of 35/35’) or O(CH2)4NSOꢀ2 (0% of 35/35’) were less successful. The
adduct 17 also reacted with LDA in THF, even though the yield of 35/35’ (6%) was low,
and 19 gave no product at all under these conditions. Further elimination reactions,
which led in moderate to good yields to some new alkylated heptalenedicarboxylates
4
are compiled in Scheme 9 (see 36/36’, 38/38’, 39/39’, and 40/40’) ).
Scheme 8
4
)
The standard elimination procedure applied on 21 did not lead to the formation of 3-
ethylheptalenedicarboxylates 37/37’ (cf. 2 ! 36/36’ in Scheme 9; R1,R3,R4 ¼ H, R2 ¼ Me). Due to a
shortage of starting material, we could not repeat the elimination reaction of 21 with t-BuOK in
THF (cf. 2 ! 36/36’ in Scheme 9).

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Scheme 9
The (phenylsulfonyl)methyl or 1-(phenylsulfonyl)ethyl moiety at C(3) of the 3,4-
dihydroheptalene-4,5-dicarboxylates should principally allow the nucleophilic intro-
duction of further alkyl groups at C(1) of the sulfonylalkyl substituents. However, the
presence of MeOOCꢀC(4) may favor a nucleophilic alkylation at C(4). This is indeed
the case. When (P*)-23 was deprotonated with NaH, followed by addition of MeI, the
C(4)-methylated 3,4-dihydroheptalene-4,5-dicarboxylate (P*)-41 was obtained almost
5
quantitatively (Scheme 10) ). Its relative configuration was determined by an X-ray
crystal-structure analysis (see below). Treatment of (P*)-41 under the established
elimination conditions led at least in a yield of 20% to the corresponding 3-ethylidene-
3,4-dihydroheptalenedicarboxylate (M*)-42 (Scheme 10). Its (3E)-configuration fol-
lows from an anti-E2 elimination of PhSOꢀ2 of (P*)-41 ), which should deliver
6
(P*,4R*)-42. However, (M*,4R*)-42 is, according to AM1 calculations, at least by ca.
0.7 kcal/mol, energetically favored; therefore, we think that we obtained 42 with
(M*,3E,4R*)-configuration as shown in Scheme 10.
Scheme 10
a) NaH/THF, 4 h, ꢀ 108 to r.t. b) MeI, 3 d, r.t. c) MeONa/MeOH, THF, 708, 12 h.
Quite astonishing was the result of the elimination reaction of 2 under our standard
conditions with MeONa in MeOH/THF. Instead of the expected heptalenedicarbox-
5
)
)
We did not verify the possibility to trap the ester enolate of (P*)-23 by silylation, followed by a
second deprotonation and then alkylation.
The (3E)-configuration of 42 is thermodynamically favored by ca. 2.5 kcal/mol with respect to the
(3Z)-form of 42.
6

Helvetica Chimica Acta – Vol. 95 (2012)
893
ylate 36, which was found only in a small amount, we isolated its cyclic anhydride 43 in
good yield (Scheme 11). Similarly, the (sulfonylmethyl)heptalenedicarboxylate 15 gave
with t-BuOK or Et3COK in THF nearly equal amounts of the expected diesters 35/35’
and their common cyclic anhydride 44 (cf. [6] for DBS in cyclic anhydrides of
heptalene-1,2- and heptalene-4,5-dicarboxylic acids). We suppose that, after deproto-
nation at C(4), the corresponding ester enolate A undergoes cyclization to B, which
then loose methoxide to yield C, which represents the enol ether form of the cyclic
anhydride of 15. The final step would then be the base-induced formal elimination of
PhSO2H to give the enol ether D. Treatment of the latter in the course of the workup
procedure with aqueous 2n HCl yields then the observed cyclic anhydride 44
(Scheme 12). Of course, we cannot exclude that the elimination already takes place at
the stage of B and that the oxido product of this reaction is present in the reaction
mixture before working up. In other words, the decisive step in the discussed reaction
sequence is the cyclization step, which might be dependent on the intramolecular
flexibility of the 3,4-dihydroheptalene-4,5-dicarboxylates. A critical point may also be
the elimination of PhSOꢀ2 , which should be dependent on the strength of the used base.
Therefore, it is conceivable that the peri-substituted 3,4-dihydro-3-(sulfonylmethyl)-
heptalene-4,5-dicarboxylates can be transformed to the corresponding heptalene-4,5-
dicarboxylates with MeONa in MeOH/THF, whereas it needs the stronger bases t-
BuOK or Et3COK in THF to observe, in addition to diester formation, also the
formation of the corresponding cyclic anhydride.
Scheme 11
It turned out that heating the 4,5-dihydro-5-[1-(phenylsulfonyl)ethyl]heptaleno-
[1,2-c]furans with MeONa/MeOH in THF was also successful for the formation of the
corresponding 2-ethylated heptalene-4,5-dicarboxylates by elimination of PhSO2H
(Scheme 13).
All new heptalenedicarboxylates were fully characterized spectroscopically and the
structure of 45 was also determined by an X-ray diffraction analysis (see Exper. Part,
Table 7). It is of interest to note that in the course of the elimination reaction of 31,
epimerization at the axis of chirality of 31 and/or 47 took place only to an extent of

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Helvetica Chimica Acta – Vol. 95 (2012)
Scheme 12
Scheme 13
10%. On standing at room temperature in CDCl3 solution, the 1:9 ratio of 47/47’ was
slowly reversed. After two months, the ratio approached a value of almost 12 :1 in favor
of 47.
2.4. Structure Characterization of the Michael Addition Products. 2.4.1. 3-Alkylated
3,4-Dihydroheptalene-4,5-dicarboxylates. In our former reports on the reaction of
higher alkylated heptalene-4,5-dicarboxylates with [(X-sulfonyl)methyl]lithium, the
relative configuration of the formed 3-alkylated heptalene-4,5-dicarboxylates had been
of minor concern [4][8]. We assumed that these compounds possessed relative cis- and
trans-configuration with respect to the spatial arrangements of the substituents
(XSO2CH2, COOMe) at C(3)ꢀC(4). This view was supported by an X-ray crystal-
7
structure determination of one of the isomers of 19 (cf. Scheme 3) ), which revealed its
7
)
See compound 6a in Scheme 3 of [4].

Helvetica Chimica Acta – Vol. 95 (2012)
895
relative cis-configuration, whereas the relative (M*)-configuration at the axis of
chirality (C(5a)ꢀC(10a)) had been overlooked, since it was not in the focus of our
interest at that time. On this basis, and without any further investigation, we assigned
8
the trans-configuration to the second isomer of 19 ), found in solution, and which,
together with its crystallized form, was only characterized by its 1H-NMR spectrum in
9
C6D6 ).
We were surprised when we found in this work that, with the exception of the
mixture of the two isomers of 10, all the simply substituted 3-alkylated 3,4-
dihydroheptalene-4,5-dicarboxylates listed in Table 1 showed, as mixtures at room
1
temperature, in their H-NMR spectra coalescence of almost all of the signals, and it
needed temperatures as low as 223 K to get sharp signals of both isomers of the Michael
adducts. Moreover, a temperature scan in steps of 10 K between 300 to 223 K revealed
that at first, most of the signals of both isomers became sharp, followed finally by the
signals of HꢀC(3) and HꢀC(4) of the isomers. These observations excluded the
existence of cis/trans pairs of isomers, but they were in full agreement with the presence
of thermally converting epimers with respect to their axis of chirality. Fortunately, we
obtained crystals of one isomer each of the 1-methyl- and 1,6-dimethyl-3,4-dihydro-
heptalenedicarboxylate 4 and 10, respectively, which were suitable for an X-ray crystal-
structure determination (Figs. 2 and 3). Both compounds showed a cis-arrangement of
the substituents at C(3) and C(4), however, with opposite relative configuration at
their axis of chirality (C(5a)ꢀC(10a)). Thus, the crystals of (P*)-4 contained the pure
10
(P*,3R*,4R*)-isomer and those of (P*)-10 the pure (P*,3S*,4S*)-form ).
Fig. 2. Stereoscopic view of the X-ray crystal structure of dimethyl (P*,3R*,4R*)-3,4-dihydro-1-methyl-3-
[(phenylsulfonyl)methyl]heptalene-4,5-dicarboxylate ((P*)-4; 50% probability ellipsoids)
1
Systematic H- and 13C-NMR analyses of all prepared dimethyl 3,4-dihydro-3-[1-
(X-sulfonyl)alkyl]heptalene-4,5-dicarboxlates (cf. Table 1, Schemes 3, 4, and 10)
revealed that all dicarboxylates, which carried no substituent at C(6) (see 2, 4, and 8)
appeared with relative (P*,3R*,4R*)-configuration, whereas those with a Me group at
C(6) (6, 10, 12, 15, 17, 19, 23, and 41) had the relative (P*,3S*,4S*)-configuration. The
observation that all Michael-addition products of the heptalene-4,5-dicarboxylates
exhibit relative cis-configuration of the substituents at C(3)ꢀC(4) is in agreement with
8
)
)
)
See compound 6b in Scheme 3 of [4].
See Table 10 in [4].
The latter, when dissolved at room temperature in C6D6, slowly equilibrated to a 2:1 mixture with
9
10
its (M*,3S*,4S*)-epimer.

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Fig. 3. Stereoscopic view of the X-ray crystal structure of dimethyl (P*,3S*,4S*)-3,4-dihydro-1,6-dimethyl-
3-[(phenylsulfonyl)methyl]heptalene-4,5-dicarboxylate ((P*)-10; 50% probability ellipsoids)
the fact that the protonation of the primarily formed C(4)-ester enolates takes place in
11
a trans-relationship to the bulky [1-(X-sulfonyl)alky] group at C(3) ).
Intramolecular H-atom transfer does not seem to play a role in the protonation
step. This is evident by the fact that the alkylation experiment of the C(4)-ester enolate
of (P*)-23 with MeI, which gave exclusively the C(4)-methylated product (P*)-41 with
retention of configuration at C(4) (Scheme 10) as revealed by its X-ray crystal-
structure analysis (Fig. 4), and which showed the same (P*,3S*,4S*)-configuration at
the 3,4-dihydroheptalene core as the starting material (P*)-23 (see [5] for the X-ray
12
structure of 23) ). However, the (R*)-configured 3-[1-(phenylsulfonyl)ethyl] group of
(P*)-23 underwent, obviously due to the basic conditions of the methylation reaction,
complete epimerization to (S*)-configuration in (P*)-41.
Fig. 4. Stereoscopic view of the X-ray crystal structure of dimethyl (P*,3S*,4S*)-3,4-dihydro-9-isopropyl-
1,4,6-trimethyl-3-[(1S*)-1-(phenylsulfonyl)ethyl]heptalene-4,5-dicarboxylate ((P*)-41; 50% probability
ellipsoids)
The global events of the formation of the Michael products are very simple
(Scheme 14). Since we found only the cis-3,4-dihydroheptalene-4,5-dicarboxylates, the
11
)
AM1 calculations of (P*)-4 and (P*)-10, which very well reproduced their crystal structures, showed
that the DHof values of their corresponding trans-forms, (P*,3R*,4S*)-4 and (P*,3S*,4R*)-10,
respectively, are lying 2.1 and 2.3 kcal/mol, respectively, higher in energy, i.e., the 3,4-cis-configured
3,4-dihydroheptalenes are the thermodynamically favored forms.
In this case, AM1 calculations showed the cis-methylation product to be 3.3 kcal/mol less stable
than the trans-product, (P*,1’S*,3S*,4R*)-41.
12
)

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897
Scheme 14
two epimers of which represent, due to their labile axis of chirality, the thermodynami-
cally controlled products.
However, there are principally two ways by which the uptake of the nucleophile can
occur. The simplest mode is shown in Scheme 15. It means that the axial attack of the
nucleophile would take place only at one of the prochiral sites of C(3). In other words,
the decisive step of the alkylation reaction happens with 100% stereoselectivity. The
other mode would be that the nucleophile attacks C(3) with a certain stereoselectivity
at both of its prochiral sites (Scheme 15).
Scheme 15
To get more insight into these two modes, which do not alter the global
stereochemical outcome, we performed a number of AM1 calculations. First of all,
X-ray crystal-structure determinations as well as calculations show for heptalene-4,5-
dicarboxylates an s-cis-conformation of the ester C¼O group at C(4) in relation to the
C(3)¼C(4) bond with a V of 208 and below, independent of the number of peri-
substituents (Table 2).
AM1 Calculations with methanide as model nucleophile show that the axial cisoid
ester enolates, formed on the re path, are energetically favored by 2.3 – 5.8 kcal/mol,
compared with those resulting from the si path (Table 3). The reason for this difference
can be seen in the almost perfect s-trans torsion angle at C(4)ꢀC(5) of the (P*,R*)-
products, which allows a much better delocalization of the negative charge of the ester-
enolates already in the transition state. This torsion angle stays almost constant (around
13
1458) on the way to the (P*,S*)-ester enolates ). Therefore, we assume that only the re
path and the respective si path are responsible for the uptake of a nucleophile at C(3)
of the discussed (P)- and (M)-heptalenedicarboxylates.
13
)
See the X-ray structures of 5 and 49 with a V(C(5a)¼C(5)ꢀC(4)ꢀCO2Me) of 145.3(2)8 and
144.6(3)8, respectively (note that in these crystal structures, the atoms have been numbered as
C(10a)¼C(10)ꢀC(9)ꢀC(12)).

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Table 2. Relevant Torsion Angles V [8]a) of Dimethyl Heptalen-4,5-dicarboxylates with Methyl Groups in
peri-Position
Torsion angles
3 (ꢀ 73.6)b) 5 (ꢀ 71.6)b)
48 (ꢀ 72.6)b)
45 (ꢀ 107.3)b)
V(C(1)¼C(2)ꢀC(3)¼C(4))
V(C(5)¼C(5a)ꢀC(10a)ꢀC(1))
V(C(6)ꢀC(5a)ꢀC(10a)¼C(10))
V(C(3)¼C(4)ꢀC¼O)
34.0
55.0
54.7
32.0 (30.3)
57.2 (56.1)
56.8 (57.8)
33.5 (33.8)
53.9 (56.2)
54.0 (59.6)
35.0 (35.4)
61.6 (62.6)
59.4 (62.0)
ꢀ 20.8
ꢀ 9.0 (ꢀ 13.0)
ꢀ 20.7 (ꢀ 19.9)
ꢀ 6.3 (ꢀ 16.5)
V(C(5a)¼C(5)ꢀC¼O)
ꢀ 23.6
ꢀ 59.6 (ꢀ 47.7)
ꢀ 23.8 (ꢀ 32.8)
ꢀ 61.0 (ꢀ 32.8)
a) AM1 calculated values; in parentheses, X-ray data (see also Exper. Part, Table 7); 3, 1-Me; 5, 6-Me; 48,
10-Me; 45, 1,6-Me2, 2-Et, and 9-iPr. b) In parentheses, AM1 calculated DHf8 values (kcal/mol).
Table 3. Change of V(C(5a)¼C(5)ꢀC(4)¼C(OMe)Oꢀ ) [8] on Axial Michael Addition of Methanide at
C(3) of Dimethyl Heptalene-4,5-dicarboxylates 1, 3, 5, and 9a)
R1 ¼ R2 ¼ H
149.5 (ꢀ 119.1)
144.6 (ꢀ 124.5)
144.9 (ꢀ 124.6)
146.0 (ꢀ 130.3)
1b)
3
5
ꢀ 175.2 (ꢀ 123.8)
ꢀ 175.6 (ꢀ 130.3)
178.0 (ꢀ 126.9)
178.2 (ꢀ 133.7)
R1 ¼ Me, R2 ¼ H
R1 ¼ H, R2 ¼ Me
R1 ¼ R2 ¼ Me
9
a) According to AM1 calculations (see also Table 2); in parentheses, DHf8 value of the shown axial forms.
b) For X-ray structure analysis of 1, see [11].
The crystal structures of (P*,3R*,4R*)-4 and (P*,3S*,4S*)-10 disclose the presence
of principally a third element of chirality, namely that of the helical turn of the 3,4-
substituted fragment C(2)ꢀC(3)ꢀC(4)ꢀC(5) with (þ)-sc torsion angles of 69.5(3)8 and
67.9(2)8, respectively. The fragment is part of a seven-membered ring in a boat-like
conformation with C(4) in the bow position. AM1 Calculations of model Michael
adducts of diesters 1, 3, 5, and 9, again with methanide as nucleophile, indicate that a
second conformation is possible, wherein the fragment possesses (ꢀ)-sc conformation,
and C(3) takes the bow position (Table 4). One recognizes that Me substituents at the
heptalene core markedly influence the thermodynamic stability of the two diaster-
eoisomers as well as the preferred conformation of their 3,4-dihydro ring. A Me group
at C(6) shifts the relative configuration from (þ)-sc-(P*,3R*,4R*) to (þ)-sc-

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Table 4. DHf8 Values (kcal/mol) of the cis-Diastereoisomers of Dimethyl 3,4-Dihydro-3-methylheptalene-4,5-
dicarboxylates 1, 3, 5, and 9a)b)
R1 ¼ R2 ¼ H
1a)
ꢀ 93.75
ꢀ 99.25
ꢀ 98.23
ꢀ 103.91
ꢀ 88.98
ꢀ 95.93
ꢀ 93.81
ꢀ 100.92
ꢀ 92.25
ꢀ 99.24
ꢀ 92.61
ꢀ 99.45
ꢀ 95.70
ꢀ 103.03
R1 ¼ Me, R2 ¼ H 3a)
R1 ¼ H, Me
5a)
9a)
ꢀ 99.09
R1 ¼ R2 ¼ Me
ꢀ 105.05
a) Key no. of the corresponding dimethyl heptalene-4,5-dicarboxylate. b) The stereochemical descriptors (þ)- and
(ꢀ)-sc refer to the sign of the ring torsion angle V(C(2)ꢀC(3)ꢀC(4)ꢀC(5)).
(P*,3S*,4S*), just as observed in the crystal structures of (P*)-4 and (P*)-10.
Moreover, one can see that the (þ)-sc-(P*,3R*,4R*) forms are without exception by
3 – 4.8 kcal/mol more stable than their (ꢀ)-sc conformers. The situation is more
complex for the (P*,3S*,4S*)-configured diastereoisomers. In the cases with no
substituent or a Me group at C(1), the (ꢀ)-sc forms are energetically slightly favored.
However, a Me substituent at C(6) (or C(1) and C(6)) makes the (þ)-sc conformations
more stable. Taking all together, one can say that the investigated 3,4-dihydrohepta-
lene-4,5-dicarboxylates contain two fixed elements of chirality (centers at C(3) and
C(4)) and two principally dynamic elements of chirality (axes at C(5a)ꢀC(10a) and
C(3)ꢀC(4)).
To learn more about the molecular dynamics of 3,4-dihydroheptalenes, we
calculated the transition state energies of the (P),(M) and (þ)-sc,(ꢀ)-sc conversion
of 3,4-dihydroheptalene (Scheme 16) and of (P,3S,4S)-3,4-dihydro-1,3,6-trimethylhep-
talene-4,5-dicarboxylic acid (Scheme 17), close to the structure of the Michael adduct
10 with the highest number of peri-substituents. The AM1-calculated data for 3,4-
dihydroheptalene itself show its (þ)-sc-(P) form more stable than its diastereoisomeric
(ꢀ)-sc form, and the data listed in Table 4 indicate that substituents in positions 1, 3, 4,
5, and 6 can enlarge this energy gap up to 4.8 kcal/mol. The rotational barrier at the ring
bond C(3)ꢀC(4) is with 3.0 and 4.4 kcal/mol expectedly low and clearly below the
transition-state energy of 6.6 and 8.0 kcal/mol, respectively, for the change of
configuration of the dihydroheptalene skeleton. The rotational barrier of 2.4 and
4.1 kcal/mol at the C(3)ꢀC(4) bond for the above mentioned analog of 10 does not
change very much, in contrast to the corresponding inversion barrier of the
dihydroheptalene configuration, which amounts to 16.9 and 17.5 kcal/mol, respectively,
and are strongly dependent on the number of peri-substituents as known from their
parent heptalenes (cf. [12]). The calculated data are in perfect agreement with the
observed rapid, respectively, slow (P*,3S*,4S*) ! (M*,3S*,4S*) conversion of 6 and
10 at room temperature in solution. Moreover, the observed mostly broad signals for
HꢀC(3) and HꢀC(4) in the 1H-NMR spectra of the lower-substituted 3,4-dihydrohep-

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Scheme 16
talene-4,5-dicarboxylates speaks for an active dynamic equilibrium of the (þ)-sc and
(ꢀ)-sc ring conformers at the temperature range used for the NMR measurements of
the 3,4-dihydroheptalene-4,5-dicarboxylates.
2.4.2. 5-Alkylated 4,5-Dihydro-3,3-Dimethoxyheptaleno[1,2-c]furan-1(3H)-ones.
The structure and relative configuration of the 4,5-dihydroheptaleno[1,2-c]furan-
1(3H)-ones (P*)-27, (P*)-30, and (P*)-31 were determined by X-ray crystal-diffraction
analyses (see Figs. 5 and 6 as well as Table 7 in the Exper. Part). Whereas the two
former structures possess the same relative configuration, the latter has (P*,1’S*,5R*)-
configuration. (P*)-27, when dissolved in CDCl3 at room temperature, rapidly formed a
2 :1 mixture with its (M*)-epimer (Scheme 6). The two other compounds showed no
noticeable epimerization during the time of their NMR measurement in CDCl3
14
solution at normal temperature ).
The different relative configuration at C(5) of the 1,6-adducts speaks for the change
of the site of the uptake of the nucleophile by the heptalenofuranone as shown in
Scheme 18. Since all three compounds exhibit the same (þ)-sc conformation at the
15
C(4)ꢀC(5) bond with V(C(3a)ꢀC(4)ꢀC(5)ꢀC(6)) of 64.8(2)8 ((P*)-27) ), 57.6(2)8
((P*)-30), and 63.0(2)8 ((P*)-31), it was of interest for us to look for the reason of this
site selectivity. Table 5 lists the AM1-calculated DHf 8 values of the dienolate
intermediates that are formed with the model nucleophiles methanide and propan-2-
14
)
)
See below for the reason.
(P*)-27 appears in the crystals with two different rotational orientations of the Pr group with
i
15
respect to the heptalene core.

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Scheme 17
Fig. 5. Stereoscopic view of the X-ray crystal structure of one of the two symmetry-independent molecules
of (P*,5S*)-4,5-dihydro-8-isopropyl-3,3-dimethoxy-5-[(1R*)-1-(phenylsulfonyl)ethyl]heptaleno[1,2-c]-
furan-1(3H)-one ((P*)-27; 50% probability ellipsoids)
ide by axial attack on the re and si site of C(5). All relaxed intermediates show (þ)-sc
conformations with V(C(3a)¼C(4)ꢀC(5)ꢀC(6)) in the range of 52 – 638 for the

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Fig. 6. Stereoscopic view of the X-ray crystal structure of (P*,5R*)-4,5-dihydro-3,3-dimethoxy-6,7,9,11-
tetramethyl-5-[(1S*)-1-(phenylsulfonyl)ethyl]heptaleno[1,2-c]furan-1(3H)-one ((P*)-31; 50% probabil-
ity ellipsoids)
Scheme 18
(P*,5S*)-forms and 42 – 498 for the (P*,5R*)-forms. The two intermediate dienolate
structures arising from 28 and methanide are reproduced in Fig. 7. From the axial re
attack results the (þ)-sc conformation with the added Me group in a pseudo-equatorial
position, whereas the addition on the si site delivers the (þ)-sc conformation with the
Me group in pseudo-axial position. The (þ)-sc-(P*,5S*)-dienolate intermediates with
methanide as nucleophile are by DHf 8 0.5 – 1.9 kcal/mol more stable than their (þ)-sc-
(P*,5R*) counterparts, a situation which changes with the a-branched 1-methyletha-
nide (propan-2-ide) as nucleophile, where only the (þ)-sc-(P*,5S*) form, derived from
30, is by 1.0 kcal/mol more stable than the corresponding (5R*) form, whereas it is the
(þ)-sc-(P*,5R*)-form in the other two cases, which is by 1.6 – 1.8 kcal/mol more stable.
Therefore, it is reasonable to assume that indeed increasing steric interaction in the

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Table 5. Dienolate Intermediates of the 1,6-Addition of Model Nucleophiles at C(5) of Heptaleno[1,2-
c]furan-1-(3H)-ones 25’, 28, and 29a)
DHf8 ((þ)-sc-(P*,5R*)) No. DHf8 (P) DHf8((þ)-sc-(P*,5S*))
R ¼ Me; R1 ¼ R3 ¼ Me, R2 ¼ H ꢀ 145.7 (42.5)
R ¼ Me; R1 ¼ R3 ¼ H, R2 ¼ Me ꢀ 146.6 (45.8)
R ¼ Me; R1 ¼ R2 ¼ Me, R3 ¼ H ꢀ 151.7 (49.0)
25’
28
29
25’
28
29
ꢀ 79.3
ꢀ 80.5
ꢀ 85.4
ꢀ 146.3 (57.9)
ꢀ 148.5 (52.2)
ꢀ 152.2 (58.6)
ꢀ 154.3 (62.8)
ꢀ 158.1 (56.3)
ꢀ 160.2 (63.0)
R ¼ iPr; R1 ¼ R3 ¼ Me, R2 ¼ H
R ¼ iPrR1 ¼ R3 ¼ H, R2 ¼ Me
R ¼ iPr; R1 ¼ R2 ¼ Me, R3 ¼ H
ꢀ 156.0 (47.7)
ꢀ 157.1 (44.8)
ꢀ 161.9 (48.3)
a) DHf8 in kcal/mol; 25’ ¼ 25 with MeꢀC(8) (R3) instead of iPrꢀC(8); in parentheses,
V(C(3a)¼C(4)ꢀC(5)ꢀC(6)).
Fig. 7. AM1-Calculated, hypothetical dienolate structures resulting from re (left) and si (right) attack,
resp., of methanide at C(5) of (P)-configured furanone 28 (see text)
transition state of the 1,6-addition of 1-(phenylsulfonyl)ethanide to the furanones leads
to a change of the site of the attack.
Protonation at C(4) of the dienolate intermediates leads to the corresponding 4,5-
dihydroheptaleno[1,2-c]furan-1(3H)-ones, which can also be regarded as furano-fused
3,4-dihydroheptalenes. The calculated DHf 8 of the (þ)- and (ꢀ)-sc forms of the model
compounds are listed in Table 6. One clear answer is that the (þ)-sc conformers are
principally more stable than the (ꢀ)-sc forms in accordance with the X-ray crystal
structures of all three heptaleno[1,2-c]furanones. Moreover, a-alkyl branching of the
substituent at C(5) is sterically mostly slightly better accommodated by the (P*,5R*)-
configured furanones.
We chose 4,5-dihydro-3,3-dihydroxy-5,6,8,11-tetramethylheptaleno[1,2-c]furan-
1(3H)-one as a model for 27 to get more insight into the molecular dynamics of the
furano-fused 3,4-dihydroheptalenes (Scheme 19). The DHf 8 values, listed in Table 6,

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Table 6. DHf8 Data of Model 4,5-Dihydro-3,3-dimethoxy-5-methylheptaleno[1,2-c]furan-1(3H)-onesa)
(þ)-sc-(P*,5R*)
(ꢀ)-sc-(P*,5R*)
ꢀ 102.45
(þ)-sc-(P*,5S*)
ꢀ 107.77
(ꢀ)-sc-(P*,5S*)
ꢀ 102.29
R ¼ Me; R1 ¼ R3 ¼ Me, R2 ¼ H ꢀ 106.40
R ¼ Me; R1 ¼ R3 ¼ H, R2 ¼ Me ꢀ 107.19 ꢀ 116.73) ꢀ 105.35 (ꢀ 114.16) ꢀ 109.74 (ꢀ 119.17) ꢀ 104.76 (ꢀ 113.44)
R ¼ Me; R1 ¼ R2 ¼ Me, R3 ¼ H ꢀ 112.56 ꢀ 121.91) ꢀ 107.54 (ꢀ 115.94) ꢀ 113.74 (ꢀ 121.68) ꢀ 107.48 (ꢀ 114.65)
b
a) Calculated with AM1; in kcal/mol. ) In parentheses, values for R ¼ iPr.
Scheme 19
demonstrated already that the (þ)-sc-(P*,5S*) forms are much more stable than their
(ꢀ)-sc relatives. The same is observed in the present case, where this energy difference

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amounts to 5.4 kcal/mol. The transition state for the mutual conversion of the two
conformers is ꢀ 115.5 kcal/mol above the ground states. The DHzf values for the (P,M)-
epimerization of the two conformers into the most stable (ꢀ)-sc-(M*,5S*) form amount
to 20.4 and 15.0 kcal/mol, in excellent agreement with the observation that (P*,5S*)-27
isomerized reversibly already at room temperature in CDCl3 solution to (M*,5S*)-27.
3. Final Remarks. – There are at least two open points left. The first one deals with
the directing and decisive steps of the base-catalyzed elimination of PhSOꢀ2 at the
structurally complex dimethyl 3,4-dihydro-3-(phenylsulfonyl)heptalene-4,5-dicarbox-
ylate and 4,5-dihydro-3,3-dimethoxy-5-[1-(phenylsulfonyl)ethyl]heptaleno[1,2-c]-
furan-1(3H)-ones.
Deprotonation and methylation of diester 23 yields the C(4)-methylated diester 41
(cf. Scheme 10), which demonstrates that HꢀC(4) is, as expected, more acidic than
HꢀC(3). Moreover, the base-catalyzed transformation of 41 into 42 indicates that the
elimination of PhSOꢀ2 takes place as a concerted E2 process with anti stereochemistry.
However, what happens when C(4) carries an H-atom as in all the other cases? One
possibility would be that deprotonation at C(4) does not hinder the base-catalyzed
concerted E2 process as discussed above, taking into account that the adjacent negative
charge will favor an early transition state on the reaction coordinate of the E2 process.
However, the fact that we found in some cases, which we have not investigated in detail,
beside the alkylated heptalenedicarboxylates also their corresponding anhydrides
speaks for an ꢃanchimericꢄ assistance of the elimination reaction by the neighbored
methoxycarbonyl group as depicted in Scheme 12.
The elimination reaction of the dihydroheptalenofuranones (P*)-27, (P*)-30, and
(P*)-31 seems to follow a concerted E2 mechanism since we did not observe an unusual
reaction behavior. Nevertheless, it is remarkable that the average yield of the
elimination reaction is higher in comparison with that of the dihydroheptalenedicar-
boxylates, which speaks for an easier E2 process of the dihydroheptalenofuranones.
The second point touches the question whether the described alkylation process
with [1-(phenylsulfonyl)alkyl]lithium as alkyl-group carrier can also be realized with
normal a,b-unsaturated carbonyl system. First experiments show that [1-(phenyl-
sulfonyl)alkyl]lithium reactants are indeed excellent Michael addends for a,b-
unsaturated compounds such as chalcone (¼(2E)-1,3-diphenylprop-2-en-1-one) or
methyl cinnamate (¼ methyl (2E)-3-phenylprop-2-enoate; Scheme 20) [13]. However,
the formed products 51 need at least two chemical steps to re-establish unsaturation of
the b-alkylated compounds 51 by elimination of benzenesulfinate.
Scheme 20
We are thankful to our NMR laboratory for specific NMR measurements and to our MS laboratory
for mass spectra. Financial support of this work by the Swiss National Science Foundation is gratefully
acknowledged.

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Experimental Part
General. See [4][5][8]16). All heptalene-4,5-dicarboxylates were prepared according to our
published procedures, whereby the corresponding azulenes were heated at 125 – 1308 with 3 mol-equiv.
of dimethyl acetylenedicarboxylate in toluene. Under these conditions, 1-methylazulene gave only 1-
methylheptalene-4,5-dicarboxylate 3 (m.p. 136.08 (Et2O)) in a yield of 25% (cf. [12]), and 4-
methylazulene led to a 3 :1 mixture (total yield 35%) of 6-methylheptalene-4,5-dicarboxylate 5 (m.p.
119.1 – 120.38 (Et2O); for X-ray data, see Table 7) and its 10-methyl analog 49 (m.p. 136.9 – 137.28 (Et2O);
for X-ray data, see Table 7) (cf. [12]). Finally, the 1,6,10-trimethylheptalene-4,5-dicarboxylate 11 (golden
yellow crystals, m.p. 139.5 – 141.08 (Et2O)) was obtained in a yield of 35% from 1,4,8-trimethylazulene,
which was prepared by established procedures from 4,8-dimethylazulene [14]. For the synthesis of the
3,3-dimethoxyheptaleno[1,2-c]furan-1(3H)-ones, see [6].
1. Dimethyl 3,4-Dihydro-3-[1-(phenylsulfonyl)alkyl]heptalene-4,5-dicarboxylates. 1.1. General Pro-
cedure. Under Ar and under stirring, methyl or ethyl phenyl sulfone (4.00 mmol) was dissolved in THF
(8 ml) and cooled to ꢀ 108. During 10 min, commercial 2.5m BuLi in hexane (1.80 ml, 4.5 mmol) was
added drop by drop, whereby the temp. was rising to ꢀ 28. After 10 min, a fine colorless precipitate was
formed. After a further 30 min at 08, the soln. was cooled to ꢀ 788, and a soln. of the heptalene-4,5-
dicarboxylate (1 mmol) in THF (5 ml) was added during 5 min. After consumption of all heptalene-
dicarboxylate (TLC (SiO2, hexane/AcOEt) monitoring), the mixture was poured on ice, acidified with
2n aq. HCl, and extracted with AcOEt. After washing of the extract with H2O and then with sat. aq. NaCl
soln, the extract was dried (Na2SO4).
1.2. Dimethyl (P*,3R*,4*R)- and (M*,3R*,4R*)-3,4-Dihydro-3-[(phenylsulfonyl)methyl]heptalene-
4,5-dicarboxylate ((P*)- and (M*)-2). Yield 0.293 g (69%) of (P*)/(M*)-2 3 :2. Yellow oil. Rf (hexane/
AcOEt 2 :1) 0.17. IR (KBr): 1733s (C¼O, ester), 1306s and 1148s (sulfone). EI-MS: 426 (15, Mþ), 366 (2,
[M ꢀ MeOCO]þ), 286 (10), 285 (53, [M ꢀ (MeOCO þ PhSO2)]þ), 272 (14), 253 (44, [M ꢀ (MeOCO þ
PhSO2 þ MeOH)]þ), 252 (85, [M ꢀ (MeOCO þ PhSO2H þ MeOH)]þ), 240 (8, [PhSO2CH¼
CHCOOMe]þ), 226 (12), 225 (55), 221 (16), 213 (14), 212 (10), 209 (11), 186 (54, [C10H7COOMe]þ),
135 (100).
NMR Data of (P*)-2: 1H-NMR (500 MHz, CDCl3): At 300 K, almost all corresponding signals of the
two epimeric forms showed coalescence; spectrum at 223 K (CHCl3 at 7.260; 60% of (P*)-2): 8.00 (d, Jo ¼
7.5, Ho of PhSO2); 7.71 (superimp. signals of Hp of PhSO2 of both forms); 7.63 (superimp. signals of Hm of
PhSO2 of both forms); 6.68 – 6.47 (superimp. signals of HꢀC(6) to HꢀC(10) and of HꢀC(7) to HꢀC(10)
of (M*)-2); 6.35 (dd, 3J(2,1) ¼ 11.9, 3J(2,3) ¼ 6.3, HꢀC(2)); 6.24 (d, 3J(1,2) ¼ 12.1, HꢀC(1)); 3.95 (dd,
2J(HS,HR) ¼ 13.7, 3J(HS,3) ¼ 1.8, HSꢀC(1’)); ca. 3.76 (br. s, HꢀC(4)), partly covered by the s of
MeOOCꢀC(5) of (M*)-2); 3.69 (s, MeOOCꢀC(5)); 3.50 (s, MeOOCꢀC(4)); 3.36 – 3.32 (superimp.
3
signals of HꢀC(3) of both forms); 3.12 (t-like, S 2J(HR,HS) þ J(HR,3) ¼ 25.7, HRꢀC(1’)). 13C-NMR
(125 MHz, CDCl3, 223 K; CDCl3 at 77.00): 171.45 (MeOOCꢀC(4)); 167.08 (MeOOCꢀC(5)); 52.17, 52.14
(MeOOCꢀC(4) and ꢀC(5)).
1
NMR Data of (M*)-2: H-NMR (500 MHz, CDCl3; 40% of the (M*)-form): 7.95 (d, Jo ¼ 7.5, Ho of
PhSO2); 7.71 (superimp. signals of Hp of PhSO2 of both forms); 7.63 (superimp. signals of Hm of PhSO2 of
both forms); 6.87 (d, 3J(6,7) ¼ 11.4 HꢀC(6)); 6.68 – 6.47 (superimp. signals of HꢀC(7) to HꢀC(10) and of
3
3
3
HꢀC(6) to HꢀC(10) of (P*)-2); 6.09 (dd, J(2,1) ¼ 12.1, J(2,3) ¼ 3.0, HꢀC(2)); 5.79 (d, J(1,2) ¼ 12.1,
HꢀC(1)); 4.56 (br. s, HꢀC(4)); 3.77 (s, MeOOCꢀC(5)); 3.62 (dd, 2J(HS,HR) ¼ 14.6, 3J(HS,3) ¼ 5.6,
HSꢀC(1’)); 3.39 (s, MeOOCꢀC(4)); 3.56 (dd, 2J(HR,HS) ¼ 14.6, 3J(HR,3) ¼ 7.1, HRꢀC(1’)); 3.36 – 3.32
(superimp. signals of HꢀC(3) of both forms). 13C-NMR (125 MHz, CDCl3, 223 K; CDCl3 at 77.00):
172.08 (MeOOCꢀC(4)); 166.16 (MeOOCꢀC(5)); 52.42, 52.27 (MeOOCꢀC(4) and ꢀC(5)).
1.3. Dimethyl (P*,1’R*,3S*,4*S)- and (M*,1’R*,3S*,4S*)-3,4-Dihydro-3-[(1-phenylsulfonyl)ethyl]-
heptalene-4,5-dicarboxylate ((P*)- and (M*)-21). Heptalenedicarboxylate 1 (1.00 g, 3.70 mmol) was
treated with ethyl phenyl sulfone (0.95g, 5.56 mmol) in the usual manner. The product was extracted with
16
)
NMR Spectra: d(H) rel. to Me4Si (¼0 ppm) or CHCl3 (¼7.26 ppm), d(C) rel. to CDCl3
(¼77.0 ppm); atoms of the [1-(R-sulfonyl)alkyl] groups have primed locants; HS ¼ Hpro-S, HR ¼
H
pro-R, and f.s. ¼ fine structure.

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Et2O and further purified by CC (SiO2, hexane/AcOEt 2 :1): 1.10 g (67%) of a dark brown oil. NMR:
(P*)/(M*)-21 ca. 45 :55; no signals were identified that could be assigned to 22 (see Scheme 4). (P*)/
(M*)-21: IR (KBr): 1733s and 1700s (C¼O, ester), 1305s and 1146s (sulfone). 1H-NMR (300 MHz,
CDC13, 300 K; identified signals): 7.9 – 7.5 (H of PhSO2 of both forms); 6.85 (d, 3J(6,7) ¼ 11.3, HꢀC(6) of
3
(M*)-21); 6.65 – 6.30 (superimp. signals of both forms); 6.05 (dd, J(2,1) ¼ 12.2, 3J(2,3) ¼ 2.7, HꢀC(2) of
3
(P*)-21); 4.47 (br. s, HꢀC(4) of (M*)-21); 4.06 (q, J(1’,MeꢀC(1’) ¼ 7.1, HꢀC(1’) of (M*)-21); 3.70 and
3.37 (2s, MeOOCꢀC(4) andꢀC(5) of (M*)-21); 3.65, 3.43 (2s, MeOOCꢀC(4) ꢀC(5) of (P*)-21); 1.22 (d,
3J(MeꢀC(1’),1’) ¼ 7.1, MeꢀC(1’) of both forms). 13C-NMR (75 MHz, CDC13; identified signals): 171.69
(MeOOCꢀC(4) of (M*)-21); 171.00 (MeOOCꢀC(4) of (P*)-21); 167.11 (MeOOCꢀC(5) of (P*)-21);
166.35 (MeOOCꢀC(5) of (M*)-21); 147.16 (C(5a) of (M*)-21); 145.73 (C(5a) of (P*)-21); 63.87 (C(1’) of
(M*)-21); 60.11 (C(1’) of (P*)-21); 13.99 (MeꢀC(1’) of (P*)-21); 13.08 (MeꢀC(1’) of (M*)-21). CI-MS:
458.1 (37, [M þ NH4]þ), 441.1 (100, [M þ l]þ), 409.1 (43, [(M þ 1) ꢀ CH3OH]þ), 299.1 (67, [(M þ 1) ꢀ
PhSO2H)]þ), 272.1 (15, [(M þ l) ꢀ PhSO2CHMe]þ), 187.0 (28 [C10H8COOMe]þ).
1.4. Dimethyl (P*,3R*,4*R)- and (M*,3R*,4R*)-3,4-Dihydro-1-methyl-3-[(phenylsulfonyl)methyl]-
heptalene-4,5-dicarboxylate ((P*)- and (M*)-4). Heptalenedicarboxylate 3 (0.200 g, 0.70 mmol) gave,
after crystallization (hexane/AcOEt), 0.206 g (67%) of colorless crystals of (P*)-4 (m.p. 1578), as shown
by an X-ray crystal-structure determination (Fig. 2 and Table 7). In CDCl3 soln. at r.t., a (P*)/(M*)-4 ca.
45 :55 was formed within minutes, and the corresponding signals of the epimers showed coalescence. Rf
(hexane/AcOEt 2 :1) 0.16.
Data of (P*)-4: IR (KBr): 1712s (C¼O, ester), 1334s and 1155s (sulfone). 1H-NMR (700 MHz,
CDCl3, 270 K; 45% of (P*)-4; CHCl3 at 7.276): 8.02 (d, Jo ¼ 7.6, Ho of PhSO2); 7.702 (t, Hp of PhSO2); 7.63
3
3
3
(t, Jo ¼ 7.6, Hm of PhSO2); 6.53 (dd, J(9,10) ꢂ 7, J(9,8) ꢂ 11, HꢀC(9)); 6.52 (d, J(10,9) ꢂ 6, HꢀC(10));
6.46 (dd, 3J(7,8) ¼ 6.3, 3J(7,6) ¼ 11.1, HꢀC(8)); 6.29 (d, 3J(2,3) ¼ 5.3, HꢀC(2)); 3.96 (d, 2J(HS,HR) ¼ 13.4,
HSꢀC(1’)); 3.80 (br. s, partly covered by the s of MeOOCꢀC(5) of (M*)-4, HꢀC(4)); 3.50 (s,
MeOOCꢀC(5)); 3.43 (br. s with spike amid, HꢀC(3)); 3.37 (s, MeOOCꢀC(4)); 3.07 (t-like, S
3
2J(HR,HS) þ J(HR,3) ¼ 26.5, HRꢀC(1’)); 1.94 (s, MeꢀC(1)). 13C-NMR (176 MHz, CDCl3, 270 K; CDCl3
at 77.02): 171.45 (MeOOCꢀC(4)); 166.57 (MeOOCꢀC(5)); 148.71 (C(5a)); 139.27 (Cipso of PhSO2);
133.71 (Cp of PhSO2); 132.50 (C(1)); 131.29 (C(10a)); 131.06 (C(6)); 130.15 (C(2)); 129.34 (Cm of
PhSO2); 129.10 (C(7)); 128.48 (C(7)); 128.03 (Co of PhSO2)); 125.81 (C(8)); 125.61 (C(9)); 120.20
(C(5)); 57.99 (C(1’)); 51.93 (MeOOCꢀC(5)); 51.88 (MeOOCꢀC(4)); 44.56 (C(4)); 34.10 (C(3)); 27.37
(MeꢀC(1)). EI-MS: 440 (6, Mþ), 299 (32, [M ꢀ (MeOCO þ PhSO2)]þ), 267 (6), 239 (10), 201 (11), 200
(100, [MeC10H6COOMe]þ). Anal. calc. for C24H24O6S (440.48): C 65.44 , H 5.49, S 7.28; found: C 65.36, H
5.43, S 7.41.
Data of (M*)-4: 1H-NMR (700 MHz, CDCl3, 270 K; 55% of (M*)-4): 7.97 (d, Jo ¼ 7.6, Ho of PhSO2);
7.698 (t, Hp of PhSO2); 7.61 (t, Jo ¼ 7.7, Hm of PhSO2); 6.76 (d, 3J(6,7) ¼ 11.1, HꢀC(6)); 6.69 (dd, 3J(9,10) ¼
7.1, 3J(9,8) ¼ 10.5, HꢀC(8)); 6.66 (d, 3J(10,9) ¼ 6.8, HꢀC(10)); 6.63 (dd, 3J(8,9) ¼ 10.6, 3J(8,7) ¼ 6.5,
HꢀC(8)); 6.43 (dd, 3J(7,8) ¼ 6.5, 3J(7,6) ¼ 10.8, HꢀC(7)); 5.64 (s, HꢀC(2)); 4.34 (br. s, HꢀC(4)); 3.79 (s,
MeOOCꢀC(5)); 3.65 (dd, 2J(HS,HR) ¼ 14.6, 3J(HS,3) ¼ 5.5, HSꢀC(1’)); 3.55 (dd, 2J(HR,HS) ¼ 14.6,
3J(HR,3) ¼ 6.8, HR ꢀC(1’)); 3.37 (s, MeOOCꢀC(4)); 3.29 (br. s, HꢀC(3)); 1.86 (s, MeꢀC(1)). 13C-NMR
(176 MHz, CDCl3, 270 K; CDCl3 at 77.02): 171.98 (MeOOCꢀC(4)); 165.83 (MeOOCꢀC(5)); 149.03
(C(5a)); 139.13 (Cipso of PhSO2); 133.83 (Cp of PhSO2); 132.55 (C(1)); 132.32 (C(10a)); 130.56 (C(8));
130.17 (C(9)); 129.34 (Cm of PhSO2); 129.14 (C(2), C(10)); 128.00 (Co of PhSO2)); 125.86 (C(6)); 125.36
(C(7)); 122.67 (C(5)); 60.44 (C(1’)); 52.17 (MeOOCꢀC(5)); 52.02 (MeOOCꢀC(4)); 45.80 (C(4)); 34.19
(C(3)); 26.83 (MeꢀC(1)).
1.5. Dimethyl (P*,3S*,4S*)- and (M*,3S*,4S*)-3,4-Dihydro-6-methyl-3-[(phenylsulfonyl)methyl]-
heptalene-4,5-dicarboxylate ((P*)- and (M*)-6). Crystallization (hexane/AcOEt) gave colorless crystals
of (P*)-6 (0.295 g, 67%; m.p. 1578). In CDCl3 soln. at r.t., a 3 :1 ratio of (P*)/(M*)-6 was established
within minutes. Over a longer period, the ratio approached a final value of 3 :2. Rf (hexane/AcOEt 2 :1)
0.14.
Data of (P*)-6: IR (KBr): 1743s (C¼O, ester), 1309s and 1132s (sulfone). 1H-NMR (500 MHz,
CDCl3, 250 K; 75% of the (P*)-6): 8.01 (dd-like, Jo ꢂ 7.3, Jm ꢂ 1.4, Ho of PhSO2); 7.71 (tt-like, Hp of
PhSO2); 7.63 (t-like, Hm of PhSO2); 6.53 – 6.48 (5 line m, HꢀC(8) and HꢀC(9) of (P*)-6, HꢀC(9) of (M*)-
6); 6.40 (d, 3J(10,9) ¼ 6.9, HꢀC(10)); 6.33 (dd, 3J(2,1) ¼ 11.7, 3J(2,3) ¼ 6.4, HꢀC(2)); 6.29 – 6.27 (br.,

910
Helvetica Chimica Acta – Vol. 95 (2012)
slightly structured signal, HꢀC(7) of both forms); 6.23 (d, 3J(1,2) ¼ 11.7, HꢀC(1)); 4.03 (dd, 2J(HS,HR) ¼
14.1, 3J(HS,3) ¼ 1.9, HSꢀC(1’)); 3.91 (d, 3J(4,3) ¼ 2.1, HꢀC(4)); 3.71 (s, MeOOCꢀC(5)); 3.47 (s,
MeOOCꢀC(4)); 3.36 – 3.32 (br., slightly structured signal, HꢀC(3)); 3.08 (dd, 2J(HR,HS) ¼ 14.0,
3J(HR,3) ¼ 11.7, HRꢀC(1’)); 2.03 (d, 4J(MeꢀC(6),7) ꢂ 0.8, MeꢀC(6)). 13C-NMR (125 MHz, CDCl3,
250 K; 75% of (P*)-6; CDCl3 at 77.00;): 171.00 MeOOCꢀC(4)); 168.16 (MeOOCꢀC(5)); 149.32 (C(5a));
138.62 (Cipso of PhSO2); 133.83 (Cp of PhSO2); 133.55 (C(2)); 131.14 (C(6)); 129.95 (C(8)); 129.88
(C(10)); 129.23 (Cm of PhSO2); 128.70 (C(10a)); 128.11 (C(1)); 128.07 (Co of PhSO2); 127.69 (C(9));
124.26 (C(7)); 122.48 (C(5)); 58.57 (C(1’)); 52.40 (MeOOCꢀC(5)); 52.06 (MeOOCꢀC(4)); 46.09 (C(4));
31.80 (C(3)); 24.88 (MeꢀC(6)). EI-MS: 440 (51, Mþ), 300 (8), 299 (44, [M ꢀ (MeOCO þ PhSO2)]þ), 283
(8), 240 (6, [PhSO2CH¼CHCOOMe]þ), 239 (26), 209 (10), 208 (10), 207 (31), 201 (13), 200 (100,
[MeC10H6COOMe]þ). Anal. calc. for C24H24O6S (440.48): C 65.44, H 5.49, S 7.28; found: 65.38, H 5.42, S
7.35.
Data of (M*)-6: 1H-NMR (500 MHz, CDCl3, 250 K; 25% of (M*)-6): 7.98 (dd-like, Jo ꢂ 7.3, Jm ꢂ 1.4,
Ho of PhSO2); 7.69 (tt-like, Hp of PhSO2); 7.61 (t-like, Hm of PhSO2); 6.50 (signals of HꢀC(8) of (M*)-6,
mostly covered by those of HꢀC(8) and HꢀC(9) of (P*)-6); 6.39 (dd, 3J(9,8) ¼ 11.3, 3J(9,10) ¼ 6.9,
HꢀC(9)); 6.31 (d, HꢀC(10), partly covered by the signals of HꢀC(2) of (P*)-6); 6.29 – 6.27 (br., slightly
3
3
structured signal, HꢀC(7) of both forms); 6.10 (dd, J(2,1) ¼ 11.9, J(2,3) ¼ 3.1, HꢀC(2)); 5.83 (dt-like,
3
3J(1,2) ¼ 11.9, HꢀC(1)); 4.35 (d-like, J(4,3) ꢂ 1.2, HꢀC(4)); 3.80 (s, MeOOCꢀC(5)); 3.475 (br. signal,
mostly covered by the signal of MeOOCꢀC(4) of (P*)-6, HꢀC(3)); 3.58, 3.57 (ABX, 2JAB ¼ 14.4, 3JAX
¼
3
4.3, JBX ¼ 8.5, CH2(1’)); 3.40 (s, MeOOCꢀC(4)); 2.09 (br. s, MeꢀC(6)). 13C-NMR (125 MHz, CDCl3,
250 K; 25% of (M*)-6; CDCl3 at 77.00;): 171.87 MeOOCꢀC(4)); 166.42 (MeOOCꢀC(5)); 151.21
(C(5a)); 139.06 (Cipso of PhSO2); 133.96 (Cp of PhSO2); 133.52 (C(1)); 132.13 (C(6)); 130.54 (C(8));
129.38 (Cm of PhSO2); 129.54 (C(10)); 128.59 (C(10a)); 127.89 (Co of PhSO2); 126.47 (C(9)); 125.87
(C(2)); 123.82 (C(5)); 123.00 (C(7)); 58.57 (C(1’)); 52.40 (MeOOCꢀC(5)); 52.06 (MeOOCꢀC(4)); 46.09
(C(4)); 31.80 (C(3)); 24.88 (MeꢀC(6)).
1.6. Dimethyl (P*,3R*,4*R)- and (M*,3R*,4R*)-3,4-Dihydro-8-methyl-3-[(phenylsulfonyl)methyl]-
heptalene-4,5-dicarboxylate ((P*)- and (M*)-8). Heptalenedicarboxylate 7 (0.200 g, 0.70 mmol) was
treated with methyl phenyl sulfone (0.440 g, 2.81 mmol) according to Exper. 1.1 to give (P*)/(M*)-8 ca.
3 :2 as a yellow oil. Rf (AcOEt/hexane 1:2) 0.18. IR (KBr): 1730s (C¼O, ester), 1308s and 1150s
(sulfone).
NMR Data of (P*)-8: 1H-NMR (500 MHz, CDCl3): At 300 K, coalescence of the corresponding
signals of (P*)- and (M*)-8 was observed; spectrum at 223 K (CHCl3 at 7.260), 60% of (P*)-8): 7.98 (d,
Jo ¼ 7.5, Ho of PhSO2); 7.69 (superimp. signals of Hp of PhSO2 of both forms); 7.60 (superimp. signals of
3
3
Hm of PhSO2 of both forms); 6.52 (d, J(6,7) ¼ 11.7, HꢀC(6)); 6.49 (d, J(9,10) ¼ 7.7, HꢀC(9)); 6.40 (d,
3J(10,9) ¼ 7.6, HꢀC(10)); 6.29 (d, 3J(7,6) ¼ 11.4, HꢀC(7)); 6.25 (dd, 3J(2,1) ¼ 12.0, HꢀC(2)); 6.19 (d,
3J(1,2) ¼ 12.1, HꢀC(1)); 3.93 (dd, 2J(HS,HR) ¼ 13.7, 3J(HS,3) ¼ 1.9, HSꢀC(1’)); 3.75 (br. s, HꢀC(4)); 3.67 (s,
MeOOCꢀC(5)); 3.49 (s, MeOOCꢀC(4)); 3.34 – 3.28 (superimp. signals of HꢀC(3) of both forms); 3.11 (t-
2
3
like, S J(HR,HS) þ J(HR,3) ¼ 25.9, HRꢀC(1’)); 2.08 (MeꢀC(8)). 13C-NMR (125 MHz, CDCl3, 223 K;
CDCl3 at 77.00; assigned signals): 171.52 (MeOOCꢀC(4)); 167.06 (MeOOCꢀC(5)); 147.91 (C(5a));
141.55 (C(8)); 138.16 (Cipso of PhSO2); 119.15 (C(5)); 58.39 (C(1’)); 52.09 (MeOOCꢀC(5)); 52.02
(MeOOCꢀC(4)); 46.32 (C(4)); 31.71 (C(3)); 24.75 (MeꢀC(8)).
1
NMR Data of (M*)-8: H-NMR (500 MHz, CDCl3, 223 K; 40% of (M*)-8): 7.93 (d, Jo ¼ 7.5, Ho of
PhSO2); 7.69 (superimp. signals of Hp of PhSO2 of both forms); 7.60 (superimp. signals of Hm of PhSO2 of
both forms); 6.83 (d, 3J(6,7) ¼ 11.9, HꢀC(6)); 6.40 (d, 3J(9,10) ¼ 7.7, HꢀC(6)); 6.34 (d, 3J(10,9) ꢂ 7.6,
HꢀC(10)); 6.25 (d, 3J(7,6) ¼ 11.4, HꢀC(6)); 6.09 (dd, 3J(2,1) ¼ 12.2, 3J(2,3) ¼ 2.8, HꢀC(2)); 5.70 (d,
3J(1,2) ¼ 12.1, HꢀC(1)); 4.56 (br. s, HꢀC(4)); 3.75 (s, MeOOCꢀC(5)); 3.62 (dd, 2J(HS,HR) ¼ 14.7,
3J(HS,3) ¼ 5.7, HSꢀC(1’)); 3.53 (dd, 2J(HR,HS) ¼ 14.7, 3J(HR,3) ¼ 7.2, HRꢀC(1’)); 3.40 (s, MeOOCꢀC(4));
3.34 – 3.28 (superimp. signals of HꢀC(3) of both forms); 2.07 (MeꢀC((8)). 13C-NMR (125 MHz, CDCl3,
223 K; assigned signals): 172.06 (MeOOCꢀC(4)); 166.22 (MeOOCꢀC(5)); 147.65 (C(5a)); 141.80
(C(8)); 138.20 (Cipso of PhSO2); 121.70 (C(5)); 60.50 (C(1’)); 52.27 (MeOOCꢀC(5)); 52.20
(MeOOCꢀC(4)); 47.54 (C(4)); 32.38 (C(3)); 24.69 (MeꢀC(8)).
1.7. Dimethyl (P*,3S*,4S*)- and (M*,3S*,4S*)-3,4-Dihydro-1,6-dimethyl-3-[(phenylsulfonyl)me-
thyl]heptalene-4,5-dicarboxylate ((P*)- and (M*)-10). Chromatography gave orange crystals of methyl

Helvetica Chimica Acta – Vol. 95 (2012)
911
1,6-dimethyl-4-[(phenylsulfonyl)acetyl]heptalene-5-carboxylate (0.011 g, 2.6%) and colorless crystals of
(P*)-10 (0.280 g, 62%).
Data of (P*)-10: M.p. 163 – 1648 (AcOEt/hexane). Rf (AcOEt/hexane 1:2) 0.13. On standing at r.t. in
C6D6 soln., (P*)-10 gave (P*)/(M*)-10 2 :1. 1H-NMR (600 MHz, C6D6, 300 K; 67% of (P*)-10; C6D5H at
7.160): 8.04 (d with f.s., Jo ꢂ 7.3, Ho of PhSO2); 6.97 – 6.93 (superimp. signals of Hm of PhSO2 with those of
3
Hm and Hp of (M*)-10); 6.91 (t with f.s., Jo ꢂ 7.6, Hp of PhSO2); 6.61 (d with f.s., J(7,8) ¼ 5.9, HꢀC(7));
6.25 – 6.23 (superimp. signals of HꢀC(8) and HꢀC(9) with one of (M*)-10); 6.15 – 6.12 (superimp. signal
3
4
of HꢀC(10) with two of (M*)-10); 5.99 (dd-like, J(2,3) ¼ 3.4, J(2,MeꢀC(1)) ¼ 1.4, HꢀC(2)); 4.78 (dd,
2J(HS,HR) ¼ 14.0, 3J(HS,3) ¼ 1.9, HSꢀC(1’)); 3.72 (d, 3J(4,3) ¼ 2.4, HꢀC(4)); 3.68 – 3.61 (superimp. signals
of HꢀC(3) of both forms); 3.36 (dd, 2J(HR,HS) ¼ 14.0, 3J(HR,3) ¼ 11.4, HRꢀC(1’)); 3.22 (s,
MeOOCꢀC(5)); 3.09 (s, MeOOCꢀC(4)); 1.76 (d-like, 4J(MeꢀC(1),2) ꢂ 1, MeꢀC(1)); 1.71 (s, MeꢀC(6)).
EI-MS: 454 (22, Mþ), 315 (5), 281 (7), 253 (5), 249 (4), 221 (8), 215 (14), 214 (100,
[Me2C10H5COOMe]þ). Anal. calc. for C25H26O6S (454.51): C 66.06, H 5.76, S 7.05; found: C 65.90, H
5.73, S 7.19.
The structure of (P*)-10 was finally established by an X-ray crystal-structure determination (see
Table 7 and Fig. 3).
Data of (M*)-10: 1H-NMR (600 MHz, C6D6, 300 K; 33% of (M*)-10): 7.83 (d with f.s., Jo ꢂ 8, Ho of
PhSO2); 6.97 – 6.93 (superimp. signals of Hm and Hp of PhSO2 with those of Hm of (M*)-10); 6.91 (t with
f.s., Jo ꢂ 7.6, Hp of PhSO2); 6.61 (d with f.s., 3J(7,8) ¼ 5.9, HꢀC(7)); 6.25 – 6.23 (superimp. signals of
HꢀC(10) with those of two H of (P*)-10); 6.15 – 6.12 (superimp. signals of HꢀC(8) and HꢀC(9) with one
3
3
H of (P*)-10); 6.04 (d, J(7,8) ¼ 6.2, HꢀC(7)); 5.64 (s with f.s., HꢀC(2)); 4.63 (d with f.s., J(4,3) ¼ 3.1,
HꢀC(4)); 3.75 (dd, 2J(HS,HR) ¼ 14.3, 3J(HS,3) ¼ 6.2, HSꢀC(1’)); 3.68 – 3.61 (superimp. signals of HꢀC(3)
2
3
of both forms); 3.51 (dd, J(HR,HS) ¼ 14.3, J(HR,3) ¼ 6.5, HRꢀC(1’)); 3.35 (s, MeOOCꢀC(5)); 3.13 (s,
MeOOCꢀC(4)); 2.00 (s, MeꢀC(6)); 1.67 (dd, 4J(MeꢀC(1),2) ¼ 1.4, 5J(MeꢀC(1),10) ¼ 2.2, MeꢀC(1)).
Methyl 1,6-Dimethyl-4-[(phenylsulfonyl)acetyl]heptalene-5-carboxylate. M.p. 216.7 – 217.18 (CH2Cl2/
hexane). Rf (AcOEt/hexane 1:2) 0.07. 1H-NMR (300 MHz, CDCl3): 7.89 – 7.86 (Ho of PhSO2); 7.66 – 7.50
(Hp and Hm of PhSO2); 7.33 (d, 3J(3,2) ¼ 5.6, HꢀC(3)); 6.48 (HꢀC(8), HꢀC(9); 6.24 (dd-like, 3J(2,3) ¼
6.3, 4J(2,MeꢀC(1)) ¼ 1.4, HꢀC(2)); 6.19 (signals of HꢀC(7)); 5.94 (signals of HꢀC(10)); 4.48, 4.44 (AB,
JAB ¼ 14.1, PhSO2CH2); 3.59 (s, MeOOCꢀC(5)); 2.09, 2.05 (2s, MeꢀC(1), MeꢀC(6)). EI-MS: 422 (22,
Mþ), 313 (9), 281 (51, [M ꢀ PhSO2]þ), 249 (39, [M ꢀ (PhSO2 þ MeOH)]þ), 239 (11), 221 (19, [M ꢀ
(PhSO2 þ MeOH þ CO)]þ), 214 (34), 179 (48), 156 (100, [Me2C10H6]þ), 152 (20), 77 (20, Ph).
1.8. Dimethyl (P*,3S*,4S*)- and (M*,3S*,4S*)-3,4-Dihydro-9-isopropyl-1,6-dimethyl-3-[(phenyl-
sulfonyl)methyl]heptalene-4,5-dicarboxylate ((P*)- and (M*)-15) and Methyl 9-Isopropyl-1,6-dimethyl-4-
[(phenylsulfonyl)acetyl]heptalene-5-carboxylate (16) [5]. Methyl phenyl sulfone (1.02 g, 6.50 mmol) and
heptalenedicarboxylate 14 (1.00 g, 2.94 mmol) gave, according to Exper. 1.1 and after workup, CC (SiO2,
hexane/AcOEt 3 :1), and crystallization from AcOEt/hexane 2 :1, colorless crystals of (P*)-15 (0.470 g,
35%) and orange crystals of 16 (0.306 g, 24%). At r.t., in CDCl3 soln., (P*)-15 epimerized rapidly to
(P*)/(M*)-15 3 :1.
1
Data of (P*)-15: See [5]. H-NMR (300 MHz, CDCl3, 300 K; in the presence of 25% of (M*)-15;
CHCl3 at 7.260): 8.02 – 7.97 (Ho of PhSO2 of both forms); 7.69 – 7.65 (Hp of PhSO2 of both forms); 7.64 –
7.55 (Hm of PhSO2 of both forms); 6.38 (s, HꢀC(10)); 6.28 (d, 3J(8,7) ¼ 6.6, HꢀC(8)); 6.20 (dd, 3J(2,3) ¼
5.8, 4J(2,MeꢀC(1)) ¼ 1.0, HꢀC(2)); 6.15 (dd, 3J(7,8) ¼ 6.5, 4J(7,MeꢀC(6)) ¼ 1.2, HꢀC(7)); 4.01 (dd,
2J(HS,HR) ¼ 14.1, 3J(HS,3) ¼ 1.9, HSꢀC(1’)); 3.88 (d, 3J(4,3) ¼ 2.5, HꢀC(4)); 3.68 (s, MeOOCꢀC(5)); 3.46
(s, MeOOCꢀC(4)); ca. 3.43 (br. s, mostly covered by ester signals of both forms, HꢀC(3)); 3.04 (dd,
2J(HR,HS) ¼ 14.1, 3J(HR,3) ¼ 11.4, HRꢀC(1’)); 2.55 (sept., Me2CHꢀC(9)); 1.98 (s, MeꢀC(6)); 1.90 (s,
MeꢀC(1)); 1.13, 1.11 (2d, superimp. to t, Jvic ¼ 6.8, Me2CHꢀC(9)). 13C-NMR (75 MHz, CDCl3, 300 K;
assigned signals): 170.98 (MeOOCꢀC(4)); 167.43 (MeOOCꢀC(5)); 151.52 (C(5a)); 146.88 (C(9));
139.83 (Cipso of PhSO2); 58.41 (C(1’)); 51.84 (MeOOCꢀC(5)); 51.64 (MeOOCꢀC(4)); 44.77 (C(4)); 35.83
(Me2CHꢀC(9)); 34.13 (C(3)); 26.10 (MeꢀC(1)); 23.45, 22.41 (Me2CHꢀC(9)); 23.28 (MeꢀC(6)). Full
1
analysis of the H-NMR showed that the crystals contained the (P*,3S*,4S*)-15.
Data of (M*)-15: 1H-NMR (300 MHz, CDCl3, 300 K; in the presence of 75% of (P*)-15;
recognizable signals): 6.31 (s, HꢀC(10)); 6.30 – 6.15 (HꢀC(8), HꢀC(7); signals covered by those of (P*)-

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Helvetica Chimica Acta – Vol. 95 (2012)
15); 5.62 (br. s, HꢀC(2)); 4.24 (dd, J ¼ 3.2, 1.1, HꢀC(4)); 2.48 (sept., Me2CHꢀC(9)); 2.00 (s, MeꢀC(6));
1.86 (dd, J ¼ 2.2, 1.4, MeꢀC(1)); 1.10, 1.09 (2d, superimp. to t, Jvic ¼ 6.8, Me2CHꢀC(9)).
Data of 16: Identical with those reported in [5].
1.9. Dimethyl (P*,3S*,4S*)- and (M*,3S*,4S*)-3,4-Dihydro-1,6,10-trimethyl-3-[(phenylsulfonyl)me-
thyl]heptalene-4,5-dicarboxylate ((P*)- and (M*)-12)) and Methyl 1,6,10-Trimethyl-4-[(phenylsulfon-
yl)acetyl]heptalene-5-carboxylate (13). From heptalenedicarboxylate 11 (1.00 g, 3.21 mmol) according to
Exper. 1.1. CC (SiO2, hexane/AcOEt 3 :1) gave crude (P*)/(M*)-12 (0.80 g, 63%) as a colorless oil and
13, after crystallization from AcOEt/hexane 2 :1, in golden yellow needles (0.445 g, 37%).
Data of (P*)/(M*)-12 55 :45: IR (film): 1731s and 1700s (C¼O, ester), 1307s and 1152s (sulfone).
13C-NMR (75 MHz, CDCl3, 300 K; identified signals, first value for (P*)-12, second for (M*)-12): 171.80,
171.57 (MeOOCꢀC(4)); 166.84, 165.57 (MeOOCꢀC(5)); 156.94, 155.31 (C(5a)); 139.78, 139.31 (Cipso of
PhSO2); 59.74, 58.58 (C(1’)); 52.03, 51.88 (MeOOCꢀC(5)); 51.30, 51.22 (MeOOCꢀC(4)); 44.73, 44.37
(C(4)); 34.50, 33.29 (C(3)).
Data of 13: M.p. 171 – 1728. 1H-NMR (300 MHz, CDCl3, 300 K; CHCl3 at 7.260): 7.87 (d with f.s., Ho
of PhSO2); 7.62 (tt-like, Hp of PhSO2); 7.51 (t, Hm of PhSO2); 7.35 (dd-like, 3J(3,2) ¼ 5.9, 5J(3, MeꢀC(1)) ¼
0.9, HꢀC(2)); 6.42 (dd, 3J(8,9) ¼ 11.1, 3J(8,7) ¼ 5.6, HꢀC(8)); 6.33 (d, 3J(9,8) ¼ 11.1, HꢀC(9)); 6.32 (dd-
3
3
like, J(2,3) ¼ 5.9, HꢀC(2)); 6.13 (d, J(7,8) ¼ 5.8, HꢀC(7)); 4.44 (s, CH2(1’)); 3.57 (s, MeOOCꢀC(5));
2.03 (t-like, MeꢀC(6)); 1.97 (t-like, MeꢀC(1)); 1.78 (MeꢀC(1)). EI-MS: 496 (98, Mþ), 295 (40, [M ꢀ
PhSO2]þ), 263 (36, [M ꢀ (PhSO2 þ MeOH)]þ), 228 (14, [M ꢀ PhSO2CH2C(O)CꢃCH]þ), 170 (100,
[Me3C10H5]þ).
1.10. Dimethyl (P*,3S*,4S*)- and (M*,3S*,4S*)-3,4-Dihydro-9-isopropyl-1,6-dimethyl-3-[(morpho-
linosulfonyl)methyl]heptalene-4,5-dicarboxylate ((P*)- and (M*)-19) [4]. We used the material prepared
in 1996. According to our present analysis, 6a in [4] represents the (P*)-epimer as shown by its 1H-NMR
(Table 10 in [4]) and its X-ray crystal-structure determination [4]. In turn, 6b in [4] is the corresponding
(M*)-form.
1.11. Dimethyl (P*,3S*,4S*)- and (M*,3S*,4S*)-3-{[(Diphenylamino)sulfonyl]methyl}-3,4-dihydro-
9-isopropyl-1,6-dimethylheptalene-4,5-dicarboxylate ((P*)- and (M*)-17)) and Methyl 4-{[(Diphenyl-
amino)sulfonyl]acetyl-9-isopropyl-1,6-dimethyl)heptalene-5-carboxylate (18). According to Exper. 1.1
with N,N-diphenylmethanesulfonamide (0.740 g, 3.00 mmol) [14] and heptalenedicarboxylate 14
(0.465 g, 1.36 mmol). Workup and CC (SiO2, hexane/AcOEt 3 :1) gave (P*)/(M*)-17 3 :1 (0.585 g,
36%) as a yellow-brown oil and 18 (0.186 g, 12%) as a dark brown oil. Both oils were not purified further.
Data of (P*)-17: Thermal equilibrium mixture of 75% of (P*)-17 and 25% of (M*)-17. IR (film):
1732s and 1712s (C¼O, ester), 1347s and 1157s (sulfonamide). 1H-NMR (300 MHz, CDCl3, 300 K; in the
presence of 25% of (M*)-17): 7.55 – 7.20 (arom. H of both forms); 6.38 (s, HꢀC(10)); 6.28 (d, 3J(8,7) ¼
5.9, HꢀC(8)); 6.14 (dd-like, 3J(7,8) ¼ 6.6, 4J(7,MeꢀC(6)) ¼ 1.4, HꢀC(7)); 6.11 (dd-like, 3J(2,3) ¼ 5.9,
2
3
3
4J(2,MeꢀC(1)) ¼ 1.0, HꢀC(2)); 4.31 (dd, J(HS,HR) ¼ 14.0, J(HS,3) ¼ 2.0, HSꢀC(1’)); 3.98 (d, J(4,3) ¼
2
3
2.4, HꢀC(4)); 3.72 (dd, partly covered by ester signals, J(HR,HS) ¼ 14.0, J(HR,3) ꢂ 8, HRꢀC(3)); 3.67
(s, MeOOCꢀC(5)); 3.58 (s, MeOOCꢀC(4)); 3.42 (br. s, HꢀC(3)); 2.54 (sept., Me2CHꢀC(9)); 1.90 (s,
5
MeꢀC(1)); 1.85 (t-like, S 4J(MeꢀC(6),7 þ J(MeꢀC(6),8)) ¼ 2.4, MeꢀC(6)); 1.13 and 1.11 (2d, Jvic ¼ 6.9,
Me2CHꢀC(9)). 13C-NMR (75 MHz, CDCl3, 300 K; in the presence of 25% of the (M*)-17; assigned
signals): 171.15 (MeOOCꢀC(4)); 167.12 (MeOOCꢀC(5)); 151.83 (C(5a)); 146.72 (C(9)); 141.10 (Cipso of
Ph); 123.96 (C(8)); 123.10 (C(7)); 120.79 (C(5)); 55.99 (C(1’)); 51.71 (MeOOCꢀC(4) and ꢀC(5)); 44.80
C(4)); 35.70 (Me2CHꢀC(9)); 34.62 (C(3)); 25.95 (MeꢀC(1)); 23.14 (Me2CHꢀC(9)); 22.33 (MeꢀC(6)).
CI-MS: 605.4 (22, [M þ NH4]þ), 588.4 (100, [M þ 1]þ), 556.4 (39, [M þ 1 ꢀ MeOH]þ), 419.2 (24, [M þ
1 ꢀ Ph2N]þ), 355.3 (54, [M þ 1 ꢀ Ph2NSO2]þ), 256.2 (11, [iPrMe2C10H4COOMe]þ).
1
Data of (M*)-17: H-NMR (300 MHz, CDCl3, 300 K; in the presence of ca. 75% of the (P*)-17;
identified signals): 6.32 (HꢀC(10)); 6.30 – 6.09 (HꢀC(8), HꢀC(7); covered by the signals of (P*)-17);
5.76 (br. s, HꢀC(2)); 3.76 (s, MeOOCꢀC(5)); 3.42 (s, MeOOCꢀC(4)); 2.48 (sept., Me2CHꢀC(9)); 2.02
4
5
(MeꢀC(6)); 1.87 (t-like, S J(MeꢀC(1),2) þ J(MeꢀC(1),10) ¼ 2.2, MeꢀC(1)); 1.11, 1.09 (2d, Jvic ¼ 6.9,
Me2CHꢀC(9)). 13C-NMR (75 MHz, CDCl3, 300 K; in the presence of ca. 75% of (P*)-17; assigned
signals): 171.33 (MeOOCꢀC(4)); 166.29 (MeOOCꢀC(5)); 151.94 (C(5a)); 145.91 (C(9)); 141.52 (Cipso of
PhSO2); 124.43 (C(8)); 122.50 (C(7)); 120.00 (C(5)); 57.36 (C(1’)); 51.89 (MeOOCꢀC(4) and ꢀC(5));
46.25 (C(4)); 35.94 (Me2CHꢀC(9)); 35.40 (C(3)); 25.69 (MeꢀC(1)); Me2CHꢀC(9)); 22.62 (MeꢀC(6)).

Helvetica Chimica Acta – Vol. 95 (2012)
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Data of 18: 1H-NMR (300 MHz, CDCl3; significant signals only): 6.3 – 6.1 (HꢀC(2), HꢀC(3),
HꢀC(7), HꢀC(8)); 5.85 (s, HꢀC(10)); 4.50, 4.44 (AB, JAB ¼ 13.9, CH2(2’)); 2.45 (sept., Me2CHꢀC(9));
2.07 (d-like, 4J(MeꢀC(1),2) ¼ 1.1, MeꢀC(1)); 1.06, 1.01 (2d, Jvic ¼ 6.9, Me2CHꢀC(9)). 13C-NMR (75 MHz,
CDCl3, 300 K): 188.45 (O¼CꢀC(4)); 167.64 (MeOOCꢀC(5)).
1.12. Dimethyl (P*,3S*,4S*)-3,4-Dihydro-isopropyl-1,6-dimethyl-3-[(1R*)-1-(phenylsulfonyl)ethyl]-
heptalene-4,5-dicarboxylate ((P*)-23) and Methyl (P*)-9-Isopropyl-1,6-dimethyl-4-[(2S*)-1-oxo-2-(phe-
nylsulfonyl)propyl]heptalene-5-carboxylate (24). See [5] for the X-ray crystal structure of (P*)-23. The
1H- and 13C-NMR spectra of (P*)-23 were again measured and all atom positions fully assigned; some
had to be corrected with respect to those reported in [5]. 1H-NMR (600 MHz, CDCl3, 300 K; CHCl3 at
7.260): 8.00 (dd-like, Jo ¼ 7.3, Jm ꢂ 1.4, Ho of PhSO2); 7.65 (tt, Jo ¼ 7.4, Jm ꢂ 1.1, Hp of PhSO2); 7.58 (t, Jo ¼ 7.7,
Hm of PhSO2); 6.32 (s, HꢀC(10)); 6.28 (d, 3J(8,7) ¼ 6.5, HꢀC(8)); 6.14 (dd-like, 3J(7,8) ¼ 6.5, 4J(7,
MeꢀC(6)) ꢂ 1, HꢀC(7)); 6.02 (dd-like, 3J(2,3) ¼ 5.2, 4J(2,MeꢀC(1)) ꢂ 0.7, HꢀC(2)); 3.98 (br. q,
3
3
3J(1’,MeꢀC(1’)) ¼ 6.8, J(1’,3) ꢄ 0.6, HꢀC(1’)); 3.97 (d, J(4,3) ¼ 3.3, HꢀC(4)); 3.85 (very br., slightly
structured s, HꢀC(3)); 3.69 (s, MeOOCꢀC(5)); 3.48 (s, MeOOCꢀC(4)); 2.55 (sept., Me2CHꢀC(9)); 1.96
(s, MeꢀC(6)); 1.95 (t-like, 4J(MeꢀC(1’)) ꢂ 2, · J(MeꢀC(1),10) ꢂ 1.3, MeꢀC(1)); 1.31 (d,
5
3J(MeꢀC(1’),1’) ¼ 7.0, MeꢀC(1’)); 1.13, 1.09 (2d, Jvic ¼ 6.9, Me2CHꢀC(9)). 13C-NMR (150 MHz, CDCl3,
300 K; CDCl3 at 77.00): 171.14 (MeOOCꢀC(4)); 167.52 (MeOOCꢀC(5)); 150.31 (C(5a)); 147.10 (C(9));
138.29 (Cipso of PhSO2); 133.98 (C(1)); 133.35 (Cp of PhSO2); 131.81 (C(10a)); 129.14 (Co of PhSO2);
129.09 (C(6)); 128.95 (Cm of PhSO2); 127.80 (C(2)); 127.08 (C(10)); 123.96 (C(8)); 123.48 (C(7)); 121.32
(C(5)); 59.93 (C(1’)); 51.91 (MeOOCꢀC(5)); 51.75 (MeOOCꢀC(4)); 44.71 (C(4)); 36.68 (C(3)); 35.95
(Me2CHꢀC(9)); 26.54 (MeꢀC(1)); 24.41, 22.46 (Me2CHꢀC(9)); 11.25 (MeꢀC(1’)).
1.13. Dimethyl (P*,3S*,4S*)-3,4-Dihydro-9-isopropyl-1,4,6-trimethyl-3-[(1S*)-1-phenylsulfonyl)-
ethyl]heptalene-4,5-dicarboxylate ((P*)-41). NaH (0.025 g, 1.05 mmol; obtained from an NaH suspension
in mineral oil by washing with hexane) in THF (0.5 ml) was cooled to ꢀ 108, followed by the addition of
(P*)-23 (0.425 g, 0.83 mmol) dissolved in THF (3 ml). The mixture was stirred for 4 h without further
cooling, and then MeI (0.185 g, 0.08 ml, 1.30 mmol) was added. After 3 d stirring at r.t., H2O was added.
The product was extracted with Et2O and crystallized from Et2O; (P*)-41 (0.420 g, 95%). Pale yellow
crystals.
M.p. 127 – 1288. IR (KBr): 1740s and 1701s (C¼O, ester), 1325s and 1148s (sulfone). 1H-NMR
(300 MHz, CDCl3, 300 K): 7.93 (d with f.s., Jo ꢂ 8, Ho of PhSO2); 7.56 – 7.47 (superimp. signals of Hp and
Hm of PhSO2); 6.35 (s, HꢀC(10)); 6.28 (d, 3J(8,7) ¼ 6.4, HꢀC(8)); 6.17(dd-like, 3J(2,3) ¼ 6.0, 4J(2,
MeꢀC(1)) ¼ 1.1, HꢀC(2)); 6.11 (dd-like, 3J(7,8) ¼ 6.5, 4J(7,MeꢀC(6)) ¼ 1.3, HꢀC(7)); 4.30 (br. q,
3J(1’,MeꢀC(1’)) ꢂ 6.5, HꢀC(1’)); 3.81 (s, MeOOCꢀC(5)); 3.57 (s, MeOOCꢀC(4)); 3.08 (br. d,
3J(3,2) ¼ 5.5, HꢀC(3)); 2.58 (sept., Me2CHꢀC(9)); 2.11 (s, MeꢀC(6)); 2.06 (s, MeꢀC(1)); 1.66 (br. s,
MeꢀC(4)); 1.51 (d, 3J(MeꢀC(1’),1’) ¼ 7.0, MeꢀC(1’)); 1.15 (d, Jvic ¼ 6.9, pro-R-Me of Me2CHꢀC(9)); 1.10
(d, Jvic ¼ 6.8, pro-S-Me of Me2CHꢀC(9)). Relevant 1H-NOE: pro-R-Me of Me2CHꢀC(9)/MeꢀC(4) and
HꢀC(8); pro-S-Me of Me2CHꢀC(9)/HꢀC(10); these 1H-NOE established also the (P*)-configuration of
the 3,4-dihydroheptalene skeleton and the (S)-configuration at C(4). 13C-NMR (75 MHz,CDCl3, 300 K):
176.36 MeOOCꢀC(4)); 170.88 (MeOOCꢀC5)); 145.79 (C(9)); 144.94 (C(5a)); 140.92 (Cipso of PhSO2);
135.23 (C(1)); 132.64 (Cp of PhSO2); 131.04 (C(6)); 130.74 (C(10a)); 128.77 (Co of PhSO2); 128.53 (Cm of
PhSO2); 127.47 (C(10)); 125.10 C(5)); 124.25 (C(2)); 124.11 (C(8)); 123.22 (C(7)); 61.89 (C(1’)); 52.45
(MeOOCꢀC(5)); 52.05 (MeOOCꢀC(4)); 51.62 (C(4)); 50.09 (C(3)); 36.23 (Me2CHꢀC(9)); 25.59
(MeꢀC(1)); 23.76 and 22.50 (Me2CHꢀC(9)); 23.18 (MeꢀC(6)); 19.36 (MeꢀC(1’)). CI-MS: 525.2 (100,
[M þ 1]þ), 493.2 (10, [M þ 1 ꢀ MeOH]þ), 404.2 (10), 386.2 (16), 286.1 (57), 257.2 (74,
[(iPrMe2C10H5COOMe]þ).
The structure and rel. configuration of (P*)-41 was finally established by an X-ray crystal-structure
analysis (cf. Table 7 and Fig. 4).
2. 4,5-Dihydro-3,3-dimethoxy-5-[1-(phenylsulfonyl)ethyl]heptaleno[1,2-c]furan-1(3H)-ones. 2.1.
General Procedure. At 08 and under Ar and stirring, a soln. of [1-(phenylsulfonyl)ethyl]lithium in
THF (25 ml) was prepared from the sulfone (1.76 mmol) and 2.5m BuLi in hexane (2.20 mmol). The soln.
was then cooled to ꢀ 788, and the 3,3-dimethoxyheptaleno[4,5-c]furan-1(3H)-one (1.50 mmol) in THF
(5 ml) was added drop by drop. After 3 h stirring at ꢀ 788, the mixture was quenched with ice-cooled

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Helvetica Chimica Acta – Vol. 95 (2012)
17% aq. HCl (soln.). After extraction with AcOEt, the AcOEt phase was washed, dried (Na2SO4) and
concentrated, and the residue re-crystallized.
2.2. (P*,5S*)- and (M*,5S*)-4,5-Dihydro-8-isopropyl-3,3-dimethoxy-6,11-dimethyl-5-[(1R*)-1-(phe-
nylsulfonyl)ethyl]heptaleno[1,2-c]furan-1(3H)-one ((P*)- and (M*)-27). Furanone (P*)-25 (0.50 g,
1.47 mmol) [7] was treated with EtSO2Ph (0.306 g, 1.76 mmol) according to Exper. 2. Recrystallization
from Et2O gave (P*)-27 as pale yellow crystals (0.625 g, 92%). Dissolution of the crystals in CDCl3 at
243 K showed only the presence of (P*)-27 (1H-NMR); at ambient r.t., a 64 :36 mixture of (P*)- and
(M*)-27 was established in a short time.
Data of (P*)-27. M.p. 158.0 – 160.18. Rf (AcOEt/hexane 1:2) 0.59. IR (KBr): 1768s (C¼O, five-ring
lactone). 1H-NMR (600 MHz, CDCl3, 300 K, in the presence of 36% of (M*)-27; CHCl3 at 7.264): 7.765
(dd-like, Jo ¼ 8.3, Jm ¼ 1.1, Ho of PhSO2); 7.627 (tt-like, J ¼ 7.5, 1.1, Hp of PhSO2); 7.504 (t with f.s., J ¼ 7.9,
Hm of PhSO2); 6.318 (dd, 3J(9,10) ¼ 11.8, 4J(9,7) ¼ 1.1, HꢀC(9)); 6.225 (d, 3J(10,9) ¼ 11.9, HꢀC(10));
5.838 (br. s, HꢀC(7)); 3.472 (s, (MeO)2C(3))17); 3.409 (br. dt-like, 3J(5,HRꢀC(4)) ¼ 12.6, S
3
3
3
3J(5,HSꢀC(4)) þ J(5,1’) ¼ 4.4, HꢀC(5)); 3.339 (qd, J(1’,MeꢀC(1’)) ¼ 7.1, J(1’,5) ¼ 2.4, HꢀC(1’)); 2.842
(dd, 2J(HS,HR) ¼ 20.0, 3J(HS,5) ¼ 2.0, HSꢀC(4)); 2.458 (sept., Me2CHꢀC(8)); 2.255 (dd, 2J(HR,HS) ¼ 20.0,
3J(HR,5) ¼ 12.5, HRꢀC(4); 1.967 (s, MeꢀC(11)); 1.590 (d-like, 5J(MeꢀC(6),7) ꢂ 0.8, MeꢀC(6)); 1.526 (d,
3J(MeꢀC(1’),1’) ¼ 7.1, MeꢀC(1’)); 1.073/1.062 (2d, t-like superimp., 3J ¼ 6.7, 6.6, Me2CHꢀC(8)).
13C-NMR (150 MHz, CDCl3, 300 K, in the presence of 36% of (M*)-27; CDCl3 at 77.00): 166.27
(C(1)); 158.71 (C(3a)); 144.13 (C(8)); 137.75 (C(11)); 137.47 (Cipso of PhSO2); 134.77 (C(6a)); 133.82
(C(10)); 133.52 (Cp of PhSO2); 131.74 (C(9)); 129.35 (C(11b)); 129.11 (Cm of PhSO2); 128.82 (C(6));
128.67 (Co of PhSO2); 121.42 (C(7)); 119.47 (C(11a)); 118.46 (C(3)); 59.89 (C(1’)); 51.59 (MeOꢀC(3),
pro-R); 51.48 (MeOꢀC(3), pro-S); 35.39 (C(5)); 34.37 (Me2CHꢀC(8)); 24.19 (C(4)); 22.76, 22.41
(Me2CHꢀC(8)); 22.41 (MeꢀC(11)); 12.08 (MeꢀC(6)); 9.99 (MeꢀC(1’)). CI-MS: 533.1 (100, [M þ Na]þ),
391.1 (15, [M þ Na ꢀ PhSO2H]þ).
The rel. configuration of (P*)-27 was established by an X-ray crystal-structure analysis (see Fig. 5
and Table 7).
Data of (M*)-27: 1H-NMR (600 MHz, CDCl3, 300 K; in the presence of 64% of (P*)-27; CHCl3 at
7.264): 7.726 (dd-like, Jo ¼ 8.3, Jm ¼ 1.1, Ho of PhSO2); 7.583 (tt-like, J ¼ 7.5, 1.1, Hp of PhSO2); 7.463 (t with
f.s., J ¼ 7.9, Hm of PhSO2); 6.456 (dd, 3J(9,10) ¼ 11.8, 4J(9,7) ¼ 1.1, HꢀC(9)); 6.365 (d, 3J(10,9) ¼ 11.8,
HꢀC(10)); 5.744 (br. s, HꢀC(7)); 3.783 (qd, 3J(1’,MeꢀC(1’)) ¼ 7.2, 3J(1’,5) ¼ 9.5, HꢀC(1’)); 3.460 (s,
3
MeOꢀC(3), pro-R); 3.290 (s, MeOꢀC(3), pro-S); 3.783 (ddd, S 3J(5,HRꢀC(4)) þ J(5,HSꢀC(4)) þ
2
3
2
3J(5,1’) ¼ 17.9, HꢀC(5)); 2.656 (dd, J(HR,HS) ¼ 21.0, J(HR,5) ¼ 3.4, HRꢀC(4)); 2.523 (dd, J(HS,HR) ¼
21.0, 3J(HS,5) ¼ 4.6, HSꢀC(4)); 2.469 (sept., Me2CHꢀC(8)); 1.930 (s, MeꢀC(11)); 1.599 (d,
5J(MeꢀC(6),7) ¼ 1.0, MeꢀC(6)); 1.231 (d, 3J(MeꢀC(1’),1’) ¼ 7.2, MeꢀC(1’)); 1.108, 1.090 (2d, 3J ¼ 6.9,
6.8, Me2CHꢀC(8)). 13C-NMR (150 MHz, CDCl3, 300 K, in the presence of 36% of (P*)-27; CDCl3 at
77.00): 166.12 (C(1)); 157.67 (C(3a)); 143.55 (C(8)); 138.53 (Cipso of PhSO2); 137.72 (C(11)); 133.63
(C(9)); 133.34 (Cp of PhSO2); 133.20 (C(10)); 133.10 (C(6)); 131.79 (C(6a)); 129.35 (Cm of PhSO2);
128.88 (C(11b)); 128.67 (Co of PhSO2); 122.76 (C(7)); 120.33 (C(11a)); 118.08 (C(3)); 60.91 (C(1’));
51.68 (MeOꢀC(3), pro-R); 51.51 (MeOꢀC(3), pro-S); 39.81 (C(5)); 34.31 (Me2CHꢀC(8)); 25.58 (C(4));
22.77, 22.69 (Me2CHꢀC(8)); 22.54 (MeꢀC(11)); 18.81 (MeꢀC(6)); 12.76 (MeꢀC(1’)).
2.3. (P*,5S*)-4,5-Dihydro-3,3-dimethoxy-7,9,11-trimethyl-5-[(1R*)-1-(phenylsulfonyl)ethyl)hepta-
leno[1,2-c]furan-1(3H)-one ((P*)-30). Furanone 28 (0.50 g, 1.60 mmol)18) in THF (5 ml) was treated
with EtSO2Ph (0.327 g, 1.92 mmol) in THF (20 ml) according to Exper. 2.1. CC (SiO2, hexane/AcOEt
3 :1) and crystallization from AcOEt/hexane gave pure (P*)-30 (0.530 g, 69%). Pale yellow crystals. M.p.
196.3 – 197.38. Rf (hexane/AcOEt 3 :2) 0.49. IR (KBr): 1766s (C¼O, five-ring lactone). 1H-NMR
(500 MHz, CDCl3, 300 K; CHCl3 at 7.264): 7.803 (d with f.s., Jo ¼ 7.3, Ho of PhSO2); 7.640 (t, Jo ¼ 7.5, Hp of
PhSO2); 7.520 (t, Jo ¼ 7.8, Hm of PhSO2); 6.124 (br. s, HꢀC(10)); 5.880 (br. s, HꢀC(8)); 5.342 (d, 3J(6,5) ¼
17
)
)
At 243 K, two s appeared at d(H) 3.458 and 3.425, corresponding presumably to the pro-R- and pro-
S-MeO group, resp.
The semi-orthoanhydride 28 (m.p. 118.0 – 119.08 (Et2O/hexane)) was prepared from the
corresponding heptalene half-ester in the described manner [7] (for spectral details, see [15]).
18