Regioselective Access to Sultam Motifs through Cobalt-Catalyzed Annulation of Aryl Sulfonamides and Alkynes using an 8-Aminoquinoline Directing Group

Article abstract of DOI:10.1002/adsc.201500690

The use of cobalt as catalyst in direct C-H activation protocols as a replacement for more expensive second row transition metals is currently attracting significant attention. Herein we disclose a facile cobalt-catalyzed C-H functionalization route towards sultam motifs through annulation of easily prepared aryl sulfonamides and alkynes using 8-aminoquinoline as a directing group. The reaction shows broad substrate scope with products obtained in a highly regioselective manner in good to excellent isolated yields. Mechanistic insights suggest the formation of a Co(III)-aryl key species via a rate-determining arene C-H activation during the annulation reaction.

Full text of DOI:10.1002/adsc.201500690

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DOI: 10.1002/adsc.201500690
Regioselective Access to Sultam Motifs through Cobalt-Catalyzed
Annulation of Aryl Sulfonamides and Alkynes using an 8-Amino-
quinoline Directing Group
Oriol Planas,a Christopher J. Whiteoak,a,* Anna Company,a and Xavi Ribasa,*
a
QBIS-CAT Research Group, Institut de Química Computacional i Catàlisi (IQCC) and Departament de Química,
Universitat de Girona, Campus Montilivi, E-17071 Girona, Catalonia, Spain
E-mail: christopher.whiteoak@udg.edu or xavi.ribas@udg.edu
Received: July 20, 2015; Revised: September 25, 2015; Published online: November 25, 2015
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201500690.
À
Abstract: The use of cobalt as catalyst in direct C H a highly regioselective manner in good to excellent
activation protocols as a replacement for more ex- isolated yields. Mechanistic insights suggest the for-
pensive second row transition metals is currently at- mation of a Co(III)-aryl key species via a rate-deter-
À
tracting significant attention. Herein we disclose mining arene C H activation during the annulation
a facile cobalt-catalyzed C H functionalization route reaction.
À
towards sultam motifs through annulation of easily
prepared aryl sulfonamides and alkynes using 8-ami-
À
noquinoline as a directing group. The reaction shows Keywords: alkynes; annulation; C H activation;
broad substrate scope with products obtained in cobalt; regioselectivity; sulfonamides; sultams
Introduction
The use of alkynes in annulation reactions has
become a very powerful tool for the construction of
Direct C H bond functionalization has revolutionized cyclic compounds. In particular, protocols using Rh,[9]
synthetic methodology providing new facile synthetic Ru,[10] Cu,[11] Pd[12] and Ni[13] have been reported for
routes to access molecules which would otherwise re- the preparation of a variety of heterocyclic com-
quire preparation through complex, time-consuming pounds. In terms of the use of these annulation reac-
synthetic procedures.[1] Sulfonamides have become an tions for the realization of sultams, in 2012 Cramer
important motif in pharmaceutical drugs.[2] In particu- and co-workers reported on a Rh-catalyzed protocol
lar, cyclic sulfonamide motifs (sultams) have found starting from aryl sulfonamides incorporating an acyl
use as anti-inflammatory drugs (piroxicam), carbonic
À
anhydrase inhibitors used to lower intraocular pres-
sure in patients with open-angle glaucoma or ocular
hypertension (brinzolamide) and calpain I inhibitors
in cell signalling dysfunctions (Scheme 1).[3]
A
number of synthetic protocols towards sultams have
been reported, although to date the majority of these
methodologies start from elaborated precursors.[4] The
À
development of a simple metal-mediated C H bond
functionalization protocol starting from easily synthe-
sized starting materials would provide a very appeal-
ing route towards the realization of sultam motifs.
À
Historically, most C H coupling protocols have
been based on relatively expensive precious transition
metals, for example Ru, Rh, Pd and Ir. More recently,
attention has turned to the use of more abundant,
cheaper first row transition metals, such as Fe,[5] Co,[6]
Cu[7] and Ni.[8]
Scheme 1. Examples of pharmaceutical drugs containing
cyclic sulfonamide (sultam) motifs.
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Oriol Planas et al.
Scheme 2. (1) Previously reported Rh-catalyzed annulation of alkynes to aryl sulfonamides forming functionalized sultam
motifs. (2) Co-catalyzed annulation of alkynes to aryl carboxamides. (3) Co-catalyzed annulation of aryl sulfonamides and al-
kynes forming functionalized sultam motifs reported herein.
directing group (Scheme 2.1).[14] The catalyst system compared with the previously described Rh-catalyzed
displayed a broad substrate scope, furnishing a range protocol and to showcase the potential of using Co in
of sultam products in good to excellent yields. The annulation reactions.
limitation of this protocol was that when unsymmetri-
cal alkynes were employed as coupling partners, both
possible regioisomers were formed, with only moder- Results and Discussion
ate regioselectivities in some cases.
More recently, Daugulis and co-workers have Initially, we attempted the annulation of the aryl sul-
shown that using Co-catalysis, alkynes can be annulat- fonamide derived from p-toluenesulfonyl chloride and
ed with aryl carboxyamides containing an 8-aminoqui- 8-aminoquinoline, 1a, with phenylacetylene, a, in a va-
noline directing group (Scheme 2.2).[6t] The 8-amino- riety of solvents using a catalytic system comprising
quinoline moiety has been shown to be a privileged of Co(OAc)2 (20 mol%), KOAc (2 equiv.) and
directing group for a number of metal-catalyzed con- Mn(OAc)2 (1 equiv.) at 1008C for 24 h under an at-
versions.[15] In this example the regioselectivities ob- mosphere of air. The observation of 22% of the de-
tained using comparable unsymmetrical alkynes were sired aryl sultam product, 1aa, using trifluoroethanol
considerably higher than for the Rh-catalyzed forma- (TFE; found to be the optimal solvent, see the Sup-
tion of sultams. For example, when 1-propynylben- porting Information for solvent optimization)
zene was employed as coupling partner using the Rh- (Table 1, entry 1) prompted us to further optimize the
catalyzed protocol, both possible regioisomers were synthetic protocol in terms of Co source, oxidant and
obtained in a 2:1 ratio, whereas in the Co-catalyzed base using this solvent.[16]
example the regioselectivity is significantly enhanced
A number of commonly used oxidants for cross-
at 14:1. With these precedents in mind we decided to coupling protocols were investigated using Co(OAc)2
investigate the possibility of realizing a Co-catalyzed and KOAc (Table 1, entries 1–7). It was found that
aryl
sulfonamide
annulation
with
alkynes the optimal oxidant amongh those tested was
(Scheme 2.3), seeking improved regioselective control Mn(OAc)3·2H2O, which furnished a 62% yield of 1aa
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Regioselective Access to Sultam Motifs through Cobalt-Catalyzed Annulation
Table 1. Optimization of the reaction conditions.[a]
Entry
Catalyst
Oxidant
Base
1aa [%][b]
1
2
3
4
5
6
Co(OAc)2
Co(OAc)2
Co(OAc)2
Co(OAc)2
Co(OAc)2
Co(OAc)2
Co(OAc)2
Co(OAc)2
Co(OAc)2
Co(OAc)2
Co(OAc)2
Co(OAc)2
Co(OAc)2
Co(OAc)2
Co(OAc)2
–
CoCl2
CoBr2
Co(NO3)2·6H2O
Co(Cp)2
Co(acac)2
Co(acac)3
Co(OTf)2(MeCN)2
Co(OAc)2·4H2O
CoCl2·6H2O
Mn(OAc)2
benzoquinone
Ag2O
AgNO3
PhI(OAc)2
Mn(OAc)3·2H2O
O2
–
Mn(OAc)3·2H2O
Mn(OAc)3·2H2O
Mn(OAc)3·2H2O
Mn(OAc)3·2H2O
Mn(OAc)3·2H2O
Mn(OAc)3·2H2O
Mn(OAc)3·2H2O
Mn(OAc)3·2H2O
Mn(OAc)3·2H2O
Mn(OAc)3·2H2O
Mn(OAc)3·2H2O
Mn(OAc)3·2H2O
Mn(OAc)3·2H2O
Mn(OAc)3·2H2O
Mn(OAc)3·2H2O
Mn(OAc)3·2H2O
Mn(OAc)3·2H2O
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
KOAc
Na2CO3
K2CO3
Cs2CO3
NaOPiv·H2O
CsOPiv
22
<1
6
50
12
62
3
<1
22
7
7
8[c]
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
4
91(90[d]
78
)
NaOAc·H2O
CsOAc
67
69
0
90
88
81
<1
28
17
NaOPiv·H2O
NaOPiv·H2O
NaOPiv·H2O
NaOPiv·H2O
NaOPiv·H2O
NaOPiv.H2O
NaOPiv·H2O
NaOPiv·H2O
NaOPiv·H2O
NaOPiv·H2O
31
90
87
[a]
Reaction conditions: aryl sulfonamide (1a) (0.17 mmol), ethynylbenzene (a) (2.0 equiv.), Co source (20 mol%), oxidant
(1.0 equiv.), base (2.0 equiv.), 2.0 mL TFE (trifluoroethanol) at 1008C, under air for 24 h.
Yield calculated by 1H NMR analysis of crude reaction mixture using mesitylene as internal standard.
Reaction prepared and performed under a N2 atmosphere.
[b]
[c]
[d]
At 1008C for 16 h.
(Table 1, entry 6). Importantly it was found that the the reaction did not proceed at all and the starting
addition of an oxidant is of significant importance as aryl sulfonamide, 1a, could be fully recovered
in its absence and under a nitrogen atmosphere, no (Table 1, entry 16). Final optimization of the reaction
product formation was observed (Table 1, entry 8). time and temperature set the preferred experimental
Thereafter, optimization of the base was studied conditions at 1008C and 16 h for further substrate
(Table 1, entries 9–15), whereby it was found that scoping (see the Supporting Information). These reac-
a yield of 91% of product 1aa could be obtained tion conditions are similar to those identified by Dau-
when using NaOPiv·H2O (Table 1, entry 12). Finally gulis and co-workers for the Co-catalyzed conversion
the Co source was optimized (Table 1, entries 17–22), of aryl carboxyamide substrates,[6t] except for the
where it was found that Co(OAc)2 was the optimal clear beneficial use of Mn(OAc)3 instead of
Co source (Table 1, entry 12). It was also observed Mn(OAc)2 with our sulfonamide substrates. Detailed
1
that there is little difference between the use of anhy- inspection of the H NMR of the final product con-
drous and hydrated Co sources [see, for example, firmed the presence of a single regioisomer. The abso-
Table 1, entries 17 and 25; CoCl2 and CoCl2·4H2O or lute configuration of 1aa was established from the
Table 1, entries 12 and 24; Co(OAc)2 and structure obtained from X-ray crystallography studies
Co(OAc)2·6H2O], indicating tolerance of the catalyst (Figure 1).
system to the presence of water. In the absence of Co
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Table 3. Scope of Co-catalyzed coupling of phenylacetylene
(a) to aryl sulfonamide derivatives (1a–1o) forming func-
tionalized sultam motifs.[a,b]
Figure 1. X-ray structure obtained for compound 1aa, hydro-
gen atoms omitted for clarity. For full details see the Sup-
porting Information.
With these optimal reaction conditions in hand, we
investigated the importance of the 8-aminoquinoline
directing group. The results obtained (Table 2) show
that the 8-aminoquinoline directing group gives supe-
rior yields compared to when no directing group is
used (0%) or when acetyl (0%) and pyridyl (32%;
Table 2. Screening of aryl sulfonamides (1a–5a) with/without
different directing groups (X) using the optimized reaction
conditions.[a,b]
[a]
Reaction
(0.35 mmol),
conditions:
aryl
(a)
sulfonamide
(2.0 equiv.),
(1a–1o)
Co(OAc)2
alkyne
(20 mol%), Mn(OAc)3·2H2O (1.0 equiv.), NaOPiv·H2O
(2.0 equiv.), 2.0 mL TFE (trifluoroethanol) at 1008C,
under air for 16 h.
Isolated yields obtained after purification by column
chromatography.
[a]
Reaction
(0.17 mmol),
conditions:
aryl
(a)
sulfonamide
(2.0 equiv.),
(1a–5a)
Co(OAc)2
alkyne
[b]
(20 mol%), Mn(OAc)3·2H2O (1.0 equiv.), NaOPiv·H2O
(2.0 equiv.), 2.0 mL TFE (trifluoroethanol) at 1008C,
under air for 16 h.
[b]
1
Yield calculated by H NMR analysis of crude reaction
mixture using mesitylene as internal standard.
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Regioselective Access to Sultam Motifs through Cobalt-Catalyzed Annulation
Table 4. Scope of Co-catalyzed coupling of substituted al-
kynes (b–t) to aryl sulfonamide (1a) forming functionalized
sultam motifs.[a,b]
single regioisomer) directing groups are present under
these conditions. The absence of activity when using
the acetyl directing group is in sharp contrast to the
Rh-catalyzed protocol reported by Cramer and co-
workers.[14]
Next, the scope of the newly optimized protocol
was probed using different aryl sulfonamide deriva-
tives, which were easily prepared from 8-aminoquino-
line and the requisite sulfonyl chloride. These studies
furnished functionalized sultam motifs in good to ex-
cellent yields (Table 3). In all cases the crude reaction
mixtures displayed three well defined species when
analyzed by TLC, corresponding to starting aryl sulfo-
namide, residual alkyne and sultam product. The
product isolated after column chromatography was
found to contain only a single regioisomer. Trace
amounts of other regioisomers were only observed in
the formation of 1da and 1ga (see the Supporting In-
formation). The highest yields were obtained with de-
rivatives containing electron-donating groups (up to
85% isolated yield), whilst those containing electron-
withdrawing substituents furnished lower yields (e.g.,
1fa was obtained in only 64% yield and 1ka, 1la, 1na
were obtained in only trace amounts). We were also
able to obtain the sultam containing a thiophene
moiety (1ia), although only traces of sultam product
were obtained when the pyridine derivative was em-
ployed (1ja), demonstrating some limitations to the
substrate scope. When the substituents are present in
the ortho-position to the sulfonamide reduced yields
are obtained, likely as a result of the blocking of one
À
of the C H bonds to activation (for example, see 1aa
and 1ma, whereby changing the position of the
methyl group decreases the isolated yield from 85%
to 54%, respectively, Table 3).
Substrates that failed to give satisfactory product
yields were then included in poisoning experiments in
order to see if the substrate was inhibiting the reac-
tion or if the reaction rate was comparatively slower
with these substrates. One equivalent of 1j, 1k, 1l or
1n was included in reactions respectively for the con-
version of 1a to 1aa (see the Supporting Information
for details). It was found that indeed in all cases these
substrates are poisoning the catalyst system, resulting
in decreased yields of 1aa. This type of poisoning has
recently been described by Glorius and co-workers.[17]
We propose that the poisoning observed in our stud-
ies arises from poorly reversible coordination of the
Co to the substrate.
[a]
Reaction conditions: aryl sulfonamide 1a (0.35 mmol),
acetylene derivatives (b–t) (2.0 equiv.), Co(OAc)2
(20 mol%), Mn(OAc)3·2H2O (1.0 equiv.), NaOPiv·H2O
(2.0 equiv.), 2.0 mL TFE (trifluoroethanol) at 1008C,
under air for 16 h.
Isolated yields obtained after purification by column
chromatography.
Product derived from 3-chloro-3-methylbut-1-yne.
Reaction at 1008C for 40 h.
Combined yield of both regioisomers. Regioisomers ob-
[b]
[c]
Following screening with substituted aryl sulfona-
mides, we turned our attention to the use of different-
ly substituted alkynes (Table 4). Again the catalyst
system displayed broad substrate tolerance for a varie-
ty of functional groups and again high regioselectivi-
ties were observed as confirmed by the presence of
[d]
[e]
tained in a ratio of 3:1; major regioisomer depicted (see
the Supporting Information for X-ray crystal structure
obtained).
1
only one species in the H NMR in most cases. When
an ester substituent was present in the alkyne (1ar)
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1
Scheme 3. Intermolecular competition reactions under optimized reaction conditions; yields calculated by H NMR analysis
of crude reaction mixture using mesitylene as internal standard.
both possible regioisomers were identified (the TLC and was fully characterized (see the Supporting Infor-
displayed a single spot for a combination of the two mation). Unexpectedly, when using 3-chloro-3-meth-
regioisomers). The major regioisomer could be sepa- ylbut-1-yne as substrate (h), the product was obtained
rated from the minor regioisomer by recrystallization (1ah’) whereby hydrogen chloride had been eliminat-
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Scheme 4. Deuterium labelling experiments: Reaction conditions: aryl sulfonamide 1a (0.35 mmol), phenylacetylene (a)
(2.0 equiv.), Co(OAc)2 (20 mol%), Mn(OAc)3·2H2O (1.0 equiv.), NaOPiv·H2O (2.0 equiv.), 2.0 mL solvent at 1008C, under
air for 16 h. KIE experiment: 0.17 mmol of both 1e and D5-1e, phenylacetylene (a) (2.0 equiv.), Co(OAc)2 (20 mol%),
Mn(OAc)3·2H2O (1.0 equiv.), NaOPiv·H2O (2.0 equiv.), 2.0 mL solvent at 1008C, under air for 16 h. Yields reported are per-
centage of isolated compounds obtained after purification by column chromatography.
ed. When electron-donating substituents are present (Scheme 3). When two equivalents of both a terminal
on the aryl group of phenylacetylene the reaction re- (a) and an internal (g) alkyne were included it was
sulted in low or trace yields (trace amounts and 30% found that insertion of the terminal alkyne was signif-
for 1ai and 1aj, respectively). In the case of 1aj, even icantly favored, resulting in a product ratio of 15:1
after an extended reaction time the yield was not sig- for terminal and internal alkyne insertion, respective-
nificantly improved.
ly (Scheme 3.1). Thereafter we also ran competition
The effectiveness of this transformation was further reactions using differently substituted aryl sulfona-
checked by performing a gram-scale reaction to mide and phenylacetylene substrates (Scheme 3.2 and
obtain 1aa and 1al, furnishing 64% (0.87 g) and 61% Scheme 3.3, respectively). As expected, in agreement
(0.89 g), respectively (see the Supporting Informa- with the results obtained from the substrate screening,
tion).
reaction with electron-donating aryl sulfonamides
In order to further compare the reactivities of the (methoxy, 1b) was found to be slightly favored over
substrates under the optimized protocol, we per- electron-withdrawing (chloro, 1c) aryl sulfonamides.
formed
intermolecular
competition
reactions Likewise, insertion of the p-nitrophenylacetylene (n)
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was favored over p-methoxyphenylacetylene (j). The
latter competition reaction only yielded 34% of the p-
nitro product (1an), whereas in the absence of the
competing p-methoxyphenylacetylene during sub-
strate screening we obtained 97% isolated yield. This
result suggests that the p-methoxyphenylacetylene is
inhibiting the reaction to some extent. This inhibition
is similar to the result obtained by Ackermann and
co-workers during their intermolecular competition
reactions.[6r]
We also performed a range of deuterium exchange
reactions (Scheme 4). We found that when the reac-
tion was performed in D4-methanol the final sultam
product was 78% deuterated on the sultam motif
(Scheme 4.1). Likewise, when deuterated phenylace-
1
tylene was used as substrate we observed 66% of H
incorporation into the sultam product (Scheme 4.2).
These results indicate that the proton/deuterium of
the terminal alkyne likely exchanges with the solvent
under the basic reaction conditions.
Additionally, we performed a reaction in the ab-
sence of alkyne in D4-methanol (Scheme 4.3). At the
end of the reaction we observed a low inclusion of
deuterium in the starting sulfonamide, suggesting the
Scheme 5. Proposed mechanistic cycle (1a substrate is shown
as example).
À
deutero-demetallation of a putative aryl-Co inter- mediate can activate the aryl C H bond through
mediate species (see the Supporting Information). a concerted metallation deprotonation (CMD) type
This is further supported by the kinetic isotope effect process as a result of its higher electrophilicity of
(KIE) of 3.5 calculated when including both 1e and Co(III) compared with Co(II), giving rise to inter-
D5-1e in the reaction (Scheme 4.4). The value ob- mediate 2, although at this point other activation pro-
tained is consistent with C H activation being the cesses cannot be completely discarded.[18] An analo-
À
rate-determining step in the reaction.
gous Co(III) species was isolated and characterized
À
The exact mechanisms of Co-catalyzed C H activa- by Daugulis and co-workers using Co(II) precursors
tion protocols are still not fully understood. Recently, for their analogous aryl carboxyamide substrates.[6t]
À
Niu, Song and co-workers identified the presence of KIE experiments indicate that this challenging C H
radicals using EPR spectroscopy in their Co-catalyzed activation event is the rate-determining step of the re-
alcohol coupling protocol.[6m] This was further evi- action (Scheme 4.4). Subsequently, insertion of the
denced by the lack of activity when the radical scav- alkyne, a, into the Co(III)-aryl bond results in the
enger 2,2,6,6-tetramethylpiperidine 1- oxyl (TEMPO) transient intermediate 3. Finally, elimination of Co(I)
was included (see the Supporting Information). We which is then reoxidized to Co(OAc)2, provides the
therefore included several different radical scavengers desired sultam product, 1aa. As suggested by the radi-
[BHT, AIBN and P(OEt)3] in our reactions and cal scavenger experiments described above, some
found that activity was almost completely inhibited in steps of the catalytic cycle may involve radical inter-
agreement with this previous work, suggesting that mediates. We propose that the improved regioselec-
our reaction likely proceeds through radical inter- tivity when using Co catalysts compared with the Rh
mediates in some steps of the mechanism.
catalyst reported by Cramer for sultam formation
We propose a mechanism (Scheme 5) in which ini- probably arises from the fact that there is poor inter-
tially the Co(OAc)2 chelates to the quinoline directing ference of the Cp* ligand in the alkyne insertion into
group and to the sulfonamide of the substrate, 1a, (in- the Rh(III)-aryl bond.[14]
termediate 1) releasing one equivalent of acetic acid.
Finally, we attempted to upgrade the products ob-
The aminoquinoline coordination environment favors tained by removing the 8-aminoquinoline directing
the stabilization of high-valent Co species; we there- group (see the Supporting Information for details), al-
fore propose that once coordinated to the aryl sulfo- though to date we have not been successful. The re-
namide substrate the Co(II) undergoes oxidation to moval of 8-aminoquinoline directing groups has been
Co(III) using oxygen as the terminal oxidant. Indeed reported to be possible using ammonia if the annulat-
our studies show that the presence of oxygen is highly ed product contains carbonyl functionalities at either
beneficial for the process to proceed (see the Sup- side of the 8-aminoquinoline, in similarity to the final
porting Information). Subsequently, this Co(III) inter- step of the Gabriel synthesis of amines.[6n,19] If two ad-
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Regioselective Access to Sultam Motifs through Cobalt-Catalyzed Annulation
and the vial was subsequently sealed. The resulting mixture
was stirred at 1008C for 16 h and thereafter cooled to room
temperature. The solvent was removed and the product pu-
rified using column chromatography (silica gel: dichlorome-
thane). After purification the product was dried under re-
duced pressure.
jacent carbonyl funtionalities are not present, the di-
recting group can be removed using cerium(IV) am-
monium nitrate (CAN) only if the 5-methoxy-8-ami-
noquinoline is used.[20] However, the CAN strategy
does not always work using this elaborated directing
group[21] as well as in our compounds. We also at-
tempted a H2:Pd(0)/C reduction, but only the pyridin-
ic moiety of the 8-aminoquinoline was reduced to
afford 1aaH4 (see the Supporting Information). We
also tried reduction with a stronger reducing agent
such as SmI2, but a complex mixture of products was
obtained. Our next goal is to develop a facile method-
ology for the 8-aminoquinoline directing group re-
moval or extrapolate the reported reactivity to more
easily removable directing groups.
1
Full characterization data obtained (including original H,
13C {1H} and COSY NMR spectra for all sultam products)
can be found in the Supporting Information. CCDC 1407285
(1aa), CCDC 1407286 (1ah’), CCDC 1411541 (1ar) and
CCDC 1407287 (1aaH4) contains the supplementary crystal-
lographic data for this paper. These data can be obtained
free of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
Acknowledgements
Conclusions
We acknowledge financial support from the ERC for the
Starting Grant Project ERC-2011-StG-277801 to X.R. and
MINECO of Spain for CTQ2013-43012-P to X.R. and A.C,
and a RyC contract to A.C. We thank the MECD for a FPU
PhD grant to O.P. X.R. also thanks ICREA for an ICREA-
Acad›mia award. We are also grateful to X. Fontrodona (X-
ray crystallography), Dr. L. Gómez (HR-MS) and STR-
UdG.
In summary, we have reported on a new Co-catalyzed
protocol for the synthesis of sultam motifs starting
from easily prepared aryl sulfonamides and alkynes.
The protocol permits the use of a broad range of sub-
stituted aryl sulfonamides and alkynes, as well as dis-
playing excellent regioselectivities compared with the
previously reported Rh-catalyzed protocol, where
moderate regioselectivity was found.[14] This protocol
demonstrates the increasing potential of Co to replace
more expensive second row transition metals as
a result of favorable reactivities and selectivities.[22]
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All reagents and solvents were purchased from Sigma Al-
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Adv. Synth. Catal. 2015, 357, 4003 – 4012