Chiral NCN Pincer Iridium(III) Complexes with Bis(imidazolinyl)phenyl Ligands: Synthesis and Application in Enantioselective C-H Functionalization of Indoles with α-Aryl-α-diazoacetates

Article abstract of DOI:10.1021/acs.organomet.0c00174

A series of chiral NCN pincer iridium(III) complexes 2a-h with bis(imidazolinyl)phenyl ligands were synthesized via the central aryl C2-H bond activation of the 1,3-bis(2′-imidazolinyl)benzene ligands. The incorporation of a 5-tert-butyl group into the central aryl ring of the ligands was found to markedly improve the efficiency of the desired C2-metalation, leading to an obvious enhancement in the yields of the Ir(III) complexes. Consequently, complexes with a tert-butyl group on the central aryl ring were obtained in 34-47percent yields, whereas those without the group were produced in only 13-16percent yields. All of the new complexes have been characterized by elemental analysis and 1H and 13C{1H} NMR spectroscopy. In addition, the molecular structures of complexes 2c, 2d, and 2g′ have been determined by X-ray single-crystal diffraction. 2c and 2d are, indeed, the anticipated six-coordinate pincer Ir(III) complexes. In contrast, 2g′ is a coordinatively unsaturated five-coordinate pincer Ir(III) complex. The Ir(III) complexes were used as the catalysts for the asymmetric C-H insertion reaction of α-aryl-α-diazoacetates with N-protected indoles. With a catalyst loading of 3 mol percent and in the presence of 6 mol percent of NaBArF, a variety of optically active indole derivatives bearing chiral functional groups at the C3 position were obtained in good yields with moderate to good enantioselectivities (up to 86percent ee).

Full text of DOI:10.1021/acs.organomet.0c00174

pubs.acs.org/Organometallics
Article
Chiral NCN Pincer Iridium(III) Complexes with
Bis(imidazolinyl)phenyl Ligands: Synthesis and Application in
Enantioselective C−H Functionalization of Indoles with α‑Aryl-α-
diazoacetates
Nan Li, Wen-Jing Zhu, Juan-Juan Huang, Xin-Qi Hao, Jun-Fang Gong,* and Mao-Ping Song*
Cite This: https://dx.doi.org/10.1021/acs.organomet.0c00174
Read Online
sı
*
Metrics & More
Article Recommendations
Supporting Information
ACCESS
ABSTRACT: A series of chiral NCN pincer iridium(III)
complexes 2a−h with bis(imidazolinyl)phenyl ligands were
synthesized via the central aryl C2−H bond activation of the
1,3-bis(2′-imidazolinyl)benzene ligands. The incorporation of a 5-
tert-butyl group into the central aryl ring of the ligands was found
to markedly improve the efficiency of the desired C2-metalation,
leading to an obvious enhancement in the yields of the Ir(III)
complexes. Consequently, complexes with a tert-butyl group on the
central aryl ring were obtained in 34−47% yields, whereas those
without the group were produced in only 13−16% yields. All of the
new complexes have been characterized by elemental analysis and
1H and 13C{1H} NMR spectroscopy. In addition, the molecular
structures of complexes 2c, 2d, and 2g′ have been determined by
X-ray single-crystal diffraction. 2c and 2d are, indeed, the anticipated six-coordinate pincer Ir(III) complexes. In contrast, 2g′ is a
coordinatively unsaturated five-coordinate pincer Ir(III) complex. The Ir(III) complexes were used as the catalysts for the
asymmetric C−H insertion reaction of α-aryl-α-diazoacetates with N-protected indoles. With a catalyst loading of 3 mol % and in the
presence of 6 mol % of NaBArF, a variety of optically active indole derivatives bearing chiral functional groups at the C3 position
were obtained in good yields with moderate to good enantioselectivities (up to 86% ee).
presence of N2, water, or the olefin product. Therefore, the
development of non-PCP-type pincer Ir catalysts for AD has
been increasingly gaining research interest in the past several
years. In this regard, research from the groups of Nishiyama,
Goldberg, Goldman, and Jones have demonstrated that the
NCN-type Ir complexes with a bis(oxazolinyl)phenyl ligand
(2,6-bis(4,4-dimethyloxazolinyl)-3,5-dimethylphenyl, abbrevi-
ated as dmPhebox) are particularly promising, even though
their applications are currently limited to being stoichiometr-
ic.2a,3 For these NCN Ir complexes, C−H activation of the
alkane occurs at an Ir(III) center, which is in sharp contrast
with the Ir(I)-based PCP catalysts. Consequently, the
stoichiometric AD mediated by the NCN Ir complexes is
not inhibited by either N2 or olefin and rather is accelerated by
water.
INTRODUCTION
■
Organometallic pincer iridium complexes, which contain a
meridionally tridentate ligand, have been applied to a wide
variety of stoichiometric and catalytic chemical transformations
including, among others, C−H bond activation, C−O bond
cleavage, olefin hydroaryloxylation, monoisomerization of 1-
alkenes to trans-2-alkenes, α-alkylation of unactivated esters
with primary alcohols, (de)hydrogenation and transfer (de)-
hydrogenation reactions, as well as tandem reactions involving
alkane dehydrogenation (AD).1,2 The high thermal stability of
the pincer Ir complexes afforded by the tridentate coordination
mode and their high modularity are the two key factors
responsible for their successful applications in various trans-
formations. In particular, the PCP-type Ir complexes based on
the motif of a central coordinating carbanion and two flanking
P-coordinating groups have been systematically investigated
and found to be highly active, regioselective, and thermally
robust catalysts for alkane dehydrogenation and the related
tandem reactions. Despite the fact that the PCP pincer Ir
complex-catalyzed alkane dehydrogenation is very efficient, the
active site for the C−H activation of the alkane, which is
believed to be an Ir(I) species, is often inhibited by the
Received: March 10, 2020
https://dx.doi.org/10.1021/acs.organomet.0c00174
© XXXX American Chemical Society
Organometallics XXXX, XXX, XXX−XXX
A

Organometallics
pubs.acs.org/Organometallics
Article
As described above, the dmPhebox ligand complexed with Ir
to form the NCN pincer (dmPhebox)Ir complexes that showed
great potentials in alkane dehydrogenation. Additionally, the
Phebox ligand is also an ideal ligand skeleton for the
introduction of chirality, which can be readily achieved by
using commercially available and optically active amino
alcohols as a chiral source, leading to the construction of
chiral NCN pincer (Phebox)Ir complexes. In fact, as early as in
2006, Nishiyama and coworkers reported the first synthesis of
this type of complex.4,5 A rather preliminary investigation of
the application of the chiral (Phebox)Ir complex in asymmetric
catalysis indicated that the complex exhibited only moderate
activity with good enantioselectivity in the asymmetric
conjugate reduction of an α,β-unsaturated ester (63% yield
with 72% ee) and the reductive aldol reaction of tert-butyl
acrylate with benzaldehyde (48% yield with 89% ee).4 In 2013,
Musaev, Davies, Blakey, and coworkers synthesized a series of
chiral (Phebox)Ir complexes with varied electronic and steric
properties. From this small library of complexes, the optimal
catalyst for the asymmetric C−H insertion reaction of α-aryl-α-
diazoacetates with 1,4-cyclohexadiene was screened and
successfully identified, giving the desired products in generally
high yields and with high enantioselectivities (up to 99% yield
and 99% ee).6
sulfonimines.7d,10 In particular, Musaev, Sigman, Davies,
Blakey, and coworkers have successfully applied the chiral
(Phebim)Ir complexes to enantioselective C−H insertion
reactions of ethyl diazoacetate into phthalan and dihydrofuran
derivatives (up to 96% ee).11 The study also clearly showed
that both the yield and enantioselectivity of the catalysis
product were influenced by the NR3 group to varying degrees.
By choosing an appropriate R3 substituent, the corresponding
(Phebim)Ir complex was then able to afford a better
enantioselectivity than the related (Phebox)Ir complex.
Despite the enduring prominent role of the achiral pincer
iridium complexes in homogeneous catalysis, the synthesis and
applications of chiral ones have, in contrast, received much less
attention and effort.4,6,11 Therefore, to fully explore the
organometallic chemistry of chiral pincer Ir complexes, and
also as a part of our effort to expand further our previous work,
we herein report the synthesis and characterization of a series
of new chiral NCN pincer (Phebim)Ir complexes as well as
their use as catalysts for the enantioselective C−H function-
alization of indoles with α-aryl-α-diazoacetates.
RESULTS AND DISCUSSION
■
Synthesis and Characterization of the Chiral NCN
Pincer (Phebim)Ir Complexes. As shown in Scheme 1, the
required Phebim pincer ligand precursors, 1,3-bis(2′-
imidazolinyl)benzene (Phebim-H) ligands 1a−h, were con-
veniently synthesized from isophthaloyl dichloride or 5-tert-
butyl isophthaloyl dichloride according to the procedure we
previously reported.8 First, reactions of the dichlorides with
several chiral amino alcohols including L-valinol, L-tert-leucinol,
(1R,2S)-2-amino-1,2-diphenylethanol, L-phenylglycinol, and L-
phenylalaninol afforded the corresponding bis(amido alcohol)-
s. Next, the eight crude bis(amido alcohol) products were,
without further purification, allowed to react with thionyl
chloride and p-toluidine successively, followed by treatment
with aqueous NaOH. During the process, chlorination (twice),
amination, and cyclization to imidazoline occurred smoothly in
sequence to give rise to the desired Phebim-H ligands 1a−h.
Among the obtained eight ligands, the ligands 1f−h are new
compounds, and the other five are known.
We have been interested in developing new chiral pincer
complexes for applications in metal-catalyzed enantioselective
transformations.7 For this purpose, we have designed and
synthesized various NCN pincer metal including Pt, Pd, Ni,
and Rh complexes with chiral bis(imidazolinyl)phenyl ligands
(abbreviated as Phebim, Chart 1).8 The Phebim ligand can be
Chart 1
With the chiral ligands 1 in hand, synthesis of the pincer
Ir(III) complexes via central aryl C2−H bond activation of the
ligands was tried by reaction of the ligands with iridium(III)
chloride trihydrate in the presence of sodium hydrogen
carbonate in refluxing ethanol. It was found that the expected
chiral NCN pincer iridium(III) complexes 2a−c were
successfully obtained, albeit in rather low yields (13−16%).
In contrast, the complexes 2d−h with a tert-butyl group on the
central aryl ring were produced in acceptable yields (34−47%).
The obviously higher yields of 2d−h are likely due to the steric
effect of a bulky tert-butyl group that promotes the desired C2-
metalation by hindering the undesired C4- or C6-metalation in
the reaction of the ligands 1d−h with the Ir(III) salt.
viewed as a structural analogue of the Phebox ligand, of which
the oxygen atom in the oxazoline ring is replaced by a NR3
group. Similar to the Phebox ligands, the chiral moiety in the
Phebim ligands can be readily introduced and tuned by using
different chiral amino alcohols, which is beneficial for obtaining
the optimal catalysts. More importantly, the NR3 group is
clearly different from the O atom in electronic and steric
properties, which may bring about enhanced reactivity or
stereoselectivity of the complexes with Phebim ligands. In
particular, the changeable feature of the R3 substituent in the
NR3 group provides an additional opportunity to modulate the
reactivity and stereoselectivity of the corresponding pincer
complexes. Works from our laboratory7,8 and other groups of
Duan9 and Nakamura10 have shown that these complexes
displayed good activities with good to excellent enantiose-
lectivities in the Pt-catalyzed Friedel−Crafts alkylation of
indoles with nitroalkenes,7c,8d the Rh-catalyzed allylation of
aldehydes, the carbonyl-ene reaction and alkynylation of
trifluoropyruvates7c,8e,f as well as the Pd-catalyzed hydro-
phosphination of enones,7c,d,8g,9 the allylation of ketimines, and
reactions of several types of nitrile compounds with
All of the above new pincer (Phebim)Ir complexes were
characterized by 1H NMR, 13C{H} NMR, and elemental
1
analysis. The H NMR spectra of complexes 2a, 2c−f, and 2h
showed a singlet (commonly a broad singlet) integrated for
two protons in the range of 1.87 to 3.11 ppm, which was
assigned to the metal-coordinated H2O protons, whereas for
complexes 2b′ and 2g′, the corresponding singlets were not
observed, suggesting the absence of the coordinated H2O
molecule. Elemental analysis results of these complexes
confirmed that their molecular formulations were consistent
B
https://dx.doi.org/10.1021/acs.organomet.0c00174
Organometallics XXXX, XXX, XXX−XXX

Organometallics
pubs.acs.org/Organometallics
Article
Scheme 1. Synthesis of the Chiral NCN Pincer Iridium(III) Complexes 2a−h with Bis(imidazolinyl)phenyl Ligands
with the structures shown in Scheme 1. That is, 2b′ and 2g′
are five-coordinate complexes without the coordination of
H2O, and the others are the expected H2O-bound six-
coordinate complexes. In addition, the molecular structures
of 2c, 2d, and 2g′ were unambiguously determined by X-ray
single-crystal diffraction analysis. The molecules with selected
bond lengths and angles are shown in Figures 1−3,
respectively. Complexes 2c and 2d are six-coordinate pincer
complexes with meridionally tridentate coordination of the
Figure 2. Molecular structure of complex 2d·C7H8·C6H6 with thermal
ellipsoids drawn at the 50% probability level. (Hydrogen atoms and
solvent molecules are omitted for clarity.) Selected bond lengths (Å)
and angles (deg): Ir(1)−C(1) 1.936(8), Ir(1)−N(1) 2.069(6),
Ir(1)−N(3) 2.060(6), Ir(1)−O(1) 2.293(7), Ir(1)−Cl(1) 2.347(3),
Ir(1)−Cl(2) 2.337(3), C(1)−Ir(1)−O(1) 179.2(3), N(1)−Ir(1)−
N(3) 158.3(3), C(1)−Ir(1)−N(1) 79.4(3), C(1)−Ir(1)−N(3)
78.9(3), C(1)−Ir(1)−Cl(1) 92.2(3), C(1)−Ir(1)−Cl(2) 93.2(3),
N(1)−Ir(1)−Cl(1) 92.6(3), N(1)−Ir(1)−Cl(2) 87.8(3), N(1)−
Ir(1)−O(1) 101.3(3), N(3)−Ir(1)−Cl(1) 89.0(3), N(3)−Ir(1)−
Cl(2) 92.6(3), N(3)−Ir(1)−O(1) 100.4(3), O(1)−Ir(1)−Cl(1)
87.4(2), O(1)−Ir(1)−Cl(2) 87.1(2), Cl(1)−Ir(1)−Cl(2)
174.52(11).
Figure 1. Molecular structure of complex 2c with thermal ellipsoids
drawn at the 50% probability level. (Hydrogen atoms are omitted for
clarity; one of the two independent molecules is shown.) Selected
bond lengths (Å) and angles (deg): Ir(1)−C(1) 1.939(7), Ir(1)−
N(1) 2.039(6), Ir(1)−N(3) 2.033(6), Ir(1)−O(1) 2.264(6), Ir(1)−
Cl(1) 2.345(2), Ir(1)−Cl(2) 2.347(3), C(1)−Ir(1)−O(1) 178.4(3),
N(1)−Ir(1)−N(3) 158.4(3), C(1)−Ir(1)−N(1) 79.3(3), C(1)−
Ir(1)−N(3) 79.1(3), C(1)−Ir(1)−Cl(1) 89.6(3), C(1)−Ir(1)−
Cl(2) 93.7(3), N(1)−Ir(1)−Cl(1) 86.7(2), N(1)−Ir(1)−Cl(2)
94.6(2), N(1)−Ir(1)−O(1) 100.9(3), N(3)−Ir(1)−Cl(1) 91.8(2),
N(3)−Ir(1)−Cl(2) 88.0(2), N(3)−Ir(1)−O(1) 100.6(3), O(1)−
Ir(1)−Cl(1) 88.8(2), O(1)−Ir(1)−Cl(2) 87.9(2), Cl(1)−Ir(1)−
Cl(2) 176.62(9).
Phebim ligand as well as coordination of a H2O molecule and
two chloride ligands to the Ir(III) center. The iridium(III)
center in each complex features a distorted-octahedral
geometry wherein the H2O ligand is located in the pincer
plane and the two chloride ligands are in a trans configuration.
The Ir−C bond lengths in the two complexes are ∼1.94 Å, and
the N−Ir−N angles are 158.4(3) and 158.3(3)°, respectively,
which are comparable to those in a related achiral (Phebox)Ir
complex.4 The Ir−O bond lengths in complexes 2c and 2d
C
https://dx.doi.org/10.1021/acs.organomet.0c00174
Organometallics XXXX, XXX, XXX−XXX

Organometallics
pubs.acs.org/Organometallics
Article
catalysts including pincer Ir catalysts performed very well in
asymmetric carbene insertion into C−H bonds.6,11,16 We
speculated that the chiral (Phebim)Ir complexes might also act
as effective and stereoselective catalysts for the enantioselective
C−H functionalization of indoles with α-aryl-α-diazoacetates.
To explore this possibility, we proceeded with the reaction of
methyl α-phenyl-α-diazoacetate with N-methylindole as the
starting point and a model to optimize reaction conditions.
The results are shown in Table 1. When the reaction was
Table 1. Enantioselective C−H Insertion of Methyl α-
Phenyl-α-diazoacetate with N-Methylindole Catalyzed by
the (Phebim)Ir Complexes: Optimization of Reaction
a
Conditions
Figure 3. Molecular structure of complex 2g′ with thermal ellipsoids
drawn at the 50% probability level. (Most hydrogen atoms are
omitted for clarity; one of the two independent molecules is shown.)
Selected bond lengths (Å) and angles (deg): Ir(1)−C(1) 1.891(6),
Ir(1)−N(1) 2.057(5), Ir(1)−N(3) 2.059(6), Ir(1)−Cl(1) 2.323(2),
Ir(1)−Cl(2) 2.333(2), N(1)−Ir(1)−N(3) 159.9(2), C(1)−Ir(1)−
N(1) 79.9(3), C(1)−Ir(1)−N(3) 80.0(3), C(1)−Ir(1)−Cl(1)
98.2(2), C(1)−Ir(1)−Cl(2) 92.2(2), N(1)−Ir(1)−Cl(1) 87.21(19),
N(1)−Ir(1)−Cl(2) 93.88(19), N(3)−Ir(1)−Cl(1) 94.90(19),
N(3)−Ir(1)−Cl(2) 87.66(19), Cl(1)−Ir(1)−Cl(2) 169.53(9).
Ir(1)···H(30C)−C(30) 2.792, Ir(1)···H(15B)−C(15) 2.984.
b
c
entry
cat. (x mol %)
temp (°C)
solvent
yield (%)
ee (%)
d
1
2d (2 mol %)
2d (2 mol %)
2d (2 mol %)
2d (2 mol %)
2d (2 mol %)
2e (2 mol %)
2f (2 mol %)
2g′ (2 mol %)
2h (2 mol %)
2d (3 mol %)
2d (3 mol %)
2d (3 mol %)
30
30
20
0
0
0
0
0
0
0
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
DCE
37
79
79
53
54
41
96
23
74
86
70
n.d.
1
31
47
84
59
22
8
23
12
84
81
e
2
e
3
4
5
f
6
7
8
9
10
11
12
were found to be slightly longer than that in the (Phebox)Ir
complex (2.264(6) to 2.293(7) Å vs 2.243 Å).4 In contrast
with complexes 2c and 2d, complex 2g′ was found to be an
uncommon five-coordinate pincer complex12 with coordina-
tion of the Phebim ligand and two chloride ligands. Unlike
complexes 2c and 2d, complex 2g′ is devoid of the
coordination of a H2O molecule and is coordinatively
unsaturated. Its structure is notable for a square-based
pyramidal geometry about the Ir(III) metal. This structural
outcome is likely a result of steric shielding of the vacant
coordination site by the tert-butyl groups of imidazoline rings
in the pincer ligand. Also notable, there exist weak Ir−H
agostic interactions13 between the tert-butyl groups of
imidazoline rings and iridium, which might have a stabilizing
effect on the Ir(III) center. The Ir···H−C distances (2.792−
2.984 Å) are comparable to those in the related five-coordinate
pincer Ir complexes (2.978(5)−3.072(3) Å).12b,c
C−H Insertion of α-Aryl-α-diazoacetates with In-
doles. Transition-metal-catalyzed asymmetric insertion reac-
tions of metal carbenes, in-situ-generated from diazo
compounds, into the C−H bonds have found broad
applications in organic synthesis for C−H functionalization
and the construction of C−C bonds.14 In this regard, the
catalytic enantioselective C−H insertion of α-aryl-α-diazo-
acetates with indoles provides an efficient method for the
synthesis of indoles bearing chiral functional groups at the C3
position that are common in many biologically active natural
products and therapeutic agents. Several effective and stereo-
selective catalytic systems including Fe-chiral spiro bisoxazo-
line ligand (up to 78% ee),15a Rh-chiral phosphoric acid (up to
94% ee),15b and Pd- and Cu-axially chiral bipyridine ligand (up
to 98% ee and 95% ee, respectively),15c,d have been recently
developed for this specific transformation. However, up to
now, there have been no reports on the Ir-catalyzed
enantioselective C−H insertion of α-aryl-α-diazoacetates with
indoles, even though it has been demonstrated that some Ir
0
0
THF
a
Reaction conditions: methyl α-phenyl-α-diazoacetate (0.20 mmol),
N-methylindole (0.24 mmol), cat. 2 (x mol %), NaBArF (2x mol %),
solvent (2 mL), Ar, 24 h. Isolated yield. n.d.: not detected.
Determined by chiral HPLC analysis. Without NaBArF. Reaction
b
c
d
e
f
time was 6 h. 100 mg of 4 Å molecular sieves was added.
carried out with 2 mol % of Ir complex 2d as the catalyst in
CH2Cl2 at 30 °C for 24 h, one nearly completely racemic
product of 3a was obtained in a 37% yield (entry 1).
Importantly, both the yield and enantioselectivity of 3a were
found to increase significantly in the presence of 4 mol % of
NaBArF with a reaction time of only 6 h (79% yield with 31%
ee, entry 2). Under the circumstance of lowering the reaction
temperature to 20 °C, a higher enantioselectivity was provided
without any loss of activity (79% yield with 47% ee, entry 3).
When the temperature was further lowered to 0 °C, a high
enantioselectivity of 84% ee was achieved. However, the
activity apparently decreased, and the yield was only 53% after
24 h (entry 4). The addition of 4 Å molecular sieves did not
afford any appreciable improvement in yield and instead
resulted in a marked drop in enantioselectivity (entry 5).
Subsequently, the catalytic potential of (Phebim)Ir complexes
2e−h was examined. All four complexes gave rather low
enantioselectivities (8−23% ee), although the yield reached as
high as 96% with complex 2f as the catalyst (entries 6−9 vs
entry 4). Upon increasing the amount of complex 2d and
NaBArF to 3 and 6 mol %, respectively, the yield was markedly
improved to 86%, whereas the enantioselectivity remained at
the highest level of 84% ee (entry 10 vs entry 4). Both
D
https://dx.doi.org/10.1021/acs.organomet.0c00174
Organometallics XXXX, XXX, XXX−XXX

Organometallics
pubs.acs.org/Organometallics
Article
Table 2. Enantioselective C−H Insertion of α-Aryl-α-diazoacetates with N-Protected Indoles Catalyzed by the (Phebim)Ir
a
Complex 2d
b
cd
,
entry
Ar
R1
R2
product
yield (%)
ee (%)
1
2
3
4
5
6
7
8
C6H5
C6H5
C6H5
C6H5
C6H5
Me
Me
Me
Et
i-Pr
i-pentyl
Bn
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Bn
TBDMS
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
3r
3s
86
67
31
47
25
42
98
87
82
87
66
41
86
98
35
>99
21
trace
70
84
74
66
70
71
77
68
79
52
46
84
86
48
58
46
37
65
e
C6H5
C6H5
4-FC6H4
4-ClC6H4
4-BrC6H4
4-MeC6H4
4-MeOC6H4
3-ClC6H4
3-CF3C6H4
3-MeOC6H4
3,4-Cl2C6H3
3,4-(MeO)2C6H3
2-ClC6H4
3-thienyl
9
10
11
12
13
14
15
16
17
18
19
Me
47
a
Reaction conditions: α-aryl-α-diazoacetate (0.20 mmol), N-protected indole (0.24 mmol), cat. 2d (3 mol %), NaBArF (6 mol %), CH2Cl2 (2 mL),
b
c
d
0 °C, 24 h, Ar. Isolated yield. Determined by chiral HPLC analysis. Absolute configuration of 3c was assigned to be S by a comparison of its
optical rotation with that for the same compound in ref 15a. The absolute configurations of other products were assigned by analogy. TBDMS,
e
tert-butyldimethylsilyl.
ClCH2CH2Cl (DCE) and THF were found to be not ideal
solvents for the reaction because the yield and ee value
decreased when DCE was used, and the reaction did not occur
in THF (entries 11 and 12). Thus on the basis of the above
data, the optimized conditions for the model reaction include
using 3 mol % of complex 2d as the catalyst in the presence of
6 mol % of NaBArF and CH2Cl2 as the solvent at a temperature
of 0 °C for 24 h.
yields with moderate to good enantioselectivities (37−86% ee,
entries 8−17). The substituents included both electron-
withdrawing groups (F, Cl, Br, and CF3) and electron-
donating groups (Me and OMe). It was found that methyl α-
aryl-α-diazoacetates with electron-withdrawing groups gener-
ally exhibited higher reactivity than those with electron-
donating groups. However, the enantioselectivities were higher
with electron-donating groups than with electron-withdrawing
groups. Compared with 3-, 4-, and 3,4-substituted methyl α-
aryl-α-diazoacetates, the 2-Cl-substituted diazo substrate
reacted poorly with N-methylindole and afforded only a
trace amount of the product (entry 18). Finally, the reaction of
the diazo substrate bearing a heteroaryl (thiophen-3-yl)
proceeded smoothly to give the product 3s in 70% yield,
albeit with a moderate ee value of 47% (entry 19).
To explore further the potential of (Phebim)Ir complex 2d
in the enantioselective C−H functionalization of indoles with
α-aryl-α-diazoacetates, reactions of various substituted N-
methylindoles with methyl α-phenyl-α-diazoacetate were
carried out (Table 3). The substituent is located at the C4-,
C5-, C6-, or C7-position of the indole ring and can be either an
electron-donating group such as Me and OMe or an electron-
withdrawing group such as F, Cl, Br, or CO2Me (entries 1−
14). A high ee value of 84% accompanied by an excellent yield
was achieved only in the case of 6-Me N-methylindole (entry
10). For the 4-F, 5-MeO, 5-CO2Me, and 7-MeO indoles, low
enantioselectivities were obtained (6−37% ee, entries 2, 8, 9
and 14). For all other reactions, moderate enantioselectivities
were observed (43−62% ee). Roughly, 4-substituted N-
Under the optimized conditions, the effects of the N-
protection group (R2) of the indole and ester (alkyl) group
(R1) in α-phenyl-α-diazoacetate on the reactions were
investigated (Table 2). In comparison with N-methylindole,
the N-benzyl and N-(tert-butyldimethylsilyl) indole gave the
corresponding products 3b and 3c in obviously decreased
yields and with decreased enantioselectivities, although the
enantioselectivities were still good (entries 1−3). Similar
trends were observed when the ester group in α-phenyl-α-
diazoacetate was changed from methyl to ethyl, i-propyl, and i-
pentyl (entries 4−6). In the case of benzyl α-phenyl-α-
diazoacetate, the enantioselectivity also decreased. However, a
very high yield of 98% was obtained (entry 7). The above
results indicate that methyl is an appropriate N-protection
group for indole and also an ideal ester group for α-
diazoacetate in the reaction. On the basis of these findings,
methyl α-phenyl-α-diazoacetate was extended to methyl α-aryl-
α-diazoacetates and then used to react with N-methylindole.
Overall, substituents with varied electronic properties at the 3-,
4-, and 3,4-positions of the aryl ring were all found to be
tolerated, delivering the desired chiral products 3h−q in good
E
https://dx.doi.org/10.1021/acs.organomet.0c00174
Organometallics XXXX, XXX, XXX−XXX

Organometallics
pubs.acs.org/Organometallics
Article
as N-benzyl or N-(tert-butyldimethylsilyl) indole as the
reactants led to significantly decreased enantioselectivity
(12−64% ee).
Table 3. Enantioselective C−H Insertion of Methyl α-
Phenyl-α-diazoacetate with Substituted N-Methylindoles
Catalyzed by the (Phebim)Ir Complex 2d
a
CONCLUSIONS
■
In summary, we have synthesized a series of new chiral NCN
pincer (Phebim)Ir complexes via C−H activation. X-ray single-
crystal diffraction analysis reveals that one of the complexes is a
coordinatively unsaturated complex that is stabilized by the
weak Ir−H agostic interactions. With the assistance of NaBArF,
the Ir complex showed good activity and stereocontrol in the
asymmetric C−H insertion reaction of α-aryl-α-diazoacetates
with N-protected indoles, delivering various chiral 3-
substituted indoles in good yields with moderate to good
enantioselectivities. The (Phebim)Ir complexes are subjects of
the ongoing research in our laboratory to explore further their
catalytic potentials in asymmetric carbene insertion reactions.
b
cd
,
entry
R3
product
yield (%)
ee (%)
1
2
3
4
5
6
7
8
4-Me
4-F
4-Cl
5-Me
5-F
5-Cl
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
49
47
44
90
73
36
40
80
63
96
32
30
89
59
trace
62
20
57
58
55
49
43
37
35
84
55
52
54
6
5-Br
EXPERIMENTAL SECTION
■
5-MeO
5-CO2Me
6-Me
6-Cl
General Procedures. Solvents were dried with standard methods
and freshly distilled prior to use if needed. Chiral amino alcohols,17 α-
aryl-α-diazoacetates,18 N-methylindoles, N-benzylindole, and N-
TBDMS indole19 were prepared according to the literature methods.
9
10
11
12
13
14
6-Br
All other chemicals were used as purchased. H, 13C{1H}, and 19F
1
7-Me
7-MeO
2-Me
NMR spectra were recorded on a Bruker DPX-400 spectrometer with
CDCl3 as the solvent and TMS as an internal standard. Chemical shift
multiplicities are represented as follows: s = singlet, d = doublet, t =
triplet, q = quartet, hept = heptet, m = multiplet, dd = doublet of
doublets, dt = doublet of triplets, app = apparent, br = broad. HRMS
was tested on a Waters Q-Tof Micro MS/MS System ESI
spectrometer. The enantiomeric excesses of (R)- and (S)-enantiomers
were determined by HPLC analysis over a chiral column with a UV
detector. Melting points were measured with a WC-1 instrument and
uncorrected. Optical rotations were recorded on a PerkinElmer 341
polarimeter.
e
15
a
Reaction conditions: methyl α-phenyl-α-diazoacetate (0.20 mmol),
substituted N-methylindole (0.24 mmol), cat. 2d (3 mol %), NaBArF
(6 mol %), CH2Cl2 (2 mL), 0 °C, 24 h, Ar. Isolated yield.
Determined by chiral HPLC analysis. Absolute configurations of the
b
c
d
e
products were assigned by analogy. Reaction was carried out at 40
°C.
methylindoles exhibited lower reactivity, possibly due to the
steric hindrance at the C4-position. In addition, the N-
methylindoles with electron-donating groups were generally
much more reactive than those with electron-withdrawing
groups, which is in direct contrast with the substituent effect in
methyl α-aryl-α-diazoacetates. Unfortunately, the reaction of a
2-substituted N-methylindole such as 1,2-dimethylindole with
methyl α-phenyl-α-diazoacetate at room temperature (∼20
°C) failed to afford the desired product (data not shown), and
the reaction was very sluggish, even at a temperature of 40 °C
(entry 15).
In comparison with the reported Fe, Rh, Pd, and Cu
catalytic systems,15 the current Ir system exhibited generally
inferior stereocontrol in the reactions. Nonetheless, in the
cases of some specific substrates such as methyl α-aryl-α-
diazoacetates bearing a 4-Me or 4-MeO group on the aryl ring,
the Ir catalyst could afford comparable15b or better
enantioselectivity.15a In addition, the sterically hindered
substrates including the diazo compounds with an ortho
substituent on the aryl ring (Table 2, entry 18) and 2-
substituted N-protected indoles (Table 3, entry 15) were
almost unreactive under the Ir-catalyzed reaction conditions.
For Fe,15a Rh,15b and Cu15d catalysts, the reactions were also
sensitive to the steric hindrance of the diazo substrates.
However, the desired products could still be obtained in
moderate to high yields and with moderate to high
enantioselectivities. Interestingly, it was found that in the Pd-
and Cu-catalyzed reactions, the presence of a substituent at the
indole C2 position was crucial for achieving high levels of
enantioselectivity.15c,d The use of 2-unsubstituted indoles such
Synthesis of Phebim-H Ligands 1a−h. The ligands 1a−h were
synthesized starting from isophthaloyl chloride or 5-(tert-butyl)-
isophthalic acid according to the procedure we previously reported.8
The characterization data of the new ligands 1f−h are given as
follows.
5-tert-Butyl-1,3-bis((S)-4-isopropyl-1-p-tolyl-4,5-dihydro-1H-imi-
dazol-2-yl)benzene (1f). Pale-yellow solid (812.5 mg, 1.52 mmol,
76% based on the 5-(tert-butyl)isophthalic acid). Mp 84−86 °C.
20
1
[α]D = −1.0 (c 0.374, CH2Cl2). H NMR (400 MHz, CDCl3): δ
7.76 (t, J = 1.4 Hz, 1H, ArH), 7.28 (d, J = 1.3 Hz, 2H, ArH), 6.94 (d,
J = 8.2 Hz, 4H, NArH), 6.65 (d, J = 8.3 Hz, 4H, NArH), 4.14 (app t, J
= 9.8 Hz, 2H, NCH2), 4.08−4.02 (m, 2H, NCH), 3.55 (dd, J = 7.4,
8.6 Hz, 2H, NCH2), 2.23 (s, 6H, CH3), 1.97−1.89 (m, 2H,
CH(CH3)2), 1.01 (d, J = 6.8 Hz, 6H, CH(CH3)2), 0.93 (s, 9H,
C(CH3)3), 0.92 (d, J = 5.8 Hz, 6H, CH(CH3)2). 13C{1H} NMR (100
MHz, CDCl3): δ 161.6, 150.2, 140.1, 133.6, 130.1, 129.2, 127.9,
127.0, 123.4, 69.5, 56.2, 34.4, 32.9, 30.6, 20.7, 18.8, 17.7. HRMS
(positive ESI): [M + H]+ calcd for C36H47N4: 535.3801. Found:
535.3796.
5-tert-Butyl-1,3-bis((S)-4-tert-butyl-1-p-tolyl-4,5-dihydro-1H-imi-
dazol-2-yl)benzene (1g). Pale-yellow solid (733.2 mg, 1.30 mmol,
65% based on the 5-(tert-butyl)isophthalic acid). Mp 99−101 °C.
20
1
[α]D = +30.2 (c 0.860, CH2Cl2). H NMR (400 MHz, CDCl3): δ
7.76 (s, 1H, ArH), 7.32 (d, J = 1.5 Hz, 2H, ArH), 6.96 (d, J = 8.1 Hz,
4H, NArH), 6.68 (d, J = 8.3 Hz, 4H, NArH), 4.20 (app t, J = 10.4 Hz,
2H, NCH2), 3.98 (dd, J = 7.1, 11.0 Hz, 2H, NCH), 3.58 (dd, J = 7.2,
9.6 Hz, 2H, NCH2), 2.23 (s, 6H, CH3), 0.96 (s, 18H, C(CH3)3), 0.93
(s, 9H, C(CH3)3). 13C{1H} NMR (100 MHz, CDCl3): δ 161.8,
150.3, 140.0, 134.1, 129.3, 128.2, 127.4, 123.8, 72.6, 55.3, 34.4, 34.3,
30.6, 25.7, 20.8. HRMS (positive ESI): [M + H]+ calcd for C38H51N4:
563.4114, found: 563.4116.
5-tert-Butyl-1,3-bis((S)-4-benzyl-1-p-tolyl-4,5-dihydro-1H-imida-
zol-2-yl)benzene (1h). Pale-yellow solid (377.8 mg, 0.60 mmol, 30%
F
https://dx.doi.org/10.1021/acs.organomet.0c00174
Organometallics XXXX, XXX, XXX−XXX

Organometallics
pubs.acs.org/Organometallics
Article
20
based on the 5-(tert-butyl)isophthalic acid). Mp 80−82 °C. [α]D
=
Bis(imidazoline) NCN Pincer Iridium(III) Complex (2e). First with
+44.1 (c 0.400, CH2Cl2). 1H NMR (400 MHz, CDCl3): δ 7.75 (t, J =
1.4 Hz, 1H, ArH), 7.31−7.17 (m, 12H, ArH and PhH), 6.89 (d, J =
8.2 Hz, 4H, NArH), 6.49 (d, J = 8.3 Hz, 4H, NArH), 4.56−4.48 (m,
2H, NCH), 4.03 (app t, J = 9.8 Hz, 2H, NCH2), 3.62 (dd, J = 6.9, 9.5
Hz, 2H, NCH2), 3.21 (dd, J = 4.5, 13.6 Hz, 2H, CH2Ph), 2.82 (dd, J
= 8.6, 13.6 Hz, 2H, CH2Ph), 2.22 (s, 6H, CH3), 0.94 (s, 9H,
C(CH3)3). 13C{1H} NMR (100 MHz, CDCl3): δ 162.0, 150.3, 139.9,
138.2, 133.6, 130.4, 129.5, 129.2, 128.4, 127.9, 126.7, 126.3, 123.2,
64.8, 58.1, 42.2, 34.4, 30.6, 20.7. HRMS (positive ESI): 0.5[M +
2H]2+ calcd for C22H24N2: 316.1939, found: 316.1938.
Synthesis of the NCN Pincer Iridium(III) Complexes 2a−h.
Under an argon atmosphere, IrCl3·3H2O (77.6 mg, 0.22 mmol),
NaHCO3 (18.5 mg, 0.22 mmol), and the ligand (0.20 mmol) were
first dissolved in 6.6 mL of anhydrous alcohol in a dry Schlenk tube.
Then, the tube was fitted with a reflux condenser, and the resulting
mixture was refluxed for 12 h. The reaction mixture was allowed to
cool to room temperature and concentrated in vacuo. The residue was
purified by chromatography on silica gel plates (for 2a−c and 2g′)
and further purified by column chromatography on silica gel (for 2d−
f and 2h) to give the corresponding bis(imidazoline) NCN pincer
iridium(III) complex.
CH2Cl2, then with CH2Cl2/petroleum ether (1/1) to CH2Cl2 as the
20
eluent; red solid (77.7 mg, 44%). Mp 230−232 °C. [α]D = +339.7
1
(c 0.475, CH2Cl2). H NMR (400 MHz, CDCl3): δ 7.61 (d, J = 7.0
Hz, 4H, PhH), 7.36 (t, J = 7.2 Hz, 4H, PhH), 7.31−7.24 (m, 10H,
NArH and PhH), 6.58 (s, 2H, ArH), 5.33−5.26 (m, 2H, ImH), 4.63
(app t, J = 10.1 Hz, 2H, ImH), 4.04 (dd, J = 9.6, 12.1 Hz, 2H, ImH),
2.40 (s, 6H, CH3), 2.25 (br s, 2H, OH2), 0.84 (s, 9H, C(CH3)3).
13C{1H} NMR (100 MHz, CDCl3): δ 173.1, 161.3, 141.9, 140.4,
138.4, 137.6, 132.4, 129.9, 128.8, 128.6, 128.2, 126.7, 125.9, 67.1,
63.7, 34.3, 31.2, 21.1. Anal. Calcd for C42H43Cl2IrN4O·0.25CH2Cl2:
C, 56.12; H, 4.85; N, 6.20. Found: C, 55.75; H, 4.90; N, 5.90.
Bis(imidazoline) NCN Pincer Iridium(III) Complex (2f). First with
CH2Cl2/ethyl acetate (20/1), then with CH2Cl2/ethyl acetate (100/1
to 80/1) as the eluent; red solid (73.2 mg, 45%). Mp 183−187 °C.
20
1
[α]D = +163.0 (c 0.216, CH2Cl2). H NMR (400 MHz, CDCl3): δ
7.22 (d, J = 8.4 Hz, 4H, NArH), 7.18 (d, J = 8.3 Hz, 4H, NArH), 6.49
(s, 2H, ArH), 4.38−4.28 (m, 4H, ImH), 4.03 (dd, J = 4.5, 7.9 Hz, 2H,
ImH), 3.11 (br s, 2H, OH2), 2.55−2.52 (m, 2H, CH(CH3)2), 2.39 (s,
6H, CH3), 1.01 (d, J = 6.6 Hz, 6H, CH(CH3)2), 0.97 (d, J = 7.0 Hz,
6H, CH(CH3)2), 0.81 (s, 9H, C(CH3)3). 13C{1H} NMR (100 MHz,
CDCl3): δ 170.6, 142.2, 138.6, 137.1, 132.2, 129.8, 126.4, 125.2, 67.8,
54.8, 34.2, 31.1, 29.6, 21.1, 19.3, 15.3. Anal. Calcd for
C36H47Cl2IrN4O·C3H6O: C, 53.66; H, 6.12; N, 6.42. Found: C,
53.90; H, 6.12; N, 6.42.
Bis(imidazoline) NCN Pincer Iridium(III) Complex (2a). With
CH2Cl2/n-hexane (5/1) as the eluent; red solid (24.3 mg, 16%). Mp
20
1
189−200 °C. [α]D = +215.9 (c 0.368, CH2Cl2). H NMR (400
MHz, CDCl3): δ 7.21 (d, J = 8.3 Hz, 4H, NArH), 7.16 (d, J = 8.4 Hz,
4H, NArH), 6.53−6.46 (m, 3H, ArH), 4.39−4.28 (m, 4H, ImH), 3.99
(dd, J = 5.3, 8.6 Hz, 2H, ImH), 2.99 (br s, 2H, OH2), 2.54−2.48 (m,
2H, CH(CH3)2), 2.40 (s, 6H, CH3), 1.00 (d, J = 6.7 Hz, 6H,
CH(CH3)2), 0.97 (d, J = 7.0 Hz, 6H, CH(CH3)2). 13C{1H} NMR
(100 MHz, CDCl3): δ 170.4, 138.7, 137.0, 133.0, 130.0, 127.4, 126.0,
119.6, 67.7, 55.1, 29.5, 21.1, 19.3, 15.3. Anal. Calcd for
C32H39Cl2IrN4O: C, 50.65; H, 5.18; N, 7.38. Found: C, 50.49; H,
5.32; N, 7.19.
Bis(imidazoline) NCN Pincer Iridium(III) Complex (2g′). With
20
CH2Cl2 as the eluent; red solid (76.9 mg, 47%). Mp > 250 °C. [α]D
1
= +214.5 (c 0.552, CH2Cl2). H NMR (400 MHz, CDCl3): δ 7.26−
7.21 (m, 8H, NArH), 6.37 (s, 2H, ArH), 4.39 (dd, J = 9.2, 10.5 Hz,
2H, ImH), 4.23 (app t, J = 11.1 Hz, 2H, ImH), 4.07 (dd, J = 9.1, 11.6
Hz, 2H, ImH), 2.40 (s, 6H, CH3), 1.29 (s, 18H, C(CH3)3), 0.78 (s,
9H, C(CH3)3). 13C{1H} NMR (100 MHz, CDCl3): δ 170.3, 143.7,
143.0, 138.5, 137.7, 132.6, 130.0, 126.6, 125.4, 72.6, 56.8, 34.1, 34.0,
31.1, 27.0, 21.1. Anal. Calcd for C38H49Cl2IrN4·0.5CH2Cl2: C, 53.31;
H, 5.81; N, 6.46. Found: C, 52.81; H, 5.97; N, 6.32.
Bis(imidazoline) NCN Pincer Iridium(III) Complex (2b′). With
CH2Cl2/n-hexane (5/1) as the eluent; red solid (23.1 mg, 15%). Mp
Bis(imidazoline) NCN Pincer Iridium(III) Complex (2h). First with
CH2Cl2/ethyl acetate (20/1), then with CH2Cl2/ethyl acetate (100/1
to 80/1) as the eluent; red solid (61.5 mg, 34%). Mp 223−225 °C.
20
1
> 250 °C. [α]D = +311.0 (c 0.280, CH2Cl2). H NMR (400 MHz,
CDCl3): δ 7.23 (d, J = 8.4 Hz, 4H, NArH), 7.20 (d, J = 8.5 Hz, 4H,
NArH), 6.45−6.37 (m, 3H, ArH), 4.42 (dd, J = 9.4, 10.6 Hz, 2H,
ImH), 4.19 (app t, J = 11.0 Hz, 2H, ImH), 4.03 (dd, J = 9.4, 11.0 Hz,
2H, ImH), 2.41 (s, 6H, CH3), 1.28 (s, 18H, C(CH3)3). 13C{1H}
NMR (100 MHz, CDCl3): δ 170.3, 138.7, 137.6, 133.5, 130.2, 127.6,
126.3, 120.0, 72.5, 57.2, 34.1, 27.0, 21.2. Anal. Calcd for
C34H41Cl2IrN4: C, 53.11; H, 5.38; N, 7.29. Found: C, 53.23; H,
5.65; N, 6.77.
20
1
[α]D = +154.0 (c 0.150, CH2Cl2). H NMR (400 MHz, CDCl3): δ
7.34−7.11 (m, 18H, PhH and NArH), 6.51 (s, 2H, ArH), 4.67 (br s,
2H, ImH), 4.19 (app t, J = 9.8 Hz, 2H, ImH), 3.96−3.91 (m, 2H,
ImH), 3.74−3.71 (m, 2H, CH2Ph), 3.01−2.95 (m, 2H, CH2Ph), 2.81
(br s, 2H, OH2), 2.38 (s, 6H, CH3), 0.82 (s, 9H, C(CH3)3). 13C{1H}
NMR (100 MHz, CDCl3): δ 171.3, 142.3, 138.3, 138.2, 137.3, 132.4,
129.7, 129.5, 128.5, 126.5, 126.3, 125.4, 64.1, 59.5, 40.8, 34.2, 31.1,
21.0. Anal. Calcd for C44H47Cl2IrN4O: C, 58.01; H, 5.20; N, 6.15.
Found: C, 57.76; H, 5.48; N, 6.91.
Bis(imidazoline) NCN Pincer Iridium(III) Complex (2c). With
CH2Cl2/n-hexane (5/1) as the eluent; red solid (25.5 mg, 13%). Mp
20
1
> 250 °C. [α]D = +302.8 (c 0.385, CH2Cl2). H NMR (400 MHz,
CDCl3): δ 7.43−7.42 (m, 4H, PhH), 7.41−7.26 (m, 18H, NArH and
PhH), 7.10 (br s, 5H, PhH), 6.82 (br s, 1H, PhH), 6.54−6.45 (m, 3H,
ArH), 5.11 (d, J = 11.7 Hz, 2H, ImH), 4.88 (d, J = 11.7 Hz, 2H,
ImH), 2.33 (s, 6H, CH3), 1.87 (s, 2H, OH2). 13C{1H} NMR (100
MHz, CDCl3): δ 179.0, 175.7, 139.3, 139.0, 138.9, 137.9, 133.6,
129.9, 128.74, 128.69, 128.56, 128.48, 128.42, 128.2, 128.1, 119.2,
81.0, 77.2, 21.1. Anal. Calcd for C50H43Cl2IrN4O: C, 61.34; H, 4.43;
N, 5.72. Found: C, 61.23; H, 4.63; N, 5.28.
Typical Procedure for C−H Insertion Reactions of α-Aryl-α-
diazoacetates with N-Protected Indoles Using the Pincer Ir−
Phebim Complex 2d as the Catalyst. Under an argon atmosphere,
the pincer Ir−Phebim complex 2d (6.2 mg, 3 mol %) and NaBArF
({sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate}, 10.6 mg, 6
mol %) were dissolved in 1.0 mL of CH2Cl2 in a dry Schlenk tube,
and the mixture was stirred at 30 °C for 2 h. Then, the substrate of N-
protected indole (0.24 mmol) diluted by CH2Cl2 (0.5 mL) was added
at room temperature, and the tube was placed at 0 °C. After stirring
for a few minutes, α-aryl-α-diazoacetate (0.20 mmol) diluted by
CH2Cl2 (0.5 mL) was added, and the resulting mixture was stirred at
0 °C for another 24 h. The solvent was evaporated under vacuum, and
the residue was purified by chromatography on silica gel plates with
petroleum ether/ethyl acetate 20/1 or 5/1 (for 4i) as the eluent to
afford products 3 and 4. The enantiomeric excesses were determined
by HPLC analysis.
Bis(imidazoline) NCN Pincer Iridium(III) Complex (2d). First with
CH2Cl2/n-hexane (3/1), then with CH2Cl2/petroleum ether (1/1 to
20
3/1) as the eluent; red solid (95.2 mg, 46%). Mp > 250 °C. [α]D
=
+277.3 (c 0.375, CH2Cl2). 1H NMR (400 MHz, CDCl3): δ 7.45 (d, J
= 6.6 Hz, 4H, PhH), 7.39−7.36 (m, 4H, PhH), 7.32−7.24 (m, 13H,
NArH and PhH), 7.11 (br s, 5H, PhH), 6.87 (br s, 2H, PhH), 6.41 (s,
2H, ArH), 5.19 (d, J = 10.5 Hz, 2H, ImH), 4.97 (d, J = 10.5 Hz, 2H,
ImH), 2.31 (s, 6H, CH3), 2.22 (br s, 2H, OH2), 0.80 (s, 9H,
C(CH3)3). 13C{1H} NMR (100 MHz, CDCl3): δ 173.5, 142.2, 139.9,
139.6, 138.1, 132.6, 129.9, 128.8, 128.6, 128.5, 128.4, 128.1, 125.8,
80.3, 76.6, 34.2, 31.1, 21.1. Anal. Calcd for C54H51Cl2IrN4O·
0.25CH2Cl2: C, 61.68; H, 4.91; N, 5.30. Found: C, 61.60; H, 5.13;
N, 4.99.
(S)-Methyl 2-(1-Methyl-1H-indol-3-yl)-2-phenylacetate
(3a).15b,18,20 Colorless oil (48.1 mg, 86%). The enantiomeric excess
was determined on a Daicel Chiralcel OD-H column with n-hexane/
2-propanol (90/10) and a flow rate of 1.0 mL/min and detected at a
UV wavelength of 254 nm. Retention times: 9.6 min (minor), 12.8
20
1
min (major), 84% ee. [α]D = +17.5 (c 0.690, CH2Cl2). H NMR
G
https://dx.doi.org/10.1021/acs.organomet.0c00174
Organometallics XXXX, XXX, XXX−XXX

Organometallics
pubs.acs.org/Organometallics
Article
20
1
(400 MHz, CDCl3): δ 7.45−7.40 (m, 3H), 7.33−7.19 (m, 5H),
7.08−7.04 (m, 2H), 5.26 (s, 1H), 3.75 (s, 3H), 3.74 (s, 3H).
(S)-Methyl 2-(1-Benzyl-1H-indol-3-yl)-2-phenylacetate (3b).15b,18
Colorless oil (47.7 mg, 67%). The enantiomeric excess was
determined on a Daicel Chiralcel OD-H column with n-hexane/2-
propanol (90/10) and a flow rate of 1.0 mL/min and detected at a
UV wavelength of 254 nm. Retention times: 12.4 min (minor), 21.5
min (major), 74% ee. [α]D = +24.6 (c 0.886, CH2Cl2). H NMR
(400 MHz, CDCl3): δ 7.45−7.41 (m, 3H), 7.33−7.22 (m, 7H), 7.18
(s, 1H), 7.16−7.09 (m, 3H), 7.07−7.03 (m, 1H), 5.30 (s, 2H), 5.28
(s, 1H), 3.74 (s, 3H).
(S)-Methyl 2-(1-(tert-Butyldimethylsilyl)-1H-indol-3-yl)-2-phenyl-
acetate (3c).15a Colorless oil (23.4 mg, 31%). The enantiomeric
excess was determined on a Daicel Chiralpak AD-H column with n-
hexane/2-propanol (96/1.2) and a flow rate of 0.8 mL/min and
detected at a UV wavelength of 254 nm. Retention times: 6.2 min
(minor), 6.9 min (major), 66% ee. [α]D20 = +36.0 (c 0.358, CH2Cl2).
1H NMR (400 MHz, CDCl3): δ 7.48 (d, J = 8.3 Hz, 1H), 7.41−7.38
min (major), 79% ee. [α]D = +33.9 (c 0.620, CH2Cl2). H NMR
(400 MHz, CDCl3): δ 7.41−7.36 (m, 3H), 7.30 (d, J = 8.2 Hz, 1H),
7.24−7.20 (m, 1H), 7.08−7.05 (m, 2H), 7.02−6.96 (m, 2H), 5.23 (s,
1H), 3.77 (s, 3H), 3.75 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3):
δ 173.4, 162.1 (d, 1JC−F = 244.1 Hz), 137.1, 134.5 (d, 4JC−F = 3.1 Hz),
130.0 (d, 3JC−F = 8.0 Hz), 127.8, 126.9, 122.0, 119.4, 119.0, 115.4 (d,
2JC−F = 21.4 Hz), 111.9, 109.5, 52.4, 48.0, 32.8. 19F NMR (376 MHz,
20
1
CDCl3): δ −115.6. HRMS (positive ESI): [M + H]+ calcd for
C18H17FNO2: 298.1243, found: 298.1244.
(S)-Methyl 2-(4-Chlorophenyl)-2-(1-methyl-1H-indol-3-yl)-
acetate (3i).15b Colorless oil (51.3 mg, 82%). The enantiomeric
excess was determined on a Daicel Chiralcel OD-H column with n-
hexane/2-propanol (90/10) and a flow rate of 1.0 mL/min and
detected at a UV wavelength of 254 nm. Retention times: 10.8 min
(minor), 16.5 min (major), 52% ee. [α]D20 = +10.8 (c 1.016, CH2Cl2).
1H NMR (400 MHz, CDCl3): δ 7.40 (d, J = 8.0 Hz, 1H), 7.36−7.34
(m, 2H), 7.31−7.25 (m, 3H), 7.23−7.20 (m, 1H), 7.08−7.04 (m,
2H), 5.22 (m, 1H), 3.76 (s, 3H), 3.75 (s, 3H).
(m, 3H), 7.32−7.28 (m, 2H), 7.24−7.21 (m, 2H), 7.15−7.11 (m,
1H), 7.06−7.02 (m, 1H), 5.25 (s, 1H), 3.74 (s, 3H), 0.92 (s, 9H),
0.592 (s, 3H), 0.586 (s, 3H).
(S)-Methyl 2-(4-Bromophenyl)-2-(1-methyl-1H-indol-3-yl)-
acetate (3j).15b Colorless oil (62.5 mg, 87%). The enantiomeric
excess was determined on a Daicel Chiralcel OD-H column with n-
hexane/2-propanol (90/10) and a flow rate of 1.0 mL/min and
detected at a UV wavelength of 254 nm. Retention times: 12.2 min
(minor), 17.8 min (major), 46% ee. [α]D20 = +5.7 (c 1.290, CH2Cl2).
1H NMR (400 MHz, CDCl3): δ 7.44−7.38 (m, 3H), 7.31−7.28 (m,
(S)-Ethyl 2-(1-Methyl-1H-indol-3-yl)-2-phenylacetate (3d).15b
Colorless oil (27.3 mg, 47%). The enantiomeric excess was
determined on a Daicel Chiralcel OD-H column with n-hexane/2-
propanol (90/10) and a flow rate of 1.0 mL/min and detected at a
UV wavelength of 254 nm. Retention times: 9.3 min (minor), 11.0
3H), 7.24−7.20 (m, 1H), 7.08−7.04 (m, 2H), 5.21 (s, 1H), 3.76 (s,
3H), 3.75 (s, 3H).
20
1
min (major), 70% ee. [α]D = +17.6 (c 0.516, CH2Cl2). H NMR
(400 MHz, CDCl3): δ 7.46−7.42 (m, 3H), 7.32−7.18 (m, 5H),
7.07−7.04 (m, 2H), 5.23 (s, 1H), 4.26−4.14 (m, 2H), 3.73 (s, 3H),
1.25 (t, J = 7.1 Hz, 3H).
(S)-Methyl 2-(1-Methyl-1H-indol-3-yl)-2-(p-tolyl)acetate (3k).15b
Colorless oil (38.9 mg, 66%). The enantiomeric excess was
determined on a Daicel Chiralcel OD-H column with n-hexane/2-
propanol (90/10) and a flow rate of 1.0 mL/min and detected at a
UV wavelength of 254 nm. Retention times: 9.1 min (minor), 13.9
min (major), 84% ee. [α]D20 = +8.5 (c 0.758, CH2Cl2). 1H NMR (400
MHz, CDCl3): δ 7.44 (d, J = 7.9 Hz, 1H), 7.31−7.27 (m, 3H), 7.22−
7.18 (m, 1H), 7.12 (d, J = 7.9 Hz, 2H), 7.08−7.03 (m, 2H), 5.22 (s,
1H), 3.75 (s, 3H), 3.73 (s, 3H), 2.32 (s, 3H).
(S)-Isopropyl 2-(1-Methyl-1H-indol-3-yl)-2-phenylacetate (3e).
Colorless oil (15.3 mg, 25%). The enantiomeric excess was
determined on a Daicel Chiralpak AS-H column with n-hexane/2-
propanol (90/10) and a flow rate of 1.0 mL/min and detected at a
UV wavelength of 254 nm. Retention times: 5.9 min (minor), 6.8 min
20
1
(major), 71% ee. [α]D = +13.0 (c 0.282, CH2Cl2). H NMR (400
MHz, CDCl3): δ 7.46−7.41 (m, 3H), 7.32−7.18 (m, 5H), 7.07−7.03
(m, 2H), 5.20 (s, 1H), 5.07 (hept, J = 6.3 Hz, 1H), 3.73 (s, 3H), 1.24
(d, J = 6.3 Hz, 3H), 1.20 (d, J = 6.3 Hz, 3H). 13C{1H} NMR (100
MHz, CDCl3): δ 172.6, 139.0, 137.0, 128.5, 128.4, 127.9, 127.14,
127.09, 121.8, 119.2, 119.1, 112.3, 109.3, 68.5, 49.1, 32.8, 21.8, 21.7.
HRMS (positive ESI): [M + H]+ calcd for C20H22NO2: 308.1651,
found: 308.1652.
(S)-Methyl 2-(4-Methoxyphenyl)-2-(1-methyl-1H-indol-3-yl)-
acetate (3l).15b Colorless oil (25.2 mg, 41%). The enantiomeric
excess was determined on a Daicel Chiralcel OD-H column with n-
hexane/2-propanol (90/10) and a flow rate of 1.0 mL/min and
detected at a UV wavelength of 254 nm. Retention times: 16.5 min
(minor), 24.7 min (major), 86% ee. [α]D20 = +10.3 (c 0.532, CH2Cl2).
1H NMR (400 MHz, CDCl3): δ 7.43 (d, J = 8.0 Hz, 1H), 7.35−7.32
(m, 2H), 7.29 (d, J = 8.2 Hz, 1H), 7.23−7.18 (m, 1H), 7.08−7.03 (m,
2H), 6.86−6.83 (m, 2H), 5.20 (s, 1H), 3.78 (s, 3H), 3.75 (s, 3H),
3.74 (s, 3H).
(S)-Isopentyl 2-(1-Methyl-1H-indol-3-yl)-2-phenylacetate (3f).
Colorless oil (28.1 mg, 42%). The enantiomeric excess was
determined on a Daicel Chiralpak AS-H column with n-hexane/2-
propanol (90/10) and a flow rate of 1.0 mL/min and detected at a
UV wavelength of 254 nm. Retention times: 5.8 min (minor), 6.5 min
(S)-Methyl 2-(3-Chlorophenyl)-2-(1-methyl-1H-indol-3-yl)-
acetate (3m).15b Colorless oil (54.1 mg, 86%). The enantiomeric
excess was determined on a Daicel Chiralcel OD-H column with n-
hexane/2-propanol (90/10) and a flow rate of 1.0 mL/min and
detected at a UV wavelength of 254 nm. Retention times: 11.1 min
(minor), 19.1 min (major), 48% ee. [α]D20 = +17.7 (c 0.928, CH2Cl2).
1H NMR (400 MHz, CDCl3): δ 7.42 (d, J = 7.9 Hz, 2H), 7.31−7.29
20
1
(major), 77% ee. [α]D = +15.9 (c 0.520, CH2Cl2). H NMR (400
MHz, CDCl3): δ 7.45−7.41 (m, 3H), 7.32−7.18 (m, 5H), 7.08−7.03
(m, 2H), 5.23 (s, 1H), 4.22−4.12 (m, 2H), 3.74 (s, 3H), 1.66−1.56
(m, 1H), 1.54−1.48 (m, 2H), 0.87 (d, J = 6.5 Hz, 3H), 0.86 (d, J =
6.6 Hz, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ 173.2, 138.9,
137.0, 128.5, 128.4, 127.9, 127.2, 127.1, 121.8, 119.2, 119.1, 112.2,
109.3, 63.8, 49.0, 37.3, 32.8, 25.0, 22.4. HRMS (positive ESI): [M +
H]+ calcd for C22H26NO2: 336.1964, found: 336.1963.
(m, 2H), 7.24−7.20 (m, 3H), 7.09−7.06 (m, 2H), 5.23 (s, 1H), 3.78
(s, 3H), 3.75 (s, 3H).
(S)-Methyl 2-(1-Methyl-1H-indol-3-yl)-2-(3-(trifluoromethyl)-
phenyl)acetate (3n). Colorless oil (68.1 mg, 98%). The enantiomeric
excess was determined on a Daicel Chiralcel OD-H column with n-
hexane/2-propanol (90/10) and a flow rate of 1.0 mL/min and
detected at a UV wavelength of 254 nm. Retention times: 9.7 min
(minor), 20.7 min (major), 58% ee. [α]D20 = +27.0 (c 1.234, CH2Cl2).
1H NMR (400 MHz, CDCl3): δ 7.70 (s, 1H), 7.61 (d, J = 7.8 Hz,
(S)-Benzyl 2-(1-Methyl-1H-indol-3-yl)-2-phenylacetate (3g).15b
Colorless oil (69.9 mg, 98%). The enantiomeric excess was
determined on a Daicel Chiralcel OD-H column with n-hexane/2-
propanol (95/5) and a flow rate of 1.0 mL/min and detected at a UV
wavelength of 254 nm. Retention times: 19.4 min (minor), 21.2 min
20
1
(major), 68% ee. [α]D = +16.6 (c 1.302, CH2Cl2). H NMR (400
MHz, CDCl3): δ 7.42−7.39 (m, 3H), 7.33−7.18 (m, 10H), 7.05−
7.00 (m, 2H), 5.30 (s, 1H), 5.21 (d, J = 12.4 Hz, 1H), 5.16 (d, J =
12.4 Hz, 1H), 3.73 (s, 3H).
1H), 7.52 (d, J = 7.8 Hz, 1H), 7.44−7.41 (m, 2H), 7.31 (d, J = 8.2
Hz, 1H), 7.25−7.21 (m, 1H), 7.10−7.06 (m, 2H), 5.31 (s, 1H), 3.78
(s, 3H), 3.76 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ 173.0,
2
139.8, 137.1, 131.9, 130.8 (q, JC−F = 31.9 Hz), 129.0, 127.9, 126.8,
(S)-Methyl 2-(4-Fluorophenyl)-2-(1-methyl-1H-indol-3-yl)acetate
(3h). Colorless oil (51.9 mg, 87%). The enantiomeric excess was
determined on a Daicel Chiralcel OD-H column with n-hexane/2-
propanol (90/10) and a flow rate of 1.0 mL/min and detected at a
UV wavelength of 254 nm. Retention times: 10.4 min (minor), 15.0
125.3 (q, 3JC−F = 3.7 Hz), 124.23 (q, 3JC−F = 3.8 Hz), 124.15 (q, 1JC−F
= 270.7 Hz), 122.1, 119.5, 118.8, 111.2, 109.5, 52.5, 48.6, 32.9. 19F
NMR (376 MHz, CDCl3): δ −62.4. HRMS (positive ESI): [M + H]+
calcd for C19H17F3NO2: 348.1211, found: 348.1212.
H
https://dx.doi.org/10.1021/acs.organomet.0c00174
Organometallics XXXX, XXX, XXX−XXX

Organometallics
pubs.acs.org/Organometallics
Article
1
(S)-Methyl 2-(3-Methoxyphenyl)-2-(1-methyl-1H-indol-3-yl)-
acetate (3o).15b Colorless oil (21.5 mg, 35%). The enantiomeric
excess was determined on a Daicel Chiralcel OD-H column with n-
hexane/2-propanol (90/10) and a flow rate of 1.0 mL/min and
detected at a UV wavelength of 254 nm. Retention times: 13.6 min
(minor), 19.4 min (major), 46% ee. [α]D20 = +4.9 (c 0.428, CH2Cl2).
1H NMR (400 MHz, CDCl3): δ 7.46 (d, J = 8.0 Hz, 1H), 7.28 (d, J =
8.2 Hz, 1H), 7.23−7.19 (m, 2H), 7.08−7.05 (m, 2H), 7.01 (d, J = 7.8
Hz, 1H), 6.99−6.98 (m, 1H), 6.81−6.78 (m, 1H), 5.23 (s, 1H), 3.77
(s, 3H), 3.75 (s, 3H), 3.74 (s, 3H).
(S)-Methyl 2-(3,4-Dichlorophenyl)-2-(1-methyl-1H-indol-3-yl)-
acetate (3p). Colorless oil (69.3 mg, >99%). The enantiomeric
excess was determined on a Daicel Chiralcel OD-H column with n-
hexane/2-propanol (90/10) and a flow rate of 1.0 mL/min and
detected at a UV wavelength of 254 nm. Retention times: 12.1 min
(minor), 22.2 min (major), 37% ee. [α]D20 = +12.1 (c 1.342, CH2Cl2).
1H NMR (400 MHz, CDCl3): δ 7.50 (d, J = 2.1 Hz, 1H), 7.40−7.36
(m, 2H), 7.31 (d, J = 8.2 Hz, 1H), 7.25−7.21 (m, 2H), 7.10−7.06 (m,
2H), 5.20 (s, 1H), 3.78 (s, 3H), 3.76 (s, 3H). 13C{1H} NMR (100
MHz, CDCl3): δ 172.7, 139.1, 137.1, 132.6, 131.4, 130.4, 127.9,
127.8, 126.7, 122.2, 119.6, 118.8, 110.8, 109.5, 52.6, 47.9, 32.9.
HRMS (positive ESI): [M + H]+ calcd for C18H16Cl2NO2: 348.0558,
found: 348.0556.
(S)-Methyl 2-(3,4-Dimethoxyphenyl)-2-(1-methyl-1H-indol-3-yl)-
acetate (3q). Colorless oil (14.3 mg, 21%). The enantiomeric excess
was determined on a Daicel Chiralcel OD-H column with n-hexane/
2-propanol (90/10) and a flow rate of 1.0 mL/min and detected at a
UV wavelength of 254 nm. Retention times: 17.5 min (minor), 25.6
min (major), 65% ee. [α]D20 = +3.0 (c 0.258, CH2Cl2). 1H NMR (400
MHz, CDCl3): δ 7.45 (d, J = 8.0 Hz, 1H), 7.29 (d, J = 8.2 Hz, 1H),
7.23−7.19 (m, 1H), 7.09−7.05 (m, 1H), 7.00 (s, 1H), 6.98−6.95 (m,
2H), 6.81 (d, J = 8.0 Hz, 1H), 5.19 (s, 1H), 3.86 (s, 3H), 3.83 (s,
3H), 3.76 (s, 3H), 3.75 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3):
δ 173.7, 148.9, 148.2, 137.1, 131.1, 127.8, 127.0, 121.9, 120.6, 119.3,
119.0, 112.4, 111.6, 111.0, 109.4, 55.91, 55.89, 52.3, 48.4, 32.8.
HRMS (positive ESI): [M + Na]+ calcd for C20H21NNaO4: 362.1368,
found: 362.1367.
(R)-Methyl 2-(1-Methyl-1H-indol-3-yl)-2-(thiophen-3-yl)acetate
(3s). Colorless oil (39.7 mg, 70%). The enantiomeric excess was
determined on a Daicel Chiralcel OD-H column with n-hexane/2-
propanol (90/10) and a flow rate of 1.0 mL/min and detected at a
UV wavelength of 254 nm. Retention times: 11.8 min (minor), 16.0
min (major), 47% ee. [α]D20 = +4.0 (c 0.728, CH2Cl2). 1H NMR (400
MHz, CDCl3): δ 7.53 (d, J = 8.0 Hz, 1H), 7.30−7.20 (m, 4H), 7.12
(dd, J = 1.2, 4.9 Hz, 1H), 7.09−7.07 (m, 1H), 6.99 (s, 1H), 5.33 (s,
1H), 3.75 (s, 3H), 3.74 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3):
δ 173.2, 139.0, 137.1, 128.0, 127.8, 126.9, 125.6, 122.5, 121.9, 119.4,
119.2, 112.0, 109.4, 52.4, 44.3, 32.8. HRMS (positive ESI): [M + H]+
calcd for C16H16NO2S: 286.0902, found: 286.0901.
13C{1H} NMR (100 MHz, CDCl3): δ 173.7, 157.0 (d, JC−F = 244.5
3
Hz), 139.7 (d, JC−F = 11.7 Hz), 138.8, 128.7, 128.4, 128.1, 127.3,
122.3 (d, 3JC−F = 7.8 Hz), 115.8 (d, 2JC−F = 19.6 Hz), 111.5 (d, 3JC−F
= 3.4 Hz), 105.6 (d, 4JC−F = 3.5 Hz), 104.5 (d, 2JC−F = 19.6 Hz), 52.4,
49.3 (d, JC−F = 2.0 Hz), 33.2. 19F NMR (376 MHz, CDCl3): δ
−123.5. HRMS (positive ESI): [M + H]+ calcd for C18H17FNO2:
298.1243, found: 298.1245.
(S)-Methyl 2-(4-Chloro-1-methyl-1H-indol-3-yl)-2-phenylacetate
(4c). Colorless oil (27.3 mg, 44%). The enantiomeric excess was
determined on a Daicel Chiralcel OD-H column with n-hexane/2-
propanol (90/10) and a flow rate of 1.0 mL/min and detected at a
UV wavelength of 254 nm. Retention times: 9.3 min (major), 10.9
min (minor), 57% ee. [α]D = +34.1 (c 0.522, CH2Cl2). H NMR
(400 MHz, CDCl3): δ 7.39−7.23 (m, 5H), 7.16−7.03 (m, 3H), 6.79
(s, 1H), 5.85 (s, 1H), 3.74 (s, 3H), 3.67 (s, 3H). 13C{1H} NMR (100
MHz, CDCl3): δ 174.1, 139.0, 138.5, 129.9, 128.7, 128.6, 127.2,
126.0, 123.9, 122.3, 120.4, 113.0, 108.3, 52.4, 48.9, 33.1. HRMS
(positive ESI): [M + H]+ calcd for C18H17ClNO2: 314.0948, found:
314.0949.
(S)-Methyl 2-(1,5-Dimethyl-1H-indol-3-yl)-2-phenylacetate
(4d).20 Colorless oil (53.0 mg, 90%). The enantiomeric excess was
determined on a Daicel Chiralcel OD-H column with n-hexane/2-
propanol (98/2) and a flow rate of 0.8 mL/min and detected at a UV
wavelength of 254 nm. Retention times: 19.1 min (minor), 21.1 min
(major), 58% ee. [α]D = +4.2 (c 1.002, CH2Cl2). H NMR (400
MHz, CDCl3): δ 7.43−7.40 (m, 2H), 7.33−7.29 (m, 2H), 7.27−7.22
(m, 2H), 7.17 (d, J = 8.4 Hz, 1H), 7.03 (dd, J = 1.4, 8.3 Hz, 1H), 6.99
(s, 1H), 5.23 (s, 1H), 3.74 (s, 3H), 3.72 (s, 3H), 2.40 (s, 3H).
(S)-Methyl 2-(5-Fluoro-1-methyl-1H-indol-3-yl)-2-phenylacetate
(4e). Colorless oil (43.6 mg, 73%). The enantiomeric excess was
determined on a Daicel Chiralcel OD-H column with n-hexane/2-
propanol (98/1.4) and a flow rate of 1.0 mL/min and detected at a
UV wavelength of 254 nm. Retention times: 20.5 min (minor), 22.3
min (major), 55% ee. [α]D20 = +6.6 (c 0.790, CH2Cl2). 1H NMR (400
MHz, CDCl3): δ 7.41−7.39 (m, 2H), 7.33−7.23 (m, 3H), 7.17 (dd, J
= 4.3, 8.9 Hz, 1H), 7.08−7.05 (m, 2H), 6.94 (dt, J = 2.4, 9.1 Hz, 1H),
5.16 (s, 1H), 3.74 (s, 3H), 3.72 (s, 3H). 13C{1H} NMR (100 MHz,
20
1
20
1
1
CDCl3): δ 173.3, 157.8 (d, JC−F = 233.2 Hz), 138.4, 133.7, 129.5,
3
4
128.7, 128.3, 127.4, 127.2 (d, JC−F = 9.6 Hz), 112.0 (d, JC−F = 4.6
Hz), 110.3 (d, 2JC−F = 26.4 Hz), 110.1 (d, 3JC−F = 10.2 Hz), 104.1 (d,
2JC−F = 23.7 Hz), 52.4, 48.8, 33.1. 19F NMR (376 MHz, CDCl3): δ
−124.8. HRMS (positive ESI): [M + H]+ calcd for C18H17FNO2:
298.1243, found: 298.1244.
(S)-Methyl 2-(5-Chloro-1-methyl-1H-indol-3-yl)-2-phenylacetate
(4f).20 Colorless oil (22.6 mg, 36%). The enantiomeric excess was
determined on a Daicel Chiralpak AD-H column with n-hexane/2-
propanol (98/2) and a flow rate of 1.0 mL/min and detected at a UV
wavelength of 254 nm. Retention times: 15.9 min (major), 18.1 min
20
1
(minor), 49% ee. [α]D = −9.5 (c 0.442, CH2Cl2). H NMR (400
MHz, CDCl3): δ 7.40−7.38 (m, 3H), 7.34−7.24 (m, 3H), 7.20−7.13
(m, 2H), 7.07 (s, 1H), 5.18 (s, 1H), 3.75 (s, 3H), 3.73 (s, 3H).
(S)-Methyl 2-(5-Bromo-1-methyl-1H-indol-3-yl)-2-phenylacetate
(4g).18 Colorless oil (28.4 mg, 40%). The enantiomeric excess was
determined on a Daicel Chiralpak AD-H column with n-hexane/2-
propanol (90/10) and a flow rate of 1.0 mL/min and detected at a
UV wavelength of 254 nm. Retention times: 8.4 min (major), 9.5 min
(minor), 43% ee. [α]D = −13.2 (c 0.522, CH2Cl2). H NMR (400
MHz, CDCl3): δ 7.56 (d, J = 1.8 Hz, 1H), 7.41−7.38 (m, 2H), 7.34−
7.25 (m, 4H), 7.14 (d, J = 8.7 Hz, 1H), 7.06 (s, 1H), 5.18 (s, 1H),
3.75 (s, 3H), 3.73 (s, 3H).
(S)-Methyl 2-(1,4-Dimethyl-1H-indol-3-yl)-2-phenylacetate (4a).
Colorless oil (28.9 mg, 49%). The enantiomeric excess was
determined on a Daicel Chiralcel OD-H column with n-hexane/2-
propanol (90/10) and a flow rate of 1.0 mL/min and detected at a
UV wavelength of 254 nm. Retention times: 10.0 min (minor), 12.0
min (major), 62% ee. [α]D = +22.0 (c 0.592, CH2Cl2). H NMR
(400 MHz, CDCl3): δ 7.35−7.22 (m, 5H), 7.13−7.06 (m, 2H), 6.97
(s, 1H), 6.79 (d, J = 6.8 Hz, 1H), 5.61 (s, 1H), 3.74 (s, 3H), 3.70 (s,
3H), 2.54 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ 174.1,
139.6, 137.5, 130.5, 128.6, 128.5, 127.2, 125.8, 121.9, 121.2, 112.4,
107.4, 52.4, 49.7, 33.0, 20.4. HRMS (positive ESI): [M + H]+ calcd
for C19H20NO2: 294.1494, found: 294.1496.
20
1
20
1
(S)-Methyl 2-(5-Methoxy-1-methyl-1H-indol-3-yl)-2-phenylace-
tate (4h).15b,20 Colorless oil (49.3 mg, 80%). The enantiomeric
excess was determined on a Daicel Chiralpak AD-H column with n-
hexane/2-propanol (90/10) and a flow rate of 1.0 mL/min and
detected at a UV wavelength of 254 nm. Retention times: 12.5 min
(minor), 15.7 min (major), 37% ee. [α]D20 = −1.4 (c 0.962, CH2Cl2).
1H NMR (400 MHz, CDCl3): δ 7.43−7.41 (m, 2H), 7.33−7.23 (m,
(S)-Methyl 2-(4-Fluoro-1-methyl-1H-indol-3-yl)-2-phenylacetate
(4b). Colorless oil (28.1 mg, 47%). The enantiomeric excess was
determined on a Daicel Chiralcel OD-H column with n-hexane/2-
propanol (90/10) and a flow rate of 1.0 mL/min and detected at a
UV wavelength of 254 nm. Retention times: 7.9 min (minor), 9.4 min
(major), 20% ee. [α]D = −8.4 (c 0.570, CH2Cl2). H NMR (400
MHz, CDCl3): δ 7.42 (d, J = 7.4 Hz, 2H), 7.35−7.31 (m, 2H), 7.28−
7.23 (m, 1H), 7.11−7.06 (m, 1H), 7.02 (d, J = 8.2 Hz, 1H), 6.86 (s,
1H), 6.74−6.69 (m, 1H), 5.45 (s, 1H), 3.73 (s, 3H), 3.68 (s, 3H).
20
1
3H), 7.18−7.15 (m, 1H), 7.00 (s, 1H), 6.88−6.85 (m, 2H), 5.20 (s,
1H), 3.78 (s, 3H), 3.74 (s, 3H), 3.72 (s, 3H).
I
https://dx.doi.org/10.1021/acs.organomet.0c00174
Organometallics XXXX, XXX, XXX−XXX

Organometallics
pubs.acs.org/Organometallics
Article
(S)-Methyl 3-(2-Methoxy-2-oxo-1-phenylethyl)-1-methyl-1H-in-
dole-5-carboxylate (4i). Colorless oil (42.3 mg, 63%). The
enantiomeric excess was determined on a Daicel Chiralpak AD-H
column with n-hexane/2-propanol (90/10) and a flow rate of 1.0 mL/
min and detected at a UV wavelength of 254 nm. Retention times:
15.7 min (major), 19.8 min (minor), 35% ee. [α]D20 = −17.7 (c 0.582,
diffractometer with graphite-monochromated Cu Kα radiation (λ =
1.54184 Å) at ambient temperature. The structures were solved by
direct methods using the SHELXS-97 program, and all non-hydrogen
atoms were refined anisotropically on F2 by the full-matrix least-
squares technique, using the SHELXL-97 crystallographic software
package.21 The hydrogen atoms were included but not refined.
Additional details of X-ray diffraction studies are provided in the
Supporting Information.
1
CH2Cl2). H NMR (400 MHz, CDCl3): δ 8.24 (d, J = 1.1 Hz, 1H),
7.91 (dd, J = 1.6, 8.7 Hz, 1H), 7.44−7.41 (m, 2H), 7.34−7.24 (m,
4H), 7.12 (s, 1H), 5.30 (s, 1H), 3.90 (s, 3H), 3.75 (s, 6H). 13C{1H}
NMR (100 MHz, CDCl3): δ 173.3, 168.1, 139.4, 138.4, 129.4, 128.7,
128.3, 127.4, 126.7, 123.3, 121.9, 121.4, 113.9, 109.1, 52.4, 51.9, 48.4,
33.0. HRMS (positive ESI): [M + H]+ calcd for C20H20NO4:
338.1392, found: 338.1391.
ASSOCIATED CONTENT
■
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.organomet.0c00174.
(S)-Methyl 2-(1,6-Dimethyl-1H-indol-3-yl)-2-phenylacetate
(4j).15b Colorless oil (56.6 mg, 96%). The enantiomeric excess was
determined on a Daicel Chiralcel OD-H column with n-hexane/2-
propanol (90/10) and a flow rate of 1.0 mL/min and detected at a
UV wavelength of 254 nm. Retention times: 8.2 min (major), 9.7 min
Crystallographic details of the Ir(III) complexes 2c, 2d,
and 2g′. NMR spectra of the new ligands 1f−h,
complexes 2a−h, and catalysis products 3 and 4 as
well as their chiral HPLC spectra (PDF)
20
1
(minor), 84% ee. [α]D = +19.6 (c 1.098, CH2Cl2). H NMR (400
MHz, CDCl3): δ 7.42−7.39 (m, 2H), 7.32−7.22 (m, 4H), 7.08 (s,
1H), 6.96 (s, 1H), 6.89 (dd, J = 0.9, 8.1 Hz, 1H), 5.23 (s, 1H), 3.74
(s, 3H), 3.71 (s, 3H), 2.46 (s, 3H).
Accession Codes
CCDC 1905111, 1915664, and 1953152 contain the
supplementary crystallographic data for this paper. These
data can be obtained free of charge via www.ccdc.cam.ac.uk/
data_request/cif, or by emailing data_request@ccdc.cam.ac.
uk, or by contacting The Cambridge Crystallographic Data
Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44
1223 336033.
(S)-Methyl 2-(6-Chloro-1-methyl-1H-indol-3-yl)-2-phenylacetate
(4k).15b Colorless oil (19.9 mg, 32%). The enantiomeric excess was
determined on a Daicel Chiralpak IC column with n-hexane/2-
propanol (90/10) and a flow rate of 1.0 mL/min and detected at a
UV wavelength of 254 nm. Retention times: 6.6 min (major), 7.2 min
20
1
(minor), 55% ee. [α]D = +8.4 (c 0.350, CH2Cl2). H NMR (400
MHz, CDCl3): δ 7.40−7.37 (m, 2H), 7.33−7.23 (m, 5H), 7.03−6.99
(m, 2H), 5.20 (s, 1H), 3.74 (s, 3H), 3.69 (s, 3H).
(S)-Methyl 2-(6-Bromo-1-methyl-1H-indol-3-yl)-2-phenylacetate
(4l). Colorless oil (21.3 mg, 30%). The enantiomeric excess was
determined on a Daicel Chiralcel OD-H column with n-hexane/2-
propanol (98/1.4) and a flow rate of 1.0 mL/min and detected at a
UV wavelength of 254 nm. Retention times: 18.0 min (major), 19.7
min (minor), 52% ee. [α]D20 = +5.8 (c 0.384, CH2Cl2). 1H NMR (400
MHz, CDCl3): δ 7.43 (d, J = 1.6 Hz, 1H), 7.39−7.37 (m, 2H), 7.33−
7.23 (m, 4H), 7.14 (dd, J = 1.6, 8.5 Hz, 1H), 7.02 (d, J = 0.4 Hz, 1H),
5.20 (s, 1H), 3.74 (s, 3H), 3.70 (s, 3H). 13C{1H} NMR (100 MHz,
CDCl3): δ 173.3, 138.4, 137.9, 128.6, 128.5, 128.3, 127.4, 125.9,
122.5, 120.4, 115.6, 112.45, 112.42, 52.4, 48.7, 32.9. HRMS (positive
ESI): [M + Na]+ calcd for C18H16BrNNaO2: 380.0262, found:
380.0261.
AUTHOR INFORMATION
■
Corresponding Authors
Jun-Fang Gong − College of Chemistry, Henan Key Laboratory
of Chemical Biology and Organic Chemistry, Green Catalysis
Center, Zhengzhou University, Zhengzhou 450001, People’s
Republic of China; orcid.org/0000-0002-5299-1323;
Phone: (+86)-371-6776-3869; Email: gongjf@zzu.edu.cn
Mao-Ping Song − College of Chemistry, Henan Key Laboratory
of Chemical Biology and Organic Chemistry, Green Catalysis
Center, Zhengzhou University, Zhengzhou 450001, People’s
Republic of China; orcid.org/0000-0003-3883-2622;
Email: mpsong@zzu.edu.cn
(S)-Methyl 2-(1,7-Dimethyl-1H-indol-3-yl)-2-phenylacetate
(4m).15b Colorless oil (52.0 mg, 89%). The enantiomeric excess
was determined on a Daicel Chiralcel OD-H column with n-hexane/
2-propanol (90/10) and a flow rate of 1.0 mL/min and detected at a
UV wavelength of 254 nm. Retention times: 9.7 min (minor), 18.8
Authors
Nan Li − College of Chemistry, Henan Key Laboratory of
Chemical Biology and Organic Chemistry, Green Catalysis
Center, Zhengzhou University, Zhengzhou 450001, People’s
Republic of China
Wen-Jing Zhu − College of Chemistry, Henan Key Laboratory of
Chemical Biology and Organic Chemistry, Green Catalysis
Center, Zhengzhou University, Zhengzhou 450001, People’s
Republic of China
Juan-Juan Huang − College of Chemistry, Henan Key
Laboratory of Chemical Biology and Organic Chemistry, Green
Catalysis Center, Zhengzhou University, Zhengzhou 450001,
People’s Republic of China
Xin-Qi Hao − College of Chemistry, Henan Key Laboratory of
Chemical Biology and Organic Chemistry, Green Catalysis
Center, Zhengzhou University, Zhengzhou 450001, People’s
Republic of China; orcid.org/0000-0003-1942-8309
20
1
min (major), 54% ee. [α]D = +20.3 (c 0.908, CH2Cl2). H NMR
(400 MHz, CDCl3): δ 7.42−7.39 (m, 2H), 7.33−7.22 (m, 4H),
6.93−6.87 (m, 3H), 5.21 (s, 1H), 4.01 (s, 3H), 3.74 (s, 3H), 2.74 (s,
3H).
(S)-Methyl 2-(7-Methoxy-1-methyl-1H-indol-3-yl)-2-phenylace-
tate (4n). Colorless oil (36.4 mg, 59%). The enantiomeric excess
was determined on a Daicel Chiralpak IC column with n-hexane/2-
propanol (90/10) and a flow rate of 1.0 mL/min and detected at a
UV wavelength of 254 nm. Retention times: 10.9 min (major), 12.9
min (minor), 6% ee. [α]D20 = +2.1 (c 0.658, CH2Cl2). 1H NMR (400
MHz, CDCl3): δ 7.41−7.39 (m, 2H), 7.31−7.27 (m, 2H), 7.25−7.21
(m, 1H), 7.00 (dd, J = 0.9, 8.0 Hz, 1H), 6.93−6.90 (m, 2H), 6.57 (d,
J = 7.6 Hz, 1H), 5.20 (s, 1H), 3.99 (s, 3H), 3.87 (s, 3H), 3.72 (s, 3H).
13C{1H} NMR (100 MHz, CDCl3): δ 173.6, 147.9, 138.8, 129.3,
128.9, 128.6, 128.4, 127.2, 126.8, 119.8, 112.0, 111.8, 102.7, 55.4,
52.3, 48.8, 36.5. HRMS (positive ESI): [M + Na]+ calcd for
C19H19NNaO3: 332.1263, found: 332.1261.
X-ray Diffraction Studies. Crystals of 2c, 2d, and 2g′ (CCDCs
1915664, 1905111, and 1953152) suitable for X-ray single-crystal
analysis were obtained by recrystallization at ambient temperature
from CH2Cl2/n-hexane, toluene, and CH2Cl2/n-hexane, respectively.
The data were collected on an Oxford diffraction Gemini E
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.organomet.0c00174
Notes
The authors declare no competing financial interest.
J
https://dx.doi.org/10.1021/acs.organomet.0c00174
Organometallics XXXX, XXX, XXX−XXX

Organometallics
pubs.acs.org/Organometallics
Article
Zhou, T.; Emge, T. J.; Mironov, O.; Saxton, R. J.; Krogh-Jespersen,
K.; Goldman, A. S. Dehydrogenation of n-Alkanes by Solid-Phase
Molecular Pincer-Iridium Catalysts. High Yields of α-Olefin Product.
J. Am. Chem. Soc. 2015, 137, 9894−9911. (k) Labinger, J. A.; Leitch,
D. C.; Bercaw, J. E.; Deimund, M. A.; Davis, M. E. Upgrading Light
Hydrocarbons: A Tandem Catalytic System for Alkane/Alkene
Coupling. Top. Catal. 2015, 58, 494−501. (l) Jia, X.; Huang, Z.
Conversion of alkanes to linear alkylsilanes using an iridium-iron-
catalysed tandem dehydrogenation-isomerization-hydrosilylation. Nat.
Chem. 2016, 8, 157−161. (m) Wang, Y.; Qin, C.; Jia, X.; Leng, X.;
Huang, Z. An Agostic Iridium Pincer Complex as a Highly Efficient
and Selective Catalyst for Monoisomerization of 1-Alkenes to trans-2-
Alkenes. Angew. Chem., Int. Ed. 2017, 56, 1614−1618. (n) Tang, X.;
Jia, X.; Huang, Z. Thermal, Catalytic Conversion of Alkanes to Linear
Aldehydes and Linear Amines. J. Am. Chem. Soc. 2018, 140, 4157−
4163. (o) Wang, Y.; Huang, Z.; Leng, X.; Zhu, H.; Liu, G.; Huang, Z.
Transfer Hydrogenation of Alkenes Using Ethanol Catalyzed by a
NCP Pincer Iridium Complex: Scope and Mechanism. J. Am. Chem.
Soc. 2018, 140, 4417−4429.
(3) (a) Allen, K. E.; Heinekey, D. M.; Goldman, A. S.; Goldberg, K.
I. Alkane Dehydrogenation by C-H Activation at Iridium(III).
Organometallics 2013, 32, 1579−1582. (b) Allen, K. E.; Heinekey,
D. M.; Goldman, A. S.; Goldberg, K. I. Regeneration of an
Iridium(III) Complex Active for Alkane Dehydrogenation Using
Molecular Oxygen. Organometallics 2014, 33, 1337−1340. (c) Zhou,
M.; Johnson, S. I.; Gao, Y.; Emge, T. J.; Nielsen, R. J.; Goddard, W.
A., III; Goldman, A. S. Activation and Oxidation of Mesitylene C-H
Bonds by (Phebox)Iridium(III) Complexes. Organometallics 2015, 34,
2879−2888. (d) Gao, Y.; Guan, C.; Zhou, M.; Kumar, A.; Emge, T. J.;
Wright, A. M.; Goldberg, K. I.; Krogh-Jespersen, K.; Goldman, A. S.
β-Hydride Elimination and C-H Activation by an Iridium Acetate
Complex, Catalyzed by Lewis Acids. Alkane Dehydrogenation
Cocatalyzed by Lewis Acids and [2,6-Bis(4,4-dimethyloxazolinyl)-
3,5-dimethylphenyl]iridium. J. Am. Chem. Soc. 2017, 139, 6338−6350.
(e) Yuan, H.; Brennessel, W. W.; Jones, W. D. Effect of Carboxylate
Ligands on Alkane Dehydrogenation with (dmPhebox)Ir Complexes.
ACS Catal. 2018, 8, 2326−2329. (f) Syed, Z. H.; Kaphan, D. M.;
Perras, F. A.; Pruski, M.; Ferrandon, M. S.; Wegener, E. C.; Celik, G.;
Wen, J.; Liu, C.; Dogan, F.; Goldberg, K. I.; Delferro, M. Electrophilic
Organoiridium(III) Pincer Complexes on Sulfated Zirconia for
Hydrocarbon Activation and Functionalization. J. Am. Chem. Soc.
2019, 141, 6325−6337.
ACKNOWLEDGMENTS
■
This research was supported by a grant from the National
Natural Science Foundation of China (21472176).
REFERENCES
■
(1) For reviews, see: (a) Choi, J.; MacArthur, A. H. R.; Brookhart,
M.; Goldman, A. S. Dehydrogenation and Related Reactions
Catalyzed by Iridium Pincer Complexes. Chem. Rev. 2011, 111,
1761−1779. (b) Haibach, M. C.; Kundu, S.; Brookhart, M.; Goldman,
A. S. Alkane Metathesis by Tandem Alkane-Dehydrogenation-Olefin-
Metathesis Catalysis and Related Chemistry. Acc. Chem. Res. 2012, 45,
947−958. (c) Hackenberg, J.; Krogh-Jespersen, K.; Goldman, A. S.
Activation of C-O and C-F Bonds by Pincer-iridium Complexes. In
Advances in Organometallic Chemistry and Catalysis: The Silver/Gold
Jubilee International Conference on Organometallic Chemistry Celebra-
tory Book; Pombeiro, A. J. L., Ed.; John Wiley & Sons, Inc.: Hoboken,
NJ, 2014; Chapter 4, pp 39−57. (d) Werkmeister, S.; Neumann, J.;
Junge, K.; Beller, M. Pincer-Type Complexes for Catalytic (De)-
Hydrogenation and Transfer (De)Hydrogenation Reactions: Recent
Progress. Chem. - Eur. J. 2015, 21, 12226−12250. (e) Kumar, A.;
Goldman, A. S. Recent Advances in Alkane Dehydrogenation
Catalyzed by Pincer Complexes. Top. Organomet. Chem. 2015, 54,
́
307−334. (f) Bezier, D.; Brookhart, M. Transfer Dehydrogenations of
Alkanes and Related Reactions Using Iridium Pincer Complexes. Top.
Organomet. Chem. 2015, 56, 189−207. (g) Kumar, A.; Bhatti, T. M.;
Goldman, A. S. Dehydrogenation of Alkanes and Aliphatic Groups by
Pincer-Ligated Metal Complexes. Chem. Rev. 2017, 117, 12357−
12384. (h) Goldberg, K. I.; Goldman, A. S. Large-Scale Selective
Functionalization of Alkanes. Acc. Chem. Res. 2017, 50, 620−626.
(i) Tang, X.; Jia, X.; Huang, Z. Challenges and opportunities for
alkane functionalisation using molecular catalysts. Chem. Sci. 2018, 9,
288−299. (j) Tang, X.; Huang, Z. Transition-metal complex-catalyzed
alkane functionalization (in Chinese). Kexue Tongbao 2018, 63,
1348−1360. (k) Das, K.; Kumar, A. Alkane dehydrogenation
reactions catalyzed by pincer-metal complexes. Adv. Organomet.
Chem. 2019, 72, 1−57.
(2) For selected examples, see: (a) Ito, J.-i.; Kaneda, T.; Nishiyama,
H. Intermolecular C-H Bond Activation of Alkanes and Arenes by
NCN Pincer Iridium(III) Acetate Complexes Containing Bis-
(oxazolinyl)phenyl Ligands. Organometallics 2012, 31, 4442−4449.
(b) Ahuja, R.; Punji, B.; Findlater, M.; Supplee, C.; Schinski, W.;
Brookhart, M.; Goldman, A. S. Catalytic dehydroaromatization of n-
alkanes by pincer-ligated iridium complexes. Nat. Chem. 2011, 3,
167−171. (c) Kundu, S.; Choi, J.; Wang, D. Y.; Choliy, Y.; Emge, T.
J.; Krogh-Jespersen, K.; Goldman, A. S. Cleavage of Ether, Ester, and
Tosylate C(sp3)-O Bonds by an Iridium Complex, Initiated by
Oxidative Addition of C-H Bonds. Experimental and Computational
Studies. J. Am. Chem. Soc. 2013, 135, 5127−5143. (d) Haibach, M.
C.; Guan, C.; Wang, D. Y.; Li, B.; Lease, N.; Steffens, A. M.; Krogh-
Jespersen, K.; Goldman, A. S. Olefin Hydroaryloxylation Catalyzed by
Pincer-Iridium Complexes. J. Am. Chem. Soc. 2013, 135, 15062−
15070. (e) Cheng, C.; Kim, B. G.; Guironnet, D.; Brookhart, M.;
Guan, C.; Wang, D. Y.; Krogh-Jespersen, K.; Goldman, A. S. Synthesis
and Characterization of Carbazolide-Based Iridium PNP Pincer
Complexes. Mechanistic and Computational Investigation of Alkene
Hydrogenation: Evidence for an Ir(III)/Ir(V)/Ir(III) Catalytic Cycle.
J. Am. Chem. Soc. 2014, 136, 6672−6683. (f) Hackenberg, J. D.;
Kundu, S.; Emge, T. J.; Krogh-Jespersen, K.; Goldman, A. S. Acid-
Catalyzed Oxidative Addition of a C-H Bond to a Square Planar d8
Iridium Complex. J. Am. Chem. Soc. 2014, 136, 8891−8894. (g) Yao,
W.; Zhang, Y.; Jia, X.; Huang, Z. Selective Catalytic Transfer
Dehydrogenation of Alkanes and Heterocycles by an Iridium Pincer
Complex. Angew. Chem., Int. Ed. 2014, 53, 1390−1394. (h) Haibach,
M. C.; Lease, N.; Goldman, A. S. Catalytic Cleavage of Ether C-O
Bonds by Pincer Iridium Complexes. Angew. Chem., Int. Ed. 2014, 53,
10160−10163. (i) Guo, L.; Ma, X.; Fang, H.; Jia, X.; Huang, Z. A
General and Mild Catalytic α-Alkylation of Unactivated Esters Using
Alcohols. Angew. Chem., Int. Ed. 2015, 54, 4023−4027. (j) Kumar, A.;
(4) Ito, J.-i.; Shiomi, T.; Nishiyama, H. Efficient Preparation of New
Rhodium- and Iridium-[Bis(oxazolinyl)-3,5-dimethylphenyl] Com-
plexes by C-H Bond Activation: Applications in Asymmetric
Synthesis. Adv. Synth. Catal. 2006, 348, 1235−1240.
(5) For reviews on chiral transition-metal pincer complexes with
Phebox ligands, see: (a) Nishiyama, H. Synthesis and use of
bisoxazolinyl-phenyl pincers. Chem. Soc. Rev. 2007, 36, 1133−1141.
(b) Nishiyama, H.; Ito, J.-i. Bis(oxazolinyl)phenyl transition-metal
complexes: asymmetric catalysis and some reactions of the metals.
Chem. Commun. 2010, 46, 203−212. (c) Ito, J.-i.; Nishiyama, H.
Synthetic Utility of Chiral Bis(oxazolinyl)phenyl Transition-Metal
Complexes. Synlett 2012, 23, 509−523. (d) Ito, J.-i.; Nishiyama, H.
Optically Active Bis(oxazolinyl)phenyl Metal Complexes as Multi-
potent Catalysts. Top. Organomet. Chem. 2013, 40, 243−270. (e) Ito,
J.-i.; Nishiyama, H. Asymmetric Catalysis Mediated by Optically
Active Bis(oxazolinyl)phenyl Metal Complexes. Yuki Gosei Kagaku
Kyokaishi 2013, 71, 791−803.
́
(6) Owens, C. P.; Varela-Alvarez, A.; Boyarskikh, V.; Musaev, D. G.;
Davies, H. M. L.; Blakey, S. B. Iridium(III)-bis(oxazolinyl)phenyl
catalysts for enantioselective C-H functionalization. Chem. Sci. 2013,
4, 2590−2596.
(7) For reviews, see: (a) Niu, J.-L.; Hao, X.-Q.; Gong, J.-F.; Song,
M.-P. Symmetrical and unsymmetrical pincer complexes with group
10 metals: synthesis via aryl C-H activation and some catalytic
applications. Dalton Trans. 2011, 40, 5135−5150. (b) Hao, X.-Q.;
Niu, J.-L.; Zhao, X.-M.; Gong, J.-F.; Song, M.-P. Development of
Pincer Catalysts with Selected Group 8∼10 Metals. Youji Huaxue
K
https://dx.doi.org/10.1021/acs.organomet.0c00174
Organometallics XXXX, XXX, XXX−XXX

Organometallics
pubs.acs.org/Organometallics
Article
2013, 33, 663−674. (c) Gong, J.-F.; Zhu, X.; Song, M.-P. Transition
Metal Pincer Complexes with Chiral Imidazoline Donor(s): Synthesis
and Asymmetric Catalysis. In Pincer Compounds: Chemistry and
Applications; Morales-Morales, D., Ed.; Elsevier: Amsterdam, 2018;
Chapter 9, pp 191−218. (d) Liu, J.-K.; Gong, J.-F.; Song, M.-P. Chiral
palladium pincer complexes for asymmetric catalytic reactions. Org.
Biomol. Chem. 2019, 17, 6069−6098.
bis(imidazoline)-Pd complexes. Chem. Commun. 2019, 55, 5391−
5394.
(11) Weldy, N. M.; Schafer, A. G.; Owens, C. P.; Herting, C. J.;
Varela-Alvarez, A.; Chen, S.; Niemeyer, Z.; Musaev, D. G.; Sigman,
M. S.; Davies, H. M. L.; Blakey, S. B. Iridium(III)-bis(imidazolinyl)-
phenyl catalysts for enantioselective C-H functionalization with ethyl
diazoacetate. Chem. Sci. 2016, 7, 3142−3146.
(12) (a) Schultz, K. M.; Goldberg, K. I.; Gusev, D. G.; Heinekey, D.
M. Synthesis, Structure, and Reactivity of Iridium NHC Pincer
Complexes. Organometallics 2011, 30, 1429−1437. (b) Gyton, M. R.;
Leforestier, B.; Chaplin, A. B. Rhodium(III) and Iridium(III)
Complexes of a NHC-Based Macrocycle: Persistent Weak Agostic
Interactions and Reactions with Dihydrogen. Organometallics 2018,
37, 3963−3971. (c) Hood, T. M.; Leforestier, B.; Gyton, M. R.;
Chaplin, A. B. Synthesis and Structural Dynamics of Five-Coordinate
Rh(III) and Ir(III) PNP and PONOP Pincer Complexes. Inorg. Chem.
2019, 58, 7593−7601.
(8) (a) Hao, X.-Q.; Gong, J.-F.; Du, C.-X.; Wu, L.-Y.; Wu, Y.-J.;
Song, M.-P. Synthesis, characterization and photoluminescent proper-
ties of platinum complexes with novel bis(imidazoline) pincer ligands.
Tetrahedron Lett. 2006, 47, 5033−5036. (b) Wu, L.-Y.; Hao, X.-Q.;
Xu, Y.-X.; Jia, M.-Q.; Wang, Y.-N.; Gong, J.-F.; Song, M.-P. Chiral
NCN Pincer Pt(II) and Pd(II) Complexes with 1,3-Bis(2′-
imidazolinyl)benzene: Synthesis via Direct Metalation, Character-
ization, and Catalytic Activity in the Friedel-Crafts Alkylation
Reaction. Organometallics 2009, 28, 3369−3380. (c) Shao, D.-D.;
Niu, J.-L.; Hao, X.-Q.; Gong, J.-F.; Song, M.-P. Neutral and cationic
chiral NCN pincer nickel(II) complexes with 1,3-bis(2′-imidazolinyl)-
benzenes: synthesis and characterization. Dalton Trans. 2011, 40,
9012−9019. (d) Hao, X.-Q.; Xu, Y.-X.; Yang, M.-J.; Wang, L.; Niu, J.-
L.; Gong, J.-F.; Song, M.-P. A Cationic NCN Pincer Platinum(II)
Aquo Complex with a Bis(imidazolinyl)phenyl Ligand: Studies
toward its Synthesis and Asymmetric Friedel-Crafts Alkylation of
Indoles with Nitroalkenes. Organometallics 2012, 31, 835−846.
(e) Wang, T.; Niu, J.-L.; Liu, S.-L.; Huang, J.-J.; Gong, J.-F.; Song,
M.-P. Chiral NCN Pincer Rhodium(III) Complexes with Bis-
(imidazolinyl)phenyl Ligands: Synthesis and Enantioselective Cata-
lytic Alkynylation of Trifluoropyruvates with Terminal Alkynes. Adv.
Synth. Catal. 2013, 355, 927−937. (f) Wang, T.; Hao, X.-Q.; Huang,
J.-J.; Niu, J.-L.; Gong, J.-F.; Song, M.-P. Chiral Bis(imidazolinyl)-
phenyl NCN Pincer Rhodium(III) Catalysts for Enantioselective
Allylation of Aldehydes and Carbonyl-Ene Reaction of Trifluoropyr-
uvates. J. Org. Chem. 2013, 78, 8712−8721. (g) Hao, X.-Q.; Zhao, Y.-
W.; Yang, J.-J.; Niu, J.-L.; Gong, J.-F.; Song, M.-P. Enantioselective
Hydrophosphination of Enones with Diphenylphosphine Catalyzed
by Bis(imidazoline) NCN Pincer Palladium(II) Complexes. Organo-
metallics 2014, 33, 1801−1811.
(9) Li, C.; Bian, Q.-L.; Xu, S.; Duan, W.-L. Palladium-catalyzed 1,4-
addition of secondary alkylphenylphosphines to α,β-unsaturated
carbonyl compounds for the synthesis of phosphorus- and carbon-
stereogenic compounds. Org. Chem. Front. 2014, 1, 541−545.
(10) For reviews, see: (a) Nakamura, S. Enantioselective Reaction
Using Palladium Pincer Complexes with C2-Symmetric Chiral
Bis(imidazoline)s. Yuki Gosei Kagaku Kyokaishi 2015, 73, 1062−
1071. (b) Hyodo, K.; Nakamura, S. Chiral NCN Pincer-Type
Catalysts Having Bis(imidazoline)s. In Pincer Compounds: Chemistry
and Applications; Morales-Morales, D., Ed.; Elsevier: Amsterdam,
2018; Chapter 10, pp 219−235. For selected examples, see:
(c) Nakamura, S.; Hyodo, K.; Nakamura, M.; Nakane, D.; Masuda,
H. Catalytic Enantioselective Allylation of Ketimines by Using
Palladium Pincer Complexes with Chiral Bis(imidazoline)s. Chem. -
Eur. J. 2013, 19, 7304−7309. (d) Hyodo, K.; Nakamura, S.; Shibata,
N. Enantioselective Aza-Morita-Baylis-Hillman Reactions of Acryl-
onitrile Catalyzed by Palladium(II) Pincer Complexes having C2-
Symmetric Chiral Bis(imidazoline) Ligands. Angew. Chem., Int. Ed.
2012, 51, 10337−10341. (e) Kondo, M.; Nishi, T.; Hatanaka, T.;
Funahashi, Y.; Nakamura, S. Catalytic Enantioselective Reaction of α-
Aminoacetonitriles Using Chiral Bis(imidazoline) Palladium Cata-
lysts. Angew. Chem., Int. Ed. 2015, 54, 8198−8202. (f) Kondo, M.;
Omori, M.; Hatanaka, T.; Funahashi, Y.; Nakamura, S. Catalytic
Enantioselective Reaction of Allenylnitriles with Imines Using Chiral
Bis(imidazoline)s Palladium(II) Pincer Complexes. Angew. Chem., Int.
Ed. 2017, 56, 8677−8680. (g) Kondo, M.; Saito, H.; Nakamura, S.
Direct catalytic enantioselective Mannich-type reaction of α,α-
dithioacetonitriles with imines using chiral bis(imidazoline)-Pd
complexes. Chem. Commun. 2017, 53, 6776−6779. (h) Nakamura,
S.; Tokunaga, A.; Saito, H.; Kondo, M. Enantioselective conjugate
addition of an α,α-dithioacetonitrile with nitroalkenes using chiral
(13) (a) Brookhart, M.; Green, M. L. H.; Parkin, G. Agostic
interactions in transition metal compounds. Proc. Natl. Acad. Sci. U. S.
A. 2007, 104, 6908−6914. (b) Lein, M. Characterization of agostic
interactions in theory and computation. Coord. Chem. Rev. 2009, 253,
625−634.
(14) For reviews, see: (a) Davies, H. M. L.; Beckwith, R. E. J.
Catalytic Enantioselective C-H Activation by Means of Metal-
Carbenoid-Induced C-H Insertion. Chem. Rev. 2003, 103, 2861−
2903. (b) Slattery, C. N.; Ford, A.; Maguire, A. R. Catalytic
asymmetric C-H insertion reactions of α-diazocarbonyl compounds.
Tetrahedron 2010, 66, 6681−6705. (c) Zhu, S.-F.; Zhou, Q.-L.
Transition-Metal-Catalyzed Enantioselective Heteroatom-Hydrogen
Bond Insertion Reactions. Acc. Chem. Res. 2012, 45, 1365−1377.
(d) Zheng, C.; You, S.-L. Recent development of direct asymmetric
functionalization of inert C-H bonds. RSC Adv. 2014, 4, 6173−6214.
(e) Ren, Y.-Y.; Zhu, S.-F.; Zhou, Q.-L. Chiral proton-transfer shuttle
catalysts for carbene insertion reactions. Org. Biomol. Chem. 2018, 16,
3087−3094.
(15) (a) Cai, Y.; Zhu, S.-F.; Wang, G.-P.; Zhou, Q.-L. Iron-Catalyzed
C-H Functionalization of Indoles. Adv. Synth. Catal. 2011, 353,
2939−2944. (b) Qiu, H.; Zhang, D.; Liu, S.; Qiu, L.; Zhou, J.; Qian,
Y.; Zhai, C.; Hu, W. Asymmetric C-H Functionalization of Indoles via
Enantioselective Protonation. Huaxue Xuebao 2012, 70, 2484−2488.
(c) Gao, X.; Wu, B.; Huang, W.-X.; Chen, M.-W.; Zhou, Y.-G.
Enantioselective Palladium-Catalyzed C-H Functionalization of
Indoles Using an Axially Chiral 2,2′-Bipyridine Ligand. Angew.
Chem., Int. Ed. 2015, 54, 11956−11960. (d) Gao, X.; Wu, B.; Yan,
Z.; Zhou, Y.-G. Copper-catalyzed enantioselective C-H functionaliza-
tion of indoles with an axially chiral bipyridine ligand. Org. Biomol.
Chem. 2016, 14, 8237−8240.
(16) For Ir-catalyzed asymmetric carbene insertion into C−H and
X−H bonds, see: (a) Suematsu, H.; Katsuki, T. Iridium(III)
Catalyzed Diastereo- and Enantioselective C-H Bond Functionaliza-
tion. J. Am. Chem. Soc. 2009, 131, 14218−14219. (b) Yasutomi, Y.;
Suematsu, H.; Katsuki, T. Iridium(III)-Catalyzed Enantioselective Si-
H Bond Insertion and Formation of an Enantioenriched Silicon
Center. J. Am. Chem. Soc. 2010, 132, 4510−4511. (c) Wang, J.-C.; Xu,
Z.-J.; Guo, Z.; Deng, Q.-H.; Zhou, C.-Y.; Wan, X.-L.; Che, C.-M.
Highly enantioselective intermolecular carbene insertion to C-H and
Si-H bonds catalyzed by a chiral iridium(III) complex of a D4-
symmetric Halterman porphyrin ligand. Chem. Commun. 2012, 48,
4299−4301. (d) Wang, J.-C.; Zhang, Y.; Xu, Z.-J.; Lo, V. K.-Y.; Che,
C.-M. Enantioselective Intramolecular Carbene C-H Insertion
Catalyzed by a Chiral Iridium(III) Complex of D4-Symmetric
Porphyrin Ligand. ACS Catal. 2013, 3, 1144−1148. (e) Schafer, A.
G.; Blakey, S. B. Ir-Catalyzed enantioselective group transfer
reactions. Chem. Soc. Rev. 2015, 44, 5969−5980.
(17) McKennon, M. J.; Meyers, A. I.; Drauz, K.; Schwarm, M. A
Convenient Reduction of Amino Acids and Their Derivatives. J. Org.
Chem. 1993, 58, 3568−3571.
(18) Fraile, J. M.; Le Jeune, K.; Mayoral, J. A.; Ravasio, N.;
Zaccheria, F. CuO/SiO2 as a simple, effective and recoverable catalyst
L
https://dx.doi.org/10.1021/acs.organomet.0c00174
Organometallics XXXX, XXX, XXX−XXX

Organometallics
pubs.acs.org/Organometallics
Article
for alkylation of indole derivatives with diazo compounds. Org.
Biomol. Chem. 2013, 11, 4327−4332.
(19) Xu, X.-H.; Liu, G.-K.; Azuma, A.; Tokunaga, E.; Shibata, N.
Synthesis of Indole and Biindolyl Triflones: Trifluoromethanesulfo-
nylation of Indoles with Tf2O/TTBP (2,4,6-tri-tert-butylpyridine)
System. Org. Lett. 2011, 13, 4854−4857.
(20) Sarkar, M.; Daw, P.; Ghatak, T.; Bera, J. K. Amide-
Functionalized Naphthyridines on a RhII-RhII Platform: Effect of
Steric Crowding, Hemilability, and Hydrogen-Bonding Interactions
on the Structural Diversity and Catalytic Activity of Dirhodium(II)
Complexes. Chem. - Eur. J. 2014, 20, 16537−16549.
(21) (a) Sheldrick, G. M. SHELXS-97, Program for Crystal Structure
̈
̈
Solution; University of Gottingen: Gottingen, Germany, 1997.
(b) Sheldrick, G. M. SHELXL-97, Program for Crystal Structure
̈
̈
Refinement; University of Gottingen: Gottingen, Germany, 1997.
M
https://dx.doi.org/10.1021/acs.organomet.0c00174
Organometallics XXXX, XXX, XXX−XXX