1,3-Dithiane-derived alkoxyamines as one-carbon radical precursors

Article abstract of DOI:10.1055/s-2005-865288

A new method for the generation of C-2 centered radicals derived from 1,3-dithiane is presented. The radical precursors, 2-dialkylaminoxyl-1,3- dithianes, are readily prepared from 1,3-dithiane and stable nitroxides. Thermal reaction of 2-dialkylaminoxyl-1,3-dithianes with electron-deficient olefins affords carboaminoxylation products oroxidative addition products depending on the nitroxide used. The 2-dialkylaminoxyl-1,3-dithianes can also be used as initiators/regulators for the controlled living free radical polymerization of styrene. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-865288

PAPER
1389
1,3-Dithiane-Derived Alkoxyamines as One-Carbon Radical Precursors
1
, 3-Dithiane-Deriv
n
ed
A
lkoxyam
t
ines
a
o
s
One-Carbo
n
n Radica
l
Pr
i
e
cursor
o
s
J. Herrera, Armido Studer*
Organisch Chemisches Institut, Westfälische Wilhelms-Universität, Corrensstraße 40, 48149 Münster, Germany
Fax +49(251)8336523; E-mail: studer@uni-muenster.de
Received 15 February 2005
Dedicated to Prof. Dr. Bernd Giese
Ph
Abstract: A new method for the generation of C-2 centered radi-
O
cals derived from 1,3-dithiane is presented. The radical precursors,
2-dialkylaminoxyl-1,3-dithianes, are readily prepared from 1,3-
dithiane and stable nitroxides. Thermal reaction of 2-dialkylami-
noxyl-1,3-dithianes with electron-deficient olefins affords car-
boaminoxylation products or oxidative addition products depending
on the nitroxide used. The 2-dialkylaminoxyl-1,3-dithianes can also
be used as initiators/regulators for the controlled living free radical
polymerization of styrene.
S
S
S
S
S
S
O
Se
Ph
O
R
S
S
N
N
R
OEt
1
2
3
4
Figure 1 One-carbon radical precursors
Key words: radical chemistry, nitroxides, 1,3-dithianes, controlled
radical polymerization, microwaves
cals cannot be generated via this approach. For example,
the activation energy for the C–O bond homolysis in
alkoxyamine 3 (Figure 1) is 150.5 kJ/mol and therefore
too high for clean thermal bond homolysis.10 We assumed
that 1,3-dithiane-derived alkoxyamines may offer a for-
mal entry into long-lived acyl radicals using our method-
ology. Herein we present results on the use of
alkoxyamines of type 4 (Figure 1) as one-carbon radical
precursors in intermolecular addition reactions. More-
over, we show that these alkoxyamines can be applied as
initiator/mediatiors for nitroxide-mediated styrene poly-
merization.11
1,3-Dithianes derived from aldehydes and ketones have
become highly important in synthetic organic chemistry
over the past 50 years.1 Aldehyde derived dithianes are
generally used as umpoled carbonyl groups in ionic chem-
istry.2 The intrinsic electrophilic behavior of an aldehyde
carbonyl carbon atom can be altered upon transformation
into the corresponding 1,3-dithiane and subsequent lithia-
tion. These lithiated 1,3-dithianes are nucleophilic acyl
equivalents, which efficiently react with various electro-
philes. Along with the umpolung, dithianes have found
widespread application as protecting groups in organic
synthesis.3
Acyl radicals are known to undergo fast decarbonylation.4
Slow radical reactions using acyl radicals are therefore not
possible. Dithiane chemistry may offer an answer to this
problem. To our surprise, only a few reports on the use of
1,3-dithianes as one-carbon radical precursors have ap-
peared in the literature to date. Byers showed that Se-sub-
stituted dithiane 1 (Figure 1) can be used in Se-group
transfer chemistry.5 Very recently, Zard reported on the
use of xanthate 2 (Figure 1) as a C-radical precursor.6 In
addition, 1,3-dithiane-derived radicals have also been
used in cyclization reactions.7 All these studies showed
that these C-radicals are nucleophilic and react efficiently
only with activated electron-deficient olefins.
TEMPO-derived dithiane 5 was readily prepared from
1,3-dithiane via lithiation and oxidation using TEMPO. In
this reaction TEMPO acts as oxidant and as C-radical
trapping reagent. Alkoxyamine 5 was isolated in 80%
yield (Scheme 1).
S
S
1) BuLi, DME, –30 °C
O
N
S
S
2) TEMPO (2.2 equiv)
–78 °C
N
O
= TEMPO
5 (80%)
Scheme 1 Synthesis of alkoxyamine 5
We have recently shown that alkoxyamines derived from
persistent nitroxides can be used as C-radical precursors
in cyclization and intermolecular addition reactions.8
Thermal reversible C–O bond homolysis delivers effi-
ciently C-radicals. These processes are controlled by the
persistent radical effect (PRE).9 Unfortunately, acyl radi-
Radical additions were first studied using n-butyl acrylate
as a radical acceptor. Reaction of 5 in DMF (0.07 M) with
5 equivalents of olefin at 135 °C for 18 hours provided a
1:1 mixture of dithiane 6 and TEMPO-adduct 7 in 16%
combined yield (Scheme 2; Table 1, run 1). We found that
alkoxyamine 5 is not perfectly stable under the applied
conditions. Dithioketeneacetal 6 results from carboami-
noxylation of n-butyl acrylate (→ 8) with subsequent
SYNTHESIS 2005, No. 9, pp 1389–1396
x
x
.
x
x
.2
0
0
5
Advanced online publication: 07.04.2005
DOI: 10.1055/s-2005-865288; Art ID: C00605SS
© Georg Thieme Verlag Stuttgart · New York

1390
A. J. Herrera, A. Studer
PAPER
elimination12 of TEMPOH to give 9, which eventually PO-acrylonitrile adduct was formed in 12% yield. Obvi-
isomerizes to 6. The side product 7 is probably formed via ously, Et3N retards TEMPOH-elimination. Similar results
TEMPO-radical addition onto n-butyl acrylate with sub- were obtained for the reaction of 5 with N,N-dimethyl-
sequent reduction.13 Reaction in ClCH2CH2Cl at 120 °C acrylamide. In the amine-free experiment, 12 was ob-
afforded 6 as the sole product in 33% yield (run 2). Addi- tained in 70% yield along with carboaminoxylation
tion is even less efficient in toluene (run 3). In order to compound 13. As above, the experiment conducted in the
succeed, reaction in toluene was conducted at higher con- presence of Et3N delivered more of the carboaminoxyla-
centration.
tion compound. Reaction of 5 with methyl methacrylate
gave oxidative addition product 15 in moderate yield as
the only regioisomer. In the presence of Et3N, compound
15 was obtained in 49% yield. In addition, olefin 14 was
formed in 19% yield. Hence, Et3N influences the regiose-
lectivity of the TEMPOH-elimination. Reaction with a-
methyl styrene showed no amine effect. The regioisomers
16 and 17 were isolated in 53% or 56% combined yield
(without or with Et3N, respectively). Regioselective elim-
ination was obtained for the carboaminoxylation/elimina-
tion reaction using styrene. Isomerization of the double
bond was not observed. Styrene derivative 18 was isolated
in 49% yield using Et3N as an additive. The amine-free
process provided 18 in lower yield (22%).
Encouraged by our recent results on microwave induced
alkoxyamine additions we decided to repeat the experi-
ments under microwave conditions.14,15 Reaction of 5
with n-butyl acrylate in DMF at 170 °C for 9 min provided
6 and 7 in 47% combined yield (run 4). Interestingly, run-
ning the experiment in the presence of Et3N (1.5 equiv)
under otherwise identical conditions yielded 6 as the sole
product in 72% yield (run 5). Microwave experiments in
o-Cl2C6H4 and in DMSO were less efficient (runs 6 and
7). Therefore, the following experiments were conducted
in DMF.
CO2Bu
(5 equiv)
N
O
S
+
5
R
N
CO2Bu
S
N
CO2Bu
S
(5 equiv)
S
O
5
+
7
6
0.07 M, 170 °C
10 min, MW
S
R
S
R
11 (R = CN)
10 (R = CN)
12 (R = CONMe2)
13 (R = CONMe2)
S
O
S
–
without Et3N
1.2 equiv Et3N
without Et3N
1.5 equiv Et3N
82% (10)v
64% (10)v
65% (12)v
30% (12)v
v
12% (11)v
15% (13)v
28% (13)v
S
CO2Bu
S
CO2Bu
8
9
Scheme 2 Oxidative addition of 5 onto n-butyl acrylate
CO2Me
(5 equiv)
S
Table 1 Reaction of 5 with n-Butyl Acrylate under Different Con-
ditions
S
5
+
0.07 M, 170 °C
10 min, MW
S
CO2Me
S
CO2Me
Run Temp
(°C)
Time
c [M]
Solvent
6
(%)
7
(%)
15
14
33%v
without Et3N
–
v
49% v
1.2 equiv Et3N
19% v
1
130
120
120
170
170
180
170
18 h
38 h
21 h
0.07
0.07
1.00
DMF
8
33
12
34
72
39
33
8
–
R
2
ClCH2CH2Cl
toluene
DMF
Ph
(5 equiv)
S
R
3
21
13
–
S
5
+
4a
5a
6a
7a
9 min 0.07
8 min 0.07
8 min 0.07
14 min 0.07
0.07 M, 170 °C
10 min, MW
S
Ph
S
Ph
DMFb
16 (R = Me)
18 (R = H)
1
7
DMSOb
o-Cl2C6H4
10
–
36%v
39% v
without Et3N
1.2 equiv Et3N
17% (16)v
17% (16)v
without Et3N
1.2 equiv Et3N
22% (18)v
49% (18)v
a Microwave-induced heating.
b Et3N (1.5 equiv) was added.
Scheme 3 Oxidative addition of 5 – variation of the olefin
Microwave-induced addition of 5 onto acrylonitrile pro-
vided the oxidative addition isomerization product 10 in a
high yield (82%, Scheme 3). In the presence of Et3N un-
der otherwise identical conditions 10 was isolated in 64%
along with 12% of carboaminoxylation product 11. TEM-
As expected,5,6 addition of 5 to electron rich olefins such
as butyl vinyl ether or 1-octene did not work. Zard showed
that oxidation of dithiane 2 to the corresponding mono
sulfoxide can readily be accomplished. Moreover the ox-
idized xanthate delivers far more reactive one-carbon-
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PAPER
1,3-Dithiane-Derived Alkoxyamines as One-Carbon Radical Precursors
1391
centered radicals than the parent dithiane 2.6 Therefore we
prepared alkoxyamine 19 (Scheme 3). m-Chloroperben-
zoic acid treatment of dithiane 5 afforded monosulfoxide
19 as a 5.8:1 mixture of diastereoisomers. The isomers
were separated by chromatography. The relative configu-
ration was not assigned. Unfortunately, both isomers of
alkoxyamine 19 turned out to be highly unstable under the
applied conditions. Attempted carboaminoxylation of n-
butyl acrylate and 1-octene using 19 failed (both isomers
were tested).
OMe
N
(5 equiv)
R
S
O
22
ClCH2CH2Cl (1 M)
Et3N (1.5 equiv)
115 °C, 1.5 h
S
R
23 (92%, R = CN)
24 (44%, R = CO2Bu)
OMe
We have previously shown that the nitroxide structure
heavily influences the outcome of nitroxide-mediated rad-
ical additions.16 Based on these results we prepared
alkoxyamine 22 from dithiane and nitroxide 21
(Scheme 4). Sterically highly hindered nitroxide 21 was
readily prepared from known nitroxide 20.17
N
O
1-octene (5 equiv)
23, 24
ClCH2CH2Cl (1 M)
135 °C, 1d
S
C6H13
S
R
25 (40%, R = CN)
26 (56%, R = CO2Bu)
Scheme 5 Carboaminoxylations using alkoxyamines 22
S
S
S
S
O
MCBPA
O
N
O
N
with 1-octene16 to provide alkoxyamines 25 and 26 in
good yields (25: 40%; 26: 56%).
CH2Cl2, 0 °C
Moreover, we tested whether alkoxyamine 5 can be used
as initiator/regulator for the controlled living radical poly-
merization of styrene.11 Polymerization was conducted in
a sealed tube using 1% of alkoxyamine initiator 5 at 125
°C and was stopped after 24 hours (neat styrene). The con-
version (61%) was determined gravimetrically. The poly-
dispersity index (PDI) and the molecular weight of the
polymer were analyzed using SEC (Mn = 6600 g/mol,
Scheme 6). The narrow PDI (1.12) obtained indicates that
controlled polymerization of styrene occurred. Important-
ly, the 1,3-dithiane-modified polystyrene should readily
be deprotonated using alkyl lithium bases. The corre-
sponding polymeric Li-derivative can then be used to ini-
tiate an anionic polymerization. Hence, 5 can be regarded
as radical and ionic polymerization initiator. Experiments
along this line are under way.
19 (90%)
5
O
OMe
1) LiAlH4, THF
2) NaH, MeI
N
O
N
O
20
21
S
S
1) BuLi, DME, –30 °C
O
N
S
S
2) 21 (2.2 equiv)
–78 °C
OMe
22 (55%)
Scheme 4 Synthesis of alkoxyamines 19 and 22
O
N
S
5 (1%)
n
Ph
Ph
S
Alkoxyamine 22 underwent highly efficient thermal addi-
tion onto acrylonitrile under conventional heating at 110
°C (Scheme 5). Product 23 was isolated in 92% yield. A
lower yield was obtained for the addition of 22 to n-butyl
acrylate (44%). Along with the desired carboaminoxyla-
tion product, telomers resulting from renewed addition of
24 onto n-butyl acrylate were observed (mainly contain-
ing 2 or 3 acrylate units). In order to decrease the propen-
sity of telomer formation, reaction was repeated with 1.1
equivalent of acrylate (115 °C). Unfortunately, formation
of telomers could not be completely suppressed. Car-
boaminoxylation product 24 was formed in 57% yield.
125 °C, 24 h
n
Mn = 6600 g/mol, PDI = 1.12
Scheme 6 Polymerization of styrene using alkoxyamine 5
Finally, we studied the kinetics of the C–O bond homoly-
sis for alkoxyamines 5 and 22. The kinetic experiments
were conducted in the EPR cavity in tert-butylbenzene in
the presence of oxygen at 403 K and 373 K for
alkoxyamines 5 and 22, respectively. Oxygen was used to
scavenge the 3-dithianyl radical and the concentration of
the released nitroxide was measured by EPR spectrosco-
py, as previously described.18 The activation energies Ea
were estimated from the experimentally determined rate
Guided by this unwanted side reaction we decided to
study controlled carboaminoxylations using adducts 23
and 24. To this end, alkoxyamines 23 and 24 were reacted
Synthesis 2005, No. 9, 1389–1396 © Thieme Stuttgart · New York

1392
A. J. Herrera, A. Studer
PAPER
aq solution of NH4Cl and extracted with Et2O. The organic phase
was washed with brine, dried over MgSO4 and concentrated in vac-
uo. The residue was purified by crystallization from CH2Cl2–MeOH
affording compound 5 (5.214 g, 18.96 mmol, 80%); crystalline sol-
id; mp 80–81 °C.
constants using the Arrhenius equation with A = 2.4 ×
1014 s–1.19
As expected, the sterically highly hindered alkoxyamine
22 shows a lower activation energy for C–O bond homol-
ysis than TEMPO-derivative 5 (Ea[5] = 136.9 kJmol–1,
Ea[22] = 127.5 kJmol–1). This is in agreement with the ad-
dition experiments where carboaminoxylation could be
performed at 90 °C using the efficient alkoxyamine 22
(acrylonitrile, 10 h, 58%). For TEMPO-alkoxyamine 5,
however, reaction was successful only at higher tempera-
tures (120 °C, see Table 1, runs 2 and 3). At 90 °C no ad-
dition product was observed using 5.
IR (film): 3001, 2972, 2925, 2865, 1479, 1381, 1264, 1238, 961,
886, 799 cm–1.
1H NMR (300 MHz, CDCl3): d = 5.63 (s, 1 H, CH), 3.22 (ddd, J1 =
J2 = 6.9 Hz, J3 = 13.9 Hz, 2 H, SCH2), 2.68 (ddd, J1 = J2 = 4.8 Hz,
J3 = 13.8 Hz, 2 H, SCH2), 2.08 (m, 2 H, SCH2CH2), 1.46 (br s, 6 H,
CCH2CH2CH2), 1.22 (br s, 12 H, 4 × CH3).
13C NMR (75 MHz, CDCl3): d = 85.7 (CH), 60.5 (C), 40.3 (CH2),
34.7 (CH3), 26.0 (2 × CH2), 25.2 (CH2), 20.4 (CH3), 17.0 (CH2).
MS (ESI): m/z = 298 [M + Na]+.
In conclusion, we have show that readily prepared 1,3-
dithiane derived alkoxyamines can be used as one-carbon
radical precursors in radical addition reactions. The nu-
cleophilic 1,3-dithane-2-yl radical reacts efficiently only
with electron-deficient olefins. Depending on the nitrox-
ide used, carboaminoxylation or oxidative addition of the
alkoxyamine is obtained. Microwave induced heating can
be applied to conduct these reactions in a short time. In ad-
dition, dithiane modified polystyrene with a narrow PDI
Anal. Calcd for C13H25NOS2: C, 56.68; H, 9.15; N, 5.08. Found: C,
56.68; H, 8.97; N, 5.02.
Oxidative Addition Reaction; General Procedure (GP 1)
A solution of 5, olefin and Et3N (in some cases) in degassed DMF
(0.07 M) was sealed off under Ar. The mixture was flash heated at
170 °C in a microwave oven for 8–25 min. The reaction mixture
was poured into an aq sat. solution of NH4Cl, extracted with Et2O
(2 ×), dried over MgSO4 and concentrated in vacuo. The crude
can be prepared using 5 as alkoxyamine initiator/regula- product was purified by flash chromatography on silica gel.
tor.
Oxidative Addition Reaction ; General Procedure (GP 2)
A solution of 5, olefin and Et3N (in some cases) in degassed DMF
1H NMR and 13C NMR spectra were recorded on Bruker AMX-400,
(0.07 M) was sealed off under Ar. The mixture was flash heated at
ARX-300 or Varian inova-500 spectrometers. TLC as performed by
using Merck silica gel coated aluminium 60 F254 plates; detection
with UV or dipping into a solution of KMnO4 (1.5 g in 400mL H2O,
5 g NaHCO3) or a solution of Ce(SO4)2·H2O (10 g), phosphomolyb-
dic acid hydrate (25 g), concd H2SO4 (60 mL) and H2O (940 mL).
Flash column chromatography was performed using Merck silica
gel 60 (40–63 mm) applying a pressure of about 0.4 bar. IR spectra
were obtained as a thin film smeared onto NaCl plates on a Bruker
IFS-28 spectrometer. Melting points were determined with a hot-
stage apparatus. Mass spectra were recorded as ESI–MS on a wa-
ters-micromass Quattro LC or a Bruker MicroTof instrument. Ele-
mental analyses were performed on an Elementar vario ELIII
instrument. Solvents were purified by standard methods. Air and
moisture sensitive compounds were handled under Ar using
Schlenk techniques. Size Exclusion Chromatography (SEC) was
carried out with THF as eluent at a flow rate of 1.0 mL/min at r.t. on
a system consisting of a L6200A Intelligent Pump (Merck Hitachi),
a set of two Plgel 5 mm MIXED-C columns (300 × 7.5 mm, Poly-
mer Laboratories), and a RI-101 detector (Shodex). Data were ac-
quired through a PL Datastream unit (Polymer Laboratories) and
analyzed with Cirrus GPC software (Polymer Laboratories) based
upon calibration curves built upon polystyrene standards (Polymer
Laboratories Polystyrene Medium MW Calibration Kit S-M-10)
with peak molecular weights ranging from 500–3000000 g/mol.
EPR spectra were recorder on a Bruker EMS 104 Analyzer. The ni-
troxide concentration was determined by double integration of the
EPR spectra and calibration with a TEMPO solution in tert-butyl-
benzene (0.1 mM).
170 °C in a microwave oven for 8–25 min. DMF and excess of ole-
fin were removed in vacuo. The crude product was purified by flash
chromatography on silica gel.
Butyl 3-(1,3-Dithian-2-ylidene)propanoate (6)20
According to GP1, compound 5 (156 mg, 0.567 mmol), n-butyl
acrylate (363 mg, 2.836 mmol), Et3N (86 mg, 0.85 mmol) in DMF
(8 mL) were employed for 8 min. Flash chromatography (pentane–
MTBE, 100:1) afforded 6 (100 mg, 0.406, 72%). Butyl 3-[(2,2,6,6-
tetramethyl-1-piperidinyl)oxy]propanoate (7) was obtained as a
side product if other conditions were applied (see text).
IR (film): 2599, 2931, 2872, 1738, 1463, 1422, 1274, 1062 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.05 (t, J = 7.0 Hz, 1 H, Hvinyl),
4.08 (t, J = 4.1 Hz, 2 H, OCH2), 3.25 (d, J = 7.1 Hz, 2 H, COCH2),
2.88 (t, J = 6.1 Hz, 2 H, SCH2), 2.87 (t, J = 6.1 Hz, 2 H, SCH2), 2.15
(m, 2 H, SCH2CH2), 1.61 (m, 2 H, OCH2CH2), 1.37 (m, 2 H,
CH3CH2), 0.92 (t, J = 7.7 Hz, 3 H, CH3).
13C NMR (75 MHz, CDCl3): d = 170.9 (C), 130.5 (C), 123.7 (CH),
64.7 (CH2), 34.8 (CH2), 30.6 (CH2), 29.9 (CH2), 29.3 (CH2), 24.8
(CH2), 19.1 (CH2), 13.6 (CH3).
MS (ESI): m/z = 269 [M + Na]+.
Anal. Calcd for C11H18O2S2: C, 53.62; H, 7.36. Found: C, 53.13; H,
7.45.
Compound 7
1H NMR (300 MHz, CDCl3): d = 4.10 (t, J = 6.7 Hz, 2 H, OCH2),
3.98 (t, J = 6.4 Hz, 2 H, NOCH2), 2.49 (t, J = 6.4 Hz, 2 H, COCH2),
1.61 (m, 2 H, OCH2CH2), 1.46 (m, 6 H, CH2CH2CH2), 1.39 (m, 2
H, CH3CH2), 1.25 (br s, 6 H, CH3), 1.11 (br s, 6 H, CH3), 0.92 (t, J =
7.2 Hz, 3 H, CH3).
1-(1,3-Dithian-2-yloxy)-2,2,6,6-tetramethylpiperidine (5)
To a solution of 1,3-dithiane (2.845 g, 23.7 mmol) in anhyd
dimethoxyethane (52 mL) was added dropwise a solution of n-BuLi
(1.6 M in hexanes) (16.3 mL, 26.08 mmol) at –35 °C under an at-
mosphere of Ar and stirring was continued at –35 °C for 1 h. The
mixture was cooled to –60 °C, TEMPO (7.817 g, 49.79 mmol) was
added in one portion and the mixture turned orange. The reaction
was slowly allowed to warm to 0 °C while the orange color changes
to a pale yellow color. After 1.5 h the mixture was poured into sat.
13C NMR (75 MHz, CDCl3): d = 172.8 (C), 72.6 (CH2), 65.6 (CH2),
60.7 (2 × C), 35.7 (CH2), 34.7 (2 × CH3), 32.4 (CH2), 26.4 (CH2),
26.2 (CH2), 25.7 (CH2), 20.9 (2 × CH3), 18.0 (CH2), 14.6 (CH3).
HRMS (ESI): m/z [M + Na]+ calcd for C16H31NO3: 286.2377;
found: 286.2365.
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1,3-Dithiane-Derived Alkoxyamines as One-Carbon Radical Precursors
1393
3-(1,3-Dithian-2-ylidene)propanenitrile (10)20 and 3-(1,3-
Dithian-2-yl)-2-[(2,2,6,6-tetramethyl-1-piperidinyl)oxy]pro-
panenitrile (11)
1H NMR (300 MHz, CDCl3): d = 6.13 (t, J = 6.9 Hz, 1 H, Hvinyl),
3.26 (d, J = 6.9 Hz, 2 H, COCH2), 3.00 (s, 3 H, CH3), 2.92 (s, 3 H,
CH3), 2.86 (m, 4 H, SCH2), 2.14 (m, 2 H, SCH2CH2).
Procedure A: According to GP 1, compound 5 (151 mg, 0.549
mmol), acrylonitrile (146 mg, 2.74 mmol) in DMF (7.8 mL) were
employed for 10 min. Flash chromatography (pentane–Et2O, 95:5)
afforded a non-separable mixture (92 mg) of 10 and 3-[(2,2,6,6-tet-
ramethyl-1-piperidinyl)oxy]propanenitrile (5.5:1) as determined by
1H NMR spectroscopy: 10 (0.450 mmol, 82%).
13C NMR (75 MHz, CDCl3): d = 170.2 (C), 128.9 (C), 125.8 (CH),
37.3 (CH3), 35.5 (CH3), 34.4 (CH2), 30.0 (CH2), 29.5 (CH2), 24.9
(CH2).
MS (ESI): m/z = 218 [M + H]+.
Anal. Calcd for C9H15NOS2: C, 49.73; H, 6.96; N, 6.44. Found: C,
49.54; H, 7.16; N, 6.38.
Procedure B: According to GP 1, compound 5 (230 mg, 0.836
mmol), acrylonitrile (222 mg, 4.18 mmol), Et3N (101 mg, 1.0
mmol) in DMF (12 mL) were employed for 10 min. Flash chroma-
tography (pentane–Et2O, 95:5) afforded 11 (33 mg, 0.1 mmol, 12%)
and a non-separable mixture (137 mg) of 10 and 3-[(2,2,6,6-tetra-
methyl-1-piperidinyl)oxy]propanenitrile (2:1) as determined by 1H
NMR spectroscopy: 10 (0.535 mmol, 64%).
Compound 13
IR (film): 2931, 1651, 1466, 1259, 1183, 1120, 909 cm–1.
1H NMR (300 MHz, CDCl3): d = 4.86 (dd, J1 = 10.7 Hz, J2 = 4.1 Hz,
1 H, OCH), 3.84 (dd, J1 = 10.9 Hz, J2 = 4.3 Hz, 1 H, SCH), 3.24 (s,
3 H, NCH3), 2.93 (s, 3 H, NCH3), 2.80 (m, 4 H, SCH2), 2.41 (m, 1
H, SCHCH2), 2.20 (m, 1 H, SCHCH2), 2.05 (m, 1 H, SCH2CH2),
1.85 (m, 1 H, SCH2CH2), 1.40 (m, 4 H, CCH2), 1.28 (m, 2 H,
CCH2CH2), 1.23 (s, 3 H, CH3), 1.09 (s, 3 H, CH3), 1.03 (s, 3 H,
CH3), 0.96 (s, 3 H, CH3).
13C NMR (100 MHz, CDCl3): d = 171.5 (C), 77.2 (CH), 60.6 (C),
59.3 (C), 43.0 (CH), 40.4 (CH2), 40.2 (CH2), 37.8 (CH3), 36.8
(CH2), 35.8 (CH3), 33.6 (CH3), 32.4 (CH3), 30.0 (CH2), 29.7 (CH2),
25.8 (CH2), 20.2 (CH3), 19.9 (CH3), 16.9 (CH2).
Compound 10
IR (film): 2975, 2916, 2248, 1678, 1580, 1420, 959 cm–1.
1H NMR (400 MHz, CDCl3): d = 5.76 (t, J = 7.1 Hz, 1 H, Hvinyl),
3.27 (d, J = 7.1 Hz, 2 H, NCCH2), 2.91 (m, 4 H, SCH2), 2.17 (m, 2
H, SCH2CH2).
13C NMR (100 MHz, CDCl3): d = 135.6 (C), 117.1 (C), 116.6 (CH),
29.3 (CH2), 29.0 (CH2), 24.2 (CH2), 17.4 (CH2).
MS (ESI): m/z = 397 [M + Na]+.
HRMS (ESI): m/z [M + Na]+ calcd for C7H9NS2: 194.0074; found:
194.0052.
Anal. Calcd for C18H34N2O2S2: C, 57.71; H, 9.15; N, 7.48. Found:
C, 57.24; H, 8.98; N, 7.27.
Compound 11
IR (film): 2973, 2934, 2873, 1467, 1423, 1259, 1132 cm–1.
Methyl 3-(1,3-Dithian-2-ylidene)-2-methylpropanoate (14),
Methyl 2-(1,3-Dithian-2-ylmethyl)acrylate (15)
Procedure A: According to GP 2, compound 5 (151 mg, 0.549
mmol), methyl methacrylate (274 mg, 2.745 mmol) in DMF (7.8
mL) were employed for 5 min at 170 °C. Flash chromatography of
the residue (pentane–Et2O, 30:1) afforded 15 (40 mg, 0.183 mmol,
33%).
1H NMR (400 MHz, CDCl3): d = 4.91 (t, J = 7.12 Hz, 1 H, OCH),
4.16 (t, J = 6.3 Hz, 1 H, SCH), 2.86 (m, 4 H, SCH2), 2.33 (m, 2 H,
SCHCH2), 2.11 (m, 1 H, SCH2CHH), 1.90 (m, 1 H, SCH2CHH),
1.48 (m, 6 H, NCH2CH2CH2), 1.31 (s, 3 H, CH3), 1.20 (s, 3 H, CH3),
1.10 (s, 3 H, CH3), 1.07 (s, 3 H, CH3).
13C NMR (100 MHz, CDCl3): d = 113.5 (C), 65.9 (CH), 55.6 (C),
54.5 (C), 36.8 (CH), 34.7 (CH2), 34.5 (CH2), 33.0 (CH2), 28.6
(CH3), 28.5 (CH3), 24.6 (CH2), 24.5 (CH2), 20.5 (CH2), 15.2 (CH3),
15.1 (CH3), 11.7 (CH2).
Procedure B: According to GP 2, compound 5 (156 mg, 0.67
mmol), methyl methacrylate (397 mg, 3.97 mmol), Et3N (86 mg,
0.850 mmol) in DMF (7 mL) were employed for 20 min at 170 °C.
Flash chromatography of the residue (pentane–Et2O, 30:1) afforded
14 (23 mg, 0.105 mmol, 19%) and 15 (60 mg, 0.275 mmol, 49%).
MS (ESI): m/z = 351 [M + Na]+.
Anal. Calcd for C16H28N2OS2: C, 58.49; H, 8.59; N, 8.53. Found: C,
58.12; H, 8.66; N, 8.76.
Compound 14
IR (film): 2974, 2933, 1735, 1453, 1433, 1168, 1143 cm–1.
3-[(2,2,6,6-Tetramethyl-1-piperidinyl)oxy]propanenitrile
1H NMR (400 MHz, CDCl3): d = 3.93 (t, J = 6.3 Hz, 2 H, OCH2),
2.52 (t, J = 6.3 Hz, 2 H, NCCH2), 1.43 (m, 6 H, CH2CH2CH2), 1.16
(s, 6 H, 2 × CH3), 1.11 (s, 6 H, 2 × CH3).
1H NMR (400 MHz, CDCl3): d = 5.92 (d, J = 9.2 Hz, 1 H, Hvinyl),
3.67 (s, 3 H, OCH3), 2.89 (m, 5 H, CH3CH, SCH2), 2.15 (m, 2 H,
SCH2CH2), 1.24 (d, J = 7.1 Hz, 3 H, CH3).
13C NMR (75 MHz, CDCl3): d = 174.2 (C), 130.6 (CH), 129.3 (C),
51.8 (CH), 39.9 (CH3), 29.8 (CH2), 29.1 (CH2), 24.8 (CH2), 17.4
(CH3).
3-(1,3-Dithian-2-ylidene)-N,N-dimethylpropanamide (12) and
3-(1,3-Dithian-2-yl)-N,N-dimethyl-2-[(2,2,6,6-tetramethyl-1-pi-
peridinyl)oxy]propanamide (13)
MS (ESI): m/z = 241 [M + Na]+.
Procedure A: According to GP 2, compound 5 (158 mg, 0.57
mmol), N,N-dimethyl acrylamide (569 mg, 5.7 mmol) in DMF (8.1
mL) were employed for 5 min at 180 °C. Flash chromatography of
the residue (pentane–acetone, 8:2) afforded 13 (32 mg, 0.085 mmol,
15%) and 12 (80 mg, 0.369 mmol, 65%).
Anal. Calcd for C9H14O2S2: C, 49.51; H, 6.46. Found: C, 49.09; H,
6.61.
Compound 15
IR (film): 2993, 2949, 2901, 2829, 1721, 1630, 1437, 1199 cm–1.
Procedure B: According to GP 2, compound 5 (173 mg, 0.629
mmol), N,N-dimethyl acrylamide (623 mg, 6.29 mmol), Et3N (95
mg, 0.943 mmol) in DMF (9 mL) were employed for 10 min. Flash
chromatography of the residue (pentane–acetone, 8:2) afforded 13
(65 mg, 0.174 mmol, 28%) and 12 (40 mg, 0.184 mmol, 30%).
1H NMR (400 MHz, CDCl3): d = 6.27 (d, J = 1.2 Hz, 1 H, Hvinyl),
5.69 (d, J = 1.2 Hz, 1 H, Hvinyl), 4.25 (t, J = 7.6 Hz, 1 H, CH), 3.76
(s, 3 H, OCH3), 2.83 (m, 4 H, SCH2), 2.76 (d, J = 7.6 Hz, 2 H,
CCH2), 1.91 (m, 2 H, SCH2CH2).
13C NMR (100 MHz, CDCl3): d = 166.7 (C), 135.7 (C), 128.2
(CH2), 51.9 (CH), 45.3 (CH3), 38.0 (CH2), 29.9 (2 × CH2), 25.7
(CH2).
Compound 12
IR (film): 2927, 1644, 1502, 1400, 1141, 1056 cm–1.
MS (ESI): m/z = 241 [M + Na]+.
Synthesis 2005, No. 9, 1389–1396 © Thieme Stuttgart · New York

1394
A. J. Herrera, A. Studer
PAPER
2,2,6,6-Tetramethyl-1-[(1-oxido-1,3-dithian-2-yl)oxy]piperi-
Anal. Calcd for C9H14O2S2: C, 49.51; H, 6.46. Found: C, 49.31; H,
6.59.
dine (19)
A solution of 5 (1.30 g, 4.745 mmol) in CH2Cl2 (9.5 mL) was cooled
to 0 °C under a N2 atmosphere. A solution of MCPBA (72%) (1.20
g, 5.03 mmol) in CH2Cl2 (11 mL) was slowly added. The resulting
white suspension was stirred at 0 °C for another 60 min before al-
lowing to warming to r.t. The mixture was then extracted with a sat.
aq solution of NaHCO3, brine, and dried over MgSO4. The residue
was purified by flash chromatography (pentane–acetone, 17:3) to
afford the two regioisomers 19a (182 mg, 0.625 mmol, 13%) and
19b (1.058 g, 3.63 mmol, 77%) as solid compounds.
2-[(1E)-2-Phenyl-1-propenyl]-1,3-dithiane (16) and 2-(2-Phe-
nyl-2-propenyl)-1,3-dithiane (17)
Procedure A: According to GP 1, compound 5 (150 mg, 0.545
mmol), styrene (515 mg, 4.36 mmol) in DMF (8 mL) were em-
ployed for 20 min at 170 °C. Flash chromatography of the residue
(pentane–MTBE, 95:5) afforded 16 and 17 as a mixture (1:2.2) as
determined by 1H NMR spectroscopy (68 mg, 0.288 mmol, 53%).
Procedure B: According to GP 1, compound 5 (150 mg, 0.545
mmol), styrene (515 mg, 4.36 mmol), Et3N (83 mg, 0.817 mmol) in
DMF (8 mL) were employed for 20 min at 170 °C. Flash chroma-
tography of the residue (pentane–MTBE, 95:5) afforded the isomers
16 and 17 as a mixture (1:2.2) as determined by 1H NMR spectros-
copy (72 mg, 0.305 mmol, 56%).
Compound 19a
IR (film): 3002, 2971, 2931, 2871, 1469, 1426, 1365, 1065, 879
cm–1.
1H NMR (400 MHz, CDCl3): d = 6.02 (s, 1 H, CH), 3.39 (dt, J1 =
13.1 Hz, J2 = 3.1 Hz, 1 H, SOCH2), 2.80 (m, 2 H, SCH2), 2.65 (m,
1 H, SOCH2), 2.39 (m, 1 H, SCH2CH2), 1.68 (m, 1 H, SCH2CH2),
1.34 (br s, 6 H, CCH2CH2CH2), 1.22 (br s, 12 H, 4 × CH3).
Compounds 16 and 17
IR (film): 3055, 3027, 2932, 2898, 2827, 1494, 1444, 763 cm–1.
MS (ESI): m/z = 275 [M + Na]+.
13C NMR (100 MHz, CDCl3): d = 94.7 (C), 63.2 (2 × C), 46.3
(CH2), 40.4 (2 × CH2), 34.3 (2 × CH3), 28.6 (CH2), 24.4 (CH2), 22.1
(2 × CH3), 16.8 (CH2).
Anal. Calcd for C13H16S2: C, 66.05; H, 6.82. Found: C, 65.89; H,
7.00.
MS (ESI): m/z = 314 [M + Na]+.
Compound 16
Anal. Calcd for C13H25NO2S2: C, 53.57; H, 8.65; N, 4.81. Found: C,
53.21; H, 8.47; N, 4.60.
1H NMR (300 MHz, CDCl3): d = 7.28–7.47 (m, 5 H, Harom), 5.76
(dq, J1 = 9.78 Hz, J2 = 1.43 Hz, 1 H, Hvinyl), 5.07 (d, J = 9.8 Hz, 1
H, SCH), 2.88 (m, 4 H, SCH2), 2.21 (d, J = 1.43 Hz, 3 H, CH3), 2.10
(m, 2 H, SCH2CH2).
Compound 19b
IR (film): 2993, 2973, 2934, 1467, 1378, 1069, 1023, 954 cm–1.
13C NMR (100 MHz, CDCl3): d = 139.1 (C), 128.2 (2 × CH), 127.5
(CH), 126.2 (2 × CH), 123.6 (CH), 44.8 (CH), 30.4 (2 × CH2), 30.2
(CH3), 24.9 (CH2).
1H NMR (400 MHz, CDCl3): d = 5.53 (s, 1 H, CH), 3.02 (dt, J1 =
13.2 Hz, J2 = 2.6 Hz, 1 H, SOCH2), 2.88 (dd, J1 = 9.7 Hz, J2 = 3.6
Hz, 2 H, SCH2), 2.66 (m, 1 H, SOCH2), 2.33 (dt, J1 = 13.5 Hz, J2 =
2.6 Hz, 1 H, SCH2CH2), 1.68 (m, 1 H, SCH2CH2), 1.49 (br s, 6 H,
CCH2CH2CH2), 1.21 (br s, 12 H, 4 × CH3).
13C NMR (100 MHz, CDCl3): d = 96.2 (CH), 62.2(2 × C), 41.1
(CH2), 40.4 (2 × CH2), 36.4 (2 × CH3), 23.2 (CH2), 21.3 (2 × CH3),
16.8 (CH2), 14.0 (CH2).
Compound 17
1H NMR (300 MHz, CDCl3): d = 7.28–7.47 (m, 5 H, Harom), 5.42 (s,
1 H, Hvinyl), 5.24 (s, 1 H, Hvinyl), 4.07 (t, J = 7.4 Hz, 1 H, SCH), 2.97
(d, J = 7.4 Hz, 2 H, CCH2), 2.80 (m, 4 H, SCH2), 1.88 (m, 2 H,
SCH2CH2).
MS (ESI): m/z = 314 [M + Na]+.
13C NMR (100 MHz, CDCl3): d = 143.5 (C), 128.3 (2 × CH), 127.6
(CH), 125.9 (2 × CH), 115.7 (CH2), 45.0 (CH), 41.4 (CH2), 30.2
(2 × CH2), 25.7 (CH2).
Anal. Calcd for C13H25NO2S2: C, 53.57; H, 8.65; N, 4.81. Found: C,
53.53; H, 8.48; N, 4.69.
2-(1-Styryl)-1,3-dithian (18)20,21
2,2,6,6-Tetraethylpiperidin-4-methoxy-N-oxyl Radical (21)
LiAlH4 (221 mg, 5.826 mmol) was added to a solution of 2017
(1.197 g, 5.296 mmol) in anhyd THF (15 mL) at r.t. and stirred for
30 min under an atmosphere of Ar. The excess of LiAlH4 was de-
stroyed by addition of small amounts of sat. aq solution of NaSO4
under vigorous stirring, until the gray suspension turned white. The
precipitate was removed by filtration and washed with MTBE. The
organic mixture was washed with a 0.5 M aq HCl solution, dried
over MgSO4 and concentrated in vacuo. The resulting oil was dis-
solved in anhyd THF (8 mL) and was added slowly to a suspension
of NaH (60% in oil) (318 mg, 7.944 mmol) in anhyd THF (8 ml) at
r.t. under Ar. After 45 min of stirring, MeI (1.656 ml, 26.48 mmol)
was added at r.t. and stirring was continued for another hour. The
reaction mixture was poured into aq sat. NH4Cl and extracted with
Et2O (3 ×). The combined organic layers were dried over MgSO4
and the solvents were removed in vacuo. Purification by flash chro-
matography (pentane–MTBE, 95:5) afforded 21 (1.229 g, 5.078
mmol, 96%) as an orange oil.
Procedure A: According to GP 1, compound 5 (160 mg, 0.582
mmol), styrene (484 mg, 4.65 mmol) in DMF (8 mL) were em-
ployed for 25 min at 170 °C. Flash chromatography of the residue
(pentane–MTBE, 99:1) always afforded 18 (28 mg, 0.126 mmol,
22%) with a small amount of not identified side products.
Procedure B: According to GP 1, compound 5 (160 mg, 0.582
mmol), styrene (484 mg, 4.65 mmol), Et3N (88 mg, 0.873 mmol) in
DMF (8 mL) were employed for 25 min at 170 °C. Flash chroma-
tography of the residue (pentane–MTBE, 99:1) always afforded 18
(63 mg, 0.284 mmol, 49%) with a small amount of non determined
contaminants.
Compound 18
1H NMR (300 MHz, CDCl3): d = 7.32–7.15 (m, 5 H, Harom), 6.69 (d,
J = 15.6, 1 H, CHvinyl), 6.19 (dd, J1 = 15.6 Hz, J2 = 7.6 Hz, 1 H,
CHvinyl), 4.74 (d, J = 7.6 Hz, 1 H, SCH), 2.86 (m, 4 H, SCH2), 2.05
(m, 1 H, SCH2CH2), 1.85 (m, 1 H, SCH2CH2).
13C NMR (75 MHz, CDCl3): d = 136.6 (C), 133.8 (CH), 128.9 (2 ×
CH), 128.5 (CH), 127.1 (2 × CH), 126 (CH), 48.0 (CH), 30.6 (2 ×
CH2), 25.7 (CH2).
Compound 21
EPR: g = 2.006; aN = 14.25 G.
IR (film): 2966, 2881, 2819, 1463, 1382, 1099, 808 cm–1.
MS (ESI): m/z = 265 [M + Na]+.
Synthesis 2005, No. 9, 1389–1396 © Thieme Stuttgart · New York

PAPER
1,3-Dithiane-Derived Alkoxyamines as One-Carbon Radical Precursors
1395
Anal. Calcd for C14H28NO2: C, 69.38; H, 11.64; N, 5.78. Found: C,
69.25; H, 11.77; N, 5.66.
for 9.5 h and was then allowed to cool to r.t. The solvent and excess
of n-butyl acrylate were removed in vacuo. The residue was purified
by flash chromatography (pentane–MTBE, 98:2) to afford 24 (20
mg, 0.041 mmol, 57%).
1-(1,3-Dithian-2-yloxy)-2,2,6,6-tetraethyl-4-methoxypiperidine
(22)
n-BuLi (1.6M) (0.625 ml, 1.0 mmol) was added to a solution of 1,3-
dithiane (120 mg, 1.0 mmol) in anhyd dimethoxyethane (2.2 ml) at
–35 °C under Ar. After 45 min of stirring, a solution of nitroxide 21
(484 mg, 2.0 mmol) in anhyd dimethoxyethane was added at –35
°C. The cooling bath was replaced by a water–ice cooling bath and
stirring at 0 °C was continued for 1 h. The reaction mixture was then
stirred at r.t. for 20 min, poured into a sat. aq solution of NH4Cl and
extracted (2 ×) with Et2O. The combined organic layers were dried
over MgSO4. Flash chromatography (pentane–MTBE, 96:4) afford-
ed 22 (197 mg, 0.545 mmol, 55%) and 21 (245 mg, 1.01 mmol) was
recovered.
Compound 24
IR (film): 2959, 2878, 2816, 1738, 1464, 1167, 1098, 990 cm–1.
1H NMR (300 MHz, CDCl3): d = 4.42 (dd, J1 = 10.0 Hz, J2 = 4.3 Hz,
1 H, COCH), 4.11 (m, 2 H, OCH2), 3.84 (dd, J2 = 4.1 Hz, J2 = 10.2
Hz, 1 H, SCH), 3.35 (m, 1 H, MeOCH3), 3.31 (s, 3 H, OCH3), 2.82
(m, 4 H, SCH2), 2.29 (m, 1 H), 2.19–1.97 (m, 2 H), 1.91–1.20 (m,
17 H), 1.00 (t, J = 7.3 Hz, 3 H, CH3), 0.94 (t, J = 7.4 Hz, 3 H, CH3),
0.90–0.82 (m, 9 H, CH3).
13C NMR (75 MHz, CDCl3): d = 172.6 (C), 80.8 (CH), 71.1 (CH),
66.1 (CH), 65.6 (C), 64.6 (CH2), 55.7 (CH3), 42.3 (CH), 38.9 (CH2),
36.2 (CH2), 36.1 (CH2), 30.6 (CH2), 30.4 (CH2), 30.3 (CH2), 30.0
(CH2), 29.9 (CH2), 27.5 (CH2), 27.2 (CH2), 25.6 (CH2), 19.2 (CH2),
13.7 (2 × CH3), 10.0 (CH3), 8.1 (2 × CH2).
Compound 22
IR (film): 2961, 1463, 1377, 1098, 912 cm–1.
HRMS (ESI): m/z [M + Na]+ calcd for C25H47NO4S2: 512.2844;
found: 512.2831.
1H NMR (400 MHz, CDCl3): d = 5.56 (s, 1 H, SCH), 3.36 (m, 1 H,
MeOCH), 3.32 (s, 3 H, OCH3), 3.25 (ddd, J1 = 14.2 Hz, J2 = 7.6 Hz,
J3 = 6.10 Hz, 2 H, SCH2), 2.68 (ddd, J1 = 13.6 Hz, J2 = 4.5 Hz, J3 =
4.3 Hz, 2 H, SCH2), 1.82 (m, 2 H, SCH2CH2), 2.06 (m, 4 H,
CH2CH3), 1.82 (m, 2 H, CCH2), 1.74 (m, 2 H, CH2CH3), 1.45 (m, 2
H, CH2CH3), 1.28 (t, J = 11.4 Hz, 2 H, CCH2), 0.92 (t, J = 7.2 Hz,
6 H, CH3), 0.91 (t, J = 7.2 Hz, 6 H, CH3).
2-(1,3-Dithian-2-ylmethyl)-4-[(2,2,6,6-tetraethyl-4-methoxy-1-
piperidinyl)oxy]decanenitrile (25)
A solution of 23 (20 mg, 0.048 mmol) and 1-octene (27 mg, 0.242
mmol) in degassed dichloroethane (48 mL, 1 M) was sealed off un-
der Ar. The mixture was heated at 135 °C in an oil bath for 24 h and
was then allowed to cool to r.t. The solvent and excess of 1-octene
were removed in vacuo. The residue was purified by flash chroma-
tography (pentane–MTBE, 98:2) to afford 25 (10 mg, 0.019 mmol,
40%).
13C NMR (100 MHz, CDCl3): d = 84.2 (CH), 71.0 (CH), 66.0 (C),
55.6 (CH3), 36.1 (2 × CH2), 30.4 (2 × CH2), 27.7 (CH2), 25.6 (2 ×
CH2), 25.0 (CH2), 10.0 (2 × CH3), 8.1 (2 × CH3).
MS (ESI): m/z = 384 [M + Na]+.
Anal. Calcd for C18H35NO2S2: C, 59.79; H, 9.76; N, 3.87. Found:
C, 59.99; H, 9.71; N, 3.71.
Compound 25 (Both Isomers)
IR (film): 2963, 2878, 2817, 2239, 1462, 1378, 1098 cm–1.
3-(1,3-Dithian-2-yl)-2-[(2,2,6,6-tetraethyl-4-methoxy-1-piperid-
inyl)oxy]propanenitrile (23)
1H NMR (300 MHz, CDCl3): d = 4.19 (m, 1 H, NOCH), 3.80 (m, 1
H, SCH), 3.37 (m, 1 H, MeOCH), 3.32 (s, 3 H, OCH3), 2.92 (m, 1
H, CHCN), 2.86 (m, 4 H, SCH2), 2.17–1.18 (m, 28 H), 0.97–0.78
(m, 15 H, 4 × CH3, OCH3).
13C NMR (500 MHz, CDCl3): d = 121.4 (C), 121.1 (C), 78.6 (CH),
78.4 (CH), 71.3 (CH), 65.8 (C), 65.7 (C), 55.5 (CH3), 55.3 (CH3),
44.4 (CH), 44.3 (CH), 38.3 (CH2), 38.3 (CH2), 37.2 (CH2), 37.0
(CH2), 36.8 (CH2), 36.7 (CH2), 35.4 (CH2), 33.1 (CH2), 32.3 (CH2),
31.8 (CH2), 31.7 (CH2), 30.9 (CH2), 30.9 (CH2), 30.7 (CH2), 30.6
(CH2), 30.4 (CH2), 30.2 (CH2), 30.1 (CH2), 29.8 (CH2), 29.7 (CH2),
29.6 (CH2), 29.5 (CH2), 29.3 (CH2), 29.2 (CH2), 26.2 (CH), 25.8
(CH2), 25.8 (CH2), 25.7 (CH2), 25.3 (CH), 25.0 (CH2), 22.6 (CH2),
14.0 (CH3), 10.2 (CH3), 8.9 (CH3), 8.7 (CH3), 8.2 (CH3), 7.6 (CH3).
A solution of 22 (35.5 mg, 0.098 mmol) and acrylonitrile (26 mg,
0.492 mmol) in degassed dichloroethane (0.13 mL, 0.75 M) was
sealed off under Ar. The mixture was heated at 110 °C in an oil bath
for 1.5 h and was then allowed to cool to r.t. The solvent and excess
of acrylonitrile were removed in vacuo. The residue was purified by
flash chromatography (pentane–MTBE, 9:1) to afford 23 (37 mg,
0.089 mmol, 92%).
Compound 23
IR (film): 2964, 2880, 2817, 1464, 1380, 1098, 906 cm–1.
1H NMR (400 MHz, CDCl3): d = 4.7 (dd, J1 = 9.7 Hz, J2 = 5.6 Hz,
1 H, NCCH), 4.14 (dd, J1 = 10.2 Hz, J2 = 5.1 Hz, 1 H, SCH), 3.33
(m, 1 H, MeOCH3), 3.30 (s, 3 H, OCH3), 2.87 (m, 4 H, SCH2), 2.38–
2.19 (m, 2 H, SCH2CH2), 2.10 (m, 1 H, SCHCH2), 1.94–1.19 (m, 13
H, SCHCH2, NCCH2), 0.98 (t, J = 7.1 Hz, 6 H, CH3), 0.89 (t, J =
7.3, 3 H, CH3), 0.87 (t, J = 7.6 Hz, 3 H, CH3).
13C NMR (100 MHz, CDCl3): d = 118.6 (C), 70.7 (CH), 70.6 (CH),
66.4 (C), 65.8 (C), 55.7 (CH3), 42.2 (CH), 38.6 (CH2), 36.5 (CH2),
36.3 (CH2), 30.8 (2 × CH2), 29.9 (CH2), 29.5 (CH2), 27.3 (2 × CH2),
25.5 (CH2), 15.1 (CH3), 9.9 (CH3), 8.6 (C3), 7.8 (CH3).
HRMS (ESI): m/z [M + Na]+ calcd for C29H54N2O2S2Na: 549.3524;
found: 549.3528.
Butyl 2-(1,3-Dithian-2-ylmethyl)-4-[(2,2,6,6-tetraethyl-4-meth-
oxy-1-piperidinyl)oxy]decanoate (26)
A solution of 24 (13 mg, 0.0266 mmol) and 1-octene (15 mg, 0.133
mmol) in degassed dichloroethane (27 mL, 1 M) was sealed off un-
der Ar. The mixture was heated at 135 °C in an oil bath for 24 h and
was then allowed to cool to r.t. The solvent and excess of 1-octene
were removed in vacuo. The residue was purified by flash chroma-
tography (pentane–MTBE, 98:2) to afford 26 (9 mg, 0.015 mmol,
56%).
MS (ESI): m/z = 437 [M + Na]+.
Anal. Calcd for C21H38N2O2S2: C, 60.83; H, 9.24; N, 6.76. Found:
C, 60.68; H, 9.10; N, 6.47.
Compound 26 (Both Isomers)
IR (film): 2958, 2926, 2877, 1731, 1464, 1378, 1158, 1066 cm–1.
Butyl 3-(1,3-Dithian-2-yl)-2-[(2,2,6,6-tetraethyl-4-methoxy-1-
piperidinyl)oxy]propanoate (24)
A solution of 22 (26 mg, 0.072 mmol) and n-butyl acrylate (10.1
mg, 0.079 mmol) in degassed dichloroethane (72 mL, 1 M) was
sealed off under Ar. The mixture was heated at 115 °C in an oil bath
1H NMR (300 MHz, CDCl3): d = 4.07 (m, 2 H, OCH2, NOCH), 3.96
(dd, J = 8.4, 6.2 Hz, 2 H, OCH2), 3.62 (m, 1 H, SCH), 3.36 (m, 1 H,
MeOCH), 3.32 (s, 3 H, OCH3), 2.86 (m, 1 H, COCH), 2.81 (m, 4 H,
SCH2), 2.16–1.17 (m, 32 H), 0.96–0.85 (m, 18 H, CH3).
Synthesis 2005, No. 9, 1389–1396 © Thieme Stuttgart · New York

1396
A. J. Herrera, A. Studer
PAPER
(5) Byers, J. H.; Whitehead, C. C.; Duff, M. E. Tetrahedron
13C NMR (500 MHz, CDCl3): d = 175.4 (C), 175.2 (C), 79.2 (CH),
78.8 (CH), 71.4 (CH), 65.9 (C), 65.7 (C), 65.3 (C), 64.4 (CH), 64.4
(CH), 55.7 (CH3), 45.1 (CH), 45.0 (CH), 39.8 (CH), 39.6 (CH), 38.3
(CH2), 36.9 (CH2), 36.8 (CH2), 36.5 (CH2), 36.0 (CH2), 33.0 (CH2),
32.2 (CH2), 31.9 (CH2), 31.8 (CH2), 30.9 (CH2), 30.7 (CH2), 30.6
(CH2), 30.5 (CH2), 30.3 (CH2), 30.0 (CH2), 30.0 (CH2), 29.9 (CH2),
29.7 (CH2), 29.6 (CH2), 25.9 (CH2), 25.9 (CH2), 24.5 (CH2), 22.6
(CH3), 19.2 (CH3), 14.1 (CH3), 13.7 (CH3), 10.5 (CH3), 10.2 (CH3),
8.8 (CH3), 8.6 (CH3), 8.2 (CH3), 8.0 (CH3).
Lett. 1996, 37, 2743.
(6) de Greef, M.; Zard, S. Z. Tetrahedron 2004, 60, 7781.
(7) Nishida, A.; Kawahara, N.; Nishida, M.; Yonemitsu, O.
Tetrahedron 1996, 52, 9713.
(8) Studer, A. Chem. Soc. Rev. 2004, 33, 267.
(9) Fischer, H. Chem. Rev. 2001, 101, 3581.
(10) Marque, S.; Fischer, H.; Baier, E.; Studer, A. J. Org. Chem.
2001, 66, 1146.
(11) Hawker, C. J.; Bosman, A. W.; Harth, E. Chem. Rev. 2001,
101, 3661.
(12) Ananchenko, G. S.; Fischer, H. J. Polym. Sci., Part A:
Polym. Chem. 2001, 39, 3604.
(13) Connolly, T. J.; Scaiano, J. C. Tetrahedron Lett. 1997, 38,
1133.
(14) (a) Wetter, C.; Studer, A. Chem. Commun. 2004, 174.
(b) Teichert, A.; Jantos, K.; Harms, K.; Studer, A. Org. Lett.
2004, 6, 3477. (c) Review on microwave chemistry: Kappe,
C. O. Angew. Chem. Int. Ed. 2004, 43, 6250.
(15) The microwave experiments were conducted using
professional laboratory microwave equipment. A MLS-
Ethos 1600 Mikrowellen System (Milestone) was used for
the present studies. The reactions were run in 40 mL MLS-
reaction high-pressure vessels (up to 15 bars), which contain
pressure control valves. An advanced temperature control
system from MLS allowing direct contactless temperature
monitoring was used. The microwave power is continuously
and dynamically adjusted to follow the defined temperature
profile.
HRMS (ESI): m/z [M + H]+ calcd for C33H64NO4S2: 602.4277;
found: 602.4273.
Polymerization of Styrene with Alkoxyamine (5)
A Schlenk tube was charged with alkoxyamine initiator 5 (72 mg,
0.262 mmol) and styrene (3 mL, 26.21 mmol). The tube was sub-
jected to three freeze-thaw cycles and sealed off under Ar. The po-
lymerization was carried out under Ar at 125 °C for 24 h. The
resulting mixture was cooled to r.t., dissolved in CH2Cl2, and
poured into a glass dish, and the residual monomer was removed in
a vacuum-drying cabinet at 60 °C for 12 h. The conversion was
evaluated gravimetrically (1.667 g, 61%), the experimental num-
ber-average molecular weight (Mn,exp) = 6600 gmol–1, and PDI =
1.12 were determined by SEC.
Acknowledgment
We thank the Alexander von Humboldt Foundation for financial
support (stipend to A. J. H.). The Fonds der Chemischen Industrie
is acknowledged for continuous support.
(16) Molawi, K.; Schulte, T.; Siegenthaler, K. O.; Wetter, C.;
Studer, A. Chem.–Eur. J. in press.
(17) Wetter, C.; Gierlich, J.; Knoop, C. A.; Müller, C.; Schulte,
T.; Studer, A. Chem.–Eur. J. 2004, 10, 1156.
(18) (a) Schulte, T.; Studer, A. Macromolecules 2003, 36, 3078.
(b) Wetter, C.; Gierlich, J.; Knoop, C. A.; Müller, C.;
Schulte, T.; Studer, A. Chem.–Eur. J. 2004, 10, 1156.
(19) Marque, S.; Le Mercier, C.; Tordo, P.; Fischer, H.
Macromolecules 2000, 33, 4403.
References
(1) Seebach, D.; Corey, E. J. J. Org. Chem. 1975, 40, 231.
(2) Gröbel, B. T.; Seebach, D. Synthesis 1977, 357.
(3) Greene, T. W.; Wuts, P. G. M. Protecting Groups in Organic
Synthesis, 3th ed.; Wiley: New York, 1999.
(4) Chatgilialoglu, C.; Crich, D.; Komatsu, M.; Ryu, I. Chem.
Rev. 1999, 99, 1991.
(20) This compound decomposes in the absence of solvents, upon
exposure to air.
(21) Jiang, B.; Chen, Z. Tetrahedron: Asymmetry 2001, 12, 2835.
Synthesis 2005, No. 9, 1389–1396 © Thieme Stuttgart · New York