Divergent reactivity of sulfinates with pyridinium salts based on one-: Versus two-electron pathways

Article abstract of DOI:10.1039/d1sc00776a

One of the main goals of modern synthesis is to develop distinct reaction pathways from identical starting materials for the efficient synthesis of diverse compounds. Herein, we disclose the unique divergent reactivity of the combination sets of pyridinium salts and sulfinates to achieve sulfonative pyridylation of alkenes and direct C4-sulfonylation of pyridines by controlling the one- versus two-electron reaction manifolds for the selective formation of each product. Base-catalyzed cross-coupling between sulfinates and N-amidopyridinium salts led to the direct introduction of a sulfonyl group into the C4 position of pyridines. Remarkably, the reactivity of this set of compounds is completely altered upon exposure to visible light: electron donor-acceptor complexes of N-amidopyridinium salts and sulfinates are formed to enable access to sulfonyl radicals. In this catalyst-free radical pathway, both sulfonyl and pyridyl groups could be incorporated into alkenes via a three-component reaction, which provides facile access to a variety of β-pyridyl alkyl sulfones. These two reactions are orthogonal and complementary, achieving a broad substrate scope in a late-stage fashion under mild reaction conditions.

Full text of DOI:10.1039/d1sc00776a

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Divergent reactivity of sulfinates with pyridinium
salts based on one- versus two-electron pathways†
Cite this: DOI: 10.1039/d1sc00776a
ab
ab
ab
ab
*
All publication charges for this article
have been paid for by the Royal Society
of Chemistry
Myojeong Kim,
Euna You,
Seongjin Park
and Sungwoo Hong
One of the main goals of modern synthesis is to develop distinct reaction pathways from identical starting
materials for the efficient synthesis of diverse compounds. Herein, we disclose the unique divergent
reactivity of the combination sets of pyridinium salts and sulfinates to achieve sulfonative pyridylation of
alkenes and direct C4-sulfonylation of pyridines by controlling the one- versus two-electron reaction
manifolds for the selective formation of each product. Base-catalyzed cross-coupling between sulfinates
and N-amidopyridinium salts led to the direct introduction of a sulfonyl group into the C4 position of
pyridines. Remarkably, the reactivity of this set of compounds is completely altered upon exposure to
visible light: electron donor–acceptor complexes of N-amidopyridinium salts and sulfinates are formed
to enable access to sulfonyl radicals. In this catalyst-free radical pathway, both sulfonyl and pyridyl
groups could be incorporated into alkenes via a three-component reaction, which provides facile access
to a variety of b-pyridyl alkyl sulfones. These two reactions are orthogonal and complementary,
achieving a broad substrate scope in a late-stage fashion under mild reaction conditions.
Received 8th February 2021
Accepted 30th March 2021
DOI: 10.1039/d1sc00776a
rsc.li/chemical-science
synthetic strategy to employ 1,4-diazabicyclo[2.2.2]octane-
bis(sulfur dioxide) for incorporating sulfur dioxide, generating
Introduction
a diverse set of metal sulnates to deliver a wide range of
sulfone compounds.8d–f,10 The Larionov group reported a transi-
tion metal-free method, where sulnate can serve as a nucleo-
phile in a persulfate-initiated SNAr-type process.11
Sulfonyl groups are key functional motifs embedded in a myriad
of biologically relevant molecules and functional materials, as
their intrinsic properties can access unexplored chemical space
by imparting hydrophilicity and biological affinity.1 They can
also serve as versatile building blocks for further modication
or as reagents in many chemical transformations.2 Accordingly,
selective incorporation of sulfonyl moieties into organic
commodities has received considerable attention in both
chemistry and biology.3 Conventional approaches include
Friedel–Cra type sulfonylation of arenes,4 oxidation of
suldes,5 and nucleophilic aromatic substitution (SNAr).6
However, the practicality of these methods is largely limited by
harsh conditions, such as high temperature and the need of
stoichiometric acids and strong oxidants. For milder condi-
tions, readily available sulnates have emerged as practical and
bench-stable reagents, and their synthetic potential has been
widely demonstrated.7 For instance, substitution reactions of
halogenated (hetero)arenes with sulnates via transition-metal
catalysis have provided efficient access to (hetero)aryl
sulfones.8,9 In addition, the Willis group has reported a robust
Alternatively, the recent advent of a photocatalytic platform
enables the utilization of sulnates as convenient sulfonyl
radical precursors9,12 toward the difunctionalization of p-
systems.13 Taking advantage of dual photoredox and Ni catal-
ysis, Nevado and colleagues developed a carbosulfonylation
reaction of activated alkenes using aryl halides to furnish b-
sulfonylated aryl products.13a In addition, unconjugated dienes
can also be applied to such transformations, as recently
demonstrated by the Rueping group.13c Despite signicant
advances within these catalytic manifolds, the majority of the
known methods are still restricted to the use of (hetero)aryl
halides as electrophilic coupling partners and exogenous cata-
lysts. Therefore, the development of more sustainable strategies
that diversify the utility of sulnates would be highly
demanding. Given the versatility of sulnates, we wondered
whether it would be possible to exploit their divergent reactivity
with pyridinium salts by carefully adjusting the reaction
conditions based on one- vs. two-electron reaction manifolds.
However, the difficulty in discriminating the inherent reactivity
of two distinct reaction pathways makes this strategy chal-
lenging, and the complete exclusion of the other reaction
pathway is required. In this regard, our design strategy arose
from the initial observation of almost no reactivity between
sulnates and pyridinium salts under catalyst-free conditions,
aDepartment of Chemistry, Korea Advanced Institute of Science and Technology
(KAIST), Daejeon, 34141, Korea. E-mail: hongorg@kaist.ac.kr
bCenter for Catalytic Hydrocarbon Functionalizations, Institute for Basic Science (IBS),
Daejeon 34141, Korea
† Electronic supplementary information (ESI) available: Experimental procedure
and characterization of new compounds (1H and 13C NMR spectra). CCDC
2057463 and 2057471. For ESI and crystallographic data in CIF or other
electronic format see DOI: 10.1039/d1sc00776a
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and thus, their reactivity would depend entirely on the suitable
activation process via either open-shell or polar reaction
pathways.
Results and discussion
An essential objective of our approach was to identify the acti-
vation modes that would selectively operate one- vs. two-
electron reaction manifolds. With this design in mind, we
commenced our investigations into the ability to induce the
association of sulnate 2a (Eox ¼ +0.32 V vs. SCE)21 with N-
amidopyridinium salt 1a (Ered ¼ ꢀ0.82 V vs. SCE) (see the ESI†).
Indeed, when both reagents were mixed, a redshi was
observed by UV/vis absorption spectroscopy as a result of the
formation of colored EDA complexes (Fig. 1a). Further analyses
using Job's method of continuous variations exhibited that the
donor–acceptor complex of 1a and 2a was formed in a 1 : 1 ratio
of mole fractions (Fig. 1b). Given that sulfonyl radicals are
generally considered to be electrophilic in nature,22 it was ex-
pected that their polarity-mismatched addition to electron-
decient heteroarenium salts would result in a poor reactivity
between them. Indeed, we did not observe any productive
reactivity between 1a and 2a under blue LED irradiation (see the
ESI†). In this context, equilibrium between two orthogonal
resting states provides the basis for controlling the divergent
reaction pathways driven by different activation modes (Fig. 1c).
Based on the above-mentioned results, we rst focused on
the proposed three-component ‘one-electron pathway’ reaction
mode, which enables access to a polarity-reversing strategy in
a radical mechanism, as illustrated in Table 1 (see the ESI†). We
exploited butyl vinyl ether (3a) to conjugate pyridyl and tosyl
groups in a single step upon irradiation with blue LEDs. Aer
extensive screening of parameters such as solvent, concentra-
tion, and temperature, the optimal reaction conditions were
identied without the need for an external photocatalyst or
additives. DMSO proved to be the optimal solvent for this
protocol, with the reaction proceeding to 90% product yield
Synthetic strategies involving photoactive electron donor–
acceptor (EDA) complexes with certain anions have been widely
explored as powerful tools to promote radical-mediated trans-
formations by harvesting visible light (Scheme 1a).14,15 We
envisioned that sulnates could also serve as a new type of
electron-donor for delivering such a radical-based reactivity
with N-activated pyridinium salts.16,17 Combined with an alkene
moiety, the generated sulfonyl radicals could be embraced in
the three-component assembly process18 without the need of
external photocatalysts and oxidants, which is preferable from
the viewpoint of green chemistry. If successful, such a modular
approach would enable the net addition of pyridyl and sulfonyl
moieties across double bonds and further expand the synthetic
horizon of sulnates (Scheme 1b, top). As another mechanistic
scenario, we postulated the possibility of direct insertion of
sulnates into pyridinium salts by exploiting them as electro-
philes within a two-electron process19,20 to give C4-sulfonyl
heteroarene derivatives (Scheme 1b, bottom).
In the course of our investigation, we discovered that the
poor kinetic prole of sulnates with N-amidopyridinium salts
could be dramatically accelerated by adding a catalytic amount
of a base, which allows an otherwise unfavorable addition
pathway in this system. Herein, we disclose the divergent use of
sulnates and pyridinium salts to explore visible-light-driven
sulfonative pyridylation of alkenes under photocatalyst-free
conditions and C4-sulfonylation of N-heteroarenes. In our
approach, a versatile platform provides distinct modes of
reaction pathways to access a variety of value-added sulfones by
controlling the one- versus two-electron reaction manifolds
under mild conditions. Remarkably, all tested reactions dis-
played excellent C4-positional selectivity regarding the pyridine
scaffolds.
Fig. 1 (a) UV-Vis absorption spectra of N-amidopyridinium salt (1a),
sodium p-toluenesulfinate (2a), and the mixture of 1a and 2a (0.15 M in
DMSO). (b) Job's plot for the ratio between 1a and 2a. (c) Two
Scheme 1 Divergent reactivity of sulfinates based on one- versus orthogonal resting states (X ¼ NTs(Me)). SET ¼ single-electron transfer.
two-electron reaction manifolds.
BET ¼ back-electron transfer.
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Table 1 Optimization of the reaction conditionsa
obtained in all cases (>20 : 1 r.r. if not denoted otherwise). Next,
we explored the reaction with respect to sulnates, and
a number of aryl sulnates with electronic perturbations on the
aromatic ring were observed to be suitable sulfonyl sources (4l–
4o). The structure of 4m was elucidated based on X-ray crys-
tallographic analysis.23 Sodium 2-naphthalenesulnate also
underwent the desired reaction smoothly, delivering 4p. Like-
wise, a pyrimidyl sulnate was effectively converted into the
desired sulfone (4q). In addition, the method could be readily
extended to alkyl sulnate substrates (4r, 4s, and 4t), including
cycloalkyl (4u and 4v). Next, the generality with respect to the
alkene component was subsequently investigated, and various
electron-rich alkenes, such as vinyl ethers and enamides, and
unactivated alkenes were subjected to the optimized reaction
conditions. Aliphatic vinyl ethers bearing ethyl and cyclohexyl
groups reacted readily, leading to the formation of 4w and 4x.
Substrates containing polar functionalities, such as hydroxyl
and chlorine groups, could be successfully engaged in this
transformation to furnish the products (4y and 4z). Phenyl vinyl
ethers also served as an effective coupling partner (4aa), and
employing substrates including tert-butyl at the para-position,
benzodioxole, and coumarin functionalities was suitable under
the reaction conditions to afford the desired products (4ab, 4ac,
and 4ad). Notably, this method could be extended to the reac-
tions of substrates bearing vinyl formamide and amide groups
(4ae–4ag). Additionally, 2,3-dihydrofuran bearing internal
olens could be employed in this protocol to afford the desired
product 4ah. Remarkably, this strategy was successfully
extended to aliphatic unactivated alkenes (4ai–4ak), which
could not be achieved by typical strategies as reported before.
Moreover, the generality of the mild reaction conditions was
well demonstrated by the facile late-stage modication of
a series of structurally diverse complex molecules. For example,
this coupling could be extended to D-fructopyranose, b-citro-
nellol, L-tyrosine, and estrone derivatives to afford desired
products (4al–4ao) with C4 selectivity, highlighting the func-
tional group compatibility. Finally, we examined the scope of
dienes. The diallyldiphenylsilane was converted to the corre-
sponding product via 6-endo-trig cyclization (4ap).24 Likewise,
we could observe a transformation of 1,5-cyclooctadiene into
a bicyclic product (4aq). In addition, a disubstituted tricyclic
pyridine was produced in the reaction of 2,4-norbornadiene
(4ar).25
Yieldb (%)
Entry
Variations from standard conditions
4a
5a
1
None
90
77
31
65
67
80
n.d.
n.d.
n.d.
n.d.
n.d.
6
2
DMF instead of DMSO
3
4
5
Green LED (525 nm) instead of blue LED
Using [Ir(dFCF3ppy)2(bpy)]PF6 (5 mol%)
Using Eosin Y (2 mol%)
6
Using NaOAc (1.2 equiv.) for 12 h
Using DBU (20 mol%) for 12 h
Using DBU (20 mol%) for 12 h in the dark
In the dark
7c
8c
9
<5
61
n.d.
n.d.
n.d.
39
78
n.d.
n.d.
n.d.
10
11
Addition of TEMPO (2.0 equiv.)
Under air atmosphere
a
Reaction conditions: 1a (0.075 mmol), 2a (0.075 mmol), and 3a (0.05
mmol) in DMSO (0.5 mL) at rt under irradiation using blue LEDs
b
(440 nm, 10 W) for 3 h under N2. Yields were determined by 1H
c
NMR spectroscopy. 1a (0.05 mmol), 2a (0.075 mmol) and 3a (0.075
mmol) were used. Tol ¼ p-tolyl. DMSO ¼ dimethylsulfoxide. DMF ¼
N,N-dimethylformamide. TEMPO ¼ (2,2,6,6,-tetramethylpiperidin-1-yl)
oxyl. n.d. ¼ not detected.
(entry 1). The light source at longer wavelengths (525 nm, green
LEDs) led to a reduced yield (entry 3). External photocatalysts
did not offer any useful improvements (entries 4 and 5). Under
neutral conditions, a two-component coupling product 5a was
not observed (entries 1–5). The use of NaOAc (1.2 equiv.)
provided a comparable yield of 80% for 4a, while compound 5a
was obtained with a 6% yield (entry 6). However, the reactivity
dramatically changed with the use of DBU (20 mol%), regard-
less of light irradiation, resulting in the formation of 5a as
a major product (entries 7 and 8). Control experiments for the
optimized conditions veried the necessity of light for the three-
component reaction to proceed (entry 9). The reactivity was
completely inhibited when the radical scavenger (2,2,6,6,-
tetramethylpiperidin-1-yl)oxyl (TEMPO) was added (entry 10).
The presence of oxygen decreased the reaction efficiency (entry
11).
Aer demonstrating the general applicability of the broad
substrate scope, we performed a series of control reactions to
gain insight into the reaction mechanism. To determine
whether the pyridines generated by intermolecular charge
transfer could act as substrates, crossover experiments were
carried out with a mixture of 1a and 2-phenyl-substituted pyri-
dines. As anticipated, the reaction occurred at the C4 position of
1a, providing 4a (Scheme 2a). Next, we conducted radical trap-
ping experiments by adding a radical scavenger, 1,1-dipheny-
lethene (Scheme 2b). The formation of the desired product was
completely inhibited, suggesting that a radical pathway is
involved in this transformation. In addition, a direct-trapping
product of the sulfonyl radical was observed by HR-MS (see
the ESI†).
Aer the successful development of sulfonative pyridylation
reactions of alkenes, we set out to examine the scope of the
current method by subjecting a wide range of substituted N-
amidopyridinium salts, as shown in Table 2. First, unsub-
stituted and C2-phenyl derivatives readily reacted to afford the
corresponding b-arylsulfonyl alkylpyridine products 4a and 4b.
Substrates bearing para-methoxy and triuoromethyl groups on
the phenyl rings and dimethyl groups at the C2 position
smoothly underwent the reaction to furnish the desired prod-
ucts (4c–4e). Notably, pyridinium salts containing a wide range
of functional groups, such as methyl, phenyl, halide, and
ester, at the C3 position, proved to be compatible with the
process (4f–4j). Remarkably, excellent C4-selectivity was
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Table 2 Substrate scope of three-component sulfonative pyridylation of alkenesa
a
Reaction conditions: 1 (0.15 mmol), 2 (0.15 mmol), and 3 (0.1 mmol) in DMSO (1.0 mL) at rt under irradiation using blue LEDs (440 nm, 10 W) for
3 h under N2. Isolated yield. Diastereomeric ratios were measured by 1H NMR spectroscopy. Unless indicated, the C4/C2 ratio >20 : 1. b MeOH was
used instead of DMSO for 12 h. 3.0 equiv. of sulnate were used for 24 h. PMB ¼ p-methoxybenzoyl.
c
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two regioisomeric intermediates, p-C and o-C. The transition
state p-B-TS leading to the C4-intermediate p-C was found to be
favored by 2.9 kcal molꢀ1 over the other transition state o-B-TS
(the red route), which is consistent with the observed C4-
selectivity. An interaction energy difference is caused by the
additional non-covalent attraction between the negatively
charged sulfonyl oxygen and the nitrogen of the pyridinium
16a
ꢀ
substrate across a distance of 2.8 A (see the ESI†). Next, the
reaction pathway proceeds through deprotonation of cationic
radical C and homolytic N–N bond cleavage from D via transi-
tion state D-TS, which delivers the desired product along with
an amidyl radical E that makes possible a radical chain prop-
agation reaction. The quantum yield (F ¼ 3.6) measured under
the standard reaction conditions suggests that the radical chain
pathway is quite productive for the overall reaction. The
generated amidyl radical appears to react with a sulnate to
furnish sulfonyl radical A and initiate the radical chain
pathway. In addition, the SET between E and tosyl sulnate is
exergonic, making the production of the sulfonyl radical A
5.8 kcal molꢀ1 lower in Gibbs free energy than that for the
amidyl radical E. Although it is reversible and possible to
regenerate an amidyl radical, the sulfonyl radical will be
predominantly populated considering the use of stoichiometric
amounts of sulnate and the thermodynamics for the genera-
tion of sulfonyl and amidyl radicals.
Scheme 2 Control experiments for the three-component reactions.
(a) Reaction with mixtures of 1a and 2-phenyl-substituted pyridine. (b)
Radical trapping experiments using 1,1-diphenylethene.
To better understand the observed regioselectivity and
mechanism, we investigated the reaction pathways using
density functional theory (DFT) calculations. A plausible reac-
tion mechanism involving the formation of photoactive EDA
complexes and the computed reaction energy proles are
depicted (Fig. 2). Upon excitation by visible light, EDA complex
I* undergoes an intermolecular single-electron transfer from
the sulnate to the salt. The resulting sulfonyl radical A adds to
the double bond to yield the corresponding alkyl radical inter-
mediate B, which adds to pyridinium salt 1a. Our calculation
suggests that the radical addition step between alkyl radical B
and 1a determines the regioselectivity (C4 vs. C2), resulting in
Given the pivotal importance of C4-sulfonylated pyridines
and quinolines as key moieties in pharmaceuticals26 and
Fig. 2 (a) Proposed mechanism for the sulfonative pyridylation of alkenes. (b) Free-energy profile for the site-selective sulfonative pyridylation of
alkenes. The blue traces represent the C4-product formation pathway. The red traces represent the C2-product formation pathway.
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Table 3 Substrate scope of C4-sulfonylationa
conditions with excellent C4 regioselectivity. The structure of
sulfone 5e was conrmed by X-ray diffraction analysis.28
Expanding the scope from pyridine derivatives to other
heterocycles, such as quinolines, was possible and desired
products 5h, 5i, and 5j wereyielded. Next, we evaluated cross-
coupling with regard to the sulnate coupling partner. Aryl
sulnates with electron-decient and electron-rich functional
groups were all tolerated (5k–5m). Similarly, 2-naphthyl and
thiophenyl sulnates were also suitable substrates, leading to
products 5n and 5o. Moreover, this method worked well with
a series of alkyl sulnates to give the desired products (5p–5r).
In addition, cyclic sulnates readily participated in this trans-
formation to afford 5s and 5t.
Further, experiments aimed at elucidating the reaction
mechanism were performed. No reactivity was observed when
an external base was not used (see the ESI†). When using
TEMPO as an additive, the reactivity was not signicantly sup-
pressed, and no TEMPO-sulfonyl radical adduct was observed in
the NMR or LC-MS of the crude reaction mixture, suggesting
that a radical intermediate pathway is not predominant in this
system (see the ESI†). A competitive experiment using a mixture
of 1a and 2-phenylpyridine showed that the reaction took place
a
Reaction conditions: 1 (0.1 mmol), 2 (0.11 mmol) and DBU (0.02
b
mmol) in DMF (1.0 mL) at rt for 16 h under N2. Isolated yield. 0.5
equiv. of DBU were used.
synthetically useful components in organic chemistry,27 we next
set out to expand the utility of our strategy by investigating the
C4-sulfonylation of pyridinium salts. Aer a survey of the
reaction parameters such as base, solvent, and concentration,
the optimized reaction conditions were identied (see the ESI†),
and the generality with respect to this protocol was explored, as
illustrated in Table 3. Pleasingly, a wide range of pyridinium
salts bearing ester, phenyl, bromide, chloride, and tri-
uoromethyl groups underwent the two-component reactions
to provide the desired products (5b–5g) under the optimized
Fig. 3 Control experiments and the proposed mechanism for the
two-component reactions. (a) Reaction with mixtures of 1a and 2- Scheme
3 Late-stage modifications of pyridine-based drug
phenyl-substituted pyridine. (b) Proposed mechanism.
derivatives.
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sulfonylation of pyridines through two distinct pathways. Har-
nessing the photochemical activity of EDA complexes from
sulnates and N-amidopyridinium salts, a three-component
reaction with alkenes was orthogonally achieved without
using external photocatalysts. This radical pathway allows for
a rapid assembly of sulfonyl and pyridyl moieties at the ethylene
linker with high functional group tolerance. DBU is found to be
capable of promoting coupling between the identical reactants,
thus enabling the selective insertion of a sulfonyl group at the
C4 position of pyridines. Furthermore, these operationally
simple protocols can be readily applied to the late-stage modi-
cation of complex molecules to provide new retrosynthetic
disconnections that would otherwise be difficult to access. This
study highlights the synthetic potential of divergent trans-
formations by leveraging the intrinsic nature of sulnates and
N-amidopyridinium salts.
Author contributions
Scheme 4 Synthetic utilities of sulfones 4ba, 5c and 5r (see the ESI†
for details).
M. K., E. Y. and S. P. performed the experiments. M. K. con-
ducted computational studies. S. H. directed the project. All
authors contributed to the preparation of the manuscript.
only with 1a, while 2-phenylpyridine was not involved in the
nucleophilic addition (Fig. 3a). Based on the several results, we
could propose a mechanism for DBU-mediated sulfonylation of
pyridinium salts as described (Fig. 3b). Parallel competition
reactions between 1a and its deuterated analog 1a–d5 were
performed, in which the kH/kD was found to be 2.2 (see the
ESI†), indicating the reversible process of nucleophilic addition
of sulnates.29
The incorporation of sulfonyl groups onto pharmaceutically
relevant building blocks is important for modulating bioactivity
and properties for the construction of diverse compound libraries.
To further highlight the broad utility of this transformation,
divergent late-stage modications of pharmaceuticals were next
investigated (Scheme 3). Pleasingly, we were able to conduct site-
selective functionalization of complex pyridine-based drug mole-
cules such as vismodegib, bisacodyl, and pyriproxyfen using two-
and three-component protocols. In this manner, the corre-
sponding products (6–11) were successfully generated.
Conflicts of interest
There are no conicts to declare.
Acknowledgements
This research was nancially supported by the Institute for
Basic Science (IBS-R010-A2). We thank Dr Dongwook Kim (IBS)
for XRD analysis.
Notes and references
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S. Repichet, C. L. Roux, P. Hernandez and J. Dubac, J. Org.
Chem., 1999, 64, 6497.
Finally, we set out to explore the utility of the current methods
for further diversication, as demonstrated in Scheme 4 (see the
ESI†). A b-methylsulfonyl pyridine derivative 4ba was readily
transformed into an enamide 12 (51% for 2-steps, Scheme 4a). In
addition, the displacement of a sulfonyl group with alcohol via
SNAr could be achieved using alkoxides to afford 13 (61% yield for
2-steps, Scheme 4b). Phenyl ethyl sulfone 5r is a versatile moiety
that can easily be converted to the corresponding sulnate. For
5 M. Jereb, Green Chem., 2012, 14, 3047.
6 K. M. Maloney, J. T. Kuethe and K. Linn, Org. Lett., 2010, 13,
102.
t
example, 5r could be modied by using BuOK, enabling the
7 For recent reviews, see: (a) D. Kaiser, I. Klose, R. Oost,
J. Neuhaus and N. Maulide, Chem. Rev., 2019, 119, 8701;
(b) J. Aziz, S. Messaoudi, M. Alami and A. Hamze, Org.
Biomol. Chem., 2014, 12, 9743; (c) J. Aziz and A. Hamze,
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V. D. Parshin and A. O. Terent'ev, Adv. Synth. Catal., 2020,
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formation of a sulnate 14 in excellent yield.30 Further trans-
formations using N-chloromorpholine as an electrophile
provided sulfonamide 15 in 85% yield.
Conclusions
In summary, we have developed a divergent system to selectively
enable the sulfonative pyridylation of alkenes and C4-
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