Primary Sulfonamide Functionalization via Sulfonyl Pyrroles: Seeing the N?Ts Bond in a Different Light

Article abstract of DOI:10.1002/chem.202102748

Despite common occurrence in molecules of value, methods for transforming sulfonamides are distinctly lacking. Here we introduce easy-to-access sulfonyl pyrroles as synthetic linchpins for sulfonamide functionalization. The versatility of the sulfonyl pyrrole unit is shown by generating a variety of products through chemical, electrochemical and photochemical pathways. Preliminary results on the direct functionalization of primary sulfonamides are also provided, which may lead to new modes of activation.

Full text of DOI:10.1002/chem.202102748

Accepted Article
Accepted Article
Title: Primary Sulfonamide Functionalization via Sulfonyl Pyrroles:
Seeing the N−Ts Bond in a Different Light
Authors: Tomoya Ozaki, Hideki Yorimitsu, and Gregory J. P. Perry
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Chem. Eur. J. 10.1002/chem.202102748
Link to VoR: https://doi.org/10.1002/chem.202102748
01/2020

10.1002/chem.202102748
Chemistry - A European Journal
COMMUNICATION
Primary Sulfonamide Functionalization via Sulfonyl Pyrroles:
Seeing the N−Ts Bond in a Different Light
Tomoya Ozaki,[a] Hideki Yorimitsu*[a] and Gregory J. P. Perry*[a]
[a]
T. Ozaki, Prof. Dr. H. Yorimitsu, Dr. G. J. P. Perry
Department of Chemistry, Graduate School of Science,
Kyoto University, Sakyo-ku, Kyoto, 606-8502 (Japan)
E-mail: yori@kuchem.kyoto-u.ac.jp; gregory.perry@org.kuchem.kyoto-u.ac.jp
Supporting information for this article is given via a link at the end of the document.
Abstract: Despite common occurrence in molecules of value,
methods for transforming sulfonamides are distinctly lacking. Here we
introduce easy-to-access sulfonyl pyrroles as synthetic linchpins for
sulfonamide functionalization. The versatility of the sulfonyl pyrrole
unit is shown by generating a variety of products through chemical,
electrochemical and photochemical pathways. Preliminary results on
the direct functionalization of primary sulfonamides are also provided,
which may lead to new modes of activation.
Installing a p-toluenesulfonyl (tosyl, Ts) group is a common way
to protect N-containing molecules.[1] Accordingly, various
methods for N−Ts deprotection are known (Scheme 1A, left). [1,2]
During deprotection, the Ts group is lost and the free amine
isolated; however, what becomes of the Ts group? Remarkably,
little consideration has been given to the outcome of the Ts unit
in these reactions, despite the possibility of accessing various
functionalities (Scheme 1A, right).[3]
Primary sulfonamides 1 are readily-available and found in a
variety of important compounds, in particular drug molecules.[4] In
2019, Fier and Maloney reported an elegant, NHC-catalyzed
method for transforming sulfonamide groups into synthetically
versatile sulfinates (Scheme 1B).[5] This represented a gear-
change in sulfonamide chemistry: sulfonamides, previously
considered end-game in drug discovery, were now recognized as
a platform for diversification. This study was aptly followed by
work from the Cornella group who demonstrated the conversion
of primary sulfonamides to sulfonic acids and sulfonyl
chlorides/fluorides (Scheme 1C).[6] These methods proceed via
activation of the sulfonamide 1 at the nitrogen atom, by in situ
conversion to sulfonyl imines i or sulfonyl pyridiniums ii. Despite
these elegant reports, examples of sulfonamide activation are still
rare, especially those suitable for late-stage functionalization of
complex molecules.[7,8]
Following the precedent set by Fier, Maloney, and the Cornella
group, we considered an alternative strategy for transforming
primary sulfonamides. Here we present sulfonyl pyrroles 2 as
reagents for synthesis (Scheme 1D). Sulfonyl pyrroles are highly
versatile and can be used to access various functional groups
(sulfinates, sulfones, sulfonic acids, sulfonamides) via chemical,
electrochemical or photochemical means. This work also acts as
a reminder to never disregard the side products of a reaction as
they may contain useful functionalities when viewed from a
different perspective. In addition, we provide preliminary results
on transforming primary sulfonamides through a direct activation
strategy.
Scheme 1. (A) Current status of the N−Ts unit. (B/C) Transforming primary
sulfonamides via imine-based and pyridinium-based activation. (D) This work:
Transforming primary sulfonamides via pyrrole-based activation.
Encouraged by previous reports on N−Ts deprotection,[1,2] we
recognized sulfonyl pyrroles
2 as possible linchpins for
sulfonamide functionalization. Understandably, these moieties
are generally accessed by reacting pyrroles with p-
toluenesulfonyl chloride (p-TsCl), however, we required an
alternative approach from sulfonamides 1. We have developed
two routes that convert a range of sulfonamides into the
corresponding sulfonyl pyrroles via a Paal-Knorr/Clauson-Kaas-
type reaction (Scheme 2).[9,10,11] These methods allow sulfonyl
pyrrole formation to occur quickly (30 min) at 100 °C, or through
a milder route at 40 °C.
With a range of activated sulfonamides 2 in hand, we began
assessing their potential in synthesis. As our aim was to apply this
chemistry to the late-stage functionalization of drug molecules, we
first considered photocatalyzed methods as they generally occur
under mild conditions with superior functional group compatibility.
Based on previous N−Ts deprotections for obtaining free
amines,[2r,2v] we found that sulfinates (isolated as the
corresponding methyl sulfones 3) were formed in excellent yield
1
This article is protected by copyright. All rights reserved.

10.1002/chem.202102748
Chemistry - A European Journal
COMMUNICATION
Table 1. Optimization of the photocatalyzed functionalization of sulfonyl pyrroles
2.
DIPEA
(X equiv)
HCO2H
(Y equiv)
Scheme 2. Preparation of sulfonyl pyrroles 2 from primary sulfonamides 1.
Entry
Solvent
Yield (%)
1
2
3
8.0
4.0
4.0
8.0
4.0
0.0
MeCN
MeCN
MeCN
96
98
60
under reductive photoredox conditions (Table 1, Entry 1). Further
optimization lowered the equivalents of additives in the reaction
(Entries 2-5).[9] Interestingly, water had a significant effect on
reactivity (Entry 3 vs 4), allowing the desired product 3aa to be
isolated in 95% yield (Entry 4).[12] Importantly, this transformation
can occur in one-pot from the parent sulfonamide 1a to give the
methyl sulfone 3aa in 90% yield (Entry 4). Our sulfonamide
functionalization occurs at lower temperatures compared to the
current state-of-the-art and uses relatively inexpensive and
MeCN/H2O
(6:1)
99
4
4.0
0
(95[a], 90[b]
)
MeCN/H2O
(6:1)
5
3.0
4.0
0
60
57
6[c]
4.0
MeCN
readily-available reagents.[5,6] Studies also indicate that
a
transition metal-free route is possible using the organic
photoredox catalyst 4CzIPN (Entry 6).
Reaction conditions: 2a (0.5 mmol), Ir(III) (0.005 mmol), DIPEA (1.5 – 4.0
mmol), HCO2H (0 – 4.0 mmol), solvent (2.0 mL), blue light irradiation, r.t., 16 h;
then Na2CO3 (4.0 mmol), DMF (1.0 mL), MeI (8.0 mmol), r.t., 2 h. [a] Isolated
yield. [b] Isolated yield for the one-pot process from sulfonamide 1a. [c] 4CzIPN
(0.025 mmol) instead of Ir(III). dtbbpy = 4,4'-di-tert-butyl-2,2'-bipyridine. ppy= [2-
(2-pyridinyl-N)phenyl-C]. DIPEA = N,N-diisopropylethylamine. DMF = N,N-
We then generated a range of sulfinates from the corresponding
sulfonamides 1 via sulfonyl pyrroles 2 (Scheme 3). The process
tolerated a range of electron-rich and electron-withdrawing
functionalities at the ortho, meta and para positions, and the
resulting methyl sulfones were isolated in excellent yields.
Various drug molecules were also compatible including celecoxib
dimethylformamide.
dicyanobenzene.
4CzIPN
=
1,2,3,5-tetrakis(carbazol-9-yl)-4,6-
Scheme 3. Scope of the photocatalyzed functionalization sulfonyl pyrroles 2. Yields are of isolated material. Reaction conditions: 2 (0.5 mmol), Ir(III) (0.005 mmol),
DIPEA (2.0 mmol), MeCN (1.7 mL), H2O (0.3 mL), blue light irradiation, r.t., 16 h; then Na2CO3 (4.0 mmol), DMF (1.0 mL), MeI (8.0 mmol), r.t., 2 h. [a] Isolated yield
for the one-pot process from sulfonamide 1. [b] 0.25 mmol scale. After irradiation: Na2CO3 (0.28 mmol), N-fluorobenzenesulfonimide (NFSI, 0.38 mmol), THF (1.0
mL), H2O (0.1 mL), r.t. 3 h. [c] 0.25 mmol scale. After irradiation: Na2CO3 (0.28 mmol), 2-chloro-5-(trifluoromethyl)pyridine (0.38 mmol), DMA (1.5 mL), 100 °C, 18
h. [d] After irradiation: Na2CO3 (0.6 mmol), NiCl2glyme (0.05 mmol), dtbbpy (0.05 mmol), 4-bromobenzonitrile (1.0 mmol), DMF (5.0 mL), blue light irradiation, r.t.,
24 h.
2
This article is protected by copyright. All rights reserved.

10.1002/chem.202102748
Chemistry - A European Journal
COMMUNICATION
1o, a sulfanilamide derivative 1p, valdecoxcib 1q and a NLRP3
inflammasome inhibitor 1r (3oa-3ra). Sulfonyl pyrroles are stable
and isolable compounds but, alternatively, the one-pot procedure
from the sulfonamide is equally efficient (3aa, 3oa) and, in the
case of 3ra, proceeds on a gram scale. Current limitations include
compounds bearing bromo-/iodo- (3fa, 3ga), nitro- (3ia), and free-
amine substituents.[9] Sulfinates are highly useful reagents,[13] so
this method can lead to other products such as sulfonyl fluorides
(3ob)[14] and, through SNAr[15] or cross-coupling reactions,[16] diaryl
sulfones (3oc, 3ad).
We were keen to further probe the versatility of sulfonyl pyrroles
2 for sulfonamide functonalization (Scheme 4). Hydrolysis is often
applied in N−Ts deprotection, but using this method for sulfonic
acid formation is not common practice.[2e,2f,2s,3a,3c] We were
pleased to find that hydrolysis proceeds to form the sulfonic acid
3ae in excellent yield (Scheme 4, i). Similarly, we demonstrated
that sulfonyl pyrroles can engage in an electrochemical process
for accessing sulfinates, isolated as the methyl sulfone 3aa
(Scheme 4, ii).[2h,2w] Encouraged by these results, we posited that
sulfonyl pyrroles would engage in a range of other transformations.
Accordingly, we have found that reaction with a Grignard reagent
provides the diaryl sulfone 3af (Scheme 4, iii), whilst
transsulfonamidation with morpholine provides sulfonamide 3ag
(Scheme 4, iv).[17] Importantly, these latter reactions (iii/iv) go
beyond procedures for deprotection and challenge current
perceptions of the N−Ts unit as just a protected amine.
Scheme 5. Late-stage diversification of celecoxib 1o via sulfonyl pyrrole 2o.
Yields are of isolated material. Reaction conditions: (i) 2o (0.5 mmol), KOH (1.5
mmol), EtOH (5.0 mL), 35 °C, 16 h. (ii) 2o (0.5 mmol), naphthalene (0.25 mmol),
0.1 M n-Bu4NBr in DMF 8.0 mL, electrolysis at r.t. under a constant current
[Mg(+) | Ni(−)] (current density 5 mA/cm2) until 2.0 F/mol total charge is passed;
then Na2CO3 (4.0 mmol), MeI (8.0 mmol), r.t., 2 h. (iii) 2o (0.25 mmol), PhMgBr
(2.6 M in Et2O, 0.5 mmol), PhMe (2.5 mL), 100 °C, 22 h. (iv) 2o (0.5 mmol),
Morpholine (1.0 mmol), LiHMDS (1.5 mmol), PhMe (2.0 mL), r.t., 30 min. [a]
Isolated as the methyl sulfone 3oa
Having repurposed N−Ts deprotection for accessing several
sulfur-containing functional groups, we then used these methods
in the late-stage diversification of the drug molecule, Celecoxib
sulfonamides 1. Thus, we tested our photoredox method on
simple unactivated sulfonamides 1 and were pleasantly surprised
to find that useful yields of the sulfinate were possible (Scheme
6).[9] A brief study of the scope showed that this reaction currently
presents several challenges: whereas electron rich sulfonamides
performed well (3aa, 3ca) and some drug molecules showed
promising reactivity (3oa, 3qa), problems were encountered when
using electron-deficient substrates (3ha) and other complex
molecules (3ra). Studies to understand the mechanism and
develop a more efficient process are ongoing in our laboratory.[12]
Nevertheless, these initial results will be of interest to those
investigating the activation of sulfonamides and related nitrogen-
containing molecules, for example amines and amides.[18]
(Scheme 5). Taken together, schemes
3 and 4 provide
opportunities for transforming sulfonamides using photo- and
electrochemical methods. Sulfonyl pyrroles are adaptable
reagents that can engage with electrophiles or nucleophiles; for
example, diaryl sulfones were accessed through reaction with aryl
halides (Scheme 3, 3oc, 3ad) or organometallics (Scheme 5, 3of).
This flexibility will prove useful when planning the synthesis of
target molecules.
Our method for sulfonamide activation via sulfonyl pyrroles 2
complements previous strategies via sulfonyl imines i and sulfonyl
pyridiniums ii (Scheme 1).[5,6] We realized that an ideal route for
sulfonamide functionalization would involve direct activation of
Scheme 4. Beyond N−Ts deprotection: diversification of sulfonyl pyrroles.
Yields are of isolated material. Reaction conditions: (i) 2a (0.5 mmol), KOH (1.5
mmol), EtOH (5.0 mL), 35 °C, 16 h. (ii) 2a (0.5 mmol), naphthalene (0.25 mmol),
0.1 M n-Bu4NBr in DMF 8.0 mL, electrolysis at r.t. under a constant current
[Mg(+) | Ni(−)] (current density 5 mA/cm2) until 2.0 F/mol total charge is passed;
then Na2CO3 (4.0 mmol), MeI (8.0 mmol), r.t., 2 h. (iii) 2a (0.5 mmol), PhMgBr
(2.6 M in Et2O, 2.0 mmol), PhMe (5.0 mL), 100 °C, 4 h. (iv) 2a (0.5 mmol),
morpholine (1.0 mmol), LiHMDS (1.5 mmol), PhMe (2.0 mL), r.t., 30 min.
[a] NMR yield. [b] Isolated as the methyl sulfone 3aa
Scheme 6. Scope of the photocatalyzed direct functionalization of sulfonamides
1. Yields are of isolated material. Reaction conditions: 1 (0.5 mmol), Ir(III) (0.005
mmol), DIPEA (2.0 mmol), MeCN (1.7 mL), H2O (0.3 mL), blue light irradiation,
r.t., 16 h; then Na2CO3 (4.0 mmol), DMF (1.0 mL), MeI (8.0 mmol), r.t., 2 h. [a]
NMR yield.
3
This article is protected by copyright. All rights reserved.

10.1002/chem.202102748
Chemistry - A European Journal
COMMUNICATION
Huang, L. Guo, W. Xia, Green Chem. 2021, 23, 2095–2103. x) Q. Wang,
X. Zhang, P. Wang, X. Gao, H. Zhang, A. Lei, Chin. J. Chem. 2021, 39,
143–148.
Stemming from a re-evaluation of N−Ts deprotection, we have
introduced sulfonyl pyrroles as synthetic linchpins for primary
sulfonamide functionalization and the late-stage diversification of
drug molecules. We have demonstrated the versatility of these
reagents through several routes, including photochemical and
electrochemical reduction to sulfinates, and the preparation of
sulfonic acids, sulfones and sulfonamides. These represent early
findings on the chemistry of sulfonyl pyrroles and we hope they
encourage further studies of these unique reagents. In addition,
we have demonstrated a direct mode of sulfonamide activation
that may lead to ideal ways for transforming N-containing
molecules.
[3]
For example, the reports listed in reference 2 do not investigate the Ts
side product. There are scant examples of the N-sulfonyl bond as a site
for functionalization. a) B. Raju, C. Wu, A. Kois, E. Verner, I. Okun, F.
Stravos, M. F. Chan, Bioorg. Med. Chem. Lett. 1996, 6, 2651–2656. b)
D. J. Jeon, D. W. Yu, H. R. Kim, E. K. Ryu, Heterocycles 1998, 48, 155–
159. c) N. Murugesan, Z. Gu, P. D. Stein, S. Bisaha, S. Spergel, R.
Girotra, V. G. Lee, J. Lloyd, R. N. Misra, J. Schmidt, A. Mathur, L. Stratton,
Y. F. Kelly, E. Bird, T. Waldron, E. C.-K. Liu, R. Zhang, H. Lee, R.
Serafino, B. Abboa-Offei, P. Mathers, M. Giancarli, A. A. Seymour, M. L.
Webb, S. Moreland, J. C. Barrish, J. T. Hunt, J. Med. Chem. 1998, 41,
5198–5218. d) N. J. Findlay, S. R. Park, F. Schoenebeck, E. Cahard, S.
Zhou, L. E. A. Berlouis, M. D. Spicer, T. Tuttle, J. A. Murphy, J. Am. Chem.
Soc. 2010, 132, 15462–15464.
[4]
[5]
[6]
[7]
a) K. A. Scott, J. T. Njardarson, Top. Curr. Chem. 2018, 376, 1–34. b)
The First Miracle Drugs: How the Sulfa Drugs Transformed Medicine
(Ed.: J. E. Lesch), Oxford University Press, Oxford, 2006.
Acknowledgements
This work was supported by JSPS KAKENHI Grant Numbers
JP19H00895 and JP21F21039 and by JST CREST Grant
Number JPMJCR19R4, Japan. H.Y. thanks The Asahi Glass
Foundation for financial support. G.J.P.P. is the recipient of a
JSPS Postdoctoral Fellowship for Research in Japan. G.J.P.P
thanks Professor David J. Procter, all the Procter group and Dr.
Marco Simonetti for much support and many helpful discussions.
a) P. S. Fier, K. M. Maloney, J. Am. Chem. Soc. 2019, 141, 1441–1445.
b) P. S. Fier, S. Kim, K. M. Maloney, J. Am. Chem. Soc. 2019, 141,
18416–18420.
a) A. Gómez‐Palomino, J. Cornella, Angew. Chem. Int. Ed. 2019, 58,
18235–18239; Angew. Chem. 2019, 131, 18403–18407. b) M. Pérez‐
Palau, J. Cornella, Eur. J. Org. Chem. 2020, 2020, 2497–2500.
a) R. R. Milburn, V. Snieckus, Angew. Chem. Int. Ed. 2004, 43, 888–891;
Angew. Chem. 2004, 116, 906–909. b) L. Chen, H. Lang, L. Fang, J. Yu,
L. Wang, Eur. J. Org. Chem. 2014, 2014, 6385–6389. c) J. Chen, K.
Zhang, Y. Zhao, S. Pu, Synth. Commun. 2018, 48, 1316–1323. d) J.
Chen, J. Wang, X. Chen, Y. Huang, S. Pu, Synth. Commun. 2019, 49,
836–843. e) G. Meng, T. Guo, T. Ma, J. Zhang, Y. Shen, K. B. Sharpless,
J. Dong, Nature 2019, 574, 86–89.
Keywords: sulfonamide • photoredox • electrochemistry • late-
stage functionalization • deprotection
[1]
a) P. G. M. Wuts in Greene`s Protective Groups in Organic Synthesis,
5th Edition, John Wiley & Sons, New Jersey, 2014, pp. 895-1193. b) P. J.
Kocienski in Protecting Groups, 3rd Edition, Thieme, Stuttgart, 2005, pp.
542-548.
[8]
[9]
Whilst this manuscript was in preparation, a related study was reported.
This procedure required multiple steps and isolation events to activate
the sulfonamide. Y. Luo, H. Ding, J.-S. Zhen, X. Du, X.-H. Xu, H. Yuan,
Y.-H. Li, W.-Y. Qi, B.-Z. Liu, S.-M. Lu, C. Xue, Q. Ding, Chem. Sci. 2021,
12, 9556–9560.
[2]
For N−Ts deprotection of pyrroles and related compounds, see: a) B.
Nyasse, L. Grehn, U. Ragnarsson, Chem. Commun. 1997, 1017–1018.
b) I. Fleming, J. Frackenpohl, H. Ila, J. Chem. Soc. Perkin Trans. 1 1998,
1229–1236. c) G. Sabitha, S. Abraham, B. V. Subba Reddy, J. S. Yadav,
Synlett 1999, 1999, 1745–1746. d) C. M. Haskins, D. W. Knight,
Tetrahedron Lett. 2004, 45, 599–601. e) J. S. Bajwa, G.-P. Chen, K.
Prasad, O. Repič, T. J. Blacklock, Tetrahedron Lett. 2006, 47, 6425–
6427. f) Y. Liu, L. Shen, M. Prashad, J. Tibbatts, O. Repič, T. J. Blacklock,
Org. Process Res. Dev. 2008, 12, 778–780. g) S. P. Patel, D. H. Nadkarni,
S. Murugesan, J. R. King, S. E. Velu, Synlett 2008, 2008, 2864–2868. h)
H. Senboku, K. Nakahara, T. Fukuhara, S. Hara, Tetrahedron Lett. 2010,
51, 435–438. i) S. W. Youn, J. H. Bihn, B. S. Kim, Org. Lett. 2011, 13,
3738–3741. j) S. Yoshida, K. Igawa, K. Tomooka, J. Am. Chem. Soc.
2012, 134, 19358–19361. k) H. S. Farwaha, G. Bucher, J. A. Murphy,
Org. Biomol. Chem. 2013, 11, 8073–8081. l) S. O’Sullivan, E. Doni, T.
Tuttle, J. A. Murphy, Angew. Chem. Int. Ed. 2014, 53, 474–478; Angew.
Chem. 2014, 126, 484–488. m) E. Hasegawa, N. Izumiya, T. Fukuda, K.
Nemoto, H. Iwamoto, S. Takizawa, S. Murata, Tetrahedron 2016, 72,
7805–7812. n) E. Hasegawa, N. Izumiya, T. Miura, T. Ikoma, H. Iwamoto,
S. Takizawa, S. Murata, J. Org. Chem. 2018, 83, 3921–3927. o) P. W.
Antoni, M. M. Hansmann, J. Am. Chem. Soc. 2018, 140, 14823–14835.
p) L. Zhang, L. Jiao, Chem. Sci. 2018, 9, 2711–2722. q) E. Hasegawa,
Y. Nagakura, N. Izumiya, K. Matsumoto, T. Tanaka, T. Miura, T. Ikoma,
H. Iwamoto, K. Wakamatsu, J. Org. Chem. 2018, 83, 10813–10825. r)
Qiang‐Liu, Y.-X. Liu, H.-J. Song, Q.-M. Wang, Adv. Synth. Catal. 2020,
362, 3110–3115. s) W. Sun, X. Chen, Y. Hu, H. Geng, Y. Jiang, Y. Zhou,
W. Zhu, M. Hu, H. Hu, X. Wang, X. Wang, S. Zhang, Y. Hu, Tetrahedron
Lett. 2020, 61, 152442. t) E. Hasegawa, T. Tanaka, N. Izumiya, T. Kiuchi,
Y. Ooe, H. Iwamoto, S. Takizawa, S. Murata, J. Org. Chem. 2020, 85,
4344–4353. u) M. D. Heredia, W. D. Guerra, S. M. Barolo, S. J. Fornasier,
R. A. Rossi, M. E. Budén, J. Org. Chem. 2020, 85, 13481–13494. v) I. A.
MacKenzie, L. Wang, N. P. R. Onuska, O. F. Williams, K. Begam, A. M.
Moran, B. D. Dunietz, D. A. Nicewicz, Nature 2020, 580, 76–80. w) B.
For further details, see the supporting information.
[10] Z. Wang, Compr. Org. Name React. Reagents 2010, 665–668.
[11] M. Abid, L. Teixeira, B. Török, Tetrahedron Lett. 2007, 48, 4047–4050.
[12] A mechanistic discussion is provided in the supporting information.
[13] a) P. J. Sarver, N. B. Bissonnette, D. W. C. MacMillan, J. Am. Chem. Soc.
2021, 143, 9737–9743. b) D. Kaiser, I. Klose, R. Oost, J. Neuhaus, N.
Maulide, Chem. Rev. 2019, 119, 8701–8780. c) A. S. Deeming, E. J.
Emmett, C. S. Richards-Taylor, M. C. Willis, Synthesis 2014, 46, 2701–
2710.
[14] A. T. Davies, J. M. Curto, S. W. Bagley, M. C. Willis, Chem. Sci. 2017, 8,
1233–1237.
[15] K. M. Maloney, J. T. Kuethe, K. Linn, Org. Lett. 2011, 13, 102–105.
[16] a) H. Yue, C. Zhu, M. Rueping, Angew. Chem. Int. Ed. 2018, 57, 1371–
1375; Angew. Chem. 2018, 130, 1385–1389. b) M. J. Cabrera-Afonso,
Z.-P. Lu, C. B. Kelly, S. B. Lang, R. Dykstra, O. Gutierrez, G. A. Molander,
Chem. Sci. 2018, 9, 3186–3191.
[17] G. Li, M. Szostak, Nat. Commun. 2018, 9, 4165.
[18] a) Y. Pang, D. Moser, J. Cornella, Synthesis 2020, 52, 489–503. b) G. Li,
S. Ma, M. Szostak, Trends Chem. 2020, 2, 914–928.
4
This article is protected by copyright. All rights reserved.

10.1002/chem.202102748
Chemistry - A European Journal
COMMUNICATION
Entry for the Table of Contents
Sulfonamides are prevalent in drug molecules, however, methods for functionalizing sulfonamides via S−N bond cleavage are
scarce. Based on a re-evaluation of N−Ts deprotection, we developed sulfonyl pyrroles as linchpins for sulfonamide functionalization.
Sulfonyl pyrroles engage in various transformations that can proceed through chemical, electrochemical or photochemical pathways.
Twitter usernames: @yorimitsu_lab, @PerryChem
5
This article is protected by copyright. All rights reserved.