Efficiency of alkoxyl radical product formation from 5-substituted 3-alkoxy-4-methylthiazole-2(3H)-thiones

Article abstract of DOI:10.1016/j.tet.2009.11.113

In a comparative study, reactions between 5-(p-methoxyphenyl)-substituted 3-alkoxy-4-methylthiazole-2(3H)-thiones and appropriate mediators (BrCCl₃, Bu₃SnH) provided higher yields of alkoxyl radical products (δ-bromohydrins, cyclic ethers, carbonyl compounds) than respective transformations of 5-phenyl- and 5-methyl-substituted derivatives. The unusual selectivity of applied thiohydroxamates to furnish products of O-alkylation, even upon treatment with soft carbon electrophiles, and the marked propensity of 3-alkoxy-5-(p-methoxyphenyl)-4-methylthiazole-2(3H)-thiones to crystallize, facilitated preparation and purification of the new family of alkoxyl radical precursors in a noteworthy manner.

Full text of DOI:10.1016/j.tet.2009.11.113

Tetrahedron 66 (2010) 1365–1374
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Efficiency of alkoxyl radical product formation from 5-substituted
3-alkoxy-4-methylthiazole-2(3H)-thiones
,
a
a
b
Jens Hartung a , Christine Schur , Irina Kempter , Thomas Gottwald
*
a Fachbereich Chemie, Organische Chemie, Technische Universita¨t Kaiserslautern, Erwin-Schro¨dinger-Straße, D-67663 Kaiserslautern, Germany
b Institut fu¨r Organische Chemie, Universita¨t Wu¨rzburg, Am Hubland, 97074 Wu¨rzburg, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 28 August 2009
Received in revised form 25 November 2009
Accepted 30 November 2009
Available online 4 December 2009
In a comparative study, reactions between 5-(p-methoxyphenyl)-substituted 3-alkoxy-4-methylthiazole-
2(3H)-thiones and appropriate mediators (BrCCl3, Bu3SnH) provided higher yields of alkoxyl radical
products (d-bromohydrins, cyclic ethers, carbonyl compounds) than respective transformations of
5-phenyl- and 5-methyl-substituted derivatives. The unusual selectivity of applied thiohydroxamates to
furnish products of O-alkylation, even upon treatment with soft carbon electrophiles, and the marked
propensity of 3-alkoxy-5-(p-methoxyphenyl)-4-methylthiazole-2(3H)-thiones to crystallize, facilitated
preparation and purification of the new family of alkoxyl radical precursors in a noteworthy manner.
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Addition
Ambident nucleophile
Bicyclic ether
Bromohydrin
C,H-Activation
Carbohydrate
Cyclization
Fragmentation
Substitution
Tetrahydrofuran
Thiazolethione
Thiohydroxamate salt
1. Introduction
radical product formation, since the compound shows a similar
electronic spectrum (lmax¼333 nm) as 1 (lmax¼334 nm, both in
Radical precursors share the common property of liberating well
defined reactive intermediates upon physical or chemical activa-
tion.1,2 The reagent 3-hydroxy-5-(p-methoxyphenyl)-4-methyl-
thiazole-2(3H)-thione (1) in this sense was developed3 to provide
in a sequence of O-alkylation and N,O-homolysis oxygen-centered
radicals under non oxidative pH-neutral conditions.4,5 Its applica-
tion has contributed to clarify important synthetic,6 mechanistic,7,8
and theoretical aspects9 of alkoxyl radical chemistry that could not
adequately be addressed using oxidative methods for oxyl radical
generation.10
EtOH) but lacks in comparable weak C,H-bonds originating
from the p-methoxy substituent. Based on our experience
with N-hydroxy-4-methylthiazole-2(3H)-thione,12,13 4,5-dimethyl-
substituted heterocycle 3 (lmax¼316 nm, in EtOH) was expected to
As part of a project directed toward further improving char-
acteristics of thiohydroxamate-based O-radical precursors, we
recently reported on the synthesis of 5-substituted 3-hydroxy-
thiazole-2(3H)-thiones 2 and 3 (Fig. 1).11 5-Phenyl-substitution in
heterocycle 2 thus was expected to raise efficiency of alkoxyl
* Corresponding author. Tel.: þ49 631 205 2431; fax: þ49 631 205 3921.
E-mail address: hartung@chemie.uni-kl.de (J. Hartung).
Figure 1. Structure formulas and indexing of 5-substituted thiazole-2(3H)-thiones 1–6
(R0¼alkyl, alkenyl, benzyl).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.11.113

1366
J. Hartung et al. / Tetrahedron 66 (2010) 1365–1374
exhibit more pronounced thermal stability compared to aryl-de-
rivatives 1 and 2, to further reduce the significance of side
reactions, for instance fragmentations, that might interfere to N,O-
homolysis.14
In order to test the hypotheses stated above, acids 1–3 were
converted into O-esters 4–6. The alkyl substituents in those com-
pounds were so chosen as to direct alkoxyl radical reactions into
R
117.0
R
114.2
R
115.5
S
S
S
159.6
176.1
159.9
S
S
S
N
N
O
8
N
O
9
133.9
137.2
137.1
–
–
+
+
OH
a
Na
NEt4
a
a
1
R
114.7
R
129.4
R
119.0
pathways of selective substitution (SR), addition (AR), or
b-frag-
S
S
140.9
S
169.2
178.2
mentation (DR; Scheme 1). Quantitative product radical trapping,
target compound analysis, and mass balancing in this approach
formed the basis for validating the quality of compounds 4–6 re-
garding their property to serve as alkoxyl radical precursors. The
results from such a comparative study showed that 5-(p-methoxy-
phenyl)-substituted thiazolethiones 4 provided higher yields of
+
S
S
S
130.0
N
132.8
137.4
N
N
O
31.0
–
H
72.1
OH
O
3.76
H
5.00
H
H
b
b
b
1
4h
10h
Figure 2. Selected 13C- (blue) and 1H NMR chemical shifts (red) of 5-(p-methoxy-
phenyl)-substituted thiazole-2(3H)-thiones [R¼p-(H3CO)C6H4]. a in DMSO-d6. b in CDCl3.
alkoxyl radical products in reactions with BrCCl3 or Bu3SnH (d-
bromohydrins, cyclic ethers, carbonyl compounds), than their 5-
phenyl- and 5-methyl-substituted congeners 5 and 6. The latter
compounds, however, stood the test to serve as O-radical pro-
genitors and therefore merit consideration for selected applications.
7–9 provided upon treatment with selected alkyl halides and
p-toluenesulfonates 3-alkoxy derivatives 4a–j as yellowish solids in
yields that ranged between 42 and 87% (Table 1; for formation
of 10a, vide infra). The target compounds crystallized upon addition
of methanol to materials that were left from organic extractions of
underlying reaction mixtures. Recrystallization of likewise
obtained solids furnished analytically pure compounds 4a–j that
were stored in a refrigerator without noteworthy decomposition.
Yields of O-alkylation product 4 were dependent on substitution
and functionalization at the electrophilic carbon atom in R–X, on
the nature of the leaving group, and the cation in thiohydroxamates
7–9. Primary allylic and benzylic halides thus were poorer sub-
strates in reactions with NEt4-salt 8 compared to primary alkyl p-
toluenesulfonates (Table 1, entries 3, 7–9, 11–13). The effectiveness
of O-ethyl ester synthesis (formation of 4b) gradually fell along the
series counter cation/leaving group combinations NEtþ4 /
OTsꢀ>NEt4þ/Iꢀ>Naþ/OTsꢀ>Naþ/Iꢀ (Table 1, entries 3–6). All alkyl-
ations starting from primary and secondary iodoalkanes occurred
exclusively (TLC) at oxygen (Table 1, entries 5, 10 and 11). Formation
of a mixture of O- and S-alkylation products was restricted in this
study to the reaction between 3,3-dimethylallyl bromide and NEt4-
salt 8 (Table 1, entry 12). Alkyl shifts from O to S or vice versa and
Scheme 1. Nomenclature for alkoxyl radical elementary reactions applied in the
present study [A¼associative step, S¼substitution, D¼dissociative step; see Sections
2.2.1–2.2.3].15
Table 1
Preparation of 3-alkoxy-5-(p-methoxyphenyl)-4-methylthiazole-2(3H)-thiones
4a–j
2. Results and interpretation
2.1. Preparation and properties of 3-alkoxythiazole-2(3H)-
thiones
For reasons of favorable balance between stability and re-
activity, O-alkyl derivatives of cyclic thiohydroxamic acid 13 have
become standard reagents for the pursuit of mechanistic and
synthetic alkoxyl radical reactions in this laboratory.6,7,8 Syn-
thesis of the compounds, which has hitherto not been reported
in detail, is feasible via selective O-alkylation of the 5-(p-
methoxyphenyl)-4-methyl-2-thiooxo-2,3-dihydrothiazol-3-olate
ion. It requires conversion of acid 1 into tetraalkylammonium
salts 7–8 or sodium salt 9 in order to increase nucleophilicity of
the thiohydroxamate entity. Salt formation and thus charge
transfer onto the heterocyclic subunit is reflected in minor
changes of the thiazole-2(3H)-thione chromophore (e.g.,
lmax¼335 nm for 9, EtOH), but marked 13C NMR chemical shift
variations of heterocyclic carbons, particularly of C2 (e.g., in
DMSO-d6, Fig. 2).
Entry
R–X
7–9a,b
4b/%
10b/%
dc
1
2
3
4
5
6
7
8
CH3OTs
CH3I
C2H5OTs
C2H5OTs
C2H5I
C2H5I
C5H11OTs
Ph(CH2)4OTs
H2C]CH–CH2CH(Ph)CH2OTs16
c-C5H9I
H2C]CH–CH2I
(H3C)2C]CH–CH2Br
PhCH2Br
7
8
8
9
8
9
8
8
8
8
8
8
8
8
4a:9 64
dc
10a:46
dc
4b:4 87
4b:57
4b:64
4b:48
4c:6 82
4d:6 77
4e:4 63
4f:60
dc
dc
dc
dc
dc
9
dc
10
11
12
13
14
dc
4g:47
4h:42
4i:54
dc
10h:26
dc
dc
PhCH(CH3)Cl
4j:77
Ammonium salts 7–8 were hygroscopic and difficult to crys-
tallize, whereas powdery sodium salt 9 was stored in open beakers
having contact to laboratory atmosphere. In solutions of DMF, salts
a
M¼NBu4 for 7, NEt4 for 8 and Na for 9.
An¼p-(H3CO)C6H4.
b
c
Not detected (TLC, 1H NMR).

J. Hartung et al. / Tetrahedron 66 (2010) 1365–1374
1367
spontaneous fragmentations via carbonyl compound formation14
were not observed. Iodomethane was the only reagent in the series
that gave rise to selective S-alkylation (10a; Table 1, entry 2).
Products of O- and S-alkylation were distinguishable via UV-
(e.g., lmax¼334 nm for 4a and lmax¼311, 254 nm for 10a) and NMR
spectroscopy. The C]S group in, e.g., O-esters 4a–j, exhibited di-
agnostic 13C chemical shifts at w178 ppm. Magnetic anisotropy
exerted by this entity,17 in combination with the electron with-
drawing effect at thioydroxamate O, gave rise to notable
Diastereomerically pure (1H NMR) cis-(2-methylcyclopentyl)
O-esters (ꢂ)-cis-4k,4 (ꢂ)-cis-5k (both colorless solids), and
(ꢂ)-cis-6k (colorless oil, Fig. 3) for investigating O-radical-induced
b
-fragmentations were prepared from racemic trans-(2-methyl-
cyclopentyl) p-toluenesulfonate (>98% de) and appropriate NEt4-
thiohydroxamates in DMF at 20 ꢁC. The yields (58–66%, see
Experimental) were slightly lower than those of cyclopentyl esters
of 4-methylthiazole-2(3H)-thiones prepared from cyclopentyl
tosylate,25 presumably for reasons of steric hinderance in case of
2-methyl substitution of the electrophile.
deshielding of
a
-protons of the ester group (e.g.,
d
¼5.00 for O–CH2
in 4h; Fig. 2). Resonances of C2 and the
a
-protons in isomeric N-
oxides were notably upfield-shifted (e.g., 140.9 ppm and 3.76 ppm
for 10h; Fig. 2).
If compared to other thiohydroxamates, the unusual selectivity of
the 5-(p-methoxyphenyl)-4-methyl-2-thiooxo-2,3-dihydrothiazol-
3-olate ion to furnish products of O-alkylation, even upon treatment
with primary or secondary alkyl iodides, merits a comment. Since
nucleophilic substitutions commonly are reversible processes, se-
lectivity described above could originate in principle from thermo-
chemical and not only from kinetic preferences as argued on the
basis of the principles of hard, soft, acids, bases (HSAB) alone.18
Tansition states associated with esterification of stabilized anions in
7–9 therefore are proposed to be located comparatively late on the
associated reaction coordinates. If so, product stability becomes
more relevant for explaining selectivity than frontier molecular
orbital interactions.19 According to theory, 3-alkoxythiazole-2(3H)-
thiones were found at 25 ꢁC to be lower in free energy than S-
alkylsulfanylthiazole-3-oxide isomers.14 For open chain and other
cyclic thiohydroxamic acids, however, the reverse situation seems to
be valid.20,21 The latter compounds therefore notably favor alkylation
at thione sulfur in substitutions with iodoalkanes.22,23 S-methylation
of 8 is expected to take profit from the low steric hinderance at
carbon in CH3I. This circumstance possibly allows soft-soft in-
teractions between the reactants to become more relevant than in
slower reactions with primary or secondary iodoalkanes.24
The parameters established for the syntheses of 3-alkoxy
compounds 4a–j from acid 1 accordingly were applied to prepare
O-alkyl thiohydroxamates 5–6 from selected alkyl- and alkenyl
p-toluenesulfonates and NEt4-salts of acids 2 and 3. The com-
pounds were obtained as yellowish (5c, 5d) to colorless oils
(6c–6e), or as colorless crystalline solid (5e). They were stored in
a refrigerator without notable decomposition. If the Rf-value of
alkylsulfanyl-N-oxides 10a and 10h (0.01, petroleum ether/Et2O,
2:1; see Experimental) served as archetype for the mobility of such
compounds on TLC-sheets in general, it could be concluded that no
products of S-alkylation were formed from N-hydroxy compounds
2–3 under the chosen conditions (Table 2).
Figure 3. Structure formulas, indexing, and yields of selected carbo- and heterocyclic
O-esters (ꢂ)-cis-4k–l, (ꢂ)-cis-5k–6k, and
a-4m [see Text and Experimental;
An¼p-(H3CO)C6H4].
Treatment of trans-2-(prop-2-en-1-yl)-cyclohexyl p-toluene-
sulfonate with NEt4-salt 8 afforded (ꢂ)-cis-2-(prop-2-en-1-yl)-
cyclohexyl ester (ꢂ)-cis-4l in a highly stereoselective manner.
Attempts to raise the comparatively low yield of 7% by elevating the
reaction temperature led to quantitative reactant decomposition
(not shown). 2,3,5-Tri-O-acetyl-
underwent stereoselective substitution of thiohydroxamate for
chloride upon treatment with NEt4-salt 8 in DMF, to afford 3-(
ribosyloxy)-thiazolethione -4m in 59% yield. Stereochemical
b-D
-ribofuranosyl chloride26
a
-
a
analysis of this compound was based on diagnostic NMR shift values
and coupling constants. The proton attached to the anomeric center,
for example, resonated as doublet in a-configured ribose derivative
a
-4m (3JH,H¼5.0 Hz), whereas a broad singlet was observed for the
same proton in 2,3,5-tri-O-acetyl-b-D
-ribosylfuranosyl chloride.26
2.2. Generation and trapping of free alkoxyl radicals
3-Alkoxythiazolethiones 4–6 were heated or photolyzed in the
presence of suitable mediators (i.e., BrCCl3 or Bu3SnH) for the
synthesis of products originating from O-radical-mediated C,H-
activation (H-atom transfer,27,28,29 Section 2.2.1), intramolecular
addition30 (Section 2.2.2), and
b
-C, C cleavage31 (Section 2.2.3;
Table 2
Scheme 1). Both trapping reagents are able to quantitatively con-
vert carbon radicals that are left from an alkoxyl radical reaction
into stable products.32–34 This circumstance allowed to validate the
utility of O-radical sources 4–6 for conducting these and pre-
sumably related transformations35 on the basis of product
quantification.
Preparation of 5-phenyl- and 5-methyl derivatives of 3-alkoxy-4-methylthiazole-
2(3H)-thione
2.2.1. 1,5-H-Atom transfer (homolytic substitution). Transformations
via 1,5-H-atom translocation from carbon to oxygen were in-
vestigated in the presence of BrCCl3 in order to label the position of
the intermediate C-radical.
Entry
R
2/3
R0–X
5/6%
1
2
3
4
5
6
C6H5
C6H5
C6H5
CH3
CH3
CH3
2
2
2
3
3
3
C5H11OTs
Ph(CH2)4OTs
H2C]CH–CH2CH(Ph)CH2OTs
C5H11OTs
Ph(CH2)4OTs
5c:80
5d:65
5e:56
6c:77
6d:76
6e:81
Adequate conditions for preparing 4-bromopentan-1-ol (11)36
required thermal activation (80 ꢁC) of 3-pentoxythiazolethiones
4c–6c in solutions of BrCCl3 and C6D6 containing minor amounts
(w10 mol %) of AIBN as initiator (Table 3, entries 3–5, 8). Yields were
determined via NMR using anisole as internal standard. The
H2C]CH–CH2CH(Ph)CH2OTs
aconditions: (i) NEt4OH, MeOH, 20 ꢁC, then freeze-dry; (ii) R0–X, DMF, 20 ꢁC.

1368
J. Hartung et al. / Tetrahedron 66 (2010) 1365–1374
Table 3
Homolytic substitutiondformation of
d-bromohydrins 11/12
Entry
R
R0
4–6
Conditionsa
11–12b/%
13–15b/%
1
2
3
4
5
6
7
8
p-(H3CO)C6H4
p-(H3CO)C6H4
p-(H3CO)C6H4
C6H5
CH3
CH3
CH3
CH3
CH3
C6H5
C6H5
C6H5
4c
4c
4c
5c
6c
4d
4d
4d
h
h
n
n
(350 nm)
(visible)
11:21
11:17
11:92 (87)c
11:81
11:77
12:6
13:42
13:44
AIBN/80 ꢁ
AIBN/80 ꢁ
AIBN/80 ꢁ
C
C
C
13:94 (89)c
14:90
CH3
15:88
p-(H3CO)C6H4
p-(H3CO)C6H4
p-(H3CO)C6H4
hn
(350 nm)
(visible)
13:dd
13:dd
13:93
hn
12:5
12:91
AIBN/80 ꢁ
C
a
Quantitative conversion of compounds 4–6 (TLC, 1H NMR).
1H NMR referenced versus anisole as internal standard.
Number in parentheses refers to yield after chromatographic purification.
Not determined.
b
c
d
reference was added directly after quantitative substrate conver-
sion. Data validation was performed via chromatographic separa-
tion of products obtained from a larger batch (1 mmol; Table 3,
entry 3). The yields of bromohydrin 11 formed in this set of exper-
iments gradually fell along the series of applied thiones 4c>5c>6c
from 92 to 77%. The efficiency of trichloromethylsulfanylthiazole
formation followed this trend, although the yields of compounds
13–15 were slightly higher than those of product 11.
atom transfer to leave respective carbon radicals (cf. Scheme 1,
top).4,38 The 1-hydroxypent-4-yl- or the 1-hydroxy-4-phenylbut-4-
yl radical are nucleophilic intermediates that homolytically displace
ꢃCCl3 from BrCCl333 to furnish bromohydrins 11 or 12.32,39 Addition
of ꢃCCl3 to thiocarbonyl groups of radical precursors 4c–6c or 4d has
been claimed to induce N,O-homolysis (alkoxyl radical liberation) to
leave corresponding trichloromethylsulfanylthiazoles. This mecha-
nistic interpretation was supported in this study by matching yields
of organobromine compounds 11/12 on one side, and thiazole-
derived by-products 13–15 on the other.
Photolysis of 3-pentoxy-5-(p-methoxyphenyl)-thiazolethione
4c in the presence of BrCCl3 using a RayonetÒ-chamber reactor
(
l
¼350 nm; Table 3, entry 1) or an incandescent light bulb (Table 3,
entry 2) was associated with complete consumption of the starting
material within 30 min at w20 ꢁC. The yield of bromoalcohol 11,
however, remained low (17–21%) and the mass balance for un-
known reasons erratic.
2.2.2. Addition. The utility of 3-alkenoxythiazolethiones (e.g.,
4e–6e) to serve as starting materials for conducting stereoselective
tetrahydrofuran synthesis via 5-exo-trig alkenoxyl radical cycliza-
tions was explored using Bu3SnH as mediator. Regio- and stereo-
selectivity of the chosen ring closure provided sufficient
information about the chemical nature of the reactive intermediate,
and therefore did not require labeling.
Reactions of 3-(4-phenylbut-1-oxy)-thiazolethione 4d and
BrCCl3 required thermal reactant activation in order to provide
excellent yields of 4-phenyl-4-bromobutanol 124 (91%) and tri-
chloromethylsulfanylthiazole 13 (93%; Table 3, entry 8). Photo-
chemical conditions were less suited for this purpose (Table 3, entry
6–7). Attempts to purify products obtained from a thermally in-
duced reaction via chromatography (SiO2) afforded mixtures of 4-
phenyl-4-bromobutanol 12 and 2-phenyltetrahydrofuran (16)37
with the latter being an artifact due to the selected work up pro-
cedure. The material was obtained as sole alkoxyl radical product
(83%), e.g., upon adsorptive filtration of a crude reaction mixture
(cf. Table 3, entry 8) through basic Al2O3 (Scheme 2).
Synthetically useful yields of racemic tetrahydrofuran (ꢂ)-1740
were obtained from 3-phenylpentenoxy-5-(p-methoxyphenyl)-4-
methylthiazolethione 4e and Bu3SnH, either by photolyzing
[RayonetÒ-chamber reactor (
heating solutions of the reactants in C6D6 (Table 4, entries 1–3). The
latter set-up required addition of an initiator (AIBN), to achieve
l
¼350 nm) or incandescent light] or
Table 4
Intramolecular addition under reductive conditionsdtetrahydrofuran formation
Entry
R
4e–6e
Conditionsa
(ꢂ)-17b%
18–20b/%
Scheme 2. Synthesis of 2-phenyltetrahydrofuran 16 [An¼p-(H3CO)C6H4].37
1
2
3
4
5
p-(H3CO)C6H4
p-(H3CO)C6H4
p-(H3CO)C6H4
C6H5
4e
4e
4e
5e
6e
h
h
n
n
(350 nm)
(visible)
63 (87:13)
59 (86:14)
64 (87:13)
62 (87:13)
61 (87:13)
18:77
18:78
18:77
19:76
20:78
AIBN/80 ꢁ
AIBN/80 ꢁ
AIBN/80 ꢁ
C
C
C
The underlying reactivity of 3-pentoxythiazolethiones 4c–6c or
3-phenylbutoxy derivative 4d in the presence of BrCCl3 is explicable
on the basis of 1-pentoxyl- or 4-phenylbut-1-oxyl radical formation
in the initialstep. O-radicals of this typeareknown to undergo 1,5-H-
CH3
a
Quantitative conversion of compounds 4e–6e (TLC and 1H NMR).
b
1H NMR, referenced versus anisole as internal standard.

J. Hartung et al. / Tetrahedron 66 (2010) 1365–1374
1369
quantitative turnover of starting thiones 4e–6e and satisfactory
yields of target compound (ꢂ)-17 (64%), besides tributyl-
(Table 5). All transformations of this type provided hexanal (22) and
tributylstannyl-substituted thiazoles 18–20, however, in slightly
diverging yields. The most effective procedure for hexanal synthesis
according to this method started from 5-(p-methoxyphenyl)-
substituted thiazolethione (ꢂ)-cis-4k and required photochemical
reactant activation (Table 5, entries 1–2). The fact that the thermal
reaction (80 ꢁC) gave less target compound, however, was corre-
lated with the volatility of aldehyde 22 (bp.¼131 ꢁC), which seemed
to be no concern in photochemical reactions at w20 ꢁC. Support for
this argumentation arose from analysis of yields of secondary
product 18 that differed only marginally across the entire set of
experiments (Table 5, entries 1–3). In view of these findings, the
remaining two cis-2-methylcyclopentyl esters (ꢂ)-cis-5k and
stannylsulfanylthiazole
18
[77%;
R¼p-(H3CO)C6H4].
This
methodology was for reasons of effectiveness applied for convert-
ing 3-pentenoxythiazolethiones 5e or 6e into tetrahydrofuran
(ꢂ)-17 (61–62%) and tributylstannyl-substituted thiazoles 19 (76%
from 5e) or 20 (78% from 6e) (Table 4, entries 4–5). Tributyl-
stannylsulfanyl-substituted thiazoles 19 and 20 were characterized
via NMR directly in solutions obtained from radical reactions, since
the compounds decomposed on attempts to separate additionally
formed butyl tin compounds via chromatography or distillation
(see Experimental and Supplementary Data).
In a synthetic application (ꢂ)-3-(cis-allylcyclohexyloxy)-thia-
zolethione (ꢂ)-cis-4l was photolyzed (350 nm, 20 ꢁC) in the pres-
ence of BrCCl3 to provide oxabicyclo[4.3.0]nonane (ꢂ)-2141 in 70%
yield (Scheme 3). This approach refrained from using an initiator
and contributed to slightly improve stereoselectivity of the cycli-
zation (6,8-cis:6,8-trans¼72:28).41
(ꢂ)-cis-6k were subjected to photochemical reactions ( ¼350 nm,
l
20 ꢁC) with Bu3SnH. Hexanal yields (1H NMR) of both experiments
were smaller than the value obtained for the reaction of (ꢂ)-cis-4k
under identical conditions (Table 5, entries 1, 4 and 5).
Photolysis of O-ribosylthiohydroxamate
a-4m and Bu3SnH
(l
¼350 nm, 20 ꢁC; Scheme 4) in a solution of C6H6 furnished
a mixture of formylester 23 and tri-O-acetylerythritol 24, with the
former being transformed into the latter in the course of chro-
matographic purification (56%).
Scheme 3. Stereoselective oxabicyclo[4.3.0]nonane formationa refers to positions 6
and 8 [An¼p-(H3CO)C6H4].
Experiments starting from 3-alkenoxythiazolethiones 4e–6e
exemplified that efficiency of alkenoxyl radical product formation
via 5-exo-trig cyclization (Scheme 1, center) was independent from
the chemical nature of the substituent in position 5 of the radical
precursor, and the applied methodology for activating these mol-
ecules. Regio- and diastereoselectivity of tetrahydrofuran synthesis
from 3-alkenoxythiazolethiones [4e–6e, (ꢂ)-cis-4l] and Bu3SnH or
BrCCl3 were consistent with the appearance of free alkenoxyl rad-
icals and their participation in chain reactions. For mechanistic
details of both model reactions the reader is referred to appropriate
references.10,40,41
Scheme 4. Carbohydrate degradation under reductive conditions [a chromatographic
purification on SiO2; An¼p-(H3CO)C6H4].
Alkoxyl radicals having a saturated five-membered ring at-
tached to the O-radical center undergo rapid fragmentation into d-
oxo-substituted carbon radicals.42,43,44 The driving force for this
C,C-disconnection originates from a relieve of ring strain and the
energy, that is, gained upon C,O-double bond formation at the
expense of a C,C-single bond in proximity to an alkoxyl radical
center.35 The reverse reaction, i.e., 5-exo-trig addition of a
d-for-
2.2.3.
b-C,C-Fragmentation. Efficiency of 5-substituted 3-alkoxy-
mylbutyl radical to a C]O group is slower than the fragmentation,
thus shifting the equilibrium onto the side of the open-chain
radical.45 Trapping of intermediates therefore provides ring-
opened products (e.g., 22) as major components. Formation of
erythritol 24 is in agreement with this mechanistic interpretation
thiazolethiones in the synthesis of carbonyl compounds under
reductive conditions was validated in reactions of O-(cis-2-
methylcyclopentyl) thiohydroxamates (ꢂ)-cis-4k–6k with Bu3SnH
Table 5
since fragmentation of the
a-2,3,5-tri-O-acetyloxylribosyloxyl
Fragmentation under reductive conditionsdpreparation of hexanal (22)
radical (not shown) is expected for thermochemical reasons to
occur via breaking of the adjacent C,C- and not of the endocyclic
C,O-bond.46,47 Reduction of the primary intermediate furnished
a 3/1-mixture of formylester 23 and erythritol 24. The former
product hydrolyzed upon chromatographic purification to leave
alcohol 24.
3. Concluding remarks
The present report on the efficiency of 5-substituted 3-alkoxy-4-
methylthiazole-2(3H)-thiones 4–6 in alkoxyl radical-based syn-
thesis allows to draw the following conclusions.
Entry
R
(ꢂ)-cis-4k–6k
Conditionsa
22b%
18–20b/%
1
2
3
4
5
p-(H3CO)C6H4
p-(H3CO)C6H4
p-(H3CO)C6H4
C6H5
4k
4k
4k
5k
6k
h
h
n
n
(350 nm)
(visible)
77
78
65
62
71
18: 82
18: 80
18: 83
19: 79
20: 81
AIBN/80 ꢁ
C
(i) The marked propensity to separate as crystalline solids from
rather crude reaction mixtures by adding MeOH simplified
isolation and subsequent purification of 5-(p-methoxy-
phenyl)-substituted thiazolethiones 4 in comparison to their
h
h
n
n
(350 nm)
(350 nm)
CH3
a
Quantitative conversion of compounds (ꢂ)-cis-4k–6k (TLC and 1H NMR).
b
1H NMR, referenced versus anisole as internal standard.

1370
J. Hartung et al. / Tetrahedron 66 (2010) 1365–1374
J¼8.5 Hz). 13C NMR (DMSO-d6, 150 MHz)
d
13.4 (4-CH3), 55.3
5-phenyl and 5-methyl congeners 5 and 6 (predominantly
oils) in a noteworthy manner.
(OCH3), 114.5, 115.5 (C5), 124.6, 129.0, 137.1 (C4), 158.6, 159.6 (C2).
(ii) All 3-alkoxythiazolethiones 4–6 applied in this study stood the
test to serve as alkoxyl radical sources.
4.3. Alkylation of thiohydroxamate salts
(iii) Reactions based on 1,5-H-atom transfer from carbon to oxygen
required for unknown reasons higher temperatures (w80 ꢁC)
to provide good to excellent yields (77–92%) of O-radical
4.3.1. General method. A solution of a 3-hydroxy-5-(p-methoxy-
phenyl)-4-methylthiazole-2(3H)-thione salt 7–9 (1.10 mmol) or NEt4-
salts of thiazolethiones 2–3 (1.10 mmol) in anhydrous DMF (2 mL) was
treated at 20 ꢁC with a respective neat alkyl tosylate or an alkyl halide
(1.00 mmol). Stirring was continued at 20 ꢁC. until complete substrate
conversion had occurred (3–6 days). Water (10 mL) was added. The
mixture was extracted with Et2O (3ꢄ5 mL). Combined organic extracts
were dried (MgSO4), and concentrated under reduced pressure. MeOH
was added for crystallizing the residue. If no solids appeared on
standing for 14 h at 5 ꢁC the solvent was evaporated. The remaining oil
was purified by column chromatography (SiO2).
products (e.g.,
d-bromohydrins 11/12).
(iv) Intramolecular additions and
b
-C,C-homolysis were feasible
using any of the 3-alkoxythiazolethiones prepared for this
purpose using thermal (w80 ꢁC, AIBN) or photochemical re-
agent activation (
(v) In case of diverging yields (1,5-H-atom transfer in Section 2.2.1
and -fragmentation in paragraph 2.2.3), 5-(p-methoxy-
l¼350 nm or incandescent light).
b
phenyl)-4-methyl-substituted thiazolethiones 4 consistently
were the more effective reagents compared to derivatives 5
and 6.
4.3.2. 5-(p-Methoxyphenyl)-4-methyl-2-(methylsulfanyl)-thiazole-
3-oxide (10a). From methyliodide (142 mg, 1.00 mmol). Yield:
124 mg (0.46 mmol, 46%), tan oil. Rf¼0.01 [petroleum ether/
The data summarized in this report clearly stressed the utility
of the 3-alkoxy-5-(p-methoxyphenyl)-4-methylthiazolethiones 4
for alkoxyl radical generation under non oxidative pH-neutral
conditions. The results furthermore pointed to the necessity to
systematically analyze in future studies effects of the 5 substituent
in thiazole-2(3H)-thiones onto barriers to N,O-homolysis and the
quality of the thione sulfur to serve as carbon radical trap. From
an experimental point of view it became obvious that the fun-
damental 3-alkoxythiazole-2(3H)-thione reactivity was largely
retained upon substitution of methyl or phenyl for p-methoxy-
phenyl at this site. This conclusion was probably is one of the
most important findings from the study. It paves the road toward
design of novel O-radical precursors having other substituents
attached to the thiazole-2(3H)-thione core than those applied in
the present investigation. Such compounds are expected to con-
tribute to future developments in order to apply the unique re-
activity of alkoxyl radicals for quite general or highly specialized
purposes.
Et2O¼2:1 (v/v)]. 1H NMR (CDCl3, 400 MHz)
d 2.43 (s, 3H, 4-CH3),
2.61 (s, 3H, SCH3), 3.85 (s, 3H, OCH3), 6.98 (mc, 2H), 7.33 (mc, 2H).
13C NMR (CDCl3, 100 MHz)
114.6, 122.9, 128.4, 129.8 (C5), 140.9 (C4), 152.8 (C2), 160.3. UV
d 12.2 (4-CH3), 15.4 (SCH3), 55.4 (OCH3),
(EtOH) lmax (lg 3
/m2 molꢀ1) 311 nm (3.38), 253 (3.42). MS (EI) m/z
267 (Mþ, 67), 250 (100), 177 (38). Anal. Calcd for C12H13NO2S2
(267.36) C, 53.91; H, 4.90; N, 5.24; S, 23.98; Found: C, 53.90; H, 4.91;
N, 5.24; S, 23.62.
4.3.3. 3-Cyclopentoxy-5-(p-methoxyphenyl)-4-methylthiazole-
2(3H)-thione (4f). From iodocyclopentane (196 mg, 1.00 mmol);
yield 193 mg (60%), yellowish solid. Rf¼0.28 [petroleum ether/
Et2O¼2:1 (v/v)]. 1H NMR (CDCl3, 400 MHz)
d 1.62–1.72 (m, 2H),
1.81–1.92 (m, 4H),1.92–2.03 (m, 2H), 2.29 (s, 3H, 4-CH3), 3.83 (s, 3H,
OCH3), 5.75 (mc, 1H), 6.94 (mc, 2H), 7.24 (mc, 2H). 13C NMR (CDCl3,
101 MHz)
d 12.7 (4-CH3), 23.8, 31.4, 55.4 (OCH3), 89.1, 114.5, 119.4
(C5), 122.7, 129.9, 133.3 (C4), 159.9, 179.2 (C2). MS (EI) m/z 321 (Mþ,
28), 237 (77), 178 (14), 57 (100). Anal. Calcd for C16H19NO2S2
(321.45): C, 59.78; H, 5.96; N, 4.36; S, 19.95; Found: C, 59.95; H,
5.98; N, 4.33; S, 20.06.
4. Experimental
4.1. General
4.3.4. 5-(p-Methoxyphenyl)-4-methyl-3-(prop-2-en-1-oxy)-thia-
zole-2(3H)-thione (4g). From 3-iodopropene (168 mg, 1.00 mmol);
yield: 138 mg (47%), yellowish solid. Rf¼0.23 [petroleum ether/
For general laboratory practice and instrumentation see Ref. 6
and the Supplementary Data.
Et2O¼2:1 (v/v)]. 1H NMR (CDCl3, 400 MHz):
d 2.32 (s, 3H, 4-CH3), 3.83
4.2. 3-Hydroxythiazole-2(3H)-thione salts
(s, 3H, OCH3), 5.00 (d, 2H, J¼6.7 Hz), 5.43 (m, 2H), 6.11 (ddt,1H, Jd¼13.3,
10.1 Hz, Jt¼6.7 Hz), 6.94 (mc, 2H), 7.24 (mc, 2H). 13C NMR (CDCl3,
4.2.1. General method. A solution of NEt4OH, NBu4OH, or NaOH in
MeOH (1.10 mmol, 0.73 mL, 1.5 M) was added to a solution of a 3-
hydroxythiazole-2(3H)-thione 1–3 (1.10 mmol) in MeOH (2 mL) at
20 ꢁC. The reaction mixture was stirred for 1 h at 20 ꢁC. The solvent
was evaporated under reduced pressure to furnish a residue that
was freeze-dried (12 h). The salts were ready for use and taken up
in DMF for thiohydroxamate alkylation as described in Section 4.3.1.
100 MHz) d 12.3 (4-CH3), 55.4 (OCH3), 76.7, 114.4, 114.7, 119.2 (C5),
122.9,129.9,130.0,132.4 (C4),159.1,178.8 (C2). MS (EI) m/z 293 (Mþ,1),
262 (8), 237 (100), 163 (18). Anal. Calcd for C14H15NO2S2 (293.40): C,
57.31; H, 5.15; N, 4.77; S, 21.85; Found: C, 57.57; H, 5.27; N, 4.74; S, 21.39.
4.3.5. Alkylation of tetraethylammonium salt 8 with 1-bromo-3-
methylbut-2-ene (149 mg, 1.00 mmol). The crude product was puri-
fied by column chromatography [petroleum ether/Et2O¼2:1 (v/v)].
5-(p-Methoxyphenyl)-4-methyl-3-(3-methylbut-2-en-1-oxy)-thiazole-
2(3H)-thione (4h). Yield: 135 mg (42%), yellowish solid. Rf¼0.28
4.2.2. 3-Hydroxy-5-(p-methoxyphenyl)-4-methylthiazole-2(3H)-thi-
one tetraethylammonium salt (8). 1H NMR (DMSO-d6, 400 MHz)
d
1.14 (t, 12H, J¼6.4 Hz), 2.18 (s, 3H, 4-CH3), 3.20 (q, 8H, J¼7.2 Hz),
3.75 (s, 3H, OCH3), 6.96 (d, 2H, J¼8.6 Hz), 7.25 (d, 2H, J¼8.6 Hz).
13C NMR (DMSO-d6, 100 MHz)
6.8, 13.0 (4-CH3), 51.5, 55.0
[petroleum ether/Et2O¼2:1 (v/v)]. 1H NMR (CDCl3, 400 MHz)
d 1.81
(d, 3H, J¼1.0 Hz), 1.82 (s, 3H), 2.30 (s, 3H, 4-CH3), 3.84 (s, 3H, OCH3),
d
5.00 (d, 2H, J¼7.8 Hz), 5.53 (mc, 1H), 6.94 (mc, 2H), 7.24 (mc, 2H). 13
C
(OCH3), 114.2, 114.3 (C5), 124.9, 128.4, 137.2 (C4), 158.0,
159.9 (C2).
NMR (CDCl3, 100 MHz) d 12.4 (4-CH3), 18.3, 26.0, 55.4 (OCH3), 72.1,
114.6, 116.3, 119.0 (C5), 122.7, 129.9, 132.8 (C4), 144.7, 159.9, 178.8
(C2). UV (EtOH) lmax (lg 3
/m2 molꢀ1) 334 nm (3.26). MS (EI) m/z 321
4.2.3. 3-Hydroxy-5-(p-methoxyphenyl)-4-methylthiazole-2(3H)-thi-
(Mþ, 8), 305 (12), 237 (100), 178 (21). Anal. Calcd for C16H19NO2S2
(321.45): C, 59.78; H, 5.96; N, 4.36; S, 19.95; Found: C, 59.83; H, 5.87;
N, 4.32; S, 20.05. 5-(p-Methoxyphenyl)-4-methyl-2-(3-methyl-2-
one sodium salt (9). 1H NMR (DMSO-d6, 600 MHz)
d
2.23 (s, 3H, 4-
CH3), 3.77 (s, 3H, OCH3), 6.98 (d, 2H, J¼8.7 Hz), 7.28 (d, 2H,

J. Hartung et al. / Tetrahedron 66 (2010) 1365–1374
1371
buten-1-ylsulfanyl)-thiazol-3-oxide (10h). Yield: 83.6 mg (0.26 mmol,
26%), colorless solid. Rf¼0.01 [petroleum ether/Et2O¼2:1 (v/v)]. 1H
was purified by column chromatography [petroleum ether/
Et2O¼2:1 (v/v)]. Yield: 235 mg (0.80 mmol, 80%), yellowish oil.
Rf¼0.53 [petroleum ether/Et2O¼2:1 (v/v)]. 1H NMR (CDCl3,
NMR (CDCl3, 400 MHz) d 1.63 (s, 3H), 1.73 (s, 3H), 2.43 (s, 3H, 4-CH3),
3.76 (d, 2H, J¼8.1 Hz), 3.86 (s, 3H, OCH3), 5.32 (mc, 1H), 6.99 (mc, 2H),
7.34 (mc, 2H). 13C NMR (CDCl3, 100 MHz)
12.4 (4-CH3), 17.7, 25.7,
31.0, 55.4 (OCH3), 114.6, 117.9, 123.0, 129.4 (C5), 129.9, 137.4 (C4),
250 MHz)
d
0.94 (t, 3H, J¼7.2 Hz), 1.30–1.58 (m, 4H), 1.87 (mc, 2H),
d
2.37 (s, 3H, 4-CH3), 4.46 (t, 2H, J¼6.6 Hz), 7.29–7.46 (m, 5H). 13C
NMR (CDCl3, 63 MHz)
d 12.1 (4-CH3), 13.9, 22.5, 27.6, 27.8, 76.5,
139.0, 140.9 (C2), 160.4. UV (EtOH) lmax (lg
3
/m2 molꢀ1) 310 (3.01),
119.3 (C5), 128.5, 128.7, 129.1, 130.4, 132.9 (C4), 179.0 (C2). UV
254 (3.07). MS (EI) m/z 321 (Mþ, 8), 304 (18), 253 (100), 146 (34).
Anal. Calcd for C16H19NO2S2 (321.45): C, 59.78; H, 5.96; N, 4.36; S,
19.95; Found: C, 59.83; H, 5.97; N, 4.32; S, 20.03.
(EtOH) lmax (lg
3
/m2 molꢀ1) 332 nm (3.45), 284 nm (2.77). Anal.
Calcd for C15H19NOS2 (293.44): C, 61.40; H, 6.53; N, 4.77; S, 21.85;
Found: C, 61.40; H, 6.41; N, 4.81; S, 21.65.
4.3.6. 3-(1-Benzyloxy)-5-(p-methoxyphenyl)-4-methylthiazole-
2(3H)-thione (4i). From benzyl bromide (127 mg, 1.00 mmol). Yield:
187 mg (0.54 mmol, 54%), colorless solid. Rf¼0.17 [petroleum ether/
4.3.11. 4-Methyl-5-phenyl-3-(4-phenylbut-1-oxy)-thiazole-2(3H)-
thione (5d). From 4-phenylbutyl tosylate (304 mg, 1.00 mmol). The
crude product was purified by column chromatography [petroleum
ether/Et2O¼2:1 (v/v)]. Yield: 231 mg (0.65 mmol, 65%), yellowish
oil. Rf¼0.51 [petroleum ether/Et2O¼2:1 (v/v)]. 1H NMR (CDCl3,
Et2O¼2:1 (v/v)]. 1H NMR (CDCl3, 400 MHz)
d 2.07 (s, 3H, 4-CH3), 3.83
(s, 3H, OCH3), 5.52 (s, 2H), 6.92 (mc, 2H), 7.17 (mc, 2H), 7.40–7.44 (m,
3H), 7.53–7.57 (m, 2H).13C NMR (CDCl3,100 MHz)
d
12.1 (4-CH3), 55.4
250 MHz) d 1.33–1.55 (m, 4H), 2.34 (s, 3H, 4-CH3), 2.73 (t, 2H,
(OCH3), 77.5, 114.5, 118.9 (C5), 122.6, 128.8, 129.7, 129.9, 130.3, 132.8
(C4), 133.3, 159.9, 178.7 (C]S). MS (EI) m/z 343 (Mþ, 3), 237 (21), 106
(87), 91 (17), 77 (100). Anal. Calcd for C18H17NO2S2 (343.46): C, 62.95;
H, 4.99; N, 4.08; S, 18.67; Found: C, 62.96; H, 4.99; N, 4.11; S, 18.37.
J¼7.1 Hz), 4.49 (t, 2H, J¼6.0 Hz), 7.19–7.22 (m, 3H), 7.28–7.33 (m,
4H), 7.36–7.46 (m, 3H). 13C NMR (CDCl3, 63 MHz)
12.1 (4-CH3),
27.5, 27.5, 35.5, 76.0, 119.3 (C5), 125.9, 128.4, 128.5, 128.5, 128.7,
d
129.1, 130.4, 132.8 (C4), 141.8, 179.0 (C2). UV (EtOH) lmax (lg 3/
m2 molꢀ1) 334 nm (3.17), 289 nm (2.91). MS (EI) m/z 355 (Mþ, 4),
207 (50), 147 (16), 104 (100), 91 (69). Anal. Calcd for C20H21NOS2
(355.51): C, 67.57; H, 5.95; N, 3.94; S,18.04; Found: C, 67.44; H, 6.22;
N, 3.91; S, 17.54.
4.3.7. (ꢂ)-5-(p-Methoxyphenyl)-4-methyl-3-(1-phenyleth-1-oxy)-thi-
azole-2(3H)-thione (ꢂ)-(4j). From 1-chloro-1-phenylethane (141 mg,
1.00 mmol). Yield: 275 mg (0.77 mmol, 77%), colorless solid. Rf¼0.42
[petroleum ether/Et2O¼2:1 (v/v)]. 1H NMR (CDCl3, 400 MHz):
d 1.61
(s, 3H, 4-CH3), 1.84 (d, 3H, J¼6.7 Hz), 3.79 (s, 3H, OCH3), 6.33 (q, 1H,
4.3.12. (ꢂ)-4-Methyl-5-phenyl-3-(2-phenylpent-4-en-1-oxy)-thia-
zole-2(3H)-thione (ꢂ)-(5e). From (ꢂ)-2-phenyl-4-penten-1-yl tosy-
late (316 mg, 1.00 mmol). The crude product was purified by column
chromatography [petroleum ether/Et2O¼2:1 (v/v)]. Yield: 206 mg
(0.56 mmol, 56%), colorless solid. Rf¼0.51 [petroleum ether/
J¼6.7 Hz), 6.87 (mc, 2H), 7.03 (mc, 2H), 7.38–7.44 (m, 5H). 13C NMR
(CDCl3, 100 MHz)
d 12.1 (4-CH3), 17.9, 55.4 (OCH3), 82.5, 114.4, 118.4
(C5), 122.7, 128.5, 128.6, 129.6, 129.8, 133.8 (C4), 138.0, 159.7, 178.7
(C2). MS (EI) m/z 357 (Mþ, 2), 253 (8), 237 (21), 178 (5), 120 (36), 105
(100), 77 (98). Anal. Calcd for C19H19NO2S2 (357.49): C, 63.84; H, 5.36;
N, 3.92; S, 17.94; Found: C, 63.49; H, 5.19; N, 3.95; S, 17.46.
Et2O¼2:1 (v/v)]. 1H NMR (CDCl3, 250 MHz)
d 2.00 (s, 3H, 4-CH3), 2.55
(ddd, 1H, J¼14.4, 7.2, 7.0 Hz), 2.72 (ddd, 1H, J¼14.4, 7.2, 7.0 Hz), 3.30
(quint, 1H, J¼7.2 Hz), 4.51 (t, 1H, J¼7.2 Hz), 4.78 (t, 1H, J¼7.2 Hz), 5.05
(mc, 2H), 5.76 (mc, 1H), 7.21–7.42 (m, 10H). 13C NMR (CDCl3, 63 MHz)
4.3.8. (ꢂ)-5-(p-Methoxyphenyl)-4-methyl-3-[cis-2-(prop-2-en-1-yl)-
cyclohexyl-1-oxy]-thiazole-2(3H)-thione (ꢂ)-cis-(4l). From (ꢂ)-trans-
2-(prop-2-en-1-yl)cyclohexyltosylate (294 mg, 1.00 mmol). The
crude product was purified by column chromatography [petroleum
d
11.7 (4-CH3), 36.5, 44.3, 79.2, 117.1, 119.1 (C5), 127.1, 128.0, 128.4,
128.5, 128.6, 129.0, 130.3, 132.9, 135.4 (C4), 140.7, 179.0 (C2). UV
(EtOH) lmax (lg 3
/m2 molꢀ1) 333 nm (3.18), 285 (2.52). MS (EI) m/z
ether/Et2O¼2:1 (v/v)]. Yield: 24.4 mg (74.0
m
mol, 7%), yellowish solid.
367 (Mþ, 1), 207 (46), 131 (76), 91 (100). Anal. Calcd for C21H21NOS2
(367.52): C, 68.63; H, 5.76; N, 3.81; S, 17.45; Found: C, 68.36; H, 5.73;
N, 3.88; S, 16.95.
Rf¼0.45 [petroleum ether/Et2O¼2:1 (v/v)]. 1H NMR (CDCl3, 400 MHz)
d
1.30–1.50 (m, 4H), 1.72–1.84 (m, 4H), 2.20–2.40 (m, 2H), 2.30 (s, 3H,
4-CH3), 2.60–2.64 (m, 1H), 3.84 (s, 3H, OCH3), 5.02–5.12 (m, 2H),
5.30–5.35 (m, 1H), 5.77–5.85 (m, 1H), 6.95 (mc, 2H), 7.24 (mc, 2H). 13
NMR (CDCl3,100 MHz) 12.9 (4-CH3), 20.5, 23.9, 26.3, 26.9, 30.6, 37.6,
55.4 (OCH3), 85.5,114.5,116.1,119.9 (C5),122.8,129.9,133.6,137.3 (C4),
159.9, 179.0 (C2). MS (EI) m/z 375 (Mþ, 3), 253 (15), 237 (57), 138 (37),
79 (100). Anal. Calcd for C20H25NO2S2 (375.54): C, 63.97; H, 6.71; N,
3.73; S, 17.07; Found: C, 64.37; H, 6.97; N, 3.80; S, 17.15.
C
4.3.13. (ꢂ)-4-Methyl-3-(cis-2-methylcyclopent-1-oxy)-5-phenyl-
d
thiazole-2(3H)-thione
(ꢂ)-cis-(5k). From
(ꢂ)-trans-2-methyl-
cyclopentyl tosylate (254 mg, 1.00 mmol). The crude product was
purified by column chromatography [petroleum ether/Et2O¼2:1 (v/
v)]. Yield: 177 mg (0.58 mmol, 58%), colorless solid. Rf¼0.78 [pe-
troleum ether/Et2O¼2:1 (v/v)]. 1H NMR (CDCl3, 250 MHz)
d 1.28 (d,
3H, J¼6.9 Hz), 1.50–1.98 (m, 6H), 2.12–2.25 (m, 1H), 2.32 (s, 3H, 4-
4.3.9. 5-(p-Methoxyphenyl)-4-methyl-3-(2,3,5-tri-O-acetyl-
bofuranosyl-1-oxy)- thiazole-2(3H)-thione -(4m). From 2,3,5-tri-
O-acetyl- -ribofuranosyl chloride (295 mg, 1.00 mmol). Yield:
302 mg (0.59 mmol, 59%), colorless solid. Rf¼0.08 [petroleum
ether/Et2O¼2:1 (v/v)]. [
25 159.6 (c 0.54, CH2Cl2). 1H NMR (CDCl3,
400 MHz) 2.11 (s, 3H), 2.16 (s, 3H), 2.21 (s, 3H), 2.31 (s, 3H, 4-CH3),
a-D-ri-
CH3), 5.64 (dt, 1H, J¼4.9, 4.8 Hz), 7.30–7.45 (m, 5H). 13C NMR (CDCl3,
a
63 MHz) d 12.6 (4-CH3), 13.6, 21.9, 29.6, 31.4, 39.3, 89.8, 119.3 (C5),
b-
D
128.5, 128.6, 129.1,130.5,134.3 (C4),179.6 (C2). UV (EtOH) lmax (lg 3/
m2 molꢀ1) 334 nm (3.38), 285 (2.69). MS (EI) m/z 305 (Mþ, 22), 223
(85), 207 (100), 147 (43), 130 (40), 115 (32). Anal. Calcd for
C16H19NOS2 (305.45): C, 62.92; H, 6.27; N, 4.59; S, 20.99; Found: C,
62.58; H, 6.56; N, 4.49; S, 20.54.
a
]
D
d
3.83 (s, 3H, OCH3), 4.23 (dd, 1H, J¼12.1, 3.7 Hz), 4.36 (dd, 1H, J¼12.1,
3.4 Hz), 4.64 (mc, 1H), 5.37 (dd, 1H, J¼6.3, 1.8 Hz), 5.50 (dd, 1H,
J¼6.3, 5.0 Hz), 6.39 (d,1H, J¼5.0 Hz), 6.94 (mc, 2H), 7.23 (mc, 2H). 13
C
4.3.14. 4,5-Dimethyl-3-(pent-1-oxy)-thiazole-2(3H)-thione
(6c). From pentyl tosylate (242 mg, 1.00 mmol). The crude product
was purified by column chromatography [petroleum ether/Et2O¼2:1
(v/v)]. Yield: 178 mg (0.77 mmol, 77%), colorless oil. Rf¼0.28 [pe-
NMR (CDCl3, 100 MHz) d 12.5 (4-CH3), 20.6, 20.7, 20.8, 55.4 (OCH3),
63.2, 69.5, 70.2, 82.4, 104.4, 114.5,118.8 (C5), 122.5, 130.0, 133.0 (C4),
160.0, 169.6 (C]O), 170.2 (C]O), 170.3 (C]O), 179.3 (C2). Anal.
Calcd for C22H25NO9S2 (511.56): C, 51.65; H, 4.93; N, 2.74; S, 12.53;
Found: C, 51.03; H, 5.11; N, 2.72; S, 12.49.
troleum ether/Et2O¼2:1 (v/v)]. 1H NMR (CDCl3, 250 MHz)
d 0.93 (t,
3H, J¼7.1 Hz), 1.31–1.53 (m, 4H), 1.82 (mc, 2H), 2.12 (s, 3H, 4-CH3),
2.18 (s, 3H, 5-CH3), 4.37 (t, 2H, J¼6.7 Hz). 13C NMR (CDCl3, 63 MHz)
4.3.10. 4-Methyl-3-(pent-1-oxy)-5-phenylthiazole-2(3H)-thione
(5c). From pentyl tosylate (242 mg, 1.00 mmol). The crude product
d 11.0 (4-CH3), 12.0 (5-CH3), 13.9, 22.5, 27.5, 27.8, 76.2, 114.4 (C5),
132.6 (C4), 178.3 (C2). UV (EtOH) lmax (lg 3
/m2 molꢀ1) 320 nm (3.13).

1372
J. Hartung et al. / Tetrahedron 66 (2010) 1365–1374
Anal. Calcd for C10H17NOS2 (231.37): C, 51.91; H, 7.41; N, 6.05; S,
27.71; Found: C, 52.13; H, 7.32; N, 6.11; S, 27.63.
consumption (TLC), additional small portions of AIBN were added
(spatula tip) until the starting material was completely consumed.
4.3.15. 4,5-Dimethyl-3-(4-phenylbut-1-oxy)-thiazole-2(3H)-thione
(6d). From 4-phenylbutyl tosylate (304 mg, 1.00 mmol). The crude
product was purified by column chromatography [petroleum ether/
Et2O¼2:1 (v/v)]. Yield: 223 mg (0.76 mmol, 76%), colorless oil.
Rf¼0.29 [petroleum ether/Et2O¼2:1 (v/v)]. 1H NMR (CDCl3,
4.5. 3-Alkoxythiazolthione reactions with BrCCl3
4.5.1. Conversion of 5-(p-methoxyphenyl)-4-methyl-3-(pent-1-oxy)-thi-
azole-2(3H)-thione (4c). 4.5.1.1. Analytic scale experiments. Reactants:
4c (16.1 mg, 50.0
(1 mL). According to procedure 4.4.2.A: Yield: 1.8 mg (21 %) of 4-bro-
mopentan-1-ol (11). 1H NMR (C6D6, 250 MHz)
1.29–1.68 (m, 7H), 3.21
mmol), BrCCl3 (98.8 mg, 500 mmol, 50 mL) in C6D6
250 MHz)
d
1.84 (mc, 4H), 2.11 (q, 3H, J¼0.9 Hz, 4-CH3), 2.16 (q, 3H,
J¼0.9 Hz, 5-CH3), 2.70 (t, 2H, J¼7.1 Hz), 4.38 (t, 2H, J¼6.0 Hz), 7.33–
7.14 (m, 5H). 13C NMR (CDCl3, 63 MHz)
11.0 (4-CH3), 12.0 (5-CH3),
27.4, 27.5, 35.5, 75.8, 114.4 (C5), 125.9, 128.3, 128.4, 132.5 (C4), 141.0,
178.3 (C2). UV (EtOH) lmax (lg
/m2 molꢀ1) 321 nm (2.98). Anal.
d
d
(t, 2H, J¼7.0 Hz), 3.77 (sext, 1H, J¼6.9 Hz). 7.4 mg (42%) of 5-(p-
methoxyphenyl)-4-methyl-2-(trichloromethylsulfanyl)-thiazole (13).
According to procedure 4.4.2.B: Yield: 1.4 mg (17%) of 11 and 7.7 mg
(44%) of 13. According to procedure 4.4.2.C: Yield: 7.7 mg (92%) of 11
and 16.7 mg (94%) of 13.
3
Calcd for C15H19NOS2 (293.44): C, 61.40; H, 6.53; N, 4.77; S, 21.85;
Found: C, 60.95; H, 6.41; N, 4.67; S, 21.75.
4.3.16. (ꢂ)-4,5-Dimethyl-3-(2-phenylpent-4-en-1-oxy)-thiazole-
2(3H)-thione (ꢂ)-(6e). From (ꢂ)-2-phenyl-4-penten-1-yl tosylate
(316 mg, 1.00 mmol). The crude product was purified by column
chromatography [petroleum ether/Et2O¼2:1 (v/v)]. Yield: 247 mg
(0.81 mmol, 81%), colorless oil. Rf¼0.36 [petroleum ether/Et2O¼2:1
4.5.1.2. Preparative scale experiment. Reactants: 4c (161 mg,
500 mmol), BrCCl3 (988 mg, 5.00 mmol, 0.49 mL), AIBN in C6H6
(6.00 mL). According to procedure 4.4.2.C. The solvent was evapo-
rated under reduced pressure and the reaction mixture purified by
column chromatography [petroleum ether/Et2O¼2:1 (v/v)]. Yield:
72.4 mg (87%) of 11 and 158 mg (89%) of 13, yellowish powder. Mp
61–62 ꢁC (dec). Rf¼0.45 [petroleum ether/Et2O¼2:1 (v/v)]. 1H NMR
(v/v)]. 1H NMR (CDCl3, 250 MHz)
d
1.82 (q, 3H, J¼0.9 Hz, 4-CH3),
2.06 (q, 3H, J¼0.9 Hz, 5-CH3), 2.51 (mc, 1H), 2.70 (mc, 1H), 3.25
(dddd, 1H, J¼8.5, 7.5, 6.4, 6.3 Hz), 4.41 (t, 1H, J¼7.5 Hz), 4.68 (dd, 1H,
J¼7.5, 6.4 Hz), 4.95–5.10 (m, 2H), 5.74 (mc, 1H), 7.20–7.37 (m, 5H).
(CDCl3, 600 MHz)
d 2.57 (s, 3H, 4-CH3), 3.86 (s, 3H, OCH3), 6.89 (d,
2H, J¼8.5 Hz), 7.41–7.49 (d, 2H, J¼8.8 Hz). 13C NMR (CDCl3,
13C NMR (CDCl3, 63 MHz)
d
10.5 (4-CH3), 11.9 (5-CH3), 36.5, 44.3,
150 MHz) d 16.4 (4-CH3), 55.5 (OCH3), 97.3 (SCCl3), 114.5, 123.1 (C5),
79.0, 114.3 (C5), 117.1, 127.0, 128.0, 128.5, 132.6, 135.4 (C4), 140.8,
130.6, 141.7, 149.9 (C4), 150.4 (C2), 160.1. UV (MeOH) lmax (lg 3/
178.3 (C2). UV (EtOH) lmax (lg
3
/m2 molꢀ1) 321 nm (3.32). Anal.
m2 molꢀ1) 324 nm (3.44), 227 nm (3.36), 203 nm (3.62). MS (EI) m/z
359 (1), 357 (7), 355 (19), 353 (18), 321 (3), 319 (4), 248 (8), 238 (10),
236 (100), 203 (27),192 (17),179 (5),177 (38),160 (21),145 (26),134
(8), 121 (3), 119 (5), 117 (5), 108 (10). Anal. Calcd for C12H10NOS2Cl3
(354.69): C, 40.64; H, 2.84; N, 3.95; S, 18.06; Found: C, 40.81; H,
2.99; N, 3.90; S, 18.51.
Calcd for C16H19NOS2 (305.45): C, 62.92; H, 6.27; N, 4.59; S, 20.99;
Found: C, 62.87; H, 6.45; N, 4.35; S, 20.50.
4.3.17. (ꢂ)-4,5-Dimethyl-3-(cis-2-methylcyclopent-1-oxy)-thiazole-
2(3H)-thione (ꢂ)-cis-(6k). From (ꢂ)-trans-2-methylcyclopentyl
tosylate (254 mg, 1.00 mmol). The crude product was purified by
column chromatography [petroleum ether/Et2O¼2:1 (v/v)]. Yield:
157 mg (0.65 mmol, 65%), colorless oil. Rf¼0.41 [petroleum ether/
4.5.2. Conversion of 5-(p-methoxyphenyl)-4-methyl-3-(4-phenylbut-
1-oxy)-thiazole-2(3H)-thione (4d). 4.5.2.1. Analytic scale experi-
Et2O¼2:1 (v/v)]. 1H NMR (CDCl3, 250 MHz)
d
1.24 (d, 3H, J¼7.0 Hz),
ments. Reactants: 4d (17.8 mg, 50.0
500 mol, 50 L) in C6D6 (1 mL). According to procedure 4.4.2.A:
Yield: 0.7 mg (3.0
mmol), BrCCl3 (98.8 mg,
1.51–1.64 (m, 1H), 1.64–1.76 (m, 2H), 1.79–1.94 (m, 3H), 2.11 (q, 3H,
m
m
J¼0.8 Hz, 4-CH3), 2.13 (q, 3H, J¼0.8 Hz, 5-CH3), 2.12–2.18 (m, 1H),
mmol, 6%) of 4-bromo-4-phenyl-1-butanol (12),
5.57 (dt, 1H, J¼4.7, 2.2 Hz). 13C NMR (CDCl3, 63 MHz)
d
11.3 (4-CH3),
Rf¼0.12 [petroleum ether/Et2O¼2:1 (v/v)]. 1H NMR (C6D6, 400 MHz)
12.1 (5-CH3), 13.5, 21.8, 29.4, 31.4, 39.2, 89.5, 114.4 (C5), 134.0 (C4),
d
1.18–1.47 (m, 2H), 1.91–2.20 (m, 2H), 3.18 (t, 2H, J¼6.2 Hz), 4.71 (t,
178.9 (C2). UV (EtOH) lmax (lg
3
/m2 molꢀ1) 321 nm (3.22). Anal.
1H, J¼7.6 Hz), 6.94–7.10 (m, 5H). 13C NMR (C6D6, 100 MHz)
d 31.6,
Calcd for C11H17NOS2 (243.38): C, 54.29; H, 7.04; N, 5.76; S, 26.35;
Found: C, 54.21; H, 7.28; N, 5.61; S, 26.12.
36.9, 55.8 (C-Br), 61.5, 121.4, 127.6, 128.1, 131.1. According to pro-
cedure 4.4.2.B: Yield: 0.6 mg (5%) of 12. According to procedure
4.4.2.C: Yield: 10.4 mg (91%) of 12 and 16.5 mg (93%) of 13.
4.4. Radical reactions
4.5.2.2. 2-Phenyltetrahydrofuran (16). From a solution of 4-
methyl-5-(p-methoxyphenyl)-3-(4-phenyl-1-butoxy)-thiazole-
4.4.1. General remarks. Product analysis was performed via 1H
NMR. Yields were determined via integration of 1H NMR signals
2(3H)-thione (4d) (17.8 mg, 50.0
mmol), BrCCl3 (98.8 mg, 500 mmol,
versus anisole (
d
3.29 ppm; C6D6, 400 MHz) as internal standard.
50 L), and AIBN in C6H6 (1 mL). According to procedure 4.4.2.C.
m
The crude product was filtered through basic Al2O3 and eluted with
Et2O. The filtrate was concentrated under reduced pressure to
furnish 6.2 mg (83%) of 16.
4.4.2. Standard procedures. Bu3SnH (3.7 equiv) or BrCCl3 (10.0 equiv)
was added under Ar to an oxygen-free solution of 3-alkoxythiazole-
2(3H)-thione 4, 5, or 6 in anhydrous C6D6 or C6H6 (20 mL/1.0 mmol
thiazolethione; standard glassware).
4.5.3. Conversion of (ꢂ)-5-(p-methoxyphenyl)-4-methyl-3-[cis-2-
A. Photochemical reaction I (
l
¼350 nm). The reaction mixture
(prop-2-en-1-yl)cyclohexyl-1-oxy]-thiazole-2(3H)-thione
(ꢂ)-cis-
was photolyzed for 30 min at 20 ꢁC in a Southern New England
RayonetÒ chamber photo reactor equipped with 350 nm light
bulbs.
(4l). Reactants: (ꢂ)-cis-4l (188 mg, 500
mmol), BrCCl3 (988 mg,
5.00 mmol, 0.49 mL) in C6H6 (6.00 ml). According to procedure
4.4.2.A. The solvent was evaporated under reduced pressure and
the residue purified by chromatography [petroleum ether/
Et2O¼5:1 (v/v)]. Yield: 76.7 mg (70%) of 8-bromomethyl-7-oxabi-
cyclo[4.3.0]nonane (ꢂ)-(21), 6,8-cis:6,8-trans¼72:28, Rf¼0.77 [pe-
troleum ether/Et2O¼5:1 (v/v)].
B. Photochemical reaction II (visible light). The reaction mixture
was photolyzed with external cooling for 30 min at 15 ꢁC with
a 250 W Osram Power Star HQI/D discharge lamp (visible light
spectrum).
C. Thermal reaction. AIBN (5.00 mg, 30.4 mmol/1.0 mmol thia-
zolethione) was added under Ar to the boiling reaction mixture. If
N2 evolution ceased prior to quantitative 3-alkoxythiazolethione
4.5.4. Conversion of 4-methyl-3-(pent-1-oxy)-5-phenylthiazole-
2(3H)-thione (5c). Reactants: 5c (14.7 mg, 50.0 mmol), BrCCl3

J. Hartung et al. / Tetrahedron 66 (2010) 1365–1374
1373
(98.8 mg, 500
m
mol, 50
m
L), and AIBN in C6D6 (1 mL). According to
(56%) of 1,2,4-tri-O-acetyl-
D
-erythritol (24), yellowish oil, Rf¼0.16
procedure 4.4.2.C: Yield: 6.8 mg (81%) of 11 and 14.5 mg (90%) of
4-methyl-5-phenyl-2-(trichloromethylsulfanyl)-thiazole (14), yel-
lowish oil. Rf¼0.59 [petroleum ether/Et2O¼2:1 (v/v)]. 1H NMR
[methyl tert-butyl ether/pentane¼1:1 (v/v)]. 1H NMR (CDCl3,
600 MHz)
d 2.09 (s, 3H), 2.10 (s, 3H), 2.11 (s, 3H), 3.97 (ddd, 1H,
J¼7.8, 5.3, 3.5 Hz), 4.16 (dd, 1H, J¼11.8, 5.3 Hz), 4.21 (dd, 1H,
J¼11.8, 3.5 Hz), 4.32 (dd,1H, J¼12.4, 4.7 Hz), 4.42 (dd, 1H, J¼12.4,
3.2 Hz), 5.02 (ddd, 1H, J¼7.8, 4.7, 3.2 Hz). 13C NMR (CDCl3,
(CDCl3, 400 MHz)
(CDCl3, 150 MHz)
d
2.60 (s, 3H, 4-CH3), 7.41–7.49 (m, 5H). 13C NMR
16.5 (4-CH3), 97.2 (SCCl3), 128.9 (C5), 129.1,
d
129.4, 130.9, 141.6, 150.8 (C4), 151.0 (C2). UV (MeOH) lmax (lg
3/
63 MHz) d 20.8, 20.9, 62.3, 65.0, 68.3, 71.1, 170.0, 171.2, 171.3. MS
m2 molꢀ1) 310 nm (3.46). [C11H8NOS2Cl3 (324.66)] MS (EI) m/z 329
(1), 327 (10), 325 (29), 323 (24), 290 (7), 288 (10), 218 (6), 206 (100),
173 (16), 162 (10), 147 (86), 130 (37), 121 (36), 119 (12), 117 (13), 115
(84), 103 (34).
(EI) m/z 145 (53), 128 (10), 115 (100), 103 (73). Anal. Calcd for
C10H16O7 (248.23): C, 48.58; H, 6.12; Found C, 48.52; H, 5.71.
4.6.4. Conversion of (ꢂ)-4-methyl-5-phenyl-3-(2-phenylpent-4-en-
1-oxy)-thiazole-2(3H)-thione (ꢂ)-(5e). Reactants: (ꢂ)-5e (18.4 mg,
4.5.5. Conversion of 4,5-dimethyl-3-(pent-1-oxy)-thiazole-2(3H)-
50.0 mmol), Bu3SnH (53.8 mg, 185.0 mmol, 50 mL), and AIBN in
thione (6c). Reactants: 6c (11.6 mg, 50.0
m
mol), BrCCl3 (98.8 mg,
C6D6 (1 mL). According to procedure 4.4.2.C: Yield: 5.0 mg (62%)
of 2-methyl-4-phenyltetrahydrofuran (ꢂ)-17, cis:trans¼87:13 and
19.9 mg (76%) of 4-methyl-5-phenyl-2-(tributylstannylsulfanyl)-
500 mol, 50 L), and AIBN in C6D6 (1 mL). According to procedure
m
m
4.4.2.C: Yield: 6.43 mg (77%) of 11 and 11.5 mg (88%) of 4,5-di-
methyl-2-(trichloromethylsulfanyl)-thiazole (15), yellowish oil.
Rf¼0.51 [petroleum ether/Et2O¼2:1 (v/v)]. 1H NMR (CDCl3,
thiazole (19). 1H NMR (CDCl3, 200 MHz)
d
0.87–0.94 (t, 9H,
J¼7.1 Hz), 1.26–1.44 (m, 12H), 1.55–1.67 (m, 6H), 2.36 (s, 3H, 4-
CH3), 7.30–7.41 (m, 5H). 13C NMR (CDCl3, 50 MHz)
13.6, 16.0 (4-
400 MHz)
150 MHz)
(C4), 152.1 (C2). UV (MeOH) lmax (lg
d
d
2.44 (s, 3H, 4-CH3), 2.45 (s, 3H, 5-CH3). 13C NMR (CDCl3,
11.9 (4-CH3), 15.0 (5-CH3), 97.4 (SCCl3), 136.8 (C5), 148.7
d
CH3), 27.0, 27.9, 28.6, 127.2 (C5), 128.5, 128.9, 132.0, 132.5, 146.7
(C4), 162.1 (C2).
3
/m2 molꢀ1) 295 nm (2.90),
224 nm (2.60), 202 nm (2.68). [C6H6NOS2Cl3 (262.60)] MS (EI) m/z
265 (11), 263 (12), 261 (3), 228 (14), 226 (18), 144 (100), 121 (2), 119
(8), 117 (9), 100 (17).
4.6.5. Conversion of (ꢂ)-4-methyl-3-(cis-2-methylcyclopentoxy)-5-
phenylthiazole-2(3H)-thione (ꢂ)-cis-(5k). Reactants: (ꢂ)-cis-(5k)
(15.3 mg, 50.0 mmol), Bu3SnH (53.8 mg, 185.0 mmol, 50 mL) in C6D6
4.6. 3-Alkoxythiazolthione reactions with Bu3SnH
(1 mL). According to procedure 4.4.2.A: Yield: 3.10 mg (66%) of 22
and 20.6 mg (79%) of 19.
4.6.1. Conversion of (ꢂ)-5-(p-methoxyphenyl)-4-methyl-3-(2-phenyl-
pent-4-en-1-oxy)- thiazole-2(3H)-thione (ꢂ)-(4e). Reactants: (ꢂ)-4e
4.6.6. Conversion of (ꢂ)-4,5-dimethyl-3-(2-phenylpent-4-en-1-oxy)-
thiazole-2(3H)-thione (ꢂ)-(6e). Reactants: (ꢂ)-6e (15.3 mg,
(19.9 mg, 50.0 mmol), Bu3SnH (53.8 mg, 185.0 mmol, 50 mL) in C6D6
(1 mL). According to procedure 4.4.2.A: Yield: 5.1 mg (63%) of 2-
methyl-4-phenyltetrahydrofuran (ꢂ)-(17), cis:trans¼87:13, and
21.2 mg (77%) of 5-(p-methoxyphenyl)-4-methyl-2-(tributyl-
stannylsulfanyl)-thiazole (18), colorless oil, Rf¼0.45 [petroleum
ether/Et2O¼5:1 (v/v)]. According to 4.4.2.B: Yield: 4.8 mg (59%) of
(ꢂ)-17, cis:trans¼86:14, and 21.6 mg (78%) of 18. According to
4.4.2.C: Yield: 5.2 mg (64%) of (ꢂ)-17, cis:trans¼87:13, and 21.2 mg
(77%) of 18.
50.0 mmol), Bu3SnH (53.8 mg, 185.0 mmol, 50 mL), and AIBN in C6D6
(1 mL). According to procedure 4.4.2.C: Yield: 5.0 mg (61%) of
(ꢂ)-17, cis:trans¼87:13 and 17.0 mg (78%) of 4,5-dimethyl-2-(tri-
butylstannylsulfanyl)-thiazole-2(3H)-thione (20). 1H NMR (CDCl3,
400 MHz)
6H), 2.16 (s, 3H, 4-CH3), 2.22 (s, 3H, 5-CH3). 13C NMR (CDCl3,
50 MHz) 11.2 (4-CH3), 13.6, 14.4 (5-CH3), 27.0, 27.8, 28.6, 126.3
d 0.87–0.92 (m, 9H), 1.22–1.36 (m, 12H), 1.54–1.61 (m,
d
(C5), 147.1 (C4), 159.2 (C2).
4.6.2. Conversion
[cis-(2-methylcyclopent-1-oxy)]-thiazole-2(3H)-thione
(4k). Reactants: (ꢂ)-cis-(4k) (16.8 mg, 50.0 mol), Bu3SnH
(53.8 mg, 185 mol, 50 L) in C6D6 (1 mL). According to pro-
cedure 4.4.2.A: Yield: 3.9 mg (77%) of hexanal (22). 1H NMR
(C6D6, 250 MHz)
(dt, 2H, Jt¼7.3 Hz, Jd¼1.7 Hz), 9.30 (t, 1H, J¼1.7 Hz), and 22.6 mg
(82%) of 18. According to 4.4.2.B: 3.9 mg (78%) of 22 and 22.1 mg
(80%) of 18. According to 4.4.2.C: Yield: 3.3 mg (65%) of 22 and
22.9 mg (83%) of 18.
of
(ꢂ)-5-(p-methoxyphenyl)-4-methyl-3-
4.6.7. Conversion of (ꢂ)-4,5-dimethyl-3-(cis-2-methylcyclopent-1-
oxy)-thiazole-2(3H)-thione (ꢂ)-cis-(6k). Reactants: (ꢂ)-cis-(6k)
(ꢂ)-cis-
m
(12.2 mg, 50.0 mmol), Bu3SnH (53.8 mg, 185.0 mmol, 50 mL) in C6D6
m
m
(1 mL). According to procedure 4.4.2.C: Yield: 3.6 mg (71%) of 22
and 17.6 mg (81%) of 20.
d
0.77 (t, 3H, J¼7.3 Hz), 1.19–1.39 (m, 6H), 1.78
Acknowledgements
This work was supported by the Deutsche For-
schungsgemeinschaft (Grant Ha1705/3–3) and is part of Ph.D.
theses of C.S., I.K., and T.G.
4.6.3. Conversion of 5-(p-methoxyphenyl)-4-methyl-3-(2,3,5-tri-O-ace-
tyl-
a
-
D
-ribofuranosyl-1-oxy)-thiazole-2(3H)-thione
a-(4m). Reactants:
Supplementary data
a
-4m (256 mg, 500
m
mol), Bu3SnH (538 mg, 1.85 mmol, 0.49 mL)
in C6H6 (10 mL). According to procedure 4.4.2.A. After complete
substrate consumption (TLC), the solvent was distilled off under
reduced pressure to furnish a residue that consisted of a 3/1-
mixture of formylester 23/erythritol 24. Erythro-butan-1,2,3,4-
tetrayl 1,2,4-triacetate-3-formate (23). Rf¼0.29 [tert-butyl methyl
Instrumentation, spectra of 3-alkoxythiazolethione
a-4m, tri-
chloromethylsulfanylthiazoles 13–15, tributylstannylsulfanylth-
iazoles 19–20, formylester 23, and erythritol 24 (7 pages).
Supplementary data associated with this article can be found in the
online version at doi:10.1016/j.tet.2009.11.113.
ether/pentane¼1:1 (v/v)]. 1H NMR (CDCl3, 600 MHz)
d 2.00 (s,
6H), 2.02 (s, 3H), 4.10 (dd, 1H, J¼12.3, 5.5 Hz), 4.16 (dd, 1H,
J¼12.4, 5.9 Hz), 4.29 (ddd, 2H, J¼12.3, 7.9, 3.3 Hz), 5.20 (dt, 1H,
J¼5.9, 3.4 Hz), 5.34 (dt, 1H, J¼6.1, 3.2 Hz), 8.01 (s 1H). 13C NMR
References and notes
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