Dual Intermolecular Allylic C–H Functionalization of the Tetrasubstituted Alkene Scaffold

Article abstract of DOI:10.1002/ejoc.201701624

Activation of chloramine-T (TsNNaCl) with a Br?nsted acid generates an active reagent for the double allylic C–H functionalization of tetrasubstituted alkenes in an intermolecular manner. The reaction generates a carbon–nitrogen and a carbon–chlorine bond, and proceeds with complete regio- and chemoselectivity. A total of 14 examples demonstrate the applicability of the dual C–H functionalization process. The mechanism involves the intermediacy of a 1,3-butadiene derivative; 1,3-butadienes can also be used directly as substrates.

Full text of DOI:10.1002/ejoc.201701624

A Journal of
Accepted Article
Title: Dual Intermolecular Allylic C-H Functionalization within the
Tetrasubstituted Alkene Scaffold
Authors: Kilian Muniz and Claudio Martinez
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201701624
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10.1002/ejoc.201701624
European Journal of Organic Chemistry
FULL PAPER
Dual Intermolecular Allylic C-H Functionalization within the
Tetrasubstituted Alkene Scaffold
Claudio Martínez[a] and Kilian Muñiz*[a,b]
Dedicated to the memory of Professor Ricardo Llavona
Abstract: Activation of chloramine-T (TsNNaCl) with Brønstedt acid
generates an active reagent for the double allylic C-H
functionalization of tetrasubstituted alkenes under intermolecular
reaction control. The reaction generates a carbon-nitrogen and a
carbon-chlorine bond, respectively, and proceeds with complete
regio- and chemoselectivity. A total of 14 examples demonstrate the
applicability of the dual C-H functionalization process. The
mechanism involves the intermediary participation of a 1,3-butadiene
derivative, which can also be employed directly as substrates.
a
metal-free aminochlorination of alkenes through an
operationally convenient Brønstedt acid activation of chloramine-
T 1.[17] This reaction is characterized by an unusually broad
substrate scope, which tolerates all different alkene classes. For
cyclic tetrasubstituted alkenes, clean vicinal aminochlorination
was observed (Scheme 1). However, this outcome was found to
change entirely in case of the corresponding class of acyclic
tetrasubstituted alkenes. We here report conditions for a dual
allylic amination/chlorination reaction through
oxidation manifold under metal-free conditions.
a
selective
TsHN
TsNNaCl (1)
(1.2 equiv)
Introduction
Intermolecular carbon-heteroatom bond formation through direct
oxidative C-H functionalization at the allylic position represents a
versatile strategy for the refinement of unsaturated hydrocarbon
compounds.[1] Such reactions are widely sought after, and
particularly well-designed, metal-based innovative C-H oxidation
reactions[2] have emerged over recent years. Despite these
broad advances, reactions that can be conducted without the
requirement of a metal promoter constitute a strategic alternative
of conceptual importance,[3,4] both for economical and ecological
reasons. Examples of such practical transformations include
selenium-mediated allylic oxygenation[5] and amination,[6]
hypervalent iodine mediated processes,[7] and related radical-
based oxidations.[8] Within this context, N-halo amines represent
powerful alternative oxidants for metal-free oxidation,[9,10] which
is well illustrated by the versatile Wohl-Ziegler reaction for allylic
halogenation[11] and the prominent Hofmann-Löffler reaction[12]
The latter is a particularly instructive reaction, since the involved
N-halogenated amines usually promote highly selective C-H
functionalization.[13] In the broader N-halo amine area,
commercially available chloramine-T (1)[14] has attracted
significant interest in the field of alkene oxidation.[15,16] Despite
the mature state in the area of expertise, it appears that the
exploration of innovative and practical reactivity based on 1 may
AcOH, 50 ºC, 12 h
Cl
60%
Ref. 17
H
R
TsNNaCl (1)
(2 equiv)
Cl
R
H
R
AcOH (1 equiv),
R
(CH2Cl)2, 50 ºC, 12 h
NHTs
This work: Double Allylic C-H Functionalization
Scheme 1. Oxidation of tetrasubstituted alkenes with the TsNHCl reagent.
Results and Discussion
The reaction was discovered and optimized for 2-phenyl-3-
methyl but-2-ene 2a. Treatment of this tetrasubstituted alkene
with 1.2 equivalents of 1 and pivalic acid in dichloroethane did
not
aminochlorination product, but gave rise to an unexpected
formation of 3a, which resembles regioselective
provide
the
expected
corresponding
vicinal
still be possible. We here report such
a case of an
unprecedented double allylic C-H functionalization within a
metal-free reaction manifold. We recently reported conditions for
a
aminochlorination at two of the allylic positions (Table 1, entry
1). Since this product 3a requires two formal allylic oxidation
events, the yield increased with the enhancement of chloramine
reagent to 2.4 equivalents (entry 2). No reaction takes place at
room temperature (entry 3). With acetic acid as activating agent,
a room temperature process was again not possible, however, a
reaction temperature of 40 ºC led to formation of 3a (entries 4,5).
An an increased yield was observed at 50 ºC (entry 6), and
finally, product 3a could be isolated in 64% from a reaction with
2 equivalents of 1 in combination with 1 equivalent of acetic acid
(entry 7). Solvents other than dichloroethane gave inferior
results (CH2Cl2, 51%, C6H5Cl, 45%, EtOAc, 42%).
[a]
[b]
Dr. C. Martínez, Prof. Dr. K. Muñiz
Institute of Chemical Research of Catalonia (ICIQ)
Av. Països Catalans 16, 43007 Tarragona (Spain)
E-mail: kmuniz@iciq.es
http://www.iciq.org/research/research_group/prof-kilian-muniz/
Prof. Dr. K. Muñiz
ICREA
Pg. Lluís Companys 23, 08010 Barcelona (Spain)
Supporting information for this article is given via a link at the end of
the document.
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10.1002/ejoc.201701624
European Journal of Organic Chemistry
FULL PAPER
single regioisomers and with exclusive (E)-double bond
geometry. The regioselectivity regarding the allylic carbon-
heteroatom bonds was assured from X-ray analysis[18,19] of
naphthyl derivative 3f (Scheme 2).
Cl
TsNNaCl (1)
conditions, 12 h
Only for substrates 2n and 2o with their sterically more
demanding ortho-substituted arenes did the products form as
1:1-(E):(Z)-isomers regarding the double bond geometry.
However, complete regioselectivity was preserved for the two
allylic oxidations.
NHTs
2a
3a
Table 1. Optimization of Reaction Conditions.
Entry
Conditions
Yield [%][a]
The scope could be further extended to the 1,2-dialkyl-(E)-
stilbenes 2p and 2q (Scheme 3). The former undergoes the
selective 1,4-functionalization and provides the product as a 3:1-
mixture with respect to the double bond geometry. The more
challenging situation of the diethyl-substituted stilbene 2q once
more exemplified the power of the current transformation: first,
an (E)-configured double bond was obtained selectively together
with a reasonably high diastereomeric excess regarding the two
newly formed stereogenic allylic centers. The relative
configurations for 3q and 3q´ were established by X-ray
analysis.[19]
1
2
3
4
5
6
7
1 (1.2 equiv.), tBuCO2H (1.2 equiv.), (CH2Cl)2, 50 ºC
1 (2.4 equiv.), tBuCO2H (2.4 equiv.), (CH2Cl)2, 50 ºC
1 (2.4 equiv.), tBuCO2H (2.4 equiv.), (CH2Cl)2, 25 ºC
1 (2.0 equiv.), AcOH (2.0 equiv.), (CH2Cl)2, 25 ºC
1 (2.0 equiv.), AcOH (2.0 equiv.), (CH2Cl)2, 40 ºC
1 (2.0 equiv.), AcOH (2.0 equiv.), (CH2Cl)2, 50 ºC
1 (2.0 equiv.), AcOH (1.0 equiv.), (CH2Cl)2, 50 ºC
34
43
n.c.[b]
n.c.[b]
40
63
64
[a] Isolated yield of 3a after purification. [b] n.c. = no conversion.
TsHN
Cl
NHTs
a)
+
TsNNaCl (1)
(2 equiv)
Cl
Cl
2p
3p:3p´ = 3:1, 75%
Ar
2a-o
Ar
3a-o'
AcOH (1 equiv),
TsHN
(CH2Cl)2, 50 ºC, 12 h
TsHN
+
NHTs
Cl
a)
Cl
Cl
Cl
Cl
R
2q
like
unlike
3q:3q´ = 5:1, 70%
R
NHTs
NHTs
NHTs
3f: 50%
3g (R = Cl): 40%
3h (R = F): 40%
3i (R = CO2Et): 44%
3j (R = Me): 57%
3k (R = OMe): 50%
3a (R = H): 64%
3b (R = Ph): 50%
3c (R = Cl): 50%
3d (R = Me): 62%
3e (R = tBu): 57%
Cl
Cl
NHTs
Scheme 3. Aminochlorination of tetrasubstituted alkenes 2p,q and X-ray
structural assignment of 3q, 3q’. Conditions: a) chloramine-T 1 (2 equiv),
acetic acid (1 equiv), dichloroethane, 50°C, 14 h.
3f (X-ray structure)
Cl
R
R
+
R
NHTs
3l (R = Cl): 40%
3m (R = F): 42%
R = Ph: 3n:3n´= 1:1, 76%
R = Me: 3o:3o´= 1:1, 75%
TsHN
At first sight, the reaction outcome appears counterintuitive,
since the two allylic C-H functionalization events would be
expected to result from radical reactivity, while the ionic
reactivity of the in situ generated TsNHCl reagent should
exclusively address oxidation at the alkene.[17] However, the
unexpected double allylic C-H functionalization can be
rationalized by the assumption of an initial oxidation at the
internal double bond to form a chloronium intermediate, which
undergoes elimination to furnish the allylic chloride A. This
intermediate could alternatively be accessed directly from 2
within an ene reaction.[20] A subsequent elimination event
Scheme 2. Aminochlorination of alkenes 2a-o.
This reaction outcome represents an attractive new synthetic
strategy through direct intermolecular double allylic oxidation
involving participation of two different heteronucleophiles. In
addition, the two allylic carbon-heteroatom bond instalments
take place with complete regioselectivity and, the resulting
double bond geometry was installed with complete (E)-
selectivity. The reaction was found to be operative for a series of
substrates 2a-o with different substitution pattern at the aryl
group. Para-substitued products 3a-e, meta-substituted products
3g-k and higher-substituted products 3l,m were formed as
generates
a 1,3-butadiene 4, which undergoes a second
regioselective oxidation with TsNHCl followed by an SN2´-
opening of the initial chloronium intermediate B or a nucelophilic
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10.1002/ejoc.201701624
European Journal of Organic Chemistry
FULL PAPER
addition to the corresponding allylic cation B’ (Figure 1). It is
important to note that the overall process liberates additional
amounts of acid, which explains why an initial 2:1-ratio between
TsNClNa and HOAc (Table 1, entry 5) is sufficient for full
conversion of the chloramine salt. Based on this current
understanding, an alternative radical mechanism can be ruled
out. No reaction proceeds in the dark laboratory.[21]
conditions. The related 1,3-cyclohexadiene 4d forms
aminochlorination derivatives 3t/3t’ in good yield as a 1:1-
diastereomeric mixture (entries 2,3). The X-ray structure of 3t
allowed for a definite structural assignment of the isomers.§
Isoprene 4j and 2,3-dimethyl-1,3-butadiene 4e undergo clean
aminochlorination reaction as well forming products 3u/3u’ in a
5:1-mixture of the corresponding double bond isomers (entry 4).
For the dibenzyl derivative 4f, steric reasons lead to the
formation of a single product 3v in high yield (entry 5). The
reaction also proceeds for higher conjugated substrates as
demonstrated for the case of 1,3,5-cycloheptatriene 7, which
forms the 1,6-aminochlorination product 8 as a single isomer in
93% isolated yield, and again demonstrates the inherent
possibilities resulting from the 1/HOAc reagent combination.
TsNHCl
E1
R
R
R
Ar
Ar
Ar
Cl
- HCl
- TsNH2
2
A
4
TsNHCl
Cl
Cl
Ar
Cl
R
R
or/
and
Ar
Ar
R
TsNNaCl (1)
(1.2 equiv)
Cl
NHTs
TsHN
NHTs
NHTs
3
AcOH (1.2 equiv),
(CH2Cl)2, 50ºC, 12h
B
B'
4b-f
3r-v
Product
Yield [%]a
Entry
1
Substrate
Figure 1. Mechanistic rationale.
NHTs
Ph
+
NHTs
Ph
Ph
60
In order to verify the intermediacy of a 1,3-butadiene derivative,
the reaction between 2,3-diphenyl-1,3-butadiene 4a and TsNHCl
was investigated. Indeed, the two products 3p and 3p´ were
formed in 64% yield and in an identical 3:1 isomeric ratio
(Scheme 4), identical to the outcome from oxidation of the
tetrasubstituted alkene 2q from Scheme 3.
Ph
Ph
Cl
Ph
3r:3r' = 1:1
4b
4c
Cl
TsHN
Cl
2
3
96
63
3sc
TsHN
TsHN
+
4d
Cl
Cl
TsNNaCl (1)
(1.2 equiv)
Cl
3t:3t´ = 1:1
Cl
NHTs
+
AcOH
(1.2 equiv),
(CH2Cl)2,
50 ºC, 12 h
NHTs
3p:3p´ = 3:1, 64%
4a
3t(X-ray structure)
Scheme 4. Aminochlorination of butadiene 4a.
TsHN
TsHN
+
Cl
Cl
4
5
4e
61
81
3u:3u´ = 5:1
TsHN
Ph
We realized the aditional attractiveness of this transformation as
it should give general access to those products 3 that cannot be
accessed through the direct allylic C-H oxidation strategy.
Indeed, treatment of several 1,3-butadienes 4b-f with the
TsNHCl reagent was studied more systematically and provided
selective 1,4-oxidation products 3r-v (Scheme 5). First, 1,4-
Disubstituted 1,3-butadiene 4b again follows the general
reactivity and provides the 1,4-aminochlorination product as a
1:1-diastereomeric mixture of 3r/3r´ due to the configurational
lability of the benzylic chloride (entry 1).[17]
Minakata and Kumatsu reported previously the single pioneering
example of an aminochlorination of 1,3-cyclooctadiene 4c with
chloramine-T under carbon dioxide pressure.[15] The yield of 3s
using our methodology compares well with the reported 70% for
the only precedence of this transformation under the previous
Ph
4f
Ph
3v
Ph
Cl
Cl
TsNNaCl (1)
(1.2 equiv)
93
6
AcOH (1.2 equiv),
(CH2Cl)2, 50ºC, 12h
NHTs
5
6
Scheme 5. Regioselective 1,4-aminochlorination of 1,3-butadienes (entries 1-
5) and 1,3,5-heptatriene (entry 6). aIsolated yield after purification. b10:1 ratio
of regioisomers. c10:1 diastereomeric mixture.
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10.1002/ejoc.201701624
European Journal of Organic Chemistry
FULL PAPER
methylbut-2-ene (1.0 equiv) and Pd(PPh3)4 (5 mol%) are added to a
Schlenk tube. The tube is evacuated and refilled with Argon three times,
and DME (31 mL) is added. The reaction mixture is then stirred at room
temperature for 20 min. Sodium carbonate (1 equiv), water (8 mL) and
the boronic acid (2.1 equiv) are added, and the reaction is heated at
reflux for 18 h. The reaction mixture is cooled to room temperature, and
the solvent is removed under reduced pressure. The product is extracted
with diethylether (3x), washed with brine, and concentrated. Column
chromatography on silica gel (100% hexane) gives the tetrasubstituted
alkene products in good yields.
Finally, the reaction could also be conducted for the 1,3-
butadiene unit of myrcene 7. In addition to the expected
regioselective aminochlorination reaction at the butadiene site of
this molecule, the product displayed an additional carbon
chlorine bond derived from an unexpected allylic chlorination
following a Wohl-Ziegler pathway (Scheme 6). This triple allylic
C-H functionalization within a single oxidative transformation
adds to a recent impressive study by Braddock on full oxidative
saturation of myrcene.[22]
1-(tert-Butyl)-4-(3-methylbut-2-en-2-yl)benzene (2e): Obtained as
colourless oil. H NMR (400 MHz, CDCl3): δ = 1.33 (s, 9H), 1.61 (s, 3H),
NHTs
NHTs
Cl
1
TsNNaCl (1)
(2 equiv)
1.82 (s, 3H), 1.96 (s, 3H), 7.06 (d, J = 8.6 Hz, 2H), 7.32 (d, J = 8.6 Hz,
2H). 13C NMR (125 MHz, CDCl3): δ = 20.8, 22.3, 31.6, 34.5, 124.9, 127.1,
128.2, 129.9, 142.3, 148.5. IR ν = 2692, 2910, 2864, 1508, 1460, 1396,
1363, 1269, 1133, 1112, 1017, 834, 758, 616 cm-1. HRMS: calcd for
C15H23: 203.1794; found: 203.1796.
+
Cl
Cl
Cl
AcOH (1 equiv),
(CH2Cl)2, 50ºC, 12h
8:8´= 5:1, 70%
7
General procedure for the dual C-H functionalization: A Pyrex tube
equipped with a stirrer bar is charged with 73 mg chloramine-T (0.22
mmol, 2.0 equiv), 0.01 mL acetic acid (0.11 mmol, 1.0 equiv) and the
alkene (0.11 mmol, 1.0 equiv) in 0.6 mL of absolute dichloroethane. The
solution is stirred at 50 ºC for 20 h. After cooling down to room
temperature, CH2Cl2 is added and the resulting solution is washed three
times with saturated aqueous solution of NaHCO3. The solvent is
evaporated under reduced pressure and the crude product is purified by
chromatography (silica gel, n-hexane/ethyl acetate, 4/1, v/v) to give the
pure product.
Scheme 6. Triple C-H oxidation of myrcene (7) with the 1/HOAc reagent
combination.
Conclusions
In summary, we have reported a new intermolecular allylic
oxidation reaction that converts tetrasubstituted alkenes into the
corresponding 4-chloro-but-2-enyl amine derivatives within a
double allylic amination process. This process proceeds with
excellent regio- and chemoselectivity under mild conditions and
without the requirement of any promoter or catalyst. It
exemplifies that efficient protocols for unprecedented oxidative
C-H functionalization from rather unexpected pathways may
readily derive exploring the reactivity pattern of well-established
(E)-N-(4-Chloro-2-methyl-3-phenylbut-2-en-1-yl)-4-
methylbenzenesulfonamide (3a): Obtained as white foam following the
general procedure. 1H NMR (400 MHz, CDCl3): δ = 1.94 (s, 3H), 2.40 (s,
3H), 3.38 (d, J = 6.3 Hz, 2H), 4.26 (s, 2H), 4.29 (t, J = 6.3 Hz, 1H, NH),
7.04-7.06 (m, 2H), 7.20 (d, J = 8.3 Hz, 2H), 7.26-7.28 (m, 3H), 7.55 (d, J
= 8.3 Hz, 2H). 13C NMR (125 MHz, CDCl3): δ = 16.5, 21.6, 45.6, 46.9,
127.1, 127.6, 128.5, 128.6, 129.8, 134.3, 136.6, 139.4, 143.5. IR ν =
3275, 2956, 2925, 2856, 1708, 1598, 1492, 1442, 1323, 1156, 1092,
1053, 908, 813 cm-1. HRMS: calcd for C18H20ClNNaO2S: 372.0796;
found: 372.0795.
haloamine reagents
.
Experimental Section
(E)-N-(3-([1,1'-Biphenyl]-4-yl)-4-chloro-2-methylbut-2-en-1-yl)-4-
methylbenzenesulfonamide (3b): Obtained as white foam following the
general procedure. 1H NMR (400 MHz, CDCl3): δ = 1.98 (s, 3H), 2.26 (s,
3H), 3.43 (d, J = 5.1 Hz, 2H), 4.30 (s, 2H), 4.42 (br t, J = 8.9 Hz, 1H, NH),
7.12 (d, J = 7.9 Hz, 2H), 7.86 (d, J = 7.2 Hz, 2H), 7.36-7.39 (m, 1H),
7.45-7.48 (m, 4H), 7.55-7.58 (m, 4H). 13C NMR (125 MHz, CDCl3): δ =
16.6, 21.5, 45.5, 47.1, 127.0, 127.1, 127.2, 127.6, 128.9, 129.7, 134.5,
136.5, 138.3, 140.5, 140.6, 143.6. IR ν =3275, 2960, 2956, 2925, 2856,
1492, 1442, 1323, 1156, 1092, 1053, 909, 813 cm-1. HRMS: calcd for
C24H24ClNNaO2S: 448.1109; found: 448.1108.
General. All solvents, reagents and all deuterated solvents were
purchased from Aldrich and TCI. Column chromatography was
performed with silica gel (Merck, type 60, 0.063-0.2 mm). NMR spectra
were recorded on a Bruker Avance 400 MHz or 500 MHz spectrometers,
respectively. All chemical shifts in NMR experiments were reported as
ppm downfield from TMS. The following calibrations were used: CDCl3
δ
= 7.26 and 77.0 ppm. MS (ESI-LCMS) experiments were performed
using an Agilent 1100 HPLC with a Bruker micro-TOF instrument (ESI). A
Supelco C8 (5 cm x 4.6 mm, 5 µm particles) column was used with a
linear elution gradient from 100% H2O (0.5% HCO2H) to 100% MeCN in
13 min at a flow rate of 0.5 mL/min. MS (EI) and HRMS experiments
were performed on a Kratos MS 50 within the service centers at ICIQ. IR
spectra were taken in a Bruker Alpha instrument in the solid state. The
following compounds were commercially available and directly used as
received: 2,3-dimethylbuta-1,3-diene, cycloocta-1,3-diene, cyclohexa-
1,3-diene, cyclohepta-1,3,5-triene, (1E, 3E)-1,4-diphenylbuta-1,3-diene,
myrcene, (2,3-dimethylenebutane-1,4-diyl)dibenzene and (E)-but-2-ene-
2,3-diyldibenzene.
(E)-N-(4-Chloro-3-(4-chlorophenyl)-2-methylbut-2-en-1-yl)-4-
methylbenzenesulfonamide (3c): Obtained as white foam following the
general procedure. 1H NMR (400 MHz, CDCl3): δ = 1.94 (s, 3H), 2.43 (s,
3H), 3.33 (d, J = 5.6 Hz, 2H), 4.22 (s, 2H), 4.46 (t br, J = 6.1 Hz, 1H, NH),
6.97 (d, J = 8.4 Hz, 2H), 7.21 (dd, J = 9.2, 8.1 Hz, 4H), 7.54 (d, J = 8.2
Hz, 2H). 13C NMR (125 MHz, CDCl3): δ = 16.5, 21.7, 45.3, 46.9, 127.1,
128.9, 129.8, 129.9, 133.7, 134.9, 135.7, 136.3, 137.7, 143.8. IR: ν =
3276, 2953, 2922, 2854, 1490, 1325, 1159, 1092, 831 cm-1. HRMS:
calcd. for C18H19Cl2NNaO2S: 406.0404; found: 406.0406.
Synthesis of tetrasubstituted alkenes 2. The synthesis of
tetrasubstituted alkenes was adapted from
a previously reported
procedure.[23]
A
representative example is as follows: 2-bromo-3-
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10.1002/ejoc.201701624
European Journal of Organic Chemistry
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(E)-N-(4-Chloro-2-methyl-3-(p-tolyl)but-2-en-1-yl)-4-
Hz, 2H), 7.53 (d, J = 8.2 Hz, 2H), 7.72 (s, 1H), 7.94 (d, J = 7.7 Hz, 1H).
13C NMR (125 MHz, CDCl3): δ = 14.5, 16.5, 21.6, 45.3, 46.9, 61.3, 127.1,
128.8, 129.5, 129.7, 130.9, 133.2, 135.1, 135.8, 136.4, 139.6, 143.6,
166.3. IR ν = 3260, 3021, 2982, 2959, 2926, 1717, 1431, 1303, 1251,
1158, 1092, 751 cm-1. HRMS: calcd for C21H24ClNNaO4S: 444.1007;
found: 444.0993.
methylbenzenesulfonamide (3d): Obtained as white foam following the
general procedure. 1H NMR (400 MHz, CDCl3): δ = 1.92 (s, 3H), 2.33 (s,
3H), 2.40 (s, 3H), 3.39 (d, J = 6.2 Hz, 2H), 4.24 (s, 2H), 4.48 (t, J = 6.2
Hz, 1H, NH), 6.93 (d, J = 8.0 Hz, 2H), 7.06 (d, J = 8.1 Hz, 2H), 7.21 (d, J
= 8.4 Hz, 2H), 7.57 (d, J = 8.3 Hz, 2H). 13C NMR (125 MHz, CDCl3): δ =
16.5, 21.3, 21.6, 45.7, 46.9, 127.2, 128.4, 129.2, 129.7, 134.0, 136.4,
136.7, 137.3, 143.4. IR ν = 3273, 3024, 2923, 2855, 1598, 1442, 1323,
1256, 1184, 1157, 1092, 1052, 950, 813, 662 cm-1. HRMS: calcd for
C19H22ClNNaO2S: 386.0952; found: 386.0957.
(E)-N-(4-Chloro-2-methyl-3-(m-tolyl)but-2-en-1-yl)-4-
methylbenzenesulfonamide (3j): Obtained as yellow foam following the
1
general procedure. H NMR (400 MHz, CDCl3): δ = 1.93 (s, 3H), 2.30 (s,
3H), 2.40 (s, 3H), 3.39 (d, J = 6.1 Hz, 2H), 4.24 (s, 2H), 4.32 (brt, 1H,
NH), 6.83 (d, J = 7.7 Hz, 1H), 6.87 (s, 1H), 7.07 (d, J = 7.6 Hz, 1H), 7.15
(t, J = 7.5 Hz, 1H), 7.20 (d, J = 8.0 Hz, 2H), 7.56 (d, J = 8.2 Hz, 2H). 13C
NMR (125 MHz, CDCl3): δ = 16.5, 21.5, 21.6, 125.6, 127.1, 128.4, 128.5,
129.1, 129.7, 134.1, 136.7, 136.9, 138.3, 139.4, 143.5. IR ν = 3277, 2956,
2922, 2852, 1455, 1322, 1157, 1092, 1053, 662, 551 cm-1. HRMS: calcd
for C19H22ClNNaO2S: 386.0941; found: 386.0952.
(E)-N-(3-(4-(tert-Butyl)phenyl)-4-chloro-2-methylbut-2-en-1-yl)-4-
methylbenzenesulfonamide (3e): Obtained as white foam following the
general procedure. 1H NMR (400 MHz, CDCl3): δ = 1.31 (s, 9H), 1.92 (s,
3H), 2.39 (s, 3H), 3.40 (d, J = 6.3 Hz, 2H), 4.25 (s, 2H), 4.49 (t, J = 6.3
Hz, 1H, NH), 6.99 (d, J = 8.3 Hz, 2H), 7.21 (d, J = 8.3 Hz, 2H), 7.26-7.28
(m, 2H), 7.59 (d, J = 8.3 Hz, 2H). 13C NMR (125 MHz, CDCl3): δ = 16.5,
21.6, 31.4, 34.6, 45.8, 47.0, 125.4, 127.2, 128.2, 129.7, 134.1, 136.4,
136.6, 136.8, 143.4, 150.5. IR ν = 3273, 2961, 2926, 2867, 1598, 1401,
1266, 1158, 1092, 1054, 837, 813, 704 cm-1. HRMS: calcd for
C22H28ClNNaO2S: 428.1417; found: 428.1421.
(E)-N-(4-Chloro-3-(3-methoxyphenyl)-2-methylbut-2-en-1-yl)-4-
methylbenzenesulfonamide (3k): Obtained as yellow foam following
1
the general procedure. H NMR (400 MHz, CDCl3): δ = 1.93 (s, 3H), 2.40
(s, 3H), 3.39 (d, J = 6.3 Hz, 2H), 3.77 (s, 3H), 4.24 (s, 2H), 4.44 (brt, 1H,
NH), 6.61-6.63 (m, 2H), 6.80 (d, J = 8.3 Hz, 1H), 7.15-7.21 (m, 3H), 7.56
(d, J = 8.2 Hz, 2H). 13C NMR (125 MHz, CDCl3): δ = 16.5, 21.6, 45.5,
46.9, 55.3, 113.3, 114.2, 120.9, 127.1, 129.6, 129.7, 134.4, 136.5, 136.6,
140.8, 143.5, 159.7. IR ν =: 3276, 3020, 2958, 2925, 2854, 1320, 1304,
1215, 1159, 746 cm-1. HRMS: calcd for C19H22ClNNaO3S: 402.0901;
found: 402.0895.
(E)-N-(4-Chloro-2-methyl-3-(naphthalen-2-yl)but-2-en-1-yl)-4-
methylbenzenesulfonamide (3f): Obtained as a white solid following
1
the general procedure. m.p: 128-129 ºC. H NMR (400 MHz, CDCl3): δ =
2.02 (s, 3H), 2.24 (s, 3H), 3.39 (d, J = 6.2 Hz, 2H), 4.34 (s, 2H), 4.45 (t, J
= 8.0 Hz, 1H, NH), 6.94 (d, J = 8.4 Hz, 2H), 7.16 (dd, J = 8.4, 1.8 Hz, 1H),
7.43 (d, J = 8.3 Hz, 2H), 7.49-7.52 (m, 3H), 7.73 (d, J = 8.5 Hz, 1H),
7.75-7.78 (m, 1H), 7.80-7.84 (m, 1H). 13C NMR (125 MHz, CDCl3): δ =
16.7, 21.5, 45.6, 47.1, 126.3, 126.5, 126.6, 126.9, 127.5, 127.8, 128.1,
128.4, 129.6, 132.7, 133.2, 134.7, 136.2, 136.8, 136.9, 143.4. IR ν =
3266, 3055, 2953, 2923, 2853, 1597, 1496, 1184, 1155, 1091, 1051, 812,
750, 721, 705, 683, 663, 573 cm-1. HRMS: calcd for C22H22ClNNaO2S:
422.0905; found: 422.0934.
(E)-N-(4-Chloro-3-(3-chloro-4-methylphenyl)-2-methylbut-2-en-1-yl)-
4-methylbenzenesulfonamide (3l): Obtained as yellow foam following
the general procedure. 1H NMR (400 MHz, CDCl3): δ = 1.93 (s, 3H), 2.35
(s, 3H), 2.40 (s, 3H), 3.36 (d, J = 6.2 Hz, 2H), 4.21 (s, 2H), 4.45 (brt, J =
6.3 Hz, 1H, NH), 6.84 (dd, J = 7.7, 1.8 Hz, 1H), 7.05 (d, J = 1.8 Hz, 1H),
7.11 (d, J = 7.7 Hz, 1H), 7.22 (d, J = 8.1 Hz, 2H), 7.57 (d, J = 8.2 Hz, 2H).
13C NMR (125 MHz, CDCl3): δ = 16.6, 19.9, 21.7, 45.4, 46.9, 127.0,
127.2, 128.9, 129.7, 131.0, 134.5, 134.9, 135.4, 135.5, 136.5, 138.4,
143.6. IR ν = 3276, 2956, 2923, 2851, 1436, 1321, 1158, 1050, 813, 550
cm-1. HRMS: calcd for C19H21Cl2NNaO2S: 420.0562; found: 420.0553.
(E)-N-(4-Chloro-3-(3-chlorophenyl)-2-methylbut-2-en-1-yl)-4-
methylbenzenesulfonamide (3g): Obtained as yellow foam following
1
the general procedure. H NMR (400 MHz, CDCl3): δ = 1.95 (s, 3H), 2.40
(s, 3H), 3.35 (d, J = 6.2 Hz, 2H), 4.22 (s, 2H), 4.39 (brt, J = 6.9 Hz, 1H,
NH), 6.94 (dt, J = 7.3, 1.5 Hz, 1H), 7.06 (t, J = 1.8 Hz, 1H), 7.18-7.25 (m,
4H), 7.56 (d, J = 8.3 Hz, 2H). 13C NMR (125 MHz, CDCl3): δ = 16.4, 21.7,
45.2, 46.8, 127.0, 127.1, 127.9, 128.6, 129.8, 129.9, 143.5, 135.3, 135.4,
136.4, 141.2, 143.7. IR ν = 3270, 2958, 2918, 2849, 1594, 1406, 1324,
1158, 1093, 813, 750, 663 cm-1. HRMS: calcd for C18H19Cl2NNaO2S:
406.0406; found: 406.0406.
(E)-N-(4-Chloro-3-(3-fluoro-4-methylphenyl)-2-methylbut-2-en-1-yl)-4-
methylbenzenesulfonamide (3m): Obtained as yellow foam following
the general procedure. 1H NMR (400 MHz, CDCl3): δ = 1.92 (s, 3H), 2.25
(s, 3H), 2.40 (s, 3H), 3.37 (d, J = 5.8 Hz, 2H), 4.21 (s, 2H), 4.51 (brt, 1H,
NH), 6.69-6.72 (m, 2H), 7.06 (t, J = 7.9 Hz, 1H), 7.22 (d, J = 7.9 Hz, 2H),
7.58 (d, J = 7.9 Hz, 2H). 13C NMR (125 MHz, CDCl3): δ = 14.5, 16.4, 21.7,
45.4, 46.9, 115.2 (d, JC-F = 22.3 Hz), 124.1 (d, JC-F = 3.5 Hz), 126.6,
127.2, 129.7, 131.6 (d, JC-F = 5.7 Hz), 134.7, 135.6, 136.5, 138.7 (d, JC-F
= 7.5 Hz), 143.6, 161.1 (d, JC-F = 246.1 Hz). 19F NMR (376 MHz, CDCl3):
δ = -116.8. IR ν = 3271, 2958, 2925, 2853, 1406, 1323, 1159, 812, 663
cm-1. HRMS: calcd for C19H21ClFNNaO2S: 404.0858; found: 404.0846.
(E)-N-(4-Chloro-3-(3-fluorophenyl)-2-methylbut-2-en-1-yl)-4-
methylbenzenesulfonamide (3h): Obtained as yellow foam following
1
the general procedure. H NMR (400 MHz, CDCl3): δ = 1.94 (s, 3H), 2.40
(s, 3H), 3.36 (d, J = 6.2 Hz, 2H), 4.22 (s, 2H), 4.51 (t, J = 6.3 Hz, 1H, NH),
6.77 (ddd, J = 9.5, 2.6, 1.5 Hz, 1H), 6.83 (dt, J = 7.6, 1.2 Hz, 1H), 6.95
(tdd, J = 8.5, 2.6, 1.0 Hz, 1H), 7.20-7.24 (m, 3H), 7.57 (d, J = 8.2 Hz, 2H).
13C NMR (125 MHz, CDCl3): δ = 16.3, 21.5, 45.1, 46.7, 114.5 (d, JC-F
20.9 Hz), 115.5 (d, JC-F = 21.3 Hz), 124.3 (d, JC-F = 3.0 Hz), 126.9, 129.7,
130.0 (d, JC-F = 8.5 Hz), 134.9, 135.3, 136.3, 141.4 (d, JC-F = 7.6 Hz),
143.6, 162.5 (d, JC-F = 247.5 Hz). 19F NMR (376 MHz, CDCl3): δ = -112.4.
IR ν = 3269, 2959, 2929, 2850, 1580, 1431, 1322, 1151, 1092, 663, 551
cm-1. HRMS: calcd for C18H19ClFNNaO2S: 390.0701; found: 390.0690.
=
(E)-N-(3-([1,1'-Biphenyl]-2-yl)-4-chloro-2-methylbut-2-en-1-yl)-4-
methylbenzenesulfonamide (3n) and (Z)-N-(3-([1,1'-Biphenyl]-2-yl)-4-
chloro-2-methylbut-2-en-1-yl)-4-methylbenzenesulfonamide
(3n´):
1
Obtained as yellow foams following the general procedure. H NMR (400
MHz, CDCl3): δ = 1.80 (s, 6H), 2.41 (s, 6H), 3.15-3.17 (m, 2H), 3.28-3.30
(m, 2H), 3.48 (brt, 2H, NH), 3.87-3.89 (m, 2H), 4.28-4.30 (m, 2H), 7.16-
7.18 (m, 3H), 7.19-7.21 (m, 2H), 7.24 (d, J = 8.3 Hz, 4H), 7.29 (dd, J =
7.2, 1.5 Hz, 4H), 7.33-7.37 (m, 9H), 7.57 (d, J = 8.3 Hz, 4H). 13C NMR
(125 MHz, CDCl3): δ = 15.9, 21.7, 45.7, 47.2, 127.1, 127.6, 127.7, 128.2,
128.5, 129.2, 129.7, 130.1, 130.3, 134.6, 135.4, 136.8, 137.5, 140.2,
140.9, 143.5. IR ν = 3275, 3060, 3022, 2925, 2855, 1495, 1156, 1119,
(E)-Ethyl 3-(1-chloro-3-methyl-4-(4-methylphenylsulfonamido)but-2-
en-2-yl)benzoate (3i): Obtained as yellow foam following the general
1
procedure. H NMR (400 MHz, CDCl3): δ = 1.40 (t, J = 7.1 Hz, 3H), 1.96
(s, 3H), 2.38 (s, 3H), 3.33 (d, J = 6.2 Hz, 2H), 4.26 (s, 2H), 4.39 (q, J =
7.2 Hz, 2H), 4.50 (brt, 1H, NH), 7.17 (d, J = 8.1 Hz, 2H), 7.34 (t, J = 7.7
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201701624
European Journal of Organic Chemistry
FULL PAPER
1092, 1052, 1009, 813, 746, 721, 701, 663 cm-1. HRMS: calcd for
C24H24ClNNaO2S: 448.1108; found: 448.1108.
127.5, 128.0, 128.1, 128.2, 128.3, 128.4, 128.5, 128.6, 128.7, 128.8,
129.4, 129.5, 143.6, 134.8, 135.4, 135.5, 136.1, 137.0, 137.2, 137.3,
143.3, 143.4. IR ν = 3270, 3060, 3029, 2958, 2922, 2865, 1494, 1324,
1155, 1118, 1066, 964, 811, 748, 694, 665, 600 cm-1. HRMS: calcd for
C23H21ClNO2S: 410.0987; found: 410.0985.
(E)-N-(4-Chloro-2-methyl-3-(o-tolyl)but-2-en-1-yl)-4-
methylbenzenesulfonamide (3o) and (Z)-N-(4-Chloro-2-methyl-3-(o-
tolyl)but-2-en-1-yl)-4-methylbenzenesulfonamide (3o´): Obtained as
white foams following the general procedure. 1H NMR (400 MHz, CDCl3):
δ = 1.90 (s, 6H), 2.12 (s, 6H), 2.42 (s, 6H), 3.22-3.24 (m, 2H), 3.31-3.33
(m, 2H), 4.12-4.14 (m, 2H), 4.21 (brt, J = 6.4 Hz, 2H, NH), 4.36-4.38 (m,
2H), 6.97 (m, 2H), 7.11-7.16 (m, 4H), 7.19-7.22 (m, 6H), 7.55 (d, J = 8.3
Hz, 4H). 13C NMR (125 MHz, CDCl3): δ = 16.1, 19.8, 21.6, 45.2, 46.9,
126.0, 127.0, 127.8, 129.4, 129.8, 130.4, 134.7, 135.5, 136.6, 138.6,
143.5. IR ν = 3274, 2957, 29221, 2853, 1598, 1488, 1400, 1166, 1056,
982 cm-1. HRMS: calcd for C19H22ClNNaO2S: 386.0952; found: 386.0941.
(Z)-N-(4-Chlorocyclooct-2-en-1-yl)-4-methylbenzenesulfonamide
(3s):[15] Obtained as a yellow oil following the general procedure. Major
diastereomer: 1H NMR (400 MHz, CDCl3): δ = 1.31-1.88 (m, 6H), 1.98-
2.13 (m, 2H), 2.43 (s, 3H), 4.45 (d, J = 7.2 Hz, 1H, NH), 4.59-4.65 (m,
1H), 4.69 (ddd, J = 10.4, 6.6, 4.6 Hz, 1H), 5.17 (ddd, J = 11.9, 7.2, 0.8 Hz,
1H), 5.66 (ddd, J = 11.9, 6.5, 1.5 Hz, 1H), 7.30 (d, J = 8.0 Hz, 2H), 7.78
(d, J = 8.3 Hz, 2H). 13C NMR (125 MHz, CDCl3): δ = 21.7, 22.8, 23.7,
34.9, 37.4, 51.5, 57.6, 127.5, 129.8, 131.1, 132.1, 137.6, 146.6. Minor
diastereomer: 1H NMR (400 MHz, CDCl3): δ = 1.31-1.88 (m, 6H), 1.98-
2.13 (m, 2H), 2.43 (s, 3H), 4.45 (d, J = 7.2 Hz, 1H, NH), 4.59-4.65 (m,
1H), 4.69 (ddd, J = 10.4, 6.6, 4.6 Hz, 1H), 5.11 (ddd, J = 10.9, 8.4, 1.5 Hz,
1H), 5.52 (ddd, J = 10.9, 7.9, 1.5 Hz, 1H), 7.30 (d, J = 8.0 Hz, 2H), 7.73
(d, J = 8.3 Hz, 2H). 13C NMR (125 MHz, CDCl3): δ = 21.7, 22.8, 23.7,
34.9, 37.4, 51.5, 57.6, 127.5, 129.8, 131.1, 132.1, 137.6, 146.6.
(E)-N-(4-Chloro-2,3-diphenylbut-2-en-1-yl)-4-
methylbenzenesulfonamide 3p and (Z)-N-(4-Chloro-2,3-diphenylbut-
2-en-1-yl)-4-methylbenzenesulfonamide (3p´): Obtained as white
foams following the general procedure. Major diastereomer: 1H NMR
(400 MHz, CDCl3): δ = 2.44 (s, 3H), 3.75 (d, J = 6.1 Hz, 2H), 4.11 (s, 2H),
4.24 (t, J = 6.3 Hz, 1H, NH), 7.18 (d, J = 8.3 Hz, 2H), 7.22-7.27 (m, 4H),
7.37-7.40 (m, 6H), 7.43 (d, J = 8.2 Hz, 2H). 13C NMR (125 MHz, CDCl3):
δ = 21.6, 46.5, 46.9, 127.2, 128.1, 128.4, 128.5, 128.6, 128.7, 128.9,
129.6, 136.3, 137.4, 138.1, 138.2, 138.3, 143.4. IR ν = 3227, 3023, 2949,
2934, 2885, 2854, 1425, 1345, 1185, 1029, 940, 790, 767, 699 cm-1.
HRMS: calcd for C23H21ClNO2S: 410.0987; found: 410.0987.
N-(4-Chlorocyclohex-2-en-1-yl)-4-methylbenzenesulfonamide
(3t):
Obtained as an inseparable 1:1 diasteromeric mixture as yellow oil
following the general procedure. 1H NMR (400 MHz, CDCl3): δ = 1.76-
1.80 (m, 2H), 1.98-2.02 (m, 2H), 2.43 (s, 3H), 3.87-3.92 (m, 1H), 4.45-
4.46 (m, 1H), 5.52 (dd, J = 9.9, 2.6 Hz, 1H), 5.84 (dtd, J = 8.3, 4.3, 2.0 Hz,
1H), 7.31 (d, J = 8.3 Hz, 2H), 7.77 (d, J = 8.2 Hz, 2H). 13C NMR (125
MHz, CDCl3): δ = 21.6, 26.2, 30.4, 49.5, 53.1, 127.1, 129.9, 131.0, 131.1,
131.2, 131.3, 138.3, 143.7. IR ν = 3247, 2958, 2923, 2866, 1494, 1433,
1080, 979, 810, 663, 582 cm-1. HRMS: calcd for C13H16ClNNaO2S:
308.0482; found: 308.0480.
(±)-N-(E)-5-Chloro-3,4-diphenylhex-3-en-2-yl)-4-
methylbenzenesulfon-amides (3q) and (3q´): Obtained as white foam
following the general procedure. Major diastereomer: 1H NMR (400 MHz,
CDCl3): δ = 1.12 (d, J = 6.3 Hz, 3H), 1.23 (d, J = 6.7 Hz, 3H), 2.46 (s, 3H),
3.99-4.04 (m, 1H), 4.56 (q, J = 6.7 Hz, 1H), 7.28 (d, J = 8.3 Hz, 2H),
7.36-7.50 (m, 10H), 7.57 (d, J = 8.2 Hz, 2H). 13C NMR (125 MHz, CDCl3):
δ = 21.7, 22.3, 24.0, 50.8, 57.6, 127.3, 127.9, 128.2, 129.7, 135.2, 135.5,
137.8, 139.5, 141.4, 143.4. IR ν = 3286, 2964, 2924, 2854, 1598, 1494,
1421, 1185, 1161, 814, 753, 701, 660, 622, 585, 566 cm-1. HRMS: calcd
for C25H25ClNO2S: 438.1306; found: 438.1300. Minor diastereomer: 1H
NMR (400 MHz, CDCl3): δ = 0.94 (d, J = 6.7 Hz, 3H), 1.30 (d, J = 6.8 Hz,
3H), 2.42 (s, 3H), 3.93-3.99 (m, 1H), 4.61 (q, J = 6.7 Hz, 1H), 7.23 (d, J =
8.2 Hz, 2H), 7.36-7.50 (m, 10H), 7.56 (d, J = 8.2 Hz, 2H). 13C NMR (125
MHz, CDCl3): δ = 21.7, 22.3, 23.5, 50.7, 58.2, 127.3, 127.7, 128.1, 129.6,
135.3, 135.5, 137.6, 139.4, 141.7, 143.4.
(E)-N-(4-Chloro-2,3-dimethylbut-2-en-1-yl)-4-
methylbenzenesulfonamide
(3u)
and
(Z)-N-(4-Chloro-2,3-
dimethylbut-2-en-1-yl)-4-methylbenzenesulfonamide (3u´): Obtained
as a 5:1 diasteromeric mixture as yellow oil following the general
1
procedure. Major diastereomer: H NMR (400 MHz, CDCl3): δ = 1.71 (s,
3H), 1.73 (s, 3H), 2.46 (s, 3H), 3.64 (d, J = 6.0 Hz, 2H), 3.99 (s, 2H), 4.41
(t, J = 6.0 Hz, 1H, NH), 7.33 (d, J = 8.1 Hz, 2H), 7.77 (d, J = 8.3 Hz, 2H).
13C NMR (125 MHz, CDCl3): δ = 16.7, 16.8, 21.7, 45.9, 46.2, 127.3,
129.9, 130.3, 130.5, 136.9, 143.7. IR ν(cm-1): 3296, 2969, 2923, 2865,
1493, 1419, 1255, 1184, 1151, 839, 812, 661, 550. HRMS: calcd for
C13H17ClNO2S: 286.0677; found: 286.0674. Minor diastereomer: 1H NMR
(400 MHz, CDCl3): δ = 1.67 (s, 3H), 1.76 (s, 3H), 2.46 (s, 3H), 3.62 (d, J
= 6.0 Hz, 2H), 3.97 (s, 2H), 4.46 (t, J = 6.0 Hz, 1H, NH), 7.34 (d, J = 8.1
Hz, 2H), 7.78 (d, J = 8.3 Hz, 2H). 13C NMR (125 MHz, CDCl3): δ = 17.7,
17.8, 21.7, 45.4, 45.5, 127.3, 129.9, 130.3, 130.5, 136.9, 143.7.
General procedure for the aminochlorination of 1,3-butadienes: A
Pyrex tube equipped with a stirrer bar is charged with 44 mg chloramine-
T (0.22 mmol, 1.2 equiv), 0.013 mL acetic acid (0.13 mmol, 1.2 equiv)
and the butadiene (0.11 mmol, 1.0 equiv) in 0.5 mL of absolute
dichloroethane. The solution is stirred at 50 ºC for 20 h. After cooling
down to room temperature, CH2Cl2 is added and the resulting solution is
washed three times with saturated aqueous solution of NaHCO3. The
solvent is evaporated under reduced pressure and the crude product is
purified by chromatography (silica gel, n-hexane/ethyl acetate, 4/1, v/v) to
give the pure product.
(E)-N-(2,3-Dibenzyl-4-chlorobut-2-en-1-yl)-4-
methylbenzenesulfonamide (3v): Obtained as a white foam following
the general procedure. 1H NMR (400 MHz, CDCl3): δ = 2.42 (s, 3H), 3.54-
3.56 (m, 4H), 3.60 (s, 2H), 4.11 (s, 2H), 7.06-7.11 (m, 4H), 7.22-7.31 (m,
8H), 7.56-7.58 (m, 2H). 13C NMR (125 MHz, CDCl3): δ = 21.7, 35.8, 36.5,
43.7, 43.8, 126.8, 126.9, 127.3, 128.6, 128.8, 129.9, 135.2, 135.8, 136.4,
138.1, 138.9, 143.7. IR ν = 3277, 3061, 3027, 2924, 1493, 1254, 1121,
1053, 843, 698, 665, 550 cm-1. HRMS: calcd for C25H26ClNNaO2S:
462.1265; found: 462.1268.
N-((1S,4S,E)-4-Chloro-1,4-diphenylbut-2-en-1-yl)-4-
methylbenzenesulfonamide (3r) and N-((1S,4R,E)-4-Chloro-1,4-
diphenylbut-2-en-1-yl)-4-methylbenzenesulfonamide (3r´): Obtained
as a 1:1-mixture as white foam following the general procedure. 1H NMR
(400 MHz, CDCl3): δ = 2.30 (s, 3H), 2.33 (s, 3H), 4.69-4.72 (m, 1H), 4.74
(dd, J = 8.0 Hz, 2H), 4.82 (dd, J = 8.9, 50 Hz, 1H), 5.63 (d, J = 7.4 Hz, 1H,
NH), 5.68 (d, J = 8.4 Hz, 1H, NH), 5.87 (dd, J = 15.7, 9.0 Hz, 1H), 6.06-
6.12 (m, 1H), 6.56 (dd, J = 15.7, 2.2 Hz, 2H), 7.07 (d, J = 8.1 Hz, 4H),
7.10-7.31 (m, 20H), 7.54-7.58 (m, 4H). 13C NMR (125 MHz, CDCl3): δ =
21.6, 62.1, 62.4, 66.3, 66.7, 125.1, 125.4, 126.9, 127.0, 127.1, 127.2,
N-(6-Chlorocyclohepta-2,4-dien-1-yl)-4-methylbenzenesulfonamide
(6): Obtained as yellow oil following the general procedure. 1H NMR (400
MHz, CDCl3): δ = 2.28 (ddd, J = 7.1, 5.5, 3.2 Hz, 2H), 2.43 (s, 3H), 4.28-
4.33 (m, 1H), 4.60-4.64 (m, 1H), 4.69 (d, J = 8.3 Hz, 1H, NH), 5.74-5.76
(m, 2H), 5.78-5.83 (m, 1H), 5.89-5.93 (m, 1H), 7.32 (d, J = 8.0 Hz, 2H),
7.80 (d, J = 8.3 Hz, 2H). 13C NMR (125 MHz, CDCl3): δ = 21.7, 41.6, 50.6,
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55.7, 123.7, 125.2, 127.4, 129.9, 133.3, 137.2, 137.4, 143.8. IR ν = 3270,
3029, 2925, 2858, 1493, 1325, 1217, 1155, 691 cm-1. HRMS: calcd for
C14H16ClNNaO2S: 320.0482; found: 320.0477.
Pérez, Chem. Rev. 2008, 108, 3379; l) R. Giri, B.-F. Shi, K. M. Engle, N.
Maugel, J.-Q. Yu, Chem. Soc. Rev. 2009, 38, 3242; m) X. Chen, K. M.
Engle, D. H. Wang, J.-Q. Yu, Angew. Chem. 2009, 121, 5196; Angew.
Chem. Int. Ed. 2009, 48, 5094.
[3]
[4]
K. Godula, D. Sames, Science 2006, 312, 67.
(E)-N-(5-Chloro-2-(2-chloroethylidene)-6-methylhept-6-en-1-yl)-4-
R. Samanta, K. Matcha, A. P. Antonchick, Eur. J. Org. Chem. 2013,
5769.
methylbenzenesulfonamide
(8)
and
(Z)-N-(5-Chloro-2-(2-
chloroethylidene)-6-methylhept-6-en-1-yl)-4-
[5]
a) K. B. Wiberg, S. D. Nielsen, J. Org. Chem. 1964, 29, 3353; b) G.
Dupont, W.Zacharewicz, Bull. Soc. Chim. Fr. 1935, 2, 533; c) A.
Guillemonat, Ann. Chem. (Warsaw) 1939, 11, 143; d) K. B. Sharpless,
R. F. Lauer, J. Am. Chem. Soc. 1972, 94, 7154; e) D. Arigoni, A.
Vasella, K. B. Sharpless, H. P. Jensen, J. Am. Chem. Soc. 1973, 95,
7917; f) D. H. R. Barton D. Crich, Tetrahedron 1985, 41, 4359 .
a) K. B. Sharpless, T. Hori, L. K. Truesdale, C. O. Dietrich, J. Am.
Chem. Soc. 1976, 98, 269; b) M. Bruncko, T. A. V. Khuong, K. B.
Sharpless, Angew. Chem. 1996, 108, 453; Angew. Chem. Int. Ed. Engl.
1996, 35, 454.
methylbenzenesulfonamide (8´): Obtained as
a
5:1 diasteromeric
mixture as yellow oil following the general procedure. Major regioisomer:
1H NMR (400 MHz, CDCl3): δ = 1.79 (s, 3H), 1.84 (m, 2H), 2.10-2.16 (m,
1H), 2.18-2.24 (m, 1H), 2.43 (s, 3H), 3.52 (d, J = 6.3 Hz, 2H), 4.02 (d, J =
7.9 Hz, 2H), 4.25 (t, J = 7.1 Hz, 1H), 4.82 (brt, 1H, NH), 4.90 (d, J = 1.3
Hz, 1H), 5.00 (d, J = 1.3 Hz, 1H), 5.60 (t, J = 7.9 Hz, 1H), 7.31 (d, J = 8.1
Hz, 2H), 7.74 (d, J = 8.1 Hz, 2H). 13C NMR (125 MHz, CDCl3): δ = 17.3,
21.6, 25.6, 34.8, 39.5, 48.3, 66.0, 114.6, 125.2, 127.2, 129.9, 136.8,
139.3, 143.8, 143.9. IR ν = 3250, 2960, 2922, 2874, 1494, 1093, 662,
552, 479 cm-1. HRMS: calcd for C17H23Cl2NNaO2S: 398.0719; found:
398.0719. Minor regioisomer: 1H NMR (400 MHz, CDCl3): δ = 1.79 (s,
3H), 1.84 (m, 2H), 2.10-2.16 (m, 1H), 2.18-2.24 (m, 1H), 2.43 (s, 3H),
3.52 (d, J = 6.3 Hz, 2H), 3.93 (d, J = 2.7 Hz, 1H), 3.97 (m, 1H), 4.82 (brt,
1H, NH), 4.89 (d, J = 1.2 Hz, 1H), 4.98 (d, J = 1.2 Hz, 1H), 5.31 (t, J = 6.9
Hz, 1H), 7.31 (d, J = 8.1 Hz, 2H), 7.74 (d, J = 8.1 Hz, 2H). 13C NMR (125
MHz, CDCl3): δ = 17.3, 21.6, 25.6, 34.8, 39.5, 48.3, 66.0, 114.6, 125.2,
127.2, 129.9, 136.8, 139.3, 143.8, 143.9.
[6]
[7]
a) J. A. Souto, D. Zian, K. Muñiz, J. Am. Chem. Soc. 2012, 134, 7242;
b) U. Atmaca, H. K. Usanmaz, M. Celik, Tetrahedron Lett. 2014, 55,
2230; c) P. Magnus, J. Lacour, J. Am. Chem. Soc. 1992, 114, 767;
d) P. Magnus, J. Lacour, J. Am. Chem. Soc. 1992, 114, 3993; e) S. V.
Kohlhepp, T. Gulder, Chem. Soc. Rev. 2016, 45, 6270.
[8]
For a recent TEMPO-mediated allylic C-H functionalization: X. Zhu, S.
Chiba, Org. Biomol. Chem. 2014, 12, 4567.
[9]
S. Minakata, Acc. Chem. Res. 2009, 42, 1172.
[10] M. M. Campbell, G. Johnson, Chem. Rev. 1978, 78, 65.
[11] C. Djerassi, Chem. Rev. 1948, 48, 271.
Acknowledgements
[12] a) R. R. Goehring, Enzyklopedia of Reagents for Organic Chemistry
(Ed.: L. A. Paquette), Wiley, New York, 1995, Vol. 2, 1054-56.
[13] a) M. E. Wolff, Chem. Rev. 1963, 63, 55; B) L. Stella, Angew. Chem.
1983, 95, 368; Angew. Chem. Int. Ed. 1983, 22, 337; c) J. L. Jeffrey, R.
Sarpong, Chem. Sci. 2013, 4, 4092
Financial support for this research was provided by the Ministry
of Economy and Competitiveness of Spain and FEDER
(CTQ2014-56474R grant to K. M., and Severo Ochoa
Excellence Accreditation 2014-2018 to ICIQ, SEV-2013-
0319). The authors acknowledge ICIQ and COST Action
CA15106 “C-H Activation in Organic Synthesis” (CHAOS)
for additional support, and E. Escudero-Adán for support
[14] For recent contributions: a) C. Martínez, K. Muñiz, Angew. Chem. 2015,
127, 8405; Angew. Chem. Int. Ed. 2015, 54, 8287; b) P. Becker, T.
Duhamel, C. J. Stein, M. Reiher, K. Muñiz, Angew. Chem. 2017, 129,
8117; Angew. Chem. Int. Ed. 2017, 56, 8004; c) E. A. Wappes, K. M.
Nakafuku, D. A. Nagib, J. Am. Chem. Soc., 2017, 139, 10204; d) J.
Long, X. Cao, L. Zhu, R. Qiu, C.-T. Au, S.-F. Yin, T. Iwasaki, N. Kambe,
Org. Lett. 2017, 19, 2793; e) C. Q. O`Broin, P. Fernández, C. Martínez,
L. Muñiz, Org. Lett. 2016, 18, 436; f) E. A. Wappes, S. C. Fosu, T. C.
Chopko, D. A. Nagib, Angew. Chem. 2016, 128, 10128; Angew. Chem.
Int. Ed. 2016, 55, 9974; g) N. R. Paz, D. Rodríguez-Sosa, H. Valdés, R.
Marticorena, D. Melián, M. B. Copano, C. C. González, A. J. Herrera,
Org. Lett. 2015, 17, 7564.
with the X-ray analyses
.
Keywords: Alkenes • Allylic Oxidation • Amination • Chlorination
• Dienes
[1]
Reviews: a) M. B. Andrus, J. C. Lashley, J. C. Tetrahedron 2002, 58,
845; b) J. Eames, M. Watkinson, Angew. Chem. 2001, 113, 3679;
Angew. Chem. Int. Ed. 2001, 40, 3567; c) Sheldon, R. A. In Fine
Chemicals Through Heterogeneous Catalysis (Eds.: R. A. Sheldon, H.
Van Bekkum), Wiley-VCH, Weinheim, 2001; p 519; d) H. Grennberg, J.
E. Bäckvall, In Transition Metals for Organic Synthesis (Eds.: M. Beller,
C. Bolm), Wiley-VCH, Weinheim, 1998; Vol. 2, p 200; e) P. C. Bulman
Page, T. J. McCarthy, In Comprehensive Organic Synthesis (Ed.: B. M.
Trost) Pergamon, Oxford, 1991; Vol. 7, p 83
[15] S. Minakata, Y. Yoneda, Y. Oderaotoshi, M. Komatsu, Org. Lett. 2006,
8, 967.
[16]
a) J. U. Jeong, B. Tao, I. Sagasser, H. Henniges, K. B. Sharpless J.
Am. Chem. Soc. 1998, 120, 6844; b) T. Ando, D. Kano, S. Minakata, I.
Ryu, M. Komatsu, Tetrahedron 1998, 54, 13485; c) S. Minakata, D.
Kano, Y. Oderaotoshi, M. Komatsu, Org. Lett. 2002, 4, 2097; d) S. C.
Coote, P. O´Brian, A. C. Whitwood, Org. Biomol. Chem. 2008, 6, 4299;
e) S. L. Jain, B. Sain, Green Chem. 2006, 11, 943; f) H. J. Wu, L. W. Xu,
C. G. Xia, J. Ge, L. Yang, Synth. Comm. 2005, 35, 1413; g) V. V.
Thakus, A. Sudalai, Tetrahedron Lett. 2003, 44, 989; h) P. Dauban, R.
H. Dodd, Tetrahedron Lett. 2001, 42, 1037; i) S. Minakata, D. Kano, Y.
Oderaotoshi, M. Komatsu, Angew. Chem. 2004, 116, 81; Angew. Chem.
Int. Ed. 2004, 43, 79; j) K. Kiyokawa, T. Kosaka, S. Minakata, Org. Lett.
2013, 15, 4858; k) G.-W. Wang, X.-L. Wu, Adv. Synth. Catal. 2007, 349,
1977; l) X.-L. Wu, G.-W. Wang, J. Org. Chem. 2007, 72, 9398.
[2]
For recent reviews on general aspects of C-H functionalization: a) H. M.
L. Davies, D. Morton, J. Org. Chem. 2016, 81, 343; b) T. Gensch, M. N.
Hopkinson, F. Glorius, J. Wencel-Delord, Chem. Soc. Rev. 2016, 45,
2900; c) J. Yamaguchi, A. D. Yamaguchi, K. Itami, Angew. Chem. 2012,
124, 9092; Angew. Chem. Int. Ed. 2012, 51, 8960; d) D. Y.-K. Chen, S.
W. Youn, Chem. Eur. J. 2012, 18, 9452; e) M. C. White, Science 2012,
335, 807; f) N. Kuhl, M. N. Hopkinson, J. Wencel-Delord, F. Glorius,
Angew. Chem. 2012, 124, 10382; Angew. Chem. Int. Ed. 2012, 51,
10236; g) T. A. Ramirez, B. Zhao, Y. Shi, Chem. Soc. Rev. 2012, 41,
931; h) L. Ackermann, Chem. Rev., 2011, 111, 1315; i) F. Collet, C.
Lescot, P. Dauban, Chem. Soc. Rev. 2011, 40, 1926; j) T. W. Lyons, M.
S. Sanford, Chem. Rev. 2010, 110, 1147; k) M. M. Díaz-Requejo, P. J.
[17] C. Martínez, K. Muñiz, Adv. Synth. Catal. 2014, 356, 205.
[18] See Supporting Information for details.
[19] Details on crystal structure analyses were deposited with the
Cambridge Crystallographic Data Centre (CCDC). They can be
obtained from the CCDC citing the following numbers: CCDC 1517902
(3f), CCDC 1007515 (3q/3q’) and CCDC 1007516 (3t).
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[20] H. M. R. Hoffmann, Angew. Chem. 1969, 81, 597; Angew. Chem. Int.
Ed. 1969, 8, 556.
[21] Control experiments in the presence of radical scavengers such as
TEMPO and 2,6-di-tert-butyl-4-methylphenol (BHT) were not conclusive
since the 1/AcOH reagent combination shows reactivity towards these
compounds, even in the absence of 2a.
[22] D. C. Braddock, A. X. Gao, A. J. P. White and M. Whyte, Chem.
Commun. 2014, 50, 13725.
[23] N. F. McKinley, D. F. O´Shea, J. Org. Chem. 2006, 71, 9552.
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Entry for the Table of Contents (Please choose one layout)
Layout 2:
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C-H Functionalisation
Claudio Martínez, Kilian Muñiz*
single step double C-H functionalisation
H
TsHN
Page No. – Page No.
TsNNaCl
(2 equiv)
Dual Intermolecular Allylic C-H
Functionalization within the
Tetrasubstituted Alkene Scaffold
Ar
Ar
AcOH (1 equiv),
(CH2Cl)2, 50ºC, 12h
Text for Table of Contents
H
Cl
14 examples, 40-76%
A simple activation of chloramine-T by Brønstedt acid generates N-chlorotosylamide, which serves as a
unique reagent for the selective double C-H functionalization in allylic position of tetrasubstituted
alkenes.
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