Substitution Effects of Hypervalent Iodine(III) Reagents in the Diamination of Styrene

Article abstract of DOI:10.1021/acs.joc.6b01070

The influence of electronic parameters on the reaction performance of hypervalent iodine(III) reagents in the vicinal diamination of styrene has been investigated. It demonstrates the influence of the relative electron density on the aryl substituent of t

Full text of DOI:10.1021/acs.joc.6b01070

Subscriber access provided by West Virginia University | Libraries
Note
Substitution Effects of Hypervalent Iodine(III)
Reagents in the Diamination of Styrene
Rafael Martín Romero, José A. Souto, and Kilian Muniz
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b01070 • Publication Date (Web): 16 Jun 2016
Downloaded from http://pubs.acs.org on June 20, 2016
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
The Journal of Organic Chemistry is published by the American Chemical Society.
1155 Sixteenth Street N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 19
The Journal of Organic Chemistry
1
2
3
4
5
6
Substitution Effects of Hypervalent Iodine(III) Reagents in the
Diamination of Styrene
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
R. Martín Romero,† José A. Souto† and Kilian Muñiz †‡*
†Institute of Chemical Research of Catalonia (ICIQ), The Barcelona Institute of Science
and Technology, Av. Països Catalans 16, E-43007 Tarragona (Spain)
‡Catalan
Institution
for
Research
and
Advanced
Studies
(ICREA)
Pg. Lluís Companys 23, 08010 Barcelona (Spain)
*Corresponding Autor. Email: kmuniz@iciq.es
Abstract Graphic/ToC
Ts2N
I
NTs2
NTs2
X
NTs2
electronic differentitation
F
F
CD2Cl2 / C6F6
different rate of
diamination
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 19
1
2
3
4
Abstract
5
6
7
8
The influence of electronic parameters on the reaction performance of hypervalent
iodine(III) reagents in the vicinal diamination of styrene has been investigated. It
demonstrates an influence of the relative electron density on the aryl-substituent of the
hypervalent iodine reagent. In these cases, compounds with donor substituents outperform
the corresponding acceptor-substituted systems. In line with this observation, a rapid
enantioselective diamination was observed for a preformed chiral bisimidoiodine(III)
reagent. For the first time, X-ray structural data could be obtained for an isolated chiral
bisimidoiodine(III).
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Hypervalent iodine(III) reagents represent versatile tools in modern organic oxidation
chemistry,1 and in the development of new synthetic methodology have recently started to
challenge traditional procedures based on transition metals.2,3
Recently, we introduced monomeric hypervalent iodine(III) compounds bearing defined
iodine-nitrogen bonds with bissulfonylimides. As exemplified for bistosylimide, these
compounds are best prepared through protonolysis events starting from
(diacetoxy)iodobenzene PhI(OAc)2 1a (Scheme 1).4,5 In these cases, treatment of 1a with
an equimolar amount of HNTs2 formed the mixed reagent 2a in an irreversible manner. The
same reaction in the presence of water forms the µ-oxo-bridged dimer 3a, which can also
be accessed from 2a upon controlled partial hydrolysis. Finally, saturation of the
coordination sphere of iodine by introduction of an additional NTs2 moiety generates the
bisimido species 4a.4,6,7
ACS Paragon Plus Environment

Page 3 of 19
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Successful applications of these aminating reagents involve allylic,8,9 acetylenic,10 and
aromatic11,12 amination events and the diamination of alkenes.13 The overall series
culminated in an enantioselective diamination of styrenes,14 which is of unsurpassed
efficiency in the field.15 ,16
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
2 Ts2NH
H2O
OAc
I
2
OAc
- 4 HOAc
1a
NTs2
2 HNTs2
- H2O
NTs2
I
O
2
I
I
Ts2N
2 Ts2NH
- 4 HOAc
NTs2
3a
4a
NTs2
H2O
2
I
- 2 HOAc
OAc
2a
Scheme 1. The phenyliodine(III)/bistosylimide pathways to aminating reagents.
For the simplest case of bismesylimide, a recent theoretical study has uncovered some
details regarding the amination pathways involved in styrene amination using hypervalent
iodine reagents.17 We here report the effect of substituents on the arene ring of the central
iodine(III), which gives additional insight into the mechanistic scenario and confirms the
general trends from the theoretical study.
Regarding the diamination of styrene 5a with an equimolar amount of the bistosylimide
reagent 4a, control experiments revealed a first order dependence on iodine(III) reagent 4a,
but a zero-order dependence on the alkene substrate (Scheme 2).18 In order to gain a better
understanding of this result, four derivatives 4b-e with the 4-substituted aryliodine(III) core
were prepared (Scheme 3). Following our literature protocol,4 their synthesis comprises the
initial formation of the corresponding dimeric µ-oxo-bridged iodine(III) derivatives 3b-e,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 19
1
2
3
4
5
6
7
8
9
which were obtained quantitatively. Upon protonolysis with bistosylimide, compounds 3b-
e cleanly convert into the corresponding monomeric reagents 4b-e in quantitative yields.
Alternatively, these reagents 4b-e can be equally accessed in a single transformation
directly from 1b-e.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
NTs2
NTs2
I
NTs2
NTs2
4a
CD2Cl2
5a
6a
first order in [4a]
zero order in [5a]
Scheme 2. Dependence of the diamination on styrene 5a and on iodine reagent 4a.
ACS Paragon Plus Environment

Page 5 of 19
The Journal of Organic Chemistry
1
2
3
4
5
AcO
I
OAc
NTs2 NTs2
HNTs2
H2O
I
I
O
6
7
CH2Cl2,
25 ºC
X
X
X
8
9
1b (X = CF3)
1c (X= Cl)
1d (X = Me)
1e (X = OMe)
3b (99%)
3c (99%)
3d (99%)
3e (99%)
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Ts2N
I
HNTs2
(2 equiv)
HNTs2
(2 equiv)
NTs2
3b (X-ray)
C6H5Cl, 55 ºC
CH2Cl2, 25 ºC
X
4b (99%)
4c (99%)
4d (99%)
4e (99%)
Ts2N
I
OMe
3a
3d
MeOH
X
7a (33%)
7d (32%)
7d (X-ray)
Scheme 3. Synthesis of 4-substituted aryliodine(III) derivatives.
The expected structures of compounds 3b-e and 4b-e match with the ones for the parent
series from Scheme 1. This was further assured from an X-ray analysis of 3b.18 Electronic
effects render compound 4d and particularly 4e less stable than the parent compound 4a as
they are sensitive to hydrolysis. While the corresponding degradation products could not be
characterized, the related reaction upon dissolution of compound 4d in methanol was
determined to provide the methoxy derivative 7d. Starting from compounds 3a,d, the
expected new mixed iodine(III) derivatives 7a,d, incorporating a single bistosylimido and a
methoxy substituent, were obtained and their structure was confirmed for 7d by X-ray
analysis.20 These compounds are remarkably stable and serve as precursor to reactive
imidoiodine(III) species upon treatment with bistosylimide.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 19
1
2
3
4
With these compounds in hand, the reactivity of compounds 4a-e in the diamination of 4-
5
6
19
fluorostyrene 5b in dichloromethane was monitored by F NMR with hexafluorobenzene
7
8
9
as internal standard (Figure 1).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
NTs2
ArI(NTs2)2 4 (0.2 equivl)
NTs2
CD2Cl2 / C6F6 (1 equiv.)
F
F
5b
6b
Figure 1. Kinetic profiles for diamination of 5b with iodine(III) reagents 4a-e.
While the highest rate was observed for the 4-methyl derivative 4d, the corresponding
initial rates for 4a and 4e were almost identical. In fact, the corresponding Hammett plot
shows almost identical outcome for donor-substitution.18 This matches with a recent
screening on catalyst structure for enantioselective diacetoxylation of alkenes, in which a 4-
methyl substituent enhanced the rate of the catalysis.19 In contrast, electron-deficient
derivatives 4b,c showed significantly lower conversion within a comparable reaction
period.
ACS Paragon Plus Environment

Page 7 of 19
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
These results are instructive as they present an unexpected electronic dependence. One
expects a kinetic preference for electron-withdrawing substituents, which enhance the
electrophilicity of the iodine(III) center in the initial alkene coordination and in the step of
the reductive elimination, where the nucleophuge character of the iodine(III)20 dominates
the scenario. Instead, it appears that the reaction is accelerated by donor-substitution. Based
on the observations from Scheme 2 and Figure 1, we now propose that the decisive step in
the diamination of alkenes with bistosylimide as nitrogen source consists of a dissociative
pre-equilibrium (Figure 2). Previously, this dissociation context had been investigated
experimentally for the neutral species 4a,4 and had been identified by theory as the
energetically most demanding step of the diamination reactions of styrene with related
bismesylimide.17 The data presented here imply that the enhanced acceleration with 4d is
based on an electronic donor stabilization of the involved cationic intermediate 4+. The
relation between donor substituent and overall rate needs to be balanced in a way that the
electrophilic character at iodine is not reduced too much due to electronic stabilization as
appears to be the case for the 4-methoxy substituent.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Ts2N
I
Ts2N
I
NTs2
+
NTs2
X
X
4+
4
Figure 2. Electronic influence on I-N bond dissociation in reagents 4.
We then turned our attention toward the structures of chiral aryl iodides. Regarding the
scenario of chirality, we had previously employed a chiral C2-symmetric hypervalent iodine
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 19
1
2
3
4
5
6
7
8
9
reagent bearing two lactate side chains in the enantioselective diamination of styrenes.14a In
these cases, bismesylimide served as the best nitrogen source by providing the highest
enantiomeric excesses of the final diamine products. Despite repeated attempts, we were
unable to obtain any evidence for the incorporation of the bissulfonylimides into the
coordination sphere of the iodine(III) center. Attempts were further hampered by the low
solubility of the involved species. However, the anticipated sequential exchange of acetate
for bistosylimide could be accomplished for the case of the chiral iodine(III) compound
1f21a,b bearing a single lactic ester side chain (Scheme 4). As in the case of the achiral
derivatives 1a-e, sequential replacement took place to initially generate the µ-oxo-bridged
compound 3f. The structure of 3f was confirmed unambiguously by single crystal X-ray
analysis.18 Its conversion into the bisimido derivative 4f under standard protonolysis with
free bistosylimide was possible, but did not proceed in quantitative manner. Instead,
compound 4f was better accessed through direct acetate for imide exchange at stage 1f. It
represents only the second iodine(III)-nitrogen derivative of a chiral iodine(III) reagent14b
and the first for the successful class of lactate derivatives.21
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
O
AcO
OAc
O
Ts2N
O
NTs2
O
HNTs2
H2O
I
O
I
I
O
O
OMe
MeO
OMe
CH2Cl2,
25 ºC
1f
3f
HNTs2 C6H5Cl,
55 ºC
Ts2N
NTs2
O
I
O
HNTs2
OMe
4f
Scheme 4. Synthesis of enantiopure iodine(III) reagents with I-N bond.
ACS Paragon Plus Environment

Page 9 of 19
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
Kinetic experiments reveal that 4f reacts with 4-fluoro styrene in a rapid conversion leading
to 50% diamination product 6b within only 8 minutes reaction time.18 Although this
product is formed with a low 24% ee, this rate effect, which is attributed to the
electronically favorable 2-oxygenated substituent, is remarkable. It compares well with the
observed rapid rate for related bislactamide derivatives, which were employed as catalysts
in the homogeneous diacetoxylation of styrenes and which could effectively override
potential background reactions from the terminal peracid oxidant.19 For styrene itself, 4f
represents the active and only required reagent in the diamination reaction16a as
demonstrated by the chemoselective formation of 6a (Scheme 5). Here, the (S)-configured
product is formed with 33% ee at a reaction temperature of 0 ºC, while the corresponding in
situ-formed reagent from bislactate 8 generates (S)-6a with 80% ee. This value is
comparable to reaction results at a slightly higher temperature as documented previously.16a
In comparing the enantioinductions obtained with 4f and 8, the outcome suggests that
ultimately both lactates within reagent 8 are required for high enantiocontrol in the
diamination and confirms that the bislactate motif represents the currently most promising
chiral iodine(III) reagent class.14a,19,21,22
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 19
1
2
3
4
I(OAc)2
O
MeO2C
O
CO2Me
5
6
7
8
8
NTs2
9
NTs2
reagent
CH2Cl2, 0 ºC
reagent:
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
5a
(S)-6a
4f (1.2 equiv)
8 (1.2 equiv)/HNTs2 (2.4 equiv)
50%, 33% ee
64%, 80% ee
Scheme 5. Enantioselective diamination of styrene.
In summary, we have succeeded in the synthesis and isolation of various structurally and
electronically diversified hypervalent iodine(III) reagents. These compounds have led to
two key insights, which round up the development of intermolecular amination reactions
with hypervalent iodine(III) reagents. First, the diamination of styrenes with bistosylimides
as nitrogen sources proceeds through a rate-determining preequilibrium with the formation
of a cationic iodine(III) reagent that engages in styrene coordination as predicted from a
theoretical investigation.17 Related studies on a chiral, non-racemic iodine(III) derivative
for the first time have allowed the isolation of reagents with defined iodine-nitrogen bonds.
These compounds lend weight to the assumption that enantioselective amination processes
such as the diamination of styrenes under the previously established in situ conditions
involve the initial formation of imidoiodine(III) species.
Experimental Section
General Remarks
ACS Paragon Plus Environment

Page 11 of 19
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Chemicals and solvents for chromatography were used as received. Solvents were obtained
from a solvent purification system. Reactions that were monitored by TLC were visualized
1
13
19
by a dual short wave/long wave UV lamp. H, C and F NMR spectra were recorded
using an internal deuterium lock on a 300 or a 500 MHz spectrometer. All chemical shifts
in NMR experiments are reported as ppm downfield from TMS. J couplings are reported in
Hz. The following calibrations were used: CDCl3 δ = 7.26 and 77.0 ppm, DMSO-d6 δ =
2.50 and 39.5 ppm. Infrared spectra were recorded on a FT-IR fitted with an ATR
accessory. Absorptions are given in wavenumbers (cm−1). High resolution mass spectra
were obtained on a HRMS-TOF spectrometer.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
General
procedure
for
synthesis
of
µ-oxo-bis[(4-methyl)-N-
tosylbenzenesulfonamidyl(aryl)iodine(III)] 3. To a solution of the corresponding
(diacetoxyiodo)arene 1 (0.3 mmol, 2 equiv.) in CH2Cl2 (0.6 mL), HNTs2 (0.3 mmol, 2
equiv.) was added in one portion and the reaction mixture was stirred at room temperature
overnight. Then, cyclohexane was added and the solvent was removed under reduced
pressure. Twice more, CH2Cl2 and cyclohexane were added and removed under reduced
pressure. After drying at reduced pressure, the corresponding iodine(III) compound was
obtained in quantitative yield.
General
procedure
for
synthesis
of
Bis[(4-methyl)-N-
tosylbenzenesulfonamidyl]iodosoarene 4. To a solution of the corresponding
(diacetoxyiodo)arene 1 (0.3 mmol, 1 equiv.) in chlorobenzene (1.5 mL), HNTs2 (0.6 mmol,
2 equiv.) was added and the reaction mixture was stirred at 55ºC. The solvent was removed
under reduced pressure. Three times, chlorobenzene was added and removed under reduced
pressure. After drying at reduced pressure, the corresponding iodine(III) compound was
obtained in quantitative yield.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 19
1
2
3
4
5
6
General
procedure
for
synthesis
of
methoxy((4-methyl)-N-
7
8
9
tosylbenzenesulfonamidyl)iodosoarene 7. To a solution of diacetoxyiodoarene 1 (1 mmol,
1 equiv.) in chlorobenzene (3.7 mL) and H2O (1 equiv.), HNTs2 (1 equiv.) was added and
the reaction mixture was stirred at 55 ºC. The solvent was removed under reduced pressure.
Three times, chlorobenzene was added removed under reduced pressure. After drying at
reduced pressure, the corresponding iodine(III) compound 3 was obtained as a yellow solid.
To this solid, MeOH was added until a white suspension formed at 4 ºC. Filtration provided
the title compounds in pure form.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Kinetic measurement of diamination reaction with diferent iodine(III) reagents 4. In a
NMR tube, the respective reagent ArI(NTs2)2 4 (1 equiv.), C6F6 (5 equiv.) and 4-
fluorostyrene 5b (0.2 mmol, 5 equiv.) were dissolved in CD2Cl2 (0.6 mL). The reaction
19
progress was monitored by F NMR spectroscopy recording individual spectra within a
time interval of 1 minute.
µ-Oxo-bis[(4-methyl)-N-tosylbenzenesulfonamidyl(p-trifluoromethyl-
1
phenyl)iodine(III)] (3b). White solid (0.181 g, 0.15 mmol, 99%). H NMR (400 MHz,
DMSO-d6): δ = 2.32 (s, 12H), 7.15 (d, J = 8.0 Hz, 8H), 7.52 (d, J = 8.1 Hz, 8H), 7.99 (d, J
13
= 8.3 Hz, 4H), 8.39 (d, J = 8.1 Hz, 4H). C NMR (100 MHz, DMSO-d6): δ = 20.8, 123.4
(q, J = 272 Hz), 126.2, 127.9 (q, J = 4 Hz), 128.3, 131.9 (q, J = 33 Hz), 134.7, 138.2, 139.8,
19
143.3. F-NMR (376 MHz, DMSO-d6): δ = -61.3. IR ν(cm-1): 3095, 3048, 2924, 1595,
ACS Paragon Plus Environment

Page 13 of 19
The Journal of Organic Chemistry
1
2
3
4
5
1398, 1335, 1316, 1142, 1081, 1065, 938. HRMS (MALDI+): calc. for [C21H18F3INO4S2]+:
595.9668; found: 595.9671. m.p.: 147-148 ºC.
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Bis[(4-methyl)-N-tosylbenzenesulfonamidyl]iodoso-p-trifluoromethylbenzene
(4b).
1
White solid (0.276 mg, 0.3 mmol, 99%). H NMR (400 MHz, DMSO-d6): δ = 2.33 (s,
12H), 7.18 (d, J = 8.0 Hz, 8H), 7.54 (d, J = 8.1 Hz, 8H), 7.99 (d, J = 8.4 Hz, 2H), 8.39 (d, J
13
= 8.3 Hz, 2H). C NMR (125 MHz, DMSO-d6): δ = 20.9, 123.5 (q, J = 273 Hz), 126.5,
127.8, 128.7, 131.9 (q, J = 33 Hz), 134.9, 138.3, 141.3, 141.4. 19F-NMR (376 MHz,
DMSO-d6): δ = -61.3. IR ν(cm-1): 3157, 3097, 1595, 1493, 1448, 1399, 1359, 1336, 1316,
1164, 1143, 1082, 1065, 1044, 1020, 999. HRMS (MALDI+): calc. for [C21H18F3INO4S2]+:
595.9668; found: 595.9705. m.p.: 162-165 ºC.
µ-Oxo-bis[(4-methyl)-N-tosylbenzenesulfonamidyl(p-chloro-phenyl)iodine(III)] (3c).
White solid (0.171 g, 0.15 mmol, 99%). 1H NMR (400 MHz, DMSO-d6): δ = 2.31 (s, 12H),
7.14 (d, J = 7.8 Hz, 8H), 7.52 (d, J = 7.8 Hz, 8H), 7.68 (d, J = 8.0 Hz, 4H), 8.20 (d, J = 7.6
13
Hz, 4H). C NMR (100 MHz, DMSO-d6): δ = 20.9, 121.4, 126.2, 128.2, 131.2, 136.3,
137.4, 139.6, 143.8. IR ν(cm-1): 3089, 2919, 1596, 1494, 1469, 1390, 1332, 1306, 1288,
1143, 1082, 1020, 997. HRMS (MALDI+): calc. for [C20H18ClNO4S2I]+: 561.9405; found:
561.9368. m.p.: 169-170 ºC.
Bis[(4-methyl)-N-tosylbenzenesulfonamidyl]iodoso-p-chlorobenzene (4c). White solid
(0.266 mg, 0.3 mmol, 99%). 1H NMR (400 MHz, DMSO-d6): δ = 2.33 (s, 12H), 7.18 (d, J
= 7.9 Hz, 8H), 7.54 (d, J = 8.1 Hz, 8H), 7.69 (d, J = 8.6 Hz, 2H), 8.22 (d, J = 8.7 Hz, 2H).
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 19
1
2
13C NMR (100 MHz, DMSO-d6): δ = 20.9, 126.3, 128.5, 130.6 131.2, 136.3, 138.9, 140.6,
3
4
5
6
7
8
142.2. IR ν(cm-1): 3156, 2921, 1596, 1494, 1469, 1359, 1334, 1305, 1164, 1143, 1082,
1019, 998. HRMS (MALDI+): calc. for [C20H18ClINO4S2]+: 561.9405; found: 561.9379.
m.p.: 154-156 ºC.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
µ-Oxo-bis[(4-methyl)-N-tosylbenzenesulfonamidyl(p-methyl-phenyl)iodine(III)] (3d).
White solid (0.165 g, 0.15 mmol, 99%). 1H NMR (400 MHz, DMSO-d6): δ = 2.31 (s, 12H),
2.42 (s, 6H), 7.14 (d, J = 7.9 Hz, 8H), 7.41 (d, J = 8.7 Hz, 4H), 7.52 (d, J = 8.0 Hz, 8H),
13
8.10 (d, J = 8.7 Hz, 4H). C NMR (100 MHz, DMSO-d6): δ = 20.9, 21.1, 120.2, 126.1,
128.2, 131.7, 134.8, 139.5, 143.1, 143.8. IR ν(cm-1): 3029, 2919, 1596, 1493, 1399, 1329,
1305, 1288, 1207, 1187, 1159, 1143, 1119, 1082, 1020, 1000, 956. HRMS (MALDI+):
calc. for [C21H21INO4S2]+: 541.9951; found: 541.9922. m.p.: 160-161 ºC.
Bis[(4-methyl)-N-tosylbenzenesulfonamidyl]iodoso-p-methylbenzene (4d). White solid
(0.260 g, 0.3 mmol, 99%). 1H NMR (400 MHz, DMSO-d6): δ = 2.32 (s, 12H), 2.42 (s, 3H),
7.17 (d, J = 8.0 Hz, 8H), 7.42 (d, J = 8.1 Hz, 2H), 7.53 (d, J = 8.2 Hz, 8H), 8.11 (d, J = 8.3
13
Hz, 2H). C NMR (125 MHz, DMSO-d6): δ = 20.9, 21.1, 126.4, 128.7, 131.5, 131.8,
134.9, 136.9, 141.2, 141.4. IR ν(cm-1): 3050, 2925, 1908, 1710, 1595, 1491, 1472, 1452,
1395, 1343, 1326, 1305, 1231, 1207, 1184, 1148, 1120, 1081, 1043, 1017, 993. HRMS
(MALDI+): calc. for [C21H21INO4S2]+: 541.9951; found: 541.9956. m.p.: 136-141 ºC.
µ-Oxo-bis[(4-methyl)-N-tosylbenzenesulfonamidyl(p-methoxy-phenyl)iodine(III)] (3e).
White solid (0.170 g, 0.15 mmol, 99%). 1H NMR (400 MHz, DMSO-d6): δ = 2.31 (s, 12H),
ACS Paragon Plus Environment

Page 15 of 19
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
13
3.85 (s, 6H), 7.10-7.16 (m, 12H), 7.52 (d, J = 8.1 Hz, 8H), 8.16 (d, J = 6.8 Hz, 4H). C
NMR (100 MHz, DMSO-d6): δ = 20.9, 55.8, 113.5, 116.7, 126.2, 128.2, 137.5, 139.7,
143.7, 162.3. IR ν(cm-1): 2920, 1572, 1487, 1457, 1403, 1328, 1301, 1250, 1175, 1141,
1080, 1019, 946. MS (MALDI+): 558.1. m.p.: 132-134 ºC.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Bis[(4-methyl)-N-tosylbenzenesulfonamidyl]iodoso-p-methoxybenzene (4e). White
solid (0.265 g, 0.3 mmol, 99%). 1H NMR (400 MHz, DMSO-d6): δ = 2.33 (s, 12H), 3.84 (s,
3H), 7.13 (d, J = 8.8 Hz, 2H), 7.19 (d, J = 7.8 Hz, 8H), 7.55 (d, J = 7.9 Hz, 8H), 8.18 (d, J
= 8.7 Hz, 2H). 13C NMR (100 MHz, DMSO-d6): δ = 20.9, 55.8, 113.5, 116.8, 126.4, 128.6,
137.6, 140.8, 142.0, 162.4. IR ν(cm-1): 3096, 2922, 1595, 1569, 1484, 1442, 1403, 1346,
1330, 1302, 1253, 1145, 1120, 1081, 1018, 918. MS (MALDI+): 558.1. m.p.: 131-132 ºC.
1
µ-Oxo-bridged chiral iodine(III) (3f). White solid (0.191 g, 0.15 mmol, 99%). H NMR
(400 MHz, DMSO-d6): δ = 1.63 (d, J = 6.8 Hz, 6H), 2.31 (s, 12H), 3.72 (s, 6H), 5.30 (q, J =
6.8 Hz, 2H), 7.14-7.16 (m, 10H), 7.24 (d, J = 8.2 Hz, 2H), 7.52 (d, J = 8.2 Hz, 8H), 7.62-
13
7.71 (m, 2H), 8.30 (d, J = 7.6 Hz, 2H). C NMR (100 MHz, DMSO-d6): δ = 18.0, 20.9,
52.5, 73.4, 113.8, 115.4, 123.6, 126.1, 128.2, 135.6, 138.0, 139.6, 143.8, 154.4, 171.0. IR
ν(cm-1): 2953, 1736, 1651, 1586, 1569, 1493, 1470, 1448, 1385, 1360, 1326, 1282, 1248,
1217, 1186, 1143, 1099, 1080, 1051, 1017, 981. HRMS (MALDI+): calc. for
27
[C24H25INO7S2]+: 630.0112; found: 630.0131. m.p.: 139-141 ºC. [α]D : -290.1 (c = 0.10,
CH2Cl2).
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 16 of 19
1
2
3
4
5
6
7
8
9
1
Chiral iodine(III) (4f). White solid (0.286 g, 0.3 mmol, 99%) H NMR (400 MHz,
DMSO-d6): δ = 1.63 (d, J = 6.7 Hz, 3H), 2.33 (s, 12H), 3.72 (s, 3H), 5.30 (q, J = 6.7 Hz,
1H), 7.13-7.26 (m, 10H), 7.55 (d, J = 7.9 Hz, 8H), 7.67 (t, J = 7.6 Hz, 1H), 8.30 (d, J = 9.0
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
13
Hz, 1H). C NMR (100 MHz, DMSO-d6): δ = 18.0, 20.9, 52.5, 73.4, 113.8, 115.4, 123.6,
126.3, 128.5, 135.6, 138.0, 140.7, 142.2, 154.4, 171.0. IR ν(cm-1): 3155, 1738, 1595, 1493,
1469, 1377, 1356, 1330, 1282, 1216, 1162, 1144, 1081, 1053, 1017, 980. HRMS
(MALDI+): calc. for [C24H25INO7S2]+: 630.0112; found: 630.0001. m.p.: 146-147 ºC.
[α]D27 : -233.0 (c = 0.10, CH2Cl2).
Methoxy((4-methyl)-N-tosylbenzenesulfonamidyl)iodosobenzene (7a) White solid
(0.185 g, 0.33 mmol, 33%). 1H NMR (400 MHz, DMSO-d6): δ = 2.31 (s, 6H), 3.17 (s, 3H),
7.14 (d, J = 8.0 Hz, 4H), 7.52 (d, J = 8.1 Hz, 4H), 7.60-7.64 (m, 2H), 7.69-7.73 (m, 1H),
8.22 (d, 7.6 Hz, 2H). 13C NMR (100 MHz, DMSO-d6): δ = 20.9, 63.2, 122.1, 126.2, 128.3,
131.4, 133.1, 135.5, 139.9, 143.4. IR ν(cm-1): 2919; 2813, 1595, 1493, 1469, 1446, 1334,
1148, 1080, 1019, 989. HRMS (MALDI+): calc. for [C20H19INO4S2]+: 527.9795; Found:
527.9859. m.p.: 163-167 ºC.
Methoxy((4-methyl)-N-tosylbenzenesulfonamidyl)-4-methyl-iodosobenzene (7d) White
solid (0.184 mg, 0.32 mmol, 32%). 1H NMR (400 MHz, DMSO-d6): δ = 2.32 (s, 6H), 2.42
(s, 3H), 3.17 (s, 3H), 7.16 (d, J = 8.0 Hz, 4H), 7.42 (d, J = 8.1 Hz, 2H), 7.53 (d, J = 8.1 Hz,
4H), 8.11 (d, J = 8.2 Hz, 2H). 13C NMR (100 MHz, DMSO-d6): δ = 20.9, 21.1, 48.6, 126.2,
128.3, 131.5, 131.7, 134.8, 136.9, 139.9, 143.1. IR ν(cm-1): 3026, 2957, 2921, 1597, 1482,
ACS Paragon Plus Environment

Page 17 of 19
The Journal of Organic Chemistry
1
2
3
4
5
6
1447, 1399, 1317, 1283, 1138, 1079, 960, 805, 771, 664, 547, 506, 483. HRMS
(MALDI+): calc. for [C21H21INO4S2]+: 541.9957; Found: 541.9983. m.p.: 132-134 ºC.
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Supporting Information
1
13
Full experimental description of control experiments and copies of H and C NMR spectra
of new compounds (pdf), and data on X-ray structure determination (cif). This material is
available free of charge via the Internet at http://pubs.acs.org.
Acknowledgements
The authors thank the ICIQ Foundation, the Spanish Ministerio de Economía y
Competitividad and FEDER (CTQ2014-56474R grant to K. M., and Severo Ochoa
Excellence Accreditation 2014-2018 to ICIQ, SEV-2013-0319) for financial support and
Eduardo Escudero-Adán for the X-ray analyses. R. M. R. thanks MEC for an FPU
fellowship.
References
(1) Zhdankin, V. V. Hypervalent Iodine Chemistry Preparation, Structure and Synthetic
Applications of Polyvalent Iodine Compounds, Wiley, Chichester 2013.
(2) (a) Hypervalent Iodine Chemistry. Modern Developments in Organic Synthesis, Wirth,
T. (Ed.), Top. Curr. Chem. 224, Springer, Berlin, 2003. (b) Stang, P. J.; Zhdankin, V. V.
Chem. Rev. 1996, 96, 1123. (c) Zhdankin, V. V.; Stang, P. J. Chem. Rev. 2002, 102, 2523.
(d) Zhdankin, V. V.; Stang, P. J. Chem. Rev. 2008, 108, 5299. (e) Yoshimura, A.;
Zhdankin, V. V. Chem. Rev. 2016, 116, 3328. (f) Singh, F. V.; Wirth, T.; Chem. Asian J.
2014, 9, 950.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 18 of 19
1
2
3
4
5
6
7
8
9
(3) (a) Richardson, R. D.; Wirth, T. Angew. Chem. Int. Ed. 2006, 45, 4402. (b) Ochiai, M.;
Miyamoto, K. Eur. J. Org. Chem. 2008, 4229. (c) Ochiai, M. Chem. Rec. 2007, 7, 12. (d)
Dohi, T.; Kita, Y. Chem. Commun. 2009, 2073. (e) Uyanik, M.; Ishihara, K. Chem.
Commun. 2009, 2086. (f) Yusubov, M. S.; Zhdankin, V. V. Reef. Tech. 2015, 1, 49.
(4) Souto, J. A.; Martínez, C.; Velilla, I.; Muñiz, K. Angew. Chem. Int. Ed. 2013, 52, 1324.
(5) For work on related compounds bearing nitrogen groups such as phthalimide and
saccharin: (a) Yoshimura, A.; Koski, S. R.; Fuchs, J. M.; Saito, A.; Nemykin, V. N.;
Zhdankin, V. V. Chem. Eur. J. 2015, 21, 5328. (b) Kiyokawa, K.; Kosaka, T.; Kojima, T.;
Minakata, S. Angew. Chem. Int. Ed. 2015, 54, 13719. (c) Hadjiaraooglou, L.; Spyroudis, S.;
Varvoglis, A. Synthesis 1983, 207. (d) Papadopoulou, M.; Varvoglis, A. Chem. Res. Synop.
1983, 66. (e) Papadopoulou, M.; Varvoglis, A. Chem. Res. Synop. 1984, 166.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(6) For related bromine(III) reagents incorporating transferable nitrogen groups: (a) Ochiai,
M.; Kaneaki, T.; Tada, N.; Miyamoto, K.; Chuman, H.; Shiro, M.; Hayashi, S.; Nakanishi,
W. J. Am. Chem. Soc. 2007, 129, 12938. (b) Ochiai, M.; Miyamoto, K.; Kaneaki, T.;
Hayashi, S.; Nakanishi, W. Science 2011, 332, 448.
(7) For the alternative concept of electrophilic amination with hypervalent iodine reagents:
(a) Tellitu, I.; Domínguez, E. Trends Heterocycl. Chem. 2011, 15, 23. (b) Narayan, R.;
Manna, S.; Antonchick, A. P. Synlett 2015, 26, 1785. (c) Samanta, R.; Matcha, K.;
Antonchick, A. P. Eur. J. Org. Chem. 2013, 5769.
(8) Souto, J. A.; Zian, D.; Muñiz, K. J. Am. Chem. Soc. 2012, 134, 7242.
(9) Kiyokawa, K.; Yahata, S.; Kojima, T.; Minakata, S. Org. Lett. 2014, 16, 4646.
(10) Souto, J. A.; Becker, P.; Iglesias, A.; Muñiz, K. J. Am. Chem. Soc. 2012, 134, 15505.
(11) Fra, L.; Millán, A.; Souto, J. A.; Muñiz, K. Angew. Chem. Int. Ed. 2014, 53, 7349.
(12) Moriyama, K.; Ishid, K.; Togo, H. Chem. Commun. 2015, 51, 2273.
ACS Paragon Plus Environment

Page 19 of 19
The Journal of Organic Chemistry
1
2
3
4
5
6
(13) Souto, J. A.; González, Y.; Iglesias, Á.; Zian, D.; Lishchynskyi, A.; Muñiz, K. Chem.
Asian J. 2012, 7, 1103.
7
8
9
(14) (a) Röben, C.; Souto, J. A.; González, Y.; Lishchynskyi, A.; Muñiz, K. Angew. Chem.
Int. Ed. 2011, 50, 9478. (b) Röben, C.; Souto, J. A.; Escudero-Adán, E. C. Muñiz, K. Org.
Lett. 2013, 15, 1008.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(15) (a) Martínez, C.; Muñiz, K. J. Org. Chem. 2013, 78, 2168. (b) Cardona, F.; Goti, A.
Nature Chem. 2009, 1, 269. (c) de Figueiredo, R. M. Angew. Chem. Int. Ed. 2009, 48,
1190. (d) De Jong, S.; Nosal, D. G.; Wardrop, D. J. Tetrahedron 2012, 68, 4067.
(16) For an overview on alkene difunctionalization with hypervalent iodine(III) reagents:
Romero, R. M.; Wöste, T. H.; Muñiz, K. Chem. Asian J. 2014, 9, 972.
(17) Funes-Ardoiz, I.; Sameera, W. M. C.; Romero, R. M.; Martínez, C.; Souto, J. A.;
Sampero, D.; Muñiz, K.; Maseras, F. Chem. Eur. J. 2016, 22, 7545.
(18) See Supporting Information for details.
(19) Haubenreisser, S.; Wöste, T. H.; Martínez, C.; Ishihara, K.; Muñiz, K. Angew. Chem.
Int. Ed. 2016, 55, 413.
(20) Ochiai, M. in Chemistry of Hypervalent Compounds (Ed.: K. Akiba), Wiley-VCH,
New York, 359, 1999.
(21) Uyanik, M.; Ishihara, K. J. Synth. Org. Chem. Jpn. 2012, 70, 1116.
(22) (a) Kong, W.; Feige, P.; de Haro, T.; Nevado, C. Angew. Chem. Int. Ed. 2013, 52,
2469. (b) Fujita, M.; Yoshida, Y.; Miyata, K.; Wakisaka, A.; Sugimura, T. Angew. Chem.
Int. Ed. 2010, 49, 7068. (c) Fujita, M.; Wakita, M.; Sugimura, T. Chem. Commun. 2011,
47, 3983. (d) Uyanik, M.; Yasui, T.; Ishihara, K. Angew. Chem. Int. Ed. 2010, 49, 2175. (e)
Farid, U.; Wirth, T. Angew. Chem. Int. Ed. 2012, 51, 3462. (f) Mizar, P.; Wirth, T. Angew.
Chem. Int. Ed. 2014, 53, 5993.
ACS Paragon Plus Environment