Sulfinyl Homo- and Hetero-Dienes from Sulfenic Acids: An Approach Towards Six-membered Nitrogen Heterocycles in Enantiomerically Pure Form

Article abstract of DOI:10.1055/s-2003-41076

Two different synthetic pathways are presented that provide access to enantiopure sulfinyl hydrazones; in both addition of sulfenic acid/unsaturation represents the crucial step of the procedure. The obtained results are discussed in terms of regioselecti

Full text of DOI:10.1055/s-2003-41076

SPECIAL TOPIC
2241
Sulfinyl Homo- and Hetero-Dienes from Sulfenic Acids: An Approach To-
wards Six-membered Nitrogen Heterocycles in Enantiomerically Pure Form
Sulfinyl
H
omo- andH
a
etero-Diene
r
s
from
S
i
ulfenic
a
A
cids C. Aversa,* Anna Barattucci, Maria C. Bilardo, Paola Bonaccorsi,* Placido Giannetto
Dipartimento di Chimica organica e biologica, Università degli Studi di Messina, Salita Sperone 31 (vill. S. Agata), 98166 Messina, Italy
Fax +39(090)393895; E-mail: aversa@unime.it
Received 6 August 2003
with a satisfying stereochemical control and/or easy sepa-
Abstract: Two different synthetic pathways are presented that pro-
ration of the diastereomeric cycloadducts by chromatog-
raphy. On the other hand, the facile access to high yields
of enantiomerically pure -sulfinyl , -unsaturated car-
vide access to enantiopure sulfinyl hydrazones; in both addition of
sulfenic acid/unsaturation represents the crucial step of the proce-
dure. The obtained results are discussed in terms of regioselectivity
in the formation of - and/or -sulfinyl , -unsaturated products bonyl compounds suggested their use as heterodienes in
when sulfenic acids are reacted with substrates showing carbonyl
inverse electron-demanding DA reactions, giving an alter-
conjugated triple bonds, and/or their derivatives. Despite its struc-
native access to enantiopure pyranoid systems (see, for in-
tural limitations, (RS,E,E)-2-[(1S)-isoborneol-10-sulfinyl]-2-buten-
stance, the synthesis of 3 in Scheme 1).6
al dimethylhydrazone (6) behaves as 1-azabuta-1,3-diene in hetero
Diels–Alder reaction with N-methylmaleimide, giving a unique cy-
cloadduct with complete endo and facial selectivities.
Key words: 1-aza-1,3-dienes, chiral auxiliaries, stereoselective
synthesis, sulfenic acids, sulfoxides
Cyclic structures represent a relevant portion of the skele-
ton of several natural substances. Six-membered rings are
building blocks in carbohydrates, alkaloids, terpenes, ste-
roids, and a tremendous number of other biomolecules.
Their widespread presence in nature represents the main
reason for the interest generated by reactions such as the
Diels–Alder (DA) cycloaddition which supplies a
straightforward and stereocontrolled access to six-mem-
bered cyclic molecules.
The development of an efficient and original methodolo-
gy to generate a diene skeleton, bearing an enantiopure
sulfinyl group,1 directed our research towards DA reac-
tions of such substrates with commonly used dienophiles,
with the aim of testing the efficiency – as chiral auxiliary
– of the sulfoxide substituent directly linked to a diene
carbon, and possibly obtaining functionalized six-mem-
bered rings in enatiomerically pure form. The high degree
of stereochemical control observed in the cycloadditions
of diene 1 with methyl acrylate in the presence of LiClO4
(Scheme 1)2 prompted us to involve several different
sulfinyl dienes in catalyzed and uncatalyzed homo-DA re-
actions.3 We were also interested in investigating the re-
Scheme 1
activity of our sulfinyl dienes in hetero-DA (HDA)
cycloadditions, which give an easy access to very useful
In this paper we discuss the effectiveness of the synthetic
heterocyclic molecules. Pyranoid4 and thiopyranoid5 de-
pathways a and b (Scheme 2) towards enantiopure sulfi-
rivatives 2–5 were synthesized following the approaches
nyl , -unsaturated dimethylhydrazones, obtained by ad-
shown in Scheme 1. The most common heterodienophiles
dition of suitable sulfenic acids to alkynyl hydrazones
such as glyoxylates for pyranoid and thioketones for thi-
(pathway a) or alternatively by addition of sulfenic acids
opyranoid systems cycloadded to suitable sulfinyl dienes
to alkynyl carbonyl compounds and subsequent derivati-
zation of the obtained , -unsaturated carbonyl com-
pounds with H2NNMe2 (pathway b). This study seemed to
be a useful framework to analyze the influence that the
substitution features of the triple bond in the acceptor
SYNTHESIS 2003, No. 14, pp 2241–2248
Advanced online publication: 24.09.2003
DOI: 10.1055/s-2003-41076; Art ID: C04203SS.pdf
© Georg Thieme Verlag Stuttgart · New York
0
2.
1
0
.
2
0
0
3

2242
M. C. Aversa et al.
SPECIAL TOPIC
molecules exert on the sulfenic acid addition. We also re-
port the use of (RS,E,E)-2-butenal dimethylhydrazones 6
and 7 and 2- and 3-[(1S)-isoborneol-10-sulfinyl] substi-
tuted, as 1-azabuta-1,3-dienes in stereoselective HDA re-
actions for access to hydrogenated pyridine derivatives.
The introduction into the azadiene moiety of an electron-
donating group, such as NMe2, has proven to be effective
in activating this system towards the normal electron-de-
manding DA reaction with electron-deficient dieno-
philes.7 Several applications of such 1-azabuta-1,3-dienes
in racemic form were directed to the synthesis of
alkaloids8 whereas few examples of enantiopure 1-azabu-
ta-1,3-dienes are reported in the literature9 and only one of
these heterodienes9a has been involved successfully in ste-
reoselective DA cycloadditions.
Scheme 3
The synthetic approach, shown as pathway a in Scheme 2
and followed at first, suffered the limitation of the desired
compounds being formed in low yields, and this restric-
tion induced us to cover pathway b whose key step con-
sisted of the addition of a sulfenic acid to a carbonyl
compound, positively corroborated by our previous stud-
ies.6 Thermolysis of cyanoethylsulfinylisoborneols 9 in
the presence of phenylpropargyl aldehyde (14) afforded
3-[(1S)-isoborneol-10-sulfinyl]-3-phenyl-2-propenals 17
and 18 and 2-[(1S)-isoborneol-10-sulfinyl-3-phenyl-2-
propenals 19 and 20 in a 43:40:11:6 ratio and 73% total
yield (Scheme 4). Despite the observed loss of stereo-
selectivity, since the two sulfur epimers 17 and 18 were
obtained in almost the same percentages, and an analo-
gous ratio was measured between 19 and 20, the addition
of sulfenic acid 10 to aldehyde 14 showed an increased re-
gioselectivity (83:17) and a much better total yield. The
sulfur configuration in the sulfinyl aldehydes 17–20 was
attributed as mentioned above. (RS)- and (SS)-3-sulfinyl-
2-propenals 17 and 18 were reacted separately with 1,1-
dimethylhydrazine. The reaction of 17 with H2NNMe2 led
to the formation of a compound which was isolated in
92% yield and identified as dimethylhydrazone 8 (see
Scheme 3), whereas the epimeric dimethylhydrazone 21
was obtained from sulfinyl propenal 18 and 1,1-dimethyl-
hydrazine in 86% yield.
Scheme 2
3-[(1S)-Isoborneol-10-sulfinyl]propanenitriles
(sulfur
epimeric mixture 9)2 were choosen as suitable precursors
of sulfenic acid 10 which was obtained by their thermoly-
sis in toluene (Scheme 3). Isoborneolsulfenic acid 10 was
generated in situ and reacted, (i) with 2-butynal dimethyl-
hydrazone (11), prepared from crotonaldehyde following
the literature procedure,10 and (ii) with a 60:40 mixture of
(E)- and (Z)-3-phenyl-2-propynal dimethylhydrazones
(12) and (13).11 Compounds 12 and 13 were prepared
from phenylpropargyl aldehyde (14) and 1,1-dimethylhy-
drazine and are separable by column chromatography.
The addition of 10 to the triple bond of hydrazone 11 af-
forded a mixture of regioisomeric sulfinyl hydrazones 7
and 6 in a total yield of 14% and in a 66:34 ratio. Thermol-
ysis of 9 in the presence of the mixture of 12 and 13 led to
the formation of sulfinyl hydrazones 8, 15, and 16 in 16%
total yield and in a 42:28:30 ratio (Scheme 3). The results
of this last reaction, in terms of regioselectivity, are com-
parable with those obtained in the addition of sulfenic acid
10 to dimethylhydrazone 11. Both reactions occurred with
complete stereoselectivity, affording (RS)-sulfinyl hydra-
zones in all cases. The sulfur configuration was assigned
on the basis of the stereochemical outcome previously ob-
served in the addition of 10 with different alkynes.1,2 Hy-
drazones 6–8, 15, and 16 were all easily separated by
column chromatography, obtained in enantiomerically
pure form, and fully characterized.
We also investigated the addition of sulfenic acid 10 to the
propiolaldehyde diethyl acetal (22) which would lead to
isoborneolsulfinyl 2-propenal dimethylhydrazones, after
removal of the acetal protection and reaction of the sulfi-
nyl aldehyde with 1,1-dimethylhydrazyne. Thermolysis
of 9 in the presence of acetal 22 (Scheme 5) afforded
epimeric sulfinyl acetals 23 and 24, together with the con-
densed tricyclic compound 25, in 65% total yield and
47:30:23 ratio, respectively. A complete regioselectivity
was observed in this reaction, in favour of 2-sulfinyl-3,3-
diethoxypropenes.12
Synthesis 2003, No. 14, 2241–2248 © Thieme Stuttgart · New York

SPECIAL TOPIC
Sulfinyl Homo- and Hetero-Dienes from Sulfenic Acids
2243
analogous trend was observed in structurally related com-
pounds such as 26,13a 27,6 and 28.13b At the same time the
C-2 resonance is observed in the range 76.4–77.2 for sul-
foxides 6, 8, 15, 18, 20, 21, 23, 24, 31, 32 but it is
deshielded to 85.1 ppm in compound 25, where the corre-
sponding carbon nucleus is identified as C-1. The assign-
ment of the absolute configuration of 25, as shown in
Scheme 5, is based on the observed formation of only one
tricyclic diastereomer among the products of the reaction
under study. This experimental result suggests a thermo-
dynamic control of the heterocyclization which follows
the addition of 10 onto the triple bond of 22.
Scheme 4
Figure 1
The addition of sulfenic acids to substrates showing car-
bonyl conjugated triple bonds, and/or their derivatives,
has a synthetic validity in the preparation of sulfinyl sub-
stituted , -unsaturated compounds, which in turn can be
involved in a variety of significant reactions. Therefore,
we were concerned in an analysis of the formation of -
and/or -sulfinyl , -unsaturated products (Table 1) and a
valuation of the results in terms of regioselectivity of this
addition. The data reported in Table 1 deserve some com-
ments. The addition of sulfenic acid 10 to alkynyl ketones
occurred with complete regioselectivity in favor of the
corresponding -sulfinyl substituted products (entries 7–
9), owing to the mesomerism of the acceptor moiety in-
volving the carbonyl group. Furthermore, the results of
the addition of 10 to 3-butyn-2-one and its 4-phenyl deriv-
ative 30 (entries 7 and 9) clearly pointed out the negligible
role that substituent R plays on regioselectivity. The re-
duced polarization induced by the hydrazone function in
substrates 11 and 12 turned into a 7:3 ratio between - and
-sulfinyl substituted final products (entries 3 and 4). Fi-
nally the thermolysis of precursors of 10 in the presence
of substrate 22 (entry 1) led just to the -sulfinyl substitut-
ed products, and these results, if compared with the ones
in entries 7–9, are in accordance with the electron-with-
drawing inductive effect exerted by the acetal function
over the carbon atoms of the triple bond.
Scheme 5
The tetrahydro-1,4-oxathiepin ring in 25 originates from
the acetal exchange between ethoxy and isoborneol hy-
droxy moieties, and represents a further example of unex-
pected and undesired products that we have seldom
obtained using the isoborneol sulfinyl group as chiral aux-
iliary, i.e. fused oxathia heterocycles 26–28 (Figure 1).6,13
Their structures are easily recognizable on the basis of
their NMR data. In particular the resonance of the geminal
proton to isoborneol oxygen atom is clearly indicative of
cyclization involving the hydroxy group. In all the synthe-
sized isoborneol sulfoxides 6–8, 15–21, 23, 24, 29, 31, 32
this H-2 resonance appears as a doublet of doublets,
sometimes further spin-spin coupled with the hydroxy
proton, in the range 4.0–4.2 ppm. The same resonance is
clearly shielded (3.71 ppm) in tricyclic derivative 25
where the corresponding proton is identified as H-1, and
Synthesis 2003, No. 14, 2241–2248 © Thieme Stuttgart · New York

2244
M. C. Aversa et al.
SPECIAL TOPIC
Table 1 Regioselectivity in the Addition of (1S)-Isoborneol-10-sulfenic Acid (10) to Alkynyl Conjugated Carbonyl Compounds and their
Derivatives
Entry
Substratea
R
R1
R2
%Products
-Sulfinyl
100 (23+24)
50
-Sulfinyl
1
2
3
4
Propiolaldehyde diethyl acetal (22)
2-Ethynyl-2-phenyl-1,3-dithiane
2-Butynal dimethylhydrazone (11)
H
H
(OEt)2
H
Ph
H
S(CH2)3S
NNMe2
NNMe2
50
Me
34 (6)
66 (7)
70 (8)
(E)-3-Phenyl-2-propynal dimethylhydrazone Ph
(12)
H
30 (16)
5
6
7
8
9
Phenylpropargyl aldehyde (14)
Ethyl propiolate
Ph
H
H
O
O
O
O
O
17 (19 + 20)
83 (17 + 18)
OEt
Me
Ph
11
89
3-Butyn-2-one
H
100
1-Phenyl-2-propyn-1-one
4-Phenyl-3-butyn-2-one (30)
H
100
Ph
Me
100 (31 + 32)
a The experiments of entries 2 and 6–8 are described in ref.6
As a part of our study on stereoselective DA reactions in- ing products. In this work, in particular, we draw up two
volving sulfinyl butadienes,2–6 we decided to investigate different synthetic pathways for the obtainment of enan-
the reactivity of sulfinyl hydrazones 6 and 7 as 1-azabuta- tiopure sulfinyl hydrazones, in both of which the addition
1,3-dienes7,10 in cycloadditions with N-methylmaleimide sulfenic acid/unsaturation represents the crucial step, and
(NMM). Cycloaddition of 7 with NMM failed, although give an example of applicability of this chemistry. The ad-
several conditions were adopted, as the reaction of 6 with dition of enantiopure sulfenic acids to enynes or suitably
NMM, performed in refluxing 1,2-dichloroethane for 96 substituted alkynes gives an easy access to homo- and het-
h, led to (4R,4aR,7aS,RS)-4,6-dimethyl-1-dimethylamino- ero-sulfinyldienes which we have involved in various ste-
3-[(1S)-isoborneol-10-sulfinyl]-4,4a,6,7a-tetrahydro-1H-
reoselective uncatalyzed and catalyzed DA reactions,
pyrrolo[3,4-b]pyridine-5,7-dione (29) as the only HDA obtaining in most of the cases a very good control of endo/
cycloadduct of the reaction among four possible exo and facial selectivities exerted by the sulfinyl
diastereoisomers. The absolute configuration of the new group.2,3a–c,4,6,14,15 Despite its structural limitations, sulfi-
formed stereocentres in cycloadduct 29 was assigned tak- nyl N,N-dimethylhydrazone 6 behaves as 1-azabuta-1,3-
ing into account the endo approach of the dienophile onto diene in HDA reaction with NMM, giving a unique prod-
the Si face of diene 6 in its A conformation around the S– uct of cycloaddition with complete endo and facial selec-
C bond (Scheme 6).2,6 The steric requirements of hydra- tivities.
zones 6 and 7, showing a trisubstituted carbon–carbon
double bond, account for the obtained results together
with the position of the sulfinyl group which plays a fun-
damental role in the lack of reactivity of hydrazone 7.
In conclusion, this work represents a further contribution
to the employment of the addition of enantiopure sulfenic
acids to alkenes or alkynes as a direct and easy methodol-
ogy for the introduction of a stereogenic sulfur atom into
a suitably unsaturated substrate. We have extensively
demonstrated1–6,14 that the structural features of the
sulfenic acids as well as the electronic nature of the unsat-
urated acceptors play a relevant role in the results of this
reaction in terms of total yield and regioselectivity, and
that there is a great possibility of modulation of the start-
Scheme 6
Synthesis 2003, No. 14, 2241–2248 © Thieme Stuttgart · New York

SPECIAL TOPIC
Sulfinyl Homo- and Hetero-Dienes from Sulfenic Acids
2245
Reaction of Phenylpropargyl Aldehyde (14) with 1,1-Dimethyl-
hydrazine; Typical Procedure
All reactions were monitored by TLC on commercially available
precoated plates (silica gel 60 F 254) and the products were visual-
ized with acidic vanillin solution. Silica gel 60, 230–400 mesh, was
used for column chromatography. Petrol refers to light petroleum,
bp 30–40 °C. Melting points were measured on a microscopic appa-
ratus and are uncorrected. Optical rotations were measured in
CHCl3 solutions whose concentrations are expressed in g/100 mL.
1H and 13C NMR spectra were recorded at 300 MHz and 75 MHz
respectively (unless otherwise specified) in CDCl3 solutions with
TMS as internal standard. The assignments are supported by At-
tached Proton Test (APT) and homodecoupling experiments. Pro-
tons and carbon nuclei, marked with ( ), pertain to the isoborneol
moiety in compounds 6–8, 15–21, 23, 29, 31, 32. Carbon nuclei,
marked with ( ), pertain to the phenyl group in compounds 8, 12,
13, 15, 18, 20, 21, 31, 32. IR spectra were taken for neat oils or nujol
mulls with a FT spectrophotometer. Mass spectra were measured by
FAB (m-nitrobenzyl alcohol as matrix).
To a solution of 14 (1.50 g, 11.5 mmol) in Et2O (10 mL) kept at 0
°C under stirring, 1,1-dimethylhydrazine (1.38 g, 23.0 mmol) in
Et2O (3 mL) was added dropwise. After allowing the mixture to
warm to the r.t., water (5 mL) was added, the crude mixture was ex-
tracted with Et2O (3 × 10 mL), and the organic layers collected and
dried over Na2SO4. After removing the solvent under reduced pres-
sure, the column chromatography of the crude product mixture,
eluted with CHCl3, afforded the stereoisomeric hydrazones 12 and
13 (in 60:40 ratio, 90% total yield). The minor isomer was the first
to elute followed by the major isomer.
(Z)-3-Phenyl-2-propynal Dimethylhydrazone (13)11a
Minor stereoisomer; oil.
IR (neat oil): 2864, 2195, 1533, 1488, 1442, 1356, 1291, 1131,
1064, 847, 757, 691 cm–1.
1H NMR: = 7.5–7.3 (m, 5 H, Ph), 6.47 (s, 1 H, H-1), 3.01 (s, 6 H,
NMe2).
13C NMR: = 131.48 (C-2 ,6 ), 128.28 (C-3 ,5 ), 128.03 (C-4 ),
123.31 (C-1 ), 112.50 (C-1), 89.13 (C-3), 87.09 (C-2), 42.35
(NMe2).
Thermolysis of (1S)-10-[(2-Cyanoethyl)sulfinyl]isoborneols 9 in
the Presence of 2-Butynal Dimethylhydrazone (11)10; Typical
Procedure
Sulfoxides 9 (mixture of sulfur epimers,2 0.46 g, 1.8 mmol) in tolu-
ene (5 mL) containing hydrazone 11 (0.30 g, 2.7 mmol) were main-
tained at reflux temperature. When the reaction appeared complete
by TLC (after ca 4 h) the solvent was removed under reduced pres-
sure. The column chromatography of the crude product mixture,
eluted with petroleum ether containing 40–60% EtOAc, afforded
the regioisomeric hydrazones 7 and 6 (in a 66:34 ratio, 14% total
yield); The minor isomer was the first to elute followed by the major
isomer.
Anal. Calcd for C11H12N2: C, 76.71; H, 7.02; N, 16.26. Found: C,
76.65; H, 7.04; N, 15.54.
(E)-3-Phenyl-2-propynal Dimethylhydrazone (12)
Major stereoisomer; oil.
IR (neat oil): 2864, 2182, 1537, 1487, 1442, 1368, 1284, 1129,
1039, 834, 756, 690 cm–1.
1H NMR: = 7.4–7.3 (m, 5 H, Ph), 6.63 (s, 1 H, H-1), 3.17 (s, 6 H,
NMe2).
13C NMR: = 130.98 (C-2 ,6 ), 128.64 (C-4 ), 128.34 (C-3 ,5 ),
122.55 (C-1 ), 115.49 (C-1), 96.41 (C-3), 84.45 (C-2), 45.80
(NMe2).
(RS,E,E)-2-[(1S)-isoborneol-10-sulfinyl]-2-butenal dimethylhy-
drazone (6)
Minor regioisomer; oil; [ ]D25 +98.1 (c 1.4).
1H NMR: = 7.14 (d, 1 H, J1,3 = 1.0 Hz, H-1), 6.35 (dq, 1 H, J3,4
=
7.4 Hz, H-3), 4.17 (m, 1 H, H-2 ), 3.24 and 2.85 (AB system, 2 H,
J10 A,10 B = 12.9 Hz, H2-10 ), 2.92 (s, 6 H, NMe2), 2.01 (d, 3 H, H3-
4), 1.7–1.1 (m, 7 H, H2-3 ,5 ,6 , H-4 ), 1.06 (s, 3 H, H3-8 ), 0.80 (s,
3 H, H3-9 ).
13C NMR: = 139.05 (C-2), 125.55 (C-1), 124.02 (C-3), 76.88 (C-
2 ), 56.33 (C-10 ), 51.79 (C-1 ), 48.01 (C-7 ), 45.16 (C-4,4 ), 42.18
(NMe2), 38.38 (C-3 ), 30.61 and 27.17 (C-5 ,6 ), 20.38 and 19.88
(C-8 ,9 ).
Anal. Calcd for C11H12N2: C, 76.71; H, 7.02; N, 16.26. Found: C,
76.35; H, 7.03; N, 15.86.
Thermolysis of (1S)-10-[(2-Cyanoethyl)sulfinyl]isoborneols 9 in
the Presence of (E)- and (Z)-3-Phenyl-2-propynal Dimethylhy-
drazones (12/13, 60:40); Typical Procedure
Sulfoxides 9 (mixture of sulfur epimers,2 0.49 g, 1.9 mmol) in tolu-
ene (5 mL) containing the mixture 12/13 (60:40) as obtained fol-
lowing the previous procedure (0.50 g, 2.9 mmol) were maintained
at reflux temperature. When the reaction appeared complete by
TLC (ca 4 h) the solvent was removed under reduced pressure. The
column chromatography of the crude product mixture, eluted with
petroleum ether containing 40–60% EtOAc, afforded sulfinyl hy-
drazones 8, 15, and 16 (in a 42:28:30 ratio, 16% total yield), which
eluted in the order given.
MS: m/z (%) = 313 (55) (M + 1), 111 (100), 69 (26), 55 (32), 43
(23).
Anal. Calcd for C16H28N2O2S: C, 61.50; H, 9.03; N, 8.97. Found: C,
61.54; H, 8.68; N, 8.89.
(RS,E,E)-3-[(1S)-Isoborneol-10-sulfinyl]-2-butenal Dimethylhy-
drazone (7)
Major regioisomer; oil.
IR (nujol): 3397 (OH), 1541, 1291, 1077, 1033 (SO) cm–1.
1H NMR: = 6.93 (d, 1 H, J1,2 = 9.2 Hz, H-1), 6.78 (dq, 1 H, J2,4
1.3 Hz, H-2), 4.13 (m, 1 H, H-2 ), 3.31 and 2.24 (AB system, 2 H,
J10 A,10 B = 13.0 Hz, H2-10 ), 3.02 (s, 6 H, NMe2), 2.09 (d, 3 H, H3-
4), 1.8–1.2 (m, 7 H, H2-3 ,5 ,6 , H-4 ), 1.08 (s, 3 H, H3-8 ), 0.80 (s,
3 H, H3-9 ).
(RS,E,E)-3-[(1S)-isoborneol-10-sulfinyl]-3-phenyl-2-propenal
dimethylhydrazone (8)
Low melting solid; [ ]D22 –116.9 (c 7.0).
=
IR (nujol): 3416 (OH), 1537, 1292, 1077 (SO), 757, 699 cm–1.
1H NMR: = 7.5–7.3 (m, 5 H, Ph), 7.06 (d, 1 H, J1,2 = 9.4 Hz, H-1),
6.95 (d, 1 H, H-2), 4.12 (dd, 1 H, J2 ,3 = 8.0, 3.8 Hz, H-2 ), 2.96 and
2.23 (AB system, 2 H, J10 A,10 B = 13.2 Hz, H2-10 ), 2.95 (s, 6 H,
NMe2), 1.8–1.0 (m, 7 H, H2-3 ,5 ,6 , H-4 ), 0.98 (s, 3 H, H3-8 ), 0.63
(s, 3 H, H3-9 ).
13C NMR: = 140.62 (C-3), 132.58 (C-1 ), 130.46 (C-1), 129.34
(C-3 ,5 ), 129.31 (C-2 ,6 ), 129.09 (C-4 ), 126.91 (C-2), 77.20
(C-2 ), 54.75 (C-10 ), 51.51 (C-1 ), 48.30 (C-7 ), 45.27 (C-4 ), 42.65
MS: m/z (%) = 313 (29) (M + 1), 69 (95), 55 (100), 43 (71).
Anal. Calcd for C16H28N2O2S: C, 61.50; H, 9.03; N, 8.97. Found: C,
61.65; H, 8.97; N, 9.04.
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2246
M. C. Aversa et al.
SPECIAL TOPIC
(NMe2), 38.60 (C-3 ), 30.98 and 27.32 (C-5 ,6 ), 20.60 and 20.02
(C-8 ,9 ).
1H NMR: = 10.05 (s, 1 H, H-1), 8.19 (s, 1 H, H-3), 7.52 (s, 5 H,
Ph), 4.12 (m, 1 H, H-2 ), 3.58 and 2.72 (AB system, 2 H, J10 A,10 B
=
13.9 Hz, H2-10 ), 2.0–1.0 (m, 7 H, H2-3 ,5 ,6 , H-4 ), 1.10 (s, 3 H,
H3-8 ), 0.82 (s, 3 H, H3-9 ).
13C NMR: = 188.82 (C-1), 149.10 (C-3), 142.66 (C-2), 132.22 (C-
1 ), 131.55 (C-4 ), 130.56 (C-3 ,5 ), 129.30 (C-2 ,6 ), 76.66 (C-
2 ), 55.29 (C-10 ), 52.51 (C-1 ), 48.84 (C-7 ), 44.60 (C-4 ), 39.16
(C-3 ), 30.77 and 27.42 (C-5 ,6 ), 20.40 and 19.89 (C-8 ,9 ).
MS: m/z (%) = 375 (21) (M + 1), 95 (51), 81 (59), 69 (71), 55 (100),
43 (67).
Anal. Calcd for C21H30N2O2S: C, 67.34; H, 8.07; N, 7.48. Found: C,
67.52; H, 8.09; N, 7.50.
(RS,1Z,2E)-3-[(1S)-Isoborneol-10-sulfinyl]-3-phenyl-2-prope-
nal Dimethylhydrazone (15)
Oil.
Anal. Calcd for C19H24O3S: C, 68.64; H, 7.28. Found: C, 68.63; H,
7.15.
1H NMR: = 7.6–7.4 (m, 5 H, Ph), 7.07 (s, 2 H, H-1,2),16 4.10 (m,
1 H, H-2 ), 3.18 and 2.29 (AB system, 2 H, J10 A,10 B = 14.2 Hz, H2-
10 ), 2.96 (s, 6 H, NMe2), 1.8–1.0 (m, 7 H, H2-3 ,5 ,6 , H-4 ), 1.00
(s, 3 H, H3-8 ), 0.63 (s, 3 H, H3-9 ).
(SS,E)-3-[(1S)-Isoborneol-10-sulfinyl]-3-phenyl-2-propenal (18)
Oil.
IR (neat oil): 3451 (OH), 2955, 1681 (CO), 1037 (SO), 758 cm–1.
13C NMR: = 139.67 (C-3), 132.79 (C-1 ), 130.08 (C-1), 129.18
(C-3 ,5 ), 129.05 (C-2 ,6 ), 128.86 (C-4 ), 127.69 (C-2), 76.43
(C-2 ), 52.38 (C-10 ), 51.42 (C-1 ), 48.83 (C-7 ), 44.40 (C-4 ), 42.37
(NMe2), 39.45 (C-3 ), 31.20 and 27.33 (C-5 ,6 ), 20.24 and 19.97
(C-8 ,9 ).
1H NMR: = 9.74 (d, 1 H, J1,2 = 7.7 Hz, H-1), 7.6–7.4 (m, 5 H, Ph),
6.86 (d, 1 H, H-2), 4.06 (m, 1 H, H-2 ), 3.20 and 2.37 (AB system,
2 H, J10 A,10 B = 13.8 Hz, H2-10 ), 1.8–1.0 (m, 7 H, H2-3 ,5 ,6 , H-4 ),
0.93 (s, 3 H, H3-8 ), 0.66 (s, 3 H, H3-9 ).
13C NMR: = 189.94 (C-1), 167.88 (C-3), 131.33 (C-2), 129.73 (C-
1 ), 129.58 (C-3 ,5 ), 129.11 (C-2 ,6 ), 128.56 (C-4 ), 76.42 (C-
2 ), 52.36 (C-10 ), 52.33 (C-1 ), 48.95 (C-7 ), 44.42 (C-4 ), 39.95
(C-3 ), 31.03 and 27.19 (C-5 ,6 ), 20.15 and 19.88 (C-8 ,9 ).
Anal. Calcd for C21H30N2O2S: C, 67.34; H, 8.07; N, 7.48. Found: C,
67.05; H, 8.03; N, 7.47.
(RS,E,E)-2-[(1S)-isoborneol-10-sulfinyl]-3-phenyl-2-propenal
Dimethylhydrazone (16)
Oil.
Anal. Calcd for C19H24O3S: C, 68.64; H, 7.28. Found: C, 68.70; H,
7.25.
1H NMR: = 7.6–7.4 (m, 5 H, Ph), 6.90 (s, 1 H, H-1), 6.87 (s, 1 H,
H-3), 4.04 (dd, 1 H, J2 ,3 = 7.5, 3.7 Hz, H-2 ), 3.21 and 2.74 (AB sys-
tem, 2 H, J10 A,10 B = 13.9 Hz, H2-10 ), 3.06 (s, 6 H, NMe2), 1.8–1.0
(m, 7 H, H2-3 ,5 ,6 , H-4 ), 1.04 (s, 3 H, H3-8 ), 0.73 (s, 3 H, H3-9 ).
(RS,E,E)-3-[(1S)-Isoborneol-10-sulfinyl]-3-phenyl-2-propenal
Dimethylhydrazone (8)
Sulfoxide 8, which is reported above as a product of the addition of
sulfenic acid 10 to (E)-3-phenyl-2-propynal dimethylhydrazone
(12), was prepared in very good yield by adding dropwise a solution
of 1,1-dimethylhydrazine (0.15 g, 2.5 mmol) in Et2O (2 mL) to a so-
lution of (RS,E)-3-[(1S)-isoborneol-10-sulfinyl]-3-phenyl-2-prope-
nal (17) (0.70 g, 2.1 mmol) in Et2O (10 mL) at 0 °C. After allowing
the solution to warm to r.t., water (5 mL) was added, the crude mix-
ture was extracted with Et2O (3 × 10 mL), and the organic layers
collected and dried over Na2SO4. After removing the solvent under
reduced pressure, the column chromatography of the crude product,
eluted with petroleum ether–EtOAc (70:30), afforded the pure sul-
foxide 8 in 92% yield.
Anal. Calcd for C21H30N2O2S: C, 67.34; H, 8.07; N, 7.48. Found: C,
67.59; H, 8.02; N, 7.47.
Thermolysis of (1S)-10-[(2-Cyanoethyl)sulfinyl]isoborneols 9 in
the Presence of Phenylpropargyl Aldehyde (14); Typical Proce-
dure
Sulfoxides 9 (mixture of sulfur epimers,2 0.98 g, 4.1 mmol) in tolu-
ene (10 mL) containing commercial aldehyde 14 (1.00 g, 7.7 mmol)
were maintained at reflux temperature. When the reaction appeared
complete by TLC (after ca 5 h) the solvent was removed under re-
duced pressure. The column chromatography of the crude product
mixture, eluted with petroleum ether containing 30–60% EtOAc,
afforded the isoborneol sulfoxides 17–20 (17/18/19/20 in a
43:40:11:6 ratio, 73% total yield), which eluted in the order given.
(SS,E,E)-3-[(1S)-Isoborneol-10-sulfinyl]-3-phenyl-2-propenal
Dimethylhydrazone (21)
To a solution of 18 (0.50 g, 1.5 mmol) in Et2O (10 mL) kept at 0 °C
under stirring, 1,1-dimethylhydrazine (0.11 g, 1.8 mmol) in Et2O (2
mL) was added dropwise. After allowing the solution to warm to the
r.t., water (5 mL) was added, the crude mixture was extracted with
Et2O (3 × 10 mL), and the organic layers collected and dried over
Na2SO4. After removing the solvent under reduced pressure, the
column chromatography of the crude product, eluted with petrol-
eum ether–EtOAc (50:50), afforded the pure sulfoxide 21 in 86%
total yield as a solid; mp 181–183 °C; [ ]D21 +138.8 (c 4.0).
(RS,E)-2-[(1S)-isoborneol-10-sulfinyl]-3-phenyl-2-propenal (19)
1H NMR: = 10.09 (s, 1 H, H-1), 8.18 (s, 1 H, H-3), 7.6–7.4 (m, 5
H, Ph), 4.12 (m, 1 H, H-2 ), 1.07 (s, 3 H, H3-8 ), 0.85 (s, 3 H, H3-9 ).
(RS,E)-3-[(1S)-Isoborneol-10-sulfinyl]-3-phenyl-2-propenal (17)
Major isomer 17 was always obtained in a mixture with 19 and was
isolated as an oil.
IR (neat oil): 3442 (OH), 2954, 1680 (CO), 1037 (SO), 756 cm–1.
1H NMR: = 9.72 (d, 1 H, J1,2 = 7.6 Hz, H-1), 7.6–7.3 (m, 5 H, Ph),
6.82 (d, 1 H, H-2), 4.10 (m, 1 H, H-2 ), 3.08 and 2.21 (AB system,
2 H, J10 A,10 B = 13.2 Hz, H2-10 ), 1.9–1.0 (m, 7 H, H2-3 ,5 ,6 , H-4 ),
0.98 (s, 3 H, H3-8 ), 0.56 (s, 3 H, H3-9 ).
IR (nujol): 3394 (OH), 1532, 1283, 1078, 1036 (SO), 766, 696 cm–1.
1H NMR: = 7.5–7.3 (m, 5 H, Ph), 7.06 (d, 1 H, J1,2 = 9.6 Hz, H-1),
7.03 (d, 1 H, H-2), 4.08 (dd, 1 H, J2 ,3 = 7.8, 3.8 Hz, H-2 ), 3.16 and
2.28 (AB system, 2 H, J10 A,10 B = 14.1 Hz, H2-10 ), 2.94 (s, 6 H,
NMe2), 1.8–1.2 (m, 7 H, H2-3 ,5 ,6 , H-4 ), 1.00 (s, 3 H, H3-8 ), 0.62
(s, 3 H, H3-9 ).
13C NMR: = 139.52 (C-3), 132.76 (C-1 ), 130.10 (C-1), 129.10
(C-3 ,5 ), 129.01 (C-2 ,6 ), 128.77 (C-4 ), 127.02 (C-2), 76.47
(C-2 ), 52.41 (C-10 ), 51.61 (C-1 ), 48.86 (C-7 ), 44.49 (C-4 ), 42.39
(NMe2), 39.57 (C-3 ), 31.31 and 27.42 (C-5 ,6 ), 20.34 and 20.09
(C-8 ,9 ).
Anal. Calcd for C19H24O3S: C, 68.64; H, 7.28. Found: C, 68.72; H,
7.30.
(SS,E)-2-[(1S)-Isoborneol-10-sulfinyl]-3-phenyl-2-propenal (20)
Oil; [ ]D23 –48.2 (c 4.5).
IR (neat oil): 3545 and 3448 (OH), 2958, 1739 (CO), 1047 (SO),
757 cm–1.
Synthesis 2003, No. 14, 2241–2248 © Thieme Stuttgart · New York

SPECIAL TOPIC
Sulfinyl Homo- and Hetero-Dienes from Sulfenic Acids
2247
MS: m/z (%) = 375 (25) (M + 1), 154 (48), 136 (60), 107 (45), 91
(71), 77 (79), 55 (100).
13C NMR: = 155.93 (C-4), 118.63 (4 = CH2), 102.06 (C-3), 85.09
(C-1), 63.46 (OCH2), 57.90 (C-6), 52.99 (C-7), 47.85 (C-12), 44.65
(C-10), 38.80 (C-11), 32.99 and 26.94 (C-8,9), 20.68 and 20.16 (C-
13,14), 14.84 (CH2CH3).
Anal. Calcd for C21H30N2O2S: C, 67.34; H, 8.07; N, 7.48. Found: C,
67.39; H, 8.04; N, 7.50.
MS: m/z (%) = 285 (59) (M + 1), 135 (52), 95 (54), 81 (62), 69 (79),
Thermolysis of (1S)-10-[(2-Cyanoethyl)sulfinyl]isoborneols 9 in
the Presence of Propiolaldehyde Diethyl Acetal (22); Typical
Procedure
55 (100).
Anal. Calcd for C15H24O3S: C, 63.35; H, 8.51. Found: C, 63.39; H,
8.47.
Sulfoxides 9 (mixture of sulfur epimers,2 0.66 g, 2.7 mmol) in tolu-
ene (5 mL) containing commercial acetal 22 (1.00 g, 7.8 mmol)
were maintained at reflux temperature. When the reaction appeared
complete by TLC (after ca 3 h) the solvent was removed under re-
duced pressure. The column chromatography of the crude product
mixture, eluted with petrol containing 10–50% EtOAc, afforded the
sulfoxides 23–25 (23/24/25 in a 47:30:23 ratio, 65% total yield),
which eluted in the order given.
Thermolysis of (1S)-10-[(2-Cyanoethyl)sulfinyl]isoborneols 9 in
the Presence of 4-Phenyl-3-butyn-2-one (30); Typical Proce-
dure
Sulfoxides 9 (mixture of sulfur epimers,2 0.37 g, 1.4 mmol) in tolu-
ene (4 mL) containing commercial butynone 30 (0.30 g, 2.1 mmol)
were maintained at reflux temperature. When the reaction appeared
complete by TLC (after ca 3.5 h) the solvent was removed under re-
duced pressure. The column chromatography of the crude product
mixture, eluted with petrol containing 7–20% EtOAc, afforded the
sulfur epimers 31 and 32 (31/32 in a 61:39 ratio, 70% total yield),
which eluted in the order given.
(RS)-3,3-diethoxy-2-[(1S)-isoborneol-10-sulfinyl]propene (23)
Oil; [ ]D22 +0.6 (c 6.2).
1H NMR: = 6.18 (br s, 1 H, H-1 cis to SO), 6.01 (br s, 1 H, H-1
trans to SO), 5.24 (t, 1 H, J1,3 = 0.9 Hz, H-3), 4.11 (dd, 1 H, J2 ,3
=
8.0, 4.2 Hz, H-2 ), 3.7–3.5 (m, 4 H, OCH2), 3.08 and 3.02 (AB sys-
tem, 2 H, J10 A,10 B = 13.2 Hz, H2-10 ), 1.9–1.6 (m, 7 H, H2-3 ,5 ,6 ,
H-4 ), 1.25 (m, 6 H, CH2CH3), 1.07 (s, 3 H, H3-8 ), 0.83 (s, 3 H, H3-
9 ).
13C NMR: = 151.65 (C-2), 119.17 (C-1), 99.60 (C-3), 76.85 (C-
2 ), 62.41 and 62.19 (OCH2), 56.39 (C-10 ), 51.62 (C-1 ), 48.05 (C-
7 ), 44.96 (C-4 ), 38.28 (C-3 ), 30.50 and 27.00 (C-5 ,6 ), 20.25 and
19.70 (C-8 ,9 ), 14.85 (CH2CH3).
(RS,E)-4-[(1S)-isoborneol-10-sulfinyl]-4-phenyl-3-buten-2-one
(31)
Oil; [ ]D25 +51.5 (c 0.1).
1H NMR: = 7.5–7.3 (m, 5 H, Ph), 6.87 (s, 1 H, H-3), 4.11 (dd, 1
H, J2 ,3 = 8.0, 4.3 Hz, H-2 ), 3.00 and 2.23 (AB system, 2 H,
J
10 A,10 B = 13.2 Hz, H2-10 ), 2.15 (s, 3 H, H3-1), 1.8–1.0 (m, 7 H, H2-
3 ,5 ,6 , H-4 ), 1.00 (s, 3 H, H3-8 ), 0.56 (s, 3 H, H3-9 ).
13C NMR: = 197.69 (C-2), 157.33 (C-4), 130.89 (C-1 ), 130.43
(C-3), 129.27 (C-3 ,5 ), 128.12 (C-2 ,6 ), 128.05 (C-4 ), 76.89
(C-2 ), 54.12 (C-10 ), 51.36 (C-1 ), 48.24 (C-7 ), 44.96 (C-4 ), 38.43
(C-3 ), 31.00 (C-1), 30.63 and 26.97 (C-5 ,6 ), 20.21 and 19.69 (C-
8 ,9 ).
MS: m/z (%) = 331 (16) (M + 1), 285 (57) (M + 1 – C2H6O), 239
(15), 135 (99), 69 (78), 55 (100), 43 (81).
Anal. Calcd for C17H30O4S: C, 61.78; H, 9.15. Found: C, 61.96; H,
9.12.
Anal. Calcd for C20H26O3S: C, 69.33; H, 7.56. Found: C, 69.45; H,
7.59.
(SS)-3,3-Diethoxy-2-[(1S)-isoborneol-10-sulfinyl]propene (24)
Oil; [ ]D22 +23.3 (c 3.0).
(SS,E)-4-[(1S)-Isoborneol-10-sulfinyl]-4-phenyl-3-buten-2-one
(32)
Oil.
IR (nujol): 3384 (OH), 1726, 1288, 1117, 1074, 1059 (SO), 940
cm–1.
1H NMR: = 6.18 (d, 1 H, J1,3 = 0.9 Hz, H-1 cis to SO), 6.03 (d, 1
H, J1,3 = 1.1 Hz, H-1 trans to SO), 5.27 (t, 1 H, H-3), 4.08 (dd, 1 H,
J2 ,3 = 7.4 and 4.1 Hz, H-2 ), 3.7–3.5 (m, 4 H, OCH2), 3.73 and 2.48
(AB system, 2 H, J10 A,10 B = 14.2 Hz, H2-10 ), 1.8–1.4 (m, 7 H, H2-
3 ,5 ,6 , H-4 ), 1.26 (m, 6 H, CH2CH3), 1.09 (s, 3 H, H3-8 ), 0.84 (s,
3 H, H3-9 ).
13C NMR: = 151.26 (C-2), 120.27 (C-1), 99.99 (C-3), 76.90 (C-
2 ), 62.98 and 61.82 (OCH2), 55.62 (C-10 ), 51.87 (C-1 ), 48.42 (C-
7 ), 44.68 (C-4 ), 39.29 (C-3 ), 30.55 and 27.35 (C-5 ,6 ), 20.40 and
19.88 (C-8 ,9 ), 14.72 (CH2CH3).
1H NMR: = 7.5–7.3 (m, 5 H, Ph), 6.88 (s, 1 H, H-3), 4.02 (t, 1 H,
J2 ,3 = 5.8 Hz, H-2 ), 3.16 and 2.30 (AB system, 2 H, J10 A,10 B = 13.9
Hz, H2-10 ), 2.15 (s, 3 H, H3-1), 1.8–1.0 (m, 7 H, H2-3 ,5 ,6 , H-4 ),
0.92 (s, 3 H, H3-8 ), 0.66 (s, 3 H, H3-9 ).
13C NMR: = 197.91 (C-2), 157.27 (C-4), 131.14 (C-1 ), 130.43
(C-3), 129.19 (C-3 ,5 ), 128.45 (C-2 ,6 ), 128.41 (C-4 ), 76.53
(C-2 ), 52.42 and 52.11 (C-1 ,10 ), 48.80 (C-7 ), 44.54 (C-4 ), 39.96
(C-3 ), 31.17 and 27.30 (C-5 ,6 ), 30.87 (C-1), 20.25 and 19.99 (C-
8 ,9 ).
Anal. Calcd for C20H26O3S: C, 69.33; H, 7.56. Found: C, 69.15; H,
7.54.
MS: m/z (%) = 285 (19) (M + 1 – C2H6O), 239 (36), 135 (100), 69
(78), 55 (96), 43 (69).
Anal. Calcd for C17H30O4S: C, 61.78; H, 9.15. Found: C, 61.66; H,
9.14.
(4R,4aR,7aS,RS)-4,6-Dimethyl-1-dimethylamino-3-[(1S)-iso-
borneol-10-sulfinyl]-4,4a,6,7a-tetrahydro-1H-pyrrolo[3,4-b]py-
ridine-5,7-dione (29)
A solution of azadiene 6 (0.03 g, 0.1 mmol) and N-methylmaleim-
ide (0.02 g, 0.2 mmol) in 1,2-dichloroethane (3 mL) was refluxed
under stirring. When the reaction appeared complete by TLC (after
4 days) the solvent was removed under reduced pressure. Purifica-
tion by column chromatography eluting with petrol–EtOAc (60:40)
afforded the adduct 29 as an oil (20% yield).
1H NMR: = 6.94 (s, 1 H, H-2), 4.24 (d, 1 H, J4a,7a = 8.0 Hz, H-7a),
4.06 (dd, 1 H, J2 ,3 = 7.4, 3.4 Hz, H-2 ), 3.76 and 2.08 (AB system,
2 H, J10 A,10 B = 13.2 Hz, H2-10 ), 3.41 (dq, 1 H, J4,4a = 3.4, J4,Me = 6.9
Hz, H-4), 2.61 (s, 6 H, NMe2), 3.08 (dd, 1 H, H-4a), 3.00 (s, 3 H, 6-
(1R,3S,7S,10R,RS)-3-Ethoxy-4-methylene-2-oxa-5-thiatricy-
clo[5.4.0.17,10]dodecane 5-Oxide (25)
Oil.
IR (nujol): 1725, 1178, 1113, 1072, 1048 (SO), 943 cm–1.
1H NMR: = 6.03 and 5.89 (2 × br s, 2 H, 4=CH2), 5.24 (t, 1 H,
Jlong-range = 1.2 Hz, H-3), 3.85 and 3.56 (16 lines, 2 H, Jgem = 9.4,
Jvic = 7.1 Hz, OCH2), 3.71 (dd, 1 H, J1,11 = 8.3, 3.7 Hz, H-1), 3.10
and 2.95 (AB system, 2 H, J6A,6B = 13.5 Hz, H2-6), 2.0–1.4 (m, 7 H,
H2-8,9,11, H-10), 1.26 (t, 3 H, CH2CH3), 1.20 (s, 3 H, H3-13), 0.96
(s, 3 H, H3-14).
Synthesis 2003, No. 14, 2241–2248 © Thieme Stuttgart · New York

2248
M. C. Aversa et al.
SPECIAL TOPIC
Me), 1.9–1.1 (m, 7 H, H2-3 ,5 ,6 , H-4 ), 1.45 (d, 3 H, 4-Me), 1.18
(s, 3 H, H3-8 ), 0.84 (s, 3 H, H3-9 ).
(5) Aversa, M. C.; Barattucci, A.; Bonaccorsi, P.; Bonini, B. F.;
Giannetto, P.; Nicolò, F. Tetrahedron: Asymmetry 1999, 10,
3919.
(6) Aversa, M. C.; Barattucci, A.; Bonaccorsi, P.; Giannetto, P.;
Policicchio, M. J. Org. Chem. 2001, 66, 4845.
13C NMR: = 175.80 and 173.35 (C-5,7), 166.98 (C-3), 133.58 (C-
2), 76.91 (C-2 ), 56.29 (C-7a), 52.80 (C-10 ), 51.10 (C-1 ), 49.46
(C-4a), 48.20 (C-7 ), 44.89 and 44.77 (C-4 , NMe2), 38.35 (C-3 ),
30.80 and 29.60 (C-5 ,6 ), 24.99 and 24.08 (4,6-Me), 21.72, 20.41,
and 19.83 (C-4,8 ,9 ).
(7) Serck-Poncin, B.; Hesbain-Frisque, A. M.; Ghosez, L.
Tetrahedron Lett. 1982, 23, 3261.
(8) Tietze, L. F.; Kettschau, G. Top. Curr. Chem. 1997, 189, 1.
(9) (a) Beaudegnies, R.; Ghosez, L. Tetrahedron: Asymmetry
1994, 5, 557. (b) Knölker, H. J.; Baum, G.; Gonser, P.
Tetrahedron Lett. 1995, 36, 8191. (c) Maywald, F.;
Eilbracht, P. Synlett 1996, 380. (d) Knölker, H. J.;
Herzberg, D. Tetrahedron Lett. 1999, 40, 3547.
(10) Severin, T.; Wanninger, G.; Lerche, H. Chem. Ber. 1984,
117, 2875.
MS: m/z (%) = 424 (3) (M + 1), 270 (7), 109 (27), 95 (54), 81 (60),
69 (80), 55 (100), 43 (78).
Anal. Calcd for C21H33N3O4S: C, 59.55; H, 7.85; N, 9.92. Found: C,
59.58; H, 7.83; N, 9.94.
Acknowledgments
(11) (a) Eremeev, A. V.; Tikhomirov, D. A.; Tyusheva, V. A.;
Liepins, E. Khim. Get. Soedin. 1978, 753; Chem. Abstr.
1978, 89, 146873. (b) Usanova, E. A.; Khramchikhin, A. V.;
Stadnichuk, M. D. Russ. J. Gen. Chem. (Engl. Trans.) 2000,
70, 1120; Chem. Abstr. 2001, 134, 295781.
We gratefully acknowledge support of this work by the University
of Messina (funds for selected topics of interdisciplinary research).
References
(12) Bell, R.; Cottam, P. D.; Davies, J.; Jones, D. N. J. Chem.
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(1) Aversa, M. C.; Bonaccorsi, P.; Giannetto, P.; Jafari, S. M.
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(13) (a) Aversa, M. C.; Barattucci, A.; Bonaccorsi, P.; Bruno, G.;
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(16) In CD3CN solution, H-1 and H-2 resonate as two doublets at
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Synthesis 2003, No. 14, 2241–2248 © Thieme Stuttgart · New York