Catalyzed tandem C-N/C-C bond formation for the synthesis of tricyclic indoles using Ir(III) pyrazolyl-1,2,3-triazolyl complexes

Article abstract of DOI:10.1021/om300792b

A series of new pyrazolyl-1,2,3-triazolyl N-N′ bidentate donor ligands (2a-c, 3a-d) were prepared via Cu(I)-catalyzed Huisgen cycloaddition reactions between 1-propargylpyrazoles and 4-substituted phenyl azides. The electron-withdrawing ability of the substituents follows the trend PhCH ₂ < p-CH₃Ph < Ph < p-CF₃Ph < p-NO₂Ph, as illustrated in the gradual downfield shift of the 1,2,3-triazolyl-C4′ ¹³C NMR resonances. A series of Rh and Ir complexes containing these pyrazolyl-1,2,3-triazolyl or bis(pyrazol-1-yl)methane donor ligands of general formulae [Ir(N-N′)Cp*Cl]X (X = BAr ^F₄, BPh₄; 5-8), [Rh(N-N′)Cp*Cl]X (X = BAr^F₄, BPh₄; 9-11), and [Rh(N-N′)(CO) ₂]BAr^F₄ (13-16) (BAr^F₄ = tetrakis[3,5-bis(trifluoromethyl)phenyl]borate) were synthesized and fully characterized. The solid-state structures of 5, 6a′, 6b, 7b, 8, 9, 10a, 10a′, 11, and 15c were determined by X-ray diffraction studies. As the electron-withdrawing strength of the phenylene substituent on the triazolyl ring is increased, the M-N3′(triazole) bond length becomes longer. The efficiency of these Rh and Ir complexes as catalysts for the synthesis of tricyclic indoles via tandem C-N and C-C bond formation reactions from 2-(hydroxyalk-1-ynyl)anilines (17S-20S) was assessed. The Ir(III) catalysts were the most efficient for the C-C bond formation step, and the Rh(I) complexes 13-16 were the most efficient catalysts for C-N bond formation, where TOFs >1000 h^-1 were reached. However, the Ir(III) complexes 5-8 were found to be the only active catalysts for the tandem C-N and C-C bond formation, as the Rh(I) complexes were not active catalysts for the C-C bond formation step. The C-N bond formation leading to the formation of indoles was found to proceed via two reaction pathways with 2-(hydroxyalk-1-ynyl)aniline substrates: (a) hydroamination and (b) hydroalkoxylation-Lewis acid mediated isomerization. Pathway (b) is likely to be the main pathway in the formation of indoles starting with 2-(hydroxyalk-1-ynyl)aniline substrates 17S, 18S, and 20S.

Full text of DOI:10.1021/om300792b

Article
pubs.acs.org/Organometallics
Catalyzed Tandem C−N/C−C Bond Formation for the Synthesis of
Tricyclic Indoles using Ir(III) Pyrazolyl-1,2,3-Triazolyl Complexes
Chin Min Wong,† Khuong Q. Vuong,† Mark R. D. Gatus,† Carol Hua,† Mohan Bhadbhade,†,‡
and Barbara A. Messerle*,†
‡
†School of Chemistry and X-ray Diffraction Laboratory, Mark Wainwright Analytical Centre, The University of New South Wales,
Kensington, New South Wales 2052, Australia
S
* Supporting Information
ABSTRACT: A series of new pyrazolyl-1,2,3-triazolyl N−N′
bidentate donor ligands (2a−c, 3a−d) were prepared via
Cu(I)-catalyzed Huisgen cycloaddition reactions between 1-
propargylpyrazoles and 4-substituted phenyl azides. The
electron-withdrawing ability of the substituents follows the
trend PhCH2 < p-CH3Ph < Ph < p-CF3Ph < p-NO2Ph, as
illustrated in the gradual downfield shift of the 1,2,3-triazolyl-
C4′ 13C NMR resonances. A series of Rh and Ir complexes
containing these pyrazolyl-1,2,3-triazolyl or bis(pyrazol-1-
yl)methane donor ligands of general formulae [Ir(N−N′)-
Cp*Cl]X (X = BArF , BPh4; 5−8), [Rh(N−N′)Cp*Cl]X (X =
4
BArF , BPh4; 9−11), and [Rh(N−N′)(CO)2]BArF (13−16) (BArF = tetrakis[3,5-bis(trifluoromethyl)phenyl]borate) were
4
4
4
synthesized and fully characterized. The solid-state structures of 5, 6a′, 6b, 7b, 8, 9, 10a, 10a′, 11, and 15c were determined by
X-ray diffraction studies. As the electron-withdrawing strength of the phenylene substituent on the triazolyl ring is increased, the
M−N3′(triazole) bond length becomes longer. The efficiency of these Rh and Ir complexes as catalysts for the synthesis of
tricyclic indoles via tandem C−N and C−C bond formation reactions from 2-(hydroxyalk-1-ynyl)anilines (17S−20S) was
assessed. The Ir(III) catalysts were the most efficient for the C−C bond formation step, and the Rh(I) complexes 13−16 were
the most efficient catalysts for C−N bond formation, where TOFs >1000 h−1 were reached. However, the Ir(III) complexes 5−8
were found to be the only active catalysts for the tandem C−N and C−C bond formation, as the Rh(I) complexes were not
active catalysts for the C−C bond formation step. The C−N bond formation leading to the formation of indoles was found to
proceed via two reaction pathways with 2-(hydroxyalk-1-ynyl)aniline substrates: (a) hydroamination and (b) hydroalkoxylation−
Lewis acid mediated isomerization. Pathway (b) is likely to be the main pathway in the formation of indoles starting with 2-
(hydroxyalk-1-ynyl)aniline substrates 17S, 18S, and 20S.
carbon to C−X bonds in Heck style coupling reactions.10
INTRODUCTION
■
Although metal-catalyzed tandem C−N and C−C bond
formation is a potentially significant reaction route for the
synthesis of amines and heterocycles, there are only limited
examples of this synthetic approach.1−5,11 Wolfe et al. have
reported the synthesis of tricyclic 1,2-substituted indolines by a
palladium-catalyzed cascade of aminopalladation and carbopal-
ladation reactions via the formation of one C−N bond and two
C−C bonds.12 Recently, Yip and Yang demonstrated Pd(II)-
catalyzed oxidative cascade reactions for the synthesis of
tricyclic 1,2-substituted indolines.13 It has also been reported
very recently by Driver and co-workers that a bimetallic Rh(II)2
species promotes tandem C−N/C−C bond formation in the
synthesis of carbolines from aryl azides.14 Palladium complexes
have been particularly useful in promoting tandem C−C
coupling (Sonogashira, Mizoroki−Heck, Suzuki, Stille) and
Performing multistep reactions in one pot has the potential to
produce sophisticated organic molecules such as pharmaceut-
icals in a more efficient, economical and environmentally
friendly manner than can be achieved using more traditional
stepwise approaches.1−5 The current challenge in applying
organometallic catalysis to promote such cascade reactions is to
find either a single metal catalyst or a combination of two or
more compatible catalysts to promote the overall reaction.1−3
Tandem C−N and C−C bond formation reactions can be
useful in the synthesis of N-containing polycyclic compounds.
The hydroamination of alkynes and alkenes is an atom-
economical method for the formation of C−N bonds and can
be catalyzed by lanthanides and actinides as well as early- and
late-transition-metal complexes.6−9 Late-transition-metal com-
plexes have greater potential for wider application as hydro-
amination catalysts, due to their lower oxophilicity and higher
functional group tolerance. The formation of C−C bonds can
be achieved through a variety of approaches, including the
coupling of unsaturated carbon centers and the addition of
Received: August 16, 2012
Published: October 17, 2012
© 2012 American Chemical Society
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hydroamination reactions, respectively, to form 2-substituted
indoles from 2-substituted aniline derivatives.15,10
ring, promote the atom-economical intramolecular hydro-
amination of alkynes.23−25 Recently, we also demonstrated
that cationic Rh(I) and Ir(I) complexes with mixed bidentate
pyrazolyl-1,2,3-triazolyl donor ligands are active catalysts for the
intramolecular hydroamination of alkynes and alkenes.26 Here
we report the synthesis of a series of Rh(III)/Ir(III) and Rh(I)/
Ir(I) complexes with pyrazolyl-1,2,3-triazolyl bidentate donor
ligands (Figure 1). A range of substituents were introduced to
the 1,2,3-triazolyl and pyrazolyl rings, leading to modification of
the steric and electronic environments around the metal center.
The efficiency of these new complexes as catalysts for the one-
pot intramolecular tandem C−N (hydroamination)/intra-
molecular C3 alkylation of indoles was established. This
approach provides an efficient route for the synthesis of
biologically relevant 1,2,3,4-tetrahydrocarbazole and other
related polycyclic indoles (Scheme 2).
The indole moiety is a privileged structure present in many
biologically active compounds, including pharmaceutical
agents,10,16 and tricyclic indole systems such as tetrahydro-
carbazoles are prevalent motifs in many pharmaceuticals.17,16
An efficient catalytic route to the synthesis of these tricylic
indoles is highly desirable. Grigg and co-workers18 have
successfully catalyzed the intermolecular C3 selective alkylation
of indole using the hydrogen borrowing strategy (Scheme
1)19,20 with an excess of alcohol as the alkylating agent and
Scheme 1. Intermolecular18,22a or Intramolecular C3
Alkylation of Indoles for the Synthesis of C3-Substituted
Indoles or Tricyclic Indoles, Respectively
Scheme 2. Tandem Intramolecular Hydroamination and C3
Alkylation with Alcohol
[Cp*IrCl2]2 (Cp* = 1,2,3,4,5-pentamethylcyclopentadienyl) as
the catalyst. Peris and co-workers have used heterobimetallic
Ma−Mb complexes (Ma, Mb: Pd, Ir; Rh, Au) as catalysts to
promote the synthesis of C3-substituted indoles from 2-
aminobenzyl alcohol in the presence of an excess of a second
alcohol as the alkylating agent, where the reaction sequence
comprises sequential C−N and C−C bond formation steps.
Both reaction steps utilize the hydrogen borrowing strategy,
and a water molecule is released in each step as the
byproduct.21,22 As an efficient approach to the synthesis of
tricyclic indole-based systems, we envisioned that the intra-
molecular C3 alkylation of a 2-(hydroxyalkyl)indole could be
achieved using the hydrogen borrowing strategy with suitable
catalysts (Scheme 1).18,19,21,22
RESULTS AND DISCUSSION
■
Synthesis of Bidentate Pyrazolyl-1,2,3-Triazolyl Li-
gands and Their Rh and Ir Complexes. (a). Synthesis of
Ligands. The N−N′ pyrazolyl-1,2,3-triazolyl bidentate ligands
(2a−c and 3a−d) were synthesized using Cu(I)-catalyzed
Huisgen alkyne−azide cycloadditions between propargylpyr-
azoles and aryl azides in a fashion similar to that in our previous
report of the synthesis of ligands 1 and 2a (Scheme 3 and
Figure 1).26
The effect of electron-withdrawing or -donating substituents
(R1 and R2) on the electronic properties of the resulting ligands
is significant, as illustrated by the variation in the 13C NMR
chemical shifts of the pyrazolyl C4 and 1,2,3-triazolyl C4′
resonances (see Table S1 in the Supporting Information). The
electron-withdrawing ability of the substituents follows the
We have previously shown that Rh and Ir complexes with
bidentate sp2-N donor ligands or hybrid bidentate phosphine−
sp2-N donors, where the N donor is a pyrazolyl or imidazolyl
Figure 1. N−N′ bidentate donor ligands and their respective Rh and Ir complexes.
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Scheme 3. Synthesis of Bidentate Pyrazolyl-1,2,3-triazolyl Ligands
trend PhCH2 < p-CH3Ph < Ph < p-CF3Ph < p-NO2Ph. Methyl
substituents on the pyrazolyl (Pz) C3 and C5 positions lead to
a notable upfield shift of 0.6−0.7 ppm in the Pz-C4 13C NMR
resonance. Electron-withdrawing substituents on the para
position of the phenylene group on the N1′ position of the
1,2,3-triazolyl ring in ligands 2a−c and 3a−d cause the 13C
NMR chemical shifts of the triazolyl-C4′ 13C resonances to
move downfield (see Table S1).
have previously reported the synthesis of several analogous
complexes containing bidentate sp2-N donor ligands [M(N−
N′)(Cp*)Cl]X (N−N′ = bis(1-pyrazolyl)methane, bis(1-
−
methylimidazolyl-2-yl)methane; X = Cl−, BF4 ) and the
unusual anion [Cp*MCl3]− (M = Ir, Rh). The anion exchange
reaction, using NaBArF or NaBPh4, led to the exclusive
4
formation of the desired complexes 5−11 with BArF − or
4
BPh4− as the counteranion, respectively. The color of the Ir(III)
complexes 5−8 varied from pale yellow to orange. The Rh(III)
complexes 9−11 are orange-brown. All of the Ir(III) and
Rh(III) complexes 5−11 are stable both in the solid state and
in solution (acetone-d6, dichloromethane-d2) at room temper-
ature.
(b). Synthesis of Ir and Rh Complexes. (i). Ir(III)/Rh(III)
−
Complexes with [Ir(N−N′)Cp*Cl]X (X = BArF −, BPh4 ; 5−8)
4
and [Rh(N−N′)Cp*Cl]X (X = BArF −, BPh4 ; 9−11). A series of
−
4
Ir(III) and Rh(III) complexes with pyrazolyl-1,2,3-triazolyl
bidentate donor ligands and the Cp* coligand (Cp* = 1,2,3,4,5-
pentamethylcyclopentadienyl), [Ir(N−N′)Cp*Cl]X (X =
The solution state structures of complexes 5−11 were
characterized using a combination of 1H, 13C, and 2D (HSQC,
HMBC, COSY and/or NOESY) NMR spectroscopic techni-
BArF −, BPh4 ; 5−8) and [Rh(N−N′)Cp*Cl]X (X = BArF −
,
4
−
4
−
BPh4 ; 9−11), were prepared by reaction of the ligand with
[M(Cp*)Cl2]2 (M = Rh, Ir), followed by anion exchange with
NaBArF (NaBArF = sodium tetrakis[3,5-bis(trifluoromethyl)-
1
ques. In all cases, the H NMR resonances due to the two
4
4
methylene protons of the CH2 linking the pyrazolyl and 1,2,3-
triazolyl moieties appear as two AB doublets with significantly
different chemical shifts, illustrating the coordination of the
ligand to the metal center. For each structure 5−11, one of the
two methylene resonances (Ha) is significantly deshielded,
which was attributed to the proton being pointed toward the
Cp* and subjected to the ring current effect of the Cp* ring.28
(ii). Rh(I) Complexes. Cationic Rh(I) complexes with
pyrazolyl-1,2,3-triazolyl bidentate donor ligands and carbonyl
phenyl]borate) or NaBPh4 (Scheme 4). We27 and others28
Scheme 4. Synthesis of Ir and Rh Complexes with Pyrazolyl-
1,2,3-triazolyl Bidentate Donor Ligands
coligands [Rh(N−N′)(CO)2]BArF (13−16; Figure 1) were
4
synthesized by reaction of the ligand with [RhCl(CO)2]2
followed by a counteranion exchange with NaBArF (Scheme
4
4).26 The color of these complexes varies from pale yellow to
dark yellow, and the complexes are air stable in the solid state
and in solution (acetone-d6 and/or dichloromethane-d2) at
ambient temperatures. All of the complexes were fully
1
characterized by H and 13C NMR and FTIR spectroscopy,
Figure 2. ORTEP depictions of (a) [Ir(2b)Cp*Cl]BArF4 (6b) and (b) [Ir(3b)Cp*Cl]BArF4 (7b) with 40% thermal ellipsoids for the non-hydrogen
atoms.
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mass spectrometry, and elemental analysis. The 1H NMR
spectra of the cationic dicarbonyl complexes 13−16 show that
the resonance arising from protons of the CH2 bridge linking
the pyrazolyl and 1,2,3-triazolyl moieties appears as a singlet, as
would be expected for a square-planar coordination around the
Rh(I) and Ir(I) metal centers. The 13C NMR spectra show the
literature for analogous Ir(III) and Rh(III) complexes with
bis(pyrazol-1-yl)methane or bis(1-methylimidazol-2-yl)-
methane.27,28 The M−N distances in each of these complexes
are also comparable to those reported in the literature,27,28,31
with the M−N(triazole) bond being slightly shorter than the
M−N(pyrazole) bond in each of these complexes, indicating a
stronger metal binding ability of the triazolyl N donor in
comparison to that of the pyrazolyl N donor. A similar trend
has also been observed in the solid-state structures of Rh(I) and
Ir(I) complexes containing pyrazolyl−triazolyl bidentate
donors.26,28 Strongly electron donating substituents (CF3) on
the para position of the phenylene ring (6b and 7b) on the
1,2,3-triazolyl ring lead to slightly longer Ir−N(triazole) bond
lengths in comparison with Ir complexes without electron-
withdrawing groups on the ligands (6a′ and 5). The presence
or absence of the CH3 groups on the 3- and 5-positions of the
pyrazolyl ring did not lead to any observable change in the M−
N(pyrazolyl) bond length in the solid-state structures of 6b and
7b.
1
presence of 13CO resonances at ∼183 ppm with JRh−C ≈ 70
Hz, where the 13C resonances due to the two carbonyls are
coincident in most cases. The FTIR (dichloromethane
solution) spectra of these complexes show two strong ν(CO)
bands indicative of cis-dicarbonyl complexes (Table S2,
Supporting Information). The ν(CO) band shifts to a
marginally higher wavenumber with more strongly electron
withdrawing groups at the N1′ position of the 1,2,3-triazolyl
ring, following the trend for νCO of the substituents at N1′:
PhCH2, p-CH3Ph < Ph < p-CF3Ph < p-NO2Ph. The δ(CO)
chemical shifts and ν(CO) frequencies are similar to those in
analogous complexes having bis(1-pyrazolyl)methane and
bis(1-methylimidazol-2-yl)methane as the N,N′-donor li-
gands.29,30
The cationic Rh(I) complex [Rh(3c)(CO)2]BArF (15c)
4
Solid-State Structures using X-ray Diffraction Anal-
ysis. Single crystals of 5, 6a′, 6b, 7b, 8, 9, 10a, 10a′, 11, and
15c suitable for X-ray diffraction studies were obtained by
layering a concentrated dichloromethane solution of each of the
complexes with pentane. ORTEP depictions of the solid-state
(Figure 3) adopts the expected square-planar coordination
around the metal center, and the six-membered metallacycle
formed upon coordination of the ligand to the metal center
adopts a boat conformation. The N−Rh−N bite angle of 84.4°
and Rh−N bond lengths are comparable to literature values for
analogous complexes.26,29,30
Catalysis: A Tandem C−N/C−C Cyclization Reaction.
The proposed tandem C−N/C−C bond formation sequence
involves a hydroamination reaction to form 2-(hydroxyalkyl)-
indoles 17I−20I as the first step followed by the intramolecular
C3 alkylation of 2-(hydroxyalkyl)indole as the second step,
leading to the formation of tricyclic indole products 17P−20P
(Scheme 2). The catalyzed intramolecular hydroamination of 2-
alkylanilines has previously been demonstrated using Rh and Ir
complexes similar to those reported here as catalysts.23,32 To
assess the feasibility of the cascade C−N bond formation/
indole C3 alkylation reaction, we initially tested the efficiency of
the complexes under investigation here as catalysts for the
intramolecular C3 alkylation (the second step) using 2-(4-
hydroxybutyl)indole (17I) as the substrate.
structures of [Ir(2b)Cp*Cl]BArF (6b) and [Ir(3b)Cp*Cl]-
4
BArF4 (7b) are shown in Figure 2, and the ORTEP depiction of
the solid-state structure of [Rh(3c)(CO)2]BArF (15c) is
4
shown in Figure 3. The ORTEP depictions for the remaining
(a). Catalyzing the Second Step: Intramolecular C3-
Alkylation of 2-(4-Hydroxybutyl)indole (17I) To Form
1,2,3,4-Tetrahydrocarbazole (17P). A number of Ir(III)
complexes (5−8; Table 2) were assessed as catalysts for the
intramolecular C3 alkylation of 2-(4-hydroxybutyl)indole
(17I), forming 1,2,3,4-tetrahydrocarbazole (17P). Reaction
conditions similar to those used by Grigg and co-workers for
the intermolecular C3 alkylation of indole with alcohols were
used here, with KOH as the base and heating to 110 °C (Table
2).18 The Ir(III) complexes 5−8 were active as catalysts for the
conversion of 17I to 17P, and no byproduct was observed in
the 1H NMR spectra. No conversion of 17I to 17P was
observed in control experiments in the absence of a metal
complex or a base. Using the iridium(III) dimer [Ir(Cp*)Cl2]2
(6 mol %) + KOH (1.2 mol equiv) as a catalyst for the reaction
only gave a TOF of 0.2 h−1, and the reaction took 1 week to
reach 94% conversion, with heating at 110 °C; thus,
[Ir(Cp*)Cl2]2 was a significantly less active catalyst for this
reaction than the Ir(III) complexes 5−8 (Table 2).
Figure 3. ORTEP depiction of [Rh(3c)(CO)2]BArF4 (15c) with 40%
thermal ellipsoids for the non-hydrogen atoms. Selected bond
distances (Å) and angle (deg): Rh1−N2(pyrazole) = 2.082(4),
Rh1−N3′ = 2.081(3), Rh1−C1B = 1.871(5), Rh1−C2B = 1.856(6);
N2−Rh1−N3′ = 84.4(1).
X-ray structures together with crystal data for all structures are
provided in the Supporting Information (Figures S1−S7,
Tables S3 and S4). Selected bond lengths and bond angles
for Ir(III) and Rh(III) complexes are given in Table 1.
The solid-state structures of the Ir(III) complexes 8, 6b, 7b,
6a′, and 5 and Rh(III) complexes 11, 10a, 10a′, and 9 (Figure
2 and Figure S1−S7) all exhibit a piano-stool conformation
about the metal center. In each structure, the metallacycle
formed upon coordination of the pyrazolyl−triazolyl bidentate
ligands to the metal center adopts a boat conformation. The
N−M−N bite angles for these complexes are between 82.3°
and 84.5° (Table 1) and are similar to those reported in the
(b). The First Step: Catalyzed C−N Bond Formation for the
Cyclization of 2-(6-Hydroxyhex-1-ynyl)aniline (17S) to 2-(4-
Hydroxybutyl)indole (17I). The efficiency of the rhodium(I)
(13−16) and iridium(III) complexes (5−8) as catalysts for the
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Table 1. Selected Bond Lengths and Bond Angles for Ir(III) Complexes 8, 6b, 7b, 6a′, and 5 and Rh(III) Complexes 11, 10a,
a
10a′, and 9 with Bidentate N−N′ Donor Ligands
8
6b
7b
6a′
5
11
10a
10a′
9
Bond Lengths (Å)
M−N(pyrazole)
M−N(triazole)
2.101(3)
2.089(5)
2.111(6)
2.117(5)
2.093(2)
2.115(2)
2.109(6)
2.125(5)
2.102(7)
2.098(2)
2.129(2)
2.102(5)
1.781
2.087(7)
1.780
2.075(2)
1.778
2.075(2)
1.779
2.085(6)
1.774
2.091(2)
1.774
2.081(2)
1.772
b
M−C*(Cp*)
1.773
1.769
M−Cl
2.387(1)
2.385(2)
2.382(2)
2.3879(5)
2.3980(7)
2.381(2)
2.379(2)
2.3870(5)
2.4031(7)
Bond Angles (deg)
83.47(7) 83.62(8)
N−M−N
83.9(2)
82.3(2)
84.0(2)
84.5(2)
84.1(2)
83.69(7)
84.00(8)
a
b
Standard deviations are given in parentheses. C* is the centroid of the Cp* ring.
Table 2. [Ir(N−N′)Cp*Cl]BArF (5−8) Catalyzed
Table 3. [Ir(N−N′)Cp*Cl]BArF (5−8) or [Rh(N−
4
4
Formation of 1,2,3,4-Tetrahydrocarbazole (17P) from 2-(4-
N′)(CO)2]BArF (13−16) Catalyzed Cyclization of 2-(6-
4
a
Hydroxybutyl)indole (17I) using KOH as the Base
Hydroxyhex-1-ynyl)aniline (17S) to 2-(4-
a
Hydroxybutyl)indole (17I)
a
The reaction was performed in a Young NMR tube with 0.6 mL of
toluene-d8 at 110 °C (heating in an oil bath) under an atmosphere of
nitrogen with 5 mol % catalyst loading and 1 mol equiv of KOH.
b
TOF = (mol of product)/((mol of catalyst) h) at 50% conversion of
substrate to product. Conditions: [Cat] = 8.5−9.0 mM; [substrate] =
c
0.17−0.19 M. An error of ca. 10% in conversions was found, due to
the low solubility of 17I in toluene-d8 in the presence of KOH.
a
first of the two reaction steps (hydroamination) was assessed
using 2-(6-hydroxyhex-1-ynyl)aniline as the substrate (17S).
The catalytic efficiency of the complexes tested here for the
cyclization of 17S to 17I varies significantly (Table 3). The
efficiency is dependent on the nature of the metal (Rh or Ir) as
well as the steric and electronic environment around the metal
center.
The reaction was performed in a Young NMR tube with 0.6 mL of
toluene-d8 at 100 °C (heating inside the NMR probe) under an
atmosphere of nitrogen with 5 mol % catalyst loading. TOF = (mol
of product)/((mol of catalyst) h) at 50% conversion of substrate to
product. Conditions: [Cat] = 8.5−9.0 mM; [substrate] = 0.17−0.19
M.
b
The cationic Rh(I) complexes were the most active catalysts
tested here for the cyclization of 17S to 17I. Using the Rh(I)
donor, as illustrated by the longer M−N(pyrazolyl) bond
length in comparison with the M−N(triazolyl) bond length
(Table 1 and also ref 26), and of all the Rh(I) complexes
complexes [Rh(4)(CO)2]BArF (16) and [Rh(2b)(CO)2]-
4
BArF (14b), the TOF reached >1000 h−1 and complete
assessed here, the complex [Rh(4)(CO)2]BArF (16) (4 =
4
4
conversion from 17S to 17I was achieved in less than 5 min.
The Rh(I) complexes 14−16 are among the most active late-
transition-metal catalysts reported for the intramolecular
hydroamination of 2-(alkynyl)aniline substrates.23,32,33 The
pyrazolyl N donor is weaker than the 1,2,3-triazolyl N3′
bis(1-pyrazolyl)methane) with two pyrazolyl donors afforded
the highest TOF for the hydroamination step of 1400 h−1. This
suggests that the weaker N donor ligands led to higher catalytic
activity of the metal complex for the hydroamination reaction,
as previously observed in our studies on the intramolecular
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hydroamination of 4-pentyn-1-amine using Rh(I) and Ir(I)
catalysts.30a,34 The presence of dimethyl substituents on the 3-
and 5-positions of the pyrazolyl ring of the pyrazolyl-1,2,3-
triazolyl donor ligands led to a decrease in the catalytic
found to be highly dependent on the nature of the base used.
t
When BuOK was used, the TOFs increased significantly (ca.
5−10 fold, except when [Ir(4)Cp*Cl]BArF (8) or [Ir(2a)-
4
Cp*Cl]BArF (6a) was used as catalyst) and the time to reach
4
efficiency of the resulting [Rh(N−N′)(CO)]BArF metal
4
complete conversion was notably reduced in comparison to
when KOH was used as the base (Tables 2 and 4). When
DABCO (1,4-diazabicyclo[2.2.2]octane) or KN(SiMe3)2 was
used as the base, the rate of reaction significantly slowed down
and complete conversion of 17I to 17P was not observed.
complex (Table 3). This decrease in catalytic reactivity is likely
due to the increase in steric hindrance around the metal center
imposed by the CH3 substituent. A correlation between the
trend in electron-donating/-withdrawing ability of the para
substituent R2 on the 1,2,3-triazolyl N1′ phenylene group and
the catalytic activity of the resulting metal complex could not be
established. The Ir(I) catalyst [Ir(2a)(CO)2]BArF (12) was
Table 4. [Ir(N−N′)(Cp*)Cl]BArF4 (5-8) Catalyzed One-Pot
Tandem C−N and C−C Bond Formation in the Synthesis of
1,2,3,4-Tetrahydrocarbazole (17P) from 2-(6-Hydroxyhex-1-
4
only moderately active for this reaction, with a TOF of 40 h−1
and the reaction reaching complete conversion after 1.10 h.
Other Ir(I) complexes were not tested for this reaction, as
complex 12 was not efficient in promoting the C−C bond
formation step (see the next section), and this complex was also
much less efficient in comparison with its analogous Rh(I)
a
ynyl)aniline (17S)
complex, [Rh(2a)(CO)2]BArF (10a).
4
Cationic Ir(III) and Rh(III) complexes [M(N−N′)(Cp*)-
Cl]BArF (5−11) were also assessed as catalysts for the
4
cyclization of 2-(6-hydroxyhex-1-ynyl)aniline (17S) to 2-(4-
hydroxybutyl)indole (17I). The complex [Ir(3c)(Cp*)(Cl]-
BArF (7c) gave the best TOF of 350 h−1, and complete
4
conversion of the starting material 17S to the hydroxyindole
product 17I was achieved in less than 0.5 h (Table 3). Ir(III)
complexes 5−8 were significantly more active than their
analogous Rh(III) complex 10a in promoting the cyclization of
17S. [Rh(2a)Cp*Cl]BArF4 (10a) or [Rh(4)Cp*Cl]BArF4 (16)
promoted cyclization of 17S to 17I with TOFs of 2.6 and 6.0
h−1, respectively, and complete conversion (>98%) after 42 h.
These results show that these Rh(III) complexes are much less
active than the Ir(III) complexes tested here, [Ir(2a)Cp*Cl]-
BArF (6a) and [Ir(4)Cp*Cl]BArF (8) (Table 3). The TOFs
4
4
(5.5−350 h−1) and the times to reach complete conversion
(0.5−19 h) for the Ir(III)-catalyzed reaction are highly
dependent on the nature of N−N′ donor ligands. However,
no clear correlation between the catalytic efficiency of the
resulting metal complex and the trend in the electron-
withdrawing/-donating ability of the substituent on the 1,2,3-
triazolyl or the pyrazolyl ring could be established.
−
The Ir(III) complex [Ir(2a)Cp*Cl]BPh4 (6a′), with BPh4
as the counteranion, is much less efficient as a catalyst for the
transformation of 17S to 17P in comparison with the analogous
complexes 5, 6a−c, 7a−d and 8 with the BArF − counteranion.
4
The TOF of the [Ir(2a)Cp*Cl]BPh4 (6a′) catalyzed
conversion of 17S to 21I was only 3.6 h−1, and the reaction
did not reach complete conversion after 71 h. No other
−
complexes with the BPh4 counteranion were tested, as they
were expected to all have low activity as catalysts.
a
(c). Catalyzed Cascade C−N and C−C Bond Formation in
One Pot: Synthesis of 1,2,3,4-Tetrahydrocarbazole (17P)
from 2-(6-Hydroxyhex-1-ynyl)aniline (17S). On using Ir(III)
catalysts 5−8 with KOH as the base to promote the second
step of the double cyclization reaction, the reaction was slow
with TOFs of only 1−2 h−1, although greater than 84%
conversion was achieved (Table 2). In an effort to increase the
efficiency of this second alkylation step, a range of bases
(tBuOK, DABCO (1,4-diazabicyclo[2.2.2]octane), KN-
The reaction was performed in a Young NMR tube with 0.6 mL of
toluene-d8 and 5.0 mol % catalyst loading under an atmosphere of
nitrogen with [Cat] = 8.5−9.0 mM and [substrate] = 0.17−0.19 M.
Upon the completion of step 1 as observed by 1H NMR spectroscopy,
1 molar equiv of tBuOK was added to the reaction mixture in a Young
b
NMR tube and the reaction mixture heated at 110 °C. See Table 3
c
for TOF of the first step. TOF = (moles of product)/((mol of
d
catalyst) h) at 50% conversion of substrate to product. Due to the
low solubility of 17I and possibly 17P in toluene-d8 in the presence of
tBuOK, there was an error in calculating the percentage conversion;
therefore, after 48 h reaction time (second step), 0.2 mL of DMSO-d6
(SiMe3)2) were tested in combination with [Ir(4)Cp*Cl]BArF
4
1
(8) as the catalyst. The base was added following completion of
the first C−N bond formation of the indole intermediate 17I.
The rate of the Ir(III)-catalyzed conversion of 17I to 17P was
was added and more accurate conversions were determined by H
e
NMR spectroscopy of the homogeneous reaction mixture. 40 h
reaction time.
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A degree of insolubility of tBuOK and product was observed
during the second-step cyclization. In order to improve the
solubility of the reagents, 0.1 mL of CDCl2CDCl2, THF-d8, and
bonds. The complex [Ir(3c)Cp*Cl]BArF (7c) is the most
4
efficient catalyst for the tandem C−N/indole C3 alkylation
reaction starting with 17S.
Substrate Scope. To assess the generality of the two-step
reaction, the scope of substrates for the tandem one-pot C−N
and C−C bond formations was expanded to include 2-(5-
hydroxypent-1-ynyl)aniline (18S), 2-(7-hydroxyhept-1-ynyl)-
aniline (19S), and 2-(6-hydroxy-6-methylhex-1-ynyl)aniline
DMSO-d6 were each added to reaction mixtures of the
t
[Ir(4)Cp*Cl]BArF (8) + BuOK catalyzed alkylation reaction
4
in toluene-d8 (0.5 mL). Unfortunately, the mixed solvent
systems led to extremely slow reaction rates or the formation of
unidentifiable byproducts and could not be used for catalysis
testing. Therefore, to ensure correct conversions were
determined, a small amount of DMSO-d6 was added at the
completion of the reaction, as confirmed using NMR, so that all
components of the mixture were soluble (Table 4).
(20S) (Table 5). The complex [Ir(3c)Cp*Cl]BArF (7c) was
4
Table 5. Catalyzed Tandem C−N and C−C Bond Formation
a
using [Ir(3c)Cp*Cl]BArF (7c)
4
t
Having established that BuOK was the most effective base
for the reaction, the efficiency of the Rh(I), Ir(I), and Ir(III)
complexes 5−12 as catalysts for the tandem one-pot C−N and
C−C bond formation reaction in the synthesis of 1,2,3,4-
tetrahydrocarbazole (17P) from 2-(6-hydroxyhex-1-ynyl)-
t
aniline (17S) was assessed using BuOK as the base for the
second step. The Ir(III) complexes 5−8 were the most active in
catalyzing the clean C−C bond formation in the conversion of
17I to 17P, with no byproducts observed in the 1H NMR. The
reaction outcomes using the Ir(III) catalysts only are given in
Table 4. The Ir(I) complex [Ir(2a)(CO)2]BArF4 (12) was also
able to promote the intramolecular alkylation reaction;
however, the reaction rate was significantly slower in
comparison with the analogous Ir(III) complex [Ir(2a)(Cp*)-
Cl]BArF (6a). The reaction catalyzed by 12 reached 42%
4
conversion after 18 h, with some unidentifiable products
formed. The Rh(I) complexes [Rh(4)(CO)2]BArF4 (16) and
a
[Rh(2b)(CO)2]BArF (14b) were not active in catalyzing this
The reaction was performed in a Young NMR tube with 0.6 mL of
4
toluene-d8 and 5.0 mol % catalyst loading under an atmosphere of
nitrogen with [Cat] = 8.5−9.0 mM and [substrate] = 0.17−0.19 M.
Upon the completion of step 1, as observed by 1H NMR spectroscopy,
1 equiv of tBuOK was added to the reaction mixture in a Young NMR
tube and the reaction mixture heated at 110 °C. TOF = (mol of
product)/((mol of catalyst) h) at 50% conversion of substrate to
transformation.
To test if the tandem reaction works effectively when the
base, substrate, and catalyst were all added simultaneously at
t
b
the beginning of the reaction, BuOK was added at the
beginning of the reaction sequence using [Ir(4)Cp*Cl]BArF
4
c
(8) as the catalyst and the substrate 2-(6-hydroxyhex-1-
ynyl)aniline (17S). This did not lead to a quantitative
conversion to the tricyclic product, 17P, but to the formation
of a mixture of products 2-((tetrahydro-2H-pyran-2-ylidene)-
methyl)aniline (24% conversion), 17P (9% conversion), and
unreacted starting material 17S (67%) after 21 h of heating at
110 °C. The formation of 2-((tetrahydro-2H-pyran-2-ylidene)-
methyl)aniline is likely due to the hydroalkoxylation reaction of
the alkynol moiety.
product. Upon complete conversion to final products, DMSO-d6 was
added to the reaction mixture to form a homogeneous solution,
whereby no indole intermediates 17I, 19I, and 20I were observed in
d
the 1H NMR spectra. The result has already been presented in Table
e
4 and is included here for comparison. A significant amount of
unidentifiable byproducts were observed. Complete conversions to
the final products were achieved after 40 h.
f
used as the catalyst for these reactions, as it was the most active
catalyst for the tandem C−N and C−C bond formations in the
reaction using 2-(6-hydroxy-6-hex-1-ynyl)aniline (17S) as the
substrate. Quantitative conversions of starting materials 17S,
19S, and 20S to the final tricyclic indole products 17P, 19P,
and 20P, respectively, were achieved (Table 5). These results
demonstrate that this methodology is a convenient route for
the synthesis of a range of highly valuable tricyclic indole
products. The synthetic method can be applied to secondary
alcohol substrate (20S) as well as different ring sizes (substrates
17S and 19S). The cyclization of both 2-(5-hydroxypentyl)-
indole (19I) and 2-(4-hydroxy-4-methylbutyl)indole (20I) to
the final products 19P and 20P is slower than the conversion of
2-(4-hydroxybutyl)indole (17I) to 17P (Table 5). This is likely
due to the fact that 19I contains a longer chain length and 20I
is a secondary alcohol.
The Rh(I) complexes were generally more reactive than the
Ir(III) complexes in promoting the C−N bond formation (first
step), and only the Ir(III) complexes were efficient as catalysts
for the alkylation step. Therefore, we tested the efficiency of the
conversion of 17S to 17P using a mixture of [Rh(2c)(CO)2]-
BArF (14c) and [Ir(3c)Cp*Cl]BArF (7c) at 2.5 mol % of
4
4
each complex. The TOF (100 h−1) of the catalyzed C−N bond
formation reaction is lower than the TOFs obtained in the
catalyzed reaction using either complex 14c (390 h−1) or 7c
(350 h−1) (Table 3). The rate of the alkylation step is also
significantly slower (TOF = 1.3 h−1) than the reaction catalyzed
by complex 7c. These results imply that there is no synergistic
cooperation between the two catalysts 14c and 7c in the
cascade reaction.
In short, a series of Ir(III) complexes with pyrazolyl-1,2,3-
triazolyl donor ligands [Ir(N−N′)(Cp*)Cl]BArF (5−8) are
For the first step of the reaction sequence with the substrates
17S−20S, the rates for the catalyzed formation of 2-
(hydroxyalkyl)indole intermediates 17I−20I follow the trend
18I > 17I > 20I > 19I. The reason for this trend is not
4
effective catalysts for the tandem catalyzed synthesis of 1,2,3,4-
tetrahydrocarbazole (17P) from 2-(6-hydroxyhex-1-ynyl)-
aniline (17S) via the sequential formation of C−N and C−C
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Scheme 5
immediately clear and is explained in Mechanism of the First
Step.
and 7, respectively. We previously observed that the formation
of 5-membered O-heterocycles is faster than that of the 6-
membered O-heterocycles in the catalyzed cyclization of
alkynols using similar metal complexes. The formation of 7-
membered O-heterocycles were not observed in these
reactions.35,36 The hydroalkoxylation of the secondary alcohol
(20S) is slower than that of the analogous primary alcohol
(17S), and this could be attributed to the steric hindrance
posed by the CH3 group during the approach of the OH group
to the metal-activated alkyne.37
To establish the contribution of pathway B (Scheme 5) to
the formation of 2-(hydroxylalkyl)indoles 17I and 18I from
17S and 18S, the catalyzed formation of the indole
intermediates was also performed with the substrates 2-(pent-
1-ynyl)aniline (21S) and 2-(hydroxyalk-1-ynyl)anilines 18S
and 17S, using [Rh(2b)(CO)2]BArF4 (14b) and [Ir(4)Cp*Cl]-
BArF4 (8) as the catalysts (Table 6). The possibility of the first
cyclization reaction going through pathway B was eliminated by
removing the alcohol functionality in substrate 21S, and the
reaction proceeded with significantly slower rates for the 2-
(pent-1-ynyl)aniline (21S) substrate in comparison with the
rates for the substrates 17S and 18S, respectively, using the
same catalyst. The results obtained confirm that the hydro-
alkoxylation−Lewis acid mediated isomerization pathway,
pathway B, is an important contributor to the rate of indole
formation for the 2-(hydroxyalk-1-ynyl)aniline 17S, 18S and
20S substrates.
The only substrate that led to less than quantitative
conversion for the second step of the reaction was the
substrate 2-(5-hydroxypent-1-ynyl)aniline (18S), where only
37% conversion to the desired tetrahydrocyclopent[b]indole
product 18P was observed at 21 h. A significant amount of
unidentifiable byproducts were also formed during the reaction,
which was attributed to the formation of polyindole products
that have been previously observed in the intermolecular C3
alkylation of indole.22
Mechanism of the First Step. The first step of the tandem
reaction, the formation of indoles 17I−20I from 17S−20S,
could follow two different reaction pathways (Scheme 5). The
differences in the rate of indole formation observed when the
first cyclization step was performed for different substrates
using the same catalyst [Ir(3c)(Cp*)Cl]BArF (7c) (Table 5)
4
could be attributed to the different rates of the two different
pathways. The mechanism of the reaction through pathway B
was confirmed on observation of the intermediate I1 (Scheme
5), which slowly isomerized to the final indole product 18I
during the cyclization of 18S at 60 °C (Figure 4).
CONCLUSION
A series of novel Rh and Ir complexes containing pyrazolyl-
■
1,2,3-triazolyl bidentate N−N′ donor ligands, [Ir(N−N′)-
(Cp*)Cl]X (X = BArF , BPh4; 5, 5′, 6a−c, 6a′, 7a−d, 8),
4
[Rh(N−N′)(Cp*)Cl]X (9, 9′, 10a, 10a′, 11), and [Rh(N−
N′)(CO)2]BArF (14a−c, 15a−c, 16), were synthesized and
4
fully characterized. The solid-state structures of 5, 6a′, 6b, 7b,
8, 9, 10a, 10a′, 11, and 15c were determined using single-
crystal X-ray diffraction studies. The effects of the electron-
donating/-withdrawing substituents on the pyrazolyl and 1,2,3-
triazolyl donors were manifested as changes in chemical shifts
of the pyrazoyl-C4 and triazolyl-C5′ 13C NMR resonances and
also in the M−N bond lengths, as determined by X-ray
diffraction. The electron-withdrawing abilities of the triazolyl
N1′ substituents follow the trend CH2Ph < p-PhCH3 < Ph < p-
PhCF3 < p-PhNO2.
Figure 4. Time course for the [Ir(4)Cp*Cl]BArF (8) catalyzed
formation of 18I from 18S at 60 °C, showing the formation and
isomerization of the furan intermediate.
4
If the reaction only proceeded through the hydroamination
pathway (pathway A), the rates of formation of indoles 17I−
20I should be very similar for all four substrates. In fact, the
observed rates vary significantly and follow the trend 18I > 17I
> 20I > 19I. The contribution of pathway B (formation of O-
heterocycles followed by fast isomerization) could explain the
differences in the observed TOFs of C−N bond formation
(Table 5). The rate of the formation of O-heterocyclic
intermediates (I1) is likely to follow the trend 18S > 17S >
20S > 19S, as the sizes of the O-heterocycles would be 5, 6, 6,
Both the Rh(I) complexes [Rh(N−N′)(CO)2]BArF (13−
4
16) and Ir(III) complexes [Ir(N−N′)(Cp*)Cl]BArF (5−8)
4
are effective catalysts for the formation of indoles via C−N
bond formation from a number of 2-(hydroxyalk-1-ynyl)-
anilines, with the Rh(I) complexes being the most efficient
catalysts. The TOFs for the cyclization reaction using the Rh(I)
complexes 15c and 16 reached >1000 h−1., which are among
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Table 6. Formation of Indoles 21I, 17I, and 18I from 2-(Pent-1-ynyl)aniline (21S), 2-(5-Hydroxypent-1-ynyl)aniline (18S), and
a
2-(6-Hydroxyhex-1-ynyl)aniline (17S) using [Rh(2b)(CO)2]BArF (14b) and [Ir(4)Cp*Cl]BArF (8) as the Catalyst
4
4
a
The reaction was performed in a Young NMR tube with 0.6 mL of toluene-d8 at 100 °C (heating inside the NMR probe) under an atmosphere of
b
nitrogen with 5 mol % catalyst loading. TOF = (mol of product)/((mol of catalyst) h) at 50% conversion of substrate to product. Conditions:
[Cat] = 8.5−9.0 mM; [substrate] = 0.17−0.19 M.
For the purposes of air-sensitive manipulations and in the
preparation of air-sensitive complexes, pentane and dichloromethane
were dispensed from a PuraSolv solvent purification system.
Triethylamine and methanol were distilled under nitrogen from
calcium hydride and magnesium methoxide, respectively. The bulk
compressed gases argon (>99.999%) and carbon monoxide (>99.5%)
were obtained from Air Liquide and used as received. Nitrogen gas for
Schlenk line operation came from in-house liquid nitrogen boil-off.
1H and 13C{1H} NMR spectra were recorded on Bruker DPX300,
DMX400, DMX500, and DMX600 spectrometers operating at 300,
400, 500, and 600 MHz (1H), respectively, and 75, 100, 125, and 150
MHz (13C), respectively. Unless otherwise stated, spectra were
recorded at 25 °C and chemical shifts (δ) are quoted in ppm.
Coupling constants (J) are quoted in Hz and have uncertainties of
the highest TOFs reported in the literature for similar
reactions.23,32,33 The metal-catalyzed formation of 2-substituted
indoles 17I and 18I from the anilines 17S and 18S,
respectively, proceeded by two different reaction pathways:
(a) hydroamination and (b) hydroalkoxylation−Lewis acid
catalyzed isomerization. Pathway b was a significant contributor
to the formation of the indole products 17I, 18I, and 20I. The
contribution from this hydroalkoxylation−isomerization path-
way resulted in the significantly enhanced rate of C−N bond
formation observed here. The complexes [Rh(2a)Cp*Cl]BArF
4
(10a) and [Ir(2a)(CO)2]BArF (12) were much less efficient
4
for the formation of 17I from 17S in comparison to their
analogous Rh(I) and Ir(III) complexes.
0.05 Hz for H and 0.5 Hz for 13C. H and 13C NMR chemical
shifts were referenced internally to residual solvent resonances.
Deuterated solvents were purchased from Cambridge Stable Isotopes
and used as received. Air-sensitive NMR samples were prepared in an
inert gas glovebox or by vacuum transfer of deuterated solvents into
NMR tubes fitted with a Young Teflon valve. For air-sensitive NMR
samples, CD2Cl2 and CDCl3 were distilled over calcium hydride.
Acetone-d6 was distilled from calcium sulfate.
Infrared spectra were measured using a Nicolet 380 Avatar FTIR
spectrometer as solutions in dichloromethane. Melting points were
measured using a Stanford Research Systems Optimelt melting point
apparatus in glass capillaries and are uncorrected. Microanalyses were
carried out at the Campbell Microanalytical Laboratory, University of
Otago, Otago, New Zealand. Mass spectra were acquired using a
Thermo LTQ Orbitrap XL located in the Bioanalytical Mass
Spectrometry Facility (BMSF). M is defined as the molecular weight
of the compound of interest or cationic fragment for cationic metal
complexes.
Synthesis of Ligands. The synthesis of ligand 2a has been
reported previously.26 A typical procedure for the synthesis of ligands
is reported here for the synthesis of ligand 2b. The experimental
details for the synthesis of ligands 2c and 3a−d are provided in the
Supporting Information.
Synthesis of 4-((1H-Pyrazol-1-yl)methyl)-1-(4-
(trifluoromethyl)phenyl)-1H-1,2,3-triazole (2b). 1-(Prop-2-yn-1-
yl)-1H-pyrazole (300 mg, 2.81 mmol) and 1-azido-4-
(trifluoromethyl)benzene (400 mg, 2.19 mmol) were added into a
deoxygenated mixture of 2-propanol and water (2/1 (v/v), 12 mL).
Sodium L-ascorbate (118 mg, 0.596 mmol, 20 mol %) was added, and
the reaction mixture was stirred for 5 min prior to the addition of
CuSO4·5H2O (23 mg, 0.14 mmol, 3.0 mol %). The reaction mixture
was stirred overnight at room temperature under nitrogen, during
1
1
A number of the Ir(III) complexes [Ir(N−N′)Cp*Cl]BArF
4
(5−8) are efficient catalysts for the one-pot tandem C−N/C−
C bond formation reaction starting from 2-(6-hydroxyhex-1-
ynyl)aniline (17S) to form 1,2,3,4-tetrahydrocarbazole (17P).
The complex [Ir(3c)(Cp*)Cl]BArF (7c) was the most
4
efficient for this two-step reaction, taking only 0.5 h for the
formation of the indole intermediate 17I with a TOF of 20 h−1
for the second step (intramolecular alkylation of the indole at
C3). Complex 7c was also efficient in promoting the cascade
C−N and C−C bond formation reactions of 20S and 19S to
form tricyclic carbazole products 20P and 19P, respectively,
demonstrating the potential of this methodology in the
synthesis of valuable tricyclic indole products.
EXPERIMENTAL SECTION
■
General Considerations. All manipulations of metal complexes
and air-sensitive reagents were performed using either standard
Schlenk techniques or in a nitrogen- or argon-filled Braun glovebox.
Reagents were purchased from Aldrich Chemical Co. Inc. or Alfa Aesar
Inc. and were used without further purification unless otherwise stated.
Iridium(III) chloride hydrate and rhodium(III) chloride hydrate were
obtained from Precious Metals Online (PMO P/L). [RhCl(CO)2]2,38
[IrCl2Cp*]2,39 [RhCl2Cp*]2,39 NaBArF ,40 1-propargylpyrazole,41 3,5-
4
dimethyl-1-propargylpyrazole,41,42 phenyl azide,43 1-azido-4-methyl-
benzene,44 1-azido-4-(trifluoromethyl)benzene,44 1-azido-4-nitroben-
zene,43 and bis(1-pyrazolyl)methane (4)30b were prepared using
literature methods. The syntheses of complexes [Ir(2a)(CO)2]BArF
4
(12),26 [Rh(1)(CO)2]BArF (13),26 [Rh(2a)(CO)2]BArF (14a),26
4
4
and [Rh(4)(CO)2]BArF (16)45 have been previously reported.
4
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3
which time a brown precipitate formed. The 2-propanol was removed
in vacuo, and the residue was filtered and washed with a saturated
aqueous solution of Na2EDTA until the filtrate became colorless. The
crude product was then dissolved in dichloromethane, dried with
anhydrous magnesium sulfate, and filtered through Celite. The solvent
was removed in vacuo to yield ligand 3 as a pale yellow solid (364 mg,
57%): mp 111−114 °C.
CH of BArF ), 6.59 (t, JH−H = 2.4 Hz, 1H, H4), 5.68 (br s, 1H, CHA
4
of CHAHB), 5.17 (br s, 1H, CHB of CHAHB), 1.70 (s, 15H, CH3 of
Cp*) ppm. 13C{1H} NMR (CD2Cl2, 150 MHz): δ 162.2 (q, JB−C
=
1
49.5 Hz, ipso-C to B, BArF ), 145.4 (C5/3), 140.5 (Cq of Triaz), 136.0
4
(Cq of Ph), 135.2 (o-CH to B, BArF ), 134.9 (C5/3), 131.6 (p-CH of
4
Ph), 130.9 (m-CH of Ph), 129.3 (q, JB−C = 30.0 Hz, CCF3, BArF ),
3
4
125.0 (q, 1JF−C = 270.0 Hz, CF3, BArF ), 122.6 (C5′), 121.5 (o-CH of
4
HR-MS (ESI+, MeOH): m/z (%) 316.1667 (100%) [M + Na]+
(calcd [M + Na]+ 316.0781). Anal. Found: C, 53.58; H, 3.65; N,
Ph), 117.9 (br s, p-CH to B, BArF ), 109.4 (C4), 97.9 (Cq of Cp*),
4
45.5 (CH2), 9.6 (CH3 of Cp*) ppm.
Rh(I) Complexes. The synthesis of [Rh(2b)(CO)2]BArF (14b),
1
23.31. Calcd for C13H10F3N5: C, 53.24; H, 3.44; N, 23.88. H NMR
4
3
(CDCl3, 600 MHz): δ 8.02 (s, 1H, TzH5′), 7.86 (d, JH−H = 8.5 Hz,
where 2b = 4-((1H-pyrazol-1-yl)methyl)-1-(4-(trifluoromethyl)-
phenyl)-1H-1,2,3-triazole, is included here. The syntheses of other
analogous complexes 14a,c, 15a−d, and 16 are provided in the
Supporting Information.
3
2H, m-CH of PhCF3), 7.78 (d, JH−H = 8.5 Hz, 2H, o-CH of PhCF3),
3
3
7.59 (d, JH4−H5 = 1.9 Hz, 1H, PzH5), 7.56 (d, JH3−H4 = 1.9 Hz, 1H,
3
PzH3), 6.30 (t, JH−H = 1.9 Hz, 1H, PzH4), 5.55 (s, 2H, CH2) ppm.
Synthesis of [Rh(2b)(CO)2]BArF (14b). [Rh(CO)2(Cl)]2 (50 mg,
13C{1H} NMR (CDCl3, 150 MHz): δ 145.1 (Cq of Triaz), 140.3
4
(PzC3), 139.4 (Cq of PhCF3), 131.1 (q, 2JC−F = 33.0, ipso-C to CF3 of
0.13 mmol) was dissolved in dichloromethane (15 mL) prior to the
1
addition of the PzT-CF3 ligand (3; 76 mg, 0.26 mmol). After 5 min of
PhCF3), 129.8 (PzC5), 127.1 (m-CH of PhCF3), 123.6 (q, JC−F
=
stirring, NaBArF (235 mg, 0.266 mmol) was added, resulting in the
270.7 Hz, CF3), 120.6 (TzC5′), 120.5 (o-CH of PhCF3), 106.5
4
formation of a white precipitate and a color change from yellow to
dark brown. The reaction mixture was stirred for 2 h at room
temperature before being filtered through Celite and rinsed with
dichloromethane. The volume of the filtrate was reduced to ca. 3 mL,
and n-pentane (20 mL) was added with vigorous stirring to yield 24 as
a brown solid (205 mg, 60%): mp 49−52 °C dec.
(PzC4), 47.4 (CH2) ppm.
Synthesis of Metal Complexes. Ir(III) Complexes. The synthesis
of [Ir(2b)(Cp*)Cl]BArF (6b), where 2b = 4-((1H-pyrazol-1-
4
yl)methyl)-1-(4-(trifluoromethyl)phenyl)-1H-1,2,3-triazole, is in-
cluded here, and the syntheses of other Ir(III) complexes [Ir-
(N−“N”)Cp*Cl]BArF4 (5, 6a,c, 7a−d, 8) and [Ir(N−N′)Cp*Cl]BPh4
(5′, 6a′) are provided in the Supporting Information.
FTIR (CH2Cl2): ν 2110 (s, ν(CO)), 2053 (s, ν(CO)) cm−1. HR-
MS (ESI+, MeOH): m/z (%) 452.0833 (57%) [M]+ (calcd [M]+
451.9837). Anal. Found: C, 42.66; H, 1.85; N, 4.89. Calcd for
C47H22BF27N5O2Rh: C, 42.92; H, 1.69; N, 5.32. 1H NMR (acetone-d6,
600 MHz): δ 9.29 (s, 1H, H5′), 8.35 (d, JH4−H5 = 2.4 Hz, 1H, H5),
8.30 (d, 3JH4−H3 = 2.4 Hz, 1H, H3), 8.28 (d, 3JH−H = 8.4 Hz, 2H, m-CH
Synthesis of [Ir(2b)(Cp*)Cl]BArF4 (6b). [IrCp*Cl2]2 (52 mg, 0.0065
mmol) and 2b (40 mg, 0.14 mmol) were dissolved in dichloromethane
(15 mL). After 5 min of stirring, NaBArF4 (130 mg, 0.147 mmol) was
added, resulting in the formation of a white precipitate in a yellow-
green solution. The reaction mixture was stirred for 1 h before being
filtered through Celite and rinsed with dichloromethane. The volume
of the filtrate was reduced to ca. 2 mL, and n-pentane (20 mL) was
added with vigorous stirring to yield 6b as an orange solid (160 mg,
80%): mp 165−168 °C dec.
3
of PhCF3), 8.10 (d, JH−H = 8.4 Hz, 2H, o-CH of PhCF3), 7.79 (br s,
8H, o-CH of BArF ), 7.66 (br s, 4H, p-CH of BArF ), 6.74 (apparent t,
4
4
3JH−H = 2.4 Hz, 1H, H4), 6.12 (s, 2H, CH2) ppm. 13C{1H} NMR
1
(acetone-d6, 150 MHz): δ 183.7 (d, JRh−C = 69.3 Hz, 2 × CO
(overlapped)), 162.7 (q, JB−C = 49.5 Hz, ipso-C to B, BArF ), 147.8
1
HR-MS (ESI+, MeOH): m/z (%) 656.2500 (100%) [M]+ (calcd
[M]+ 656.1374). Anal. Found: C, 43.61; H, 2.46; N, 4.25. Calcd for
4
(C3), 142.9 (Cq of Triaz), 139.6 (Cq of PhCF3), 137.0 (C5), 135.6 (br
s, o-CH to B, BArF ), 133.3 (q, 2JC−F = 32.4, ipso-C to CF3 of PhCF3),
1
C55H37BClF27IrN5: C, 43.48; H, 2.45; N, 4.61. H NMR (acetone-d6,
4
130.1 (q, 2JF−C = 31.5 Hz, 3JB−C = 3.0 Hz, ipso-C of CF3, BArF ), 128.2
600 MHz): δ 9.18 (s, 1H, TzH5′), 8.25 (d, 3JH−H = 8.5 Hz, 2H, m-CH
4
(o-CH of PhCF3), 125.5 (q, JF−C = 270.3 Hz, CF3, BArF ), 124.3 (q,
1
3
of PhCF3), 8.22 (d, JH4−H5 = 2.5 Hz, 1H, PzH5), 8.08 (d, JH−H = 8.5
4
1JC−F = 274.8 Hz, CF3 of PhCF3), 125.3 (C5′), 123.2 (m-CH of
3
Hz, 2H, o-CH of PhCF3), 7.93 (d, JH4−H3 = 2.5 Hz, 1H, PzH3), 7.79
(br s, 8H, o-CH of BArF ), 7.67 (br s, 4H, p-CH of BArF ), 6.67
PhCF3), 118.5 (br s, p-CH to B, BArF ), 109.0 (C4), 46.2 (CH2) ppm.
4
4
4
(apparent t, 3JH−H = 2.5 Hz, 1H, PzH4), 6.28 (d, 2JH−H = 16.1 Hz, 1H,
X-ray Crystallography. Please see the Supporting Information for
experimental and X-ray crystal data.
Synthesis of Substrates (SI) 17S−20S. The syntheses of organic
substrates are provided in the Supporting Information.
Catalysis Procedure. The procedures for catalyzed reactions are
provided in the Supporting Information.
2
CHa of CHaHb), 5.42 (d, JH−H = 16.1 Hz, 1H, CHb of CHaHb), 1.79
(s, 15H, CH3 of Cp*) ppm. 13C{1H} NMR (acetone-d6, 150 MHz): δ
162.6 (q, JB−C = 49.5 Hz, ipso-C to B, BArF ), 145.9 (C3), 141.6 (Cq
1
4
of Triaz), 139.8 (Cq of PhCF3), 135.8 (C5), 135.5 (o-CH to B, BArF ),
4
132.4 (q, 2JC−F = 32.4, ipso-C to CF3 of PhCF3), 130.0 (q, 2JF−C = 31.3
Hz, JB−C = 2.8 Hz, ipso-C of CF3, BArF ), 128.1 (o-CH of PhCF3),
3
4
125.5 (q, JF−C = 270.2 Hz, CF3, BArF ), 124.6 (q, JC−F = 269.8 Hz,
1
1
4
ASSOCIATED CONTENT
■
CF3 of PhCF3), 124.5 (C5′), 122.7 (m-CH of PhCF3), 118.4 (br s, p-
CH to B, BArF ), 109.2 (C4), 90.1 (Cq of Cp*), 46.1 (CH2), 9.1 (CH3
S
* Supporting Information
4
Text, tables, figures, and CIF files giving syntheses of ligands 2c
and 3a−d, syntheses of Ir(III) complexes 5, 5′, 6a, 6a′, 6c, 7a−
d, and 8, Rh(III) complexes 9, 9′, 10a, 10a′, and 11, and Rh(I)
complexes 14a,c, 15a−d, and 16, ORTEP pictures of the
cationic fragments of the solid-state X-ray structures of 5, 6a′,
8, 9, 10a, 10a′, and 11, crystal data for all of the single-crystal
structures (CCDC numbers 895848−895857), syntheses of
substrates, time course profiles for two of the tandem catalyzed
reactions, characterization data for products 17P−20P and
intermediates 17I−20I, and crystallographic data for all of the
solid-state X-ray structures in this paper. This material is
available free of charge via the Internet at http://pubs.acs.org.
of Cp*) ppm.
Rh(III) Complexes. The synthesis of [Rh(2a)Cp*Cl]BArF (10a),
4
where 2a = 4-((1H-pyrazol-1-yl)methyl)-1-phenyl-1H-1,2,3-triazole, is
reported here. The syntheses of analogous Rh(III) complexes 9, 9′,
10a′, and 11 are reported in the Supporting Information.
Synthesis of [Rh(2a)Cp*Cl]BArF (10a). [RhCp*Cl2]2 (50.0 mg,
4
8.09 × 10−5 mol) and ligand 2a (36.4 mg, 1.62 × 10−4 mol) were
dissolved in CH2Cl2 (10 mL). NaBArF (158 mg, 1.78 × 10−4 mol)
4
was added, resulting in the formation of a white precipitate. The
reaction mixture was stirred for 2 h before being filtered through
Celite. The volume of the filtrate was reduced to ca. 2 mL and pentane
added (20 mL), yielding 10a as an orange solid (154 mg, 71%): mp
125−130 °C.
HR-MS (ESI+, MeOH): m/z 498.0923 [M]+ (calcd [M]+
498.0932). Anal. Found: C, 47.82; H, 2.96; N, 5.19. Calcd for
AUTHOR INFORMATION
1
■
C54H38BClF24N5Rh: C, 47.62; H, 2.81; N, 5.14. H NMR (CD2Cl2,
Corresponding Author
*Tel: +61-2-9385 4653. Fax: +61-2- 9385 6141. E-mail: b.
messerle@unsw.edu.au.
600 MHz): δ 8.20 (s, 1H, H5′), 7.82 (br s, 1H, H5/H3), 7.74 (d,
3JH−H = 2.4 Hz, 1H, H5/H3), 7.72 (br s, 10H, o-CH of BArF and o-
4
CH of Ph), 7.66−7.62 (m, 3H, p- and m-CH of Ph), 7.55 (br s, 4H, p-
7509
dx.doi.org/10.1021/om300792b | Organometallics 2012, 31, 7500−7510

Organometallics
Article
Kennedy, D. F.; Messerle, B. A. Electrophoresis 2008, 29 (2), 491.
(c) Kennedy, D. F.; Messerle, B. A.; Rumble, S. L. New J. Chem. 2009,
33 (4), 818.
Notes
The authors declare no competing financial interest.
(26) Hua, C.; Vuong, K. Q.; Bhadbhade, M.; Messerle, B. A.
Organometallics 2012, 31 (5), 1790.
(27) Kennedy, D. F.; Messerle, B. A.; Smith, M. K. Eur. J. Inorg.
ACKNOWLEDGMENTS
■
Financial support from the University of New South Wales and
the Australian Research Council is gratefully acknowledged. We
thank Professor David St. C. Black and Dr. Gavin Edwards for
helpful discussions. We also thank the staff of the NMR Facility,
Mark Wainwright Analytical Centre, UNSW.
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dx.doi.org/10.1021/om300792b | Organometallics 2012, 31, 7500−7510