Synthesis of Chiral-Substituted 2-Aryl-ferrocenes by the Catellani Reaction

Article abstract of DOI:10.1021/acs.joc.0c01360

A palladium-catalyzed and norbornene-mediated methodology has been developed for the synthesis of chiral 2-aryl-ferroceneamides from chiral 2-iodo-N,N-diisopropylferrocencarboxamide, iodoarenes, and alkenes using a JohnPhos ligand and potassium carbonate as a base in dimethylformamide at 105 °C. The developed three-component coupling protocol allows the compatibility of electron-withdrawing fluoro, chloro, ester, and nitro and electron-donating methyl, methoxy, dimethoxy, benzyl ether-substituted iodo-benzenes, other iodoarenes, such as iodo-naphthalene, heteroarenes, such as iodothiophene, and terminating substrates, such as methyl, ethyl, tert-butyl acrylates, and substituted styrenes with 2-iodo-N,N-diisopropylferrocencarboxamide. Furthermore, the developed three-component Catellani method proceeded with the retention of the configuration of the planar chiral ferrocene, which depends on the role of the participating carbon-iodine bond in ferrocene. Consequently, the developed protocol enabled the formation of densely substituted chiral 2-aryl ferroceneamides, exhibiting good to excellent enantioselectivity. The conversion of an ester of the synthesized chiral 2-aryl ferroceneamides has also been carried out to further accommodate the easily expendable acid and alcohol functionalities.

Full text of DOI:10.1021/acs.joc.0c01360

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Synthesis of Chiral-Substituted 2‑Aryl-ferrocenes by the Catellani
Reaction
Raviraj Ananda Thorat, Saket Jain, Moh. Sattar, Prateek Yadav, Yogesh Mandhar, and Sangit Kumar*
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ABSTRACT: A palladium-catalyzed and norbornene-mediated methodology has been developed for the synthesis of chiral 2-aryl-
ferroceneamides from chiral 2-iodo-N,N-diisopropylferrocencarboxamide, iodoarenes, and alkenes using a JohnPhos ligand and
potassium carbonate as a base in dimethylformamide at 105 °C. The developed three-component coupling protocol allows the
compatibility of electron-withdrawing fluoro, chloro, ester, and nitro and electron-donating methyl, methoxy, dimethoxy, benzyl
ether-substituted iodo-benzenes, other iodoarenes, such as iodo-naphthalene, heteroarenes, such as iodothiophene, and terminating
substrates, such as methyl, ethyl, tert-butyl acrylates, and substituted styrenes with 2-iodo-N,N-diisopropylferrocencarboxamide.
Furthermore, the developed three-component Catellani method proceeded with the retention of the configuration of the planar
chiral ferrocene, which depends on the role of the participating carbon−iodine bond in ferrocene. Consequently, the developed
protocol enabled the formation of densely substituted chiral 2-aryl ferroceneamides, exhibiting good to excellent enantioselectivity.
The conversion of an ester of the synthesized chiral 2-aryl ferroceneamides has also been carried out to further accommodate the
easily expendable acid and alcohol functionalities.
enantioselective or diastereoselective ortho-metalation strat-
egies are widely used to generate chiral ortho-substituted
ferrocenes (vide supra).10−12 Nonetheless, quenching of
diversely substituted electrophiles, particularly with OH,
CO2Et, and CO2H functionalities with in situ generated chiral
carbanion of ferrocene, is difficult because of the preferential
reaction of carbanion with an acidic proton of alcohol and acid
groups present in the electrophiles. Recently, transition-metal
(TM)-catalyzed enantioselective arylation of ferrocenes has
also been developed using aryl boronic acids. Despite this,
diversely substituted boronic acids are neither available nor
accessible.12a−d
INTRODUCTION
■
Ferrocene and its derivatives are ubiquitous because of their
fascinating structural properties in organometallic chemistry.1
Chiral ferrocene has gained a great deal of interest in various
fields such as organometallic chemistry, asymmetric synthesis,
and catalysis, as it possesses planar chirality.2 As a matter of
fact, it is one of the most stable organometallic compounds
with a unique sandwich structure; consequently, it has
applications not only in academia but also in industry, namely,
Josiphos ligand is being used for asymmetric hydrogenation of
alkenes at a large scale.3 Therefore, new approaches have been
developed by Ugi,4 Hayashi,5 Snieckus,6 Richards,7 and
Uemura8 to synthesize having planar chirality ferrocenes.
Chiral biaryls possess numerous applications as chiral
auxiliaries, such as binaphthyl in enantioselective synthesis,
privileged ligands, and promising materials (e.g., liquid
crystals). Also, this chiral unit exists in a diverse range of
natural products, bioactive materials, and drugs, namely,
vancomycin, korupensamin, and steganacin.9
In 1997, Catellani discovered a new reaction in which the
double functionalization of iodoarenes has been achieved using
the palladium−norbornene (NBE) catalyst for the synthesis of
Received: June 8, 2020
In order to have the desired properties in biaryls, diverse
functionalizations such as the presence of ester, alcohol, and
acid are necessary for the target molecules. Generally,
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Scheme 1. Double Functionalization of Arenes by the Catellani Reaction
a
Table 1. Optimization of the Reaction Conditions
a
The reaction was performed on 0.1 mmol scale using 2-iodoferroceneamide 1 (0.1 mmol), 2-iodotoluene 2a (0.1 mmol), Pd(OAc)2 (0.01 mmol),
b
JohnPhos (0.02 mmol), NBE (0.1 mmol), and K2CO3 (0.24 mmol) in anhydrous DMF (3 mL) under a N2 atmosphere. N2-cocatalyst was used
c
d
in-place of NBE. N3 norbornadiene was used in-place of NBE. Chiral substrate 1 (97% ee) was employed.
densely substituted biaryls.13 It utilizes a cooperative strategy
between palladium and NBE to facilitate sequential C−H bond
functionalization of ortho and ipso substitution in aryl halides,
bromides, iodides, and boronic acids (Scheme 1, lower
reaction sequence). The precise formation of the aryl-NBE
palladacycle (ANP) intermediate is the key step in a Catellani
reaction, followed by coupling with an electrophile and a
nucleophile, afforded ortho- and ipso-functionalized arenes,
respectively.14 Consequently, the Catellani reaction has been
extended to a wide variety of substrates.15−22
Inspired by the above finding, we were curious to see the
compatibility of ferrocene under the Catellani reaction and
further studied the fate of chiral aryl iodide substrates, which
could racemize during the course of the reaction. Recently, our
B
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Table 2. Substrate Scope: Synthesis of Chiral Aryl Ferroceneamides
group has investigated various C−H bond functionalization
reactions, and one of the ongoing research is the functionaliza-
tion of ferrocene, in which the C−H bond functionalization
has been achieved using various TM catalysts for carbon−
carbon and carbon−chalcogen bond formation.23,24 However,
the synthesis of diversely substituted chiral-aryl ferrocenes has
not been established by us and others. Herein, we report a
palladium-catalyzed and NBE-assisted Catellani reaction for
the synthesis of chiral 2-aryl ferroceneamides (Scheme 1).
terminating agent in the presence of the palladium catalyst and
NBE N1 mediator by using cesium carbonate as a base in
dimethylformamide (DMF). Unfortunately, the desired C−C
coupled ferroceneamide 3a could not be observed (entry 1,
Table 1). Similarly, changes in the solvent to CH3CN failed to
afford any desired C−C coupled product 3a (entry 2, Table 1).
The use of a mild base potassium carbonate afforded a good
yield (79%) of the C−C coupled ferroceneamide 3a (entry 3,
Table 1). Screening of solvents, namely, dimethylacetamide,
toluene, tetrahydrofuran (THF), and CH3CN in the presence
of potassium carbonate, could not further improve the yield of
3a (entries 4−7, Table 1). Next, various ligands in place of
triphenylphosphine were explored under the reaction con-
ditions. Nitrogen-donor pyridine and trimethyl pyridine L1
RESULTS AND DISCUSSION
■
For the optimization of the reaction conditions, racemic N,N-
diisopropyl-2-iodoferroeneamide 1 was chosen as the coupling
partner with 2-iodotoluene 2a and methyl acrylate as a
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Table 3. Substrate Scope with Regards to Alkenes
and L2 were ineffective and afforded poor yields 22 and 27% of
3a, respectively (entries 8 and 9, Table 1).
purity of the crystal as the Flack parameter is close to zero
(0.016). The absolute configuration of chiral 2-substituted
ferroceneamides is assigned based on the absolute config-
uration of the molecules in the crystal structure of 3b.
Gratifyingly, the sterically hindered JohnPhos L3 ligand
improved the yield of 3a by 13% from 79 to 92% (entry 10 vs
entry 3, Table 1). Next, NBE derivates:25 N2 and
norbornadiene N3 were tested instead of NBE N1. However,
low yields of 3a were realized (entries 11 and 12, Table 1).
After a screening of bases, solvents, ligands, and cocatalysts, we
tested chiral 2-iodoferroceneamide substrate 1 under the
optimized reaction conditions (entry 10), which resulted in 3a
in the same yield with excellent enantioselectivity (98% ee,
entry 13, Table 1). The procedure for the preparation of chiral
2-iodoferroceneamide was also modified because of the
scarcity of the (−)-sparteine chiral base, which is required
for the enantioselective deprotonation of ferroceneamide by n-
butyl lithium.6a It has been observed that one equiv of
(−)-sparteine with an excess of n-butyl lithium (4 equiv) is
equally effective to generate chiral 2-lithium ferroceneamide
anion enantioselectively, as its quenching with iodine afforded
chiral 2-iodoferroceneamide 1 in good yield (77%) and ee
(97%). Further, (−)-sparteine has been separated from the
reaction mixture and could be reused for the enantioselective
ortho-lithiation reaction in a precedent manner as described by
Snieckus and co-workers.6a Consequently, chiral 2-iodoferro-
ceneamide 1 was generated in a gram quantity for the Catellani
reaction by using a small quantity of (−)-sparteine.
Further, the substrate scope was explored with regards to
various aryl iodides (Table 2). Electron-donating 2-methyl, 2-
methoxy, 2,4-dimethoxy, 2-benzylmethoxy, and 2-benzylphe-
noxy-phenyl iodides coupled smoothly with chiral 2-
iodoferroceneamide 1 under palladium-catalyzed and NBE-
mediated systems and afforded respective 2-acrylate-substi-
tuted phenyl ferroceneamides 3a, 3b, 3d, 3e, and 3j in (70−
92%) yields with high ee (92−98%). 2-Acrylate-substituted
phenyl ferroceneamide 3b has also been obtained in 72% yield
when the reaction was carried out at the gram scale. The
structure of 2-aryl ferroceneamide 3b is also studied by single-
crystal X-ray crystallography (Figure S124, page S125). A unit
cell of 3b contains four molecules, having the same chiral
configuration and thus crystallize in the chiral space group
P212121. Further, the crystal study suggests the enantiomeric
Dimethylamine-substituted phenyl iodide coupled poorly
with 2-iodoferroceneamide, and only 16% yield of expected
aryl-amide 3g was realized yet high ee (94%) was noticed. We
have also shown that 3-methyl-phenyl iodide could be coupled
with 2-iodoferroceneamide 1 to afford mono-coupled 2-tolyl-
ferrocenenamide 3n in a comparatively low yield (68 vs 92%
for 3a), and this could be because of the steric effect of the
methyl substituent. Electron-withdrawing chloro, chloro-
fluoro, and ester-substituted 2-iodobenzene also coupled with
ferroceneamide, albeit moderate yields (31, 67, and 37%) of
coupled 2-arylferroceneamide 3g, 3l, and 3h, respectively, were
obtained. Desirably, erosion in ee was not observed as ee
remains unchanged for 3g, 3l, and 3h. Electron-withdrawing 2-
nitro-substituted iodobenzene failed to provide any three-
component coupled product when methyl and tert-butyl
acrylates were used as a terminating substrate. Next, another
aromatic 1-naphthyl iodide and heteroaromatic 2-iodothio-
phene also underwent three component couplings to enable 2-
naphthyl and 2-thiophenyl ferroceneamides 3c and 3o in 79
and 68% yields, respectively. Different acrylates were also
explored under the Catellani reaction of 2-iodoferrocenea-
mides. The reaction was observed to be equally effective for
ethyl acrylate and tert-butyl acrylates, after exploring various
iodoarenes as terminating substrates, which afforded nearly
unchanged yields (72 and 78%) and ee (97 and 97%) of the
respective 2-aryl ferroceneamides 3i and 3k.
Interestingly, the optimized Pd and NBE combination is also
compatible with styrenes as terminating substrates (Table 3).
Gratifyingly, styrene reacted with 2-iodoferroceneamide and 2-
iodotoluene quantitatively under the multicomponent Cat-
ellani reaction and yielded styrene coupled product 3m in 76%
yield. Next, various substituted styrenes were reacted as the
terminated substrate under the reaction conditions. Styrene,
para-nitrostyrene, and phenyl diene coupled smoothly with the
2-iodoferroceneamide and various phenyl iodides to afford the
desired tri-coupled products 3p−3u in 60−74% yields,
respectively. It is observed that the reaction with styrenes is
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Scheme 2. Conversion of Ester to Acid and Alcohols
Scheme 3. Plausible Catalytic Cycle
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more facile in comparison to acrylates presumably due to ester
functionality, which could coordinate with the Pd catalyst and
may hinder the reactivity. Further, styrene coupled products
are crystalline solid, easy to process and purify by
crystallization. Moreover, 2-iodo-nitrobenzene was also
successfully coupled, which could not be coupled in the
presence of methyl and tert-butyl acrylate-terminating sub-
strates, with 2-iodoferroceneamide forming nitrophenyl
ferroceneamide 3t when styrene was used as a terminating
substrate.
Next, we sought for the conversion of ester to alcohol easily
expendable groups, which are desirable for late-stage trans-
formations (Scheme 2). Basic treatment of 3c with basic
aqueous and ethanolic solution at room temperature afforded
the conversion of ester to acid 4a (70% yield). The reduction
of ester 3c into aldehyde functionality failed despite a repeated
attempt by varying the stoichiometry of diisobutylaluminum
hydride (DIBAL-H) and lowering the reaction temperature.
Instead, the exclusive formation of alcohol 4b was realized.
After transforming, ester into acid and alcohol functional
groups, we also sought for the removal of the N,N-diisopropyl
amide group. Our attempts to remove the diisopropyl amide
group by our earlier applied standard Schwartz’s reagent26
were unsuccessful, and either the substrate was recovered from
the reaction or ester functionality present in 3c was converted
into alcohol 4b (72% yield, Scheme 2).
The tentative mechanism of the reaction is depicted in
Scheme 3. Pd coordinates with the JohnPhos ligand to form
PdLn complex A, which undergoes oxidative addition with
iodotoluene to afford PdII complex B. Further, the π-
coordination of NBE with PdII complex B followed by the
insertion of NBE afforded the PdII intermediate C.
Deprotonation of ortho-hydrogen in the presence of potassium
carbonate and subsequent removal of iodide provided ANP
intermediate D. Subsequently, the oxidative addition of chiral
ferroceneamide iodide to ANP enables PdIV complex E.27
Reductive elimination gave the desired aryl-ferrocene carbon−
carbon bond formation. Next, β-carbon elimination leads to
the expulsion of NBE, and the construction of the Pd−carbon
bond at the ipso position provides complex G. Finally,
quenching with acrylates or alkenes by the Heck coupling
reaction formed chiral aryl-ferroceneamide 3a with concom-
itant release of the Pd0 catalyst.28
GENERAL EXPERIMENTAL DETAILS
■
All NMR experiments were carried out on a Bruker 500 MHz
spectrometer in CDCl3. The NMR chemical shift is reported in ppm
referenced to the solvent peaks of CDCl3 (7.26 ppm for H and 77
1
ppm for 13C). The following abbreviations were used to indicate
multiplicity: s (singlet), d (doublet), t (triplet), q (quartet), dd
(doublet of doublet), td (triplet of doublet), and m (multiplate).
High-resolution mass spectroscopic (HRMS) analysis is performed on
a quadrupole time flight microTOF-Q II mass spectrometer equipped
with an electrospray ionization (ESI) and atmospheric pressure
chemical ionization source. Gas chromatography−mass spectrometry
analysis is performed on a MS-S975C inert XLEI/CIMSD with a
triple-axis detector. IR spectra of the synthesized compounds
recorded on a Fourier transform infrared spectrophotometer. Single-
crystal X-ray data for compounds 3b (CCDC 1965471) were
collected on a diffractometer equipped with a CMOS Photon 100
detector and Mo Kα (λ = 0.71073 c5) radiation. Thin-layer
chromatography (TLC) plates (silica gel) used for monitoring the
reactions were purchased. Reagents were purchased from Sigma-
Aldrich and Alfa Aesar. Solvents were dried over calcium hydride and
sodium metal. N,N-Diisopropylferroceneamide6a were prepared by
following the literature procedure. Melting points were recorded on a
digital melting point apparatus. All reactions were performed in a dry
environment under an inert atmosphere of nitrogen using a Schlenk
tube and septa. Chiral analysis were carried out using high-
performance liquid chromatography (HPLC), CHIRALCELL OD-
3, AD-3, IC-3, and AD-H chiral HPLC column.
Synthesis of N,N-Diisopropylferroceneamide (1a).6a To the
solid suspension of ferrocene carboxylic acid (670 mg, 2.90 mmol),
oxalyl chloride (2.2 mL, 17.4 mmol) was added via a syringe at room
temperature under nitrogen inside the hood. Gas evolution was
accompanied by the formation of a dark red colored homogenous
solution. After 30 min, oxalyl was removed under vacuo. The resultant
crude ferrocenoyl chloride was isolated as red oil that crystallized on
standing, dissolved in CH2Cl2 (20 mL), and cooled to 0 °C. To this, a
solution of diisopropylamine (2.0 mL, 14.53 mmol) and triethylamine
(2.0 mL, 14.5 mmol) was added dropwise over 15 min under nitrogen
at 0 °C. The mixture was stirred overnight from 0 °C to room
temperature. The dark red colored reaction mixture was washed with
water (50 mL × 2), extracted with CH2Cl2 (50 mL × 2), dried over
Na2SO4, and concentrated under vacuum. The crude product was
dissolved in hexane and filtered to give ferroceneamide 1a as an
1
orange-brown solid. Yield 720 mg (79.3%), H NMR (500 MHz,
CDCl3): δ 4.59 (t, J = 2.1 Hz, 2H), 4.29 (t, J = 2.0 Hz, 2H), 4.26 (s,
5H), 1.68 (br s, 2H), 1.56−1.21 (m, 12H). 13C{1H} NMR (126
MHz, CDCl3): δ 169.4, 81.3, 72.7, 70.8, 70.2, 69.9, 69.7, 68.8, 22.2.
HRMS (ESI-TOF) m/z: [M + H]+ calcd for C17H24FeNO, 314.1202;
found, 314.1222.
CONCLUSIONS
Synthesis of Chiral N,N-Diisopropyl-2-iodoferroceneamide
(1).6a Freshly distilled (−)-sparteine (320 μL, 1.2 mmol) was
dissolved in Et2O (8 mL) in a single neck flask under N2 and cooled
to −78 °C. n-BuLi (2.8 mL, 4.6 mmol, 1.6 M solution in hexane) was
added dropwise to the sparteine solution. After 15 min of stirring at
−78 °C, ferroceneamide (360 mg, 1.1 mmol in 10 mL of Et2O) was
(10 mL) was added dropwise to the solution by a cannula. The
resulted reaction mixture was stirred for 1 h at −78 °C under N2.
After this, iodine (1.6 g, 6.3 mmol) in dry THF (10 mL) was added
by a syringe to the reaction mixture at −78 °C. The resulted reaction
mixture was stirred for 30 min and then slowly raised to room
temperature, and stirred for another 1 h at room temperature. After
completion of the reaction, the mixture was poured into a saturated
sodium thiosulfate solution (20 mL), the organic layer extracted with
Et2O (30 mL × 3), and concentrated under vacuo to afford crude 2-
iodoferroceneamide. The basification of aqueous layer was made by
adding 2 N NaOH aqueous solution (20 mL) and extracted with
diethyl ether (10 mL × 3), a standard workup afforded crude
(−)-sparteine, 230 μL recovery. 2-Iodoferroceneamide was purified
with column chromatography with hexane/ethyl acetate (90:10) to
obtain a orange solid 330 mg (65.3%), [α]2D5 = +85 (CHCl3, c = 0.9).
■
In summary, densely substituted 2-aryl-ferrocene compounds
were constructed in a pure enantiomeric form by exploiting
multicomponent Catellani reaction conditions. We have also
shown that planar chirality possessing ferrocenyl iodide can be
utilized in the Catellani multicomponent reaction without
erosion in planar chirality. Furthermore, aryl-ferroceneamides
are observed to retain their chirality in the solution for a long
period (60 days) of time, as aryl-ferroceneamides are
crystallized in a pure enantiomeric form. Chiral aryl-
ferroceneamides have also converted into acid and alcohol
functionalities, and hence, they are easily manipulatable for
further derivatization at a later stage. Overall, the developed
strategy provides access to various acid-, ester-, alcohol-, nitro-,
heteroaryl-, and alkene-substituted 2-aryl ferroceneamides with
high enantiomeric purity, which are not possible to construct
by conventional methodologies. Currently, efforts are being
made to develop chiral ferrocene catalysts for enantioselective
organic transformations and will be presented in the future.
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1H NMR (500 MHz, CDCl3): δ 4.46 (dd, J = 2.4, 1.3 Hz, 1H), 4.38
enantiomeric excess (94% ee) was observed using the CHIRALCELL
OD-3 chiral HPLC column with 2-propanol/hexane (1.5:98.5). X-ray
quality crystals were obtained by the slow evaporation of the solvent
at 0−5 °C. 2-Aryl ferrocenamide 3b (80 mg) was dissolved in CH2Cl2
(2 mL) and filtered through the filter paper in a single neck 10 mL
glass to obtain a transparent particle-free orange solution. After this, a
layer of hexane (1 mL) was added by a dropper through the wall of
the vial. Next, the vial was capped and kept in a fridge at 0−5 °C for
the slow evaporation of the solvent. Orange brown colored crystals
were obtained, which were separated by decantation of the solvent.
Preparation of 3b at 1 g Scale. A dry Schlenk tube (50 mL) was
equipped with a nitrogen balloon, and racemic 2-iodoferroceneamide
2 (1 equiv, 2.27 mmol, 1.0 g) was added; further, the tube was
charged with 2-iodoanisole (1 equiv, 2.27 mmol, 333 μL), methyl
acrylate (2 equiv, 4.5 mmol, 434 μL), Pd(OAc)2 (0.1 equiv, 0.23
mmol, 50 mg), JohnPhos (0.2 equiv, 0.02 mmol, 135 mg), and NBE
(1 equiv, 2.3 mmol, 222 mg) under a nitrogen atmosphere and add
dry DMF (40 mL) was added in the mixture. The Schlenk tube was
set up in a preheated oil bath at 105 °C. The progress of the reaction
was checked by TLC. After the completion of the reaction, the
resulting reaction mixture was passed through Celite pad, ethyl
acetate (30 mL) was added to the reaction mixture and washed with
water (100 mL × 3). The organic layer was dried over Na2SO4 (5 g),
concentrated on rotatory evaporator and purified by column
chromatography using hexane/ethyl acetate (80:20) on silica gel to
get the desired product 3b (830 mg, 72%).
(s, 5H), 4.32 (dd, J = 2.5, 1.3 Hz, 1H), 4.20 (t, J = 2.4 Hz, 1H), 1.54
(s, 6H), 1.14 (d, J = 6.1 Hz, 3H), 1.02 (d, J = 6.7 Hz, 3H). 13C{1H}
NMR (126 MHz, CDCl3): δ 166.3, 92.6, 73.6, 72.7, 67.6, 66.8, 40.4,
20.9, 20.6. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for
C17H22FeINONa, 461.9988; found, 461.9996. The enantiomeric
excess was found to be 97% using the CHIRALCELL OD-3 chiral
HPLC column with 2% 2-propanol in hexane as the mobile phase at a
flow rate of 1 mL/min.
Preparation of 1-N,N-Diisopropyl-2-(2′-(E)-acrylate-3′-
methyl)phenylferroceneamide (3a). Typical Procedure. A dry
Schlenk tube was equipped with a nitrogen balloon, and racemic 2-
iodoferroceneamide 1 (1 equiv, 0.113 mmol, 50 mg) was added;
further, the tube was charged with 2-iodotoluene (1 equiv, 0.1 mmol,
14 μL), Pd(OAc)2 (0.1 equiv, 0.01 mmol, 2.3 mg), JohnPhos (0.2
equiv, 0.02 mmol, 6 mg), NBE (1 equiv, 0.1 mmol, 9 mg), K2CO3
(2.4 equiv, 0.24 mmol, 33 mg), and methyl acrylate (2.0 equiv, 0.20
mmol, 18 μL) under a nitrogen atmosphere, and dry DMF (3 mL)
was added in the mixture. The tube was set up in a preheated oil bath
at 105 °C. The progress of the reaction was checked by TLC. After
completion of the reaction, the resulting reaction mixture was passed
through a Celite pad, and the combined organic layers were extracted
using ethyl acetate and water. The organic layer was passed through
Na2SO4, concentrated using a rotatory evaporator, and purified by
column chromatography using hexane/ethyl acetate (80:20) on silica
gel to get the desired product 3a (50 mg, 92%).
1-N,N-Diisopropyl-2-(methyl(E)-3-(naphthalen-1-yl)-
acrylate)ferroceneamide (3c). Orange-red solid, yield 47 mg (79%
at 0.113 mmol scale), column chromatography in hexane/ethyl
acetate (90:10), mp 122.9−123.4 °C, [α]2D5 = +78.9 (CHCl3, c =
0.15). 1H NMR (500 MHz, CDCl3): δ 8.22 (d, J = 8.6 Hz, 1H), 8.15
(dd, J = 6.3, 3.5 Hz, 1H), 8.03 (d, J = 16.3 Hz, 1H), 7.85 (dd, J = 6.2,
3.3 Hz, 1H), 7.80 (d, J = 8.6 Hz, 1H), 7.50 (dt, J = 6.4, 3.3 Hz, 2H),
6.26 (d, J = 16.7 Hz, 1H), 4.59−4.55 (m, 1H), 4.51−4.49 (m, 1H),
4.41 (d, J = 2.6 Hz, 1H), 4.33 (d, J = 2.6 Hz, 5H), 3.87 (s, 3H), 3.63−
3.57 (m, 1H), 3.16 (p, J = 6.8 Hz, 1H), 1.51 (d, J = 6.7 Hz, 3H), 1.32
(d, J = 6.8 Hz, 3H), 0.89 (d, J = 6.6 Hz, 3H), 0.16 (d, J = 6.6 Hz, 3H).
13C{1H} NMR (126 MHz, CDCl3): δ 167.6, 166.9, 143.7, 134.7,
132.5, 130.8, 130.2, 130.1, 128.4, 127.9, 126.7, 125.7, 125.0, 124.9,
92.0, 83.7, 71.4, 70.1, 69.2, 67.0, 51.8, 50.6, 45.7, 21.1, 21.0, 19.7,
19.5. IR (film) νmax: 3419, 2962, 1722, 1627, 1455, 1171, 736. HRMS
(ESI-TOF) m/z: [M]+ calcd for C31H33FeNO3, 523.1805; found,
523.1783. The enantiomeric excess (95% ee) was observed using the
CHIRALCELL OD-3 chiral HPLC column with 2-propanol/hexane
(1.5:98.5).
1-N,N-Diisopropyl-2-(methyl(E)-3-(2,4-dimethoxyphenyl)-
acrylate)ferroceneamide (3d). Orange-brown solid, yield 48 mg
(74% at 0.113 mmol scale), column chromatography in hexane/ethyl
acetate (90:10), mp 85.1−85.6 °C, [α]2D5 = +30 (CHCl3, c = 0.10). 1H
NMR (500 MHz, CDCl3): δ 7.81 (d, J = 16.1 Hz, 1H), 7.43 (d, J =
2.5 Hz, 1H), 6.65 (d, J = 16.0 Hz, 1H), 6.42 (d, J = 2.5 Hz, 1H), 4.52
(dd, J = 2.5, 1.4 Hz, 1H), 4.46 (dd, J = 2.5, 1.4 Hz, 1H), 4.52 (dd, J =
2.5, 1.4 Hz, 1H), 4.46 (dd, J = 2.5, 1.4 Hz, 1H), 4.40 (t, J = 2.4 Hz,
1H), 4.33 (s, 5H), 3.94 (s, 3H), 3.88 (s, 3H), 3.76 (s, 3H), 3.56−3.50
(m, 1H), 3.23−3.17 (m, 1H), 1.49 (d, J = 6.8 Hz, 3H), 1.31 (d, J =
6.8 Hz, 3H), 0.90 (d, J = 6.7 Hz, 3H), 0.34 (d, J = 6.7 Hz, 3H).
13C{1H} NMR (126 MHz, CDCl3): δ 168.9, 167.4, 160.4, 160.2,
Preparation of Chiral Sp-1-N,N-Diisopropyl-2-(2′-(E)-acryl-
ate-3′-methyl)phenylferroceneamide (3a). Typical Procedure. A
dry Schlenk tube was equipped with a nitrogen balloon, and chiral 2-
iodoferroceneamide 2 (1 equiv, 0.05 mmol, 20 mg) was added;
further, the tube was charged with 2-iodotoluene (1 equiv, 0.05 mmol,
6 μL), Pd(OAc)2 (0.20 equiv, 0.09 mmol, 2 mg), JohnPhos (0.2
equiv, 0.009 mmol, 2.7 mg), NBE (1.5 equiv, 0.068 mmol, 6.6 mg),
K2CO3 (3.0 equiv, 0.18 mmol, 25 mg), and methyl acrylate (2.0
equiv, 0.09 mmol, 11 μL) under a nitrogen atmosphere, and dry DMF
(3 mL) was added in the mixture. The tube was set up in preheated
oil bath at 105 °C. The progress of the reaction was checked by TLC.
(S)-1-N,N-Diisopropyl-2-(methyl(E)-3-(o-tolyl)acrylate)-
ferroceneamide (3a). Orange-red viscous solid, yield 50 mg (92%
at 0.113 mmol scale), and column chromatography in hexane/ethyl
acetate (90:10), mp 88.2−89.0 °C, [α]2D5 = +40 (CHCl3, c = 0.15). 1H
NMR (500 MHz, CDCl3): δ 7.96−7.94 (m, 1H), 7.22 (t, J = 7.7 Hz,
1H), 7.68 (d, J = 16.4 Hz, 1H), 7.13−7.11 (m, 1H), 5.97 (d, J = 16.4
Hz, 1H), 4.49 (dd, J = 2.5, 1.3 Hz, 1H), 4.37−4.35 (m, 1H), 4.31 (t, J
= 2.5 Hz, 1H), 4.28 (s, 5H), 3.79 (s, 3H), 3.58−3.52 (m, 1H), 3.21−
3.13 (m, 1H), 2.38 (s, 3H), 1.49 (d, J = 6.7 Hz, 3H), 1.29 (d, J = 6.7
Hz, 3H), 0.90 (d, J = 6.7 Hz, 3H), 0.25 (d, J = 6.7 Hz, 3H). 13C{1H}
NMR (126 MHz, CDCl3): δ 167.6, 167.0, 144.4, 137.1, 135.8, 133.2,
130.4, 129.3, 127.8, 123.2, 91.7, 84.3, 71.4, 69.3, 69.1, 66.6, 51.6, 50.4,
45.6, 21.6, 21.1, 21.0, 19.7, 19.3. IR (film) νmax: 3446, 2968, 1712,
1631, 1274, 750. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for
C28H33FeNO3Na, 510.1702; found, 510.1722. The enantiomeric
excess (98% ee) was observed using the CHIRALCELL OD-3 chiral
HPLC column with 2-propanol/hexane (1.5:98.5).
1-N,N-Diisopropyl-2-(methyl(E)-3-(2-methoxyphenyl)-
acrylate)ferroceneamide (3b). Orange-red solid, yield: 46 mg
(78% at 0.113 mmol scale), column chromatography in hexane/ethyl
acetate (90:10), mp 142.5−143 °C, [α]2D5 = +28 (CHCl3, c = 0.10).
1H NMR (500 MHz, CDCl3): δ 7.81−7.75 (m, 1H), 7.32−7.28 (m,
141.7, 139.7, 119.0, 115.7, 108.7, 98.0, 92.7, 84.8, 71.4, 69.2, 69.1,
66.7, 55.4, 55.3, 51.3, 50.6, 45.5, 20.9, 20.8, 20.1, 19.6. IR (film) νmax
:
1H), 6.84 (d, J = 8.2 Hz, 1H), 6.69 (d, J = 16.1 Hz, 1H), 4.53 (dd, J =
2.6, 1.4 Hz, 1H), 4.43 (dd, J = 2.5, 1.4 Hz, 1H), 6.69 (d, J = 16.1 Hz,
1H), 4.53 (dd, J = 2.6, 1.4 Hz, 1H), 4.43 (dd, J = 2.5, 1.4 Hz, 1H),
4.38 (t, J = 2.5 Hz, 1H), 4.31 (s, 5H), 3.78 (s, 3H), 3.90 (s, 3H),
3.60−3.51 (m, 1H), 3.22−3.15 (m, 1H), 1.50 (d, J = 6.7 Hz, 3H),
1.28 (d, J = 6.6 Hz, 3H), 0.90 (d, J = 6.6 Hz, 3H), 0.29 (d, J = 6.7 Hz,
3H). 13C{1H} NMR (126 MHz, CDCl3): δ 168.4, 167.4, 158.7, 140.0,
139.8, 129.2, 125.6, 122.1, 121.8, 109.1, 92.1, 84.1, 71.4, 69.4, 69.2,
66.8, 55.5, 51.4, 50.5, 45.6, 21.1, 21.0, 19.7, 19.4. IR (film) νmax: 3462,
2968, 1712, 1624, 1259, 752. HRMS (ESI-TOF) m/z: [M + Na]+
calcd for C28H33FeNO4Na, 526.1652; found, 526.1678. The
3464, 2962, 1712, 1598, 1157, 736. HRMS (ESI-TOF) m/z: [M +
H]+ calcd for C29H36FeNO5, 534.1938; found, 534.1932. The
enantiomeric excess (92% ee) was observed using the CHIRALCELL
IC-3 chiral HPLC column with 2-propanol/hexane (1.5:98.5).
1-N,N-Diisopropyl-2-(methyl(E)-3-(2-(benzyloxy)phenyl)-
acrylate)ferroceneamide (3e). Yellow-brown solid, yield 46 mg
(70% at 0.113 mmol scale), column chromatography in hexane/ethyl
acetate (90:10), mp 115.0−115.5 °C, [α]2D5 = +32 (CHCl3, c = 0.10).
1H NMR (500 MHz, CDCl3): δ 7.85−7.30 (m, 2H), 7.44−7.25 (m,
6H), 6.88 (d, J = 8.2 Hz, 1H), 6.74 (d, J = 16.1 Hz, 1H), 5.25−5.15
(m, 2H), 4.58−4.51 (m, 1H), 4.44 (d, J = 2.2 Hz, 1H), 4.40 (d, J =
G
https://dx.doi.org/10.1021/acs.joc.0c01360
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
2.4 Hz, 1H), 4.31 (s, 5H), 3.76 (s, 3H), 3.61−3.51 (m, 1H), 3.25−
3.13 (m, 1H), 1.50 (d, J = 6.8 Hz, 3H), 1.27 (d, J = 6.9 Hz, 3H), 0.91
(d, J = 6.6 Hz, 3H), 0.28 (d, J = 6.7 Hz, 3H). 13C{1H} NMR (126
MHz, CDCl3): δ 168.4, 167.4, 157.5, 140.1, 139.8, 136.5, 129.1,
128.5, 127.9, 127.1, 125.8, 122.7, 122.3, 110.8, 92.1, 84.0, 71.4, 70.5,
4.32 (t, J = 2.5 Hz, 1H), 4.29 (s, 5H), 4.25 (dd, J = 7.1, 0.9 Hz, 1H),
3.56−3.54 (m, 1H), 3.18−3.16 (m, 1H), 2.39 (s, 3H), 1.49 (d, J = 6.7
Hz, 3H), 1.33 (t, J = 7.2 Hz, 3H), 0.89 (d, J = 6.7 Hz, 3H), 0.25 (d, J
= 6.7 Hz, 3H). 13C{1H} NMR (126 MHz, CDCl3): δ 167.6, 166.6,
144.2, 137.1, 135.8, 133.3, 130.4, 129.3, 127.7, 123.5, 91.7, 84.4, 71.3,
69.2, 69.2, 66.6, 60.4, 50.4, 45.6, 21.6, 21.1, 21.0, 19.7, 19.3, 14.3. IR
(film) νmax: 2966, 1714, 1633, 1303, 1174, 819. HRMS (ESI-TOF)
m/z: [M + H]+ calcd for C29H36FeNO3, 502.2039; found, 502.2047.
The enantiomeric excess (97% ee) was observed using the
CHIRALCELL OD-3 chiral HPLC column with 2-propanol/hexane
(1.5:98.5).
1-N,N-Diisopropyl-2-(methyl(E)-3-(2-(methoxymethyl)-
phenyl)acrylate)ferroceneamide (3j). Red viscous liquid, yield 45
mg (76% at 0.113 mmol scale), column chromatography in hexane/
ethyl acetate (90:10), [α]2D5 = +38 (CHCl3, c = 0.10). 1H NMR (500
MHz, CDCl3): δ 8.09 (dd, J = 7.6, 1.6 Hz, 1H), 7.68 (d, J = 16.2 Hz,
1H), 7.40−7.32 (m, 2H), 6.20 (d, J = 16.2 Hz, 1H), 4.50 (t, J = 1.8
Hz, 1H), 4.46−4.37 (m, 2H), 4.46−4.37 (m, 2H), 4.28 (s, 5H), 3.81
(s, 3H), 3.53 (p, J = 6.8 Hz, 1H), 3.43 (s, 3H), 3.16 (p, J = 6.8 Hz,
1H), 1.49 (d, J = 6.8 Hz, 3H), 1.27 (d, J = 3.1 Hz, 3H), 0.89 (d, J =
6.8 Hz, 3H), 0.22 (d, J = 6.6 Hz, 3H). 13C{1H} NMR (126 MHz,
CDCl3): δ 167.5, 167.1, 143.2, 137.6, 135.5, 133.8, 132.4, 128.7,
127.9, 123.3, 91.9, 83.7, 73.1, 71.4, 69.4, 69.1, 66.8, 57.9, 51.7, 50.5,
45.6, 21.1, 21.0, 19.6, 19.3. IR (film) νmax: 3477, 1728, 1631, 1274,
750. HRMS (ESI-TOF) m/z: [M]+ calcd for C29H35FeNO4,
517.1910; found, 517.1924. The enantiomeric excess (94% ee) was
observed using the CHIRALCELL OD-3 chiral HPLC column with
2-propanol/hexane (1.5:98.5).
69.4, 69.2, 66.8, 51.4, 50.5, 45.6, 21.1, 21.0, 19.7, 19.4. IR (film) νmax
:
2964, 1712, 1624, 1166, 734. HRMS (ESI-TOF) m/z: [M + H]+
calcd for C34H38FeNO4, 580.2145; found, 580.2124. The enantio-
meric excess (93% ee) was observed using the CHIRALCELL OD-3
chiral HPLC column with 2-propanol/hexane (5:95).
1-N,N-Diisopropyl-2-(methyl(E)-3-(2-chlorophenyl)-
acrylate)ferroceneamide (3f). Red solid, yield 18 mg (31% at
0.113 mmol scale), in hexane/ethyl acetate (90:10), and mp of 84.1−
84.6 °C, [α]2D5 = +39 (CHCl3, c = 0.10). 1H NMR (500 MHz,
CDCl3): δ 8.06 (dd, J = 7.8, 1.4 Hz, 1H), 7.62 (d, J = 16.4 Hz, 1H),
7.34 (dd, J = 7.9, 1.3 Hz, 1H), 7.25 (t, J = 7.9 Hz, 1H), 6.24 (d, J =
16.4 Hz, 1H), 4.53 (dd, J = 2.5, 1.4 Hz, 1H), 4.37 (dd, J = 2.5, 1.4 Hz,
1H), 4.35 (t, J = 2.5 Hz, 1H), 4.30 (s, 5H), 3.81 (s, 3H), 3.63−3.58
(m, 1H), 3.25−3.20 (m, 1H), 1.51 (d, J = 6.7 Hz, 3H), 1.30 (d, J =
6.9 Hz, 5H), 0.95 (d, J = 6.6 Hz, 3H), 0.39 (d, J = 6.7 Hz, 3H).
13C{1H} NMR (126 MHz, CDCl3): δ 167.6, 166.9, 143.7, 134.7,
132.5, 130.8, 130.2, 130.1, 128.4, 127.9, 126.7, 125.7, 125.0, 124.9,
92.0, 83.7, 71.4, 70.1, 69.2, 67.0, 51.8, 50.6, 45.7, 21.1, 21.0, 19.7,
19.5. IR (film) νmax: 2927, 1724, 1303, 1170, 752. HRMS (ESI-TOF)
m/z: [M]+ calcd for C27H30ClFeNO3, 507.1259; found, 507.1275.
The enantiomeric excess (97% ee) was observed using the
CHIRALCELL OD-3 chiral HPLC column with 2-propanol/hexane
(1.5:98.5).
1-N,N-Diisopropyl-2-(tert-butyl(E)-3-(o-tolyl)acrylate ferro-
ceneamide) (3k). Red solid, yield 47 mg (78% at 0.113 mmol
scale), column chromatography in hexane/ethyl acetate (90:10), mp
1-N,N-Diisopropyl-2-(methyl(E)-3-(2-(dimethylamino)-
phenyl)acrylate)ferrocenecamide (3g). Yellow viscous liquid,
yield 11 mg (16% at 0.113 mmol scale), column chromatography in
157.9−158.3 °C, [α]2D5 = +19 (CHCl3, c = 0.05). H NMR (500
1
hexane/ethyl acetate (90:10), [α]2D5 = +14 (CHCl3, c = 0.10). H
1
MHz, CDCl3): δ 7.94−7.97 (m, 1H), 7.57 (d, J = 16.4 Hz, 1H), 7.22
(t, J = 7.6 Hz, 1H), 7.13 (d, J = 7.4 Hz, 1H), 5.92 (d, J = 16.4 Hz,
1H), 4.49 (dd, J = 2.5, 1.3 Hz, 1H), 4.38 (dd, J = 2.5, 1.4 Hz, 1H),
4.32 (t, J = 2.5 Hz, 1H), 4.30 (s, 5H), 3.58−3.47 (m, 1H), 3.23−3.12
(m, 1H), 2.41 (s, 3H), 1.53 (s, 9H), 1.50 (d, J = 6.8 Hz, 3H), 1.28 (d,
J = 6.8 Hz, 3H), 0.88 (d, J = 6.7 Hz, 3H), 0.25 (d, J = 6.6 Hz, 3H).
13C{1H} NMR (126 MHz, CDCl3): δ 167.6, 166.0, 143.1, 137.1,
135.8, 133.4, 130.4, 129.3, 127.6, 125.2, 91.9, 84.3, 80.4, 71.3, 69.2,
NMR (500 MHz, CDCl3): δ 7.90 (d, J = 16.3 Hz, 1H), 7.79 (dd, J =
7.8, 1.2 Hz, 1H), 7.00 (dd, J = 8.1, 1.2 Hz, 1H), 6.42 (d, J = 16.3 Hz,
1H), 4.54 (dd, J = 2.5, 1.4 Hz, 1H), 4.39 (dd, J = 2.5, 1.4 Hz, 1H),
4.33 (t, J = 2.5 Hz, 1H), 4.31 (s, 5H), 3.77 (s, 3H), 3.66−3.59 (m,
1H), 3.22−3.13 (m, 1H), 2.68 (s, 6H), 1.49 (d, J = 6.7 Hz, 3H), 1.29
(s, 2H), 0.91 (d, J = 1.5 Hz, 3H), 0.30 (d, J = 6.6 Hz, 3H). 13C{1H}
NMR (126 MHz, CDCl3): δ 168.3, 167.5, 153.6, 142.4, 138.7, 128.7,
127.6, 126.9, 120.4, 117.1, 91.4, 85.3, 73.0, 71.4, 69.2, 66.4, 51.4, 50.4,
45.6, 44.5, 21.1, 19.7, 19.5. IR (film) νmax: 2966, 2241, 1716, 1628,
1304, 733. HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C29H37FeN2O3, 517.2148; found, 517.2175. The enantiomeric excess
(94% ee) was observed using the CHIRALCELL OD-3 chiral HPLC
column with 2-propanol/hexane (2:98).
69.1, 66.5, 50.4, 45.6, 28.2, 21.7, 21.1, 20.9, 19.7, 19.3. IR (film) νmax
:
2970, 2360, 1710, 1151, 750. HRMS (ESI-TOF) m/z: [M + H]+
calcd for C31H40FeNO3, 530.2353; found, 530.2354. The enantio-
meric excess (97% ee) was observed using the CHIRALCELL OD-3
chiral HPLC column with 2-propanol/hexane (1.5:98.5).
1-N,N-Diisopropyl-2-(methyl(E)-3-(2-(methoxy-2-oxethyl)-
phenyl)acrylate)ferroceneamide (3h). Red solid, yield 37 mg
(59% at 0.113 mmol scale), column chromatography in hexane/ethyl
acetate (90:10), mp 115.0−115.5 °C, [α]2D5 = +40 (CHCl3, c = 0.10).
1H NMR (500 MHz, CDCl3): δ 8.04 (dd, J = 7.8, 1.3 Hz, 1H), 7.64
1-N, N-Diisopropyl-2-(methyl(E)-3-(4-chloro-2-
fluorophenyl)acrylate)ferroceneamide (3l). Yellow solid, yield
40 mg (67% at 0.113 mmol scale), column chromatography in
hexane/ethyl acetate (90:10), mp 159.0−160.6 °C, [α]2D5 = +28
(CHCl3, c = 0.05). 1H NMR (500 MHz, CDCl3): δ 7.91 (s, 1H), 7.65
(d, J = 16.3 Hz, 1H), 7.05 (dd, J = 10.9, 2.0 Hz, 1H), 6.55 (dd, J =
16.3, 1.8 Hz, 1H), 4.58 (dd, J = 2.5, 1.3 Hz, 1H), 4.43 (dt, J = 13.2,
2.5 Hz, 2H), 4.33 (s, 4H), 3.81 (s, 3H), 3.59−3.51 (m, 1H), 3.28−
3.20 (m, 1H), 1.52 (d, J = 6.7 Hz, 3H), 1.34 (d, J = 6.8 Hz, 3H), 0.95
(d, J = 6.7 Hz, 3H), 0.39 (d, J = 6.7 Hz, 3H). 13C{1H} NMR (126
MHz, CDCl3): δ 167.4, 166.8, 162.1, 160.1, 142.1, 136.8, 134.7,
128.4, 123.6, 120.2, 114.8, 92.0, 81.8, 71.7, 69.8, 68.8, 67.5, 51.7, 50.6,
45.8, 21.0, 19.8. IR (film) νmax: 2966, 2360, 1718, 1631, 1313, 821.
HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C27H29ClFFeNO3Na,
548.1062; found, 548.1084. The enantiomeric excess (97% ee) was
observed using the CHIRALCELL OD-3 chiral HPLC column with
2-propanol/hexane (1.5:98.5).
1-N,N-Diisopropyl-2-((E)-1-methyl-2-styrylbenzene)-
ferroceneamide (3m). Orange red solid, yield 43 mg (76% at 0.113
mmol scale), column chromatography in hexane/ethyl acetate
(90:10), mp 68.0−68.9 °C, [α]2D5 = +14 (CHCl3, c = 0.10). 1H
NMR (500 MHz, CDCl3): δ 7.93−7.96 (m, 1H), 7.43−7.36 (m, 4H),
7.32−7.29 (m, 1H), 7.21−7.14 (m, 2H), 6.95 (d, J = 16.7 Hz, 1H),
6.53 (d, J = 16.7 Hz, 1H), 4.50 (dt, J = 7.9, 1.5 Hz, 2H), 4.31 (s, 5H),
4.26 (t, J = 2.4 Hz, 1H), 3.63 (p, J = 6.7 Hz, 1H), 3.20 (p, J = 6.8 Hz,
(d, J = 16.4 Hz, 1H), 7.33−7.28 (m, 1H), 7.20 (dd, J = 7.7, 1.3 Hz,
1H), 6.01 (d, J = 16.3 Hz, 1H), 4.50 (dd, J = 2.5, 1.4 Hz, 1H), 4.36
(dd, J = 2.5, 1.4 Hz, 1H), 4.33 (d, J = 2.5 Hz, 1H), 4.30 (s, 5H), 3.81
(s, 3H), 3.79−3.70 (m, 1H), 3.69 (s, 3H), 3.56−3.49 (m, 1H), 3.23−
3.16 (m, 1H), 1.50 (d, J = 6.7 Hz, 3H), 1.30 (d, J = 6.8 Hz, 3H),
0.92−0.89 (m, 4H), 0.28 (d, J = 6.7 Hz, 3H). 13C{1H} NMR (126
MHz, CDCl3): δ 171.9, 167.5, 166.6, 144.1, 137.2, 134.2, 131.8,
131.6, 129.4, 127.9, 123.9, 91.9, 83.8, 71.4, 69.3, 68.9, 66.7, 52.0, 51.7,
50.5, 45.6, 39.4, 29.6, 21.1, 19.7, 19.3. IR (film) νmax: 3477, 2966,
1728, 1631, 1274, 750. HRMS (ESI-TOF) m/z: [M]+ calcd for
C30H35FeNO5, 545.1860; found, 545.1867. The enantiomeric excess
(96% ee) was observed using the CHIRALCELL OD-3 chiral HPLC
column with 2-propanol/hexane (2:98).
1-N,N-Diisopropyl-2-(ethyl(E)-3-(o-tolyl)acrylate)-
ferroceneamide (3i). Red solid, yield 42 mg (72% at 0.113 mmol
scale), column chromatography in hexane/ethyl acetate (90:10), mp
117.2−117.9 °C, [α]2D5 = +66 (CHCl3, c = 0.05). H NMR (500
1
MHz, CDCl3): δ 7.95 (d, J = 7.7 Hz, 1H), 7.68 (d, J = 16.4 Hz, 1H),
7.22 (t, J = 7.7 Hz, 1H), 7.13 (d, J = 7.5 Hz, 1H), 5.98 (d, J = 16.4 Hz,
1H), 4.49 (dd, J = 2.5, 1.3 Hz, 1H), 4.37 (dd, J = 2.5, 1.4 Hz, 1H),
H
https://dx.doi.org/10.1021/acs.joc.0c01360
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
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Article
1H), 2.45 (s, 3H), 1.52 (d, J = 6.8 Hz, 3H), 1.33 (d, J = 6.8 Hz, 3H),
0.92 (d, J = 6.7 Hz, 3H), 0.28 (d, J = 6.7 Hz, 3H). 13C{1H} NMR
(126 MHz, CDCl3): δ 167.8, 137.5, 136.1, 136.0, 135.6, 133.5, 130.2,
129.1, 128.7, 127.7, 127.5, 126.3, 126.6, 91.6, 85.0, 71.3, 69.2, 69.0,
66.1, 50.4, 45.6, 21.6, 21.2, 19.7, 19.3. IR (film) νmax: 2964, 1629,
1452, 1037, 817. HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C32H36FeNO, 506.2141; found, 506.2148. The enantiomeric excess
(97% ee) was observed using the CHIRALCELL IC-3 chiral HPLC
column with 2-propanol/hexane (20:80).
1-N,N-Diisopropyl-2-(methyl(E)-3-(m-tolyl)acrylate)-
ferroceneamide (3n). Orange red viscous liquid, yield 38 mg (68%
at 0.113 mmol scale), column chromatography in hexane/ethyl
acetate (90:10), [α]2D5 = +23 (CHCl3, c = 0.10). 1H NMR (500 MHz,
CDCl3): δ 7.96 (dd, J = 11.9, 3.9 Hz, 2H), 7.33 (s, 1H), 7.19 (dd, J =
8.0, 1.8 Hz, 1H), 6.37 (d, J = 15.8 Hz, 1H), 4.51 (t, J = 1.8 Hz, 1H),
4.40−4.37 (m, 1H), 4.31 (s, 5H), 3.80 (s, 3H), 3.51 (p, J = 6.7 Hz,
1H), 3.18 (p, J = 6.9 Hz, 1H), 2.37 (s, 3H), 1.50 (d, J = 6.8 Hz, 3H),
1.30 (s, 3H), 0.91−0.89 (m, 3H), 0.25 (d, J = 6.6 Hz, 3H). 13C{1H}
NMR (126 MHz, CDCl3): δ 167.5, 167.4, 144.1, 136.5, 134.8, 1330,
132.8, 130.2, 126.8, 118.5, 91.5, 83.4, 71.3, 69.4, 68.8, 66.9, 51.6, 50.5,
45.6, 29.7, 21.1, 21.0, 19.7, 19.4. IR (film) νmax: 3523, 1716, 1631,
817, 750. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C28H34FeNO3,
488.1892; found, 488.1883. The enantiomeric excess (97% ee) was
observed using the CHIRALCELL OD-3 chiral HPLC column with
2-propanol/hexane (1.5:98.5).
1-N,N-Diisopropyl-2-(methyl(E)-3-(thiophen-2-yl)acrylate)-
ferroceneamide (3o). Orange red viscous liquid, yield 20 mg (37%
at 0.113 mmol scale), column chromatography in hexane/ethyl
acetate (90:10), [α]2D5 = +43 (CHCl3, c = 0.10). 1H NMR (500 MHz,
CDCl3): δ 8.01 (d, J = 15.6 Hz, 1H), 7.45 (d, J = 5.2 Hz, 1H), 7.27
(d, J = 5.2 Hz, 1H), 6.27 (d, J = 15.6 Hz, 1H), 4.54−4.51 (m, 1H),
4.50 (dd, J = 2.5, 1.4 Hz, 1H), 4.41 (d, J = 2.5 Hz, 1H), 4.34 (s, 5H),
3.81 (s, 3H), 3.52−3.46 (m, 1H), 3.27−3.20 (m, 1H), 1.50 (d, J = 6.8
Hz, 3H), 1.36 (d, J = 6.8 Hz, 3H), 0.93 (d, J = 6.7 Hz, 3H), 0.39 (d, J
= 6.6 Hz, 3H). 13C{1H} NMR (126 MHz, CDCl3): δ 167.5, 167.2,
141.9, 136.5, 133.9, 132.3, 126.0, 116.4, 90.7, 78.4, 71.2, 71.2, 69.9,
67.6, 67.0, 51.6, 50.6, 45.7, 21.0, 20.8, 19.8, 19.3. IR (film) νmax: 2924,
1714, 1456, 1307, 1166, 819. HRMS (ESI-TOF) m/z: [M + H]+
calcd for C25H30FeNO3S, 480.1317; found, 480.1291. The enantio-
meric excess (94% ee) was observed using the CHIRALCELL IC-3
chiral HPLC column with 2-propanol/hexane (20:80).
118.4, 108.3, 98.3, 92.3, 71.3, 69.3, 69.0, 66.1, 55.6, 55.2, 50.6, 45.6,
21.0, 20.9, 20.1, 19.7. IR (film) νmax: 2964, 1597, 1456, 1311, 1155,
758. HRMS (ESI-TOF) m/z: [M + H]+ calcd for C33H38FeNO3,
552.2196; found, 552.2200. The enantiomeric excess (93% ee) was
observed using the CHIRALCELL AD-3 chiral HPLC column with 2-
propanol/hexane (2:98).
1-N,N-Diisopropyl-2-((E)-1-nitro-2-styrylbenzene)-
ferroceneamide (3r). Orange red solid, yield 33 mg (60% at 0.113
mmol scale), column chromatography in hexane/ethyl acetate
1
(90:10), mp 178.2−178.9 °C, [α]2D5 = +30 (CHCl3, c = 0.10). H
NMR (500 MHz, CDCl3): δ 8.23 (d, J = 8.7 Hz, 2H, 1H), 7.99−7.95
(m, 1H), 7.52 (d, J = 8.5 Hz, 2H), 7.23 (t, J = 7.6 Hz, 1H), 7.12−7.19
(m, 2H), 6.61 (d, J = 16.7 Hz, 1H), 4.53 (t, J = 1.8 Hz, 1H), 4.39 (t, J
= 1.8 Hz, 1H), 4.31 (s, 5H), 4.28 (s, 1H), 3.64 (p, J = 6.7 Hz, 1H),
3.20 (p, J = 6.7 Hz, 1H), 2.46 (s, 3H), 1.52 (d, J = 6.8 Hz, 3H), 1.32
(d, J = 6.7 Hz, 3H), 0.94 (d, J = 6.6 Hz, 3H), 0.44 (d, J = 6.7 Hz, 3H).
13C{1H} NMR (126 MHz, CDCl3): δ 167.6, 146.8, 143.9, 136.5,
135.6, 132.6, 131.3, 130.4, 129.4, 127.1, 126.5, 124.1, 91.6, 84.9, 71.4,
69.3, 69.0, 66.3, 50.4, 45.6, 21.6, 21.1, 19.7, 19.4. IR (film) νmax: 2927,
1593, 1516, 1340, 750. HRMS (ESI-TOF) m/z: [M]+ calcd for
C32H34FeN2O3, 550.1914; found, 550.1927. The enantiomeric excess
(95% ee) was observed using the CHIRALCELL OD-3 chiral HPLC
column with 2-propanol/hexane (2:98).
1-N,N-Diisopropyl-2-(1-methyl-2-((1E,3E)-4-phenylbuta-1,3-
dien-1yl)benzene)ferroceneamide (3s). Orange red solid, yield
39 mg (74% at 0.113 mmol scale), column chromatography in
hexane/ethyl acetate (90:10), mp 150.2−151.5 °C, [α]2D5 = +28
1
(CHCl3, c = 0.10). H NMR (400 MHz, CDCl3): δ 7.93 (d, J = 7.4
Hz, 1H), 7.46 (d, J = 7.7 Hz, 2H), 7.35 (t, J = 7.6 Hz, 2H), 7.26 (t, J =
7.4 Hz, 1H), 7.19−7.12 (m, 2H), 7.15 (dt, J = 13.6, 7.4 Hz, 2H), 6.92
(dd, J = 15.6, 10.3 Hz, 1H), 6.55 (dd, J = 15.8, 9.0 Hz, 2H), 6.40 (dd,
J = 16.0 Hz, 1H), 4.51 (dd, J = 9.6, 2.2 Hz, 1H), 4.31 (s, 5H), 4.29 (d,
J = 2.4 Hz, 1H), 3.64−3.55 (m, 1H), 3.19 (p, J = 6.8 Hz, 1H), 2.43 (s,
3H), 1.52 (d, J = 6.7 Hz, 3H), 1.32 (d, J = 6.8 Hz, 3H), 0.92 (d, J =
6.7 Hz, 3H), 0.27 (d, J = 6.7 Hz, 3H). 13C{1H} NMR (101 MHz,
CDCl3): δ 167.8, 137.3, 136.7, 135.9, 135.5, 134.6, 131.9, 131.8,
130.3, 129.5, 129.2, 128.6, 127.5, 126.3, 126.3, 91.5, 85.2, 71.3, 69.4,
69.0, 66.1, 50.4, 45.6, 21.8, 21.1, 19.7, 19.3. IR (film) νmax: 3523,
1624, 1454, 1303, 991, 750. HRMS (ESI-TOF) m/z: [M + H]+ calcd
for C34H38FeNO, 532.2298; found, 532.2296. The enantiomeric
excess (98% ee) was observed using the CHIRALCELL OD-3 chiral
HPLC column with 2-propanol/hexane (2:98).
1-N,N-Diisopropyl-2-((E)-1-methoxy-2-styrylbenzene)-
ferroceneamide (3p). Orange red solid, yield 39 mg (74% at 0.113
mmol scale), column chromatography in hexane/ethyl acetate
1-N,N-Diisopropyl-2-((E)-1-methyl-2-(4-nitrostyryl)-
benzene)ferroceneamide (3t). Orange red solid, yield 41 mg (74%
at 0.113 mmol scale), column chromatography in hexane/ethyl
acetate (90:10), mp 156.2−157.5 °C, [α]2D5 = +32 (CHCl3, c = 0.10).
1H NMR (500 MHz, CDCl3): δ 8.34 (d, J = 7.8 Hz, 1H), 7.59 (d, J =
(90:10), mp 115.2−116.0 °C, [α]2D5 = +20 (CHCl3, c = 0.10). H
1
NMR (500 MHz, CDCl3): δ 7.74 (d, J = 7.8 Hz, 1H), 7.40 (d, J = 7.6
Hz, 2H), 7.35 (t, J = 7.6 Hz, 2H), 7.28−7.14 (m, 3H), 7.07 (d, J =
16.5 Hz, 1H), 6.86 (d, J = 8.2 Hz, 1H), 4.55 (t, J = 1.9 Hz, 1H), 4.51
(t, J = 1.8 Hz, 1H), 4.31 (s, 6H), 3.91 (s, 3H), 3.65 (p, J = 6.6 Hz,
1H), 3.20 (p, J = 6.8 Hz, 1H), 1.52 (d, J = 6.8 Hz, 3H), 1.32 (d, J =
6.7 Hz, 3H), 0.91 (d, J = 6.7 Hz, 3H), 0.31 (d, J = 6.6 Hz, 3H).
13C{1H} NMR (126 MHz, CDCl3): δ 167.7, 157.6, 138.5, 137.6,
7.9 Hz, 1H), 7.39 (t, J = 8.0 Hz, 1H), 7.36 (d, J = 4.3 Hz, 4H), 7.29−
7.33 (m, 1H), 7.01 (d, J = 16.6 Hz, 1H), 6.46 (d, J = 16.6 Hz, 1H),
4.53−4.56 (m, 1H), 4.48−4.50 (m, 1H), 4.34 (d, J = 2.5 Hz, 1H),
4.32 (s, 5H), 3.62 (p, J = 6.7 Hz, 1H), 3.24 (p, J = 6.9 Hz, 1H), 1.52
(d, J = 6.8 Hz, 3H), 1.31 (d, J = 7.0 Hz, 3H), 0.96 (d, J = 6.7 Hz, 3H),
0.44 (d, J = 6.7 Hz, 3H). 13C{1H} NMR (126 MHz, CDCl3): δ 167.2,
150.7, 139.2, 136.5, 135.5, 134.4, 130.3, 128.7, 128.3, 126.8, 126.6,
122.8, 121.6, 91.8, 83.1, 71.5, 69.2, 68.8, 66.9, 50.6, 45.7, 21.0, 19.8.
IR (film) νmax: 2926, 1622, 1527, 1261, 752. HRMS (ESI-TOF) m/z:
[M + Na]+ calcd for C31H32FeN2O3Na, 559.1655; found, 559.1667.
The enantiomeric excess (93% ee) was observed using the
CHIRALCELL AD-H chiral HPLC column with 2-propanol/hexane
(1.5:98.5).
1 - N , N- D i i s o p r o p y l - 2 - ( ( E) - 4 - c h l o r o - 1 - fl uor o-2 -
styrylbenzene)ferroceneamide (3u). Orange red solid, yield 41
mg (74% at 0.113 mmol scale), column chromatography in 10:90
(ethyl acetate/hexane), mp 147.0−147.9 °C, [α]2D5 = +35 (CHCl3, c =
0.10). 1H NMR (500 MHz, CDCl3): δ 7.89 (d, J = 2.1 Hz, 1H), 7.43
(d, J = 7.6 Hz, 2H), 7.38 (t, J = 7.5 Hz, 2H), 7.31 (d, J = 7.3 Hz, 1H),
7.14 (d, J = 16.6 Hz, 1H), 7.06 (dd, J = 10.8, 2.2 Hz, 1H), 6.89 (d, J =
16.7 Hz, 1H), 4.60 (dd, J = 2.5, 1.3 Hz, 1H), 4.51 (d, J = 1.8 Hz, 1H),
4.40 (t, J = 2.5 Hz, 1H), 4.34 (s, 5H), 3.56 (p, J = 6.4 Hz, 1H), 3.23
(p, J = 6.8 Hz, 1H), 1.53 (d, J = 6.8 Hz, 3H), 1.36 (d, J = 6.7 Hz, 3H),
133.2, 128.5, 127.2, 126.9, 126.2, 125.6, 125.1, 123.8, 109.3, 91.8,
84.8, 71.4, 69.2, 69.2, 66.2, 55.6, 50.5, 45.6, 29.7, 21.2, 19.7, 19.4. IR
(film) νmax: 3444, 1631, 1455, 1300, 750. HRMS (ESI-TOF) m/z: [M
+ H]+ calcd for C32H36FeNO2, 522.2090; found, 522.2078. The
enantiomeric excess (93% ee) was observed using the CHIRALCELL
IC-3 chiral HPLC column with 2-propanol/hexane (1.5:98.5).
1-N,N-Diisopropyl-2-((E)-2,4-dimethoxy-1-styrylbenzene)-
ferroceneamide (3q). Orange red solid, yield 40 mg (76% at 0.113
mmol scale), column chromatography in hexane/ethyl acetate
(90:10), mp 145.5−147.0 °C, [α]2D5 = +25 (CHCl3, c = 0.10). H
1
NMR (500 MHz, CDCl3): δ 77.39 (d, J = 2.5 Hz, 1H), 7.37−7.31
(m, 4H), 7.20−7.24 (m, 1H), 7.13 (d, J = 16.5 Hz, 1H), 7.05 (d, J =
16.5 Hz, 1H), 6.46 (d, J = 2.5 Hz, 1H), 4.54 (d, J = 2.0 Hz, 1H), 4.53
(d, J = 2.0 Hz, 1H), 4.34 (s, 5H), 4.32 (t, J = 2.5 Hz, 1H), 3.94 (s,
3H), 3.89 (s, 3H), 3.63 (p, J = 6.7 Hz 1H), 3.22 (p, J = 6.8 Hz 1H),
1.52 (d, J = 6.7 Hz, 3H), 1.35 (d, J = 6.8 Hz, 3H), 0.92 (d, J = 6.8 Hz,
3H), 0.38 (d, J = 6.6 Hz, 3H). 13C{1H} NMR (126 MHz, CDCl3): δ
167.6, 158.9, 158.3, 138.9, 138.6, 131.4, 128.5, 126.8, 126.0, 123.6,
I
https://dx.doi.org/10.1021/acs.joc.0c01360
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
0.94 (d, J = 6.7 Hz, 3H), 0.37 (d, J = 6.7 Hz, 3H). 13C{1H} NMR
(126 MHz, CDCl3): δ 167.0, 161.5, 159.5, 140.0, 137.5, 134.7, 132.1,
128.7, 127.9, 126.4, 122.9, 120.5, 114.8, 92.2, 82.4, 71.6, 69.7, 68.6,
66.8, 50.6, 45.8, 21.1, 19.8, 19.5. IR (film) νmax: 3422, 1633, 1300,
821, 748. HRMS (ESI-TOF) m/z: [M + H]+ calcd for
C31H32FeClFNO, 544.1501; found, 544.1500. The enantiomeric
excess (95% ee) was observed using the CHIRALCELL IC-3 chiral
HPLC column with 2-propanol/hexane (20:80).
Accession Codes
CCDC 1965471 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
via www.ccdc.cam.ac.uk/data_request/cif, or by emailing
data_request@ccdc.cam.ac.uk, or by contacting The Cam-
bridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
1-N,N-Diisopropyl-2-((E)-3-(naphthalen-1-yl)acrylic acid)-
ferroceneamide (4a). A solution of 1-N,N-diisopropyl-2-(methyl-
(E)-3-(naphthalen-1-yl)acrylate)ferroceneamide 3c (50 mg, 0.095
mmol) in ethanol (5 mL) was added dropwise to sodium hydroxide
(10 mL, 2.0 M aqueous solution) and refluxed for 2 h. The mixture
was quenched with water (20 mL) and acidified to pH 2 with
hydrochloric acid (2.0 M aqueous solution, 10 mL).Then, the
solution was extracted with ethyl acetate (30 mL × 3), dried over
sodium sulfate, and filtered and concentrated under vacuo to give 1-
N,N-diisopropyl-2-((E)-3-(naphthalen-1-yl)acrylic acid)-
AUTHOR INFORMATION
Corresponding Author
■
Sangit Kumar − Department of Chemistry, Indian Institute of
Science Education and Research Bhopal, Bhopal, Madhya
Pradesh 462066, India; orcid.org/0000-0003-0658-
8709; Email: sangitkumar@iiserb.ac.in
Authors
Raviraj Ananda Thorat − Department of Chemistry, Indian
Institute of Science Education and Research Bhopal, Bhopal,
Madhya Pradesh 462066, India; orcid.org/0000-0001-
6106-556X
Saket Jain − Department of Chemistry, Indian Institute of
Science Education and Research Bhopal, Bhopal, Madhya
Pradesh 462066, India; orcid.org/0000-0002-3350-
2731
Moh. Sattar − Department of Chemistry, Indian Institute of
Science Education and Research Bhopal, Bhopal, Madhya
Pradesh 462066, India; orcid.org/0000-0001-6529-
4255
Prateek Yadav − Department of Chemistry, Indian Institute of
Science Education and Research Bhopal, Bhopal, Madhya
Pradesh 462066, India; orcid.org/0000-0003-1055-
9185
ferroceneamide (yield 35 mg, 70%), mp 142.3−143.6 °C, [α]D25
=
1
+39 (CHCl3, c = 0.10). H NMR (500 MHz, CDCl3): δ 8.13−8.26
(m, 3H), 7.82−7.90 (m, 2H), 7.54 (dd, J = 7.1, 3.2 Hz, 2H), 7.54 (dd,
J = 7.1, 3.2 Hz, 2H), 6.33 (d, J = 16.3 Hz, 1H), 4.61 (s, 1H), 4.54 (s,
1H), 4.44 (t, J = 2.4 Hz, 1H), 4.36 (s, 5H), 3.62 (dd, J = 13.7, 7.1 Hz,
1H), 3.17 (q, J = 6.8 Hz, 1H), 1.52 (d, J = 6.7 Hz, 3H), 1.33 (d, J =
6.9 Hz, 3H), 0.91 (d, J = 6.5 Hz, 3H), 0.19 (d, J = 6.7 Hz, 3H).
13C{1H} NMR (126 MHz, CDCl3): δ 171.0, 167.8, 145.7, 135.0,
132.5, 130.7, 130.1, 129.9, 128.5, 126.9, 125.8, 124.9, 91.9, 83.7, 71.5,
70.2, 69.2, 67.1, 50.7, 45.8, 29.7, 21.1, 21.0, 19.7, 19.5, 14.1. IR (film)
νmax: 3428, 2922, 1725, 1633, 1463, 1261, 757. HRMS (ESI-TOF) m/
z: [M + H]+ calcd for C30H32FeNO3, 509.1648; found, 509.1615. The
enantiomeric excess (96% ee) was observed using the CHIRALCELL
AD-H chiral HPLC column with 2-propanol/hexane (30:70).
1-N,N-Diisopropyl-2-((E)-3-(2-methylnaphthalen-1-yl)prop-
2-en-1-ol)ferroceneamide (4b). A solution of 1-N,N-diisopropyl-2-
(methyl(E)-3-(naphthalen-1-yl)acrylate)ferroceneamide 3c (70 mg,
0.13 mmol) in dichloromethane (DCM, 10 mL) was cooled at −78
°C and then a mixture of DIBAL-H (100 μL, 0.13 mmol, 1.0 M
solution in hexane) was added dropwise. After 10 min, Rochelle salt
(1 g) was added and stirred for 2 h. Finally, a solution was extracted
with DCM (30 mL × 3), dried over sodium sulfate, and filtered and
concentrated in vacuo to give alcohol 4b as an orange solid (yield 54
Yogesh Mandhar − Department of Chemistry, Indian Institute
of Science Education and Research Bhopal, Bhopal, Madhya
Pradesh 462066, India; orcid.org/0000-0001-8304-
1518
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.0c01360
mg, 72%), mp 152.2−153.5 °C, [α]2D5 = +35 (CHCl3, c = 0.10). H
1
NMR (500 MHz, CDCl3): δ 8.16−8.19 (m, 1H), 8.14 (d, J = 8.5 Hz,
1H), 7.81−7.87 (m, 1H), 7.75 (d, J = 8.6 Hz, 2H), 7.51−7.46 (m,
2H), 6.85 (d, J = 16.2 Hz, 1H), 5.92 (dt, J = 16.3, 5.6 Hz, 1H), 4.58
(t, J = 1.9 Hz, 1H), 4.55 (t, J = 1.8 Hz, 1H), 4.38−4.41 (m, 2H), 4.37
(t, J = 2.5 Hz, 1H), 4.35 (s, 5H), 3.81 (p, J = 6.7 Hz, 1H), 3.16 (p, J =
6.8 Hz, 1H), 1.48 (d, J = 6.7 Hz, 3H), 0.92 (d, J = 7.1 Hz, 3H), 0.74
(d, J = 6.7 Hz, 3H), 0.26 (d, J = 6.7 Hz, 3H). 13C{1H} NMR (126
MHz, CDCl3): δ 168.2, 135.4, 133.0, 132.9, 132.6, 131.5, 130.1,
128.2, 128.1, 126.5, 126.1, 125.6, 125.5, 90.7, 85.5, 71.1, 69.8, 69.8,
66.6, 63.8, 50.6, 45.8, 21.0, 20.7, 20.0, 19.9. IR (film) νmax: 3462,
2062, 1629, 1320, 1130, 450. HRMS (ESI-TOF) m/z: [M]+ calcd for
C30H33FeNO2, 495.1856; found, 495.1828. The enantiomeric excess
(96% ee) was observed using the CHIRALCELL AD-3 chiral HPLC
column with 2-propanol/hexane (30:70).
Author Contributions
The article was written through contributions of all the
authors. All the authors have given approval to the final version
of the manuscript.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
S.K. thanks to SERB New Delhi (CRG/2019/000017) and
IISER Bhopal for generous funding. S.K. is thankful to Dr.
Debaditya De, Merck Bangalore, India, for arranging sparteine.
S.K. is thanks to Dr. Sreenivas Katukojvala and Tarun Kumar
Roy for their support in chiral HPLC analysis and Dr. Deepak
Chopra for proofreading the manuscript. R.A.T. and S.J.
acknowledge the Council of Scientific and Industrial Research
New Delhi [09/1020(0113)/2017-EMR-I] and UGC [14/
(CSIR-UGC NET JUNE 2017)] for fellowships, respectively.
S.K. would like to dedicate this work in memory of Professor
Christopher Peter Morley (1957−2018) School of Chemistry,
Cardiff University for his contribution to ferrocene chemistry.
ASSOCIATED CONTENT
■
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.0c01360.
1H NMR, 13C NMR, and HRMS, HPLC traces and CIF
file (CCDC no. 1965471) of ferroceneamide 3b and
FAIR data (PDF)
REFERENCES
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Article
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