Reactions of dimethoxycarbene with N-tosylated imines

Article abstract of DOI:10.1002/hlca.200790210

The reactions of dimethoxycarbene (DMC; 2), which was generated in situ by thermal decomposition of 2,5-dihydro-2,2-dimethoxy-5,5-dimethyl-l,3,4-oxadiazole (1), with N-tosylated imines of xanthone and 2,3:6,7-dibenzosuberenone, 3a and 3d, respectively, le

Full text of DOI:10.1002/hlca.200790210

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Helvetica Chimica Acta – Vol. 90 (2007)
Reactions of Dimethoxycarbene with N-Tosylated Imines
by Grzegorz Mloston´*
´
´
´
´
University of Łodz, Department of Organic and Applied Chemistry, Narutowicza 68, PL-90-136 Łodz
(phone: þ 48426355761; fax: þ 48426355380; e-mail: gmloston@uni.lodz.pl)
and John Warkentin
Department of Chemistry, McMaster University, 1280 Main Street West, Hamilton, Ontario L8S 4M1,
Canada
and Anthony Linden and Heinz Heimgartner*
Organisch-chemisches Institut der Universität Zürich, Winterthurerstrasse 190, CH-8057 Zürich
(phone: þ 41446354282; fax: þ 41446356812; e-mail: heimgart@oci.unizh.ch)
Dedicated to Professor Günther Maier (Giessen) on the occasion of his 75th birthday
The reactions of dimethoxycarbene (DMC; 2), which was generated in situ by thermal
decomposition of 2,5-dihydro-2,2-dimethoxy-5,5-dimethyl-1,3,4-oxadiazole (1), with N-tosylated imines
of xanthone and 2,3 :6,7-dibenzosuberenone, 3a and 3d, respectively, led to different adducts with
rearranged skeletons. In the case of 3a, the 1:1 adduct 5 as well as the 2 :1 adduct 6 were obtained
(Scheme 2). The formation of both products can be explained by a migration of a MeO group of the
DMC fragment in a zwitterionic intermediate. On the other hand, migration of a Me group of DMC is
necessary for the formation of the two 1:1 adducts 13 and 14 of 2 and 3d (Scheme 5). The structures of all
products have been established by X-ray crystallography.
1. Introduction. – The thermal decomposition of 2,5-dihydro-2,2-dimethoxy-5,5-
dimethyl-1,3,4-oxadiazole (1), elaborated by Warkentin and co-workers [1][2], is a
convenient method for the generation of dimethoxycarbene (2), which enabled the
exploration of this nucleophilic carbene for synthetic purposes. Similarly to other
carbenes, the reactions with diverse multiple bonds are of special interest. In the case of
2, the reactions with C¼C bonds are limited to ethenes, which are activated by electron-
withdrawing groups. Whereas, with dimethyl dicyanofumarate, a multistep reaction
leads to a 2,2-dimethoxy-2,3-dihydrofuran derivative [3], dicyanomethylidene-substi-
tuted adamantane and 9H-fluorene yield the corresponding cyclopropanes [4]. The
reactions of 2 with cycloaliphatic ketones lead either to spirocyclic 2,2-dimethoxyox-
iranes or to ring-enlarged 2,2-dimethoxy ketones [2][5][6]. Cycloaliphatic thioketones
react efficiently with 2 to give dimethoxythiiranes [6][7].
The reactions of 2 with C¼N-containing compounds have been examined with
isocyanates only [8]. Recently, we reported the first example of a successful conversion
of 2 with 9H-fluorene-9-imine 3a, which is activated by a toluenesulfonyl substituent
(Scheme 1). The isolated product 4 is formed in a multi-step reaction, in which the
sulfonyl group has migrated from the N- to the C-atom [9].
ꢀ 2007 Verlag Helvetica Chimica Acta AG, Zürich

Helvetica Chimica Acta – Vol. 90 (2007)
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Scheme 1
The detailed reaction mechanism is not known to date, but the presence of an
aziridine and/or an azomethine ylide as key intermediate is likely. The influence of the
fluorene system is decisive, as neither the analogous benzaldehyde N-tosylimine nor
benzophenone N-tosylimine reacted with 2.
The present study is aimed at the explanation of the influence of the structure of the
N-tosylated imine of type 3 on the reactivity towards 2. For this reason, the
corresponding imines 3b – 3e were prepared and used as potential substrates in the
reactions with the carbene 2 generated by thermal decomposition of 1.
2. Results and Discussion. – 2.1. Reactions of 2 with 3b and 3c. A solution of 3b and
3 equiv. of 1 in toluene was heated under reflux for 8 h. The 1H-NMR spectrum of the
mixture showed the presence of two products 5 and 6 (Me signals of the Ts residue at
2.40 and 2.35 ppm, resp.; Scheme 2) along with the starting imine 3b (Me signal at
2.45 ppm). Then, 2 additional equiv. of 1 were added, and the heating was continued for
1
another 6h, until 3b was consumed completely. The H-NMR analysis of the mixture
confirmed the presence of 5 and 6, and the ratio of both products, established on the
basis of the intensity of the Me signals for the Ts residue, was ca. 1 :3.
Scheme 2

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Helvetica Chimica Acta – Vol. 90 (2007)
The products were separated by preparative layer chromatography, and the less-
polar fraction gave the minor product 5 as a colorless, crystalline material. The
1H-NMR spectrum showed three singlets for Me groups at 2.40, 3.00, and 3.45 ppm in a
1:1:1 ratio. The 13C-NMR signal at 170.7 ppm, as well as an intensive absorption in the
IR spectrum at 1637 cmÀ1, revealed the presence of a C¼N group. The ESI-MS with
m/z 462 and 446 ([M þ K]þ and [M þ Na]þ, resp.) indicated that 5 is a 1:1 product.
However, the two non-equivalent MeO groups suggested that, similar to the reaction
with 3a, the isolated product 5 is not an aziridine derivative. Based on these data, a
structure analogous to 4 could tentatively be formulated. Finally, an X-ray crystal
structure determination established unambiguously structure 5 with the two MeO
groups located at two different C-atoms (Scheme 2 and Fig.1 ). In contrast to 4, the
formation of 5 requires a migration of one MeO group of the carbene fragment.
Fig. 1. ORTEP Plot [10] of the molecular structure of 5 (arbitrary numbering of the atoms; 50%
probability ellipsoids)
The more-polar fraction was also obtained as a colorless crystalline substance. In
this case, the 1H-NMR spectrum showed one signal for an aromatic Me group
(2.35 ppm) and three signals for MeO groups located at 2.95, 3.35, and 3.45 ppm in the
ratio of 1:2 :1. The ESI-MS with m/z 536and 520 ([ M þ K]þ and [M þ Na]þ, resp.)
showed that this product corresponds to a 2 :1 stoichiometry with respect to 2 and 3b.
Again, the 13C-NMR spectrum as well as the IR spectrum confirmed the presence of a
C¼N group (165.8 ppm and 1633 cmÀ1, resp.). The structure 6 was also established by
X-ray crystallography (Fig.2 ).
The structures of the isolated products 5 and 6 indicate a different pathway of the
reaction of dimethoxycarbene (2) and 3b compared with that of 2 and 3a. Whereas, in
the case of 3a, the intermediate rearranges by a N ! C migration of the sulfonyl group
to give 4, the intermediate formed from 2 and 3b undergoes a C ! C migration of a
MeO group. The formation of the aziridine 7, most likely via the initially formed
zwitterion B, followed by the cleavage of the NÀC(9) bond to give 8, offers a plausible

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Fig. 2. ORTEP Plot [10] of the molecular structure of 6 (arbitrary numbering of the atoms; 50%
probability ellipsoids)
explanation for the sequence of the atoms in 5. The latter is formed via a 1,2-shift of a
MeO group (Scheme 3). Whether this shift occurs as a concerted process or via the ion
pair 9 cannot be answered.
The structure of 6 shows that this product was formed either from 5 or from an
intermediate precursor of 5 via insertion of a second carbene 2 into a C,C bond.
However, a control experiment with 5 and 1 in boiling toluene evidenced that no 6 was
formed and, therefore, 5 is not an intermediate in the formation of 6.
In some reactions of dimethoxycarbene (2), the tetramethoxyethene (dimer of 2),
formed in situ, is proposed to react with electron-deficient p-systems to yield the four-
membered [2 þ 2] cycloadducts [8b]. In the reaction with 3b, which requires a large
excess of the carbene precursor 1, the [2 þ 2] cycloaddition with tetramethoxyethene
would lead to the azetidine derivative 10. The negative result of a control experiment
with 3b and tetramethoxyethene, carried out in boiling toluene, showed that 3b was
inert under these conditions.
Taking into account the results of both control experiments, a plausible explanation
for the formation of 6 is based on the assumption that the initially formed zwitterion B
reacts with a second molecule of 2 to give a new zwitterion C, which subsequently
undergoes ring closure to yield the azetidine 10. The ring opening of the latter results in
the formation of the isomeric zwitterion 11, which is converted to the final product 6 via
migration of a MeO group. Again, this MeO migration may occur in two steps via an
ion pair or via two consecutive 1,2-shifts of MeO groups.
Another candidate for the reaction with the second molecule of 2 may be the cation
of the ion pair 9. The nucleophilic attack of 2 onto 9 could lead to the intermediate 12,

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Helvetica Chimica Acta – Vol. 90 (2007)
Scheme 3
which undergoes a 1,2-shift of the imido ester group. The isolated product 6 is then
formed by addition of methoxide (Scheme 4).
The analogous reaction of the thioxanthone imine 3c and 1 led to a complex mixture
of products, which, after consumption of 3c, showed absorption signals of MeO groups
between 3 and 4 ppm. However, the separation of the products by fractional
crystallization was unsuccessful, and the attempted chromatographic separation led
to decomposition of the products.
2.2. Reactions of 2 with 3d and 3e. The complete consumption of 3d in boiling
toluene was achieved with a threefold excess of 1. After evaporation of the solvent,
trituration of the residue with Et2O led to a crystalline, colorless material. The 1H-NMR
spectrum showed a signal for an aromatic Me group at 2.39 ppm, and two signals at 2.68
and 4.08 ppm in a ratio of 1:1:1. Only the latter is a typical shift for a MeO group.
Surprisingly, the IR spectrum of this product showed a strong absorption band at
1736cm À1, indicating the presence of a C¼O group instead of the C¼N group. This
conclusion was confirmed by the signal at 172.3 ppm in the 13C-NMR spectrum. These
data suggest the presence of a methyl ester. Finally, the structure of the ester 13 was
established by X-ray crystallography (Scheme 5 and Fig.3 ).

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Scheme 4
Scheme 5
The analysis of the mother liquor by 1H-NMR spectroscopy showed that, along with
traces of 13, a second product was present, which also displayed three Me signals at
2.48, 3.54, and 3.56ppm in a ratio of 1:1:1. Whereas the first one is characteristic for
the Me group of the tolyl residue, the others are in the range of MeO groups. In the IR
spectrum (KBr), the absorption of a C¼O group was located at 1737 cmÀ1, almost
identical with that of 13. The presence of an ester group was confirmed by the
13C-NMR spectrum, in which the C¼O signal appeared at 171.8 ppm. Furthermore, the

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Helvetica Chimica Acta – Vol. 90 (2007)
Fig. 3. ORTEP Plot [10] of the molecular structure of 13 (arbitrary numbering of the atoms; 50%
probability ellipsoids)
ESI-MS showed that the product is an isomer of 13 (m/z 456, [M þ Na]þ).
Unexpectedly, the X-ray crystal-structure determination revealed the structure 14,
which contains a methyl carboxylate and a methyl iminosulfonate (Scheme 5 and
Fig.4 ).
To test their thermal stability, the separated products 13 and 14 were heated in
refluxing toluene. After 4 h, no isomerization was observed, and each substance was
recovered from the solution unchanged. This result is consistent with the observation
that the ratio of 13 and 14, determined in the crude reaction mixture of 1 and 3d after
different lengths of heating time, was constant.
The structures of 13 and 14 show that both compounds are formed via migration of
a Me group. To the best of our knowledge, this is the first case in which an intermediate,
formed by the addition of dimethoxycarbene (2), is stabilized by a Me and not a MeO
shift (cf. [11]). A plausible reaction pathway is depicted in Scheme 6. The zwitterion B’
is probably the crucial intermediate for the formation of both products. However, the
labile aziridine 15 can also be involved in the reaction. The formation of 13 from B’ can
be rationalized by an O ! N Me shift. In principle, this reaction could occur by either

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Fig. 4. ORTEP Plot [10] of the molecular structure of one of the two symmetry-independent molecules of
14 (arbitrary numbering of the atoms; 50% probability ellipsoids)
an intra- or intermolecular process, but neither of them is favorable. Whereas the
intramolecular 5-endo-tet transition state is disfavored in terms of the Baldwin rules
[12] (cf. also [13]), the intermolecular pathway seems unlikely because of the low
concentration of the reactive intermediate [11]. In spite of this fact, intermolecular
transfers of the Me group are reported for certain systems [14].
The intermediate B’ can also be proposed as the precursor of 14. In this case, the
observed O ! O migration of the Me group corresponds to a 1,6-shift, which involves a
seven-membered transition state. According to the Baldwin rules, this is a favored
process (however, see [13b]). Nonetheless, an intermolecular transfer of the Me group
cannot be excluded. Upon the assumption that the aziridine 15 is an intermediate, the
Me shift 15 ! 14 can be recognized as a retro-ene reaction (Scheme 6).
Under the conditions applied for the reaction of 1 and 3d, the 2,3 :6,7-
dibenzosuberone derivative 3e did not react with 2, and, after chromatographic
separation, it was recovered almost quantitatively. This result shows again that small
structural differences in the N-sulfonylated imines influence the outcome of the
reaction with 2 significantly.
3. Conclusions. – In addition to the reaction of 2 with N-tosylated 9H-fluoren-9-one
imine 3a described earlier [9], the present study shows that the corresponding imines,
derived from 9H-xanthen-9-one 3b and 2,3 :6,7-dibenzosuberenone 3d, are able to
react with 2 to give 1:1 or 1:2 adducts. The course of the reaction depends strongly on
the structure of the imine used. In none of the cases studied, could the aziridine
derivatives, which might be expected as typical carbene adducts to the C¼N bond, be

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Helvetica Chimica Acta – Vol. 90 (2007)
Scheme 6
isolated or detected. Nevertheless, the intermediacy of these heterocycles offers a
plausible explanation of the mechanisms leading to the final products. Depending on
the nature of the imine, each of the three bonds of the aziridine can be broken under the
reaction conditions. Whereas, in the case of 3a, the final product can be formed via
formation of an azomethine ylide (cleavage a; Fig.5 ), in the cases of 3b and 3d, the
alternative cleavages of a CÀN bond are observed (cleavage b and c, resp.).
Fig. 5. Cleavage possibilities
´
´
We thank Mrs. M.Celeda , University of Łodz, for technical assistance, and Dr. M.Wçrle , ETH-
Zürich, for collecting the diffraction data for 6. G.M. thanks the Polish Ministry of Education and Science
for a grant (No. PBZ-KBN-126/T09/12), and H.H. acknowledges financial support by F.Hoffmann-La
Roche AG, Basel.

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Experimental Part
1. General. M.p.: in capillary with a Meltemp 2 apparatus; uncorrected. IR Spectra: in KBr pellets
with a Nexus FT-IR spectrophotometer; in cmÀ1 1H- and 13C-NMR spectra: Bruker 200 and 400
.
spectrometer, resp. (200 and 100 MHz, resp.) with TMS (¼0 ppm) as an internal standard; d in ppm, J in
Hz. CI-MS: Finnigan MAT-90 spectrometer; in m/z (rel.). Elemental analyses were performed in the
Analytical Laboratory of the University of Zürich.
2. Starting Materials.2,2-Dimethoxy-5,5-dimethyl-2,5-dihydro-1,3,4-oxadiazole (1) was prepared and
purified according to the procedure published by Warkentin and co-workers [1]. The sulfonylated imines
3b – 3e were prepared from the corresponding commercially available ketones and 4-methylbenzene-
sulfonamide by heating in 1,2-dichloroethane soln. in the presence of Et3N and TiCl4 according to [15].
Crystalline products were obtained in good yields (70 – 90%) and were purified by crystallization or
column chromatography (CC).
4-Methyl-N-(9H-xanthen-9-ylidene)benzenesulfonamide (3b). Pale yellow crystals. M.p. 174 – 1768
(MeOH/CH2Cl2) ([16]: 170 – 1718).
4-Methyl-N-(9H-thioxanthen-9-ylidene)benzenesulfonamide (3c). Pale yellow crystals. M.p. 207 –
2108 (MeOH/CH2Cl2) ([17]: 2128).
N-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-4-methylbenzenesulfonamide (3d). Pale yellow crystals.
M.p. 156– 159 8 (purified by CC (SiO2; CH2Cl2/petroleum ether 4 :1)). IR (KBr): 1599s, 1574vs (C¼N),
1548m, 1319vs, 153vs, 1090s, 843s, 804s, 788s, 6 73s, 56 6s. 1H-NMR (CDCl3): 8.10 – 7.05 (m, 12 arom. H);
6.96 (s, CH¼CH); 2.30 (s, Me). Anal. calc. for C22H17NO2S (359.45): C 73.51, H 4.77, N 3.90, S 8.90;
found: C 73.38, H 4.69, N 3.68, S 8.79.
N-(10,11-Dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-4-methylbenzenesulfonamide (3e). Pale
yellow crystals. M.p. 112 – 1158 (purified by CC (SiO2; petroleum ether with increasing amount of
1
CH2Cl2)). IR (KBr): 1595vs, 1564vs (C¼N), 1323vs, 1155vs, 1091s, 838s, 750vs, 6 70s, 561vs. H-NMR
(CDCl3): 7.90 – 7.60 (m, 4 arom. H); 7.40 – 7.00 (m, 8 arom. H); 3.02 (s, 2 CH2); 2.35 (s, Me). Anal. calc. for
C22H19NO2S (361.47): C 73.10, H 5.30, N 3.87, S 8.85; found: C 69.87, H 5.28, N 3.72, S 8.69.
3. Reactions of DMC (2) with 3b – 3e. General Procedure. A soln. of 1 (480 mg, 3 mmol) and the
corresponding imine 3 (1 mmol) in abs. toluene (4 ml) was heated to reflux for 8 h under Ar. When the
imine 3 was completely consumed, the solvent was evaporated, and the crude residue was analyzed by
1H-NMR spectroscopy. In the case of 3e, after 8 h of heating, the major component of the mixture was
identified as the starting material (TLC; 1H-NMR: m at 7.90 – 7.60 ppm and s for 2 CH2 at 3.02 ppm). The
mixtures obtained with 3b, 3c, and 3d were separated by CC (SiO2). However, the products formed with
3c decomposed during the attempted chromatographic separation and subsequent crystallization.
Separation of the crude mixtures obtained with 3b and 3d yielded two products in each case.
Reaction with 3b. In this case, 800 mg (5.0 mmol) of 1, added in two portions, were used to achieve
complete conversion of 3b after 14 h of heating. Prep. layer chromatography (PLC) on plates coated
with SiO2 (CH2Cl2/petroleum ether 8 :2) was applied to separate the products 5 and 6.
(E)-N-[Methoxy(9-methoxy-9H-xanthen-9-yl)methylidene]-4-methylbenzenesulfonamide (5). Less-
polar fraction. Yield: 84 mg (20%). Colorless crystals. M.p. 192 – 1948 (MeOH). IR (KBr): 1637vs
(C¼N), 1481m, 1447s, 1322s, 1299m, 1155s, 1092m, 756s, 676vs, 6 08s. 1H-NMR (CDCl3): 7.85 (d, 3J ¼ 7.0, 2
3
arom. H); 7.72 (d, J ¼ 7.0, 2 arom. H); 7.42 – 7.15 (m, 8 arom. H); 3.45, 3.00 (2s, 2 MeO); 2.40 (s, Me).
13C-NMR: 170.7 (s, C¼N); 151.5 (s, 2 arom. C); 142.1, 142.0 (2s, 2 arom. C); 130.4, 129.1, 128.4, 126.2,
123.6(5 d, 2 arom. CH each); 118.6( s, 2 arom. C); 116.8 (d, 2 arom. CH); 77.4 (s, C(9’’)); 56.1, 51.0 (2q,
2 MeO); 21.6( q, Me). ESI-MS: 462 (9, [M þ K]þ), 446(62, [ M þ Na]þ), 392 (100, [M À MeO]þ). Anal.
calc. for C23H21NO5S (423.48): C 65.23, H 5.00, N 3.31, S 7.57; found: C 64.94, H 4.83, N 3.15,
S 7.54.
(E)-4-Methyl-N-[1,2,2-trimethoxy-2-(9-methoxy-9H-xanthen-9-yl)ethylidene]benzenesulfonamide
(6). More-polar fraction. Yield: 250 mg (50%). Colorless crystals. M.p. 143 – 1458. IR (KBr): 1633vs
(C¼N), 1477m, 1447s, 1314s, 1241m, 1161vs, 1093vs, 757m, 6 74s, 6 07m. 1H-NMR (CDCl3): 7.69 – 7.08 (m,
12 arom. H); 3.45 (s, MeO); 3.35 (s, 2 MeO); 2.95 (s, MeO); 2.35 (s, Me). 13C-NMR (CDCl3): 165.8 (s,
C¼N); 152.6( s, 2 arom. C); 141.9, 141.7 (2s, 2 arom. C); 130.1, 129.5, 129.0, 125.9, 122.4, 115.9 (6d, 2
arom. CH each); 118.8 (s, 2 arom. C); 105.3 (s, C(2’)); 80.5 (s, C(9’’)); 55.7 (q, MeO); 52.7 (q, 2 MeO);

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Helvetica Chimica Acta – Vol. 90 (2007)
51.3 (q, MeO); 21.5 (q, Me). ESI-MS: 536(44, [ M þ K]þ), 520 (100, [M þ Na]þ), 466 (34, [M À MeO]þ).
Anal. calc. for C22H27NO7S (497.56): C 62.76, H 5.47, N 2.82, S 6.44; found: C 62.66, H 5.72, N 2.72, S 6.39.
Reaction with 3d. After heating for 7 h, no starting material was detected (TLC) in the soln. Toluene
was evaporated to dryness, and separation of 13 and 14 was achieved either by trituration of the oily
residue with Et2O at r.t. (in this case, 13 precipitated from the solution), or by PLC (SiO2) with
petroleum ether/AcOEt 8 :2 as the eluent. Anal. pure products were obtained by crystallization.
Methyl 5-[Methyl(4-methylphenylsulfonyl)amino]-5H-dibenzo[a,d]cycloheptene-5-carboxylate (13).
Less-polar fraction. Yield: 135 mg (31%). Colorless crystals. M.p. 233 – 2358 (MeOH/CH2Cl2). IR
(KBr): 1736vs (C¼O), 1632m (br.), 1332vs, 1243s, 1156s, 1011m, 972m, 839s, 795s, 6 71m, 594s, 553m.
1H-NMR (CDCl3): 7.95 (br. s, 2 arom. H); 7.33 (t-like, 2 arom. H); 7.21 (t-like, 2 arom. H); 7.08 – 6.98 (m, 4
arom. H); 6.82 (d-like, 2 arom. H); 6.45 (br. s, CH¼CH); 4.08 (s, MeO); 2.68 (s, MeN); 2.39 (s, Me).
13C-NMR (CDCl3): 172.3 (s, C¼O); 142.3, 138.9, 134.7, 128.1 (4 br. s, 6arom. C); 134.9, 131.5 (2 br. s,
4 CH); 129.5, 128.7, 128.4, 127.4, 126.5 (5d, 12 CH); 75.9 (s, C(5)); 52.9 (q, MeO); 37.6( q, MeN); 21.6( q,
Me). ESI-MS: 472 (85, [M þ K]þ), 456(100, [ M þ Na]þ), 249 (50). Anal. calc. for C25H23NO4S (433.53):
C 69.26, H 5.35, N 3.23, S 7.40; found: C 69.34, H 5.32, N 3.21, S 7.49.
Methyl N-[5-(Methoxycarbonyl)-5H-dibenzo[a,d]cyclohepten-5-yl]-4-methylbenzenesulfonimidate
(14). More-polar fraction. Yield: 152 mg (35%). Colorless crystals. M.p. 171 – 1738 (MeOH). IR
(KBr): 1737vs (C¼O), 1629m (br.), 1332vs (br.), 1210s (br.), 1014m, 982m, 807m, 76 5m, 729m, 6 6 m9 ,
580m. 1H-NMR (CDCl3): 8.25 – 7.82 (m, 4 arom. H); 7.55 – 7.15 (m, 6arom. H); 7.03 ( s, CH¼CH); 3.56,
3.54 (2s, 2 MeO); 2.48 (s, Me). 13C-NMR (CDCl3): 171.8 (s, CO); 143.8, 141.0, 140.4, 135.9 (4s, 6arom.
C); 132.9, 131.0, 129.7, 127.9, 127.7, 126.4, 124.7 (7d, 12 arom. CH, CH¼CH); 70.5 (s, C(5)); 56.5, 52.5 (2q,
2 MeO); 21.6( q, Me). ESI-MS: 472 (6, [M þ K]þ), 456(100, [ M þ Na]þ), 249 (10). Anal. calc. for
C25H23NO4S (433.53): C 69.26, H 5.35, N 3.23, S 7.40; found: C 69.27, H 5.43, N 3.11, S 7.35.
4. Control Experiments.a ) A soln. of 5 (30 mg, 0.07 mmol) and 1 (22 mg, 0.14 mmol) in toluene
(0.5 ml) was heated under reflux for 8 h. After evaporation of the solvent, the colorless residue was
analyzed by 1H-NMR spectroscopy, which evidenced the presence of unchanged 5, exclusively.
b) A soln. of 1 (80 mg, 0.5 mmol) in toluene (1 ml) was heated under reflux for 8 h. Then, the soln.
was cooled to r.t., and, after addition of 3b (139 mg, 0.4 mmol), heating under reflux was continued for
6h. The solvent was evaporated, and the residue was analyzed by 1H-NMR spectroscopy, which showed
the presence of unchanged 3b. No traces of either 5 or 6 were detected in the spectrum.
5. X-Ray Crystal-Structure Determination of 5, 6, 13, and 14 (Table and Figs.1 – 4 )1). All
measurements for 5, 13, and 14 were performed on a Nonius KappaCCD area-detector diffractometer
[18] using graphite-monochromated MoKa radiation (l 0.71073 Š) and an Oxford Cryosystems
Cryostream 700 cooler. Data reduction was performed with HKL Denzo and Scalepack [19]. In the
case of 6, all measurements were performed on a BRUKER SMART-CCD area-detector diffractometer
using graphite-monochromated MoKa radiation. Data reduction was performed with the Bruker SAINT
software [20]. For each data set, the intensities were corrected for Lorentz and polarization effects, and
an absorption correction based on the multi-scan method [21] was applied. The data collection and
refinement parameters are given in the Table, and views of the molecules are shown in Figs.1 – 4 . Each
structure was solved by direct methods using SIR92 [22], which revealed the positions of all non-H-
atoms. In the case of 14, there are two symmetry-independent molecules in the asymmetric unit. The
atomic coordinates of the two molecules were tested carefully for a relationship from a higher symmetry
space group using the program PLATON [23], but none could be found. For each structure, the non-H-
atoms were refined anisotropically. All of the H-atoms were placed in geometrically calculated positions
and refined using a riding model where each H-atom was assigned a fixed isotropic displacement
parameter with a value equal to 1.2 Ueq of its parent C-atom (1.5 Ueq for the Me groups). The refinement
of each structure was carried out on F2 using full-matrix least-squares procedures, which minimized the
function Sw(Fo2 À Fc2 )2. A correction for secondary extinction was applied in the cases of 5 and 14. For 13,
the refinement of the absolute structure parameter [24] yielded a value of 0.04(9), which confidently
1
)
CCDC-656139 – 656142 contain the supplementary crystallographic data for this paper. These data
can be obtained free of charge from the Cambridge Crystallographic Data Centre via http://
www.ccdc.cam.ac.uk/data_request/cif.

Helvetica Chimica Acta – Vol. 90 (2007)
2035
confirms that the refined model corresponds with the true enantiomorph. For 14, the absolute structure
parameter of 0.60(11) suggests that the structure may be an inversion twin. The absolute structure of the
model was chosen arbitrarily. In the case of 14, two reflections, whose intensities were considered to be
extreme outliers, were omitted from the final refinement. Neutral atom scattering factors for non-H-
atoms were taken from [25], and the scattering factors for H-atoms were taken from [26]. Anomalous
dispersion effects were included in Fc [27]; the values for f ’ and f ’’ were those of [28]. The values of the
mass attenuation coefficients are those of [29]. All calculations were performed using the SHELXL97
program [30].
Table. Crystallographic Data for Compounds 5, 6, 13, and 14
5
6
13
14
Crystallized from
Empirical formula
Formula weight
Crystal color, habit
Crystal dimensions [mm]
Temp. [K]
Crystal system
Space group
Z
EtOH
C23H21NO5S
423.48
hexane/CH2Cl2
C26H27NO7S2
497.56433.52
MeOH
C25H23NO4S
433.52
MeOH
C25H23NO4S
colorless, prism colorless, prism colorless, prism colorless, tablet
0.12 ꢀ 0.22 ꢀ 0.28 0.40 ꢀ 0.40 ꢀ 0.50 0.17 ꢀ 0.25 ꢀ 0.28 0.12 ꢀ 0.22 ꢀ 0.25
160(1)
monoclinic
P21/n
233(1)
monoclinic
P21/c
4
160(1)
monoclinic
P21
160(1)
monoclinic
Cc
4
2
8
Reflections for cell determination 26834
2q Range for cell determination [8] 4 – 6 0
Unit cell parameters:
985
5 – 6 0
20737
4 – 55
92876
4 – 50
a [Š]
b [Š]
c [Š]
10.8564(2)
11.4689(9)
17.107(1)
13.078(1)
106.404(2)
2461.3(3)
1.343
7.6740(1)
12.7363(3)
11.0467(2)
103.012(1)
1051.96(3)
1.369
13.1687(3)
12.9675(4)
25.5922(8)
101.091(2)
4288.6(2)
1.343
8.9071(2)
21.6690(5)
98.673(1)
2071.41(8)
1.358
0.191
f and w
6
b [8]
V [Š3]
Dx [g cmÀ3
]
m(MoKa) [mmÀ1
Scan type
]
0.178
w
0.187
f and w
0.183
f and w
2q(max) [8]
0
6
1
55
50
Transmission factors [min; max]
Total reflections measured
0.867; 0.978
54323
0.840; 1.000
33531
0.841; 0.974
22909
0.841; 0.990
31147
Symmetry independent reflections 6040
7531
4773
7243
Reflections with I > 2s(I)
3912
4901
4272
5151
Reflections used in refinement
Parameters refined; restraints
6040
275; 0
7531
321; 0
4773
283; 1
7241
566; 2
Final R(F) (I > 2s (I) reflections) 0.0497
0.0460
0.1196
0.056; 0.4736
1.007
0.0592
0.1533
0.0938; 0.5154
1.097
0.0639
0.1553
0.0734; 5.7909
1.045
wR(F2) (all data)
0.1366
Weighting parameters (a; b)a)
Goodness-of-fit
0.064; 0.7213
1.023
Secondary extinction coefficient
0.025(2)
0.001
0.44; À 0.33
–
–
0.0046(4)
0.001
0.44; À 0.36
Final Dmax/s
D1 (max; min) [e Š
0.001
0.33; À 0.27
0.001
0.49; À 0.59
À3
]
a) wÀ1 ¼ s2(Fo2 ) þ (aP)2 þ bP, where P ¼ (Fo2 þ 2Fc2 )/3.

2036
Helvetica Chimica Acta – Vol. 90 (2007)
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Received August 8, 2007