Palladium-catalysed aminosulfonylation of aryl-, alkenyl- and heteroaryl halides: Scope of the three-component synthesis of N-aminosulfonamides

Article abstract of DOI:10.1039/c2ob07034k

By using DABCO·(SO₂)₂, DABSO, as a solid bench-stable SO₂-equivalent, the palladium-catalysed aminosulfonylation of aryl-, alkenyl- and heteroaryl halides has been achieved. N,N-Dialkylhydrazines are employed as the N-nucleophiles and provide N-aminosulfonamides as the products in good to excellent yields. The reactions are operationally simple to perform, requiring only a slight excess of SO ₂ (1.2-2.2 equiv.), and tolerate a variety of substituents on the halide coupling partner. Variation of the hydrazine component is also demonstrated. The use of N,N-dibenzylhydrazine as the N-nucleophile delivers N-aminosulfonamide products that can be converted into the corresponding primary sulfonamides using a high-yielding, telescoped, deprotection sequence. The ability to employ hydrazine·SO₂ complexes as both the N-nucleophile and SO₂ source is also illustrated.

Full text of DOI:10.1039/c2ob07034k

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Volume 10 | Number 20 | 28 May 2012 | Pages 3957–4136
ISSN 1477-0520
FULL PAPER
Michael C. Willis et al.
Palladium-catalysed aminosulfonylation of aryl-, alkenyl- and heteroaryl
halides: scope of the three-component synthesis of N-aminosulfonamides
1477-0520(2012)10:20;1-H

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PAPER
Palladium-catalysed aminosulfonylation of aryl-, alkenyl- and heteroaryl
halides: scope of the three-component synthesis of N-aminosulfonamides†
Edward J. Emmett,a Charlotte S. Richards-Taylor,a Bao Nguyen,a Alfonso Garcia-Rubia,a Barry R. Hayterb
and Michael C. Willis*a
Received 5th December 2011, Accepted 10th February 2012
DOI: 10.1039/c2ob07034k
By using DABCO·(SO2)2, DABSO, as a solid bench-stable SO2-equivalent, the palladium-catalysed
aminosulfonylation of aryl-, alkenyl- and heteroaryl halides has been achieved. N,N-Dialkylhydrazines are
employed as the N-nucleophiles and provide N-aminosulfonamides as the products in good to excellent
yields. The reactions are operationally simple to perform, requiring only a slight excess of SO2 (1.2–2.2
equiv.), and tolerate a variety of substituents on the halide coupling partner. Variation of the hydrazine
component is also demonstrated. The use of N,N-dibenzylhydrazine as the N-nucleophile delivers
N-aminosulfonamide products that can be converted into the corresponding primary sulfonamides using a
high-yielding, telescoped, deprotection sequence. The ability to employ hydrazine·SO2 complexes as both
the N-nucleophile and SO2 source is also illustrated.
The absence of transition metal-catalysed methods for sulfo-
namide synthesis is conspicuous. Our aim, therefore, was to
Introduction
The sulfonamide functional group is abundant in medicinal
agents, where it features in a number of top selling drug mol-
ecules active against a wide variety of conditions.1 Despite their
widespread presence, a general and versatile method for sulfona-
mide preparation does not exist, with the most common route
involving a linear approach of sulfonyl chloride formation and
subsequent amination. In addition, sulfonyl chloride synthesis
can often present a challenge due to the forcing conditions and
functional group incompatibility of the required strong chlorinat-
ing reagents.2,3 The frequently used aryl sulfonyl chlorides can
be prepared via electrophilic aromatic substitution chemistry
using [HSO3]+ or [ClSO2]+ synthons;2 however, this is generally
limited to electron-rich aromatic substrates and those that can tol-
erate the harsh acidic conditions. In addition, the positions to
which the sulfonyl moiety can be introduced are governed by the
intrinsic electronic and steric properties of the aromatic ring.
Alternative methods to form sulfonamides avoiding a sulfonyl
chloride intermediate have been developed to address some of
these issues.4,5 However, these methods often require starting
materials at the sulfinate oxidation level, which in turn are fre-
quently prepared using difficult to handle sulfur dioxide gas and
sensitive organometallics.4
develop a catalytic method of sulfonamide formation that would
eliminate many of the limitations of current methodologies. We
drew inspiration from the analogies, in terms of transition metal
chemistry, between sulfur dioxide and carbon monoxide. The
frontier molecular orbitals of CO and SO2 carry striking simi-
larities; they both have a σ symmetry HOMO and π* LUMO in
a similar spatial arrangement,6 hinting at comparable behaviour
as ligands.7 Sulfur dioxide is also well precedented to undergo
co-ordination to metal centres,8 through a large variety of
bonding modes, and insertion into metal–carbon bonds.9
Despite this literature precedent for stoichiometric reactions of
metal complexes and sulfur dioxide, reports documenting the
incorporation of sulfur dioxide into organic molecules via tran-
sition metal-catalysed processes are scarce.10 Examples include
the copper-catalysed coupling of aryl diazonium chloride salts
with sulfur dioxide to form sulfonyl chlorides,11 and the palla-
dium-catalysed coupling of aryl diazonium tetrafluoroborate salts
with sulfur dioxide and hydrogen gas to form sulfinic acids.12
Examples of metal-catalysed alkene–sulfur dioxide co-poly-
merisation13 and alkene hydrosulfination are also known.14 The
comparison with the catalytic chemistry of carbon monoxide is
marked, with many transition metal-catalysed carbonylation pro-
cesses being useful synthetic tools.15 In particular, the palla-
dium-catalysed aminocarbonylation of aryl halides, in which an
aryl halide, carbon monoxide gas and an amine are combined to
deliver an arylamide product, is a well-established synthetic
transformation (Scheme 1, eqn (1)).16 However, no correspond-
ing preparation of sulfonamides based on the combination of an
aryl halide, SO2 gas and an amine has been reported (Scheme 1,
aDepartment of Chemistry, University of Oxford, Chemistry Research
Laboratory, Mansfield Road, Oxford, OX1 3TA, UK. E-mail:
michael.willis@chem.ox.ac.uk; Fax: +44 (0) 1865 285002
bOncology Innovative Medicines, AstraZeneca, Alderley Park,
Macclesfield, Cheshire, SK10 4TG, UK
†Electronic supplementary information (ESI) available: Full data for all
new compounds. See DOI: 10.1039/c2ob07034k
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Table 1 Optimisation of the reaction conditions for the preparation of
aminosulfonamide 4aa
Scheme 1 Palladium-catalysed aminocarbonylation and aminosulfony-
lation processes.
Entry Ligand Base (equiv.) DABSO (equiv.) Solvent Yieldb (%)
1
2
3
4
5
6
7
8
PtBu3 Cs2CO3 (2.2) 2.2
PtBu3
2.2
Toluene 77
Toluene 12
Dioxane 17
Dioxane 83
Dioxane 89
Dioxane 64
Dioxane 99c
Dioxane 35
Dioxane 12
Dioxane 68
Dioxane 62
eqn (2)). In this paper we describe the development of such a
process, based on the use of DABCO·(SO2)2 as a stable, easy to
handle SO2 equivalent, and N,N-dialkylhydrazines as the N-
nucleophiles. Our preliminary results in this area have recently
been communicated.17
—
PtBu3 Cs2CO3 (2.2) 2.2
PtBu3
PtBu3
PtBu3
—
—
—
2.2
1.1
0.6
PtBu3 DABCO (0.5) 0.6
5a
5b
5c
5d
DABCO (0.5) 0.6
DABCO (0.5) 0.6
DABCO (0.5) 0.6
DABCO (0.5) 0.6
9
10
11
Results and discussion
a Conditions: iodotoluene (1.0 equiv.), hydrazine (1.5 equiv.), DABSO
(as indicated), Pd(OAc)2 (10 mol%), PtBu3·HBF4 (20 mol%), solvent,
70 °C, 16 h. b Determined by 1H NMR spectroscopy. c Corresponding to
a 93% isolated yield.
Due to the difficulties associated with the handling and use of a
toxic gas, such as SO2,18 we were attracted to the possibility of
employing a SO2-equivalent in the proposed aminosulfonylation.
In particular, we were interested in exploring the use of amine–
SO2 charge transfer complexes as substitutes for SO2 gas in cata-
lytic applications. The first reports on these charge transfer com-
pounds appear in the literature (some as early as 1900)19 mainly
for spectroscopic studies on the nature of the N–S dative
bond.20,21 However, these complexes have found some signifi-
cant uses;22 for example, a method for determining the concen-
tration of sulfur dioxide in solution using a metalloporphyrin
n
assay relies on amine complexation23 and Bu3N solutions are
used as industrial sulfur dioxide gas scrubbers.24 We were also
attracted to these complexes by the work of Olah, who used the
trimethylamine–sulfur dioxide complex to perform a range of
reduction reactions.25 Some of these transformations were also
known with sulfur dioxide gas,26 suggesting that these com-
plexes could be used to deliver sulfur dioxide to the reaction,
thus eliminating the operational difficulties and safety concerns
of using the gas.
Due to ease of handling we have focused on the complex
formed between DABCO (1,4-diazabicyclo[2.2.2]octane) and
sulfur dioxide (Scheme 2). The bis-adduct, DABCO·(SO2)2,
which we have abbreviated to DABSO, is a bench-stable, colour-
less solid which was first synthesised by Santos and Mello for
spectroscopic studies.21 We have recently reported the use of
DABSO as a replacement for sulfur dioxide gas in a number of
established transformations.27 The focus of the present report is
the use of DABSO in a novel palladium-catalysed aminosulfony-
lation process.17
chemistry (Table 1). We initially employed conditions developed
for related palladium-catalysed aminocarbonylation reactions28
and quickly established that the formation of the desired C–SO2–
N linkage was indeed possible under the action of palladium cat-
alysis. For example, the sulfonylative union of iodotoluene and
N-aminomorpholine could be achieved in 77% yield when using
Pd(OAc)2 in combination with the ligand PtBu3 and Cs2CO3 as
the base in toluene at 70 °C (entry 1). We found that Cs2CO3
could be removed from the system provided that dioxane was
employed as solvent (entries 2–4). Variation of the loading of
DABSO was explored next, and we established that reducing the
amount of DABSO from 2.2 equivalents to 1.1 equivalents
increased the yield of the aminosulfonamide product (4a) to
89% (entry 5), possibly due to less catalyst poisoning from free
SO2. However, reducing the amount of DABSO further, to 0.6
equivalents (1.2 equivalents of SO2), reduced the yield of 4a to
64% (entry 6). We attributed this reduction in yield to insuffi-
cient base being present in the reaction, and therefore repeated
this loading but with the addition of 0.5 equivalents of DABCO;
gratifyingly, the yield was then increased to 99% (entry 7).
Although these early experiments established that PtBu3 was an
effective ligand for the targeted transformation, we were also
interested in evaluating alternative phosphines: entries 8–11
Scheme 2 DABSO, an easy to handle, solid SO2-equivalent.
We selected the coupling of 4-iodotoluene (2a), DABSO and
N-aminomorpholine (3a) as a platform to evaluate the proposed
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Table 2 Scope of aryl iodides employed in Pd-catalysed aminosulfonylations with DABSO and N-aminomorpholinea
Entry
1
Aryl halide
Yieldb
93%
Entry
10
Aryl halide
Yieldb
77%c
2
3
79%c
87%
11
12
43%c
80%c
4
5
86%c
93%
13
14
35%c
90%c
6
86%
15
76%c
7
8
9
76%c
85%
88%
16
17
18
64%d
84%c
77%c
a Conditions: aryl halide (1.0 equiv.), hydrazine (1.5 equiv.), DABSO (0.6 equiv.), DABCO (0.5 equiv.), Pd(OAc)2 (10 mol%), PtBu3·HBF4
(20 mol%), 1,4-dioxane, 70 °C, 16 h. b Isolated yields. c DABSO (1.1 equiv.) used, no DABCO added. d Reaction performed at 90 °C.
demonstrate that while the use of several alternative phosphines
does deliver the aminosulfonamide 4a, for this particular trans-
formation PtBu3 is the superior ligand.
substrates containing unprotected hydroxyl and amino groups,
respectively. Electron-withdrawing substituents could also be
readily employed, although in the majority of examples the
modified reaction conditions were needed to ensure high yields
(entries 10–13). Although aryl iodides were employed for the
majority of examples, it was possible to employ aryl bromide
substrates, albeit in a less efficient manner. For example, para-
bromotoluene was combined with DABSO and N-aminomor-
pholine to generate the expected sulfonamide in a 64% yield,
compared to the 93% achieved with the iodo substrate (entry
16). To secure this level of reactivity with the bromo substrate
the reaction temperature was increased from 70 °C to 90 °C. The
increased reactivity of iodo-substituted benzenes relative to their
bromo equivalents allowed two simple chemoselective examples
to be included: in the first reaction para-iodochlorobenzene was
With optimised conditions for the sulfonylative union of 2a
and 3a established we next explored the scope of the aryl iodide
component (Table 2). A range of electron-donating substituents
could be readily incorporated into the aryl ring (entries 1–9)
using the optimised conditions. However, the yields obtained
using ortho-substituted arenes were only moderate under these
conditions and we found that the addition of extra DABSO (1.1
equiv. in total), with no added DABCO, was preferential for
slower reacting substrates. For example, using these modified
conditions, substrates featuring either an ortho-methyl or an
ortho-methoxy group underwent efficient coupling (entries 2 and
7). Entries 8 and 9 illustrate that it was possible to employ
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Table 3 Scope of hydrazines employed in Pd-catalysed aminosulfonylations with DABSO and 4-iodotoluenea
Entry
1
Hydrazine
Yieldb
93%
Entry
6
Hydrazine
Yieldb
85%
2
3
87%
75%
7
8
57% (100% conv.)
84%
4
5
65%
80%
9
0%
10
9%c
a Conditions: iodotoluene (1.0 equiv.), hydrazine (1.5 equiv.), DABSO (0.6 equiv.), DABCO (0.5 equiv.), Pd(OAc)2 (10 mol%), PtBu3·HBF4
(20 mol%), 1,4-dioxane, 70 °C, 16 h. b Isolated yields. c 1H NMR conversion.
converted into the corresponding aminosulfonamide in 84%
yield from reaction exclusively at the iodo-substituent (entry 17).
Similarly, para-iodobromobenzene also underwent selective
reaction at the iodo-functionality (entry 18).
For convenience, all of the reactions shown in Table 2 were
performed employing 10 mol% of Pd(OAc)2. However, lower
catalyst loadings were possible; for example, N-aminosulfona-
mide 4a was synthesised on a preparative 0.5 g scale using
5 mol% of Pd(OAc)2 in 89% yield (cf. 93% using 10 mol%),
and in 73% yield when using 2.5 mol% palladium.
Employing 4-iodotoluene as the C-coupling partner allowed
variation of the hydrazine component to be explored (Table 3).
N,N-Dialkyl hydrazines generally delivered good yields of
the aminosulfonamide products (entries 1–7). Slightly
reduced yields were obtained with the N,N-dimethyl example
(entry 4), attributed to the volatility of the reagent, and with
the proline-derived hydrazine (entry 7), which, despite the
reaction reaching complete conversion only delivered a 57%
yield of the product. This latter yield was attributed to product
decomposition during chromatographic purification. Although
the N-methyl-N-phenyl hydrazine underwent the coupling reac-
tion in high yield (entry 8), the corresponding diphenyl example
(entry 9) was essentially inert to the reaction conditions. Finally,
the use of a carbamate-protected hydrazine was also incompati-
ble with the sulfonylation reaction (entry 10). Variation away
from hydrazine coupling partners, for example to amines, did
not deliver sulfonamide products under these reaction
conditions.
The next parameter explored was the use of alternative coup-
ling partners to aryl halides; we first considered the use of
alkenyl halide substrates (Table 4). A variety of (E)-configured
1,2-disubstituted alkenyl iodides underwent smooth coupling
with N-aminomorpholine and DABSO, delivering the expected
(E)-configured alkenyl sulfonamides in moderate to good yields
(entries 1–3). Entry 4 demonstrates that although a (Z)-confi-
gured alkenyl iodide underwent the sulfonylative coupling with
similar efficiency to the corresponding (E)-substrate, the product
suffered from Z/E isomerisation. α-Iodostyrene was not a pro-
ductive substrate, suffering decomposition under the reaction
conditions (entry 5). More pleasingly, a variety of tri- and tetra-
substituted alkenyl iodides underwent the sulfonylative process
in high yields (entries 6–10). We speculate that the higher yields
associated with the more highly-substituted examples reflects the
greater stability of the corresponding substrates or products to
the reaction conditions.
Heteroaryl halides could also be employed as coupling part-
ners (Table 5). N-Aminomorpholine in combination with
DABSO was again employed as standard; reactions with 3-
iodothiophene and 3-iodobenzothiophene smoothly delivered the
coupled products in high yields (entries 1 and 2). However, the
use of similar N-heterocycles was less successful, with only low
yields of the sulfonamides being obtained (entries 3 and 4).
Indole-derived substrates could be employed provided that the
iodo-substituent was positioned in the benzo-ring of the indole.
For example, both 5-iodoindole, and N-Boc-5-iodoindole under-
went the desired sulfonylation in good yields (entries 5 and 6).
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Table 4 Scope of alkenyl iodides employed in Pd-catalysed aminosulfonylations with DABSO and N-aminomorpholinea
Entry
1
Alkene
Yieldb
60%
Entry
6
Alkene
Yieldb
86%
2
3
74%
53%
7
8
57%
79%
4
5
51%c
0%
9
89%
72%
10
a Conditions: alkenyl halide (1.0 equiv.), hydrazine (1.5 equiv.), DABSO (1.1 equiv.), Pd(OAc)2 (10 mol%), PtBu3·HBF4 (20 mol%), 1,4-dioxane,
70 °C, 16 h. b Isolated yields. c Starting material >20 : 1 Z : E; product 3.5 : 1 ratio of Z : E isomers.
Table 5 Scope of heteroaryl iodides employed in Pd-catalysed aminosulfonylations with DABSO and N-aminomorpholinea
Entry
1
Heterocycle
Yieldb
76%
Entry
5
Heterocycle
Yieldb
81%
2
3
73%
20%
6
7
74%
89%
4
48%
8
92%
a Conditions: heteroaryl halide (1.0 equiv.), hydrazine (1.5 equiv.), DABSO (1.1 equiv.), Pd(OAc)2 (10 mol%), PtBu3·HBF4 (20 mol%), 1,4-dioxane,
70 °C, 16 h. b Isolated yields.
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Table 6 Scope of N-aminomorpholine·SO2 complex functioning as both nucleophile and SO2-carrier in the Pd-catalysed aminosulfonylation of
aryl-, heteroaryl- and alkenyl iodidesa
Entry
1
Halide
Yieldb
92%
Entry
5
Halide
Yieldb
72%
2
3
93%
86%
6
7
87%
76%
4
64%
8
86%
a Conditions: aryl (or alkenyl) halide (1.0 equiv.), N-aminomorpholine·SO2 (1.5 equiv.), DABCO (1.1 equiv.), Pd(OAc)2 (10 mol%), PtBu3·HBF4
(20 mol%), 1,4-dioxane, 70 °C, 16 h. b Isolated yields.
Similarly, iodo-substituted dibenzofuran and dibenzothiophene
underwent high-yielding transformations (entries 7 and 8).
The methodology as described so far, i.e., employing a SO2-
carrier molecule and a variety of nucleophiles, is attractive if
variation of the nucleophilic component is the main goal of the
study. However, if the use of a single N-nucleophile is all that is
required, a more attractive, less involved reaction system might
involve a single molecule acting as both the nucleophile and the
SO2-carrier. Such a system would remove the need to use
DABSO as the SO2 source. In the event, it was found to be poss-
ible to complex SO2 with N-aminomorpholine and to employ
this complex for this dual role (Table 6).29 The reaction con-
ditions involved combining the N-aminomorpholine–SO2
Scheme 3 In situ generation and use of DABSO in the sulfonylative
complex with an aryl halide in the presence of DABCO (as the
coupling of 4-iodotoluene and N-aminomorpholine.
base) and the standard Pd(OAc)2–PtBu3 combination. Using this
protocol it was possible to couple a range of electronically- and
sterically-varied aryl iodides (entries 1–6), as well as heteroaryl-
and alkenyl-iodide examples (entries 7 and 8). In almost all of
the cases studied the yields obtained using the N-aminomorpho-
line–SO2 complex were comparable to the results achieved using
the original DABSO conditions (compare with Tables 2, 4
and 5).
We investigated a third protocol for achieving the desired ami-
nosulfonylation reactions in which an amine–SO2 complex was
generated in situ but was not isolated. This particular scenario
was felt to be attractive if the separate preparation, isolation and
storage of SO2-complexes was not desired, and the handling of
SO2 gas was not problematic. We again studied the formation of
aminosulfonamide 4a from the combination of iodotoluene, N-
aminomorpholine and an equivalent of SO2: DABSO was gener-
ated in situ by bubbling SO2 gas into a solution of DABCO in
dioxane at room temperature. After stirring for 4 h while purging
with nitrogen gas, the remaining components of the reaction –
iodotoluene, N-aminomorpholine, Pd(OAc)2 and PtBu3 – were
added, and the temperature increased to 70 °C. After 16 h (as
standard), aminosulfonamide 4a was isolated in a 93% yield
(Scheme 3).
Although access to simple primary sulfonamides by employ-
ing amines directly as the N-nucleophiles was not possible with
the current methodology, we sought to explore the conversion of
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and SO2 source, removing the need to employ an external SO2
carrier. Finally, we have shown that the isolation of a SO2 charge
transfer complex can be avoided completely if they are generated
in situ and used directly in the coupling reactions.
Experimental
For general experimental details, including information on
solvent purifications, the spectrometers used in this research and
full product characterization data, see ESI.†
General procedure of the palladium-catalysed
aminosulfonylation of aryl iodides using DABSO, exemplified by
the preparation of aminosulfonamide 4a
A glass reaction tube was charged with 4-iodotoluene (50 mg,
0.23 mmol), 4-aminomorpholine (33 μl, 0.34 mmol),
DABCO·(SO2)2 complex (1) (33 mg, 0.14 mmol), 1,4-diazabi-
cyclo[2.2.2]octane (13 mg, 0.11 mmol), palladium(II) acetate
(5 mg, 21 μmol) and tri-tert-butylphosphonium tetrafluoroborate
(13 mg, 42 μmol) and sealed under N2 gas. 1,4-Dioxane
(1.6 mL) was added and the tube heated at 70 °C for 16 h. After
cooling, the reaction mixture was filtered through Celite and
washed sequentially with dichloromethane (10 mL) and diethyl-
ether (5 mL) before being concentrated in vacuo. Purification by
flash column chromatography (50–100% diethylether in petrol)
afforded the N-aminosulfonamide 4a as colourless crystals
(55 mg, 93%).
Scheme 4 Preparation of primary sulfonamides via an N-aminosulfo-
namide deprotection sequence.
the readily accessible N-aminosulfonamides to the corresponding
sulfonamides. We have already shown that N,N-dibenzylhydra-
zine was a competent N-nucleophile in the developed chemistry,
and so we focused on converting the dibenzylated aminosulfona-
mide to the parent sulfonamide (Scheme 4). The two benzyl
groups of aminosulfonamide 4b could be efficiently cleaved
under a balloon atmosphere of H2 using a Pd(OH)2 catalyst to
generate hydrazone 9; the use of acetone as solvent was key to
the success of the deprotection, presumably allowing the facile
formation of the intermediate hydrazone.30 Direct treatment of 9
with zinc in acetic acid led to the primary sulfonamide 10a in
83% for the two-step process. The primary sulfonamide derived
from meta-iodoanisole was also prepared using an identical
three-step sequence; thus, coupling with N,N-dibenzylhydrazine,
benzyl group removal and finally N–N bond cleavage provided
primary sulfonamide 10b in a 63% yield for the three-step (two-
pot) process.
Acknowledgements
We thank the EPSRC and AstraZeneca for support of this study.
Stuart Wells (AstraZeneca) is thanked for the DSC experiments,
and Maria Gerelle and Fiona Truscott (both University of
Oxford) for the preparation of selected alkenyl iodide substrates.
Notes and references
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2 B. S. Furniss, A. J. Hannaford, P. W. G. Smith and A. R. Tatchell, Vogel’s
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3 H. H. Bossard, R. Mory, M. Schmid and H. Zollinger, Helv. Chim. Acta,
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Conclusions
In conclusion, we have shown for the first time that it is possible
to construct C–SO2–N linkages using palladium-catalysed ami-
nosulfonylation processes. Key to the success of the chemistry
was the use of DABCO·(SO2)2, DABSO, as a solid, easy to
handle and bench-stable equivalent of sulfur dioxide. Using this
reagent it was possible to achieve efficient aminosulfonylation
reactions between a range of aryl-, heteroaryl- and alkenyl
iodides, and N,N-dialkyl hydrazines, providing aryl N-aminosul-
fonamides in good to excellent yields. Significant variation of
the dialkylhydrazine was also possible. The reactions are opera-
tionally simple and employ only a slight excess (1.2–2.2 equiv.)
of sulfur dioxide. Employing N,N-dibenzylhydrazine as the
coupling partner gives access to N-aminosulfonamides that can
be readily ‘deprotected’, allowing preparation of the correspond-
ing primary sulfonamides. We have also demonstrated that
hydrazine·SO2 complexes can function as both the N-nucleophile
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