Preparation of Symmetrical and Nonsymmetrical Fluorene -Sulfonamide Scaffolds

Article abstract of DOI:10.1055/s-0036-1588916

Methods for the preparation of symmetrical and nonsymmetrical 2,7-disubstituted 9H-fluorene derivatives are described.

Full text of DOI:10.1055/s-0036-1588916

SYNLETT
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
© Georg Thieme Verlag Stuttgart · New York
2016, 27, A–F
letter
A
D. H. Jones et al.
Letter
Synlett
Preparation of Symmetrical and Nonsymmetrical Fluorene
Sulfonamide Scaffolds
R4
4 steps
O
D. Heulyn Jonesa
James P. Tellama
Stefano Bresciania
N
O
S
R3
N
R1
R2
Justyna Wojno-Picona,b
Anthony W. J. Cooperb
Nicholas C. O. Tomkinson*a
O
O
O
O
O
5 steps
3 steps
S
O
O
S
S
O
Br
S
R4
N
Cl
N
R1
R3
Cl
R2
a WestCHEM, Department of Pure and Applied Chemistry,
Thomas Graham Building, University of Strathclyde, 295
Cathedral Street, Glasgow, G1 1XL, UK
Nicholas.Tomkinson@strath.ac.uk
b GlaxoSmithKline Medicines Centre, Gunnels Wood Road,
Stevenage, SG1 2NY, UK
O
O
O
4 steps
S
R4
N
N
R1
R3
R2
Received: 11.08.2016
Accepted after revision: 27.10.2016
Published online: 17.11.2016
O
O
O
S
O
S
DOI: 10.1055/s-0036-1588916; Art ID: st-2016-b0523-l
HN
NH
Abstract Methods for the preparation of symmetrical and nonsym-
metrical 2,7-disubstituted 9H-fluorene derivatives are described.
H2N
NH2
1
2
fluorene
ligand for catalysis
Key words fluorene, sulfonamide, microwave-assisted synthesis
O
O
S
O
NMe2
O
S
Fluorene (1, Figure 1) represents a privileged structure
that has found a wide variety of applications in synthetic,
medicinal, and materials chemistry. The defined shape and
electronics of 1 impart important functional properties on
derivatives.1 For example, C2-symmetric bis-sulfonamide 2
is an effective ligand in the rhodium-catalysed asymmetric
transfer hydrogenation of ketones.2 Bis-sulfonamides are
also prevalent in many commercial screening libraries and
have been identified as hit compounds on diverse protein
targets including alanine racemase,3 cysteine protease,4 and
17β-HSD1.5 In addition, bis-sulfonamide 3 has been used in
chemical biology as a novel DNA G quadruplex ligand
showing further applications for this class of compound.6
For each of these examples the rigid scaffold of fluorene
provides the requisite geometry for function, holding sub-
stituents in a specific position. Along with the structural
properties imparted by the framework, the conjugated na-
ture of the two aromatic rings and the acidic methylene
protons dictate the properties of derivatives. For example,
bis-sulfonylated fluorenes have found use in areas such as
self-assembled monolayer arrays for molecular electronic
devices,7 compounds with room-temperature phosphores-
cent emission properties,8 charge-transfer complexes,9 and
merocyanine dyes.10 Therefore, new methods for the prepa-
ration of fluorene derivatives that allow access to alterna-
tive and more complex scaffolds will be of interest to the
synthetic community.
Me2N
HN
NH
3
DNA quadruplex ligand
Figure 1 Fluorene (1) and symmetrical bis-sulfonamide derivatives
A key feature of fluorene chemistry that directs many of
the applications of this framework is the regiospecific elec-
trophilic aromatic sulfonylation,7a nitration,11 and haloge-
nation,12 which leads to 2,7-disubstituted systems for fur-
ther elaboration. Surprisingly, the majority of fluorene de-
rivatives reported to have function within the literature are
symmetrical, presumably due to their ease of synthesis, and
we were unable to identify effective methods to prepare
nonsymmetrical compounds despite the potential applica-
tions of these products. Within this paper we describe sim-
ple and effective methods for the preparation of monosul-
fonamides together with symmetrical and nonsymmetrical
bis-sulfonamides from commercial fluorene building blocks
and also provide preliminary data to show a method for the
preparation of aniline- and amide-substituted fluorene mo-
nosulfonamides.
As part of our ongoing investigations in nuclear receptor
chemistry,13 virtual screening identified the symmetrical
bis-sulfonamide 9 as a potential hit compound which was
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–F

B
D. H. Jones et al.
Letter
Synlett
therefore physically required for biological evaluation. Bis-
sulfonyl chloride 4 was prepared by a modified literature
procedure7a and isolated without the need for purification
by chromatography (see the Supporting Information for full
details).
To our surprise, an experimental procedure for the mo-
nosulfonylation of fluorene has not been detailed in the lit-
erature.14 Application of standard reaction conditions with
careful control of stoichiometry led to the selective sulfo-
nylation of fluorene, and subsequent chlorination gave mo-
nosulfonyl chloride 6 in 75% yield over two steps.
Thermal methods have been described for the prepara-
tion of sulfonamides from the corresponding sulfonyl chlo-
ride. Whilst these methods proved effective, an alternative
microwave procedure was established which proved more
convenient due to the short reaction times involved (typi-
cally <15 min, Table 1).
Heating bis-sulfonyl chloride 4 in the presence of two
equivalents of aniline in a mixture of THF, NaOH (2 M), and
acetone at 100 °C for 15 minutes provided the bis-sulfon-
amide 8 (Table 1, entry 1, 93%) after purification by column
chromatography. This method proved effective for both pri-
mary (Table 1, entries 1–3) and secondary (Table 1, entry 4)
anilines. Aliphatic amines were also shown to be efficient
substrates for the transformation (Table 1, entries 5–7) and
suggest this should be an effective and general method for
the preparation of this class of compound. Reaction of mo-
nosulfonyl chloride 6 with one equivalent of amine gave the
corresponding monosulfonamides in good yields. The reac-
tion was found to be tolerant of primary and secondary
amines along with aniline substrates (Table 1, entries 8–
10).
Having prepared a series of symmetrical bis- and mono-
sulfonamides we were eager to discover if we could also ac-
cess nonsymmetrical derivatives. Attempts were made to
use monosulfonamides 7 as precursors to nonsymmetrical
bis-sulfonamides, however, standard sulfonylation condi-
tions (HSO3Cl, AcOH, 140 °C) proved incompatible with the
existing sulfonamide functionality, leading to intractable
mixtures of products.
Recent work has shown that aryl sulfonamides can be
accessed in a two-step one-pot procedure through a palla-
dium-catalysed sulfination followed by reaction of the aryl
sulfinate intermediate with an amine in the presence of N-
bromosuccinimide (NBS).15 With this in mind, we envis-
aged nonsymmetrical bis-sulfonamides could be accessed
by the route outlined in Scheme 1.
Table 1 Preparation of Fluorene-Derived Sulfonamides
O
O
O
O
O
O
O
O
S
S
S
S
R2
N
Cl
Cl
N
R1
R1
R2
4
5
R1R2NH
or
or
2 M NaOH
THF, acetone
MW 100 °C, 15 min
O
O
O
O
S
S
R2
N
Cl
R1
6
7
Entry
Reactant
R1
R2
Product
Yield (%)a
1
2
4
4
4
4
4
4
4
6
6
6
H
Ph
8
9
93
54
34
85
60
71
55
77
62
83
H
4-MeC6H4
3b
4
H
4-HOC6H4
4-MeC6H4
Cy
10
11
12
13
14
15
16
17
Me
H
5
6
H
i-Pr
7
H
4-THP
i-Pr
8
H
9
H
4-MeC6H4
10
–CH2(CH2)2CH2–
a Isolated yield after purification by column chromatography.
b Reaction heated for 1 h.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–F

C
D. H. Jones et al.
Letter
Synlett
p-toluidine (1 equiv)
NaOH (2 M)
THF, acetone
1. HSO3Cl, AcOH
140 °C, 18 h
O
Br
Br
MW 100 °C, 15 min
O
S
2. (COCl)2, DMF (cat)
CH2Cl2, 40 °C, 2 h
Cl
18
19 (80%)
1. K2S2O5, NaO2CH
Pd(OAc)2, PPh3
Phen, TBAB, DMSO
time, 70 °C
O
O
O
O
Br
S
O
O
S
S
N
O
NHTol
2. morpholine, NBS
DMSO, THF
0 °C to r.t., 1 h
NHTol
20 (63%)
21 (77%)
Scheme 1 Preparation of nonsymmetrical fluorene-derived bis-sulfonamides
Conversion of 2-bromofluorene 18 into the sulfonyl
chloride 19 proceeded smoothly under standard reaction
conditions (80%, two steps), which was treated with p-tolu-
idine (1 equiv) to give the corresponding sulfonamide 20
(63%). Reaction of this substrate with morpholine under the
conditions described by Shavnya et al.15 gave the corre-
sponding sulfonamide 21 in 77% yield. Unfortunately, com-
plex mixtures of products were observed when performing
this protocol using aniline or primary amine starting mate-
rials. The fluorene scaffold can readily undergo both oxida-
tion and deprotonation which we believe to be the origin of
the multiple products observed when using alternative
amines within this protocol.
We also examined alternative palladium-catalysed cou-
pling processes for the introduction of additional functional
groups of relevance to catalysis, medicinal chemistry, and
materials chemistry (Scheme 2). Treatment of bromo sul-
fonamide 20 with morpholine in the presence of RuPhosPd
under microwave irradiation at 120 °C for 30 minutes pro-
vided the Buchwald–Hartwig coupling product 22 in 72%
isolated yield after purification by column chromatogra-
phy.16 We were also able to directly access amide deriva-
tives of 20 by microwave irradiation at 90 °C for 30 minutes
in the presence of morpholine, Pd(OAc)2, Xantphos as a
supporting ligand, Mo(CO)6, and DMAP, providing 23 in 76%
isolated yield.17 These initial examples suggest that 20
should be an effective substrate for a variety of palladium-
catalysed coupling procedures, further adding to the poten-
tial diversity and subsequent application of the products.
It is established that aryl iodides can be beneficial in
palladium-catalysed transformations due to an increased
rate of oxidative addition. We envisaged that the scope of
the sulfonamide forming reaction could be improved
through the use of aryl iodide substrate 24 (Scheme 3). Sul-
fonyl chloride 25 was prepared using standard conditions
in an excellent yield over two steps (88%), without the need
for chromatographic purification. The intermediate sulfonyl
chloride 25 was sensitive to heating in the presence of a
base, but a modified procedure employing two equivalents
of amine and stirring at room temperature overnight over-
came this problem, giving sulfonamides 26 and 27 in good
yields (see Supporting Information for full details).
Sulfonamide 26 was reacted with morpholine under the
conditions described by Shavnya et al.,15 however, a com-
plex mixture of products was observed by LC–MS. A modest
yield (48%) of 21 was achieved by using five equivalents of
K2S2O5, however, despite extensive exploration of reaction
morpholine (1.2 equiv)
RuPhosPd (5 mol%)
RuPhos (5 mol%)
O
N
O
O
O
S
O
NaOt-Bu (1.5 equiv
Br
Br
O
NHTol
S
dioxane [0.2 M]
MW, 120 °C, 30 min
NHTol
20
22 (72%)
morpholine (1.5 equiv)
Pd(OAc)2 (5 mol%)
Xantphos (7.5 mol%)
Mo(CO)6 (2.0 equiv)
O
O
S
O
N
O
NHTol
S
DMAP (1.5 equiv)
dioxane [0.2 M]
MW, 90 °C, 30 min
NHTol
O
20
23 (76%)
Scheme 2 Palladium-catalysed synthesis of nonsymmetrical fluorene derivatives
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–F

D
D. H. Jones et al.
Letter
Synlett
sulfonamide 28 in 15% yield after purification by column
chromatography (Scheme 4). Subsequent reaction with ox-
alyl chloride gave sulfonyl chloride 29 which was then re-
acted with ethanolamine or 3-hydroxypropylamine to give
the nonsymmetrical bis-sulfonamides 30 (95%) and 31
(43%), respectively. Of the methods examined this provided
the most convenient process to access arrays of nonsym-
metrical bis-sulfonamide targets in a reliable, time-effi-
cient, and cost-effective manner.
O
I
O
S
NH
p-Tol
26 (98%)
p-toluidine (2.2 equiv)
THF, acetone
r.t., overnight
In summary, we have described methods for the prepa-
ration of symmetrical and nonsymmetrical fluorene sulfon-
amide derivatives. Mono- and symmetrical bis-sulfon-
amides can be readily accessed through the microwave irra-
diation of the corresponding sulfonyl chloride in the
presence of an amine, allowing access to the products in
short reaction times. Nonsymmetrical bis-sulfonamides
can be prepared in lower yields through the monofunction-
alisation of bis-sulfonyl chloride 4, followed by purification,
reaction with oxalyl chloride, and then treatment with a
second amine. Application of a palladium-catalysed sulfo-
nylation process also provides access to selected nonsym-
metrical bis-sulfonamides but this transformation proved
dependent on the structure of the amine nucleophile. Ani-
line and amide derivatives of the fluorene scaffold can also
be prepared using transition-metal-catalysed coupling pro-
cesses, adding to the structural diversity accessible through
this methodology. Given the significant number of applica-
tions known for symmetrical fluorene derivatives in di-
verse areas including asymmetric catalysis, medicinal
chemistry, and materials science it is expected that this
work will provide the impetus for further discovery in the
application of the fluorene skeleton.
1. HSO3Cl, AcOH
140 °C, 18 h
O
I
O
I
S
2. (COCl)2
DMF (cat)
CH2Cl2
Cl
24
25 (88%)
40 °C, 2 h
morpholine (2.2 equiv)
THF, acetone
r.t., overnight
O
I
O
S
N
27 (65%)
O
Scheme 3 Preparation of iodo sulfonamides
conditions, a number of unidentified products predominat-
ed when using primary amines or anilines in this reaction.
Alternative reported methods for the preparation of aryl
sulfonamides from aryl halides were applied to sulfon-
amides 26 and 27, however, in each case multiple products
were observed.18
A nonelegant, transition-metal free solution to the
preparation of nonsymmetrical bis-sulfonamides was
found by treating bis-sulfonyl chloride 4 with one equiva-
lent of p-toluidine under basic reaction conditions, giving
Acknowledgment
We thank the EPSRC for financial support and the Mass Spectrometry
Service, Swansea, for high-resolution spectra.
O
O
O
p-toluidine (1 equiv)
O
O
O
S
O
S
S
O
S
NHTol
2 M NaOH, THF
acetone
Cl
HO
Cl
MW 100 °C, 15 min
4
28 (15%)
(COCl)2
DMF (cat)
CH2Cl2
40 °C, 2 h
O
NHR1 (1 equiv)
O
O
O
O
S
O
O
S
S
O
S
TolNH
2 M NaOH, THF
acetone
NH
NHTol
R1
Cl
R1 = HOCH2CH2 30 (95%)
R1 = HOCH2CH2CH2 31 (43%)
MW 100 °C, 15 min
29
Scheme 4 Preparation of nonsymmetrical fluorene-derived bis-sulfonamides
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–F

E
D. H. Jones et al.
Letter
Synlett
Supporting Information
(19) General Procedure for the Microwave-Assisted Formation of
Sulfonamides
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0036-1588916.
9H-Fluorene-2,7-disulfonyl dichloride (4, 100 mg, 0.28 mmol),
acetone (1.52 mL), THF (0.28 mL), amine (0.56 mmol), and 2 M
NaOH (aq, 0.32 mL) were added to a 5 mL microwave vial
equipped with a magnetic stirrer bar. The mixture was heated
in a Biotage Initiator at 100 °C for 15 min and allowed to cool to
r.t. CH2Cl2 (10 mL) was added, and the mixture washed with
water (10 mL), sat. Na2CO3 solution (10 mL), 2 M HCl (aq) solu-
tion (10 mL),and brine (10 mL). The organic extract was dried
over MgSO4, filtered, and concentrated under reduced pressure
to give the crude product.
N,N-Diisopropyl-9H-fluorene-2,7-disulfonamide (13)
Prepared by the General Procedure, using isopropylamine (0.05
mL, 0.58 mmol). Purified by column chromatography on silica
(PE–EtOAc = 2:1, followed by 1:1) to give 13 as a yellow-orange
solid (80 mg, 71%); mp 194–195 °C. IR (ATR): 3054, 2990, 1456,
1403, 1304, 1235, 1181, 1103 cm–1. 1H NMR (400 MHz, DMSO-
d6): δ = 8.21 ( 2H, d, J = 8.1 Hz), 8.06 (2 H, d, J = 0.8 Hz), 7.89 (2 H,
dd, J = 8.1, 1.5 Hz), 7.61 (2 H, d, J = 7.2 Hz), 4.18 (2 H, s), 3.22–
3.35 (2 H, m), 0.96 (12 H, d, J = 6.5 Hz). 13C NMR (101 MHz,
DMSO-d6): δ = 144.7 (Cq), 143.0 (Cq), 141.1 (Cq), 125.5 (CH),
123.4 (CH), 121.5 (CH), 45.2 (CH), 36.7 (CH2), 23.2 (CH3). LC–
MS: m/z = 407.1 [M – 1]+. HRMS: m/z calcd for C19H23O4N2S2:
407.1105; found: 407.1107.
S
u
p
p
ortioInfgrmoaitn
S
u
p
p
ortiInfogrmoaitn
References and Notes
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Palladium-Catalysed Procedures
7-(Morpholinosulfonyl)-N-(p-tolyl)-9H-fluorene-2-sulfon-
amide (21)
A microwave vial was charged with 20 (30.0 mg, 0.062 mmol),
K2S2O5 (33.0 mg, 0.148 mmol), TBAB (26.3 mg, 0.082 mmol),
NaO2CH (12.0 mg, 0.176 mmol), Pd(OAc)2 (1.0 mg, 5 mol%), Ph3P
(3.0 mg, 0.013 mmol), 1,10-phenanthroline (2.0 mg, 0.011
mmol), and DMSO (0.2 mL). The mixture was degassed by bub-
bling nitrogen through the solvent for 10 min, and then heated
under argon at 70 °C for 3 h. Following cooling to r.t., a solution
of morpholine (12.6 mg, 0.145 mmol) in anhydrous THF (1.0
mL) was added, and the mixture cooled to 0 °C. A solution of
NBS (25.8 mg, 0.145 mmol) in THF (1.0 mL) was added drop-
wise and the mixture left to warm to r.t. over 1 h. Water (10 mL)
was added, and the mixture extracted with EtOAc (3 × 10 mL).
The organics were combined and washed with water (20 mL),
brine (20 mL), dried over MgSO4, filtered, and concentrated
under reduced pressure to give the crude product, which was
purified by column chromatography (PE–EtOAc = 1:1) to give 21
as a yellow solid (27 mg, 77%). 1H NMR (400 MHz, acetone-d6):
δ = 8.87 (1 H, s), 8.19 (1 H, d, J = 8.0 Hz), 8.11 (1 H, d, J = 8.4 Hz),
8.01–8.06 (2 H, m), 7.81–7.88 (2 H, m), 7.11 (2 H, d, J = 8.4 Hz),
7.04 (2 H, d, J = 8.4 Hz), 4.14 (2 H, s), 3.62–3.72 (4 H, m), 2.93–
3.03 (4 H, m), 2.21 (3 H, s). 13C NMR (101 MHz, acetone-d6): δ =
146.2 (Cq), 145.9 (Cq), 145.2 (Cq), 144.8 (Cq), 140.5 (Cq), 136.1
(Cq), 135.7 (Cq), 135.3 (Cq), 130.5 (CH), 128.0 (CH), 127.3 (CH),
125.8 (CH), 125.1 (CH), 122.5 (CH), 122.3 (CH), 122.2 (CH), 66.7
(CH2), 47.1 (CH2), 37.7 (CH2), 20.7 (CH3). LC–MS m/z = 483.2
[M – 1]+. HRMS: m/z calcd for C25H25N2O5S2: 485.1199; found:
485.1189.
(10) (a) Kurdyukova, I. V.; Derevyanko, N. A.; Ischenko, A. A.; Mysyk,
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Org. Biomol. Chem. 2016, 14, 172. (b) Trump, R. P.; Bresciani, S.;
Cooper, A. W. J.; Tellam, J. P.; Wojno, J.; Blaikley, J.; Orband-
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(14) The monosulfonation of fluorene has been reported, see:
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2259.
(15) Shavnya, A.; Coffey, S. B.; Smith, A. C.; Mascitti, V. Org. Lett.
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7-Morpholino-N-(p-tolyl)-9H-fluorene-2-sulfonamide (22)
A mixture of RuPhos palladacycle (7 mg, 0.05 equiv), RuPhos (5
mg, 0.05 equiv), NaOt-Bu (29 mg, 0.30 mmol), 7-bromo-N-(p-
tolyl)-9H-fluorene-2-sulfonamide (83 mg, 0.20 mmol), and
morpholine (0.021 mL, 0.24 mmol) in 1,4-dioxane (0.50 mL)
was sealed and heated in a Biotage Initiator at 120 °C for 30 min.
After cooling, the sample was passed through a plug of Celite
using MeOH (10.0 mL), then concentrated under reduced pres-
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–F

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D. H. Jones et al.
Letter
Synlett
sure to give the crude product, which was purified by column
chromatography (PE–EtOAc = 1:1) to give 21 (59 mg, 72%) as a
yellow solid; mp 170 °C (decomp.); IR (ATR): 2922, 1612, 1512,
1451, 1419, 1243, 1189, 1111 cm–1. 1H NMR (400 MHz, CDCl3):
δ = 7.82 (1 H, d, J = 1.2 Hz), 7.70 (1 H, dd, J = 8.0, 0.8 Hz), 7.67 (1
H, d, J = 8.8 Hz), 7.64 (1 H, d, J = 8.4 Hz), 7.10 (1 H, d, J = 2.0 Hz),
6.99–7.04 (2 H, m), 6.92–6.98 (3 H, m), 6.41 (1 H, s), 3.86–3.92
(4 H, m), 3.83 (2 H, s), 3.20–3.28 (4 H, m), 2.26 (3 H, s). 13C NMR
(101 MHz, CDCl3): δ = 152.1 (Cq), 146.8 (Cq), 146.2 (Cq), 143.1
(Cq), 135.6 (Cq), 135.4 (Cq), 134.0 (Cq), 133.3 (Cq), 130.0 (CH),
126.7 (CH), 123.8 (CH), 122.7 (CH), 121.8 (CH), 118.9 (CH),
115.2 (CH), 112.1 (CH), 67.0 (CH2), 49.5 (CH2), 37.1 (CH2), 21.0
(CH3). LC–MS: m/z = 421.1 [M + 1]+. HRMS: m/z calcd for
(83.0 mg, 0.20 mmol), and morpholine (0.034 mL, 0.39 mmol)
in 1,4-dioxane (0.50 mL) was sealed and heated in a Biotage Ini-
tiator at 90 °C for 30 min. After cooling, the reaction mixture
was passed through Celite using MeOH (10.0 mL), then concen-
trated under reduced pressure to give the crude product, which
was purified by column chromatography (PE–EtOAc = 4:1) to
give 22 as a yellow solid (0.068 g, 76%); mp 210 °C (decomp.). IR
(ATR): 2925, 2853, 1619, 1605, 1445, 1332, 1243, 1191, 1148,
1111, 1049 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.92 (1 H, d, J =
0.7 Hz), 7.82 (1 H, d, J = 8.0 Hz), 7.75–7.80 (2 H, m), 7.62 (1 H, d,
J = 0.8 Hz), 7.45 (1 H, dd, J = 8.0, 1.2 Hz, 1 H), 7.02 (2 H, d, J = 8.0
Hz), 6.96 (2 H, d, J = 8.0 Hz), 6.77 (1 H, br s), 3.91 (2 H, s), 3.50–
3.87 (8 H, m), 2.25 (3 H, s). 13C NMR (101 MHz, CDCl3): δ = 170.5
(Cq), 145.3 (Cq), 144.6 (Cq), 144.1 (Cq), 141.6 (Cq), 137.9 (Cq),
135.7 (Cq), 135.2 (Cq), 133.8 (Cq), 130.0 (CH), 126.7 (CH), 126.4
(CH), 124.4 (CH), 124.2 (CH), 122.7 (CH), 121.0 (CH), 120.6 (CH),
67.0 (CH2), 37.1 (CH2), 21.0 (CH3), one carbon missing. LC–MS:
m/z = 449.1 [M + 1]+. HRMS: m/z calcd for C25H25N2O4S:
449.1530; found: 449.1530.
C24H25N2O3S: 422.1580; found: 422.1577.
7-(Morpholine-4-carbonyl)-N-(p-tolyl)-9H-fluorene-2-sul-
fonamide (23)
A mixture of Pd(OAc)2 (2.0 mg, 0.05 equiv), Xantphos (6.0 mg,
0.05 equiv), Mo(CO)6 (53.0 mg, 0.05 equiv), DMAP (37.0 mg,
0.30 mmol), 7-bromo-N-(p-tolyl)-9H-fluorene-2-sulfonamide
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–F