Synthesis of Ferrocenesulfonyl Chloride: Key Intermediate toward Ferrocenesulfonamides

Article abstract of DOI:10.1055/a-1478-7002

Ferrocenesulfonyl chloride is the key intermediate in the synthesis of ferrocenesulfonamides, a family of underexplored derivatives. A one-pot synthesis of this compound, able to easily deliver multigram quantities of product, is reported. An original protocol for the synthesis of ferrocenesulfonamides is described along with highlighting the reactivity difference between arene and ferrocenesulfonyl chlorides. Finally, an example of diastereoselective deprotolithiation of chiral ferrocenesulfonamides is described.

Full text of DOI:10.1055/a-1478-7002

SYNTHESIS
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart
2021, 53, A–I
psp
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W. Erb et al.
PSP
Synthesis
Synthesis of Ferrocenesulfonyl Chloride: Key Intermediate toward
Ferrocenesulfonamides
William Erb*
Min Wen
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1) ClSO3H, Et2O
0 °C to rt, 24 h
O
S
Cl
Fe
Fe
O
2) PCl3, Et2O
rt, 24 h
Thierry Roisnel
Florence Mongin
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Large-scale synthesis: 400 mmol
Purification by crystallization
65% yield - 74 g in one batch
Univ Rennes, CNRS, ISCR (Institut des Sciences Chimiques de
Rennes)-UMR 6226, 35000 Rennes, France
william.erb@univ-rennes1.fr
WUeMniilavliCalRomwernirElenlriseabpsmo, Cn.eNdribRn@Sg,uAInSuCivtRh-ro(eIrnsnteitsu1t.fdres Sciences Chimiques de Rennes)-UMR 6226, 35000 Rennes, France
Received: 24.02.2021
Accepted after revision: 09.04.2021
Published online: 09.04.2021
sporanic ferrocenesulfonamide derivatives.9 Finally, a few
other reports were dedicated to specific structures and
their study at the solid state.10
DOI: 10.1055/a-1478-7002; Art ID: ss-2021-z0085-psp
Whatever their applications, all the ferrocenesulfon-
amides described are prepared from bare ferrocene by sul-
fonation, chlorination, and nucleophilic substitution
(Scheme 1).
Abstract Ferrocenesulfonyl chloride is the key intermediate in the
synthesis of ferrocenesulfonamides, a family of underexplored deriva-
tives. A one-pot synthesis of this compound, able to easily deliver multi-
gram quantities of product, is reported. An original protocol for the syn-
thesis of ferrocenesulfonamides is described along with highlighting the
reactivity difference between arene and ferrocenesulfonyl chlorides. Fi-
nally, an example of diastereoselective deprotolithiation of chiral ferro-
cenesulfonamides is described.
SO3H
SO2Cl
SO2NR2
Sulfonation
Chlorination
Substitution
Fe
Fe
Fe
Fe
1
2
3
Scheme 1 Step order toward ferrocenesulfonamides
Key words ferrocene, sulfonyl chloride, sulfonamide, scale-up, diaste-
reoselective deprotolithiation
Weinmayr and Nesmeyanov were the first to inde-
pendently report the sulfonation of ferrocene using concen-
trated sulfuric acid and the 1,4-dioxane·SO3 complex, re-
spectively, with the isolation of the ammonium 1·NH3 salt
(78% yield) or dihydrate 1·2H2O (62% yield).11 Pauson then
introduced the use of chlorosulfonic acid toward the same
1·2H2O hydrate (60% yield)12 while Schlögl reported a mod-
ification of its isolation protocol to deliver the p-toluidini-
um salt (1·p-toluidine, 92% yield).13 Since then, most of the
studies involving ferrocenesulfonic acid relied on the proto-
cols described by Pauson and Schlögl.
While the chlorination of ferrocenesulfonic acid (1) to-
ward ferrocenesulfonyl chloride (2) was first described by
Nesmeyanov using phosphorus trichloride in 69% yield,11b,14
Pauson later reported that phosphorus pentachloride and
thionyl chloride were not suitable chlorinating reagents.12
More recently, oxalyl chloride was used in the synthesis of
2, although different yields were reported under similar re-
action conditions.4,6 Interestingly, Slocum proposed a two-
step one-pot protocol to convert ferrocene into 2 by the se-
quential use of chlorosulfonic acid and PCl3.15 Although the
yield was lower than in the other approaches (23%), this
protocol does not require the isolation of 1.
Although discovered seventy years ago, ferrocene still
remains one of the most important organometallic scaf-
folds with multiple applications in all areas of chemistry.1
This results from its three-dimensional structure, revers-
ible redox behavior, planar chirality properties, and high
stability in various conditions. While many ferrocene deriv-
atives have been the focus of detailed studies, ferrocenesul-
fonamides remain a class of compounds barely explored al-
though promising applications have already been reported.
They can be found in a few macrocycles acting as multielec-
tron systems2 or behaving as efficient ligands in catalysis.3
They have also been used to reach original N-heterocyclic
carbenes, studied for their metal coordinating properties.4
Ferrocenesulfonamides are also interesting substrates to-
ward sulfur-containing derivatives as described by Herber-
hold and Sato,5 or original materials as proposed by Wurm.6
Concerning the redox properties of ferrocenesulfonamide
derivatives, they were exploited in
a
ferrous ion
rhodamine-based sensor7 or in self-bleaching electrochro-
mic devices.8 Applications in medicinal chemistry have also
been reported with antibacterial penicillanic and cephalo-
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–I
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
W. Erb et al.
PSP
Synthesis
While all the syntheses of 1 and 2 employ similar re-
agents and conditions, the reported protocols to access the
ferrocenesulfonamides 3 are more diverse. Indeed, some
ferrocenesulfonamides were prepared with heating in the
presence of an excess of amine at reflux of a given sol-
vent9,10b,12,14 while others were obtained by performing re-
actions between 0 °C and 25 °C using various solvents.5d,13,15
Reactive amines such as methylaziridine can react with 2 at
–30 °C6 while imidazole and benzimidazole require heating
at acetonitrile reflux in the presence of an inorganic base.4
It can be finally noticed that 1,1′-bis(ferrocenesulfonyl)
chloride reacts in a stepwise manner with an excess of
amine, the second substitution being slower than the first
one.10e
While we recently described the synthesis of various
polysubstituted ferrocenesulfonamides,16 we were limited
by the low-yielding synthesis of ferrocenesulfonyl chloride
(2; 30% yield). With a view to developing a more efficient
approach toward ferrocenesulfonamides, we decided to
evaluate the use of 1,4-diazabicyclo[2.2.2]octane-bis(sulfur
dioxide) (DABSO) in the ferrocene series. Indeed, Willis de-
scribed the reaction of various organometallics with this
surrogate of gaseous SO2 toward sulfonamides,17 sulfones,18
sulfoxides,19 and sulfinamides.20
Therefore, we reacted ferrocenyllithium, obtained by
treating ferrocene by tert-butyllithium in the presence of
potassium tert-butoxide,21 with DABSO. After conversion of
the intermediate sulfinate to 2 using sulfuryl chloride, the
addition of pyrrolidine afforded the desired (N-pyrrolidi-
no)sulfonylferrocene (3a) in a moderate 41% yield (Scheme
2). However, facing reproducibility troubles, we suspected
the chlorinating reagent used to be incompatible with the
oxidation-sensitive ferrocene. We therefore evaluated alter-
natives such as N-chlorosuccinimide22 and oxalyl chloride.
While the former led to compound 3a in a 21% yield, the use
of the later only delivered low amounts of the thiosulfon-
ates 4–6 (see SI for a putative reaction mechanism and for
the solid-state structures of 5 and 6).
cene rather than in the chlorination step. While chlorosul-
fonic acid is employed in both protocols, the former used
acetic anhydride, proposed to reduced competitive oxida-
tion of ferrocene,11a while the latter used diethyl ether. Keen
to avoid the use of large amounts of acetic anhydride, we
decided to keep diethyl ether as solvent but under more di-
luted reaction conditions. Furthermore, to avoid the use of
anhydrous solvent, we used a slight excess of chlorosulfonic
acid (1.2 equiv instead of 1.1). This led to an increase of the
formation of 2 on a 250 mmol scale (46 g isolated, 64%
yield, Scheme 3). Our optimized conditions involve the
dropwise addition of chlorosulfonic acid onto an ice-cooled
solution of ferrocene in diethyl ether followed by 24 hours
stirring at room temperature. After addition of phosphorus
trichloride, another 24 hours stirring period is required be-
fore removal of volatiles under vacuum to give the crude
product. While Slocum uses petroleum ether (bp 30–60 °C
fraction) to recrystallize 2, we found that repeated tritura-
tion of the crude product with hot heptane, followed by
crystallization, was a more efficient process. Pleasingly, we
were able to conduct the reaction on a 400 mmol scale with
reproducible results (reaction done two times in 65 and
71% yield; 74 and 80 g of 2 isolated, respectively).
1) ClSO3H, Et2O
O
0 °C to rt, 24 h
S
Cl
Fe
Fe
O
2) PCl3, Et2O
rt, 24 h
2
Reported conditions
200 mmol scale
Optimized conditions
250 mmol scale
400 mmol scale
64% - 46 g
65% - 74 g
30% - 17 g
Scheme 3 Large-scale synthesis of ferrocenesulfonyl chloride (2)
With the possibility to easily obtain large amounts of
ferrocenesulfonyl chloride (2), we next focused our efforts
on the synthesis of sulfonamides. Indeed, we were in-
trigued by the various reaction conditions described in the
literature and by a report from Koppang on some low-yield-
ing smooth reaction conditions.23 Therefore, we reacted 2
with different amines under reaction conditions inspired
from the literature (Scheme 4). However, in our hands,
most of the reaction conditions applied only led to traces of
expected product with various degrees of starting material
recovery. The only successful conditions were the ones re-
ported by Sato5c for the synthesis of 3b in a THF/water mix-
ture (91% yield on a 26 mmol scale).
Chlorinating reagent
SO2Cl2 41%
1) tBuLi, tBuOK
2) DABSO
O
S
N
Fe
NCS
21%
Fe
O
3) Chlorinating reagent
4) Pyrrolidine
(COCl)2 trace
3a
O
O
O
S
S
S
S
S
S
Fe
O
Fe
O
O
Fe
Fe
4
5
6
In search for harsher reaction conditions, 2 was reacted
at 60 °C with a three-fold excess of morpholine in chloro-
form at a 5 molar concentration. Pleasingly, (N-morpholi-
no)sulfonylferrocene (3c) was isolated in 94% yield after
only 30 minutes (Scheme 5). As we recognized that such
high concentration might be incompatible with some solid
amines, the reaction was repeated by adding a solution of
morpholine in chloroform, leading to a final 2.5 molar con-
centration, with similar results (96% yield). We next studied
the scope of these new reaction conditions with various
Scheme 2 Attempts to use DABSO in the synthesis of ferrocenesulfon-
amides
Therefore, to progress toward a practical large-scale
synthesis of ferrocenesulfonyl chloride (2), we decided to
focus our efforts on the one-pot protocol described by Slo-
cum.15 We reasoned that the main difference between the
high-yielding protocol of Pauson12 and the low-yielding
from Slocum15 preferably lies in the sulfonation of ferro-
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–I

C
W. Erb et al.
PSP
Synthesis
O
O
O
R
O
R
S
S
CHCl3 (2.5 or 5 M)
60 °C, 30 min
S
O
Et2
H2N
Cl
N
HN
R
S
Cl
+
+
Fe
O
Fe
N
Fe
Fe
Fe
Fe
O
O
O
Fe
Fe
R
H
O
0 °C to rt, 6 h
2
3
2
trace
97% recovered starting material
O
O
O
O
O
N
S
S
S
S
S
Et2O
S
N
N
N
N
Cl
HN
Fe
Fe
Fe
Fe
+
+
+
O
O
O
O
NBoc
O
O
O
0 °C to rt, 2 h
trace
2
3a - 95% (2.5 M)
3c - 94% (5 M)
3d - 80% (2.5 M)
3e - 36% (5 M)a
98% recovered starting material
N
O
O
O
O
O
N
S
S
S
S
S
N
N
Cl
N
Fe
Fe
H
Fe
O
O
Fe
Fe
O
H
O
H
H2N
O
Et2O
0 °C to rt, 6 h
trace
2
3f - trace (5 M)b
3g - 94% (5 M)
3h - 76% (5 M)c
76% recovered starting material
O
Ph
O
O
N
O
S
THF, H2O
rt, 14 h
S
Cl
O
HN
S
S
N
O
N
S
O
Fe
N
Fe
H
O
H
O
Fe
H
O
3b - 91%
2
3i - 44% (5 M)d
3j - trace (5 M)b
3k - 15% (2.5 M)e
Scheme 4 Synthetic attempts toward ferrocenesulfonamides using
protocols adapted from the literature
Scheme 5 Synthesis of ferrocenesulfonamides. a) 34% recovered start-
ing material; b) 98% recovered starting material; c) 15% recovered
starting material; d) 46% recovered starting material; e) 53% recovered
starting material.
amines. Although pyrrolidine led to the sulfonamide 3a in a
similar 95% yield, it was found so reactive that the reaction
needed to be done at a 2.5 molar concentration. For solubil-
ity reason, the same concentration was required when us-
ing Boc-protected piperazine to deliver 3d in 80% yield, to-
gether with the recovery of 15% of unreacted 2. However,
moving to other acyclic secondary amines resulted in a ma-
jor drop of the yield, diethylamine leading to only 36% of 3e
while diallylamine was found unreactive in our conditions
toward compound 3f. Although primary amines were found
more reactive, the yield of the sulfonamides 3 was strongly
influenced by their steric hindrance. Indeed, while n-butyl-
amine afforded 3g in 94% yield, isopropylamine led to com-
pound 3h in 76% yield. A further drop in the yield was re-
corded with (R)--methylbenzylamine, even after 1 hour of
reaction (compound 3i, 44% yield), while only traces of the
sulfonamide 3j were noticed using tert-butylamine. How-
ever, we found that increasing the reaction time favored the
substitution as the sulfonamide 3i was isolated in 85% yield
after 4 hours at 60 °C. Aromatic amine such as p-toluidine
was also found to be poorly reactive as compound 3k was
only isolated in 15% yield. It should be noted that the yields
recorded are in good agreement with the nucleophilicity of
the amine used. Indeed, Mayr reported the following order
of reactivity for secondary and primary amines, respective-
ly: pyrrolidine > morpholine > diethylamine and n-butyl-
amine > isopropylamine > tert-butylamine.24
lighted when they were reacted with diethylamine in our
new reaction conditions. While 3e was formed in 36% yield,
the sulfonamide 8 was obtained in 95% yield after 30 min-
utes. Although one could have suspected 2 to be less reac-
tive than other aromatic sulfonyl chlorides, these results
clearly show the difference between ferrocene and more
classical aromatic compounds. This might result from both
the electron-rich nature of ferrocene and unfavorable steric
parameters, the approach of the nucleophile opposite to the
leaving being probably disfavored by the unsubstituted cy-
clopentadienyl ring as observed at the solid state (Scheme
3).
NEt3 (2 equiv)
DMAP (0.1 equiv)
O
S
O
S
Cl
O
N
HN
HN
+
+
O
THF, rt , 1 h
7 - quant
DIPEA (2 equiv)
DMAP (0.1 equiv)
O
O
S
S
Cl
N
Fe
Fe
O
O
THF, rt , 14 h
2
3b - 74%
Et
O
O
S
Cl
N
S
Et
HN
+
+
O
O
CHCl3
60 °C, 30 min
8 - 95%
O
O
Et
S
S
Cl
N
HN
Fe
Fe
O
O
CHCl3
60 °C, 30 min
Et
3e - 36%
While the amine nucleophilicity plays an important role
in the reaction outcome, we were also keen to compare the
reactivity of ferrocenesulfonyl chloride (2) with more clas-
sical sulfonyl chloride such as the widely used p-tosyl chlo-
ride (Scheme 6).25 Under smooth reaction conditions, the
latter was converted into the sulfonamide 7 in a quantita-
tive way after only one hour at room temperature. However,
the use of ferrocenesulfonyl chloride (2) required prolonged
reaction time to deliver 3b in 74% yield. The reactivity dif-
ference between 2 and p-tosyl chloride was further high-
2
Scheme 6 Reactivity studies of p-tosyl chloride and ferrocenesulfonyl
chloride (2). DIPEA: diisopropylethylamine; DMAP: 4-(dimethylamino)-
pyridine.
As previously observed by Ziegler,10e,g hydrogen bonds
can be observed at the solid state. For the ferrocenesulfon-
amides bearing a free NH, a single string of hydrogen bonds
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–I

D
W. Erb et al.
PSP
Synthesis
linking all sulfonamide groups in compounds 3h and 3k
was observed while two intermolecular hydrogen bonds
link two sulfonamides in compound 3g (see SI).
but promising diastereoselectivity. Considering the already
reported applications of ferrocenesulfonamides and our re-
cent work toward their polysubstituted derivatives, we
strongly believe that further important developments in
this field could be expected.
Finally, we were eager to evaluate the ability of chiral
sulfonamides to direct a diastereoselective deprotolithia-
tion in the ferrocene series (Scheme 7).26 Therefore, we re-
acted the sulfonamides 3i and 3i-Me (obtained by depro-
tonation of 3i with NaH and subsequent trapping with
methyl iodide) with n-BuLi in THF at –80 °C and added
trimethylsilyl chloride after 1 hour of contact. From 3i-Me,
the disubstituted ferrocene 9 was obtained in 63% yield
with a moderate 52% diastereoselective excess (de), esti-
mated from the 1H NMR spectrum. While 2-dimensional
NMR experiments suggested the Sp configuration for the
minor diastereoisomer (see SI), we found that the major
isomer selectively crystallized from the mixture. The X-ray
diffraction analysis allowed us to attribute the R,Rp configu-
ration to the major isomer, thus validating the Sp configura-
tion for the minor one, as suggested from NMR analysis.
From 3i, we isolated the two products 10-TMS (69%, 48%
de) and 10-H (11%, 26% de). For 10-TMS, although we were
not able to grow crystals suitable for X-ray diffraction anal-
ysis, the 1H NMR suggested the same configuration (R,Rp) as
for 9 while we propose the other configuration (R,Sp) for the
sulfonamide 10-H. Although the most used chiral directing
groups can lead to higher yields and diastereoselectivities,27
these results highlight the ability of chiral sulfonamides to
act in a similar way.
Unless otherwise stated, all the reactions were performed under air
using reagent grade solvents. Deprotolithiation experiments were
performed under an argon atmosphere with anhydrous solvents us-
ing Schlenk technics and THF distilled over Na/benzophenone. Unless
otherwise stated, all reagents were used without prior purification.
n-BuLi was titrated before use.28 tBuOK (99.99% quality) was pur-
chased from Sigma-Aldrich and used without further purification.
Room temperature (rt) refers to 25 °C. Column chromatography sepa-
rations were achieved on silica gel (40–63 m). For the purification of
sulfonamides, 2% of CHCl3 was added to the eluent at the beginning of
the purification to avoid the precipitation of compound on silica gel.
All TLC analyses were performed on aluminum-backed plates pre-
coated with silica gel (Merck, Silica Gel 60 F254). They were visualized
by exposure to UV light. PE refers to petroleum ether. Melting points
were measured on a Kofler bench. IR spectra were taken on a Perkin-
1
Elmer Spectrum 100 spectrometer. H and 13C NMR spectra were re-
corded either (i) on a Bruker Avance III spectrometer at 300 MHz and
75.4 MHz, or (ii) on a Bruker Avance III at 400 MHz and 100 MHz, or
(iii) on a Bruker Avance III HD at 500 MHz and 126 MHz, respectively.
1H chemical shifts () are given in ppm relative to the solvent residual
peak and 13C chemical shifts are relative to the central peak of the sol-
vent signal.29 Cp refers to the unsubstituted cyclopentadienyl ring of
ferrocene. The numbering used in this experimental section is de-
fined in the Supporting Information.
Ferrocenesulfonyl Chloride (2)30
Ph
1) NaH, THF
2) MeI, DMF
Ph
O
O
S
[CAS Reg. No. 33010-70-7]
S
N
N
Fe
Fe
Fe
Fe
3i-Me - 91%
Ph
H
O
O
ClSO3H (31.9 mL, 55.9 g, 480 mmol, 1.20 equiv) was added dropwise
to an ice-cold solution of ferrocene (74.4 g, 400 mmol, 1.00 equiv) in
Et2O (1.3 L). After addition, the dark reaction mixture was allowed to
warm to rt and stirred for 24 h. PCl3 (80.4 mL, 126 g, 920 mmol, 2.30
equiv) was added dropwise to the reaction mixture at rt and the mix-
ture was then stirred at rt for 24 h. Volatiles were removed under vac-
uum to give the crude product as dark solids, which were scrapped
with a spatula and kept under high vacuum for 10 min. Heptane (320
mL) was added and the mixture was heated at 90 °C. After 10 min at
this temperature, the red-colored heptane was transferred to a hot
flask, which was allowed to cool to rt. The extraction process was re-
peated until most of ferrocenesulfonyl chloride was extracted. De-
pending on the exact amount of heptane, the temperature, the con-
tact time and the size of the solids, 2 to 4 extractions could be re-
quired. As ferrocenesulfonyl chloride was extracted, the initial solids
evolved to a gummy blue-green paste, which can be scrapped with a
spatula for a better extraction. Caution: If a heat gun is used, atten-
tion must be paid to avoid hot spots as thermal decomposition might
happen if the crude product becomes dry. The heptane solutions
were allowed to cool slowly to rt and the resulting red crystals were
filtered using a sintered glass funnel (porosity 3). The solids were
washed with a small amount of cold pentane and allowed to dry un-
der high vacuum to give the title product 2 as a red solid; yield: 74.3 g
(65%); Rf = 0.40 (PE/EtOAc 90:10); mp 99–100 °C.
3i
Ph
1) nBuLi, THF
–80 °C, 60 min
O
O
S
S
N
N
Me3Si
Fe
O
O
2) Me3SiCl
–80 °C to rt, 1 h
3i-Me
9 - 63% - 52% de
SiMe
3 Ph
Ph
O
Ph
O
1) nBuLi, THF
–80 °C, 60 min
O
S
S
S
N
H
N
N
H
Me3Si
Fe
Fe
O
O
O
2) Me3SiCl
–80 °C to rt, 1 h
SiMe3
3i
10-TMS - 69% - 48% de 10-H - 11% - 26% de
Scheme 7 Diastereoselective deprotolithiation of ferrocenesulfon-
amides 3i and 3i-Me
In conclusion, although we proved possible the use of
DABSO to reach ferrocenesulfonamides, we focused our ef-
forts on the large-scale synthesis of ferrocenesulfonyl chlo-
ride using a more classical route. Furthermore, we have de-
scribed a new protocol for the synthesis of various ferroce-
nesulfonamides and identified its limitations in terms of
both amine and ferrocenesulfonyl chloride reactivity. Final-
ly, an example of diastereoselective deprotolithiation of chi-
ral ferrocenesulfonamides was described with moderate
IR (film): 817, 831, 889, 1003, 1015, 1031, 1109, 1141, 1203, 1371,
1395, 1413, 1734, 2234, 3113 cm–1
.
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–I

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Synthesis
1H NMR (500 MHz, CDCl3):  = 4.45 (s, 5 H, Cp), 4.60 (t, J = 1.75 Hz, 2
H, H3 and H4), 4.85 (t, J = 1.75 Hz, 2 H, H2 and H5).
13C NMR (126 MHz, CDCl3):  = 68.6 (2 × CH, C2 and C5), 71.9 (5 × CH,
dried (MgSO4), filtered over cotton wool, and concentrated under vac-
uum to give the product. This was purified by recrystallization from
heptane/CHCl3 to give the title product 3b as a yellow solid; yield:
6.93 g (91%); Rf = 0.50 (PE/EtOAc 70:30); mp 172 °C.
Cp), 72.3 (2 × CH, C3 and C4), 94.2 (C, C1, CSO2Cl).
IR (film): 655, 675, 701, 717, 754, 825, 845, 950, 1000, 1030, 1047,
1070, 1108, 1136, 1165, 1222, 1264, 1318, 1336, 1391, 1446, 1488,
Analytical data analogous to those reported previously.12
1580, 2849, 2960, 3057, 3418 cm–1
.
Ferrocenesulfonamides; General Procedure
1H NMR (300 MHz, CDCl3):  = 2.59 [s, 6 H, N(CH3)2], 4.39 (s, 2 H, H3
and H4), 4.41 (s, 5 H, Cp), 4.59 (s, 2 H, H2 and H5).
13C NMR (75 MHz, CDCl3):  = 38.0 [2 × CH3, N(CH3)2], 69.2 (2 × CH, C2
and C5), 70.7 (2 × CH, C3 and C4), 70.8 (5 × CH, Cp), 82.3 (C, C1,
CSO2NMe2).
The required amine (18.0 mmol, 3.00 equiv) was added dropwise to a
solution of compound 2 (1.70 g, 6.00 mmol, 1.00 equiv) in CHCl3 (1.2
or 2.4 mL) at 60 °C. After addition, the reaction mixture was stirred at
the same temperature for 30 min before being cooled to rt. Aq 1 M
HCl (20 mL) was added and the reaction mixture was extracted with
CH2Cl2. The combined organic layers were dried (MgSO4), filtered over
cotton wool, and concentrated under vacuum to give the product.
This was purified by column chromatography over silica gel, using
PE/EtOAc (proportions given for each product) to give the title prod-
uct.
Analytical data analogous to those reported previously.5c
(N-Morpholino)sulfonylferrocene (3c)30
[CAS Reg. No. 63453-44-1]
By following the general procedure, using morpholine (1.60 mL) and
CHCl3 (1.20 mL), 3c was obtained after column chromatography
(PE/EtOAc 50:50) as an orange solid; yield: 1.90 g (94%); Rf = 0.13
(PE/EtOAc 70:30); mp 208 °C.
(N-Pyrrolidino)sulfonylferrocene (3a)30
From Ferrocene by Using DABSO and SO2Cl2: tBuLi (1.5 M, 6.60 mL, 10.0
mmol, 2.00 equiv) was added dropwise to a solution of ferrocene (930
mg, 5.00 mmol, 1.00 equiv) and tBuOK (56.0 mg, 0.50 mmol, 0.10
equiv) in THF (45 mL) at –80 °C. After addition, the reaction mixture
was stirred at the same temperature for 1 h before being cannulated
onto a suspension of DABSO (2.60 g, 10.0 mmol, 2.20 equiv) in THF
(45 mL) at –40 °C. After addition, the mixture was stirred at –40 °C for
1h. SO2Cl2 (0.90 mL, 1.50 g, 10.0 mmol, 2.20 equiv) was added drop-
wise and the mixture was warmed to rt and stirred for 1 h. Pyrroli-
dine (4.20 mL, 3.60 g, 50.0 mmol, 10.0 equiv) was added dropwise
and the mixture was stirred at rt for 3 h. Aq 1 M HCl (1 M, 50 mL) was
added and the mixture was extracted with EtOAc. The combined or-
ganic layers were dried (MgSO4), filtered over cotton wool, and con-
centrated under vacuum to give the product. This was purified by col-
umn chromatography over silica gel using PE/EtOAc (80:20) to give
the product, which was recrystallized to give the title product 3a as a
yellow solid; yield: 658.0 mg (41%).
IR (film): 656, 719, 755, 819, 943, 959, 1002, 1046, 1077, 1112, 1148,
1188, 1246, 1259, 1327, 1340, 1412, 1453, 1719, 2860, 2901, 2960,
3104 cm–1
.
1H NMR (300 MHz, CDCl3):  = 2.90 (t, J = 4.7 Hz, 4 H, 2 × NCH2), 3.70
(t, J = 4.4 Hz, 4 H, 2 × OCH2), 4.42 (s, 7 H, H3, H4, and Cp), 4.56 (t, J =
1.65 Hz, 2 H, H2 and H5).
13C NMR (126 MHz, CDCl3):  = 46.0 (2 × CH2, NCH2), 66.1 (2 × CH2,
OCH2), 69.3 (2 × CH, C2 and C5), 70.9 (5 × CH, Cp), 71.0 (2 × CH, C3 and
C4), 82.2 (C, C1, CSO2N-morpholino).
Analytical data analogous to those reported previously.31
(N′-tert-Butoxycarbonyl-N-piperazino)sulfonylferrocene (3d)
By following the general procedure, a solution of N-Boc-piperazine
(3.35 g) in CHCl3 (1.20 mL) was added to compound 2 in CHCl3 (1.20
mL). Product 3d was obtained after column chromatography (PE/EtOAc
80:20 to 70:30) as a yellow solid; yield: 2.09 g (80%); Rf = 0.46
(PE/EtOAc 70:30); mp 194–196 °C.
From Ferrocenesulfonyl Chloride: By following the general procedure,
using pyrrolidine (1.50 mL) and CHCl3 (2.40 mL), 3a was obtained af-
ter column chromatography (PE/EtOAc, 50:50) as a yellow solid; yield:
1.81 g (95%); Rf = 0.25 (PE/EtOAc 70:30); mp 216 °C.
IR (film): 730, 768, 822, 859, 924, 999, 1018, 1054, 1093, 1126, 1146,
1166, 1188, 1251, 1284, 1307, 1323, 1348, 1362, 1391, 1426, 1453,
IR (film): 656, 718, 755, 818, 832, 944, 959, 1002, 1045, 1077, 1113,
1135, 1149, 1188, 1217, 1246, 1259, 1301, 1327, 1340, 1412, 1453,
1682, 2865, 2970 cm–1
.
2859, 2900, 2960, 3104 cm–1
.
1H NMR (500 MHz, CDCl3):  = 1.40 (s, 9 H, t-C4H9), 2.87 (t, J = 5.0 Hz, 4
H, 2 × CH2NSO2), 3.46 (t, J = 5.0 Hz, 4 H, 2 × CH2NBoc), 4.40 (t, J = 1.9
Hz, 2 H, H3 and H4), 4.41 (s, 5 H, Cp), 4.55 (t, J = 1.9 Hz, 2 H, H2 and
H5).
1H NMR (300 MHz, CDCl3):  = 1.67–1.72 (m, 4 H, 2 × NCH2CH2), 3.13
(t, J = 6.6 Hz, 4 H, 2 × NCH2CH2), 4.37 (t, J = 1.65 Hz, 2 H, H3 and H4),
4.40 (s, 5 H, Cp), 4.62 (t, J = 1.65 Hz, 2 H, H2 and H5).
13C NMR (75 MHz, CDCl3):  = 28.4 (3 × CH3, t-C4H9), 42.9 (2 × CH2,
CH2NBoc), 45.9 (2 × CH2, CH2CH2NBoc), 69.2 (2 × CH, C2 and C5), 70.9
(5 × CH, Cp), 71.0 (2 × CH, C3 and C4), 80.4 (C, CMe3), 82.5 (C, C1,
CSO2N).
13C NMR (75 MHz, CDCl3):  = 25.3 (2 × CH2, NCH2CH2), 48.0 (2 × CH2,
NCH2), 69.0 (2 × CH, C2 and C5), 70.6 (2 × CH, C3 and C4), 70.8 (5 CH,
Cp), 83.8 (C, C1, CSO2N-pyrrolidino).
N,N-Dimethylferrocenesulfonamide (3b)30
N,N-Diethylferrocenesulfonamide (3e)
[CAS Reg. No. 63453-42-9]
[CAS Reg. No. 63495-23-8]
A solution of NaOH (4.80 g, 120 mmol, 4.80 equiv) in H2O (20 mL) was
added to a solution of dimethylamine hydrochloride (10.2 g, 125
mmol, 5.00 equiv) in H2O (100 mL). The resulting aqueous solution of
Me2NH was added to a solution of compound 2 (7.33 g, 26.0 mmol,
1.00 equiv) in THF (150 mL) at rt. After addition, the reaction mixture
was stirred overnight at rt. Layers were separated and the aqueous
layer was extracted with EtOAc. The combined organic layers were
By following the general procedure, using Et2NH (1.90 mL) and CHCl3
(1.20 mL), 3e was obtained after column chromatography (PE/EtOAc
90:10; Rf = 0.30) as an orange solid; yield: 701 mg (36%); mp 88–89
°C.
IR (film): 796, 814, 928, 1017, 1067, 1105, 1134, 1182, 1324, 1336,
1356, 1383, 1412, 1467, 2937, 2979, 3108, 3684 cm–1
.
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–I

F
W. Erb et al.
PSP
Synthesis
1H NMR (500 MHz, CDCl3):  = 1.08 (t, J = 7.1 Hz, 6 H, 2 × CH2CH3), 3.10
(q, J = 7.1 Hz, 4 H, 2 × CH2Me), 4.34 (s, 2 H, H3 and H4), 4.40 (s, 5 H,
Cp), 4.59 (s, 2 H, H2 and H5).
13C NMR (126 MHz, CDCl3):  = 14.0 (2 × CH3, Et), 42.0 (2 × CH2, Et),
68.5 (2 × CH, C2 and C5), 70.2 (2 × CH, C3 and C4), 70.7 (5 × CH, Cp),
87.7 (C, C1, CSO2NEt2).
N-(4-Tolyl)ferrocenesulfonamide (3k)30
[CAS Reg. No. 115417-89-5]
By following the general procedure, a solution of p-toluidine (1.93 g)
in CHCl3 (1.20 mL) was added to compound 2 in CHCl3 (1.20 mL).
Product 3k was obtained after column chromatography (PE/EtOAc
90:10 to 80:20) as an orange solid; yield: 330 mg (15%); Rf = 0.17
(PE/EtOAc 90:10); mp 174–175 °C.
Analytical data analogous to those reported previously.15
IR (film): 773, 814, 889, 915, 1020, 1057, 1107, 1131, 1192, 1220,
N-Butylferrocenesulfonamide (3g)30
1278, 1299, 1326, 1392, 1457, 1508, 1614, 2988, 3236 cm–1
.
1H NMR (500 MHz, CDCl3):  = 2.28 (s, 3 H, CH3), 4.30 (t, J = 1.9 Hz, 2
H, H3 and H4), 4.37 (s, 5 H, Cp), 4.49 (t, J = 1.9 Hz, 2 H, H2 and H5),
6.32 (br s, 1 H, NH), 6.94 (d, J = 8.2 Hz, 2 H, H2′ and H6′), 7.04 (d, J = 8.2
Hz, 2 H, H3′ and H5′).
By following the general procedure, using BuNH2 (1.80 mL) and CHCl3
(1.20 mL), 3g was obtained after column chromatography (PE/EtOAc
80:20; Rf = 0.43) as an orange solid; yield: 1.82 g (94%); mp 102–103
°C.
13C NMR (126 MHz, CDCl3):  = 21.0 (CH3, ArCH3), 69.0 (2 × CH, C2 and
C5), 70.6 (2 × CH, C3 and C4), 70.9 (5 × CH, Cp), 86.8 (C, C1,
CSO2NHtolyl), 122.7 (2 × CH, C2′ and C6′), 129.9 (2 × CH, C3′ and C5′),
134.3 (C, C1′ or C4′), 135.4 (C, C1′ or C4′).
IR (film): 741, 819, 845, 866, 909, 980, 1000, 1021, 1055, 1083, 1108,
1116, 1144, 1190, 1225, 1260, 1320, 1336, 1391, 1413, 1426, 1467,
1659, 2872, 2953, 3253 cm–1
.
1H NMR (300 MHz, CDCl3):  = 0.85 (t, J = 7.3 Hz, 3 H, CH3), 1.28 (sext,
J = 7.2 Hz, 2 H, CH2Me), 1.41 (quint, J = 7.2 Hz, 2 H, CH2CH2Me), 2.91
[q, J = 6.8 Hz, 2 H,CH2(CH2)2Me], 4.06 (t, J = 6.2 Hz, 1 H, NH), 4.37 (t, J =
1.9 Hz, 2 H, H3 and H4), 4.40 (s, 5 H, Cp), 4.63 (t, J = 1.9 Hz, 2 H, H2
and H5).
13C NMR (126 MHz, CDCl3):  = 13.7 (CH3, Bu), 19.9 (CH2, CH2Me), 31.7
(CH2, CH2CH2Me), 43.1 [CH2, CH2(CH2)2Me], 68.7 (2 × CH, C2 and C5),
70.5 (2 × CH, C3 and C4), 70.9 (5 × CH, Cp), 87.8 (C, C1, CSO2NHBu).
Analytical data analogous to those reported previously.32
N,N,4-Trimethylbenzenesulfonamide (7)
[CAS Reg. No. 599-69-9]
A solution of Me2NH in THF (2 M, 15.0 mL, 30.0 mmol, 1.50 equiv)
was added to a solution of p-tosyl chloride (3.81 g, 20.0 mmol, 1.00
equiv) and Et3N (5.60 mL, 4.05 g, 40.0 mmol, 2.00 equiv) in THF (50
mL). After addition, the reaction mixture was stirred at rt for 1 h be-
fore volatiles were removed under vacuum. The residue was dissolved
in EtOAc and the organic phase was washed with 1 M aq HCl, sat. aq
NaHCO3, dried (MgSO4), filtered over cotton wool, and concentrated
under vacuum to give the title product 7 as a white solid; yield: 3.98 g
(quant); Rf = 0.33 (PE/EtOAc 80:20); mp 79–80 °C.
N-Isopropylferrocenesulfonamide (3h)30
By following the general procedure, using i-PrNH2 (1.60 mL) and
CHCl3 (1.20 mL), 3h was obtained after column chromatography
(PE/EtOAc 80:20; Rf = 0.35) as an orange solid; yield: 1.40 g (76%); mp
165–166 °C.
IR (film): 819, 879, 905, 1003, 1022, 1107, 1128, 1191, 1300, 1385,
IR (film): 721, 801, 814, 824, 954, 1054, 1091, 1159, 1188, 1264, 1290,
1435, 1463, 2959, 3236 cm–1
.
1309, 1332, 1381, 1455, 1472, 1596, 2875, 3037 cm–1
.
1H NMR (500 MHz, CDCl3):  = 1.05 [d, J = 6.1 Hz, 6 H, CH(CH3)2], 3.44
(oct, J = 6.1 Hz, 1 H, CHMe2), 4.07 (br d, J = 6.1 Hz, 1H, NH), 4.37 (s, 2 H,
H3 and H4), 4.39 (s, 5 H, Cp), 4.64 (s, 2 H, H2 and H5).
1H NMR (400 MHz, CDCl3):  = 2.43 (s, 3 H, ArCH3), 2.68 [s, 6 H,
N(CH3)2], 7.33 (d, J = 8.2 Hz, 2 H, H3 and H5), 7.65 (d, J = 8.2 Hz, 2 H,
H2 and H6).
13C NMR (126 MHz, CDCl3):  = 24.0 [2 × CH3, CH(CH3)2], 46.1 (CH,
CHMe2), 68.6 (2 × CH, C2 and C5), 70.5 (2 × CH, C3 and C4), 70.9 (5 ×
CH, Cp), 89.1 (C, C1, CSO2NHiPr).
13C NMR (100 MHz, CDCl3):  = 21.6 (CH3, ArCH3), 38.1 [2 × CH3,
N(CH3)2], 127.9 (2 × CH, C2 and C6), 129.7 (2 × CH, C3 and C5), 132.6
(C, C1, CSO2N), 143.6 (C, C4).
Analytical data analogous to those reported previously.33
(R)-N-(1-Phenylethyl)ferrocenesulfonamide (3i)
By following the general procedure, using (R)--methylbenzylamine
(2.30 mL) and CHCl3 (1.20 mL), 3i was obtained after column chroma-
tography (PE/EtOAc 80:20; Rf = 0.28) as an orange solid; yield: 981 mg
(44%). The reaction was also performed for 4 h starting from 12.0
mmol of compound 2; yield: 3.79 g (85%); mp 111–112 °C; []D +50.0
(c 0.01 in CHCl3).
N,N-Diethyl-4-methylbenzenesulfonamide (8)
[CAS Reg. No. 649-15-0]
By following the analogous procedure as above for 7, using Et2NH
(1.90 mL) and CHCl3 (1.20 mL), 8 was obtained after column chroma-
tography (PE/EtOAc 80:20 to 70:30) as a white solid; yield: 1.29 g
(95%); Rf = 0.49 (PE/EtOAc 80:20); mp 60–61 °C.
IR (film): 757, 783, 814, 836, 862, 920, 959, 1001, 1021, 1059, 1096,
1133, 1191, 1318, 1336, 1388, 1412, 1437, 1455, 1495, 1606, 2988,
IR (film): 713, 777, 815, 928, 1013, 1072, 1087, 1155, 1200, 1306,
1330, 1354, 1375, 1467, 1495, 1598, 2936, 2976 cm–1
.
3245 cm–1
.
1H NMR (400 MHz, CDCl3):  = 1.11 (t, J = 7.1 Hz, 6 H, 2 × CH2CH3), 2.40
(s, 3 H, ArCH3), 3.22 (q, J = 7.1 Hz, 4 H, CH2Me), 7.27 (d, J = 8.3 Hz, 2 H,
H3 and H5), 7.68 (d, J = 8.3 Hz, 2 H, H2 and H6).
13C NMR (100 MHz, CDCl3):  = 14.3 (2 × CH3, Et), 21.6 (CH3, ArCH3),
42.1 (2 × CH2, Et), 127.2 (2 × CH, C2 and C6), 129.7 (2 × CH, C3 and C5),
137.6 (C, C1, CSO2N), 143.0 (C, C4).
1H NMR (500 MHz, CDCl3):  = 1.41 (d, J = 6.6 Hz, 3 H, CH3), 4.24 (s, 1
H, H3 or H4), 4.30 (s, 1 H, H3 or H4), 4.36 (s, 5 H, Cp), 4.42 (s, 1 H, H2
or H5), 4.45 (quint, J = 6.6 Hz, 1 H, CHMe), 4.56 (s, 1 H, H2 or H5), 4.61
(d, J = 5.9 Hz, 1 H, NH), 7.14 (d, J = 7.5 Hz, 2 H, H2′ and H6′), 7.17–7.24
(m, 3 H, H3′, H4′, and H5′).
13C NMR (126 MHz, CDCl3):  = 23.8 (CH3, CHCH3), 53.6 (CH, CHMe),
68.4 (CH, C2 or C5), 69.0 (CH, C2 or C5), 70.4 (CH, C3 or C4), 70.5 (CH,
C3 or C4), 70.8 (5 × CH, Cp), 88.6 (C, C1, CSO2NHR), 126.3 (2 × CH, C2′
and C6′), 127.6 (CH, C4′), 128.6 (2 × CH, C3′ and C5′), 142.6 (C, C1′).
Analytical data analogous to those reported previously.34
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–I

G
W. Erb et al.
PSP
Synthesis
(R)-N-Methyl-N-(1-phenylethyl)ferrocenesulfonamide (3i-Me)
and 72.7* (CH, C4), 73.0 and 73.3* (C, C2, CSiMe3), 77.4 and 77.4* (CH,
C3), 93.5 and 93.5* (C, C1, CSO2N), 127.5* and 128.4* (5 × CH, C2′, C3′,
C4′, C5′ and C6′), 140.1* and 140.4 (CH, C1′).
NaH (60% in mineral oil, 651 mg, 15.0 mmol, 3.00 equiv) was added
portionwise to a solution of compound 3i (1.84 g, 5.00 mmol, 1.00
equiv) in anhyd THF (50 mL) under argon before being warmed to rt
and stirred for 1 h. The reaction mixture was cooled to 0 °C, then MeI
(965 L, 2.20 g, 15.0 mmol, 3.00 equiv) and DMF (10 mL) were added.
After addition, the reaction mixture was warmed to rt and stirred for
2 h. Sat aq NH4Cl was added dropwise to the reaction mixture, which
was then extracted with EtOAc. The combined organic layers were
washed with H2O, brine, dried (MgSO4), filtered over cotton wool, and
concentrated under vacuum to give the crude product. This was puri-
fied by column chromatography over silica gel using PE/EtOAc (80:20)
to give the title product 3i-Me as an orange solid; yield: 1.75 g (91%);
Rf = 0.59 (PE/EtOAc 80:20); mp 128–129 °C; []D +56.3 (c 0.01 in
CHCl3).
(R)-N-(1-Phenylethyl)-N,2-bis(trimethylsilyl)ferrocenesulfon-
amide (10-TMS) and (R)-N-(1-Phenylethyl)-2-(trimethylsilyl)-
ferrocenesulfonamide (10-H)
10-TMS
nBuLi (1.4 M, 2.60 mL, 3.60 mmol, 3.00 equiv) was added dropwise to
a solution of 3i (443 mg, 1.20 mmol, 1.00 equiv) in anhyd THF (8 mL)
at –80 °C under argon. After addition, the reaction mixture was
stirred at the same temperature for 1 h before Me3SiCl (457 L, 391
mg, 3.60 mmol, 3.00 equiv) was added. After addition, the reaction
mixture was warmed to rt and stirred for a further 15 min. Sat. aq
NH4Cl was added dropwise to the mixture, which was then extracted
with EtOAc. The combined organic layers were washed brine, dried
(MgSO4), filtered over cotton wool, and concentrated under vacuum
to give the crude product. This was purified by column chromatogra-
phy over silica gel using PE/EtOAc (15:1). The title product 10-TMS
(2.8:1 diastereoisomeric mixture) was isolated as an orange solid;
yield: 427 mg (69%); 48% de; Rf = 0.66 (PE/EtOAc 15:1); mp 127–130
°C; []D +111.2 (c 0.01 in CHCl3).
IR (film): 709, 767, 785, 827, 893, 913, 979, 1018, 1028, 1046, 1107,
1126, 1154, 1188, 1325, 1336, 1381, 1413, 1455, 2982, 3101 cm–1
.
1H NMR (500 MHz, CDCl3):  = 1.28 (d, J = 7.0 Hz, 3 H,CHCH3), 2.47 (s,
3 H, NCH3), 4.37–4.39 (m, 2 H, H3 and H4), 4.43 (s, 5 H, Cp), 4.62
(quint, J = 1.2 Hz, 1 H, H2 or H5), 4.65 (quint, J = 1.2 Hz, 1 H, H2 or H5),
5.16 (q, J = 7.0 Hz, 1 H, CHMe), 7.23–7.25 (m, 1 H, H4′), 7.28–7.31 (m,
4 H, H2′, H3′, H5′, and H6′).
13C NMR (126 MHz, CDCl3):  = 15.2 (CH3, CH3CHPh), 28.3 (CH3, NCH3),
54.9 (CH, CHMe), 68.6 (CH, C2 or C5), 68.7 (CH, C2 or C5), 70.4 (CH, C3
or C4), 70.5 (CH, C3 or C4), 70.9 (5 × CH, Cp), 87.8 (C, C1, CSO2N),
127.4 (2 × CH, C2′ and C6′), 127.5 (CH, C4′), 128.4 (2 × CH, C3′ and C5′),
140.4 (C, C1′).
IR (film): 750, 784, 822, 837, 907, 970, 1003, 1025, 1042, 1068, 1101,
1122, 1136, 1190, 1245, 1281, 1315, 1381, 1410, 1448, 1498, 2956
cm–1
.
In the NMR description below, * is used to spot the signals of the mi-
nor diastereoisomer.
1H NMR (500 MHz, CDCl3):  = 0.11* and 0.14 [s, 9 H, NSi(CH3)3], 0.30*
and 0.31 [s, 9 H, FcSi(CH3)3], 1.17 and 1.73* (d, J = 7.2 Hz, and d, J = 6.9
Hz, 3 H, respectively, CHCH3), 4.28* and 4.33 (dd, J = 2.4, 1.4 Hz, 1 H,
H3), 4.42* and 4.42 (s, 5 H, Cp), 4.55 and 4.57* (t, J = 2.4 Hz, 1 H, H4),
4.59* and 4.69 (q, J = 6.9 Hz, and q, J = 7.2 Hz, 1 H, respectively;
CHMe), 4.79 and 4.92* (dd, J = 2.4, 1.4 Hz, and dd, J = 2.3, 1.4 Hz, 1 H,
respectively, H5), 7.01* and 7.48 (d, J = 7.5 Hz and d, J = 8.1 Hz, 2 H,
respectively, H2′ and H6′), 7.10–7.12* and 7.30 (m and t, J = 7.5 Hz, 2
H, respectively, H3′ and H5′), 7.10–7.12* and 7.22 (m and t, J = 7.5 Hz,
1 H, respectively, H4′).
13C NMR (126 MHz, CDCl3):  = 1.1* and 1.1 [3 × CH3, FcSi(CH3)3], 3.1*
and 3.2 [3 × CH3, NSi(CH3)3], 18.3 and 20.2* (CH3, CH3CHPh), 53.7 and
54.0* (CH, CHMe), 70.9 and 71.0* (5 × CH, Cp), 72.1 and 72.2* (CH, C5),
72.9* and 72.9 (CH, C4), 75.1 and 75.3 (C, C2, CSiMe3), 77.0 and 77.3*
(CH, C3), 94.2* and 94.8 (C, C1, CSO2N), 126.7* and 127.2 (2 × CH, C2′
and C6′), 126.8* and 127.0 (CH, C4′), 128.1* and 128.2 (C3′ and C5′),
142.3 and 142.6* (C, C1′).
(R)-N-Methyl-N-(1-phenylethyl)-2-(trimethylsilyl)ferrocenesul-
fonamide (9)30
nBuLi (1.4 M, 1.30 mL, 1.80 mmol, 1.50 equiv) was added dropwise to
a solution of 3i-Me (460 mg, 1.20 mmol, 1.00 equiv) in anhyd THF (6
mL) at –80 °C under argon. After addition, the reaction mixture was
stirred at the same temperature for 1 h before Me3SiCl (228 L, 195
mg, 1.8 mmol, 1.50 equiv) was added. After addition, the mixture was
warmed to rt and stirred for a further 15 min. Sat. aq NH4Cl was add-
ed dropwise to the mixture, which was then extracted with EtOAc.
The combined organic layers were washed with brine, dried (MgSO4),
filtered over cotton wool, and concentrated under vacuum to give the
crude product. This was purified by column chromatography over sil-
iac gel using PE/EtOAc (10:1) to give the title product 9 (3.2:1 diaste-
reoisomeric mixture) as an orange solid; yield: 345 mg (63%); 52% de;
Rf = 0.70 (PE/EtOAc 10:1); mp 90–92 °C;[]D +136.6 (c 0.01 in CHCl3).
IR (film): 713, 760, 784, 827, 858, 929, 957, 988, 1029, 1046, 1109,
1125, 1139, 1167, 1189, 1243, 1280, 1312, 1329, 1357, 1385, 1414,
1450, 1498, 1686, 2948, 3092 cm–1
.
10-H
In the NMR description below, * is used to spot the signals of the mi-
nor diastereoisomer.
The title product 10-H (1.7:1 diastereoisomeric mixture) was similar-
ly isolated as an orange oil; yield: 59.0 mg (11%); 26% de; Rf = 0.15
(PE/EtOAc 15:1); []D +43.7 (c 0.01 in CHCl3).
1H NMR (500 MHz, CDCl3):  = 0.36 and 0.37* [s, 9 H, FcSi(CH3)3], 1.25
and 1.42* (d, J = 7.1 Hz, and d, J = 6.9 Hz, 3 H, respectively; CHCH3),
2.46* and 2.51 (s, 3 H, NCH3), 4.32–4.33* (m, 1 H, H3), 4.40* and 4.41
(s, 5 H, Cp), 4.53* and 4.54 (t, J = 2.4 Hz, 1 H, H4), 4.81* and 4.82 (dd,
J = 2.3, 1.4 Hz, and dd, J = 2.2, 1.5 Hz, 1 H, respectively; H5), 5.13 and
5.18* (q, J = 7.1 Hz, and q, J = 6.9 Hz, 1 H, respectively; CHMe), 7.23–
7.31* (m, 5 H, H2′, H3′, H4′, H5’, and H6′).
13C NMR (126 MHz, CDCl3):  = 1.1 and 1.2* [3 × CH3, Si(CH3)3], 15.0
and 16.0* (CH3, CH3CHPh), 28.4 and 28.6* (CH3, NCH3), 54.2 and 54.6*
(CH, CHMe), 70.9 and 71.0* (5 × CH, Cp), 72.3 and 72.5* (CH, C5), 72.6
IR (film): 731, 755, 782, 822, 910, 948, 966, 1002, 1041, 1068, 1084,
1108, 1119, 1147, 1191, 1245, 1319, 1377, 1411, 1455, 1495, 1605,
2955, 3274 cm–1
.
In the NMR description below, * is used to spot the signals of the mi-
nor diastereoisomer.
1H NMR (500 MHz, CDCl3):  = 0.28 and 0.37* [s, 9 H, FcSi(CH3)3],
1.29* and 1.46 (d, J = 6.9 Hz, and d, J = 6.7 Hz, 3 H, respectively;
CHCH3), 4.23 and 4.33–4.34* (dd, J = 2.4, 1.4 Hz, and m, 1 H, respec-
tively, H3), 4.34 and 4.38* (s, 5 H, Cp), 4.41* and 4.46 (quint, J = 7.3 Hz,
and quint, J = 6.7 Hz, 1 H, respectively; CHMe), 4.33–4.34 and 4.50* (m
© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–I

H
W. Erb et al.
PSP
Synthesis
and t, J = 2.4 Hz, 1 H, respectively, H4), 4.58 and 4.81* (dd, J = 2.3, 1.5
Hz, and dd, J = 2.2, 1.4 Hz, 1 H, respectively, H5), 7.00–7.02 and 7.22–
7.25* (m, 2 H, H2′ and H6′), 7.15–7.19 and 7.22–7.25* (m, 1 H, H4′),
7.15–7.19 and 7.28–7.32* (m, 2 H, H3′ and H5′).
13C NMR (126 MHz, CDCl3):  = 0.8 and 1.0* [3 × CH3, FcSi(CH3)3], 23.2*
and 24.0 (CH3, CH3CHPh), 53.2* and 53.6 (CH, CHMe), 70.8 and 70.9*
(5 × CH, Cp), 71.8 and 72.2* (CH, C4), 71.8 and 72.4* (C, C2, CSiMe3),
73.6* and 73.8 (CH, C5), 77.8 and 77.9* (CH, C3), 92.6 and 92.9* (C, C1,
CSO2N), 126.3 and 126.3* (2 × CH, C2′ and C6′), 127.6 and 127.6* (CH,
C4′), 128.6 and 128.7* (C3′ and C5′), 142.4 and 142.9* (C, C1′).
Pleixats, R.; Moreno-Mañas, M.; Parella, T.; Benet-Buchholz, J.
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Conflict of Interest
The authors declare no conflict of interest.
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Chem. 1985, 292, 269.
Funding Information
(10) (a) Besenyei, G.; Párkányi, L.; Németh, S.; Simándi, L. I.
J. Organomet. Chem. 1998, 563, 81. (b) Li, M.; Bai, Y.; Lu, J.; Yang,
B.; Zhu, K.; Ma, H. J. Organomet. Chem. 2001, 637–639, 738.
(c) Yang, Y. T.; Yang, B. Q.; Li, M.; Ning, W.; Lu, Z. H. Synth.
Commun. 2008, 38, 530. (d) Yue, K.; Zhuo, F.; Zhai, G.; Hou, L.;
Hou, Y.; Yin, B.; Wang, Y. Chin. J. Chem. 2011, 29, 223.
(e) Chanawanno, K.; Holstrom, C.; Crandall, L. A.; Dodge, H.;
Nemykin, V. N.; Herrick, R. S.; Ziegler, C. J. Dalton Trans. 2016,
45, 14320. (f) Chanawanno, K.; Holstrom, C.; Nemykin, V. N.;
Herrick, R. S.; Ziegler, C. J. ChemistrySelect 2016, 1, 6438.
(g) Chanawanno, K.; Blesener, T. S.; Schrage, B. R.; Nemykin, V.
N.; Herrick, R. S.; Ziegler, C. J. J. Organomet. Chem. 2018, 870,
121.
This work was supported by the Agence Nationale de la Recherche
(Ferrodance project) and the Université de Rennes 1.
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Acknowledgment
We thank Rennes Métropole and the Fonds Européen de Développe-
ment Régional (FEDER; D8 VENTURE Bruker AXS diffractometer).
Supporting Information
Supporting information for this article is available online at
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https://doi.org/10.1055/a-1478-7002.
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© 2021. Thieme. All rights reserved. Synthesis 2021, 53, A–I