Catalytic sp3–sp3Functionalisation of Sulfonamides: Late-Stage Modification of Drug-Like Molecules

Article abstract of DOI:10.1002/chem.201605464

A new application of Pd-catalysed allylation is reported that enables the synthesis of a range of branched sp³-functionalised sulfonamides, a compound class for which few reported methods exist. By reacting benzyl sulfonamides with allylic acetates in the presence of Pd⁰catalysts and base at room temperature, direct allylation was efficiently performed, yielding products that are analogues of structural motifs seen in biologically active small molecules. The reaction was performed under mild conditions and could be applied to nanomolar sigma-receptor binders, thus enabling a late-stage functionalisation and efficient expansion of drug-like chemical space.

Full text of DOI:10.1002/chem.201605464

A Journal of
Accepted Article
Title: Catalytic sp3-sp3 functionalisation of sulfonamides: late-stage
modification of drug-like molecules
Authors: Joseph B. Sweeney, Othman Abdulla, Adam Clayton, Robert
Faulkner, Duncan Gill, Craig Rice, and Scarlett Walton
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
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To be cited as: Chem. Eur. J. 10.1002/chem.201605464
Link to VoR: http://dx.doi.org/10.1002/chem.201605464
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10.1002/chem.201605464
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COMMUNICATION
Catalytic sp3-sp3 functionalisation of sulfonamides: late-stage
modification of drug-like molecules**
Othman Abdulla, Adam D. Clayton, Robert A. Faulkner, Duncan M. Gill, Craig R. Rice, Scarlett M. Walton, and
Joseph B. Sweeney*
Abstract: A new application of Pd-catalysed allylation is reported
which enables the synthesis of
range of branched sp3-
substituted benzylsulfonamides as products. Furthermore, to date
there have been few disclosures of methods to enable catalytic sp3-
sp3 coupling to allow α-functionalisation of sulfonamides: [12] we
report herein the first application of catalytic sulfonamide
allylation, which can be applied to both simple substrates and also
to drug-like receptor ligands.
a
functionalised sulfonamides, a compound class for which few
reported methods exist. By reacting benzyl sulfonamides with
allylic acetates in the presence of Pd(0) catalysts and base at room
temperature, direct allylation can be efficiently carried out,
yielding products which are analogues of structural motifs seen in
biologically active small molecules. The reaction is carried out
under mild conditions and can be applied to nanomolar sigma-
receptor binders, thus enabling a late-stage functionalisation and
efficient expansion of drug-like chemical space.
a. Benzylsulfonamides: marketed drugs and useful probes
R1R2N
1
1a Sumatriptan R , R2 = Me; R3 = H, R4 = Me
1
1b Almotriptan R , R2 = Me; R3R4 = –(CH2)4–
O
O
1
1c Avitriptan R , R2
=
; R3R4 = –(CH2)4–
N
N
S
NR3R4
N
H
MeO
N
The difficulties in accessing non-planar ‘hard-to-make’ chemical
matter for incorporation into drug molecules have been well-
enumerated,[1] and in some therapeutic areas these difficulties have
significant consequences. Thus there has been a drive to deliver
novel small molecules with enhanced biological relevance, and a
concomitant call for late-stage functionalisation[ 2 ] to enable
Selective sigma-receptor binders
R1
O
O
2a R1 = I, R2 = H; Kiσ1 = 1.8 nm σ1/σ2 = 65
2b R1 = R2 = H; Kiσ1 = 11.2 nm, σ1/σ2 = 4.3
2c R1 = H, R2 = Br; Kiσ1 = 13.4 nm, σ1/σ2 = 21.5
2d R1 = Me, R2 = H; Kiσ1 = 15.0 nm, σ1/σ2 = 10.1
S
R2
N
N
3
]
improvements (such as the ‘magic methyl’ effect[
) in
b. α-Branched sulfonamides: traditional alkylation method
LG
O
O
O
O
pharmacological properties. Within the traditional chemical space
of drug-like molecules, the sulfonamide motif is a frequently seen
subunit of synthetic biologically-active molecules. The motif is a
robust, pharmacologically-reliable unit which appears in both drug
substances (1a-c, Figure 1a) and drug-like molecules (such as
nanomolar receptor ligands 2a-d, Figure 1b).[4] α-Substitution with
alkyl groups can improve the binding properties,[ 5 ] however,
despite the wide interest in the exploitation of sulfonamides, many
of the compounds reported bear sparse substitution patterns
adjacent to the sulfonyl moiety. Bearing this fact in mind, and in
the context of the drive for late-stage molecular functionalisation,
there has been a recent interest in the development of new methods
for direct α-functionalisation of sulfonamides. However, despite
the considerable effort directed towards de novo synthesis of
sulfonamides,[6] there are still few generally applicable methods for
the efficient preparation of α-branched sulfonamides.
Traditional methods (Figure 1c) for direct alkylations of
sulfonamides[7] require strong bases, reactive electrophiles, low
temperatures and the use of stoichiometric amounts of polar
additives (such as TMEDA,[8] HMPA,[9] phenanthroline,[5]); several
recent reports have described metal-catalyzed α-arylation of
alkyl[10] sulfonamides (Figure 1c),[11] but only the methods from
Zhou et al[11d] (who reported a single example of branched
sulfonamide synthesis) and Knauber and Tucker[11a] deliver α-sp3-
S
R3
S
R3
• strong base
R1
R1
N
N
• reactive electrophiles
• low temperature
• stoichiometric additives
R2
R2
c. Catalytic branched sulfonamide synthesis: sp3-sp2 coupling
Knauber and Tucker11a
Ar–Br
Pd(dba)2 (10 mol%)
X-Phos (10 mol%)
O
O
O
O
Me
S
R3
Me
S
R3
12 – 93% yield
N
N
TMP–ZnCl•LiCl (2.5 eq.)
THF, µW, 130 ˚C
R2
Ar
R2
Zhou et al.11d
Ph–Br
Pd(OAc)2 (1.2 mol%)
X-Phos (2 mol%)
O
O
O
O
Et
S
Et
S
66% yield
N
N
LHMDS (1 eq.)
ZnCl2 (1.2 eq.), 70 ˚C, 24 h
Ph
Northrup et al.10
Ar–Br
Pd(OAc)2 (5 mol%)
O
O
O
O
R(O)C
S
R3
R(O)C
S
R3
7 – 85% yield
N
N
tBu3PH•BF4 (15 mol%)
NaOtBu (3.0 eq.)
Dioxane, 90 ˚C
R2
Ar
R2
d. This work: Direct catalytic sp3-sp3 functionalisation of sulfonamides
O
O
O
O
Pd(0), base
OAc
• mild conditions
• room temperature
• regioselective
S
S
N
R
N
R
Ar
XR
Ar
XR
Figure 1. Bioactive benzylsulfonamides: properties and synthetic access.
[*]
O. Abdulla, A. D. Clayton, R. A. Faulkner, Dr. D. M. Gill, Prof. C. R.
Rice, S. M. Walton, Prof. J. B. Sweeney
Department of Chemical Sciences, University of Huddersfield,
Queensgate, Huddersfield, HD1 3DH (UK)
E-mail: j.b.sweeney@hud.ac.uk
We hypothesized that anions derived from benzyl sulfonamides
would be amenable to palladium-catalyzed allylation (Figure 1d);
however, there are relatively few reports of the use of nucleophiles
other than carbonyl-stabilised carbanions in such reactions,[13 and
]
Homepage:
fewer examples of the use of non-carbonyl α-branched anions.[13b]
In addition, the pKa of sulfonamide-derived anions is not
definitively established: direct deprotonation even of benzyl
sulfonamides often requires strong base,[6] suggesting that the
anions thus obtained might be considered to be ‘hard’, and
https://www.hud.ac.uk/ourstaff/profile/index.php?staffid=957
We are grateful to the University of Huddersfield (R. A. F. and S. M.
W.) for studentships and the Royal Society for an Industry
Fellowship (J.B.S.).
Supporting information for this article is given via a link at the end of
the document.
[**]
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10.1002/chem.201605464
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COMMUNICATION
therefore likely to lead to products of inversion upon reaction with
excellent exemplar of the reaction scope, this product also
enabled confirmation of the stereochemical course of the
allylation process (vide infra, Scheme 3).
[15]
π-allylpalladium species.[14],
Thus, in addition to being an
unknown process when we commenced our study, there was a
mechanistic question to be answered about the proposed reaction.
We commenced our study with an examination of the reaction of
dimethylsulfonamide 4a with allyl acetate 5a under Pd-catalysed
allylation conditions. Given that the transformation was previously
unreported, we were gratified to observe that the reaction gave the
desired sp3-functionalised allylated product 6a, in moderate yield
(Table 1, entry 1); after an extensive catalyst and solvent screen
(key experiments delineated in Table 1) we alighted upon the use
of [Pd(C3H5)Cl]2 and dppb ligand in DME solvent (Table 1, entries
9 and 10) as the most appropriate combination (featuring readily
available catalyst and ligand, and low-boiling solvent, thereby
facilitating work-up and product processing). The use of other
bases (including NaOtBu, LHMDS, BTPP, and powdered NaOH)
was not uniformly productive.
[Pd(C3H5)Cl]2 (2.5 mol%)
dppb (11 mol%)
O
S
O
O
S
O
+
R
NMe2
R
OAc
NMe2
NaH, DME, 25 ˚C
Ph
Ph
5a – 5l
6a – 6l
O
S
O
O
O
O
O
S
S
NMe2
NMe2
NMe2
Ph
Ph
Ph
6a, 79 %a
6c, 94 % b , c
6b, 96 %
O
S
O
O
O
O
O
S
S
NMe2
NMe2
Ph
NMe2
catalyst
(2.5 mol%)
Ph
Ph
Ph
6e, 79 %c
O
O
O
S
O
6f, 83 %c
S
6d, 86 %
+
R
OAc
R
NMe2
NMe2
solvent
dppb (11 mol%)
NaH, 25 ˚C
Ph
Ph
Ph
O
O
H
4a
5a R = H
5b R = (E)–nC3H7
6a R = H
6b R = (E)–nC3H7
H
Ph
Ph
S
Ph
NMe2
H
H
SO2NMe2
SO2NMe2
6i, 79 %
dr = 50:50
Ph
Entry
Acetate
Catalyst
Solvent
THF
Yield/%a
54
40
48
12
55
30
27
11
79
96
21
30
43
90
0
6g, 87 %
dr 70: 30
6h, 74 %
dr 60 : 40
5a
1
2
3
[Pd(C3H5)Cl]2
[Pd(C3H5)Cl]2
[Pd(C3H5)Cl]2
[Pd(C3H5)Cl]2
[Pd(C3H5)Cl]2
[Pd(C3H5)Cl]2
[Pd(C3H5)Cl]2
[Pd(C3H5)Cl]2
[Pd(C3H5)Cl]2
[Pd(C3H5)Cl]2
Pd(OAc)2
5a
5a
5a
5a
5a
5a
5a
5a
5b
5b
5b
5b
5b
5b
Dioxane
DMF
O
O
H
S
Ph
SO2NMe2
NMe2
O
O
H
4
5
EtOAc
NMP
Ph
TBSO
S
NMe2
6l, 85 %
cis:trans = 100:0
Ph
6k, 84 %d
dr 75 : 25e
6
MeCN
CH2Cl2
PhH
6j, 82 %
7
Table 2. Substrate scope in allyl component for the catalytic sulfonamide
allylation reaction. Conditions: sulfonamide (0.5 mmol), acetate (0.55 mmol),
catalyst (0.0125 mmol), ligand (0.055), NaH (3 mmol), DME (1 mL), 48h. a)
obtained as a 67:33 E:Z mixture. b) Yields are quoted for isolated compounds.
c) dppe used as ligand. d) dppf used as ligand. e) dr refers to relative
configuration at exocyclic stereogenic centre
8
9
DME
DME
DME
DME
DME
DME
DME
10
11
12
13
14
15
In all cases where isomerism was possible, linear products
was exclusively favoured over branched isomers (giving
compounds 6m-o, Scheme 1)
Pd2(dba)3
Pd(PPh3)4
R
PdCl2(MeCN)2
OAc
O
O
[Pd(C3H5)Cl]2 (2.5 mol%)
6m R = Me, 62% yield
6n R = Ph, 57% yielda
6o R = Me2, 39% yield
O
S
O
-
S
Ph
R
NMe2
Table 1. Catalyst and solvent screen for sp3-sp3-sulfonamide coupling.
Conditions: sulfonamide (0.5 mmol), acetate (0.55 mmol), catalyst (0.0125
mmol), ligand (0.055 mmol), NaH (3 mmol), DME (1 mL), 48h. a) Yields are
quoted for isolated products.
NMe2
dppb (11 mol%)
NaH, DME, 25 ˚C
Ph
Scheme 1. Linear isomers are preferred over branched. Conditions: sulfonamide
(0.5 mmol), acetate (0.55 mmol), catalyst (0.0125 mmol), ligand (0.055 mmol),
NaH (4 mmol), DME (1 mL), 48h. a) dppf used as ligand.
Armed with these initial data, we proceeded next to probe the
scope of the reaction with regard to the allyl component
(Table 2), using a range of commercial or easily prepared
substrates. It quickly transpired that the catalytic allylation
reaction proceeded in generally good yield under mild
conditions, using a diverse range of allyl donors, to give α-
substituted sulfonamides 6a-6l. Both acyclic and cyclic
acetates delivered the corresponding C-allylated sulfonamides
efficiently, and where present alkene stereochemistry was
generally retained (for compounds 6b, 6e-f, and 6k).
Exclusive cis-stereoselectivity was observed in the synthesis
of cyclohexenyl sulfonamide 6l; in addition to providing an
Since the allylated products still bear an acidic α-proton, the
possibility exists for a second functionalization. Thus, when
reacted with excess allyl acetate, sulfonamide 4a was directly
converted to the doubly-allylated product 7 (93% yield),
which could converted by ring-closing metathesis[16] in high
yield into the previously unreported [17] tertiary sulfonamide 8
(Scheme 2).
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[Pd(C3H5)Cl]2 (2.5 mol%)
dppb (11 mol%)
The mildness of the method is emphasised by the fact that,
where present, halogeno substituents are tolerated, allowing
for subsequent synthetic development.
O
S
O
Ph
SO2NMe2
+
OAc
2 eq.
NMe2
NaH, DME, 25 ˚C, 48h
96% yield
Ph
7
R1
R1
O
O
O
O
R
OAc
Ph
S
R2
S
R2
N
R
N
[Pd(C3H5)Cl]2 (2.5 mol%)
dppb (11 mol%)
N
Ph
N
Ph
SO2NMe2
Grubbs G2 (5 mol %)
NaH, DME, 25 ˚C, 48h
10a-h
CH2Cl2, 25 ˚C, 16 h.
93% yield
2a R1 = I, R2 = H; 2b R1 = R2 = H; 2c R1 = H, R2 = Br; 2d R1 = Me, R2 = H;
2e R1 = F, R2 = H; 2f R1 = Cl, R2 = H; 2g R1 = H, R2 = OMe;
8
Scheme 2. Access to novel tertiary sulfonamides via catalytic double allylation.
Conditions: 1. sulfonamide (0.5 mmol), acetate (2.5 mmol), catalyst (0.0125
mmol), ligand (0.055 mmol), NaH (4 mmol), DME (1 mL), 48h; 2. sulfonamide
(0.36 mmol) Grubbs G2 (0.018 mmol), CH2Cl2 (6 mL,) 25 ˚C, 16h.
F
O
S
O
O
O
S
N
N
Ph
N
Ph
N
Having conclusively demonstrated the feasibility of the
sulfonamide allylation reaction, our attention turned to an
examination of the structural scope possible in the nitrogen
subunit: again we observed generally efficient reaction of
sulfonamides 4b-g under the catalytic allylation conditions,
leading to novel sulfonamides 9a-9l (Table 2).
10a, 76 %a
10b, 67 %
Ph
Cl
Cl
O
O
O
O
S
S
N
Ph
N
Ph
N
Ph
N
10c and 10d, 62 %
(linear: branched = 60:40)
[Pd(C3H5)Cl]2 (2.5 mol%)
dppb (11 mol%)
O
S
O
O
S
O
O
O
S
O O
S
Br
Ph
+
R
OAc
NR2
4b – g
R
NR2
N
N
NaH, DME, 25 ˚C, 48h
9a – 9l
Ph
Ph
N
Ph
N
4b NR2 = Boc-piperazinyl; 4c NR2 = morpholinyl; 4d NR2 = piperidinyl; 4e NR2 = pyrrolidinyl
4f NR2 = N(Me)OMe; 4g NR2 = tetrahydropyridinyl
10e, 58 %
10f, 63 %
Me
O
O
O
O
O
S
O
S
N
O
S
O
S
OMe
O
S
O
N
N
N
NBoc
Ph
N
Ph
N
N
Ph
NBoc
Ph
Ph
NBoc
10g 37 %
10h, 53 %
9a, 71 %a
9b, 52 %
9c, 52 %a
Table 3. Late-stage functionalisation of sigma-receptor binding sulfonamides.
Conditions: sulfonamide (0.5 mmol), acetate (0.55 mmol), catalyst (0.0125
mmol), ligand (0.055 mmol), NaH (4 mmol), DME (1 mL), 48h. a) Yields are
quoted for isolated products.
O
S
O
O
S
O
O
O
S
N
N
N
Ph
NBoc
Ph
NBoc
Ph
O
9d, 59 %
9e, 52 %b
9f, 98 %c
The mechanism of Pd-catalysed allylation reactions is well-
predicated to occur by one of two pathways, depending on the
polarisation of the nucleophile component.[10] When the
allylation reaction was carried out with cis-cyclohexenyl
acetate 11,[18] the cis-products 6l were obtained exclusively
(as confirmed by x-ray analysis of a single crystal of a p-
bromobenzoyl derivative, 12, of the major product, Scheme
3). Since obtention of cis-configured products indicates direct
attack at carbon rather than palladium, this confirms that the
anions derived from benzylsulfonamides can be considered to
be ‘soft’ reagents, at least in the context of palladium
catalysis.
O
O
O
O
S
O
O
N
S
S
N
N
Ph
O
Ph
O
Ph
9g, 79 %
dr
9h, 45 %
9i, 77 %
O
O
O
O
O
O
S
S
S
O
N
N
N
Ph
Ph
Ph
9j, 61 %
9k, 59 %
9l, 82 %
[Pd(C3H5)Cl]2 (2.5 mol%)
OAc
O
1. LiAlH4, THF, 0 ˚C
dppb (11 mol%)
Table 2. Substrate scope in amide component for the catalytic allylation
reaction. sulfonamide (0.5 mmol), acetate (0.55 mmol), catalyst (0.0125 mmol),
ligand (0.055 mmol), NaH (4 mmol), DME (1 mL), 48h. a) Yields are quoted
for isolated products..
O
2. TBS–Cl, imidazole, DMF, rt
3. Ac2O, pyridine, CH2Cl2, 0 ˚C
NaH, DME, 25 ˚C
85 % yield
TBSO
(±)–11
To probe the suitability of the reaction as a late-stage
functionalisation tool, we next examined nanomolar receptor
ligands as substrates. Thus, sigma-receptor binding
sulfonamides 2a-g reacted smoothly under the reaction
conditions, to give novel α-functionalised products 10a-h
(Table 3). It is noteworthy that reaction with cinnamyl acetate
gave both linear and branched products (10c and 10d,
respectively, 60:40 ratio), whereas reactions with hexenyl and
crotyl acetates gave only linear products 10e, 10f and 10g.
H
H
H
TBSO
H
Ph
Ph
+
H
H
SO2NMe2
TBSO
SO2NMe2
75 : 25
12
Scheme 3. Stereochemical course of the catalytic allylation reaction.
Conditions: sulfonamide (1 mmol), acetate (1.1 mmol), catalyst (0.0125 mmol),
ligand (0.055), NaH (4 mmol), DME (1 mL), 48h.
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10.1002/chem.201605464
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COMMUNICATION
The use of asymmetric protocols[19] (likely to be challenging
given the inherent difficulties of asymmetric α-
functionalisation of S=O bonds[20], [21]) in this process have, to
date, proved non-productive, delivering allylated products in
variable yields and with no discernable enantioselectivity.
This matter is currently the focus of intense interest in our
laboratories.
2003, 1503-1505; c) S. Kosiński, K. Wojciechowski, Eur. J.
Org. Chem. 2000, 1263-1270; d) M. Mladenova, Synth. Comm.
1986, 16, 1089-1098.
8. See, for instance: D. Enders, C. R. Thomas, N. Vignola, G.
Raabe Helv. Chim. Acta 2002, 85, 3657-3677.
9. J. Goliński, A. Jonćzyk, M. Makosza, Synthesis 1979, 461.
10. Pd-catalysed
arylation
of
2-alkoxymethyl
and
2-
In summary, we have developed a new application of Pd-
catalysed allylation for direct sp3- sp3 coupling of
sulfonamides, and demonstrated that the reaction is applicable
to late-stage functionalisation of bioactive small molecules.
The transformation takes place at ambient temperature, is
tolerant to a wide range of functional groups and provides
ready access to novel compounds in good yields. We believe
that this method will be of utility to a range of academic and
industrial chemists.
amidoylsulfonamides: J. B. Grimm, M. H. Katcher, D. J.
Witter, A. B. Northrup, J. Org. Chem. 2007, 72, 8135–8138.
11. a) Τ. Knauber, J. Tucker, J. Org. Chem. 2016, 81, 5636-5648;
b) B. Zheng, M. Li, G. Gao, Y. He, P. J. Walsh, Adv. Synth.
Catal. 2016, 358, 2156 – 2162; c) O. René, B. P. Fauber, S.
Malhotra, H. Yajima, Org. Lett. 2014, 16, 3468–3471; d) G.
Zhou, P. Ting, R. Aslanian, J. J. Piwinski, Org. Lett. 2008, 10,
2517–2520; e) J. G. Zeevaart, C. J. Parkinson, C. B. de Koning,
Tetrahedron Lett. 2005, 46, 1597–1599.
12. J. Choi, P. Martin-Gago, G. C. Fu, J. Am. Chem. Soc. 2014,
136, 12161–12165.
Keywords: • Late-stage functionalisation • sulfonamide • sigma
receptor • catalytic • palladium
13. For recent examples, see: a) Y.-X. Li, Q.-Q. Xuan, L. Liu, D.
Wang, Y.-J. Chen, C.-J. Li, J. Am. Chem. Soc. 2013, 135,
12536-12539; b) S.-C. Sha, J. Zhang, P. J. Carroll, P. J. Walsh,
J. Am. Chem. Soc. 2013, 135, 17602-17609; c) B. M. Trost, D.
A. Thaisrivongs, J. Am. Chem. Soc. 2008, 130, 14092–14093.
14.B. M. Trost, T. R. Verhoeven, J. Org. Chem. 1976, 41, 3215; H.
Matsushita, E. J. Negishi, Chem. Soc., Chem. Comm. 1982, 160.
15. For recent discussion of the mechanistic factors involved in Pd-
catalysed allylation, see: a) J. A. Keith, D. C. Behenna, N.
Sherden, J. T. Mohr, S. Ma, S. C. Marinescu, R. J. Nielsen, J.
Oxgaard, B. M. Stoltz, W. A. Goddard III, J Am Chem Soc.
2012, 134, 19050–19060; b) L. A. Evans, N. Fey, J. N. Harvey,
D. Hose, G. C. Lloyd-Jones, P. Murray, A. G. Orpen, R.
Osborne, G. J. J. Owen-Smith, M. Purdie, J. Am. Chem. Soc.
2008, 130, 14471–14473.
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This article is protected by copyright. All rights reserved.

10.1002/chem.201605464
Chemistry - A European Journal
COMMUNICATION
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Author(s), Corresponding Author(s)*
Page No. – Page No.
Title
OAc
[Pd(C3H5)Cl2 (2.5 mol%)
dppb (11 mol%)
O
S
H
Ph
Ph
+
NMe2
TBSO
NaH, DME
25 ˚C, 48h
85% yield
H
O
TBSO
SO2NMe2
Abstract:
A new application of Pd-catalysed allylation is
reported which enables the synthesis of a range of branched
sp3-functionalised sulfonamides, a compound class for which
few reported methods exist. By reacting benzyl sulfonamides
with allylic acetates in the presence of Pd(0) catalysts and base
at room temperature, direct allylation can be efficiently carried
out, yielding products which are analogues of structural motifs
seen in biologically active small molecules. The reaction is
carried out under mild conditions and can be applied to
nanomolar sigma-receptor binders, thus enabling a late-stage
functionalisation and efficient expansion of drug-like chemical
space.
Catalytic sp3-sp3 functionalisation of sulfonamides: late-
stage modification of drug-like molecules
Othman Abdulla, Adam D. Clayton, Robert A. Faulkner,
Duncan M. Gill, Craig R. Rice, Scarlett M. Walton, and
Joseph B. Sweeney*
Page No. – Page No.
This article is protected by copyright. All rights reserved.