Air-Stable NNS (ENENES) Ligands and Their Well-Defined Ruthenium and Iridium Complexes for Molecular Catalysis

Article abstract of DOI:10.1021/acs.organomet.5b00432

We introduce ENENES, a new family of air-stable and low-cost NNS ligands bearing NH functionalities of the general formula E(CH₂)_mNH(CH₂)_nSR, where E is selected from -NC₄H₈O, -NC₄H₈, or -N(CH₃)₂, m and n = 2 and/or 3, and R = Ph, Bn, Me, or SR (part of a thiophenyl fragment). The preparation and characterization of more than 15 examples of well-defined Ru and Ir complexes supported by these ligands that are relevant to bifunctional metal-ligand M/NH molecular catalysis are reported. Reactions of NNS ligands with suitable Ru or Ir precursors afford rich and diverse solid-state and solution chemistries, producing monometallic molecules as well as bimetallics in which the ligand coordinates to the metal via either bidentate (κ²[N,N'] or κ²[N',S]) or tridentate (κ³[N,N',S]) binding modes, depending on the basicity of the sulfur atom, CH₂ chain length (m or n parameter), or identity of the transition metal. In the case of Ir, ligands bearing benzyl substituents lead to unprecedented κ⁴[N,N',S,C]-tetradentate core-structure complexes of the type [Ir^IIIHCl{κ⁴(N,N',S,C)-ligand}], resulting from ortho-metalation via C-H oxidative addition. Fourteen of these Ru and Ir complexes have been crystallographically characterized. Air- and moisture-stable complexes of the type trans-[Ru^IICl₂{κ³[N,N',S]-ligand}(L)] (L = PPh₃, PCy₃, DMSO), and others, effect the selective hydrogenation of methyl trifluoroacetate into the important synthon trifluoroacetaldehyde methyl hemiacetal in basic methanol under relatively mild conditions (35-40 °C, 25 bar H₂) with reasonable turnover numbers (i.e., > 1000), whereas the air-stable Ir monohydride complexes [Ir^IIIHCl{κ⁴(N,N',S,C)-ligand}] exhibit excellent catalytic activities and high chemoselectivity for the same reaction, reaching turnover numbers of >10 000.

Full text of DOI:10.1021/acs.organomet.5b00432

Article
pubs.acs.org/Organometallics
Air-Stable NNS (ENENES) Ligands and Their Well-Defined Ruthenium
and Iridium Complexes for Molecular Catalysis
Pavel A. Dub,*,† Brian L. Scott,‡ and John C. Gordon*,†
‡
†Chemistry Division, and Materials and Physics Applications Division, Los Alamos National Laboratory, Los Alamos, New Mexico
87545, United States
S
* Supporting Information
ABSTRACT: We introduce ENENES, a new family of air-
stable and low-cost NNS ligands bearing NH functionalities of
the general formula E(CH2)mNH(CH2)nSR, where E is
selected from −NC4H8O, −NC4H8, or −N(CH3)2, m and n
= 2 and/or 3, and R = Ph, Bn, Me, or SR (part of a thiophenyl
fragment). The preparation and characterization of more than
15 examples of well-defined Ru and Ir complexes supported by
these ligands that are relevant to bifunctional metal−ligand M/
NH molecular catalysis are reported. Reactions of NNS ligands
with suitable Ru or Ir precursors afford rich and diverse solid-state and solution chemistries, producing monometallic molecules
as well as bimetallics in which the ligand coordinates to the metal via either bidentate (κ2[N,N′] or κ2[N′,S]) or tridentate
(κ3[N,N′,S]) binding modes, depending on the basicity of the sulfur atom, CH2 chain length (m or n parameter), or identity of
the transition metal. In the case of Ir, ligands bearing benzyl substituents lead to unprecedented κ4[N,N′,S,C]-tetradentate core-
structure complexes of the type [IrIIIHCl{κ4(N,N′,S,C)−ligand}], resulting from ortho-metalation via C−H oxidative addition.
Fourteen of these Ru and Ir complexes have been crystallographically characterized. Air- and moisture-stable complexes of the
type trans-[RuIICl2{κ3[N,N′,S]−ligand}(L)] (L = PPh3, PCy3, DMSO), and others, effect the selective hydrogenation of methyl
trifluoroacetate into the important synthon trifluoroacetaldehyde methyl hemiacetal in basic methanol under relatively mild
conditions (35−40 °C, 25 bar H2) with reasonable turnover numbers (i.e., > 1000), whereas the air-stable Ir monohydride
complexes [IrIIIHCl{κ4(N,N′,S,C)−ligand}] exhibit excellent catalytic activities and high chemoselectivity for the same reaction,
reaching turnover numbers of >10 000.
ketones,10d,g,h,13c various acceptorless dehydrogenation-
1. INTRODUCTION
s,9e,g,h,p,q,10c,12b,c,e,13b,16,17 catalytic hydrolysis10f or dehydrogen-
Ligand design plays a determining role in developing
ation9j,r−t of ammonia or amine boranes, domino-synthesis of
unprecedented catalytic transformations.1 The vast majority
indoles,9f stereospecific polymerization of 1,3-butadiene,13e,f
of ligands used in homogeneous catalysis are based on P and/or
N donor atoms, and an enormous number of such ligands have
ethylene tetra-11a and trimerization,11b and others.9o,10i,18 The
been designed and synthesized over the past four decades.1c,e,2
Schneider group reported a variety of PNP-based complexes of
Ru,19 Ir,20 Pd,21 Fe,22 and Rh,23 some of which are relevant to
It is generally accepted that polydentate chelating ligands
stoichiometric molecular nitrogen cleavage19c,23a or C−H20g
bond activation, respectively. Gusev reported Re complexes
supported by a PNP scaffold.24
bearing NH functionalities3 play a crucial role in so-called
bifunctional metal−ligand (M/NH) cooperative molecular
catalysis,4 in which a noninnocent ligand is proposed to
directly participate in substrate activation via an N−H group
and/or an act of bond cleavage/formation via N−H proton
transfer, respectively. Most practical bifunctional catalysts, e.g.,
(R)-RUCY-XylBINAP5 or Ru-MACHO6 developed by Taka-
sago International Corp., are typically composed of oxygen-
sensitive phosphorus (P)-containing ligands,4c−g usually with
C2-symmetry.7 The commercially available PNP ligand family8
of the general formula R2P(CH2)2NH(CH2)2PR2, as shown in
Figure 1, in combination with Ru6,9 and Ir,9q,10 as well as Cr,11
Fe,9i,12 Co,13 Ni,14 Mo,15 W,15 and Os,16 have been used as
(pre)catalysts in numerous homogeneous hydrogenations of
CO2,9a,10j carbonates,9u esters,6,9b,d,i,k−n,10a,12a,d,f,g heterocy-
cles,12c ketones,10e,13a,d imines,15 and alkenes,10e,13a,d,14 transfer
hydrogenation of organic formates and cyclic carbonates9c and
Progress in catalysis science and technology requires the
development of novel ligands bearing tunable functions.
Insensitivity to air, the ability to easily vary structures based
on cheap, readily available starting materials (i.e., fine-tuning of
ligand conformational, steric, and electronic properties), and
the use of simple synthetic procedures and protocols should all
be key factors taken into account for successful ligand design
within the concept of green chemistry.25 Here we introduce
“ENENES”,26 a new family of NNS ligands of the general
formula E(CH2)mNH(CH2)nSR, where E is selected from
−NC4H8O, −NC4H8, or −N(CH3)2, m and n = 2 and/or 3,
Received: May 21, 2015
© XXXX American Chemical Society
A
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Article
sulfoxide), and [IrCl(η2-COE)2]2 (COE = cyclooctene) in a
suitable solvent at room temperature or under reflux afford rich
and diverse solid-state and solution chemistries. Monometallic
molecules or dimers in which the ligand coordinates to the
metal via bidentate κ2[N,N′] vs κ2[N′,S], tridentate κ3[N,N′,S],
and even unprecedented κ4[N,N′,S,C]-tetradentate binding
motifs are obtained, depending on the basicity of the sulfur
atom, CH2 chain length (m or n parameters), R substituent, and
the nature of the transition metal. Syntheses, solution
characterization, and crystallographic studies of these new
complexes are described. As a demonstration of the utility of
the ligands particularly in homogeneous hydrogenation
catalysis, we show that a suitable combination of ENENES/
transition metal effects the selective hydrogenation of methyl
trifluoroacetate into the important synthon trifluoroacetalde-
hyde methyl hemiacetal under relatively mild conditions (35−
40 °C, 25 bar, in basic methanol) and with good turnover
numbers (i.e., >1000 or even >10 000 in some cases), an
indispensable requirement for industrial use.
2. EXPERIMENTAL DETAILS
2.1. General Procedures. All organic syntheses were performed
in a fume hood in air. Solvents and reagents for organic synthesis such
as phosphorus tribromide, 2-(phenylthio)ethanol, 2-(methylthio)-
ethanol, ethylene sulfide, trimethylene sulfide, 2-(4-morpholinyl)-
ethanamine, 3-morpholinopropylamine, 1-(2-aminoethyl)pyrrolidine,
1-(2-aminoethyl)piperazine, and 2-chloroethyl methyl sulfide were
purchased from Sigma-Aldrich and used as received. 2-Thiophene-
carbaldehyde (Sigma-Aldrich) was distilled prior to use. Benzyl
bromide (Alfa Aesar), N,N-dimethylethylenediamine (TCI), and
anhydrous potassium carbonate (Fischer Scientific) were used as
received. 2-Bromoethyl phenyl sulfide (PhSCH2CH2Br),27 2-bro-
moethyl methyl sulfide (MeSCH2CH2Br),28 2-bromoethyl benzyl
sulfide (BnSCH2CH2Br),29 and 3-bromopropyl benzyl sulfide
(BnCH2CH2CH2Br),30 used in the preparation of ENENES ligands
Figure 1. A commercially available PNP family of ligands (top) and
air-stable NNS ligands (ENENES) from this work (bottom) relevant
to bifunctional molecular catalysis originating as accepted from metal−
ligand (M/NH) synergism.
and R = Ph, Bn, Me, or SR (part of a thiophenyl fragment) (9
representative examples, ligands 1a−1d, 2a−5a, and 4b, Figure
1), that satisfy all of the criteria outlined above. Reactions of
ENENES ligands with [RuCl2(PPh3)3], [RuCl2(η4-COD)]n/
PR3 (COD = cycloocta-l,5-diene, PR3 = PPh3, PCy3, P(C6F5)3),
[RuCl2(η4-COD)]n, [RuCl2(DMSO)4] (DMSO = dimethyl
Scheme 1. Synthesis of ENENES Ligands 1−5: Isolated Yields after Fractional or Simple (Ligand 5a) Vacuum Distillations
a
b
c
Contains ∼6% BnBr. Crude yield in the 21:79 mixture with 2-(4-(2-(phenylthio)ethyl)piperazin-1-yl)ethanamine.38 Was also prepared from
MeSCH2CH2Cl in 34% isolated yield, albeit using a longer reaction time (40 h).
B
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1−4, were synthesized via the reaction of 2-(phenylthio)ethanol or 2-
(methylthio)ethanol with PBr3 or by ring opening of ethylene sulfide
or propylene sulfide with BnBr using published or partially modified
procedures as described in the SI and shown in Scheme 1. All products
were isolated in ∼90% yield, except MeSCH2CH2Br, possibly because
of its instability28a during the workup procedure. The latter could be
obtained from ethylene and MeSBr in 74% yield.28d All organometallic
complexes and catalytic samples were prepared in a glovebox under an
argon atmosphere. Anhydrous solvents (dichloromethane, toluene,
THF, diethyl ether, pentane, methanol), [RuCl2(PPh3)3],
[RuCl2(DMSO)4, [IrCl(η2-COE)2]2, and sodium methoxide (95%,
powder) were purchased from Sigma-Aldrich and used as received.
[RuCl2(η4-COD)]n (Strem), Ru-MACHO (739103 Aldrich), Gusev’s
Ru-SNS (97%, 746339 Aldrich), Milstein’s Ru-PNN (735809 Aldrich),
(R,R)-Ts-DENEB (T3078, TCI), (R)-RUCY-XylBINAP (R0139,
TCI), and Abdur-Rashid’s Ir-PNP (min 98%, 77-0500 Strem) were
used as received. Elemental analysis was performed by Midwest
Microlab, LLC (Indianapolis, IN, USA), under air or under inert
atmosphere, respectively. All NMR experiments were carried out on a
3JH−H = 7 Hz, 2H), 2.82 (t, 3JH−H = 7 Hz, 2H), 3.05 (t, 3JH−H = 7 Hz,
3
3
2H), 3.69 (t, JH−H ≈ 4 Hz, 4H), 7.16 (t, JH−H ≈ 7 Hz, 1Hpara), 7.26
3
3
(t, JH−H ≈ 8 Hz, 2Hmeta), 7.34 (d, JH−H ≈ 7 Hz, 2Hortho). 13C{1H}
NMR (100.5 MHz, CDCl3, rt): δ 26.7 (s, 1C), 34.2 (s, 1C), 48.1 (s,
1C), 48.3 (s, 1C), 53.8 (s, 2C), 57.3 (s, 1C), 67.0 (s, 2C), 126.1 (s,
1Cpara, Ph), 128.9 (s, 2Cortho, Ph), 129.6 (s, 2Cmeta, Ph), 135.9 (s,
1Cipso).
2-(Phenylthio)-N-(2-(pyrrolidin-1-yl)ethyl)ethylamine (1c). To a
solution of 1-(2-aminoethyl)pyrrolidine (4.57 g, 0.04 mol) in MeCN
(80 mL) were added successively 2-bromoethyl phenyl sulfide (8.70 g,
0.04 mol) and anhydrous potassium carbonate (15.20 g, 0.11 mol)
with stirring. The resulting suspension was refluxed for 16 h, cooled to
room temperature, and filtered (the filter was washed with MeCN, 2 ×
10 mL), and the solvent was removed by evaporation on a Rotavap to
afford 9.72 g of the viscous, orange-yellow oil (60 °C, 1 h). The
desired product was obtained by fractional vacuum distillation on a
simple distillation kit containing two theoretical plates. The first
collected fraction that boiled at 26−28 °C corresponds to residual 1-
(2-aminoethyl)pyrrolidine (recovery ∼1 mL). The second collected
fraction that boiled at 130−142 °C corresponds to the desired
product. Isolated yield: 4.94 g (49%, based on 2-bromoethyl phenyl
sulfide) of a clear yellowish oil. Anal. Calcd for C14H22N2S (250.40):
1
Bruker AV400 MHz spectrometer. H, 13C{1H}, and 31P{1H} NMR
spectra were calibrated relative to TMS and H3PO4, respectively, in
ppm (δ). 19F NMR spectra were measured without lock but properly
shimmed in methanol and calibrated relative to 2,2,2-trifluoroethanol
(product C), δ taken as −77.0 ppm. A detailed description of catalytic
experiments is deposited in the SI. NMR spectra and/or charts for all
ligands and complexes are deposited in the SI.
1
C, 67.15; H, 8.86; N, 11.19. Found: C, 66.88; H, 8.59; N, 10.79. H
NMR (400 MHz, CDCl3, rt): δ 1.67 (brs, 1H, NH), 1.78 (brs, 4H),
2.50 (brs, 4H), 2.59 (t, 3JH−H = 6 Hz, 2H), 2.74 (t, 3JH−H = 6 Hz, 2H),
2.88 (t, 3JH−H ≈ 6 Hz, 2H), 3.08 (t, 3JH−H ≈ 6 Hz, 2H), 7.19 (t, 3JH−H
≈ 7 Hz, 1Hpara), 7.29 (t, 3JH−H ≈ 8 Hz, 2Hmeta), 7.37 (d, 3JH−H ≈ 8 Hz,
2Hortho). 13C{1H} NMR (100.5 MHz, CDCl3, rt): δ 23.5 (s, 2C), 34.2
(s, 1C), 48.3 (s, 1C), 48.6 (s, 1C), 54.2 (s, 2C), 56.0 (s, 1C), 126.1 (s,
1Cpara, Ph), 128.9 (s, 2Cortho, Ph), 130.0 (s, 2Cmeta, Ph), 136.0 (s,
1Cipso).
2.2. Syntheses. 2-Morpholino-N-(2-(phenylthio)ethyl)-
ethylamine (1a). To a solution of 2-(4-morpholinyl)ethanamine
(13.1 mL, 0.1 mol) in MeCN (200 mL) were added successively 2-
bromoethyl phenyl sulfide (15.1 mL, 0.1 mol) and anhydrous
potassium carbonate (38.9 g, 0.28 mol) with stirring. The resulting
suspension was refluxed for 16 h, cooled to room temperature, and
filtered (the residue on the filter was washed with MeCN, 2 × 15 mL),
and the solvent was removed by evaporation on a Rotavap to afford
N1,N1-Dimethyl-N2-(2-(phenylthio)ethyl)ethane-1,2-diamine (1d).
To a solution of N,N-dimethylethylenediamine (10.9 mL, 0.1 mol) in
MeCN (200 mL) were added successively 2-bromoethyl phenyl sulfide
(15.08 mL, 0.1 mol) and anhydrous potassium carbonate (38.9 g, 0.28
mol) with stirring. The resulting suspension was refluxed for 16 h,
cooled to room temperature, and filtered (the filter was washed with
MeCN, 2 × 15 mL), and the solvent was removed by evaporation on a
Rotavap to afford 18.54 g of the viscous, yellowish oil (60 °C, 1 h).
The desired product was obtained by fractional vacuum distillation on
a simple distillation kit containing two theoretical plates. The first
collected fraction that boiled at 30−33 °C corresponds to N,N-
dimethylethylenediamine (recovery ∼2.9 mL). The second collected
fraction that boiled at 90−110 °C corresponds to the desired product.
Isolated yield: 11.22 g (50%, based on 2-bromoethyl phenyl sulfide) as
a clear, almost transparent (slightly yellowish) oil. Anal. Calcd for
C12H20N2S (224.37): C, 64.24; H, 8.99; N, 12.49. Found: C, 64.19; H,
8.87; N, 12.46. 1H NMR (400 MHz, CDCl3, rt): δ 1.83 (brs, 1H, NH),
1
24.78 g of a viscous yellow oil (55 °C, 1 h, 40 mbar). H NMR
specroscopy performed on the oil revealed a mixture of three amines:
the starting 2-morpholinoethylamine (16%), the desired product, 2-
morpholino-N-(2-(phenylthio)ethyl)ethylamine (68%), and 2-mor-
pholino-N,N-bis(2-(phenylthio)ethyl)ethylamine (16%) as shown in
Scheme S1. The desired product was obtained by fractional vacuum
distillation on a simple distillation kit without theoretical plates. The
first collected fraction that boiled at 35−39 °C corresponds to residual
2-(4-morpholinyl)ethanamine (recovery 1.97 g, ∼2 mL, transparent
liquid). The second collected fraction that boiled at 145−167 °C
corresponds to the desired product. Isolated yield: 15.45 g (58%, based
on 2-bromoethyl phenyl sulfide) as a clear yellowish oil. Anal. Calcd
for C14H22N2OS (266.40): C, 63.12; H, 8.32; N, 10.52. Found: C,
63.04; H, 8.22; N, 10.42. 1H NMR (400 MHz, CDCl3, rt): δ 1.77 (brs,
3
3
3
3
1H, NH), 2.43 (vt, JH−H ≈ 5 Hz, 4H), 2.48 (t, JH−H = 6 Hz, 2H),
2.19 (s, 6H), 2.37 (t, JH−H = 6 Hz, 2H), 2.65 (t, JH−H = 6 Hz, 2H),
2.83 (t, 3JH−H ≈ 7 Hz, 2H), 3.04 (t, 3JH−H ≈ 7 Hz, 2H), 7.15 (t, 3JH−H
≈ 7 Hz, 1Hpara), 7.25 (t, 3JH−H ≈ 8 Hz, 2Hmeta), 7.33 (d, 3JH−H ≈ 8 Hz,
2Hortho). 13C{1H} NMR (100.5 MHz, CDCl3, rt): δ 34.1 (s, 1C), 45.5
(s, 2C), 47.0 (s, 1C), 48.6 (s, 1C), 59.1 (s, 1C), 126.1 (s, 1Cpara, Ph),
128.9 (s, 2Cortho, Ph), 130.0 (s, 2Cmeta, Ph), 136.0 (s, 1Cipso).
2.70 (t, 3JH−H = 6 Hz, 2H), 2.86 (t, 3JH−H = 6 Hz, 2H), 3.08 (t, 3JH−H
=
6 Hz, 2H), 3.70 (t, 3JH−H ≈ 5 Hz, 4H), 7.19 (t, 3JH−H ≈ 7 Hz, 1Hpara),
3
3
7.28 (t, JH−H ≈ 8 Hz, 2Hmeta), 7.36 (d, JH−H ≈ 8 Hz, 2Hortho).
13C{1H} NMR (100.5 MHz, CDCl3, rt): δ 34.1 (s, 1C), 45.7 (s, 1C),
48.4 (s, 1C), 53.7 (s, 2C), 58.3 (s, 1C), 67.0 (s, 2C), 126.2 (s, 1Cpara
,
Ph), 128.9 (s, 2Cortho, Ph), 130.0 (s, 2Cmeta, Ph), 135.9 (s, 1Cipso).
2-(Methylthio)-N-(2-morpholinoethyl)ethanamine (2a). Method
A (from MeSCH2CH2Br). To a solution of 2-(4-morpholinyl)-
ethanamine (5.87 mL, 0.045 mol) in MeCN (90 mL) were added
successively 2-bromoethyl methyl sulfide (6.94 g, 0.045 mol) and
anhydrous potassium carbonate (17.4 g, 0.13 mol) with stirring. The
resulting suspension was refluxed for 16 h, cooled to room
temperature, and filtered (the residue on the filter was washed with
MeCN, 2 × 10 mL), and the solvent was removed by evaporation on a
Rotavap to afford 9.06 g of a yellow suspension (55 °C, 1 h, 40 mbar).
The desired product was obtained by fractional vacuum distillation on
a simple distillation kit without theoretical plates. The first collected
fraction that boiled at 30−31 °C presumably corresponds to residual
2-(4-morpholinyl)ethanamine (recovery ∼1.6 mL, transparent liquid).
The second collected fraction that boiled at 91−115 °C corresponds
to the desired product. Isolated yield: 3.50 g (38%, based on 2-
bromoethyl methyl sulfide) as a transparent liquid. Caution: Higher
3-Morpholino-N-(2-(phenylthio)ethyl)propan-1-amine (1b). This
was prepared similarly to 1a by using 3-morpholinopropylamine (14.6
mL, 0.1 mol) instead of 2-(4-morpholinyl)ethanamine. After solvent
evaporation on a Rotavap, 27.6 g of a viscous, yellow oil was obtained
(55 °C, 1 h, 40 mbar). The desired product was obtained by fractional
vacuum distillation on a simple distillation kit containing two
theoretical plates. The first collected fraction that boiled at 41−46
°C corresponds to residual 3-morpholinopropylamine (recovery ∼2.8
mL, transparent liquid). The second collected fraction that boiled at
141−156 °C corresponds to the desired product. Isolated yield: 15.98
g (57%, based on 2-bromoethyl phenyl sulfide) as a clear almost
transparent (slightly yellowish) oil. Anal. Calcd for C15H24N2OS
(280.43): C, 64.25; H, 8.63; N, 9.99. Found: C, 64.13; H, 8.88; N,
9.99. 1H NMR (400 MHz, CDCl3, rt): δ 1.56 (brs, 1H, NH), 1.64 (q,
3JH−H ≈ 7 Hz, 2H), 2.36 (t, 3JH−H = 8 Hz, 2H), 2.40 (brs, 4H), 2.63 (t,
C
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boiling fraction (>115 °C) contains a mixture of the desired product and
tertiary amine. Anal. Calcd for C9H20N2OS (204.33): C, 52.90; H, 9.87;
N, 13.71. Found: C, 52.98; H, 9.90; N, 13.53. H NMR (400 MHz,
hydrogen evolution. Ten milliliters of MeOH was used to rinse the
residual NaBH4 into the flask, and the system was stirred for 20 h at
room temperature. To the white suspension were slowly added 30 mL
of H2O and then 100 mL of CH2Cl2. The organic phase was extracted.
The residual inorganic phase was washed with 100 mL of CH2Cl2. The
combined phases afforded the crude product as a yellow liquid after
solvent evaporation (7.08 g). The product was purified by vacuum
distillation (109−113 °C). Isolated yield: 5.20 g (60%), transparent
oil. Anal. Calcd for C11H18N2OS (226.34): C, 58.37; H, 8.02; N, 12.38.
Found: C, 58.13; H, 8.20; N, 12.41. 1H NMR (400 MHz, CDCl3, rt):
δ 2.11 (brs, 1H, NH), 2.40 (m, 4H), 2.49 (t, 3JH−H = 6 Hz, 2H), 2.73
(t, 3JH−H = 6 Hz, 2H), 3.68 (m, 4H), 4.01 (s, 2H), 6.89−6.96 (m, 2H),
1
CDCl3, rt): δ 2.08 (s, 3H), 2.18 (brs, 1H, NH), 2.42 (m, 4H), 2.48 (t,
3JH−H = 6 Hz, 2H), 2.64 (t, 3JH−H = 6 Hz, 2H), 2.71 (t, 3JH−H = 6 Hz,
2H), 2.82 (t, 3JH−H = 6 Hz, 2H), 3.68 (vt, 3JH−H ≈ 5 Hz, 4H). 13C{1H}
NMR (100.5 MHz, CDCl3, rt): δ 15.3 (s, 1C), 34.3 (s, 1C), 45.7 (s,
1C), 48.0 (s, 1C), 53.7 (s, 2C), 58.2 (s, 1C), 67.0 (s, 2C).
Method B (from MeSCH2CH2Cl). A similar procedure was used,
although the reaction mixture was refluxed for 40 h. Isolated yield:
3.13 g (34% from 5 g of MeSCH2CH2Cl). Anal. Calcd for C9H20N2OS
(204.33): C, 52.90; H, 9.87; N, 13.71. Found: C, 52.82; H, 10.03; N,
13.50.
2-Morpholino-N-(2-(benzylthio)ethyl)ethylamine (3a). To a sol-
ution of 2-morpholinoethylamine (6.56 mL, 0.05 mol) in MeCN (100
mL) were added successively 2-bromoethyl benzyl sulfide (11.56 g,
0.05 mol) and anhydrous potassium carbonate (19.35 g, 0.14 mol)
with stirring. The resulting suspension was refluxed for 16 h, cooled to
room temperature, and filtered (the residue on the filter was washed
with MeCN, 2 × 10 mL), and the solvent was removed by evaporation
on a Rotavap to afford 13.75 g of a viscous, orange-yellow suspension
(55 °C, 1 h, 40 mbar). The desired product was obtained by fractional
vacuum distillation on a Vigreux column composed of two theoretical
plates. The first collected fraction that boiled at 34−38 °C corresponds
to residual 2-(4-morpholinyl)ethanamine (recovery 1.64 g, ∼1.7 mL).
The second collected fraction that boiled at 132−158 °C corresponds
to the desired product. Isolated yield: 4.81 g (34%, based on 2-
bromoethyl benzyl sulfide) of a clear, dark yellowish oil. Anal. Calcd
for C15H24N2OS (280.43): C, 64.25; H, 8.63; N, 9.99. Found: C,
64.44; H, 8.33; N, 10.23. 1H NMR (400 MHz, CDCl3, rt): δ 1.88 (brs,
3
4
7.20 (dd, JH−H ≈ 5 Hz, JH−H ≈ 1 Hz, 1H). 13C{1H} NMR (100.5
MHz, CDCl3, rt): δ 44.9 (s, 1C), 48.3 (s, 1C), 53.7 (s, 2C), 58.1 (s,
1C), 67.0 (s, 2C), 124.4 (s, 1C), 125.0 (s, 1C), 126.6 (s, 1C), 144.1 (s,
1C).
trans-[RuIICl2{κ3(N,N′,S)-1a}(PPh3)] (I). Method A as shown in
Scheme S3 was used. To [RuCl2(PPh3)3] (360 mg, 0.375 mmol) was
added a solution of 1a (100 mg, 0.375 mmol) in 5 mL of CH2Cl2 with
stirring. The resulting burgundy solution was stirred at rt for 2 h (31P
NMR analysis of the reaction mixture performed after 1 h reveals full
conversion of the starting material into the product, indicated by a
resonance at δ 40.9 ppm, and the presence of free PPh3, δ −5.5 ppm)
and then concentrated to ∼40% in volume. The solution was layered
with Et2O (22 mL) and left for 6 days. After decantation of the mother
liquor, the obtained light pink powder was transferred to a filter frit,
washed with Et2O (3 × 10 mL), and vacuum-dried overnight. Isolated
yield: 236 mg (90%). Anal. Calcd for C32H37Cl2N2OPRuS (700.66):
C, 54.86; H, 5.32; N, 4.00. Found: C, 54.96; H, 5.19; N, 4.03. 31P{1H}
NMR (162 MHz, CD2Cl2, rt): δ 41.0 (s). 1H NMR (400 MHz,
CD2Cl2, rt): δ 2.81 (vt, J ≈ 14 Hz, 1H), 2.93−3.07 (m, 2H), 3.16−
3.39 (m, 7H), 3.46−3.58 (m, 2H), 3.62−3.68 (m, 3H), 3.81 (vt, J ≈
13 Hz, 1H), 5.88 (brs, NH, 1H), 6.98 (t, J ≈ 8 Hz, 2H), 7.20−7.33 (m,
12H), 7.72 (vt, J ≈ 9 Hz, 6H). 13C{1H} NMR (100.5 MHz, CD2Cl2,
rt): δ 44.9 (s, 1C), 47.0 (s, 1C), 48.4 (s, 1C), 52.9 (s, 1C), 54.7 (s,
1C), 59.3 (s, 1C), 60.2 (s, 1C), 61.6 (s, 1C), 127.1 (d, JC−P = 8.7 Hz,
1H, NH), 2.43 (brm, 4H), 2.46 (t, 3JH−H = 6 Hz, 2H), 2.59 (t, 3JH−H
=
3
3
6 Hz, 2H), 2.66 (t, JH−H ≈ 7 Hz, 2H), 2.77 (t, JH−H ≈ 7 Hz, 2H),
3.70 (t, 3JH−H ≈ 7 Hz, 4H), 3.72 (s, 2H), 7.20−7.31 (m, 5H). 13C{1H}
NMR (100.5 MHz, CDCl3, rt): δ 31.7 (s, 1C), 36.2 (s, 1C), 45.7 (s,
1C), 48.4 (s, 1C), 53.8 (s, 2C), 58.3 (s, 1C), 67.0 (s, 2C), 127.0 (s,
1Cpara, Ph), 128.5 (s, 2Cmeta, Ph), 128.8 (s, 2Cortho, Ph), 138.5 (s,
1Cipso).
6Cmeta, PPh3), 127.9 (s, 2Cmeta, Ph), 128.5 (d, JC−P = 1.5 Hz, 3Cpara
,
PPh3), 128.6 (s, 1Cpara, Ph), 133.1 (s, 2Cortho, Ph), 134.5 (d, JC−P = 9.5
Hz, 6Cortho, PPh3), 134.8 (s, 1Cipso, Ph), 137.7 (d, J = 36 Hz, 3Cipso).
3-(Benzylthio)-N-(2-morpholinoethyl)propan-1-amine (4a). To a
solution of 2-(4-morpholinyl)ethanamine (3.4 mL, 0.026 mol) in
MeCN (50 mL) were added successively 3-bromopropyl benzyl sulfide
(6.36 g, 0.026 mol) and anhydrous potassium carbonate (10 g, 0.072
mol) with stirring. The resulting suspension was refluxed for 16 h,
cooled to room temperature, and filtered (the residue on the filter was
washed with MeCN, 2 × 10 mL), and the solvent was removed by
evaporation on a Rotavap to afford 7.15 g of a viscous, orange-yellow
liquid (55 °C, 1 h, 40 mbar). The desired product was obtained by
fractional vacuum distillation on a Vigreux column composed of two
theoretical plates. The first collected fraction that boiled at 25−26 °C
corresponds to residual 2-(4-morpholinyl)ethanamine (recovery ∼0.5
mL). The collected yellow fraction that boiled at 145−176 °C
corresponds to the analytically pure product (3.57 g, 47%, based on 3-
bromopropyl benzyl sulfide). Anal. Calcd for C16H26N2OS (294.46):
1
31P{1H} NMR (162 MHz, CDCl3, rt): δ 40.3 (s). H NMR (400
MHz, CDCl3, rt): δ 2.74 (vt, J ≈ 14 Hz, 1H), 2.94−3.02 (m, 2H),
3.11−3.45 (m, 7H), 3.51−3.70 (m, 5H), 3.78 (vt, J ≈ 13 Hz, 1H), 5.87
(brs, NH, 1H), 6.95 (t, J ≈ 8 Hz, 2H), 7.15−7.32 (m, 12H), 7.72 (t, J
≈ 9 Hz, 6H). 13C{1H} NMR (100.5 MHz, CDCl3, rt): δ 45.2 (s, 1C),
47.2 (s, 1C), 48.5 (s, 1C), 52.8 (s, 1C), 54.8 (s, 1C), 58.9 (s, 1C), 60.2
(s, 1C), 61.6 (s, 1C), 127.3 (d, JC−P = 8.7 Hz, 6Cmeta, PPh3), 128.1 (s,
2Cmeta, Ph), 128.7 (d, JC−P = 1.5 Hz, 3Cpara, PPh3), 128.8 (s, 1Cpara
,
Ph), 133.2 (s, 2Cortho, Ph), 134.6 (d, JC−P = 9.5 Hz, 6Cortho, PPh3), 134.5
(s, 1Cipso, Ph), 137.1 (d, J = 36 Hz, 3Cipso).
Method B, unoptimized as shown in Scheme S3. A mixture of
[RuCl2(COD)]n (359 mg, 1.281 mmol), PPh3 (336 mg, 1.281 mmol),
and ligand 1a (341 mg, 1.281 mmol) was stirred in THF (15 mL) at
75 °C for 39 h in a Kontes pressure tube. After cooling, the resulting
brick-colored precipitate was collected on a filter frit, washed with
Et2O (3 × 5 mL), and vacuum-dried. Recrystallization from hot
CH2Cl2 following layering with Et2O afforded analytically pure
product in 29% yield (260 mg).
1
C, 65.26; H, 8.90; N, 9.51. Found: C, 65.56; H, 9.08; N, 9.75. H
NMR (400 MHz, CDCl3, rt): δ 1.42 (brs, 1H, NH), 1.75 (q, J = 7 Hz,
3
2H), 2.35−2.53 (overlapped m, 8H), 2.66 (t, JH−H = 7 Hz, 4H),
3.65−3.73 (overlapped m, 6H), 7.23 (m, 1H), 7.26−7.35 (overlapped
m, 4H). 13C{1H} NMR (100.5 MHz, CDCl3, rt): δ 29.2 (s, 1C), 29.5
(s, 1C), 36.3 (s, 1C), 46.1 (s, 1C), 48.9 (s, 2C), 53.8 (s, 1C), 58.3 (s,
2C), 67.0 (S, 1C), 126.9 (s, 1Cpara, Ph), 128.4 (s, 2Cmeta, Ph), 128.8 (s,
2Cortho, Ph), 138.5 (s, 1Cipso).
trans-[RuIICl2{κ3(N,N′,S)-2a}(PPh3)] (II). This was prepared similarly
to I, following method A. After decantation of the mother liquor, the
obtained red rhombic crystals were washed with Et2O (3 × 10 mL)
and vacuum-dried overnight. Isolated yield: 225 mg (75%) of
3-(Benzylthio)-N-(3-morpholinopropyl)propan-1-amine (4b).
This was prepared similarly to 4a in 53% isolated yield. Details will
be published in a separate contribution. NMR spectra are shown in
Figure S12.
2-Morpholino-N-(thiophen-2-ylmethyl)ethanamine (5a). To a
solution of 2-(4-morpholinyl)ethanamine (5 g, 5.1 mL, 0.038 mol)
in MeOH (80 mL) was added freshly distilled thiophenecarbaldehyde
(3.6 mL, 0.038 mol). The obtained mixture was stirred for 24 h to
afford a yellow solution, to which was slowly added NaBH4 (4 equiv,
5.8 g, 20 min) through a funnel into the reaction mixture, resulting in
1
C33H39Cl2N2OPRuS·1CH2Cl2 (based on H NMR with rd = 10s).
Anal. Calcd for C33H39Cl2N2OPRuS·1CH2Cl2 (768.20): C, 51.07; H,
5.17; N, 3.50. Found: C, 52.53; H, 5.38; N, 3.54. The elemental
analysis better fits the C33H39Cl2N2OPRuS·0.63CH2Cl2 (768.20)
formulation (Calcd: C, 52.58; H, 5.28; N, 3.65), suggesting that
some cocrystallized CH2Cl2 was likely lost during combustion analysis.
We also noticed from independent experiments that the amount of
solvate depends on the drying time. The compound exists in CDCl3 or
CD2Cl2 as a mixture of presumably two diastereomers (79:21 ratio).
D
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31P{1H} NMR (162 MHz, CDCl3, rt): δ 39.6 (s, major, 79%), 40.3 (s,
minor, 21%). 31P{1H} NMR (162 MHz, CD2Cl2, rt): δ 40.6 (s, major,
79%), 40.9 (s, minor, 21%).
[Ru2(μ2-Cl)2Cl2{κ2(N,N′)-5a}2(PPh3)2] (VIII). This was prepared
similarly to I following method A. 31P{1H} NMR analysis of the
reaction mixture after 1 h reveals a complicated reaction mixture as
shown in Figure S14. In a separate experiment, the composition
remained unchanged after 5 h. In 2 h the solution was concentrated to
∼40% of the original volume and layered with Et2O (22 mL). After 20
days, the mother liquor was decanted and the resulting scarlet powder
was transferred to a filter frit, washed with Et2O (3 × 10 mL), and
vacuum-dried overnight. Isolated yield: 201 mg (81%). Anal. Calcd for
C58H66Cl4N4O2P2Ru2S2 (1321.20): C, 52.73; H, 5.04; N, 4.24. Found:
C, 51.70; H, 4.85; N, 4.24. 1H NMR (400 MHz, CD2Cl2, rt, major): δ
1.42 (d, J ≈ 14 Hz, 1H), 1.84 (dd, J ≈ 5 Hz, J ≈ 14 Hz, 1H), 2.16 (t, J
≈ 14 Hz, 1H), 2.47 (d, J ≈ 13 Hz, 1H), 2.63 (d, J ≈ 16 Hz, 1H), 2.85
(brs, 1H), 3.28 (d, J ≈ 13 Hz, 1H), 3.45 (d, J ≈ 13 Hz, 1H), 3.54−3.79
(overlapped m, 4H), 3.84−4.06 (overlapped, 2H), 4.29 (dt, J ≈ 3 Hz, J
≈ 14 Hz, 1H), 6.87 (brs, 1H), 7.02 (m, 1H), 7.39 (brs, 10H), 7.83 (d,
J ≈ 5 Hz, 2H), 8.07 (brs, 5H). The compound is air-stable at least in
the solid state. It is sparingly soluble in CD2Cl2 and CDCl3 and almost
insoluble in THF-d8, MeOD, and acetone-d6. These solutions are air-
sensitive. We noted that if the scarlet precipitated powder was
collected after 10 days, the yield dropped to 14%. Under these
conditions X-ray analysis of the red crystals produced from the mother
liquor of VIII identifies ion-pair complex [Ru2 (μ2 -
Cl)3Cl2(PPh3)4]−5aH+ (IX), consisting of a binuclear trichloro-
bridged anion33 [Ru2(μ2-Cl)3Cl2(PPh3)4]− and protonated 5a;34 see
Scheme S6 and Figure S25, respectively.
trans-[RuIICl2{κ3(N,N′,S)-3a}(PPh3)] (III). This was prepared sim-
ilarly to I, following method A. After decantation of the mother liquor,
the obtained red crystals were washed with Et2O (3 × 10 mL) and
vacuum-dried overnight. Isolated yield: 209 mg (87%). Anal. Calcd for
C27H35Cl2N2OPRuS (638.59): C, 50.78; H, 5.52; N, 4.39. Found: C,
50.77; H, 5.51; N, 4.29. The compound exists in CD2Cl2 as a mixture
of presumably two diastereomers (74:26 ratio). 31P{1H} NMR (162
MHz, CD2Cl2, rt): δ 40.9 (s, minor, 24%), 41.9 (s, major, 76%).
trans-[RuIICl2{κ3(N,N′,S)-4a}(PPh3)] (IV). This was prepared sim-
ilarly to I, following method A. After decantation of the mother liquor,
a large (>1 cm) red crystal was transferred onto a filter frit, washed
with Et2O (3 × 10 mL), dried under vacuum, broken, and dried under
vacuum overnight. Isolated yield: 238 mg (87%). Anal. Calcd for
C34H41Cl2N2OPRuS (728.72): C, 56.04; H, 5.67; N, 3.84. Found
(under nitrogen): C, 56.32; H, 5.75; N, 3.85. The compound exists in
CD2Cl2 as a mixture of presumably two diastereomers (99:1 ratio).
31P{1H} NMR (162 MHz, CD2Cl2, rt): δ 42.9 (s, minor, 1%), 46.0 (s,
1
major, 99%). H NMR (400 MHz, CD2Cl2, rt, major): δ 2.03 (d, J ≈
13 Hz, 1H), 2.17 (t, J ≈ 13 Hz, 1H), 2.25 (q, J ≈ 13 Hz, 1H), 2.25 (d,
J ≈ 14 Hz, 2H), 2.92−3.23 (overlapped m, 10H), 3.52 (d, J ≈ 19 Hz,
1H), 3.58−3.83 (overlapped m, 4H), 4.78 (brs, 1H, NH), 6.87 (brs,
2H), 7.20 (brs, 3H), 7.39 (brs, 9H), 7.93 (brs, 6H). 13C{1H} NMR
(100.5 MHz, CD2Cl2, rt, major): δ 24.4 (s, 1C), 25.2 (s, 1C), 37.2 (s,
1C), 49.6 (s, 1C), 50.1 (s, 1C), 51.5 (s, 1C), 51.7 (s, 1C), 58.0 (s, 1C),
60.1 (s, 1C), 61.2 (s, 1C), 127.0 (s, 1Cpara, Ph), 127.2 (d, JC−P = 9 Hz,
6Cmeta, PPh3), 128.3 (s, 2Cmeta, Ph), 128.7 (brs, 3Cpara, PPh3), 129.2 (s,
2Cortho, Ph), 135.2 (d, JC−P = 9 Hz, 6Cortho, PPh3), 136.6 (s, 1Cipso, Ph),
136.9 (d, J = 36 Hz, 3Cipso).
trans-[RuIICl2{κ3(N,N′,S)-1c}(PPh3)] (X). This was prepared similarly
to I, following method A. After decantation of the mother liquor, the
obtained light pink precipitate was collected on a filter frit, washed
with Et2O (3 × 10 mL), and vacuum-dried overnight. Isolated yield:
218 mg (85%). Anal. Calcd for C32H37Cl2N2PRuS (684.67): C, 56.14;
H, 5.45; N, 4.09. Found: C, 56.33; H, 5.36; N, 3.79. 31P{1H} NMR
(162 MHz, CDCl3, rt): δ 42.2 (s). 1H NMR (400 MHz, CD2Cl2, rt): δ
1.15 (vq, J ≈ 8 Hz, 1H), 1.35 (vq, J ≈ 8 Hz, 1H), 1.60 (m, 2H), 2.41
(vq, J ≈ 12 Hz, 1H), 2.53 (d, J ≈ 12 Hz, 1H), 2.93 (t, J ≈ 13 Hz, 1H),
3.05 (m, 3H), 3.15 (d, J ≈ 9 Hz, 1H), 3.29 (d, J ≈ 9 Hz, 1H), 3.39 (d,
J ≈ 11 Hz, 1H), 3.56 (m, 2H), 3.15 (vq, J ≈ 11 Hz, 1H), 5.85 (brs,
NH, 1H), 6.94 (t, J ≈ 8 Hz, 2H), 7.14 (t, J ≈ 7 Hz, 1H), 7.14−7.25 (m
overlapped, 6H), 7.26−7.33 (d, J ≈ 8 Hz, 6H), 7.66 (t, J ≈ 9 Hz, 5H).
13C{1H} NMR (100.5 MHz, CD2Cl2, rt): δ 20.5 (s, 1C), 22.1 (s, 1C),
45.4 (s, 1C), 47.3 (s, 1C), 49.3 (s, 1C), 57.7 (s, 1C), 61.2 (s, 1C), 62.5
(s, 1C), 127.0 (d, JC−P ≈ 8 Hz, 6Cmeta, PPh3), 128.0 (s, 2Cmeta, Ph),
128.4 (d, JC−P ≈ 1.5 Hz, 3Cpara, PPh3), 128.5 (s, 1Cpara, Ph), 133.0 (s,
2Cortho, Ph), 134.6 (d, JC−P ≈ 9 Hz, 6Cortho, PPh3), 135.0 (s, 1Cipso, Ph),
137.2 (d, J = 36 Hz, 3Cipso). The X-ray structure is shown in Figure
S30.
[Ru2(μ2-Cl)2Cl2{κ2(N′,S)-1b}2(PPh3)2] (V). This was prepared sim-
ilarly to I, following method A. 31P{1H} NMR analysis of the reaction
mixture after 1 h reveals full conversion of the starting material into
presumably cis-[Ru(PPh3)2Cl2(N′,S-1b)],31 δ 26.8 ppm (brs, 1P), 36.7
2
ppm (d, JP−P = 31 Hz, 1P), and free PPh3, δ −5.5 ppm, as shown in
Scheme S4 and Figure S23, respectively. The air-sensitive mixture was
stirred for 2 h and then concentrated to ∼40% of the original volume
level. The solution was layered with Et2O (22 mL) and left for 8 days.
After decantation of the mother liquor, the obtained red, needle-like
crystals were transferred to a filter frit, washed with Et2O (3 × 10 mL),
and vacuum-dried overnight. Isolated yield: 162 mg (60%). Anal.
Calcd for C66H78Cl4N4O2P2Ru2S2 (1429.38): C, 55.46; H, 5.50; N,
3.92. Found: C, 55.68; H, 5.49; N, 3.79. The compound is air-stable at
least in the solid state. The obtained needle-like crystals are sparingly
soluble in CD2Cl2, CDCl3, CD3OD, acetone-d6, and DMF-d7.
Saturated solutions of small concentrations exhibit complicated
31P{1H} NMR spectra.
trans-[RuIICl2{κ3(N,N′,S)-1d}(PPh3)] (XI). Method A. This was
prepared similarly to I. In contrast to I, layering with Et2O afforded
burgundy crystals, rather than a light pink powder. These crystals were
collected on a filter frit, washed with Et2O (3 × 10 mL), and vacuum-
dried overnight. According to elemental analysis, NMR spectroscopy,
and X-ray crystallography as shown in Figure S33, these crystals exist
as a CH2Cl2 solvate. Isolated yield: 218 mg (78%). Anal. Calcd for
C30H35Cl2N2PRuS·1CH2Cl2 (743.55): C, 50.08; H, 5.02; N, 3.77.
Found: C, 50.33; H, 5.12; N, 3.93. 31P{1H} NMR (162 MHz, CD2Cl2,
rt): δ 44.3 (s). 1H NMR (400 MHz, CD2Cl2, rt): δ 2.20 (d, J ≈ 12 Hz,
1H), 2.35 (s, 3H), 2.48 (s, 3H), 3.05 (vd, J ≈ 12 Hz, 1H), 3.17−3.26
(m, 1H), 3.26−3.35 (m, 2H), 3.43 (d, J ≈ 11 Hz, 1H), 3.59 (m, 2H),
5.37 (CH2Cl2), 5.88 (brs, NH, 1H), 6.99 (t, J ≈ 8 Hz, 2H), 7.19−7.26
(m, 6H), 7.26−7.35 (m, 6H), 7.69 (t, J ≈ 9 Hz, 6H). 13C{1H} NMR
(100.5 MHz, CD2Cl2, rt): δ 44.9 (s, 1C), 47.1 (s, 1C), 48.5 (s, 1C),
51.2 (s, 1C), 49.3 (s, 1C), 52.8 (s, 1C), 53.8 (S, 1C, CH2Cl2), 67.0 (s,
1C), 127.1 (d, JC−P ≈ 8 Hz, 6Cmeta, PPh3), 127.9 (s, 2Cmeta, Ph), 128.4
[Ru2(μ2-Cl)2Cl2{κ2(N′,S)-4b}2(PPh3)2] (VI). This was prepared
similarly to complex V. After decantation of the mother liquor, the
resulting orange solid was transferred to a filter frit, washed with Et2O
(3 × 10 mL), and vacuum-dried overnight. Isolated yield: 134 mg
(48%), orange solid. Anal. Calcd for C70H86Cl4N4O2P2Ru2S2
(1485.49): C, 56.60; H, 5.84; N, 3.77. Found: C, 56.42; H, 5.85; N,
3.73. Similarly to V, dimeric VI is sparingly soluble in CD2Cl2, CDCl3,
CD3OD, acetone-d6, and DMF-d7. Upon standing, the mother liquor
produced red crystals after ∼1 week (not quantified). The X-ray
structural analysis identifies the product as a rare32 unsymmetrical,
trichloro-bridged bimetallic complex containing a κ2[N′,S]-bidentate
ligand, [Ru{κ2(N′,S)-4b}(PPh3)(μ-Cl)3RuCl(PPh3)2] (VII) as shown
in Scheme S5 and Figure S24, respectively. This could be formally
viewed as the product of an association reaction involving a 16e−
monomer of VI, i.e., complex [RuCl2{κ2(N′,S)-4b}(PPh3)]), and a
14e− unsaturated fragment, [RuCl2(PPh3)2], that intercept each other
within the reaction mixture. Thus, this product may be an intermediate
or a byproduct formed as a result of this complicated reaction.
Similarly to V, compound VI is sparingly soluble in CD2Cl2, CDCl3,
CD3OD, acetone-d6, and DMF-d7. Saturated solutions (low concen-
trations) exhibit complicated 31P{1H} NMR spectra.
(d, JC−P ≈ 1.5 Hz, 3Cpara, PPh3), 128.6 (s, 1Cpara, Ph), 133.1 (s, 2Cortho
,
Ph), 134.3 (d, JC−P ≈ 9 Hz, 6Cortho, PPh3), 135.2 (s, 1Cipso, Ph), 138.0
(d, J ≈ 37 Hz, 3Cipso).
Method B, unoptimized. A mixture of [RuCl2(COD)]n (309 mg,
1.103 mmol), PPh3 (289 mg, 1.103 mmol), and 1a (248 mg, 1.103
mmol) was stirred in toluene (10 mL) at 115 °C for 24 h (in a Kontes
pressure tube). After cooling, the brick-colored precipitate was filtered
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on a filter frit, washed with Et2O (3 × 10 mL), and vacuum-dried to
afford 494 mg of a light pink crude material (Found C, 53.43; H, 5.26;
N, 4.08). Recrystallization from hot THF, filtering, and layering with
Et2O afforded burgundy crystals (261 mg, 32% yield as a THF
solvate). On the basis of NMR analysis, these crystals do indeed
represent a THF solvate. The crystals were found to lose solvent based
on elemental analysis. Anal. Calcd for C30H35Cl2N2PRuS (658.63): C,
54.71; H, 5.36; N, 4.25. Found: C, 54.37; H, 5.66; N, 3.87.
(t, J ≈ 7 Hz, 2H), 7.46 (t, J ≈ 6 Hz, 1H), 7.98 (d, J ≈ 7 Hz, 2H).
13C{1H} NMR for major diastereomer (100.5 MHz, CD2Cl2, rt): δ
45.0 (s, 1C), 47.5 (s, 1C), 47.6 (s, 1C), 48.3 (s, 1C), 49.1 (s, 1C), 54.0
(s, 1C, overlapped with CD2Cl2 peak), 55.4 (s, 1C), 58.4 (s, 1C), 60.7
(s, 1C, CH3), 61.7 (s, 1C, CH3), 128.9 (s, 2Cmeta, Ph), 130.1 (s, 1Cpara
,
Ph), 133.3 (s, 2Cortho, Ph), 133.6 (s, 1Cipso, Ph).
[IrICl(η2-COE){κ2(N′,S)-1a}] (XV). Method A. To [IrCl(COE)2]2
(145 mg, 0.162 mmol) was added a solution of ligand 1a (86 mg,
0.324 mmol) in THF (4 mL) with stirring. The initially formed red
solution afforded a precipitate after ca. 10 min. The mixture was stirred
for 4 h at rt, and a yellow precipitate was collected on a frit, washed
with Et2O (3 × 10 mL), and vacuum-dried overnight to afford 152 mg
of a yellow product (78%). Anal. Calcd for C22H36ClIrN2OS (604.27):
C, 43.73; H, 6.01; N, 4.64. Found: C, 43.46; H, 5.93; N, 4.42. If the
same procedure was carried out in 3 mL of THF, the product was
isolated in 90% yield. Elemental analysis for this sample, however, was
not acceptable for unknown reasons: Found: C, 40.85; H, 5.43; N,
3.91. The compound is slightly oxygen-sensitive in solution. NMR
spectra of the complex depend on the nature of the solvent and are
time-dependent, as shown in Figure S38. A series of a complicated
equilibria (including H for Cl exchange in chlorinated solvents) is
proposed, Scheme S8.
trans-[RuIICl2{κ3(N,N′,S)-1a}(PCy3)] (XII).
A mixture of
[RuCl2(COD)]n (309 mg, 1.103 mmol), PCy3 (309 mg, 1.103
mmol), and 1a (294 mg, 1.103 mmol) was stirred in toluene (10 mL)
at 115 °C for 48 h in a Kontes pressure tube. After cooling, the brick-
colored precipitate was collected on a filter frit, washed with Et2O (3 ×
10 mL), and vacuum-dried to afford 642 mg of the crude material. To
the crude material was added CH2Cl2 (∼32 mL), and the obtained
mixture was brought to reflux and filtered using a Whatman syringe
filter (PTFE membrane, pore size 0.45 μm). Layering the obtained
red-brown solution with Et2O (125 mL) afforded 327 mg (41%) of the
product as a pink-brown powder after 5 days. Anal. Calcd for
C32H55Cl2N2OPRuS (718.81): C, 53.47; H, 7.71; N, 3.90. Found: C,
53.11; H, 8.00; N, 3.86. 31P{1H} NMR (162 MHz, CD2Cl2, rt): δ 24.0
1
(s). H NMR (400 MHz, CD2Cl2, rt): δ 0.09 (brs, 1H), 0.92 (brs,
2H), 1.04−1.63 (m, 15H), 1.63−2.05 (m, 9H), 2.10−2.45 (brs, 3H),
2.45−2.70 (brs, 1H), 2.83−3.28 (overlapped, 7H), 3.31−3.56
(overlapped, 6H), 3.56−3.90 (overlapped, 4H), 3.98 (t, J ≈ 8 Hz,
1H), 5.57 (brs, NH, 1H), 7.31 (t, J ≈ 7 Hz, 2H), 7.38 (t, J ≈ 6 Hz,
1H), 8.15 (d, J ≈ 7 Hz, 2H). 13C{1H} NMR for the coordinated 1a
ligand (100.5 MHz, CD2Cl2, rt): δ 46.6 (s, 1C), 46.8 (s, 1C), 48.3 (s,
1C), 53.9 (s, 1C, overlapped with CD2Cl2 peak), 54.8 (s, 1C), 60.0 (s,
Method B. To an orange suspension of [IrCl(COE)2]2 (145 mg,
0.162 mmol) in CH2Cl2 (1 mL) was added a solution of ligand 1a (86
mg, 0.324 mmol) in CH2Cl2 (3 mL) with stirring. Within ∼30 s a red
solution formed. This was stirred for 3 h at rt, concentrated to ca. 2
mL, and layered with Et2O (20 mL). After 2 days, the mixture
consisting of yellow crystals and a yellow powder was filtered, washed
with Et2O (3 × 5 mL), and dried under vacuum to afford 142 of a
gold-colored material identified as 4[Ir]·CH2Cl2 based on elemental
analysis. Anal. Calcd for 4[C22H36ClIrN2OS]·CH2Cl2: C, 42.72; H,
5.88; N, 4.48. Found: C, 42.55; H, 5.90; N, 4.34.
1C), 60.7 (s, 1C), 61.7 (s, 1C), 128.1 (s, 2Cmeta, Ph), 129.3 (s, 1Cpara
,
Ph), 134.9 (s, 2Cortho, Ph), 138.0 (s, 1Cipso, Ph).
[RuCl2{mer-κ3(N,N′,S*)-1a}(μ-Cl)(μ-S*Ph)RuCl{fac-κ3(N,N′,S)-1a}]
(XIII). A mixture of [RuCl2(COD)]n (155 mg, 0.552 mmol) and 1a
(147 mg, 0.552 mmol) was stirred in toluene (10 mL) at 115 °C for
48 h in a Kontes pressure tube. After cooling, a brick-colored
precipitate was collected on a filter frit, washed with Et2O (3 × 10
mL), and vacuum-dried on the filter. The material was extracted on the
filter with 5 × 3 mL of CH2Cl2, allowing the filtrates to be collected in
five separate vials. A red solution in each vial was layered with Et2O
(20 mL). In 1 week, the combined precipitates (or red crystals) from
each vial were collected, washed with Et2O (3 × 10 mL), and vacuum-
dried to afford 144 mg of the desired product (60%). Anal. Calcd for
C28H44Cl4N4O2Ru2S2 (876.75): C, 38.36; H, 5.06; N, 6.39. Found: C,
38.38; H, 4.99; N, 6.32. Anal. Calcd for C28H44Cl4N4O2Ru2S2
(876.75): C, 38.36; H, 5.06; N, 6.39. Found (under nitrogen): C,
38.61; H, 4.99; N, 6.17. The complex is poorly soluble in CDCl3 and
slightly better in CD2Cl2. 1H NMR (400 MHz, CD2Cl2, rt, saturated):
δ 2.00 (brs, 1H), 2.15 (d, J ≈ 14 Hz, 1H), 2.37 (t, J ≈ 12 Hz, 1H),
2.15 (m, 4H), 2.75−2.94 (m, 3H), 3.04 (d, J ≈ 14 Hz, 1H), 3.07−3.23
(m, 5H), 3.38 (m, 2H), 3.44−3.62 (m, 3H), 3.61−3.75 (m, 3H), 3.79
(d, J ≈ 12 Hz, 1H), 3.87 (t, J ≈ 14 Hz, 1H), 3.93−4.09 (overlapped m,
3H), 4.06 (brs, 1H), 4.44 (t, J ≈ 11 Hz, 1H), 4.72 (brs, 1H, possibly
NH), 5.07 (d, J ≈ 18 Hz, 1H), 6.72−8.85 (overlapped, 10H), 9.19
(brs, 1H, NH···Cl). The same product was isolated in 41% yield when
the reaction was carried out in the presence of P(C6F5)3 (294 mg,
0.552 mmol), as shown in Scheme S7.
[IrHCl{κ4(N,N′,S,C)-2a}] (XVI). This was prepared similarly to XV
following method A. To [IrCl(COE)2]2 (145 mg, 0.162 mmol) was
added a solution of ligand 3a (91 mg, 0.324 mmol) in THF (3 mL)
with stirring. The orange-yellow suspension was stirred for 3 h at rt,
after which a white precipitate was collected on a frit, washed with
Et2O (3 × 10 mL), and vacuum-dried overnight to afford 100 mg of
the final off-white product (61%). Anal. Calcd for C15H24ClIrN2OS
(508.10): C, 35.46; H, 4.76; N, 5.51. Found (under nitrogen): C,
35.96; H, 4.75; N, 5.09. The same compound was obtained when the
synthesis was carried out in CH2Cl2 under the same conditions, except
6 mL of the solvent was used; 50% isolated yield (82 mg). The
compound is sparingly soluble in CD2Cl2 (a hydride resonance is
observed at δ −19.49 ppm) and DMF-d7.
[IrHCl{κ4(N,N′,S,C)-4a}] (XVII). This was prepared similarly to XV
following method A. To [IrCl(COE)2]2 (145 mg, 0.162 mmol) was
added a solution of ligand 4a (95 mg, 0.324 mmol) in THF (3 mL)
with stirring. The initially formed red solution afforded a precipitate
after ca. 2 min. The orange-yellow mixture was stirred for 3 h at rt,
after which a white precipitate was collected on a frit, washed with
Et2O (3 × 10 mL), and vacuum-dried overnight to afford 57 mg of the
final off-white product (34%). Anal. Calcd for C16H26ClIrN2OS
(522.12): C, 36.81; H, 5.02; N, 5.37. Found (under nitrogen): C,
37.71; H, 5.10; N, 5.05. The compound is stable in CD2Cl2 at least
overnight. 1H NMR (400 MHz, CD2Cl2, rt): δ −21.35 (s, 1H), 1.94 (t,
J ≈ 3 Hz, 1H), 2.27 (t, J ≈ 3 Hz, 1H), 2.48 (td, J ≈ 13 Hz, J ≈ 3 Hz,
1H), 2.56 (td, J ≈ 13 Hz, J ≈ 3 Hz, 1H), 2.63−2.84 (overlapped m,
3H), 2.86−3.00 (m, 1H), 3.01−3.11 (m, 1H), 3.53 (d, J ≈ 11 Hz, 1H),
3.61 (t, J ≈ 3 Hz, 1H), 3.68−3.86 (overlapped m, 5H), 3.91 (d, J ≈ 12
Hz, 2H), 4.07 (d, J ≈ 14 Hz, 1H), 4.41 (q, J ≈ 11 Hz, 2H), 6.77−6.92
(overlapped, 2H), 7.13 (d, J ≈ 7 Hz, 1H), 7.94 (d, J ≈ 8 Hz, 1H).
13C{1H} NMR (100.5 MHz, CD2Cl2, rt): δ 23.1 (s, 1C), 25.6 (s, 1C),
29.0 (s, 1C), 47.1 (s, 1C), 47.6 (s, 1C), 57.9 (s, 1C), 59.9 (s, 1C), 63.7
(s, 1C), 65.6 (s, 1C), 67.2 (s, 1C), 120.4 (s, 1C), 123.0 (s, 1C), 124.6
(s, 1C), 136.5 (s, 1C), 139.4 (s, 1C), 147.5 (s, 1C).
[RuIICl2 (DMSO){κ3 (N,N′,S)-1a}] (XIV).
A mixture of
[RuCl2(DMSO)4] (190 mg, 0.392 mmol) and ligand 1a (105 mg,
0.392 mmol) was stirred in toluene (5 mL) at 115 °C for 24 h in a
Kontes pressure tube. After cooling, the red precipitate was collected
on a filter frit, washed with Et2O (3 × 10 mL), and vacuum-dried to
afford 116 mg of crude material. The material was dissolved in CH2Cl2
(3 mL), filtered via a Whatman syringe filter (PTFE membrane, pore
size 0.45 μm), and layered with Et2O (∼20 mL). A red crystalline solid
was obtained in 41% yield (84 mg). Anal. Calcd for
C16H28Cl2N2O2RuS2 (516.50): C, 37.21; H, 5.46; N, 5.42. Found:
1
C, 37.37; H, 5.41; N, 5.25. H NMR for major diastereomer (400
[IrHCl{κ4(N,N′,S,C)-4b}] (XVIII). This was prepared similarly to XVII
in 33% isolated yield. Full details will be published in a separate
contribution. NMR spectra are shown in Figures S41 and S42,
respectively.
MHz, CD2Cl2, rt): δ 2.81 (s, 3H), 2.91 (t, J ≈ 13 Hz, 1H), 3.11 (m,
1H), 3.24 (s, 3H), 3.29−3.74 (m, 11H), 3.79 (t, J ≈ 12 Hz, 1H), 3.93
(t, J ≈ 13 Hz, 1H), 4.05 (t, J ≈ 13 Hz, 1H), 5.40 (brs, NH, 1H), 7.37
F
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Scheme 2. Reaction of ENENES Ligands with [RuCl2(PPh3)3], [RuCl2(η4-COD)]n/PR3, [RuCl2(η4-COD)]n, and
[RuCl2(DMSO)4] Used to Prepare Various Precatalysts for Hydrogenations (Isolated Yields Are Shown; Stability Refers to
That in the Solid State)
a
b
100% 31P{1H} NMR yield after 1 h. Reaction affords cis-[RuCl2{κ2(N′,S)-1b}(PPh3)2] (100% in 1 h, in situ 31P{1H} NMR) prior to crystallization.
c
d
e
Complicated mixture as observed by 31P{1H} NMR spectroscopy prior to crystallization (in situ 31P{1H} NMR). Possible structure. The yield was
not optimized.
2.3. X-ray Diffraction Studies. X-ray crystallographic data for all
the complexes are deposited in the SI. Data for III, IV, VII, X, XVII·
CH2Cl2·pentane, and XVIII were collected on a Bruker D8 Quest
diffractometer, with a CMOS detector in shutterless mode. The crystal
was cooled to 100 K employing an Oxford Cryostream liquid nitrogen
cryostat. Data for I, II·0.5CH2Cl2, V, IX·0.5Et2O, XI·CH2Cl2, XIII·
CH2Cl2·pentane, XIV, and XV were collected on a Bruker D8
diffractometer, with an APEX II CCD detector. The crystal was cooled
to 140 K using a Bruker Kryoflex liquid nitrogen cryostat. Both data
collections employed graphite-monochromatized Mo Kα (λ =
0.710 73 Å) radiation. For XVII·CH2Cl2·pentane and XVIII the
hydride position was found on the difference Fourier map and
subsequently refined with fixed temperature factors. The structures for
II·0.5CH2Cl2, IX·0.5Et2O, XIII·CH2Cl2·pentane, and XVII·CH2Cl2·
pentane had disordered lattice solvent molecules, which were treated
with Platon/Squeeze. Cell indexing, data collection, integration,
structure solution, and refinement were performed using Bruker and
Shelxtl software. Additional details are included in the SI. The X-ray
structures for complexes VII, IX·0.5Et2O, X, and XI·CH2Cl2 are
shown in Figures S24, S25, S30, and S33, respectively. Details of the X-
ray structure for XVIII will be published in a separate contribution.
3. RESULTS AND DISCUSSION
3.1. Synthesis of ENENES. N-Alkylation of primary amines
with alkyl halides (Hofmann alkylation) affords a mixture of
primary amine, secondary amine, tertiary amine, and a
quaternary ammonium salt.35 When an N,N-dialkyldiamine of
G
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Figure 2. X-ray molecular structures for Ru complexes I, II·0.5CH2Cl2, III, IV, V, XIII·CH2Cl2·pentane, and XIV, respectively (50% level of thermal
ellipsoids). H atoms (except NH) and solvent molecules are omitted for clarity.
the general formula R2N(CH2)nNH2 (n = 1, 2, 3, ...) is used, it
is expected that five possible quaternary ammonium salts could
be formed. By refluxing commercially available 4-(2-
aminoethyl)morpholine with one equivalent of 2-bromoethyl
phenyl sulfide, PhSCH2CH2Br,27 in MeCN containing K2CO3
for 16 h as shown in Scheme 1, we found that desired ligand 1a
could be isolated in 58% yield after a simple workup consisting
of filtration, solvent evaporation, and fractional vacuum
H
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distillation.36 This reaction is highly scalable and practical; that
is, 13 g of inexpensive 4-(2-aminoethyl)morpholine afforded
15.5 g of pure product in a single loading. In addition, ∼2 g of
the starting material was recovered during fractional vacuum
distillation. This general reaction could easily be expanded to a
range of commercially available N,N-dialkyldiamines, R2N-
(CH2)nNH2 (n = 2 or 3). This allowed for the preparation of
1b (y. 57%, 16 g), 1c (y. 49%, 12.4 g37), and 1d (y. 50%, 11.2
g). The synthesis of 1e was also attempted from 1-(2-
aminoethyl)piperazine; however alkylation primarily took place
at the secondary nitrogen atom of the piperazine moiety to
afford 2-(4-(2-(phenylthio)ethyl)piperazin-1-yl)ethanamine,
and the desired product was obtained in only 7% crude
yield.38 Similarly, ligands 2a−4a and 4b were prepared using
MeSCH2CH2Br, BnSCH2CH2Br, or BnSCH2CH2CH2Br in-
stead as shown in Scheme 1 (isolated yields after fractional
vacuum distillation: 38−53%). Ligand 2a was also synthesized
from commercially available MeSCH2CH2Cl in 34% isolated
yield, albeit using longer reaction times. Ligand 5a was isolated
in 60% yield from 2-thiophenecarbaldehyde via an adapted one-
pot reaction with 4-(2-aminoethyl)morpholine and following
reduction with NaBH4 in methanol at room temperature.
The ENENES ligands 1−5 are transparent to yellow liquids
and were characterized by elemental analysis and 1H and
13C{1H} NMR spectroscopy.
3.2. Synthesis, Characterization, and Crystallographic
Studies of Well-Defined Ruthenium Complexes of ENENES.
Morpholine, pyrrolidine, and dimethylamine ENENES deriva-
tives (Morph-ENENES: ligands 1−4a, 1b, 4b, and 5a; Pyrr-
ENENES: ligand 1c; DMA-ENENES: ligand 1d) were reacted
with Ru complexes [RuCl2(PPh3)3], [RuCl2(η4-COD)]n/PR3
(PR3 = PPh3, PCy3, P(C6F5)3), [RuCl2(η4-COD)]n, and
[RuCl2(DMSO)4] in order to explore their fundamental
coordination chemistries and to prepare various catalyst
precursors for hydrogenations. A summary of the reaction
chemistry of ENENES ligands and [Ru] precursors is presented
in Scheme 2.
The complex [RuCl2(PPh3)3] was identified as the most
suitable for rapid synthesis of a variety of Ru ENENES
complexes. Reactions of [RuCl2(PPh3)3] with ligands 1a, 2a,
3a, and 4a in dichloromethane at room temperature (2 h)
afforded isostructural κ3[N,N′,S]-tridentate39 trans-
[RuIICl2{κ3(N,N′,S)-ENENES}(PPh3)] complexes of I
(prune-colored solid, isol. y. 90%), II (red crystals, isol. y.
75% of a CH2Cl2 solvate), III (red crystals, isol. y. 87%), and IV
(red crystals, isol. y. 87%), respectively. Clean reactions with
ligands 1a, 2a, and 3a were essentially completed in 1 h at room
temperature, as evidenced by in situ 31P{1H} NMR
spectroscopic monitoring of the reaction mixtures as shown
in Figure S14. Complexes I−IV are readily handled in air and
were characterized by elemental analysis, NMR (1H, 13C{1H},
31P{1H}) spectroscopy, and X-ray structural analysis. In
solution, I−IV exist as a mixture of two isomers, presumably
diastereomers40 likely due to slow lone-pair inversion around
the sulfur center.41 In the case of I, which bears the bulkiest
substituent (phenyl group) on the sulfur atom, no detectable
quantity of the second isomer was observed by NMR
spectroscopy in CD2Cl2 at ambient temperature (see spectra
in the SI). In the cases of II and III, the quantity of the second
isomer slightly increases with the decrease in bulkiness of the
sulfur-based substituent (21% for II and 24% for III). Notably
for complex IV, which is a 5,6-metallacycle, the second isomer
is present at only 1% of the total amount (compared to 21% for
complex II, a 5,5-metallacycle). The X-ray structures of these
complexes closely resemble each other, being 5,5- or 5,6-
ruthenacycles in which the three heteroatoms (N, N, and S) are
located in a single plane, as shown in Figure 2. The chlorine
atoms are located in trans orientation to each other, and the
PPh3 moiety is located trans to the NH group. These structures
resemble Baratta’s Ru-PNN42 and Gusev’s Ru-PNN43 com-
plexes or other pincer Ru complexes based on P/N tridentate
ligands.18b,44 All complexes crystallize in the centrosymmetric
P1 space group, which does not allow for determination of the
̅
absolute configuration of the stereocenters originating from N′-
nitrogen and sulfur atoms, respectively.
Under identical conditions, the reaction between complex
[RuCl2(PPh3)3] and ligands 1b and 4b, bearing a chain of three
methylene groups between the two nitrogen atoms, afforded Ci-
dimeric κ2 [N′,S]-bidentate complexes [Ru2 (μ2 -
Cl)2Cl2{κ2(N′,S)-1b}2(PPh3)2] (V) (red needle-like crystals,
isol. y. 60%) and [Ru2(μ2-Cl)2Cl2{κ2(N′,S)-4b}2(PPh3)2] (VI)
(orange solid, isol. y. 48%). The identity of these complexes is
supported by elemental analyses, and the mode of ligand
coordination in V was determined via single-crystal X-ray
structural analysis.45 ORTEP representations are shown in
Figure 2. Ligand 1b binds to each Ru atom in a bidentate
κ2[N′,S]-fashion, affording a five-membered NS ring. The
morpholine moieties are directed out of the complex, away
from the metal centers. The Ru atoms are connected via the
agency of two bridging Cl atoms. Each terminal Cl atom
participates in hydrogen bonding with the NH group of the
ligand coordinated to the other Ru atom. Notably, compared
with ligands 1−3a, in situ 31P{1H} NMR spectrocopic
monitoring of these reactions indicated more complicated
mixtures prior to crystallization. Details, including the X-ray
structure of the rare32 unsymmetrical, trichloro-bridged
bimetallic complex [Ru{κ2(N′,S)-4b}(PPh3)(μ-Cl)3RuCl-
(PPh3)2] (VII) produced after several days from the mother
liquor of VI, are reported in the SI.
The reaction between [RuCl2(PPh3)3] and ligand 5a, bearing
a thiophene moiety, under identical conditions used with
ligands 1a−4a, 1b, and 4b presumably affords the binuclear
κ2[N,N′]-bidentate complex [Ru2(μ2-Cl)2Cl2{κ2(N,N′)-
5a}2(PPh3)2] (VIII) (scarlet powder, isol. y. 81%). NMR
spectrocopic data (1H, 31P{1H}) and elemental analysis for this
complex are consistent with this formulation.46,47 In a similar
fashion to ligands 1b and 4b, in situ 31P{1H} NMR monitoring
of the reaction between complex [RuCl2(PPh3)3] and ligand 5a
also revealed a complicated reaction mixture prior to
crystallization (1−5 h, Figure S14). Details, including the X-
ray structure of the red crystals belonging to ion-pair complex
[Ru2(μ2-Cl)3Cl2(PPh3)4]−5aH+ (IX), consisting of a binuclear
trichloro-bridged anion33 [Ru2(μ2-Cl)3Cl2(PPh3)4]− and pro-
tonated 5a34 produced from the mother liquor of VIII, are
reported in the SI.
Pyrr-ENENES ligand 1c and DMA-ENENES ligand 1d were
also reacted with the Ru precursor [RuCl2(PPh3)3] to afford
isostructural κ3[N,N′,S]-tridentate trans-[RuIICl2{κ3(N,N′,S)-
ENENES}(PPh3)] complexes of X (prune-colored solid, isol.
y. 85%) and XI (red crystals, isol. y. 78% as a CH2Cl2 solvate),
as shown in Scheme 2, respectively. The identity of these
complexes in both the solid state and in solution is confirmed
by elemental analysis, solution NMR spectroscopy, and single-
crystal X-ray analysis, as reported in the SI. The X-ray
structures of X and XI are identical to complexes I−IV.
Similarly to I, no detectable amount of a second isomer was
I
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Scheme 3. Reactions between [IrCl(η2-COE)2]2 and Ligands 1a, 2a, 4a, and 4b in THF at Room Temperature
observed for either X or XI in solution. These complexes have
been tested as precatalysts for hydrogenation, vide infra.
3.3. Synthesis, Characterization, and Crystallographic
Studies of Well-Defined Iridium Complexes of Morph-
ENENES. Morph-ENENES ligands 1−4a, 4b, and 5a were
reacted with [IrCl(η2-COE)2]2 in order to explore their
fundamental coordination chemistries and to prepare various
hydrogenation precatalysts. The outcome of these reactions
depends on the nature of the R substituent bound to the sulfur
atom. When R = Ph or Bn, well-defined complexes were
isolated. The reactions between [IrCl(η2-COE)2]2 and ligands
1a, 2a, 4a, and 4b in THF at room temperature are shown in
Scheme 3.
When R = Ph (ligand 1a), the yellow, slightly oxygen-
sensitive complex [IrICl(η2-COE){κ2(N′,S)-1a}] (XV) was
obtained in 78% yield. This compound was also obtained in
dichloromethane, wherein it crystallized as a dichloromethane
solvate. The nature of XV in the solid state was confirmed by
elemental analysis and single-crystal X-ray structural analysis, as
shown in Figure 3.
Potentially tetradentate 1a binds to iridium in a bidentate
fashion via the nitrogen and sulfur atoms connected by a chain
of two methylene groups. The complex exhibits a distorted
square-planar geometry around the iridium(I) center. The
chlorine atom is located in a trans fashion to the SPh group,
whereas the NH moiety is located trans to the cyclooctene
double bond. Notably, one ortho-C−H group of the S-phenyl
ring is directed toward Ir, with Ir−C ≈ 2.98 Å. Complex XV
exhibits complicated NMR spectra upon dissolution, possibly
because of dynamic behavior (likely via multiple equilibria)
and/or decomposition. These spectra are solvent- and time-
dependent, as shown in Figure S38. The formation or
disappearance of hydride species (∼5%) and free cyclooctene
was detected in some of these solvents (see the SI for details for
the possible nature of these equlibria).
When ligands containing R = Bn (2a, 4a, and 4b) were
reacted with [IrCl(η2-COE)2]2, the unprecedented
κ4[N,N′,S,C] hydride complexes [IrHCl{κ4(N,N′,S,C)-2a}]
(XVI, isol. y. 50%), [IrHCl{κ4(N,N′,S,C)-4a}] (XVII, isol. y.
34%), and [IrHCl{κ4(N,N′,S,C)-4b}] (XVIII, isol. y. 33%)
were obtained as off-white powders. Related κ4[P,N,P,C] IrIII
dihydride complexes are obtained as a result of ortho-metalation
of an NBn moiety reported by Bianchini and co-workers.48
XVI−XVIII each exhibit remarkable stability toward air,
possibly because of the tetradentate nature of the ligand. For
example when XVIII was exposed to air and left in a loosely
capped vial for 1 week in a fume hood, no color change was
observed. The NMR properties also remain unchanged when
the complex was dissolved in CD2Cl2 in air; see Figure S43.
Complexes I and XI were also independently prepared from
[RuCl2(η4-COD)]n/PPh3 in refluxing toluene or THF, albeit in
lower isolated yields. This method allows for the preparation of
various phosphine derivatives of the type trans-
[RuIICl2{κ3(N,N′,S)-ENENES}(PR3)]. Thus, trans-
[RuIICl2{κ3(N,N′,S)-1a}(PCy3)] (XII) was isolated in 41%
yield and characterized by elemental analysis and NMR
spectroscopy. In a similar manner to the SPh derivatives I, X,
and XI, XII exist as a single isomer in solution. As a point of
note, the use of P(C6F5)3 did not work in such a fashion, and
instead, an unusual C1-bimetallic complex, [RuCl2{mer-
κ3(N,N′,S*)-1a}(μ-Cl)(μ-S*Ph)RuCl{fac-κ3(N,N′,S)-1a}]
(XIII), was isolated in 41% yield. XIII was independently
synthesized via the reaction of [RuCl2(η4-COD)]n with 1 equiv
of 1a in refluxing toluene (brick-red microcrystalline, isol. y.
60%). The structure of XIII is shown in Figure 2. One ligand
coordinates to one Ru atom in a mer-fashion, while a second
ligand coordinates to the other Ru atom in a fac-manner. The
Ru centers are bridged by a Cl atom and one S(Ph) atom being
a part of mer-coordinated 1a. There is a hydrogen-bonding
interaction between one NH group of the fac-coordinated
ligand and the terminal Cl atom attached to the first Ru atom.
Interestingly this complex exists as a single species in solution.
The NH hydrogen atom that is H-bonded to the chlorine
ligand appears at δ 9.19 ppm in the 1H NMR spectrum
(CD2Cl2). It is shifted to lower field by Δδ = 4.47 ppm relative
to the NH resonance of the non-H bonded NH group. In this
context it is interesting to compare XIII with the C2h-dimeric
Ru complex [RuCl{fac-κ3(P,N,P)}(μ-Cl)2RuCl{fac-
10f
i
κ3(P,N,P)}], obtained by refluxing the PNP ligand Pr2P-
(CH2)2NH(CH2)2PiPr2 and [Ru(η6-benzene)2]2 in THF. In
this dimeric complex, each ligand coordinates in a fac-fashion,
and each NH group participates in H-bonding with the
terminal Cl atom attached to the neighboring Ru atom.
Finally, the reaction of 1a with [RuCl2(DMSO)4] in toluene
under reflux afforded [RuIICl2(DMSO){κ3(N,N′,S)-1a}] (XIV)
in 41% yield as a red, crystalline solid. The latter was
characterized via elemental analysis and NMR spectroscopy.
The X-ray structure of XIV is shown in Figure 2. This complex
crystallized in space group P21, allowing the observation of four
different steroisomers, where stereocenters originate from the
N′-nitrogen and sulfur atoms, respectively. Upon dissolution of
these crystals, however, two diastereomers in an ∼9:1 ratio are
observed.
J
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resulting from an increase in methylene chain length. The X-ray
structures of complexes XVII and XVIII are shown in Figure 3.
For each molecule, the tetradentate ligand forms a frustum-type
structure, in which the N, N′, and C atoms are located in one
plane and form the bottom of a pyramid, whereas the S atom is
located out-of-plane and forms the fourth position of the
pyramid. The Cl atom is located trans to sulfur, whereas the
hydride group is located trans to the NH group. The structures
of XVII and XVIII correspond to 5,6,5 and 6,6,5 metallacycles,
respectively. The most interesting feature of these structures is
the large H−N−Ir−Cl dihedral angle of 23.9° for XVII and
even larger angle of 52.4° for XVIII, respectively. To the best of
our knowledge, these are the first such examples of this type of
molecular architecture. More importantly, H−N−M−X (M =
Fe, Ru, Rh, Ir; X = Cl, H) dihedral angles in bifunctional
molecular catalysts are usually close to 0°, which according to
Noyori and others, is an important factor responsible for the
metal−ligand bifunctional mechanism.4h,j,k,49 A small H−N−
M−H dihedral angle was proposed to be crucial in forming a
1,4-dipole, which interacts with the CO dipole to
simultaneously deliver M−H and N−H groups to the CO
moiety of a ketone via a putative thermally allowed [σ2s + σ2s
+ π2s] six-membered pericyclic transition state that is highly in-
plane aromatic,50 occurs in the outer-sphere, and demands the
presence of at least one NH group.3
The reactivity of [IrCl(η2-COE)2]2 toward 1a, 2a, 4a, and 4b
is in sharp contrast to its reported reactivity toward the above-
mentioned PNP ligands of the type R2P(CH2)2NH(CH2)2PR2.
The outcome of these reactions also depends on the nature of
i
the R group and the conditions applied. When R = Pr, the
iridium(III) dihydride [IrIIIClH2{(iPr2PC2H4)2NH}] was iso-
lated when the synthesis was carried out in iPrOH at 80 °C.10g
When the same reaction was carried out at room temperature,
the presumably ionic iridium(I) complex [IrI(η2-COE)-
{(iPr2PC2H4)2NH}]Cl was identified using multinuclear
NMR spectroscopy.20f This ionic species exhibited highly
fluxional behavior in solution.20f When R = Cy10f or Ad,10f
isostructural iridium(III) dihydride complexes [IrIIIClH2{(Cy2-
PC2H4)2NH}] and [IrIIIClH2{(Ad2PC2H4)2NH}] were isolated
from the reaction carried out in toluene and THF, respectively,
t
at room temperature. When R = bulky Bu, the iridium(III)
monohydride complex [IrCl(C8H13)H{(tBu2PC2H4)2NH}]
was isolated as a result of oxidative addition of a vinylic COE
C−H bond.10f,20g Among these Ir complexes, notably the
commercially available PNP system [IrIIIClH2{(iPr2PC2H4)2-
NH}] (Ir-PNP) has been reported as a (pre)catalyst in CO2
hydrogenation10j and electroreduction,10i ester hydrogenatio-
n,10a ketone transfer hydrogenations,10h solvolysis of ammonia
borane,10b and amination of aliphatic alcohols.10c
3.4. Ruthenium- and Iridium-Catalyzed Hydrogenation of
Methyl Trifluoroacetate. The catalytic activity of Ru and Ir
ENENES complexes was examined in the hydrogenation of
methyl trifluoroacetate (A), as shown in Scheme 4. We focused
our attention on this particular ester, because its homogeneous
hydrogenation may afford either (or both) trifluoroacetalde-
hyde methyl hemiacetal (B) or 2,2,2-trifluoroethanol (C),
depending on the conditions used.9l−n,51 Together with
recently disclosed fluoroform,52 B is one of the most important
synthons in the production of various fluorinated chemicals
containing CF3 groups,53 used in medicinal chemistry,54
agrochemical,55 and materials research.56 B is produced from
fluoral and methanol at −78 °C57 or via a complicated two-step
Swartz-type reaction (including one step with HF in the gas
Figure 3. X-ray molecular structures for Ir complexes XV, XVII·
CH2Cl2·pentane, and XVIII, respectively (50% level of thermal
ellipsoids). H atoms (except NH) and solvent molecules are omitted
for clarity.
Complexes XVI, XVII, and XVIII were characterized by
elemental analysis, NMR (1H, 13C) spectroscopy, and, in the
case of XVII and XVIII, X-ray structural analysis. The solubility
of these complexes in CD2Cl2 at room temperature increases
with an increase of methylene chain length: XVI < XVII <
XVIII, with XVI being almost insoluble. The chemical shifts
1
(δ) of the hydride resonance in H spectra of these species,
−19.49 ppm for XVI, −21.35 ppm for XVII, and −22.21 ppm
for XVIII, are in agreement with greater electron density
K
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Article
Scheme 4
phase).57 An alternative pathway includes stoichiometric
hydrogenation of A using borohydride as a reducing agent.58
This method generates waste and is thus not environmentally
and economically attractive.4c Complicated synthetic proce-
dures probably explain the relatively high price of B, $50 for
250 mg.59 Thus, direct, mild, and selective catalytic hydro-
genation of commercially available and inxepensive A ($46.9 for
25 g) into B using molecular hydrogen may offer an excellent,
green alternative possibility for its synthesis.
Entries 2−7, 20, and 21 in Table 1 describe results obtained
using various commercially available Ru and Ir complexes,
whereas entries 8−19 and 22−30 represent the results obtained
with Ru and Ir ENENES complexes under the same conditions
as shown in Scheme 4. Since the vast majority of esters (and
other carboxylic and carbonic acid derivatives) are methyl
derived, methanol was chosen as the solvent. The reduction of
these compounds will necessarily produce methanol; thus its
direct use as the reaction medium greatly simplifies solvent
recycle. In this case, no solvent separation steps are required,
thus positively impacting environmental aspects of such
chemistries (a very important consideration in pharmaceutical
and large-scale industrial processes).60 Unfortunately, many
bifunctional catalysts, in particular those used for ester
hydrogenations, are not active in methanol.61 This is
presumably due to the formation of inactive carbonyl
complexes.6b We therefore aimed toward developing practical
catalysts sufficiently stable and active in methanol solvent.
Hydrogenation with Takasago’s Ru-MACHO complex6
proceeded smoothly in good agreement with literature data
gleaned from reaction in a 200−1000 mL autoclave.9l Under
substrate-to-catalyst (S/C) = 2000, C was obtained almost
quantitatively and with 99% selectivity (run 2). When S/C was
increased to 20 000 (run 3), the reaction proceeded with >96%
conversion and the desired compound, B, was obtained with
75% selectivity. Under these conditions the total turnover
number (TON) reached 24 000. Surprisingly, Gusev’s Ru-SNS
complex63 was 2 times less active than the Ru-MACHO
complex (S/C = 2000), possibly due to catalyst deactivation in
methanol (run 4). Milstein’s Ru-PNN complex64 afforded
hemiacetal B with an excellent selectivity of 98%, but with a low
reaction yield of 42% (run 5). Catalysis with Takasago’s (R,R)-
Ts-DENEB65 and (R)-RUCY-XylBINAP5 was relatively slow
(runs 6 and 7). For comparison, the chiral ruthenabicyclic
complex (R)-RUCY-XylBINAP hydrogenates acetophenone
L
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Article
a
Table 1. Hydrogenation of Methyl Trifluoroacetate A Catalyzed by Various Bifunctional Catalysts
b
b
c
run
cat
S/C
temp, °C
conv, %
yield, %
B
C
0
TON
1
40
0
92
96
71
43
26
62
53
69
77
46
20
27
39
66
60
88
50
36
97
86
90
29
96
58
96
58
91
53
0.3
0
0
0
3660
24 000
1660
860
2
Ru-MACHO
2000
20 000
2000
40
92
96
71
42
26
62
52
69
77
45
1
72
59
41
21
44
35
42
57
31
19
22
25
39
36
75
46
34
13
51
75
27
68
56
44
56
62
51
0
91
3
Ru-MACHO
40
24
12
1
4
Ru-SNS
40
5
Ru-PNN
2000
40
6
(R,R)-Ts-DENEB
2000
40
5
620
7
(R)-RUCY-XylBINAP
2000
40
18
17
27
20
14
1
1600
1380
1920
1940
1180
420
8
I
2000
40
9
II
2000
40
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
III
2000
40
IV
2000
40
d
V
2000
40
20
d
VI
2000
40
26
4
600
d
VIII
X
2000
40
38
13
27
23
12
3
1020
1860
1640
1980
1040
720
2000
40
66
60
87
49
XI
2000
40
XII
2000
40
XIII
XIV
Ir-PNP
Ir-PNP
XV
2000
40
e
2000
40
35
1
f
2000
40
97
86
90
29
96
58
96
58
91
53
0.3
84
35
15
1
3620
24 200
2100
5800
2440
11 600
2920
11 600
2400
11 000
120
20 000
2000
40
40
XV
20 000
2000
40
XVI
XVI
XVII
XVII
XVIII
XVIII
XVIII
42−46
40
27
1
20 000
2000
42−46
40
51
1
20 000
2000
40
29
2
20 000
40
g
20 000
40
0.3
a
b
Experimental conditions: substrate (10 mmol, 1 mL), 5 mL of MeOH containing 2.5 mmol of MeONa (135 mg), 24 h, 50 mL Parr autoclave. 19F
NMR area; see SI for details. TON = turnover number, calculated as TON(B) + 2 × TON(C).62 Reaction mixture was heterogeneous in the end.
c
d
e
f
g
Reaction mixture became green upon exposure to air. 30 min. Base = 13.5 mg (0.025 equiv relative to A).
quantitatively into (S)-1-phenylethanol with >99% ee under 50
atm H2 pressure within 6 min (11−35°) in the presence of
0.001 mol % of the catalyst (S/C = 100 000) in a 1:1 ethanol/
2-propanol mixed solvent. The turnover frequency (TOF)
reaches about 35 000 min−1 in the best case.5
XVIII) hydrogenated A rapidly, as evidenced by the rapid drop
in hydrogen pressure, but were more selective for the
production of B (runs 22−29). For example, with S/C =
20 000, catalyst XVIII hydrogenates A into B with 53%
conversion and 96% selectivity (run 29). Under these
conditions, turnover reaches 11 000, whereas the TOF is 301
min−1 after 30 min (45% conversion of A into B with >99%
selectivity). Thus, the activity of complex XVIII (an example
that that does not contain any P atoms) is slightly lower but
comparable to the PNP-based Ru-MACHO and Ir-PNP
catalysts, respectively. A large excess of base plays a determining
role in this catalysis. For example, when the reaction with
complex XVIII was performed under 0.025 equiv of base
relative to substrate (500 equiv relative to XVIII), the reaction
proceeded at only 0.3% conversion (run 30).
All Ru complexes based on ENENES ligands hydrogenate A
with TON > 1000, except V, VI, and XIV (runs 12, 13, and 19).
The catalytic activity increases in the order I < II < III,
consistent with higher electron donation from SPh < SBn <
SMe (runs 8−10). Pyrr-ENENES ligand 1c and DMA-
ENENES ligand 1d exhibit slightly higher catalytic activity
than Morph-ENENES ligand 1a possibly due to lower
hemilability of these ligands (runs 8, 15, and 16). PCy3
provides the best activity, whereas the DMSO ligand is
prohibitive, consistent with an electron donation effect (runs
8, 17, and 19). Notably, complex XII performs the best among
all Ru complexes, except Ru-MACHO, affording B with 90%
selectivity and with 88% conversion (run 17).
When performing the catalytic reaction with Abdur-Rashid’s
catalyst Ir-PNP (S/C = 2000), we noticed an immediate, very
rapid decrease in hydrogen pressure when stirring was applied.
Under these conditions, the conversion of A was >97% into C,
with 87% selectivity after only 30 min. With S/C = 20 000,
conversion reached 86%, but the selectivity toward B was low
(59%, run 21). It appears that this complex is too active toward
formation of C (TON = 24 200). All of our Ir catalysts (XV−
4. CONCLUSIONS
We have developed ENENES, a novel family of chelating NH-
containing ligands that do not contain any oxygen-sensitive
atoms. ENENES ligands are air-stable and can be easily
accessed on gram-scales and in a variety of identities, as a range
of building blocks for their preparation are commercially
available. The basicity of the sulfur atom, the nature of the R-
group, and the methylene chain length (m or n parameter) of
these ligands determine the coordination mode resulting from
reactions with various Ru and Ir precursors. Four different
M
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Article
motifs, κ2[N,N′], κ2[N′,S], κ3[N,N′,S], and κ4[N,N′,S,C], were
identified in reactions with [RuCl2(PPh3)3], [RuCl2(η4-
COD)]n/PR3, [RuCl2(η4-COD)]n, [RuCl2(DMSO)4], and
[IrCl(η2-COE)2]2, respectively. In particular, unusual and
unprecedented coordination chemistries were observed in the
cases of [RuCl2{mer-κ3(N,N′,S*)-1a}(μ-Cl)(μ-S*Ph)RuCl{fac-
κ3(N,N′,S)-1a}] (XIII) and [IrIIIHCl{κ4(N,N′,S,C)−ligand}]
(XVI−XVIII), respectively. Ru- and Ir-containing ENENES
complexes effect the selective hydrogenation of methyl
trifluoroacetate into the important synthon trifluoroacetalde-
hyde methyl hemiacetal in basic methanol under relatively mild
conditions (35−40 °C, 25 bar H2) and with reasonable
turnover numbers (i.e., S/C > 1000). The air-stable Ir
monohydride complexes [IrIIIHCl{κ4(N,N′,S,C)−ligand}]
(XVI−XVIII) exhibit excellent catalytic activities (TON >
10 000), comparable within a factor of ∼2 to the best
bifunctional catalysts (Ru-MACHO and Ir-PNP) supported
by P atoms. Substrate scope for Ru and Ir ENENES catalysts
will be reported in a separate contribution.26
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ASSOCIATED CONTENT
■
S
* Supporting Information
Descriptions of catalytic experiments, NMR spectra and/or
charts, and details of X-ray diffraction studies. The Supporting
Information is available free of charge on the ACS Publications
website at DOI: 10.1021/acs.organomet.5b00432.
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AUTHOR INFORMATION
■
Corresponding Authors
*E-mail: pdub@lanl.gov.
*E-mail: jgordon@lanl.gov.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
P.A.D. is a recipient of a J. Robert Oppenheimer (JRO)
Distinguished Postdoctoral Fellowship at Los Alamos National
Laboratory.
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(37) Extrapolated to 0.1 mol loading. The original procedure was
carried out with 0.04 mol loading.
(38) See the SI for details.
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1
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O
DOI: 10.1021/acs.organomet.5b00432
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