Bulky 1,1′-Ferrocenyl Ligands Featuring Diazaphospholene or Dioxaphosphepine Donor Fragments: Catalytic Screening in Nickel-Catalyzed C-N Cross-Coupling

Article abstract of DOI:10.1002/ejic.201900972

1,1′-Ferrocenyl ligands featuring either bulky dioxaphosphepine (L1) or diazaphospholene (L2) donor moieties have been prepared, crystallographically characterized, and tested in representative nickel-catalyzed C–N cross-coupling reactions. Ligand L1 prov

Full text of DOI:10.1002/ejic.201900972

DOI: 10.1002/ejic.201900972
Full Paper
Ligand Design | Very Important Paper |
Bulky 1,1′-Ferrocenyl Ligands Featuring Diazaphospholene or
Dioxaphosphepine Donor Fragments: Catalytic Screening in
Nickel-Catalyzed C-N Cross-Coupling
Ryan. T. McGuire,[a] Jillian S. K. Clark,[a] Alexandre V. Gatien,[a] M. Yue Shen,[a]
Michael J. Ferguson,[b] and Mark Stradiotto*[a]
Abstract: 1,1′-Ferrocenyl ligands featuring either bulky dioxa- ing primary/secondary alkylamine or indole nucleophiles with
phosphepine (L1) or diazaphospholene (L2) donor moieties (hetero)aryl chlorides, with the catalytic performance of rac and
have been prepared, crystallographically characterized, and meso-L1 differing in the case of some substrate pairings. Con-
tested in representative nickel-catalyzed C–N cross-coupling re- versely, L2 proved ineffective under analogous conditions.
actions. Ligand L1 proved competent in cross-couplings involv-
Introduction
The palladium-catalyzed C–N cross-coupling of NH substrates
and (hetero)aryl (pseudo)halides (i.e., Buchwald-Hartwig amin-
ation, BHA) is used widely in the synthesis of sought-after
(hetero)anilines, including those found in pharmaceuticals and
conjugated materials (Figure 1).[1] The successful evolution of
BHA from an academic curiosity to a robust synthetic protocol
can be attributed in large part to advances in ancillary ligand
design,[2] with sterically demanding and electron-rich ligands
such as monophosphines[3] and N-heterocyclic carbenes[4]
proving particularly effective, especially in transformations of
inexpensive and abundant (hetero)aryl chlorides where oxid-
ative addition can be challenging.[5] Notwithstanding the suc-
cess of BHA, the costly and relatively rare nature of palladium
has created motivation for the development of competitive
“drop-in” catalyst replacements that make use of base metals.[6]
The generally poor performance of copper-catalyzed C–N
cross-coupling methods[7] and nickel-catalyzed photoredox[8] or
electrochemical[9] protocols with (hetero)aryl chloride electro-
Figure 1. C–N cross-coupling employing group 10 metals, highlighting some
effective bisphosphine-type ligands used with nickel, and the bulky ferro-
cenyl ligands L1 and L2 examined in this work.
philes has prompted the exploration of alternative approaches.
One strategy involves the repurposing of useful ancillary li-
gands from the BHA domain, including bisphosphines[10] (e.g.,
DPPF,[11] Figure 1) and N-heterocyclic carbenes (e.g., IPr[12]), as
methods; furthermore, state-of-the-art ligands from BHA (e.g.,
Buchwald's biaryl monophosphines) have generally proven inef-
fective in C–N cross-couplings employing nickel. In this context,
the success of ancillary ligand design in enabling the advance-
ment of BHA methods suggests that efforts tailored specifically
to the properties of nickel may similarly prove advantageous.
Despite such opportunities, little attention has been focussed
on the design of ancillary ligands for use in nickel-catalyzed
C–N cross-coupling.
a means of enabling photoredox/electrochemical-free nickel-
catalyzed C–N cross-coupling. However, the collective scope at-
tained by such means falls short of that achieved by use of BHA
[a] Department of Chemistry, Dalhousie University,
6274 Coburg Road, PO Box 15000, Halifax, Nova Scotia, Canada, B3H 4R2
E-mail: mark.stradiotto@dal.ca
https://www.dal.ca/sites/stradiotto.html
[b] X-ray Crystallography Laboratory, Department of Chemistry,
University of Alberta,
Our research efforts over the past few years have been
focussed in part on advancing nickel-catalyzed C–N cross-cou-
pling, including through the synthesis and screening of new
Edmonton, Alberta, Canada, T6G 2G2
Supporting information and ORCID(s) from the author(s) for this article are
available on the WWW under https://doi.org/10.1002/ejic.201900972.
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and known ancillary ligands. One particularly successful aspect benzo[d,f][1,3,2]-dioxaphosphepinyl groups within each dia-
of this work involved the development of the PAd-DalPhos[13] stereomer are related either by a C2 (rac-L1) or a CS (meso-L1)
bisphosphine ligand class, featuring a phosphaadamantane symmetry element. In this regard, crystallographically imposed
(CgP) donor fragment (Figure 1). Given the established propen- symmetry relating the phosphorus donor fragments is observed
sity of LnNi0 species to engage in (hetero)aryl chloride oxidative in the solid-state structure of meso-L1 (Figure 2). The solid-state
addition,[5] we envisioned that bulky and only modestly elec- structure of meso-L1 can be compared to a related bis(phos-
tron-donating ligands featuring the CgP group would work par- phonite)ferrocene ligand reported by Pastor and co-workers;[22]
ticularly well in promoting rate-limiting C–N reductive elimina- however, unlike L1, the lack of substitution at the 6,6′ positions
tion within a presumptive Ni(0/II) (“palladium-like”) catalytic in their system results in rapid ring inversion within their
cycle, while also discouraging unwanted comproportionation to chosen dibenzo[d,f][1,3,2]-dioxaphosphepinyl groups, and
form potentially less active NiI species.[14] Indeed, PAd-DalPhos atropisomerism is not observed.
and related variants[13,15] are amongst the most effective li-
gands known for nickel-catalyzed C–N cross-coupling, enabling
a range of challenging NH substrate/(hetero)aryl (pseudo)halide
pairings, in a manner that is commonly competitive with, or
superior to, the best palladium catalysts known.
Encouraged by this success, we continue to explore new an-
cillary ligand designs that adhere to these design principles,
with the goal of gaining an increased understanding of the
ligand structure/properties that give rise to effective nickel
C–N cross-coupling catalysis. In this vein, we recently showed
that replacing the CgP group with a bulky N-heterocyclic phos-
phine[16] moiety, or phosphonite donor group derived from
commercially available 5,5′,6,6′-tetramethyl-3,3′-di-tert-butyl-
Scheme 1. Synthesis of L1 (TMEDA = tetramethylethylenediamine).
1,1′-biphenyl-2,2′-diol, affords ancillary ligands (i.e., NHP-Dal-
Phos[17] and Phen-DalPhos,[18] Figure 1) that are highly effective
in enabling otherwise challenging classes of nickel-catalyzed
C–N cross-couplings involving (hetero)aryl chlorides, including
at room temperature. Building on this work, we sought to
merge the beneficial structural features of DPPF, NHP-DalPhos,
and Phen-DalPhos through the preparation and application of
1,1′-ferrocenyl ligands[19] featuring sterically demanding and
modestly electron-donating NHP or phosphonite donor frag-
ments. Herein we report on the synthesis and characterization
of L1 and L2 (Figure 1), and our efforts to apply such ligands
in nickel-catalyzed C–N cross-coupling chemistry.
Results and Discussion
Preparation of the BIPHEN-derived ferrocene L1 (98 % purity)
was carried out in high yield on gram-scale as outlined in
Scheme 1, via treatment of (BIPHEN)PCl[20] with 1,1′-dilithio-
ferrocene-tetramethylethylenediamine adduct[21] in toluene.
Figure 2. Single-crystal X-ray structure of meso-L1 shown with 30 % displace-
ment ellipsoids and with hydrogen atoms and solvate omitted for clarity.
Primed atoms are generated via crystallographic symmetry (inversion center
at 0.5, 0.5, 0.5).
The stereogenic nature of the BIPHEN unit arising from
atropisomerism about the aryl–aryl linkage results in both meso
(RS,SR) and rac (RR,SS) isomers of L1, which are formed in ≈ 1:1
ratio as is apparent in the 31P{1H} NMR (180.7 and 180.3 ppm,
In surveying the literature we identified a publication by
corresponding to the rac and meso isomers of L1, respectively) Gudat and co-workers[23] in which the preparation of P-cyclo-
1
and H NMR spectroscopic data. Crystallization of L1 afforded pentadienyl-substituted 1,3,2-diazaphospholenes is reported,
a minute quantity of meso-L1, which was characterized by use including lithiation of an N-mesityl variant and quenching with
of NMR spectroscopic and X-ray crystallographic methods. FeCl2 to afford L2, which in turn was spectroscopically charac-
Moreover, use of enantiopure (S)-(BIPHEN)PCl allowed for the terized. Herein we report an alternative complementary route
selective synthesis of L1SS (i.e., representative of rac-L1), to L2 by using a method similar to that employed in the synthe-
thereby allowing for the independent spectroscopic characteri- sis of L1 (Scheme 1) starting from 1,1′-dilithioferrocene-tetra-
zation of meso and rac L1. For each diastereomer of L1, the methylethylenediamine. The crystal structure of L2 is presented
chiral dibenzo[d,f][1,3,2]-dioxaphosphepinyl units themselves in Figure 3, and exhibits geometrical parameters associated
possesses no internal symmetry; however, the two di- with the NHP unit that are analogous to those found in some
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other N-mesityl-substituted 1,3,2-diazaphospholene com-
pounds.[17]
Figure 4. Reaction screening involving L1 (meso + rac mixture), L1SS, and L2
in selected nickel-catalyzed C–N cross-couplings of (hetero)aryl chlorides,
with conversion to the product given on the basis of calibrated GC data
employing authentic materials and using dodecane or 1-phenyldodecane as
internal standards. In all cases the mass balance corresponds primarily to
unreacted starting materials. aIsolated yield following column chromatogra-
phy on silica. See the Experimental Section for complete details.
Figure 3. Single-crystal X-ray structure of L2 shown with 30 % displacement
ellipsoids and with the solvate and selected hydrogen atoms omitted for
clarity.
With L1 (meso + rac), L1SS, and L2 in hand, we conducted
a reactivity survey employing these ligands in a selection of
representative nickel-catalyzed C–N cross-couplings involving
(hetero)aryl chlorides (5 mol % Ni, 80 °C, 16 h; Figure 4). Cross-
couplings involving furfurylamine, 2-thiophenemethylamine, or
N-octylamine, with 4-chlorobenzonitrile or 4-chloroquinaldine,
afforded synthetically useful conversions to the target C–N
cross-coupling products 1a–1c when using L1; in the case of
1b the product was isolated in 89 % yield following chromato-
graphic purification. In contrast, <10 % conversion of the start-
ing materials was achieved when using L2 under analogous
conditions, with these or the other substrate pairings examined
herein. Given that L1 is composed of a mixture of meso and rac
isomers (vide supra), we became interested in exploring further
the performance of L1 vs. L1SS (representative of rac-L1) in
cross-couplings leading to the formation of 1d–1g. While mod-
est differences in conversion were noted in reactions involving
furfurylamine (giving 1d and 1e), more pronounced and diver-
gent variation in conversion was noted in transformations of
indole or morpholine with 4-chlorobenzonitrile (giving 1f and
1g), with rac-L1 apparently proving more effective in the former
and meso-L1 in the latter. These observations are in keeping
with our prior findings that the meso and rac isomers of PAd2-
DalPhos, featuring two chiral (racemic) phosphaadamantane
(CgP) donor fragments, exhibit different catalytic competencies
in nickel-catalyzed C–N cross-coupling.[15c] While the results fea-
tured in Figure 4 establish the basic competence of L1 in such
transformations, the poor (< 10 %) conversion achieved by use
of Ni(COD)2/L1 in reactions of more challenging electron-rich
electrophiles such as 4-chloroanisole or 2-chloro-1,4-dimethyl-
benzene with furfurylamine or indole highlights the inferiority
of L1 vs. DPPF itself and variants featuring substitution on the
P-aryl rings.[24]
Conclusion
In conclusion, we have developed synthetic routes to bulky,
crystallographically characterized 1,1′-ferrocenyl ligands featur-
ing either dioxaphosphepine (L1) or diazaphospholene (L2) do-
nor moieties, and have tested their ability to promote some
representative nickel-catalyzed C–N cross-coupling reactions.
While L2 proved ineffective in the test reactions examined un-
der the conditions employed, L1 proved competent in cross-
couplings involving primary/secondary alkylamine or indole
nucleophiles with (hetero)aryl chlorides, with the catalytic per-
formance of rac and meso-L1 differing in the case of some sub-
strate pairings. While the catalytic performance of L1 did not
exceed that of DPPF or related P-aryl variants disclosed previ-
ously, the competence of L1 in the nickel-catalyzed C–N cross-
couplings disclosed herein serves to expand the “tool box” of
ligands that are available to synthetic chemists in the quest to
solve currently unmet challenges in cross-coupling chemistry
and beyond.
Experimental Section
General Considerations: Unless otherwise indicated, all experi-
mental procedures were conducted in a nitrogen-filled, inert atmos-
phere glove-box using oven-dried glassware and purified solvents,
with the exception of the workup of catalytic reaction mixtures,
which was conducted on the benchtop in air using unpurified sol-
vents. For solvents used within the glove-box, the following purifi-
cation methods were used: tetrahydrofuran was dried with
Na/benzophenone followed by distillation under an atmosphere of
nitrogen gas; toluene and hexanes were each deoxygenated by
sparging with nitrogen gas followed by passage through a double
column solvent purification system packed with alumina and cop-
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per-Q5 reactant and storage over activated 4 Å molecular sieves;
CH2Cl2 was deoxygenated by sparging with nitrogen gas followed
by passage through a double column solvent purification system
packed with alumina and storage over activated 4 Å molecular
(s, 6H, CH3), 1.70 (s, 6H, CH3), 1.51 (s, 18H, C(CH3)3), 1.00 (s, 18H,
C(CH3)3). 13C{1H} UDEFT NMR (125.8 MHz, CDCl3): δ = 148.0 (ArC),
145.9 (d, JC-P = 5.8 Hz, ArC), 138.1 (ArC), 137.2 (ArC), 135.0 (ArC),
133.7 (ArC), 133.3 (d, JC-P = 5.3 Hz, ArC), 132.4 (ArC), 131.4 (d, JC-P
=
=
sieves; cyclopentyl methyl ether (CPME) and CH3CN were each de- 2.3 Hz, ArC), 131.2 (ArC), 128.4 (ArC), 127.9 (ArC), 78.8 (d, JC-P
gassed by use of three freeze-pump-thaw cycles and was stored
over activated 4 Å molecular sieves. (BIPHEN)PCl,[20] 1,1′-dilithio-
ferrocene-tetramethylethylenediamine adduct,[21] and 2-bromo-1,3-
dimesityl-1,3,2-diaza-phospholene[25] were prepared according to
37.7 Hz, CpC), 74.4 (d, JC-P = 40.8 Hz, CpC), 71.7 (CpC), 71.3
(d, JC-P = 7.5 Hz, CpC), 70.7 (CpC), 35.0 [C(CH3)3], 34.9 [C(CH3)3], 32.3
[C(CH3)3], 31.4 (d, JC-P = 4.8 Hz, (C(CH3)3)), 20.8 (CH3), 20.5 (CH3), 16.7
(CH3), 16.5 (CH3). 31P{1H} NMR (202.5 MHz, CDCl3): δ = 180.7 (s).
literature protocols. All other commercial solvents, reagents, and Diastereomerically pure crystals of meso-L1 (confirmed through X-
materials were used as received. GC data were obtained on an in- ray crystallographic analysis) were obtained through vapor diffusion
strument equipped with an SGE BP-5 column (30 m, 0.25 mm i.d.).
Flash column chromatography was carried out in air using Silicycle
Siliaflash 60 silica (particle size 40–63 μm; 230–400 mesh). All 1H
NMR (500 and 300 MHz), 13C{1H} NMR (125.8 and 75.4 MHz), and
31P{1H} NMR (202.5 and 121.5 MHz) spectra were recorded at 300 K
and were referenced to residual protio solvent peaks (1H), deuter-
ated solvent peaks (13C{1H}), or external 85 % H3PO4 (31P{1H}). Split-
ting patterns are indicated as follows: br, broad; s, singlet; d, dou-
blet; t, triplet; q, quartet; m, multiplet. All coupling constants (J) are
reported in Hertz (Hz). Mass spectra were obtained using ion trap
(ESI) instruments operating in positive mode. Crystallographic data
were obtained at or below –80 °C, on a Bruker D8/APEX II CCD
diffractometer equipped with a CCD area detector using Cu-Kα
of acetonitrile into a solution of L1 in tetrahydrofuran, allowing for
full independent NMR characterization of the as-prepared meso/rac
mixture. Data for meso-L1: 1H NMR (500 MHz, CDCl3): δ = 7.16 (s,
2H, ArH), 6.89 (s, 2H, ArH), 4.57 (br s, 2H, CpH), 4.52 (br s, 2H, CpH),
4.40 (br s, 2H, CpH), 3.87 (br s, 2H, CpH), 2.26 (s, 6H, CH3), 2.24 (s,
6H, CH3), 1.89 (s, 6H, CH3), 1.73 (s, 6H, CH3), 1.54 (s, 18H, C(CH3)3),
1.00 (s, 18H, C(CH3)3). 13C{1H} UDEFT NMR (125.8 MHz, CDCl3): δ =
148.0 (ArC), 145.7 (d, JC-P = 5.6 Hz, ArC), 138.1 (d, JC-P = 2.4 Hz, ArC),
137.2 (ArC), 135.1 (ArC), 133.8 (ArC), 133.3 (d, JC-P = 5.0 Hz, ArC),
132.4 (ArC), 131.5 (d, JC-P = 2.9 Hz, ArC), 131.3 (ArC), 128.5 (ArC),
127.9 (ArC), 79.0 (d, JC-P = 38.8 Hz, CpC), 74.6 (d, JC-P = 40.3 Hz, CpC),
71.7 (CpC), 71.4 (d, JC-P = 7.3 Hz, CpC), 70.4 (CpC), 35.0 (C(CH3)3,
two overlapping resonances) 32.3 [C(CH3)3], 31.5 (d, JC-P = 4.9 Hz,
(α = 1.54178 Å) (microfocus source) radiation for meso-L1 or graph- C(CH3)3), 20.8 (CH3), 20.6 (CH3), 16.9 (CH3), 16.5 (CH3). 31P{1H} NMR
ite-monochromated Mo-Kα (α = 0.71073) radiation for L2 employ- (202.5 MHz, CDCl3): δ = 180.3 (s). HRMS m/z ESI+ found 973.4114
ing samples that were mounted in inert oil and transferred to a
cold gas stream on the diffractometer. Data reduction, correction
for Lorentz polarization, and absorption correction (Gaussian inte-
gration; face-indexed) were each performed. Structure solution by
using intrinsic phasing was carried out, followed by least-squares
refinement on F2. All non-hydrogen atoms were refined with aniso-
tropic displacement parameters, while all hydrogen atoms were
added at calculated positions and refined by use of a riding model
employing isotropic displacement parameters based on the iso-
tropic displacement parameter of the attached atom.
[M + Na]+ calculated for C58H72FeNaO4P2 973.4147.
Synthesis of L2: Although this compound has been reported previ-
ously,[23] an alternative synthetic method is described herein. The
reaction was setup using an inert-atmosphere protocol similar to
that described for the synthesis of L1, employing 1,1′-dilithioferro-
cene-tetramethylethylenediamine adduct (1.08 mmol), and 2-
bromo-1,3-dimesityl-1,3,2-diazaphospholene (2.26 mmol) in place
of (BIPHEN)PCl, in toluene (6 mL) at –33 °C. Upon combination of
the reagents, the reaction mixture was stirred magnetically with
warming to room temperature over the course of 4 h. The reaction
mixture was dried in vacuo, subsequently dissolved in dichloro-
methane (10 mL) and filtered through a sintered glass frit contain-
ing Celite and silica. The solvent from the collected eluent was re-
moved in vacuo, the resultant residue was washed with hexanes
(3 × 4 mL), and the resultant solid was dried in vacuo to afford the
product in 32 % yield (290 mg, 0.35 mmol) as a yellow solid. NMR
spectroscopic data for L2 were in agreement with the literature.[23]
CCDC 1885150 (for meso-L1), and 1885151 (for L2) contain the sup-
plementary crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge Crystallographic Data
Centre.
Synthesis of L1: In a dinitrogen filled glove-box, a Schlenk flask
containing a magnetic stir bar was charged with 1,1′-dilithioferro-
cene-tetramethylethylenediamine adduct (933 mg, 2.97 mmol) and
toluene (10 mL), and was cooled to –33 °C. A separate vial contain-
ing a magnetic stir bar was charged with racemic (BIPHEN)PCl
(2.49 g, 5.94 mmol) and toluene (18 mL), and magnetic stirring was
initiated to dissolve (BIPHEN)PCl, followed by cooling to –33 °C. To
the stirring solution of 1,1′-dilithioferrocene-tetramethylethylenedi-
amine adduct was added the solution of (BIPHEN)PCl dropwise, and
the resulting mixture was allowed to reach room temperature be-
fore the flask was sealed, taken out of the glove-box, and heated
at 110 °C for 24 h under the influence of magnetic stirring. The flask
was then brought back into the glove-box and was cooled to –33 °C
for 30 minutes. The resulting mixture was filtered through Celite
and the collected eluent was concentrated in vacuo to afford L1 in
a ≈ 1:1 ratio of meso (RS,SR) and rac (RR,SS) isomers as estimated
General Procedure for the Monoarylation of Primary Amines
and Indoles with Aryl Chlorides (GP1): For primary amines: Within
a dinitrogen filled glove-box, L1 (0.05 equiv.), NaOtBu (2.0 equiv.),
and aryl chloride (1.0 equiv.) were added to a screw capped vial
containing a magnetic stir bar, followed by the addition of bis(cyclo-
octadiene)-nickel(0) (0.05 equiv.) dissolved in toluene (0.12
M aryl
halide). To this solution was added furfurylamine (1.1 equiv.), and
the vial was sealed with a cap containing a PTFE septum, removed
from the glove-box and placed in a temperature-controlled alumi-
num heating block set to 80 °C for 16 h under the influence of
magnetic stirring. For indoles: Analogous conditions were followed
except LiOtBu (1.5 equiv.) was utilized as base, and indole was
added just prior to the addition of bis(cyclooctadiene)-nickel(0) so-
lution. After cooling to room-temperature, either dodecane or 1-
phenyldodecane (0.12 mmol) was added to the reaction mixture
as an internal standard, so that the resulting mixtures could be
quantitatively analyzed by using GC methods following the workup
method stated below.
1
on the basis of both 31P{1H} NMR and H NMR spectroscopic data
(2.55 g, 90 %). In synthesizing L1SS, an analogous procedure was
followed implementing enantiopure (S)-(BIPHEN)PCl, giving rise to
a similarly high yield of L1SS (88 %). Data for L1SS (i.e., representa-
1
tive of rac-L1) H NMR (500 MHz, CDCl3): δ = 7.15 (s, 2H, ArH), 6.86
(s, 2H, ArH), 4.60 (br s, 2H, CpH), 4.50, (br s, 2H, CpH), 4.40 (br s, 2H,
General Procedure for the N-Arylation of Morpholine with Aryl
CpH), 3.61 (br s, 2H, CpH), 2.25 (s, 6H, CH3), 2.19 (s, 6H, CH3), 1.81
Chlorides (GP2): Within
a dinitrogen filled glove-box, L1
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(0.05 equiv.), LiOtBu (1.5 equiv.), and aryl chloride (1.0 equiv.) were
added to a screw capped vial containing a magnetic stir bar, fol-
lowed by the addition of bis(cyclooctadiene)-nickel(0) (0.05 equiv.)
dissolved in CPME (0.5
M aryl halide). To this solution was added
morpholine (1.5 equiv.), and the vial was sealed with a cap contain-
ing a PTFE septum, removed from the glove-box and placed in a
temperature-controlled aluminum heating block set to 80 °C for
16 h under the influence of magnetic stirring. After cooling to
room-temperature, dodecane (0.12 mmol) was added to the reac-
tion mixture as an internal standard, so that the resulting mixture
could be quantitatively analyzed by using GC methods following
the workup method stated below.
Workup Method for Preparation of GC Samples: Following GP1
or GP2, (employing 0.12 mmol aryl halide) in air the reaction mix-
ture was diluted using ethyl acetate and was passed through a
Kimwipe filter containing Celite and silica gel, with the eluent col-
lected in a GC vial. Response-factor calibrated GC estimates are
given on the basis of data obtained from authentic materials using
dodecane or 1-phenyldodecane as internal standards.
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Isolation of 2-Methyl-N-(2-thienylmethyl)–4-quinolinamine
(1b): The title compound was synthesized from the corresponding
aryl chloride (1.0 mmol) according to GP1. The reaction mixture was
diluted with ethyl acetate (20 mL) and washed with brine
(3 × 20 mL), and the organic layer was dried with sodium sulfate.
The solvent was removed in vacuo and the compound was purified
by flash column chromatography on silica gel using a trimethyl-
amine/ethyl acetate eluent (4 % triethylamine) which afforded the
title product in 89 % isolated yield (226 mg, 0.89 mmol) as an off-
white solid. 1H NMR (300 MHz; CDCl3): δ = 7.93 (m, 1H), 7.69 (m,
1H), 7.61 (m, 1H), 7.38 (m, 1H), 7.29 (dd, 1H, J1 = 5.1 Hz, J2 = 1.2),
7.10 (m, 1H), 7.02 (dd, 1H, J1 = 5.1 Hz, J2 = 3.5), 6.46 (s, 1H), 5.22
(br. s, 1H), 4.70 (d, 2H, J = 5.2 Hz), 2.63 (s, 3H). 13C{1H} UDEFT NMR
(125.8 MHz, CDCl3): δ = 160.0, 149.3, 148.7, 141.0, 129.7, 129.5,
127.5, 126.4, 125.7, 124.5, 119.4, 117.7, 100.1, 43.0, 26.2. HRMS m/z
ESI+ found 255.0957 [M + H]+ calculated for C15H15N2S 255.0950.
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We are grateful to the NSERC of Canada (Discovery Grant
RGPIN-2014-04807 for M. S.; PGS-D for J. S. K. C.; CGS-M for
R. T. M.), the Province of Nova Scotia (Graduate Scholarship for
R. T. M.), the Killam Trusts, and Dalhousie University for their
support of this work. M. Y. S. acknowledges NSERC-CREATE Sus-
tainable Synthesis for supporting an internship in the Stradiotto
group. We also thank Dr. Michael Lumsden and Mr. Xiao Feng
(Dalhousie) for technical assistance in the acquisition of NMR
and MS data.
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Keywords: Amination · C–N cross-coupling · Ferrocenyl
ligands · Ligand design · Nickel
Received: September 9, 2019
Eur. J. Inorg. Chem. 2019, 4112–4116
www.eurjic.org
4116
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim