Base-Free Transfer Hydrogenation of Ketones Using Cp?Ir(pyridinesulfonamide)Cl Precatalysts

Article abstract of DOI:10.1021/acs.organomet.5b00864

N-(2-(Pyridin-2-yl)ethyl)benzenesulfonamide derivatives and 1,1,1-trifluoro-N-(2-(pyridin-2-yl)ethyl)methanesulfonamide (1-4), along with three-legged piano stool Cp?Ir^IIICl complexes (5-11) (Cp? = pentamethylcyclopentadienyl) bearing pyridinesulfonamide ligands with varying electronic parameters, were synthesized. These ligands and air-stable complexes were characterized by ¹H and ¹³C{¹H} NMR spectroscopy, elemental analysis, and single-crystal X-ray diffraction. Precatalysts, 5-11, were assessed for transfer hydrogenation of aryl, diaryl, dialkyl, linear, cycloaliphatic, and α,β-unsaturated ketones, diones, β-ketoesters, and a biomass-derived substrate with 2-propanol, using 1 mol % precatalyst. Catalysis was also efficient using a 0.1 mol % loading. Remarkably, all catalysis experiments can be conducted in air without dried and degassed substrates, and basic additives and halide abstractors are not required for high activity in transfer hydrogenation. Control experiments and a mercury poisoning experiment support a homogeneous catalyzed pathway. Overall, the fastest reactions are observed using electron-poor substrates and precatalysts bearing electron-rich ligands.

Full text of DOI:10.1021/acs.organomet.5b00864

Article
pubs.acs.org/Organometallics
Base-Free Transfer Hydrogenation of Ketones Using
Cp*Ir(pyridinesulfonamide)Cl Precatalysts
Andrew Ruff, Christopher Kirby, Benny C. Chan, and Abby R. O’Connor*
Department of Chemistry, The College of New Jersey, 2000 Pennington Road, Ewing, New Jersey 08628, United States
S
* Supporting Information
ABSTRACT: N-(2-(Pyridin-2-yl)ethyl)benzenesulfonamide derivatives and
1,1,1-trifluoro-N-(2-(pyridin-2-yl)ethyl)methanesulfonamide (1−4), along
with three-legged piano stool Cp*IrIIICl complexes (5−11) (Cp* =
pentamethylcyclopentadienyl) bearing pyridinesulfonamide ligands with
varying electronic parameters, were synthesized. These ligands and air-
stable complexes were characterized by 1H and 13C{1H} NMR spectroscopy,
elemental analysis, and single-crystal X-ray diffraction. Precatalysts, 5−11,
were assessed for transfer hydrogenation of aryl, diaryl, dialkyl, linear,
cycloaliphatic, and α,β-unsaturated ketones, diones, β-ketoesters, and a
biomass-derived substrate with 2-propanol, using 1 mol % precatalyst. Catalysis was also efficient using a 0.1 mol % loading.
Remarkably, all catalysis experiments can be conducted in air without dried and degassed substrates, and basic additives and
halide abstractors are not required for high activity in transfer hydrogenation. Control experiments and a mercury poisoning
experiment support a homogeneous catalyzed pathway. Overall, the fastest reactions are observed using electron-poor substrates
and precatalysts bearing electron-rich ligands.
the reduction of ketones and nitroarenes via transfer hydro-
genation, was developed by Noyori14 and Beller,15 respectively,
and these systems tolerate an array of functional groups.
The use of Cp*Ir (Cp* = pentamethylcyclopentadienyl)
complexes for transfer hydrogenation has been recently
reviewed.3 Cp*Ir fragments containing different classes of
ligands, such as NHCs (N-heterocyclic carbenes), triazolyls,
cyclometalated imines, and diamines, are active for transfer
hydrogenation catalysis (Figure 1). For example, complex A
reduces imines and ketones using 1 mol % catalyst in basic
solution.16 Complex B, an air- and moisture-tolerant complex,
converts 2-cyanoacetophenone to the alcohol product using
sodium formate and water as the hydrogen source and
INTRODUCTION
■
The reduction of unsaturated bonds of alkenes, ketones, and
imines is a common reaction with importance in both industrial
and pharmaceutical applications. Traditionally, reduction of
aldehydes and ketones is achieved using stoichiometric
reagents, such as NaBH4, LiAlH4, or metal catalysts and H2.1
However, these reagents have drawbacks; for example, NaBH4
and LiAlH4 are air and moisture sensitive and the use of
molecular hydrogen for reduction reactions can be dangerous
in instances where high pressures of H2 are required.2 Thus,
alternatives, such as transfer hydrogenation, have received
attention.
Transfer hydrogenation involves simultaneous oxidation of a
hydrogen source and reduction of an unsaturated acceptor
substrate. An organometallic complex is often used to catalyze
this reaction;3 however there are organocatalysts for this
transformation.4 Hydrogen donor sources tend to be
inexpensive, abundant, derived from renewable feedstocks,
and nontoxic. Common donor sources are 2-propanol,
azeotropic mixtures of formic acid and triethylamine, and
sodium formate in water.5 Hydrogen acceptors include the
unsaturated bonds of aliphatic and aromatic ketones,6,7 primary
and secondary imines,8,9 internal alkynes,10 alkenes, α,β-
unsaturated ketones, and nitroarenes.11 Transfer hydrogenation
has advantages over other reduction methods, as the reaction
conditions are comparatively milder and involve more benign
reagents.12 Therefore, transfer hydrogenation provides a
greener method for reduction by removing toxic reagents and
utilizing safer reaction conditions.13 In addition, reactions using
H2 and Pd/C catalysts often impart little selectivity in
reductions. In contrast, an example of a selective reduction,
Figure 1. Recently reported Cp*Ir(III) complexes A−E used for
transfer hydrogenation.
Received: October 14, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.organomet.5b00864
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
selectively reduces α-nitroketones to the alcohol without
reduction of the nitro group.17 Complex C has one of the
largest substrate scopes of recently reported half-sandwich Ir
complexes and performs transformations including the
conversion of ketones and aldehydes to alcohols,18,19 imines
to amines,20 and ketones to secondary20,21 and primary
amines22,23 through reductive amination. These reactions
were performed using formate at low pH. The Cp*Ir triazolyl
complex D was used for the reduction of nitrobenzenes to
create aniline, azobenzene, and azoxybenzene derivatives with
2-propanol as a hydrogen source.24 Additionally, it was
demonstrated that dinuclear iridium triazolyl complexes exhibit
improved reduction compared to mononuclear analogues.25
Crabtree also reported Cp*Ir precatalysts containing NHC
ligands (E) and observed quantitative reduction of acetophe-
none using 10 mol % KOH additive.26 This is one of the most
active Cp*Ir precursors known.
Although Cp*Ir-based complexes are active for transfer
hydrogenation, there are still limitations. For example, many
transfer hydrogenation reactions using Cp*Ir complexes
Figure 2. Complexes F−J containing pyridinesulfonamide ligands.
Here we report the synthesis and NMR characterization of
four pyridinesulfonamide ligands containing an ethylene linker
(Figure 3, 1−4). Also, X-ray crystal structures for ligands 1 and
t
require base, KOH or BuOK, for high catalytic activity.
There are however limited examples of Ir complexes that
catalyze base-free transfer hydrogenation.27−29 Peris’s Cp*Ir-
(NHC) catalyst hydrogenates ketones and imines at room
temperature without base, but requires a 3-fold excess of
AgOTf.27 An in situ generated iridium hydride catalyst,
although active for reduction of aromatic ketones without
additives, requires an inert atmosphere for high activity.28
Although there are examples of catalysts active under base-free
conditions, these drawbacks make the above systems less
commercially viable.
Another common issue is the inability to reduce unactivated
forms of unsaturation. For example, complex B hydrogenates
only substrates possessing electron-withdrawing groups, thus
limiting the substrate scope. Some systems need extreme
reaction conditions in order to force catalysis. Reactions
utilizing complex C operate only at low pH. In addition, the
catalytic conditions required for transfer hydrogenation using
many Cp*Ir complexes require a dry solvent and inert
atmosphere. There is a limited number of Cp*Ir complexes
that catalyze transfer hydrogenation of an array of substrates
without the need for additives and predried solvents and in air.
The use of pyridinesulfonamide compounds as ligands in
organometallic complexes is an underexplored area in catalysis.
These ligands are advantageous for transfer hydrogenation over
other typical diamine ligands due to two chemically distinct
nitrogen atoms that can act as a proton acceptor during
catalysis. Complexes containing a methylene linker between the
pyridine and sulfonamide groups (F−I) are more common
than those containing ethylene linkers (J) (Figure 2).
Complexes using pyridinesulfonamide ligands perform different
catalytic reactions. For example, complex F catalyzes α-
oxygenation of ethers,30 while complex G acts as a catalyst
for the A3 coupling of a ketone, terminal alkyne, and secondary
amine.23 Methylene-linked pyridinesulfonamides coordinated
to Ru (H) catalyze transfer hydrogenation.31,32 A pyridine-
sulfonamide ligand possessing an ethylene linker coordinated
Au (J) catalyzes the addition of methyl furan to methyl vinyl
ketone.33 Additionally, coordination complexes of Co contain-
ing ethylene-linked pyridinesulfonamides are known.34 There
are no reports of Cp*Ir complexes containing pyridinesulfona-
mides linked by an ethylene bridge.
Figure 3. Library of pyridinesulfonamide ligands and Cp*Ir(III)
precatalysts for transfer hydrogenation.
2 are included. In addition, we describe the synthesis and
characterization of air- and moisture-tolerant iridium half-
sandwich complexes containing electronically different pyr-
idinesulfonamide ligands (Figure 3, 5−11). These complexes
serve as precatalysts for transfer hydrogenation of acetophe-
none derivatives, diaryl, aliphatic, and α,β-unsaturated ketones,
as well as diones, and biomass-derived levulinic acid, using 2-
propanol, as the hydrogen source. In contrast to other catalysts,
base is not required for catalyst activation and catalysis is
conducted in air without predried solvents. The electronics of
the sulfonamide moiety on the ligand influence the catalytic
conversion rate to product, and the electronics of the substrate
also impact the conversion of ketone to alcohol. Control and
mercury poisoning experiments support a homogeneously
catalyzed process.
RESULTS AND DISCUSSION
■
Synthesis and Characterization of Pyridinesulfona-
mide Ligands and Cp*Ir(Pyridinesulfonamide)Cl Preca-
talysts. Different synthetic strategies to prepare pyridinesulfo-
namide ligands with an ethylene linker have been reported.
B
DOI: 10.1021/acs.organomet.5b00864
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
However, derivatives that possess a cyano (CN), nitro (NO2),
or methoxy (OMe) functional group in the para-position of the
benzene ring of the sulfonamide moiety and a CF3 group at the
sulfonamide have not been previously characterized in detail.
Ligands 1−4 were synthesized using modified literature
procedures in good yields.35,36 Compounds 1−3 were
characterized via 1H and 13C{1H} NMR spectroscopy and
elemental analysis. Elemental analysis for the CF3 derivative 4
and base that were not predried. An immediate color change
from orange to light orange or yellow was observed upon the
addition of base. An aqueous extraction was used to remove the
triethylammonium chloride. Upon removal of solvent in vacuo,
an orange or yellow oil forms, which turns into an orange or
yellow powder upon vigorous stirring in hexanes overnight.
The complexes were isolated in high yields and stored at room
temperature. The precatalysts are stable in air, and degradation
has not been observed.
has been described elsewhere;37 however H, 13C{1H}, and
1
Each complex was characterized by elemental analysis and 1H
19F{1H} NMR for this compound are not reported.
Compounds 1−4 possess four unique aromatic resonances
for the pyridine and a quartet at ∼3.4 ppm and triplet at ∼2.9
ppm for the CH2 groups of the ethylene linker. X-ray quality
crystals were obtained by slow evaporation of 1 in methanol,
and X-ray quality crystals of 2 were obtained by vapor diffusion
of hexanes into a saturated solution of 2 in CH2Cl2. The
ORTEP diagrams for compounds 1 and 2 are seen in Figure 4.
Similar X-ray parameters and structures were obtained for other
pyridinesulfonamides reported by our group.38
1
and 13C{1H} NMR spectroscopy. H NMR spectra of the
complexes have diagnostic features for each complex. Within
the aromatic region (7−9 ppm), four downfield peaks correlate
to the hydrogen atoms on the pyridine ring and have
integration ratios of 1H:1H:1H:1H. Additionally, two 2H
doublets are observed downfield for the sulfonamide moiety for
benzenesulfonamide analogues 8−11. A 5H multiplet is
observed in the aromatic region for the sulfonamide moiety
of 7. Due to the cyclometalation of the pyridinesulfonamide
group, the ethylene linker is structurally rigid, and each
hydrogen within the ethylene linker generates a unique
resonance in the 2.0−4.0 ppm region. The hydrogens of the
ethylene backbone for complexes 5−11 are diastereotopic and
appear as individual signals with complex coupling patterns
(Supporting Information). The absence of a 1H triplet in the
6.0 ppm range indicates metalation at the sulfonamide moiety.
X-ray crystal structures were obtained for complexes 5, 9, and
10 to verify the structure of each complex in the solid state
(Figure 5). Selected bond distances and angle are found in
Figure 4. X-ray crystal structures for compounds 1 (NO2, top) and 2
(OMe, bottom). Hydrogen atoms are omitted for clarity.
Synthesis of the iridium half-sandwich precatalysts is
achieved via exposure of the [Cp*IrCl2]2 dimer and 2 equiv
of the pyridinesulfonamide ligand to excess triethylamine
(NEt3) in dichloromethane for 2 h at room temperature
(Scheme 1). Synthesis was performed in air, utilizing solvents
Figure 5. X-ray crystal structures of complex 5, 9, and 10. Hydrogen
atoms and solvent are omitted for clarity.
Table 1, and all other crystallographic parameters are found in
the Supporting Information. X-ray quality crystals of 5, 9, and
10 were obtained via vapor diffusion of hexanes into a saturated
solution of the complex in CH2Cl2. Complexes 5, 9, and 10
exhibit three-legged piano stool geometry around the Ir center,
where the three legs are the chloride, pyridine, and sulfonamide
moiety. A six-membered metallacycle is observed between the
metal center and the two nitrogen atoms of the pyridinesulfo-
namide ligand. The N−Ir−N bond angle is 88.3°, 84.98°, and
83.94°, respectively for 5, 9, and 10. The two Ir−N bond
distances were roughly equal for 5 (2.120 vs 2.115 Å), 9 (2.130
vs 2.110 Å), and 10 (2.130 vs 2.114 Å). The Ir to Cp* centroid
Scheme 1. Synthesis of Cp*Ir(pyridinesulfonamide) Halide
Precatalysts
C
DOI: 10.1021/acs.organomet.5b00864
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
Table 1. Selected Bond Distances and Angle for Complexes
5, 9, and 10
5
9
10
Distances (Å)
Ir1−N1
Ir1−N2
2.115(3)
2.120(3)
2.4206(8)
1.7864(5)
2.110(5)
2.107(2)
2.116(2)
2.4311(7)
1.7929(3)
2.130(4)
Ir1−Cl1
2.4083(15)
1.7912(3)
Ir1−Cp*centroid
Angle (deg)
N1−Ir1−N2
88.33(11)
84.98(17)
83.94(9)
distances are all approximately equivalent at 1.79 Å, as seen in
Table 1.
T r a n s f e r H y d r o g e n a t i o n U s i n g C p * I r -
(pyridinesulfonamide)Cl Precatalysts. The benchmark
reaction for the transfer hydrogenation of ketones is the
reduction of acetophenone (Table 2). All catalytic experiments
Figure 6. Plot demonstrating increased conversion vs σ-constant for
the reduction for acetophenone derivatives.
conversion in 6 h drops when compared to substrates with
electron-poor substituents in the para-position (Table 2, entries
4 and 7 vs 8 and 9). This finding agrees with prior systems
reported using iridium and ruthenium precatalysts.5,39,40 From
this, it can be concluded that electron-poor substrates are
reduced faster under these catalytic conditions.
a
Table 2. Reduction of Acetophenone Derivatives
A positional study using ortho-, meta-, and para-methox-
yacetophenone was performed in order to determine the effects
the substituent position has upon transfer hydrogenation using
precatalyst 5. ortho-Methoxyacetophenone showed the highest
conversion rate, 98% after 6 h (Table 2, entry 6). meta-
Methoxyacetophenone was reduced with a slightly lower
conversion when compared to 2-methoxyacetophenone, 90%
in 6 h (entry 5). para-Methoxyacetophenone displayed the
slowest rate and afforded only 56% alcohol product in 6 h
(entry 4). This supports the claim that the inductive effects of
the substituent play more of a role in influencing reduction
rates in comparison to resonance effects, as methoxy is
inductively withdrawing and the highest conversion to product
is observed when the substituent is in the ortho-position.
To verify the high activity of the precatalysts, a catalytic trial
was conducted using (Cp*IrCl2)2. Acetophenone was con-
verted to 1-phenylethanol in 12% in 24 h (Table 2, entry 10).
Lower conversion was observed using the Ir dimer when
compared to trial s conducted using Cp *Ir-
(pyridinesulfonamide)Cl precatalysts (12% vs 88%). In
addition, lower conversion was observed using the Ir dimer
in conjunction with 2 equiv of a 4-methyl-N-(2-(pyridin-2-
yl)ethyl)benzenesulfonamide ligand. Only 14% conversion of
acetophenone to 1-phenylethanol was observed after 3 h (entry
11). The active catalyst cannot be readily formed in situ from
the Ir dimer and ligand. Although the dimer and dimer in
conjunction with ligand do show activity, these species are not
the cause of the high catalytic activity observed in these
systems.
entry
1
X
precat
t (h)
conv (%)
TON
4-H
8
8
8
5
5
5
8
8
8
3
3
88
1
1
1
2
1
1
1
1
88
14
28
56
90
98
77
91
99
12
14
b
2
4-H
14
28
56
90
98
77
91
c
3
4-H
3
4
4-OMe
3-OMe
2-OMe
4-Me
4-Br
6
5
6
6
6
7
6
8
6
9
4-NO2
4-H
6
99 1 (99)
12
10
(Cp*IrCl2)2
(Cp*IrCl2)2/2L
24
d
11
4-H
3
14
1
a
1H NMR spectroscopy used to determine yield. Yields reported as an
average of three trials. 1,4-Dimethoxybenzene used as standard. A 1.0
M solution of substrate in 2-propanol. Yield in parentheses was
isolated after 3 h. Reaction conducted at 30 °C. Reaction conducted
b
c
d
at 50 °C. L = 4-methyl-N-(2-(pyridin-2 yl)ethyl)benzenesulfonamide.
were conducted in air without dried or degassed reagents at 85
°C. Acetophenone was reduced to 1-phenylethanol in 88%
conversion in 3 h using precatalyst 8. At 30 and 50 °C,
temperatures below the boiling point of the acetone byproduct,
much lower conversions were observed, 14% and 28%,
respectively (entries 2 and 3). Both electron-rich (entries 4
and 7) and electron-poor (entries 8 and 9) aromatic ketones
were reduced.
Additionally, transfer hydrogenation of 4-nitroacetophenone
yielded 1-(4-nitrophenyl)ethanol in 99% isolable yield after 3 h
(Table 2, entry 9). 4-Nitroacetophenone exhibited the highest
conversion to the alcohol product in the shortest time. The plot
in Figure 6 demonstrates the electronic effects of the substrate
on conversion. On the basis of the positive slope, the addition
of electron-withdrawing groups on the substrate increases
conversion to product. This is likely due to a weaker carbonyl
bond, which is easier to reduce. With electron-donating groups
on the para-substituted acetophenone derivative, the observed
The addition of additives was also evaluated (Table 3). Silver
triflate, AgOTf, was added in catalytic quantities (1 or 5 mol %)
to evaluate the need for precatalyst activation by loss of a
chloride. Conversion to product was not improved under
standard transfer hydrogenation conditions, as only 3% alcohol
product was observed after 1 h using 1 mol % AgOTf, while 5%
alcohol was observed at 5 mol % AgOTf (entries 2 and 3).
Analogous catalytic conditions without AgOTf afforded 62%
conversion in 1 h (entry 1). Addition of KOH did not improve
the amount of 1-phenylethanol observed; in fact the conversion
D
DOI: 10.1021/acs.organomet.5b00864
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
a
precatalysts yield more product in less time, as an electron-
rich precatalyst facilitates reduction. This trend agrees with
Noyori’s [RuCl2(η6-benzene)]-N-substituted-1,2-diphenylethy-
lenediamine catalyst system, in which the transfer hydro-
genation reactivity decreases with electron-withdrawing groups
on the sulfonamide.7 However, this trend contrasts Carriera’s
observations that electron-poor substituents on the sulfonamide
moiety of a diamine ligand coordinated to Cp*IrIII yield more
product in the transfer hydrogenation of α-cyano/nitro-ketones
in water using formic acid as the hydrogen source.29 This
relationship is verified in Figure 7, where the negative slope
Table 3. Assessing the Effects of Additives
entry
additive
mol %
conversion (%)
TON
1
2
3
4
5
none
N/A
62
3
62
3
AgOTf
AgOTf
KOH
KOH
1
5
1
5
5
5
17
17
5
5
a
1H NMR spectroscopy used to determine yield. Yield reported from
one trial. 1,4-Dimethoxybenzene used as standard. A 1.0 M solution of
substrate in 2-propanol.
is dramatically reduced. After 1 h, 5−17% product was formed
compared to the 62% conversion obtained without the addition
of base (entries 1 vs 4 and 5), which is caused by
decomposition of the complex under these conditions. In the
presence of base, the solutions darken to a purple color,
indicative of an inactive complex, and at elevated temperatures
in the presence of AgOTf a black precipitate and dark solution
form. From these results, base and AgOTf are not necessary for
high activity with Cp*Ir(pyridinesulfonamide)Cl precatalysts
when reactions are conducted in air.
After demonstrating the precatalyst’s ability to reduce
aromatic methyl ketones, a study was performed to determine
how the electronics of each precatalyst impact conversion
under the same reaction conditions (Table 4). For this study, 4-
Figure 7. Plot illustrating the electronic effects of the precatalyst on
conversion of 4-nitroacetophenone.
supports that electron-rich precatalysts yield more product than
electron-poor precatalysts in the same time period. Reactions
were also conducted at 0.1 mol % catalyst loading (Table 4,
entries 8 and 9). The ketone starting material is converted 77%
in 1 h, and 91% is reduced after 2 h. Lastly, a mercury
poisoning experiment was conducted to test for heterogeneous
catalysis (entry 10). There was no significant impact on
conversion from the addition of Hg(0) (entry 2 vs entry 10);
thus it is unlikely that heterogeneous sources of Ir are
responsible for the high activity observed.
The substrate scope was expanded to include aliphatic,
cycloaliphatic, and aromatic ketones. All trials were conducted
using precatalyst 5 (Table 5). Benzophenone and methyl
isobutyl ketone were reduced in moderate yields, 82% and 52%,
respectively, in 24 h (entries 1 and 2). Decanone was reduced
to 2-decanol, 65% in 3 h (entry 3). The cycloaliphatic ketones,
cyclopentanone, cyclohexanone, and cycloheptanone were also
converted to their corresponding alcohols in moderate to high
yields, 86%, 99%, and 63%, respectively (entries 4−6). The α,β-
unsaturated ketone, cyclohex-2-enone, demonstrated selectivity
in reduction. After 3 h, cyclohex-2-enone was converted to
cyclohexanone (entries 7 and 8). This supports selective
reduction of activated alkene bonds over ketones. After 6 h,
cyclohexanol was observed in 95% yield, as the major product
(entry 8). This reduction may proceed by a 1,4-addition
mechanism as seen in other systems.41,42 To further probe this
reduction, ketone substrates containing unconjugated alkenes,
2-allyl cyclohexanone and 5-hexen-2-one, were evaluated
(entries 9 and 10). Once again selective reduction of the
alkene occurred first. However, in these substrates, evidence of
isomerization of the alkene to the more stable conjugated
isomer is observed by 1H NMR and GCMS. The Ir precatalyst
also catalyzes isomerization of olefins. A 1,4-addition
Table 4. Reduction of 4-Nitroacetophenone with Varying
a
Precatalyst
entry
precatalyst
conversion (%)
TON
1
2
3
4
5
6
7
8
98
97
97
96
91
86
78
77
91
99
1
1
1
1
1
1
1
98
97
5
10
7
97
96
11
9
91
86
6
78
b
8
5
770
910
99
c
9
5
d
10
5
a
1H NMR spectroscopy used to determine yield. Yields reported as an
average of three trials. 1,4-Dimethoxybenzene used as standard. A 1.0
b
c
M solution of substrate in 2-propanol. 0.1 mol % catalyst loading. 0.1
mol % catalyst loading for 2 h. Trial run with Hg.
d
nitroacetophenone was selected as the substrate due to its fast
rate of reduction, and therefore the effects of the precatalyst are
more distinguishable. Precatalysts bearing electron-rich sub-
stituents on the pyridinesulfonamide (complexes 5, 7, 8, and
10) exhibited the highest conversion to alcohol in 1 h (entries
1−4), while precatalysts 6, 9, and 11, which possess electron-
poor substituents on the ligand, afforded only moderate
conversion after 1 h (entries 5−7). Thus, electron-rich
E
DOI: 10.1021/acs.organomet.5b00864
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
a
precatalyst’s tolerance of acidic functionalities and ability to
reduce biomass-relevant substrates selectively.
Table 5. Substrate Scope
CONCLUSION
■
Pyridinesulfonamide ligands containing an ethylene linker with
different functional groups were synthesized. These ligands
were used to create a library of air- and moisture-stable, half-
sandwich Cp*IrIII chloride complexes. The ligands and Cp*IrIII
complexes were characterized by NMR, elemental analysis, and
X-ray crystallography. The Cp*Ir(pyridinesulfonamide)Cl
complexes serve as precatalysts for the transfer hydrogenation
of electron-rich and -poor acetophenone derivatives at 1 mol %
catalyst loading, with 2-propanol as the hydrogen source in air
without predried solvents and reagents. These precatalysts
exhibit a wide functional group tolerance. Electron-poor
substrates were hydrogenated at a faster rate than electron-
poor ketones, whereas, electron-rich precatalysts demonstrated
higher conversion rates and favored transfer hydrogenation. A
positional study demonstrated that ortho- and meta-methox-
yacetophenone isomers were converted to their respective
alcohols faster than the para-isomer. KOH and AgOTf were
found to have deleterious effects on the reduction of
acetophenone and were not needed to see high catalytic
conversions. Mercury poisoning experiments support homoge-
neous catalysts as the active species. Work is currently under
way to elucidate the mechanism to determine the active Ir
species and to evaluate the role of the linker length upon
catalysis. The substrate scope includes diaryl, dialkyl, linear, and
cycloaliphatic ketones, diones, β-ketoesters, α,β-unsaturated
ketones, and ketones containing alkenes. Lastly, levulinic acid
was reduced and underwent lactonization under normal
catalytic conditions.
EXPERIMENTAL SECTION
■
Materials. Solvents and materials involved in the synthesis of the
ligands and all substrates were purchased from Aldrich or Alfa Aesar
and used as received. Chloroform-d and dichloromethane-d2 were
purchased from Cambridge Isotope Laboratories and dried over
molecular sieves. IrCl3·H2O was purchased from Pressure Chemical.
The [Cp*IrCl2]2 dimer was prepared according to a literature
procedure43 and stored at room temperature. Pyridinesulfonamide
ligands were synthesized using a literature procedure.35,36 All iridium
precatalysts and ligands were synthesized in air without predried or
degassed solvents and reagents.
a
1H NMR spectroscopy used to determine yield. Yields reported as an
average of three trials. 1,4-Dimethoxybenzene used as standard. A 1.0
b
M solution of substrate in 2-propanol. GCMS used to determine
General Methods. A Bruker Biospin Ascend 400 MHz nuclear
magnetic resonance spectrometer and a Bruker Biospin Ultra Shield
400 MHz nuclear magnetic resonance spectrometer were used to
yield.
1
collect 13C{1H}, 19F{1H}, and H NMR spectra. Chemical shifts are
1
referenced to residual CHCl3 (δ 7.24 for H), CH(D)Cl2 (δ 5.32 for
mechanism is still likely; however another mechanism could be
operative for alkene reduction using these precatalysts.
1H), 13CDCl3 (δ 77.0 for 13C), and 13CD2Cl2 (δ 54.0 for 13C). All
NMR spectra were collected at 300 K. GCMS was carried out by the
Agilent 6890 gas chromatograph/5873 quadrupole mass spectrometer
system with a 7683B autoinjector. Elemental analyses were performed
by Intertek (Whitehouse Station, NJ, USA).
In addition to ketone substrates, the reduction of diones was
also examined. Acetylacetone displayed slower rates of
conversion when compared to other ketone substrates (Table
5). After 6 h, only 68% conversion to 4-hydroxypentan-2-one,
and no diol product, was observed (entries 11 and 12).
Ethylacetoacetate exhibited faster rates of reduction (entry 13).
Selective reduction of the ketone to form ethyl 3-
hydroxybutanoate in 100% yield was observed. This supports
the trend that substrates that bear electron-withdrawing groups
are reduced faster. Reduction of the ester group has not been
observed. Lastly, the biomass-derived substrate levulinic acid
was reduced and then underwent intramolecular lactonization
to form γ-butyrolactone in 69% yield after 12 h (entries 14 and
15). The reduction of levulinic acid demonstrates the
4-Nitro-N-(2-(pyridin-2-yl)ethyl)benzenesulfonamide (1). An
adapted literature procedure was used to prepare this compound.36
4-Nitrobenzenesulfonyl chloride (0.891 g, 4.02 mmol) was dissolved
in 4 mL of THF. This solution was added to another solution
containing 2-(2-pyridyl)ethylamine (0.502 g, 4.11 mmol), NaOH
(0.199 g, 4.98 mmol), 4 mL of THF, and 4 mL of distilled water to
produce a cloudy yellow solution with a bilayer. This reaction was
stirred for 3 h at room temperature. The solvent was removed in vacuo,
and the product was collected by vacuum filtration. The solid
precipitate was a light yellow powder (0.752 g, 2.45 mmol, 61%).
Compound 1 can be recrystallized from ethanol. X-ray quality crystals
of 1 were obtained by slow evaporation of a saturated solution of 4-
F
DOI: 10.1021/acs.organomet.5b00864
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
nitro-N-(2-(pyridin-2-yl)ethylbenzenesulfonamide in methanol. 1H
NMR (400 MHz, CDCl3): δ 8.43 (br d, 1H, JH−H = 4.9 Hz, Py-
yield (1.50 g, 5.91 mmol). 1H NMR (400 MHz, CDCl3): δ 8.48 (br d,
1H, 3JH−H = 4.7 Hz, Py-H), 7.90 (br s, 1H, Py-H), 7.69 (dt, 1H, 3JH−H
= 7.7 Hz, 4JH−H = 1.8 Hz, Py-H), 7.22 (overlapping signals, 2H, Py-H),
3.70 (t, 2H, 3JH−H = 5.8 Hz, CH2), 3.09 (t, 2H, 3JH−H = 6.0 Hz, CH2).
13C{1H} NMR (100 MHz, CDCl3): δ 158.6, 148.8, 137.2, 123.7,
3
H), 8.29 (d, 1H, 3JH−H = 8.9 Hz, SO23PhONO2), 8.01 (d, 2H, 3JH−H
=
4
8.9 Hz, SO2PhONO2), 7.57 (dt, 1H, JH−H = 7.7 Hz, JH−H = 1.8 Hz,
Py-H), 7.14 (dd, 1H, 3JH−H = 5.3 Hz, 3JH−H = 7.0 Hz, Py-H), 7.05 (d,
1H, 3JH−H = 7.8 Hz, Py-H), 6.67 (br t, 1H, NH), 3.40 (q, 2H, 3JH−H
=
122.2, 119.9 (q, 1JC−F = 319 Hz), 43.2, 36.0. 19F{1H} NMR (376 MHz,
CDCl3): δ 76.2.
5.9 Hz, CH2−NH), 2.94 (t, 2H, 3JH−H = 5.9 Hz, CH2). 13C{1H} NMR
(100 MHz, CDCl3): δ 158.8, 149.9, 148.9, 146.3, 137.0, 128.2, 124.3,
123.6, 122.0, 42.3, 35.5. Anal. Calcd for C13H13N3O4S: C, 50.81; H,
4.26; N, 13.67. Found: C, 50.56; H, 4.18; N, 13.65.
Pentamethylcyclopentadienyl(iridium(N-(2-(pyridin-2-yl)ethyl)-
methanesulfonamide)) Chloride (5). A round-bottom flask was
charged with pentamethylcyclopentadienyl iridium dichloride dimer
(0.126 g, 0.158 mmol), N-(2-(pyridin-2-yl)ethyl)methanesulfonamide
(0.0633 g, 0.316 mmol), and dichloromethane (10 mL). Triethylamine
(91.0 μL, 0.509 mmol) was added to the solution. The solution was
then stirred for 2 h at room temperature. The solution was then
washed with three 10 mL portions of deionized water. The organic
phase was then washed with a brine solution. After, the methylene
chloride layer was collected and dried over MgSO4 for 30 min. The
resultant solution was concentrated in vacuo to yield a yellow oil,
which was stirred vigorously in hexanes overnight. The product was
isolated through vacuum filtration to form a yellow-orange powder in
94% yield (0.167 g, 0.297 mmol). X-ray quality crystals were grown
from vapor diffusion of hexanes into a saturated solution of 5 in
dichloromethane at 0 °C. 1H NMR (400 MHz, CDCl3): δ 8.90 (d, 1H,
4-Methoxy-N-(2-(pyridin-2-yl)ethyl)benzenesulfonamide (2). An
adapted literature procedure was used to prepare this compound.36 4-
Methoxybenzenesulfonyl chloride (0.830 g, 4.01 mmol) was dissolved
in 4 mL of THF. This solution was added to another solution
containing 2-(2-pyridyl)ethylamine (0.500 g, 4.09 mmol), NaOH
(0.170 g, 4.25 mmol), 4 mL of THF, and 4 mL of distilled water to
produce a cloudy yellow solution with a bilayer. This reaction was
stirred for 3 h at room temperature. The solvent was removed in vacuo,
and the product was collected by vacuum filtration. The solid
precipitate was a light yellow powder (0.789 g, 2.70 mmol, 67%).
Compound 2 can be recrystallized from ethanol. X-ray quality crystals
of 2 were obtained by slow vapor diffusion of hexanes into a saturated
solution of 4-methoxy-N-(2-(pyridin-2-yl)ethylbenzenesulfonamide in
1
3
3
3JH−H = 4.7 Hz, Py-H), 7.68 (t, 2H, overlapping, JH−H = 7.7 Hz, Py-
CH2Cl2. H NMR (400 MHz, CDCl3): δ 8.45 (br d, 1H, JH−H = 4.1
3
3
3
Hz, Py-H), 7.77 (d, 1H, JH−H = 9.0 Hz, SO2PhOMe), 7.58 (dt, 1H,
H), 7.31 (d, 1H, JH−H = 8.9 Hz, Py-H), 3.57 (apparent dt, JH−H
=
3JH−H = 7.7 Hz, 4JH−H = 1.8 Hz, Py-H), 7.17 (dd, 1H, 3JH−H = 5.0 Hz,
2,3
10.6 Hz,
J
= 3.6 Hz, 1H, CH2), 3.01 (m, 1H, CH2), 2.93 (ddd,
H−H
1H, 3JH−H = 11.5 Hz, 3JH−H = 10.7 Hz, 2JH−H = 1.5 Hz, CH2), 2.85 (s,
3JH−H = 6.6 Hz, Py-H), 7.09 (d, 1H, JH−H = 7.8 Hz, Py-H), 6.92 (d,
3
3
3
2
3
3
3H, CH3), 2.73 (ddd, 1H, JH−H = 13.0 Hz, JH−H = 12.1 Hz, JH−H
=
2H, JH−H = 9.0 Hz, SO2PhOMe), 5.96 (br t, 1H, JH−H = 5.8 Hz,
3.5 Hz, CH2), 1.49 (s, 15H, Cp*). 13C{1H} NMR (100 MHz, CDCl3):
δ 162.5, 155.7, 138.6, 132.0, 124.1, 86.9, 43.7, 41.2, 40.9, 9.19. Anal.
Calcd for C18H26IrN2O2SCl: C, 38.46; H, 4.66; N, 4.98. Found: C,
38.33; H, 4.85; N, 4.99.
NH), 3.83 (s, 3H, OMe), 3.34 (q, 2H, 3JH−H = 6.1 Hz, CH2NH), 2.94
(t, 2H, JH−H = 6.2 Hz, CH2). 13C{1H}NMR (100 MHz, CDCl3): δ
3
162.7, 158.9, 149.0, 136.8, 131.8, 129.2, 123.6, 121.8, 114.2, 55.6, 42.2,
36.1. Anal. Calcd for C14H16N2O3S: C, 57.52; H, 5.52; N, 9.58. Found:
C, 57.05; H, 5.31; N, 9.50.
Pentamethylcyclopentadienyl(iridium(1,1,1-trifluoro-(N-(2-(pyri-
din-2-yl)ethyl)methanesulfonamide)) Chloride (6). Complex 6 was
synthesized via the same procedure as 5 using pentamethylcyclo-
pentadienyl iridium dichloride dimer (0.104 g, 0.131 mmol), 1,1,1-
trifluoro-N-(2-(pyridine-2-yl)ethyl)methanesulfonamide (0.0664 g,
0.261 mmol), and triethylamine (110 μL, 0.783 mmol). The product
4-Cyano-N-(2-(pyridin-2-yl)ethyl)benzenesulfonamide (3). An
adapted literature procedure was used to prepare this compound.36
4-Cyanobenzenesulfonyl chloride (0.412 g, 2.05 mmol) was dissolved
in 4 mL of THF. This solution was added to another solution
containing 2-(2-pyridyl)ethylamine (243 μL, 2.05 mmol), NaOH
(0.0821 g, 2.05 mmol), 4 mL of THF, and 4 mL of distilled water to
produce a cloudy yellow solution with a bilayer. This reaction was
stirred for 3 h at room temperature. The solvent was removed in vacuo,
and the product was collected by vacuum filtration. The solid
precipitate was isolated as a light yellow powder (0.399 g, 1.39 mmol,
68%). Compound 3 can be recrystallized from ethanol. 1H NMR (400
1
was afforded as a yellow powder in 83% (0.134 g, 0.217 mmol). H
3
4
NMR (400 MHz, CD2Cl2): δ 8.88 (dd, 1H, JH−H = 5.8 Hz, JH−H
=
3
4
1.1 Hz, Py-H), 7.75 (dt, 1H, JH−H = 7.6 Hz, JH−H = 1.6 Hz, Py-H),
3
3
7.36 (d, 1H, JH−H = 7.8 Hz, Py-H), 7.32 (dt, 1H, JH−H = 7.0 Hz,
4JH−H = 0.9 Hz,), 3.54 (br s, 1H, CH2), 3.04 (m, 2H, CH2), 2.71 (ddd,
1H, 3JH−H = 13.9 Hz, 3JH−H = 13.0 Hz, 2JH−H = 3.9 Hz, CH2), 1.48 (s,
15H, Cp*). 13C{1H} NMR (100 MHz, CD2Cl2): δ 162.1, 155.8, 139.6,
125.0, 124.7, 121.2 (q, 1JC−F = 314 Hz), 87.5, 44.3, 41.5, 9.51. 19F{1H}
3
MHz, CDCl3): δ 8.43 (br d, 1H, JH−H = 4.7 Hz, Py-H), 7.94 (d, 1H,
3JH−H = 8.2 Hz, SO2PhCN), 7.75 (d, 2H, 3JH−H = 8.3 Hz, SO2PhCN),
3
4
NMR (376 MHz, CD2Cl2):
δ −72.6. Anal. Calcd for
7.57 (dt, 1H, JH−H = 7.7 Hz, JH−H = 1.8 Hz, Py-H), 7.13 (dd, 1H,
3JH−H = 5.0 Hz, JH−H = 7.0 Hz, Py-H), 7.05 (d, 1H, JH−H = 7.8 Hz,
3
3
C18H23F3IrN2O2SCl·0.9CH2Cl2: C, 32.78 H, 3.61; N, 4.04. Found:
1
3
C, 32.54; H, 3.48; N, 3.96. H NMR spectra obtained in CDCl3 for
Py-H), 6.59 (br t, 1H, NH), 3.38 (q, 2H, JH−H = 5.8 Hz, CH2NH),
3
2.93 (t, 2H, JH−H = 6.0 Hz, CH2). 13C{1H} NMR (100 MHz,
three different samples of 6 submitted for elemental analysis verified
the presence of 0.9 equiv of CH2Cl2 per Ir complex (Supporting
Information). The samples submitted for elemental analysis were dried
in vacuo overnight in attempts to remove the CH2Cl2 from the sample.
Pentamethylcyclopentadienyl(iridium(N-(2-(pyridin-2-yl)ethyl)-
benzenesulfonamide)) Chloride (7). Complex 7 was synthesized via
the same procedure as 5 using pentamethylcyclopentadienyl iridium
dichloride dimer (0.122 g, 0.153 mmol), N-(2-(pyridin-2-yl)ethyl)-
benzenesulfonamide (0.0803 g, 0.306 mmol), and triethylamine (92.0
μL, 0.660 mmol). A bright yellow solid was produced (0.172 g, 90%).
CDCl3): δ 158.8, 148.9, 144.7, 137.0, 132.8, 127.6, 123.6, 122.0, 117.4,
116.1, 42.2, 35.6. Anal. Calcd for C14H13N3O2S: C, 58.52; H, 4.56; N,
14.62. Found: C, 58.01; H, 4.35; N, 14.48.
1,1,1-Trifluoro-N-(2-(pyridin-2-yl)ethyl)methane Sulfonamide (4).
This compound has been synthesized via an alternate route, and
elemental analysis was previously described.37 An adapted literature
procedure was used to prepare this compound for this project.35
A
round-bottom flask was charged with 2-(2-pyridyl)ethylamine (735
μL, 6.13 mmol), triethylamine (1.06 mL, 7.64 mmol), and 15 mL of
dichloromethane. The solution was cooled to 0 °C. A solution of
trifluoromethylsulfonyl chloride (813 μL, 7.63 mmol) in dichloro-
methane (10 mL) was added dropwise over 5 min. The solution was
then stirred for 1 h at 0 °C and warmed to room temperature for 3 h.
The solution was washed with two 15 mL portions of a saturated
sodium bicarbonate solution and washed twice with a saturated
sodium chloride solution (15 mL). The organic phase was reduced in
vacuo. To purify, the product was passed through a silica gel plug on a
fritted funnel and eluted using 10% methanol/90% ethyl acetate. The
solvent was removed in vacuo to yield the product as a tan solid in 96%
3
1H NMR (400 MHz, CDCl3): δ 8.94 (d, 1H, JH−H = 4.8 Hz, Py-H),
7.94 (m, 2H, Py-H), 7.62 (dt, 1H, 3JH−H = 7.6 Hz, 4JH−H = 1.6 Hz, Py-
3
H), 7.22 (m, 5H SO2Ph), 3.53 (apparent dt, 1H, JH−H = 10.2 Hz,
2,3
3
3
J
= 3.9 Hz, CH2), 2.94 (ddd, JH−H = 14.0 Hz, JH−H = 3.8 Hz,
H−H
2JH−H = 1.7 Hz, 1H, CH2), 2.74 (apparent dt, 1H, JH−H = 13.9 Hz,
3
2,3
J
= 3.8 Hz, CH2), 2.63 (ddd, 1H, 3JH−H = 11.3 Hz, 3JH−H = 10.0
H−H
Hz, JH−H = 1.4 Hz, CH2), 1.58 (s, 15H, Cp*). 13C{1H} NMR (100
MHz, CDCl3): δ 162.2, 155.6, 143.2, 138.7, 129.9, 128.6, 127.9, 124.1,
124.1, 86.8, 43.4, 41.2, 9.6. Anal. Calcd for C23H28IrN2O2SCl: C,
44.26; H, 4.52; N, 4.49. Found: C, 44.18; H, 4.62; N, 4.58.
2
G
DOI: 10.1021/acs.organomet.5b00864
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
Pentamethylcyclopentadienyl(iridium(4-methyl-N-(2-(pyridin-2-
yl)ethyl)benzenesulfonamide)) Chloride (8). This was synthesized via
the same procedure as 5 using pentamethylcyclopentadienyl iridium
dichloride dimer (0.121 g, 0.152 mmol), 4-methyl-N-(2-(pyridin-2-
yl)ethyl)benzenesulfonamide (0.0839 g, 0.304 mmol), and triethyal-
mine (90.0 μL, 0.654 mmol). The product was isolated as a bright
yellow solid (0.175 g, 90%). 1H NMR (400 MHz, CDCl3): δ 8.93 (dd,
3JH−H = 12.8 Hz, 2,3JH−H = 3.8 Hz, CH2), 2.57 (ddd, 1H, 3JH−H = 11.6
3
2
Hz, JH−H = 3.7 Hz, JH−H = 1.6 Hz), 1.56 (s, 15H, Cp*). 13C{1H}
NMR (100 MHz, CDCl3): δ 161.7, 155.5, 147.87, 133.7, 131.2, 129.1,
124.2, 124.1, 118.6, 113.3, 87.0, 43.4, 41.0, 9.43. Anal. Calcd
C24H27IrN3O2SCl: C, 44.40; H, 4.19; N, 6.47. Found: C, 44.24; H,
4.20; N, 6.54.
Catalytic Transfer Hydrogenation. A 0.005 mmol (1 equiv)
amount of the precatalyst was massed into an empty vial. If a solid
substrate was used, 0.500 mmol (100 equiv) of substrate was massed
and added to the vial containing the precatalyst. A 500 μL aliquot of a
0.1 M solution of 1,4-dimethoxybenzene in 2-propanol was added to
the vial by syringe. If the substrate was a liquid, a 500 μL aliquot of a
solution containing 1.0 M substrate and 0.10 M 1,4-dimethoxybenzene
in 2-propanol was injected into a vial containing only precatalyst.
If necessary, an appropriate amount of additive (Hg, KOH, or
AgOTf) was introduced to the reaction mixture. The vials were then
heated to 85 °C in an OptiMag-ST aluminum heating plate containing
wells fit for the vials for a designated amount of time. After the
reaction, the vials were cooled to room temperature. Conversions were
3
4
3
1H, JH−H = 6.3 Hz, JH−H = 1.7 Hz, Py-H), 7.81 (d, 2H, JH−H = 8.2
Hz, CH Ph), 7.61 (dt, 1H, 3JH−H = 7.6 Hz, 4JH−H = 1.6 Hz, Py-H), 7.19
3
(m, 2H, Py-H), 7.03 (d, 2H, JH−H = 8.0 Hz, CH Ph), 3.51 (apparent
dt, 1H, 3JH−H = 10.2 Hz, 2,3JH−H = 3.5 Hz, CH2), 2.93 (ddd, 1H, 3JH−H
3
2
= 14.1 Hz, JH−H = 3.3 Hz, JH−H = 1.4 Hz, CH2), 2.73 (apparent dt,
3
2,3
3
1H, JH−H = 13.8 Hz,
J
= 3.8 Hz, CH2), 2.63 (ddd, 1H, JH−H =
H−H
3
2
11.2 Hz, JH−H = 10.3 Hz, JH−H = 1.4 Hz, CH2), 2.24 (s, 3H, CH3),
1.58 (s, 15H, Cp*). 13C{1H} NMR (100 MHz, CDCl3): δ 162.3,
155.7, 140.4, 140.0, 138.5, 129.8, 128.7, 127.2, 124.1, 86.9, 43.5, 41.3,
21.4, 9.6. Anal. Calcd for C24H30IrN2O2SCl: C, 45.17; H, 4.74; N, 4.39.
Found: C, 44.83; H, 4.52; N, 4.49.
Pentamethylcyclopentadienyl(iridium(4-nitro-N-(2-(pyridin-2-yl)-
ethyl)benzenesulfonamide)) Chloride (9). Complex 9 was synthe-
sized via the same procedure as 5 using pentamethylcyclopentadienyl
iridium dichloride dimer (0.122 g, 0.153 mmol), 4-nitro-N-(2-
(pyridin-2-yl)ethyl)benzenesulfonamide (0.0940g, 0.309 mmol), and
triethylamine (92.0 μL, 0.660 mmol) The product was afforded as a
bright orange solid (0.203 g, 99%). X-ray quality crystals were grown
from vapor diffusion of hexanes into a saturated solution of 9 in 1,2-
1
determined using H NMR spectroscopy by integration of resolved
characteristic resonances for ketone starting material and alcohol
1
product. Conversions not determined by H NMR were established
using GCMS by comparing the peak area to concentration using a
standard calibration curve. The final reported values with error are an
average of three trials.
Isolation of Alcohol Product. This procedure was performed
after the transfer hydrogenation catalysis in order to remove the
alcohol product from the reaction mixture. The procedure was adapted
from a literature procedure.15 The reaction mixture was diluted with a
3:1 mixture of hexanes and ethyl acetate. The resulting solution was
then filtered through a fritted funnel containing silica gel. The silica gel
was rinsed with 10 mL of the mixture of hexanes and ethyl acetate.
The eluent was then collected, and the solvent was removed in vacuo
to afford an orange oil.
X-ray Crystallography. Single crystals were selected for analysis
on a Bruker-AXS SMART Apex II X-ray diffractometer using Mo Kα
radiation with a graphite monochromator.44 All samples were mounted
using a MiTeGen MicroMount and NVH oil. Data were collected at
100 °C. Unit cells were determined by taking 12 data frames, 0.5° ϕ, in
three sections of the Ewald sphere. Full hemispheres were collected on
each crystal and integrated using SAINT Plus.45 Data were corrected
for absorption correction using SADABS. Structures were solved by
the use of direct methods.46 Least squares refinement on F2 was used
for all reflections.47 Straightforward structure solution, refinement, and
the calculations of measurements were accomplished with the
SHELXTL package.48 Non-hydrogen atoms were refined anisotropi-
cally. Hydrogen atoms were placed in idealized, theoretical positions.
Compounds 1 and 2 and complexes 5 and 10 were solved in
centrosymmetric space groups. Complex 9 was solved in a non-
centrosymmetric space group, P212121, and refined as an inversion
twin using the TWIN and BASF commands. The Flack parameter
indicated the crystal was a single enantiomer.
1
dichloroethane at 0 °C. H NMR (400 MHz, CDCl3): δ 8.88 (d, 1H,
3JH−H = 5.7 Hz, Py-H), 8.10 (roofed doublet, 2H, 3JH−H = 9.0 Hz, CH
Ph), 8.04 (roofed doublet, 2H, 3JH−H = 9.0 Hz, CH Ph), 7.65 (dt, 1H,
4
3JH−H = 7.6 Hz, JH−H = 1.6 Hz, Py-H), 7.23 (m, 2H, Py-H), 3.61
(apparent dt, 1H, 3JH−H = 10.4 Hz, 2,3JH−H = 3.8 Hz, CH2), 2.99 (ddd,
3
3
2
1H, JH−H = 14.3 Hz, JH−H = 3.7 Hz, JH−H = 1.9 Hz, CH2), 2.76
(apparent dt, 1H, 3JH−H = 12.6 Hz, 2,3JH−H = 3.8 Hz, CH2), 2.61 (ddd,
3
3
2
1H, JH−H = 11.5 Hz, JH−H = 9.6 Hz, JH−H = 1.8 Hz, CH2), 1.57 (s,
15H, Cp*). 13C{1H} NMR (100 MHz, CDCl3): δ 161.8, 155.6, 149.6,
148.5, 138.9, 129.7, 124.3, 124.2, 123.2, 87.1, 43.6, 41.2, 9.62. Anal.
Calcd for C23H27IrN3O4SCl: C, 41.28; H, 4.07; N, 6.28. Found: C,
41.71; H, 4.05; N, 6.54.
Pentamethylcyclopentadienyl(iridium(4-methoxy-N-(2-(pyridin-
2-yl)ethyl)benzenesulfonamide)) Chloride (10). Complex 10 was
synthesized via the same procedure as 5 using pentamethylcyclo-
pentadienyl iridium dichloride dimer (0.108 g, 0.156 mmol), 4-
methoxy-N-(2-(pyridin-2-yl)ethyl)benzenesulfonamide (0.0792 g,
0.271 mmol), and triethylamine (80.0 μL, 0.574 mmol). The product
was yielded as a bright yellow solid (0.170 g, 96%). X-ray quality
crystals were grown from vapor diffusion of hexanes into a saturated
1
solution of 9 in 1,2-dichloroethane at 0 °C. H NMR (400 MHz,
CDCl3): δ 8.93 (dd, 1H, 3JH−H = 6.5 Hz, 4JH−H = 1.5 Hz, Py-H), 7.88
(d, 2H, 3JH−H = 6.9 Hz, CH Ph), 7.62 (dt, 1H, 3JH−3H = 7.6 Hz, 4JH−H
=
1.5 Hz, Py-H), 7.20 (m, 2H, Py-H), 6.73 (d, 2H, JH−H = 8.9 Hz, CH
3
Ph), 3.71 (s, 3H, OCH3), 3.50 (apparent dt, 1H, JH−H = 10.3 Hz,
2,3
3
3
J
= 3.6 Hz, CH2), 2.93 (ddd, 1H, JH−H = 14.1 Hz, JH−H = 3.4
H−H
2
3
Hz, JH−H = 1.6 Hz, CH2), 2.73 (apparent dt, 1H, JH−H = 14.6 Hz,
2,3
3
3
J
= 3.6 Hz, CH2), 2.62 (ddd, 1H, JH−H = 11.3 Hz, JH−H = 9.5
ASSOCIATED CONTENT
* Supporting Information
H−H
■
Hz, JH−H = 1.3 Hz, CH2), 1.58 (s, 15H, Cp*). 13C{1H} NMR (100
MHz, CDCl3): δ 162.3, 160.8, 155.7, 138.6, 135.4, 132.1, 130.5, 124.1,
113.1, 86.8, 55.4, 43.4, 41.3, 9.6. Anal. Calcd for C24H30IrN2O3SCl: C,
44.06; H, 4.62; N, 4.28. Found: C, 43.69; H, 4.57; N, 4.22.
2
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.organo-
met.5b00864. CCDC 1418441−1418445 contain the supple-
mentary crystallographic data for 1, 2, 5, 9, and 10. This
material is available free of charge via http://www.ccdc.cam.ac.
uk/conts/retrieving.html, or from the Cambridge Crystallo-
graphic Data Centre, 12 Union Road, Cambridge CB2 1EZ,
UK; fax (+44) 1223-336-033; or e-mail deposit@ccdc.cam.ac.
uk.
Pentamethylcyclopentadienyl(iridium(4-cyano-N-(2-(pyridin-2-
yl)ethyl)benzenesulfonamide)) Chloride (11). Complex 11 was
synthesized via the same procedure as 5 using pentamethylcyclo-
pentadienyl iridium dichloride dimer (0.126 g, 0.158 mmol), 4-cyano-
N-(2-(pyridin-2-yl)ethyl)benzenesulfonamide (0.0909 g, 0.316 mmol),
and triethylamine (90.0 μL, 0.643 mmol). The product was afforded as
1
a bright yellow solid (0.175 g, 85%). H NMR (400 MHz, CDCl3): δ
8.85 (d, 1H, 3JH−H = 5.8 Hz, Py-H), 8.00 (d, 2H, 3JH−H = 8.4 Hz, CH
Ph), 7.68 (dt, 1H, 3JH−H = 7.6 Hz, 4JH−H = 1.5 Hz, Py-H), 7.53 (d, 2H,
3JH−H = 8.4 Hz, CH Ph), 7.25 (m, 2H, Py-H), 3.54 (apparent dt, 1H,
3JH−H = 10.5 Hz, 2,3JH−H = 3.8 Hz, CH2), 3.00 (ddd, 1H, 3JH−H = 14.4
Original representative NMR spectra of the precatalysts
and ligands (PDF)
X-ray crystallographic data and CIF files of 1, 2, 5, 9, and
3
2
Hz, JH−H = 3.7 Hz, JH−H = 1.9 Hz, CH2), 2.75 (apparent dt, 1H,
10 (CIF)
H
DOI: 10.1021/acs.organomet.5b00864
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
(26) Hintermair, U.; Campos, J.; Brewster, T. P.; Pratt, L. M.; Schley,
AUTHOR INFORMATION
Corresponding Author
*E-mail (A. R. O’Connor): oconnora@tcnj.edu.
Notes
■
N. D.; Crabtree, R. H. ACS Catal. 2014, 4, 99−108.
́
(27) Corberan, R.; Peris, E. Organometallics 2008, 27, 1954−1958.
(28) Dong, Z.-R.; Li, Y.-Y.; Chen, J.-S.; Li, B.-Z.; Xing, Y.; Gao, J.-X.
Org. Lett. 2005, 7, 1043−1045.
The authors declare no competing financial interest.
(29) Solatani, O.; Ariger, M. A.; Vazquez-Villa, H.; Carriera, E. M.
́
Org. Lett. 2010, 12, 2893−2895.
(30) Gonzalez-de-Castro, A.; Robertson, C. M.; Xiao, J. J. Am. Chem.
Soc. 2014, 136, 8350−8360.
ACKNOWLEDGMENTS
■
This work was supported by the Donors of the American
Chemical Society Petroleum Research Fund (ACS PRF UNI#3
53605 to A.R.O’C). X-ray crystallography (#0922931) and
NMR data (#1125993) were collected on instruments
purchased through MRI grants from the National Science
Foundation. We also acknowledge The College of New Jersey
for start-up funding. We acknowledge the work of M.
Kunitomo, M. Higgins, and K. Webb, who contributed the
initial preparation of ligands 1 and 2.
̈
(31) Gunnaz, S.; Ozdemir, N.; Dayan, S.; Dayan, O.; C
̧
etinkaya, B.
̈
Organometallics 2011, 30, 4165−4173.
(32) Watanabe, M.; Hori, J.; Murata, K. Novel organometallic
complex and process for preparing amine compound. EP2228377,
September 15, 2010.
(33) Kilpin, K. J.; Jarman, B. P.; Henderson, W.; Nicholson, B. K.
Appl. Organomet. Chem. 2011, 25, 810−814.
(34) Duran, M. L.; García-Vazquez, J. A.; Gomez, C.; Sousa-Pedrares,
́ ́ ́
A.; Romero, J.; Sousa, A. Eur. J. Inorg. Chem. 2002, 2002, 2348−2354.
(35) Trova, M. P.; Wissner, A. Pyridinium compounds which are
useful as antagonists of platelet activating factor. US5208247, May 4,
1993.
REFERENCES
■
(1) Hudlicky, M. Reductions in Organic Chemistry; Ellis Horwood
́
(36) Klingele, M. H.; Moubaraki, B.; Murray, K. S.; Brooker, S. Chem.
- Eur. J. 2005, 11, 6962−6973.
Limited: West Sussex, England, 1984.
(2) Zassinovich, G.; Mestroni, G. Chem. Rev. 1992, 92, 1051−1069.
(3) Wang, D.; Astruc, D. Chem. Rev. 2015, 115, 6621−6686.
(4) Tuttle, J. B.; Ouellet, S. G.; MacMillan, D. W. C. J. Am. Chem. Soc.
2006, 128, 12662−12663.
(5) Ikariya, T.; Blacker, A. J. Acc. Chem. Res. 2007, 40, 1300−1308.
(6) Schlatter, A.; Woggon, W.-D. Adv. Synth. Catal. 2008, 350, 995−
1000.
(37) Harrington, J. K.; Trepka, R. D. N-(2-benzimidazolyl)-
fluoroalkanesulfonamides. US3897449, July 29, 1975.
(38) Jacobs, D. L.; Chan, B. C.; O’Connor, A. R. Acta Crystallogr.,
Sect. C: Cryst. Struct. Commun. 2013, C69, 1397−1401.
(39) Faller, J. W.; Lavoie, A. R. Organometallics 2001, 20, 5245−
5247.
(40) Noyori, R.; Hashiguchi, S. Acc. Chem. Res. 1997, 30, 97−102.
(7) Hashiguchi, S.; Fujii, A.; Takehara, J.; Ikariya, T.; Noyori, R. J.
́ ́ ́
(41) Jimenez, M. V.; Fernandez-Tornos, J.; Perez-Torrente, J. J.;
Am. Chem. Soc. 1995, 117, 7562−7563.
Modrego, F. J.; Winterle, S.; Cunchillos, C.; Lahoz, F. J.; Oro, L. A.
(8) Uematsu, N.; Fujii, A.; Hashiguchi, S.; Ikariya, T.; Noyori, R. J.
Am. Chem. Soc. 1996, 118, 4916−4917.
Organometallics 2011, 30, 5493−5508.
́
(42) Carrion, M. C.; Ruiz-Castaneda, M.; Espino, G.; Aliende, C.;
̃
(9) Samec, J. S. M.; Backvall, J.-E. Chem. - Eur. J. 2002, 8, 2955−
̈
Santos, L.; Rodríguez, A. M.; Manzano, B. R.; Jalon
́ ́
, F. A.; Lledos, A.
2961.
ACS Catal. 2014, 4, 1040−1053.
(10) Hauwert, P.; Boerleider, R.; Warsink, S.; Weigand, J. J.; Elsevier,
C. J. J. Am. Chem. Soc. 2010, 132, 16900−16910.
(11) Hillier, A. C.; Lee, H. M.; Stevens, E. D.; Nolan, S. P.
Organometallics 2001, 20, 4246−4252.
(43) White, C.; Yates, A.; Maitlis, P. M.; Heinekey, D. M. In Inorganic
Syntheses; Grimes, R. N., Ed.; John Wiley & Sons, Inc., 1992; pp 228−
234.
(44) Bruker Instrument Service, Version 2010.1.0.0; Bruker AXS Inc.:
Madison, WI, USA, 2010.
(45) SAINT Plus, Data Reduction Software, Version 7.68A; Bruker
(12) Cho, C. S.; Kim, B. T.; Kim, T.-J.; Shim, S. C. J. Org. Chem.
2001, 66, 9020−9022.
(13) Gnanamgari, D.; Moores, A.; Rajaseelan, E.; Crabtree, R. H.
Organometallics 2007, 26, 1226−1230.
AXS Inc.: Madison, WI, USA, 2009.
(46) Sheldrick, G. M. Acta Crystallogr., Sect. A: Found. Crystallogr.
2008, A64, 112−122.
(14) Fujii, A.; Hashiguchi, S.; Uematsu, N.; Ikariya, T.; Noyori, R. J.
Am. Chem. Soc. 1996, 118, 2521−2522.
(47) Sheldrick, G. M. Acta Crystallogr., Sect. A: Found. Adv. 2015,
C71, 3−8.
(15) Wienhofer, G.; Sorribes, I.; Boddien, A.; Westerhaus, F.; Junge,
̈
K.; Junge, H.; Llusar, R.; Beller, M. J. Am. Chem. Soc. 2011, 133,
12875−12879.
(48) APEX2, Data Refinement Software, Version 2010.1-2; Bruker
AXS Inc.: Madison, WI, USA, 2010.
(16) Zhu, X.-H.; Cai, L.-H.; Wang, C.-X.; Wang, Y.-N.; Guo, X.-Q.;
Hou, X.-F. J. Mol. Catal. A: Chem. 2014, 393, 134−141.
́
(17) Vazquez-Villa, H.; Reber, S.; Ariger, M. A.; Carreira, E. M.
Angew. Chem., Int. Ed. 2011, 50, 8979−8981.
(18) Wei, Y.; Xue, D.; Lei, Q.; Wang, C.; Xiao, J. Green Chem. 2013,
15, 629−634.
(19) Talwar, D.; Wu, X.; Saidi, O.; Salguero, N. P.; Xiao, J. Chem. -
Eur. J. 2014, 20, 12835−12842.
(20) Wang, C.; Pettman, A.; Bacsa, J.; Xiao, J. Angew. Chem., Int. Ed.
2010, 49, 7548−7552.
(21) Lei, Q.; Wei, Y.; Talwar, D.; Wang, C.; Xue, D.; Xiao, J. Chem. -
Eur. J. 2013, 19, 4021−4029.
(22) Talwar, D.; Salguero, N. P.; Robertson, C. M.; Xiao, J. Chem. -
Eur. J. 2014, 20, 245−252.
(23) Trose, M.; Dell’Acqua, M.; Pedrazzini, T.; Pirovano, V.; Gallo,
E.; Rossi, E.; Caselli, A.; Abbiati, G. J. Org. Chem. 2014, 79, 7311−
7320.
(24) Hohloch, S.; Suntrup, L.; Sarkar, B. Organometallics 2013, 32,
7376−7385.
(25) Maity, R.; Hohloch, S.; Su, C.-Y.; van der Meer, M.; Sarkar, B.
Chem. - Eur. J. 2014, 20, 9952−9961.
I
DOI: 10.1021/acs.organomet.5b00864
Organometallics XXXX, XXX, XXX−XXX