Intermolecular addition reactions of N-alkyl-N-chlorosulfonamides to unsaturated compounds

Article abstract of DOI:10.3762/bjoc.11.136

N-Alkyl-N-chlorosulfonamides add to alkenes under copper(I) catalysis. In reactions of styrene derivatives with terminal double bonds the addition products were obtained in excellent yield and high regioselectivity. Lower yields are obtained in addition r

Full text of DOI:10.3762/bjoc.11.136

Intermolecular addition reactions of
N-alkyl-N-chlorosulfonamides to unsaturated compounds
Gerold Heuger1 and Richard Göttlich*1,2
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2015, 11, 1226–1234.
1Organisch-Chemisches Institut, WWU Münster, Corrensstraße 40,
48149 Münster, Germany and 2Institut für Organische Chemie,
Justus-Liebig-Universität Giessen, Heinrich-Buff-Ring 58, 35392
Giessen, Germany
doi:10.3762/bjoc.11.136
Received: 21 March 2015
Accepted: 29 June 2015
Published: 21 July 2015
Email:
Richard Göttlich* - richard.goettlich@org.chemie.uni-giessen.de
Associate Editor: C. Stephenson
* Corresponding author
© 2015 Heuger and Göttlich; licensee Beilstein-Institut.
License and terms: see end of document.
Keywords:
addition reactions; catalysis; N-chlorosulfonamides; haloamination;
radical reaction
Abstract
N-Alkyl-N-chlorosulfonamides add to alkenes under copper(I) catalysis. In reactions of styrene derivatives with terminal double
bonds the addition products were obtained in excellent yield and high regioselectivity. Lower yields are obtained in addition reac-
tions to non-aromatic alkenes. The reaction most likely proceeds via a redox catalysis and amidyl radicals, a concerted mechanism
has been ruled out and a polar mechanism via chloronium ions would lead to the opposite regiochemistry.
Introduction
In earlier publications we described the cyclisation of various Addition reactions with N-alkyl-N-halosulfonamides to unsatu-
unsaturated N-hetero-substituted amines and amides via radi- rated compounds have not been examined in detail so far. In
cals [1-3] and other mechanistic pathways [4-8]. Although earlier works Komori added a secondary N-chloro-sulfonamide
reported by other groups [9-11] in our hands an efficient inter- to 1-hexene under photoirridation [12,13] and Priestly [14],
molecular addition reaction of N-hetero substituted amines via Seden [15] and Daniher [16] published addition reactions of
radicals was not possible in appreciable yields. The reactivity of secondary N-halosulfonamides and N,N-dihalosulfonamides to
the intermediate aminyl radicals towards alkenes was simply alkenes. Neale [17] discussed a radical mechanism via nitrogen
not high enough and various side reactions became predomi- radicals as intermediates. In a more recent series of publica-
nant. We therefore turned our attention to more electrophilic, tions Li developed a new aminohalogenation of cinnamic esters
thus more reactive, nitrogen-centered radicals and chose sulfon- using N,N-dichloro-p-toluenesulfonamide and ZnCl2 or
amidyl radicals as such electrophilic intermediates for an effi- Cu(OTf)2 [18] as catalysts and transferred these conditions to
cient intermolecular addition reaction.
reactions with alkynes [19-21] and α,β-unsaturated ketones [19-
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Beilstein J. Org. Chem. 2015, 11, 1226–1234.
21]. An ionic mechanism via halonium ions was proposed. The
amidofluorination of alkenes has been achieved by Zhang [22]
using copper or palladium catalysts and proceeds via radicals
and fluoropalladation, respectively. Cyclisation reactions of
unsaturated sulfonamides which proceed via amidyl radicals
have been described by Li [23] and by Oshima [24]. Chemler
[25,26] discusses radical and polar pathways as competing
mechanisms and has developed a nice copper-catalyzed oxida-
tive amidation of alkenes whilst Muñiz [27] in a recent publica-
Scheme 1: Preparation of the chloroamides.
tion proposes a polar sulfonamido-chlorination mechanism of Other procedures for the synthesis of these compounds
alkenes.
including N-chlorination with an fivefold excess of Oxone® in
the presence of NaCl/Al2O3 [35] or deprotonation and reaction
Similar, intramolecular and intermolecular additions of with NCS [36,37] did not lead to higher or led in distinctly
N-chlorosulfonamides and derivatives like Chloramine-T to lower yields to the N-chloro compounds.
alkenes have been described by Sharpless [28,29], Komatsu
[30-32] and Dodd [33]. In these examples the nitrogen center We chose styrene as the model compound for the first addition
carries no substituents, which limits the scope of the reactions. reactions of N-chlorosulfonamide 2a and used the complex
In our own studies we wanted to develop a radical addition, [(MeCN)4Cu]PF6 as catalyst (Scheme 2). However even after a
using amidyl radicals with an N-alkyl substituent, which we prolonged reaction time of 24 hours no addition product could
anticipated to generate readily from the corresponding be detected by TLC (Table 1, entry 1). Increasing the reaction
N-chloroamides by electron transfer from copper(I) catalysts. temperature to 50 °C led to the formation of the addition prod-
uct 3 in low yield. The yield was further raised to 30% by a
Results and Discussion
The N-chlorosulfonamides can be easily prepared by reaction of
longer reaction time of 48 h (Table 1, entries 2 and 3).
the sulfonamide with calcium hypochlorite and moist alumina Increasing the amount of catalyst led to no better results whilst
[34], which produced the corresponding N-chloro compounds rising the temperature to 75 °C and adding an excess of styrene
2a and 2b in quantitative yield (Scheme 1).
increased the yield to 43%. Under these conditions the
Scheme 2: First experiments for the intermolecular radical addition.
Table 1: Optimized addition reactions of 2a with styrene.
Entry
2a (equiv)
Styrene
(equiv)
Catalyst
Solvent
Reaction
time (h)
Temperature
(°C)
Yield of 3
(%)
1
2
3
4
5
6
7
8
9
1.2
1.2
1.2
1.2
1
1
1
1
1
3
3
3
1
1
10% [(MeCN)4Cu]PF6
10% [(MeCN)4Cu]PF6
10% [(MeCN)4Cu]PF6
50% [(MeCN)4Cu]PF6
10% [(MeCN)4Cu]PF6
10% CuCl
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
PhCN
PhCN
PhCN
24
24
48
48
48
48
48
48
48
rt
–
50
16
30
25
43
60
92
48
34
50
50
75
1
75
1
10% CuCl
100
100
100
1
10% CuCl
2
10% CuCl
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Beilstein J. Org. Chem. 2015, 11, 1226–1234.
N-chlorosulfonamide 2a was completely consumed, undesired In a next step we added chloroamide 2a to a variety of styrene
products were the sulfonamide 1a as well as oligostyrenes. The derivatives (Table 2). Whilst the addition proceeds well with
oligomerisation should be slowed down by using copper(I) electron-poor styrenes such as 4-nitro and 4-fluorostyrene, an
chloride as the catalyst, which (after oxidation to copper(II) electron rich substrate with a methoxy substituent (Table 2,
chloride) captures carbon radicals at a diffusion controlled rate entry 4) leads to a complex mixture of products. Most likely the
[38].
electron-rich aromatic ring is oxidized under these conditions,
leading to a variety of products which could not be separated.
Indeed using copper(I) chloride as the catalyst we obtained a
yield of 60% of the addition product with sulfonamide 1a being With styrene derivatives giving high yields of addition prod-
the remaining side product. We supposed that this sulfonamide ucts, we next turned our attention to the less reactive non-
was generated by H-abstraction from the solvent and therefore aromatic alkenes.
we used benzonitrile, a solvent from which hydrogen cannot
easily be abstracted and which allowed us a higher reaction Addition to non-aromatic alkenes
temperature (100 °C). Using these conditions we obtained a As expected non-aromatic alkenes are less good substrates for
nearly quantitative yield of 92% of 3 (Table 1, entry 7), whilst the radical addition of amidyl radicals and the yields of addi-
changing the chloroamide/styrene ratio led to reduced yields.
tion products of 2a decreased significantly (Table 3). A conju-
gated diene like cyclooctadiene (Table 3, entry 4) and a
We next wanted to check the scope of this addition reaction and terminal, sterically not hindered alkene like 1-decene (Table 3,
used, with the chloroamide 2b, a sulfonamide with an extreme entry 1) still gave reasonable yields of the addition product. The
sterical hinderance (tert-butyl group). This led to the addition yield is lower in addition to norbornene and cyclooctene, both
product 4 in a distinct lower yield (Scheme 3).
of which are more sterically hindered and do not allow any
mesomeric stabilization of the intermediate radical (Table 3,
entries 2 and 3). Addition to an alkyne (Table 3, entry 5)
produced a complex mixture of products, which could not be
separated. Electron poor alkenes like an unsaturated ketone
(Table 3, entry 6) are not good substrates for the addition of
amidyl radicals either, as amidyl radicals are expected to be
electrophilic themselves. Therefore we expected the addition to
electron-rich enol ethers to proceed smoothly, however, with
Scheme 3: Reaction of sterically hindered N-chlorosulfonamides.
Table 2: Addition reactions of 2a with styrene derivatives.
Entry
Olefine
Product
Yield (%)
92
1
3
5
2
82
3
4
96
–
6
unidentified
reaction mixture
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Beilstein J. Org. Chem. 2015, 11, 1226–1234.
Table 3: Addition reactions of 2a with electron-deficient olefines.
Entry
Olefine
Producta
Yield (%)
34
1
1-decene
7
8
2
3
cyclooctene
norbornene
13
26
dr 2:1
9
33
(10a)
10
4
(10b)
unidentified
reaction mixture
5
6
–
no addition
–
7
8
cyclohexene
17
11
12
26
34
9
13
aAll products are obtained as racemates.
such electron-rich alkenes polar reaction pathways seem to reaction temperature, the formation of regioisomers of 12 and
become predominant (Table 3, entries 8 and 9).
especially the formation of 13 can be explained by a halonium-
ion transfer to the alkene. This could produce an chloro-substi-
Whilst the formation of 11 from cyclohexene could result from tuted alkene 14, which in a second step would undergo radical
an elimination of HCl after the radical addition due to the high addition of 2b (Scheme 4).
Scheme 4: Proposed mechanism of the chlorination.
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Beilstein J. Org. Chem. 2015, 11, 1226–1234.
This result surprised us, as we did not regard the chloroamide as amidyl radicals. Addition to non-aromatic alkenes proceeds less
a chloronium ion source. For the addition reactions to styrenes a readily in lower yield and electron-rich alkenes react via a
polar mechanism can be ruled out due to the observed regio- competing polar reaction pathway.
chemistry, however, in all other cases a polar mechanism is
possible too and we therefore wanted to verify the radical-type Experimental
mechanism which we initially anticipated.
All solvents were purified by distillation and dried, if necessary,
prior to use. Products were purified by flash chromatography on
silica gel (40–63 μm). 1H and 13C NMR spectra were recorded
Ionic or radical reaction mechanism
For these studies we first chose vinylcyclopropane as the sub- on Bruker WM 300 and ARX400 spectrometers or on a Varian
strate to rule out a concerted mechanism, as this alkene upon Unity plus 600 spectrometer in CDCl3 using TMS as internal
addition of a radical or a cation should react fast under ring- standard.
opening [39], producing an acyclic product. Upon copper(I)
catalyzed addition of 2a to vinylcyclopropane only the ring- Preparation of the N-chlorosulfonamides 2a, 2b; general
opend product 15 was obtained, which rules out a concerted procedure: 5.72 g Ca(OCl)2 (40 mmol, 2 equiv), moist alumina
mechanism and is, due to the observed regiochemistry, a strong (10 g) and chloroform (50 mL) were efficiently stirred at 40 °C
indication for a radical pathway of the addition reaction for 10 min. The sulfonamide (20 mmol) was then added, and
(Scheme 5).
the mixture was stirred at 40 °C until the sulfonamide had
disappeared (monitored by TLC (pentane/ether 1:1), 1.5–3 h).
The crude product was separated from solids and purified by
chromatography (silica gel, pentane/ether 3:1).
N-Chloro-N,4-dimethylbenzenesulfonamide (2a) as white
crystals. Rf 0.48 (pentane/ether 3:1); 1H NMR (400 MHz,
CDCl3) δ 2.49 (s, 3H), 3.11 (s, 3H), 7.42 (d with fine-splitting,
J = 8.0 Hz, 2H), 7.84 (d with fine-splitting, J = 8.4 Hz);
13C NMR (100 MHz, CDCl3) δ 21.6, 45.3, 128.5, 129.6, 129.8,
145.5.
Scheme 5: Ring opening in the case of cationic or radical intermedi-
ates.
N-tert-Butyl-N-chlorobenzenesulfonamide (2b) as white crys-
Another strong argument for a mechanism via radicals is the tals. Rf 0.52 (pentane/ether 3:1); 1H NMR (400 MHz, CDCl3) δ
complete surpression of the reaction of 2a with decene in the 1.50 (s, 9H), 7.52–7.57 (m, 2H), 7.62–7.66 (m, 1H), 7.99 (dd, J
presence of TEMPO (2,2,6,6-tetramethyl-1-piperidinyloxy) as a = 8.4, 1.2 Hz, 2H) ppm; 13C NMR (100 MHz, CDCl3) δ 29.1,
radical trap, which we observed.
68.1, 128.80, 128.84, 133.5, 138.5.
In a last experiment we added 2a to 5-hexen-1-ol, a substrate Metal-catalyzed addition reactions; general procedure: In a
that easily reacts with halonium ions in a halocyclization [40] heat-dried Schlenk vessel 0.1 equiv (related to the N-chlorosul-
(Scheme 6).
fonamide) of the metal salt were dissolved in anhydrous
benzonitrile under an Ar atmosphere and heated to 100 °C. To
this solution the N-chlorosulfonamide and the olefine were
added and stirred for 48 h at this temperature. The solvent was
removed by bulb-to-bulb distillation and the residue was taken
up in dichloromethane. Approx. 10 g of silica gel were added
and the solvent was removed in vacuo. Purifying by flash chro-
matography (pentane/ether 10:1 to 1:1) gave the addition prod-
ucts as described below.
Scheme 6: Addition to unsaturated alcohols prone to halocyclization.
We only obtained the simple addition product 16 with no traces
of halocyclization, again ruling out a polar pathway.
N-(2-Chloro-2-phenylethyl)-N-methylbenzenesulfonamide
(3) as a colourless oil [27]. Rf 0.47 (pentane/ether 3:1);
1H NMR (600 MHz, CDCl3) δ 2.41, (s, 3H), 2.62 (s, 3H), 3.40
Conclusion
In summary we have shown that N-chlorosulfonamides can be (dd, J = 14.4, 7.2 Hz, 1H), 3.58 (dd, J = 14.4, 7.8, 1H), 5.10 (t,
added to styrenes efficiently under copper(I) catalysis via 7.2 Hz, 1H), 7.29–7.38 (m, 5H), 7.41 (m, 2H), 7.63 (d, J = 8.4
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Beilstein J. Org. Chem. 2015, 11, 1226–1234.
Hz, 2H); 13C NMR (150 MHz, CDCl3) δ 21.4, 36.8, 57.9, 61.2, 198 (99) [M − C7H5ClNO2+], 170 (5) [C7H5ClNO2+], 155
127.2, 127.4, 128.71, 128.78, 129.7, 134.6, 138.6, 143.5; MS (100) [C7H7O2S+], 127 (7), 91 (97) [C7H7+], 65 (16) [C5H5+];
(ESI, 1.57 kV, MeOH) m/z (%): 324 (38) [M+], 310 (20), 288 Anal. calcd for C16H17N2ClO4S (368.841): C, 52.10; H, 4.65;
(70) [M − Cl+], 262 (8); HRMS (ESI) m/z: [M+] calcd for N, 7.59; found, C, 52.35; H, 4.81; N, 7.40.
C1 6 H1 8 N3 5 ClO2 S, 324. 0796; found, 324. 0820.
C16H18N37ClO2S [M+]: 326.0770; found: 326.0793. N-(2-Chlorodecyl)-4,N-dimethylbenzenesulfonamide (7) as a
C16H18N35ClO2S + Na [M + Na]+, 346.0608; found, 346.0639; colourless oil. Rf 0.60 (pentane/ether 3:1); 1H NMR (400 MHz,
C16H18N37ClO2S + Na [M + Na]+, 348.0584; found, 348.0613; CDCl3) δ 0.86 (t, J = 6.9 Hz, 3H), 1.25–1.39 (m, 10H),
Anal. calcd for C15H16NClO2S (323.843): C, 59.34; H, 5.60; N, 1.52–1.63 (m, 3H), 1.85–1.91 (m, 1H), 2.41 (s, 3H), 2.80 (s,
4.33; found: C, 59.51; H, 5.69; N, 4.06.
3H), 3.06 (dd, J = 14.1, 6.6 Hz, 1H) oder (10’), 3.34 (dd, J =
14.4, 6.6 Hz, 1H), 4.01–4.05 (m, 1H), 7.30 (d with fine-split-
N-tert-Butyl-N-(2-chloro-2-phenylethyl)benzenesulfon- ting, J = 7.8 Hz, 2H), 7.65 (d with fine-splitting, J = 8.4 Hz,
amide (4) as a colourless oil. Rf 0.61 (pentane/ether 3:1); 2H); 13C NMR (100 MHz, CDCl3) δ 14.0, 21.4, 22.6, 26.1,
1H NMR (400 MHz, CDCl3) δ 1.25 (s, 9H), 3.71 (dd, J = 15.6, 29.0, 29.1, 29.3, 31.8, 35.3, 36.9, 56.8, 60.8, 127.3, 129.7,
8.8 Hz, 1H), 3.91 (dd, J = 15.8, 4.6 Hz, 1H), 5.55 (dd, J = 8.8, 134.4, 143.5; MS (EI, 70 eV) m/z (%): 359 (11) [M+], 310 (29)
4.4 Hz, 1H), 7.32–7.41 (m, 5H), 7.46–7.56 (m, 3H), 7.93 (dd, J [M − CH2Cl+], 282 (3) [M − C6H5+], 246 (13), 198 (97), 186
= 7.2, 1.2 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 29.5, 53.3, (10), 155 (98) [C7H7O2S+], 91 (100) [C7H7+], 65 (38)
59.7, 62.8, 127.1, 127.5, 128.62, 128.66, 128.9, 132.2, 139.2, [C5H5+]; HRMS (EI) m/z: [M+] calcd for C18H30N35ClO2S,
143.9; MS (ESI, 1.57 kV, MeOH) m/z (Intens. ×106): 374 359.16778; found, 359.16858; Anal. calcd for C18H30NClO2S
(1.15) [M + Na+], 338 (0.64) [M − Cl+], 316 (0.43), 282 (0.5), (359.961): C, 60.06; H, 8.40; N, 3.89; found, C, 60.29; H, 8.41;
260 (0.8); HRMS (ESI) m/z: [M + Na]+ calcd for N, 3.90.
C18H22N35ClO2S + Na, 374.0952; found, 374.0960;
C18H22N37ClO2S + Na [M + Na]+, 376.0927; found, 376.0933. N-(2-Chlorocyclooctyl)-N-methylbenzenesulfonamide (8) as
a colourless oil. Rf 0.32 (pentane/ether 3:1); 1H NMR
N-[2-Chloro-2-(4-fluorphenyl)ethyl]-N-methylbenzenesul- (600 MHz, CDCl3) δ 1.38–1.44 (m, 1H), 1.49–1.71 (m, 7H),
fonamide (5) as a yellow oil. Rf 0.34 (pentane/ether 3:1); 1.72–1.79 (m, 1H), 1.89–1.95 (m, 1H), 2.01–2.06 (m, 1H),
1H NMR (300 MHz, CDCl3) δ 2.42 (s, 3H), 2.63 (s, 3H), 3.39 2.10–2.16 (m, 1H), 2.41 (s, 3H), 2.70 (s, 3H), 4.11 (m, 1H),
(dd, J = 14.5, 7.8 Hz, 1H), 3.55 (dd, J = 14.5, 6.9 Hz, 1H), 5.09 4.30 (m, 1H), 7.28 (d with fine-splitting, J = 8.4 Hz, 2H), 7.74
(t, J = 7.5 Hz, 1H), 7.05 (t, J = 8.5 Hz, 2H), 7.30 (d, J = 8.4 Hz, (d with fine-splitting, J = 8.4 Hz, 2H); 13C NMR (150 MHz,
2H), 7.39 (dd, J = 8.7, 5.1 Hz, 2H), 7.64 (d, J = 8.4 Hz, 2H); CDCl3) δ 21.4, 22.2, 24.7, 26.1, 27.8, 28.1 (broad), 30.85,
13C NMR (75 MHz, CDCl3) δ 21.4, 37.0, 58.0, 60.4, 115.8 (d, J 30.88, 62.2 (broad), 62.5, 127.4, 129.3, 137.1, 142.9; MS (EI,
= 26.8 Hz), 127.3, 129.3 (d, J = 8.3 Hz), 129.8, 134.5, 134.7, 70 eV) m/z (%): 329 (15) [M+], 294 (24) [M − Cl+], 272 (3) [M
143.6, 162.8 (d, J = 246.8 Hz); 19F NMR (282 MHz, CDCl3) δ − C4H9+], 225 (8), 224 (47), 198 (5), 155 (21) [C7H7O2S+], 127
−112.79; MS (EI, 70 eV) m/z (%): 341 (3) [M+], 305 (7) [M − (42), 110 (42) [C8H14+], 84 (100), 57 (37) [C4H9+]; HRMS (EI)
HCl+], 198 (97) [M − C7H5ClF+], 168 (2), 155 (71) m/z: [M+] calcd for C16H24N35ClO2S, 329.12164; found
[C7H7O2S+], 113 (19), 91 (100) [C7H7+], 65 (17) [C5H5+]; 329.12040; Anal. calcd for C16H24NClO2S (329.891): C, 58.25;
HRMS (ESI) m/z: [M + Na]+ calcd for C16H17N35ClFO2S + H, 7.33; N, 4.25; found: C, 58.47; H, 7.18; N, 4.03.
Na, 364.0545; found, 364.0574; C16H17N37ClFO2S + Na [M +
Na]+, 366.0518; found, 366.0546; Anal. calcd for N-(3-Chlorobicyclo[2.2.1]hept-2-yl)-N-methylbenzenesulfon-
C15H16NClFO2S (341.834): C, 56.22; H, 5.01; N, 4.10; found, amide (9) as a colourless oil. 9a (endo-Product): Rf 0.26
C, 56.43; H, 5.01; N, 4.05.
(pentane/ether 3:1); 1H NMR (400 MHz, CDCl3) δ 1.29–1.37
(m, 2H), 1.40–1.60 (m, 3H), 1.86–1.93 (m, 2H), 2.39–2.41 (m,
N-[2-Chloro-2-(3-nitrophenyl)ethyl]-N-methylbenzenesul- 1H), 2.42 (s, 3H), 2.78 (s, 3H), 3.71 (dd, J = 5.4, 1.8Hz, 1H),
fonamide (6) as a yellow resin. Rf 0.14 (pentane/ether 3:1); 4.06 (m, 1H), 7.30 (d with fine-splitting, J = 8.0 Hz, 2H), 7.71
1H NMR (600 MHz, CDCl3) δ 2.43 (s, 3H), 2.69 (s, 3H), 3.50 (d with fine-splitting, J = 8.4 Hz, 2H); 13C NMR (100 MHz,
(dd, J = 14.0, 8.0 Hz, 1H), 3.55 (dd, J = 14.4, 6.8 Hz, 1H), 5.21 CDCl3) δ 20.9, 21.4, 29.3, 30.5, 35.8, 39.7, 43.1, 64.9, 69.1,
(t, J = 7.6 Hz, 1H), 7.32 (d, J = 8.0 Hz, 2H), 7.59 (t, J = 8.0 Hz, 127.3, 129.5, 135.9, 143.2; MS (EI, 70 eV) m/z (%): 313 (36)
1H), 7.64 (d, J = 8.4 Hz, 2H), 7.80 (d, 7.6 Hz, 1H), 8.22 (m, [M+], 278 (6) [M − Cl+], 250 (9) [M − C2H4Cl+], 238 (21), 224
1H), 8.28 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 21.4, 37.1, (5), 198 (51), 158 (100) [M − C7H7O2S+], 131 (13), 121 (31),
57.8, 59.5, 122.5, 123.7, 127.3, 129.82, 129.88, 133.8, 134.3, 91 (88) [C7H7+], 65 (20) [C5H5+]; HRMS (EI) m/z: [M+] calcd
140.7, 143.9, 148.4; MS (EI, 70 eV) m/z (%): 368 (0.1) [M+], for C15H20N35ClO2S, 313.09033; found, 313.08982.
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Beilstein J. Org. Chem. 2015, 11, 1226–1234.
9b (exo-Product): Rf 0.42 (pentane/ether 3:1); 1H NMR N-(2-Chlorotetrahydropyran-3-yl)-N-methylbenzenesulfon-
(400 MHz, CDCl3) δ 1.19–1.22 (m, 3H), 1.44–1.54 (m, 1H), amide (12) as a yellow oil. Rf 0.21 (pentane/ether 3:1);
1.59–1.72 (m, 1H), 1.93 (m, 1H), 2.06 (m, 1H), 2.42–2.44 (m, 1H NMR (400 MHz, CDCl3) δ 1.63–1.73 (m, 2H), 1.87–1.97
1H), 2.42 (s, 3H), 2.93 (s, 3H), 4.06 (m, 1H), 4.14 (m, 1H), 7.29 (m, 1H), 2.42 (s, 3H), 2.42–2.46 (m, 1H), 2.75 (s, 3H),
(d with fine-splitting, J = 8.0 Hz, 2H), 7.86, d with fine-split- 3.56–3.62 (m, 1H), 3.77 (ddd, J = 11.6, 11.6, 4.6 Hz, 1H),
ting, J = 8.0 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 21.4, 3.90–3.96 (m, 1H), 5.10 (d, J = 9.2 Hz, 1H), 7.29 (d, J = 8.0 Hz,
25.6, 29.2, 31.7, 34.7, 38.6, 45.0, 63.2, 68.5, 127.0, 129.5, 2H), 7.77 (d with fine-splitting, J = 8.4 Hz, 2H); 13C NMR (100
136.8, 143.0; MS (EI, 70 eV) m/z (%): 313 (50) [M+]; 278 (10) MHz, CDCl3) δ 21.4, 26.4, 28.0, 34.6, 54.3, 67.5, 89.0, 127.8,
[M − Cl+]; 250 (6) [M − C2H4Cl+], 238 (31), 224 (7), 198 (67), 129.3, 136.2, 143.3; MS (EI, 70 eV) m/z (%): 303 (80) [M+],
158 (100) [M − C7H7O2S+], 139 (11), 122 (34), 91 (88) 259 (4) [M − C2H4O+], 241 (11), 214 (14), 196 (12), 155 (31)
[C7H7+], 65 (15) [C5H5+].
[C7H7O2S+], 127 (41), 108 (100), 91 (66) [C7H7+], 55 (42)
[C3H3O+]; HRMS (EI) m/z: [M+] calcd for C13H18N35ClO3S,
N-(4-Chlorocyclooct-2-enyl)-N-methylbenzenesulfonamide 303.06958; found, 303.06931.
(10b) as a colourless oil. Rf 0.32 (pentane/ether 3:1); 1H NMR
(600 MHz, CDCl3) δ 1.49–1.60 (m, 4H), 1.63–1.71 (m, 2H), N-(1,2-Dichloro-2-isobutoxyethyl)-N-methylbenzenesulfon-
1.73–1.79 (m, 1H), 2.12–2.17 (m, 1H), 2.40 (s, 3H), 2.74 (s, amide (13) as a yellow oil. Rf 0.56 (pentane/ether, 3:1);
3H), 4.72–4.80 (m, 2H), 5.19 (ddd, J = 11.1, 8.4, 1.2 Hz, 1H), 1H NMR (400 MHz, CDCl3) δ 0.88 (d, J = 1.6 Hz, 3H), 0.89 (d,
5.50 (ddd, J = 10.8, 7.8, 1.2 Hz, 1H), 7.27 (d, J = 8.4 Hz, 2H), J = 1.6 Hz, 3H), 1.85 (sept, J = 6.6 Hz, 1H), 2.44 (s, 3H), 2.76
7.63 (d, J = 8.4 Hz); 13C NMR (150 MHz, CDCl3) δ 21.4, 23.6, (s, 3H), 3.20 (d, J = 6.8 Hz, 2H), 5.30 (d, J = 6.4 Hz, 1H), 5.58
25.0, 28.8, 34.4, 40.1, 54.5, 56.7, 125.2, 127.3, 129.5, 132.8, (d, J = 6.4 Hz, 2H), 7.32 (d, J = 8.4 Hz, 2H), 7.77 (d with fine-
135.7, 143.2; MS (EI, 70 eV) m/z (%): 327 (36) [M+], 292 (14) splitting, J = 8.4 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 19.0,
[M − Cl+], 250 (26) [M − C6H5+], 231 (4), 224 (12) [M − 19.1, 21.4, 27.6, 28.0, 71.2, 76.5, 89.6, 127.5, 129.5, 136.1,
C8H7+], 198 (8), 172 (43) [M − C7H7O2S+], 127 (45), 106 (16), 143.8; MS (ESI, 1.30 kV, MeOH) m/z (%): 376 (60) [M + Na+],
91 (100) [C7H7+], 57 (37) [C4H9+]; HRMS (Schubstange) m/z 318 (11), 304 (3) [M − C4H8O+], 285 (6) [M − C7H7+], 262 (6),
[M+]: calcd for C16H22N35ClO2S, 327.10599; found, 226 (60), 208 (4), 197 (11), 187 (4), 163 (9), 155 (56)
327.10532.
[C7H7O2S+], 139 (11) [C7H7OS+], 128 (4), 106 (9), 91 (6)
[C7H7+], 72 (58) [C4H8O+], 57 (17) [C4H9+]; HRMS (ESI) m/z:
Byproduct: N-(2-Chlorocyclooct-3-enyl)-N-methylbenzene- [M + Na]+ calcd for C14H21N35Cl2O3S + Na, 376.0511; found,
sulfonamide (10a) as a colourless oil. Rf 0.39 (pentan/ether 376.0506; C14H21N37Cl2O3S + Na [M + Na]+, 378.0483;
3:1); 1H NMR (300 MHz, CDCl3) δ 1.26–1.35 (m, 1H), found, 378.0480.
1.57–1.76 and 1.85–1.92 (m, 6H), 2.21–2.28 (m, 1H), 2.42 (s,
3H), 2.76 (s, 3H), 4.44–4.51 (m, 1H), 4.90–5.03 (m, 1H), 5.66 N-(5-Chloropent-2-enyl)-N-methylbenzenesulfonamide (15)
(ddd, J = 12.3, 6.5, 1.6 Hz, 1H), 5.77–5.86 (m, 1H), 7.29 (d, J = as a yellow liquid and a non separable 4:1 mixture of isomers.
8.1 Hz, 2H), 7.73 (d, J = 7.8 Hz, 2H); 13C NMR (150 MHz, Rf 0.23 (pentane/ether 3:1). Main isomer 15a (probably the
CDCl3) δ 21.9, 23.5, 29.1, 30.3, 37.5, 57.3, 62.1, 127.2, 128.3, E-isomer): 1H NMR (400 MHz, CDCl3) δ 2.43 (s, 3H),
129.4, 131.8 (selected peaks); MS (ESI, 1.30 kV, MeOH) m/z 2.45–2.51 (m, 2H), 2.66 (s, 3H), 3.50 (t, J = 6.6 Hz, 2H), 3.60
(Intens. ×106): 677 (2.2) [2*M + Na+], 350 (3.1) [M + Na+], (d, J = 6.4 Hz, 2H), 5.43–5.53 (m, 1H), 5.56–5.65 (m, 1H), 7.32
314 (1.8) [MNa − Cl+].
(d, J = 8.0 Hz, 2H), 7.67 (d with fine-splitting, J = 8.4 Hz, 2H);
13C NMR (100 MHz, CDCl3) δ 21.4, 34.1, 35.1, 43.7, 52.0,
N-Cyclohex-2-enyl-N-methylbenzenesulfonamide (11) as a 127.45, 127.48, 129.61, 131.0, 134.5, 143.3. Minor isomer 15b
colourless oil [41]. Rf 0.42 (pentane/ether 3:1); 1H NMR (probably the Z-isomer)(selected Peaks): 1H NMR (400 MHz,
(600 MHz, CDCl3) δ 1.46–1.52 (m, 1H), 1.57–1.61 (m, 1H), CDCl3) δ 2.44 (s, 3H), 2.67 (s, 3H), 3.51 (t, J = 6.6 Hz, 2H),
1.74 (m, 2H), 1.93 (m, 2H), 2.43 (s, 3H), 2.70 (s, 3H), 5.11 (m, 3.68 (d, J = 6.4 Hz, 2H), 7.33 (d, J = 8.0 Hz, 2H), 7.67 (d, J =
1H), 5.57 (m, 1H), 5.81 (m, 1H), 7.30 (d, J = 8.4 Hz, 2H), 7.71 8.0 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 30.3, 34.2,
(d with fine-splitting, J = 8.4 Hz, 2H); 13C NMR (150 MHz, 46.8, 126.7, 129.68, 130.2, 143.4; MS (EI, 70 eV) m/z (%):
CDCl3) δ 21.3, 21.4, 24.3, 26.7, 29.1, 54.2, 127.0, 127.1, 129.6, 287 (2) [M+], 272 (5) [M − CH3+], 238 (8) [M − CH2Cl+],
132.3, 137.2, 142.9; MS (EI, 70 eV) m/z (%): 265 (15) [M+], 224 (16) [M − C2H4Cl+], 198 (14), 186 (100), 155 (58)
237 (100) [M − C2H4+], 213 (24) [M − C4H4+], 186 (6), 155 [C7H7O2S+], 132 (53), 91 (93) [C7H7+], 57 (46) [C4H9+];
(27) [C7H7O2S+], 126 (25) [M − C7H7OS+], 110 (66) HRMS (ESI) m/z: [M + Na]+ calcd for C13H18N35ClO2S + Na,
[C7H12N+], 91 (75) [C7H7+], 55 (25); HRMS (ESI) m/z: [M + 310.0639; found, 310.0620; C13H18N37ClO2S + Na [M + Na]+,
Na+] calcd for C14H19NO2SNa, 288.1029; found, 288.0984.
312.0611; found, 312.0594; Anal. calcd for C13H18NClO2S
1232

Beilstein J. Org. Chem. 2015, 11, 1226–1234.
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(287.806): C, 54.25; H, 6.30; N, 4.87; found, C, 54.18; H, 6.40;
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Li, G. J. Am. Chem. Soc. 2003, 125, 13340. doi:10.1021/ja0304188
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N-(2-Chloro-6-hydroxyhexyl)-N-methylbenzenesulfon-
amide (16) as a colourless oil. Rf 0,06 (pentane/ether 3:1);
1H NMR (400 MHz, CDCl3) δ 1.49–1.79 (m, 6H), 1.92–2.01
(m, 1H), 2.44 (s, 3H), 2.83 (s, 3H), 3.08 (dd, J = 14.0, 6.4 Hz,
1H), 3.39 (dd, J = 14.2, 7.0 Hz, 1H), 3.67 (t, J = 6.2 Hz, 2H),
4.05–4.11 (m, 1H), 7.33 (d, J = 8.0 Hz, 2H), 7.67 (d with fine-
splitting, J = 8.8 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 21.4,
22.2, 32.0, 34.8, 36.9, 56.6, 60.4, 62.4, 127.3, 129.7, 134.4,
143.6; MS (EI, 70 eV) m/z (%): 318 (1) [M+], 283 (16) [M −
Cl+], 270 (12), 246 (3), 198 (88), 186 (8), 155 (100)
[C7H7O2S+], 127 (15), 91 (93) [C7H7+], 65 (43) [C5H5+];
HRMS (ESI) m/z: [M + Na]+ calcd for C14H22N35ClO3S + Na
342.0901; found, 342.0890; C14H22N37ClO3S + Na [M + Na]+:
344.0874; found, 344.0864.
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