Synthesis and hydroamination catalysis with 3-aryl substituted pyrrolyl and dipyrrolylmethane titanium(iv) complexes

Article abstract of DOI:10.1039/c1dt10127g

Using an iridium-catalyzed borylation/Suzuki-Miyaura coupling sequence several 3-aryl-pyrroles were accessed; in addition, dipyrrolylmethanes incorporating these 3-arylpyrroles were synthesized. Using the monodentate pyrrolyls, Ti(NMe₂)₂(HNMe₂)(pyr ^3,5-CF3)₂ (1) and a 2,4-diarylpyrrolyl complex Ti(NMe ₂)₃(pyr^Ar/Ar′) (2) were prepared and structurally characterized. Titanium species bearing the new dipyrrolylmethane ligands Ti(NMe₂)₂(NHMe₂)(dpm^3,5-CF3) (3) and Ti(NMe₂)₂(NHMe₂)(dpm^F3) (4) were also generated. Kinetics under pseudo-first order conditions with 3 and 4 showed them to be measurably more active than the parent derivative without the electron-withdrawing aryl groups.

Full text of DOI:10.1039/c1dt10127g

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Synthesis and reactivity of cationic niobium and tantalum methyl complexes supported by imido
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PAPER
Synthesis and hydroamination catalysis with 3-aryl substituted pyrrolyl and
dipyrrolylmethane titanium(IV) complexes†
Douglas L. Swartz II,‡ Richard J. Staples and Aaron L. Odom*
Received 21st January 2011, Accepted 28th April 2011
DOI: 10.1039/c1dt10127g
Using an iridium-catalyzed borylation/Suzuki–Miyaura coupling sequence several 3-aryl-pyrroles were
accessed; in addition, dipyrrolylmethanes incorporating these 3-arylpyrroles were synthesized. Using
the monodentate pyrrolyls, Ti(NMe2)2(HNMe2)(pyr3,5-CF3)2 (1) and a 2,4-diarylpyrrolyl complex
Ti(NMe2)3(pyrAr/Ar¢) (2) were prepared and structurally characterized. Titanium species bearing the new
dipyrrolylmethane ligands Ti(NMe2)2(NHMe2)(dpm3,5-CF3) (3) and Ti(NMe2)2(NHMe2)(dpmF3) (4) were
also generated. Kinetics under pseudo-first order conditions with 3 and 4 showed them to be
measurably more active than the parent derivative without the electron-withdrawing aryl groups.
Introduction
The direct addition of amines to C–C unsaturated bonds is
a reaction of growing utility in the production of nitrogen-
containing compounds.1 The reaction can be catalyzed by a host of
different metal complexes with varying success strongly dependent
on the substrates being investigated. Titanium-based catalysts have
proven quite adept for the addition of primary amines to alkynes,
for example.2,3
In our studies, we have focused on pyrrole-based ancillaries
because of their ease of synthesis, tunability, and effectiveness for
these reactions.4,5 One of the most common ancillaries we have
employed are 5,5-dimethyldipyrrolylmethanes (H2dpm), which
are prepared by Brønsted acid-catalyzed condensation of excess
Scheme 1 Synthesis of H2dpm and Ti(NMe2)2(dpm).
pyrrole with acetone.6 The ligand is added to solutions of
5
1
Ti(NMe2)4 to generate Ti(NMe2)2(dpm), which has an h ,h -dpm
due to unfavorable steric interactions.4 However, addition of
electron-withdrawing groups seemed to increase catalytic rates in
near isosteric systems.4 Consequently, we sought electron-deficient
pyrrolyl substituents with small steric profiles.
Here we report the synthesis of several new 3-aryl substi-
tuted pyrrolyl ligands prepared in an attempt to add electron-
withdrawing groups to the system while not overcrowding the
metal center. The structure and properties of new titanium
complexes bearing these 3-aryl-pyrrolyl ancillaries are discussed
with some kinetic results regarding their catalytic activity under
pseudo-first order conditions.
in the solid state (Scheme 1).7
While hydroamination of alkynes using the dpm catalyst can
have advantages for the production of imines in certain circum-
stances over other routes,8 the same pyrrolyl catalysts can also
be used in a 3-component coupling reaction, iminoamination,9
where an amine, alkyne, and isonitrile are fashioned into tautomers
of 1,3-diimines. New one-pot methodologies for the synthesis
of substituted quinolines,10 pyrazoles,11 and pyrimidines12 have
recently been reported based on the iminoamination reaction.
In previous work, we found that adding substituents to the
2-positions of the dpm framework slowed catalysis, presumably
Michigan State University, Department of Chemistry, East Lansing, MI,
48824, USA. E-mail: odom@chemistry.msu.edu
Results and discussion
† Electronic supplementary information (ESI) available: 1H and 13C NMR
spectra for 1, and table from X-ray diffraction studies. CCDC reference
numbers 809525–809527. For ESI and crystallographic data in CIF or
other electronic format see DOI: 10.1039/c1dt10127g
3-aryl-pyrroles and their titanium complexes
The preparation of 3-aryl-pyrroles in a selective fashion is greatly
enabled by recent developments in iridium-catalyzed borylation
(Scheme 2). Addition of a slight excess of pinacolborane (HBPin)
to N-BOC-pyrrole in the presence of catalytic [Ir(OMe)(COD)]2
‡ Current address: Kutztown University, Department of Chemistry,
117 Boehm Science Center, Kutztown, PA 19530, USA; E-mail:
swartz@kutztown.edu
7762 | Dalton Trans., 2011, 40, 7762–7768
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The Royal Society of Chemistry 2011
©

Scheme 2 Synthesis of 3-arylpyrroles. Hpyr3,5-CF3: Pd catalyst = 0.5 mol%
◦
Pd(PPh3)4; deprotection: 170 C for 20 min; Yield: 76%. HpyrC6F5: Pd
catalyst = 1 mol% Pd(PPh3)4; deprotection: 170 ◦C for 20 min; Yield: 53%.
HpyrF3: Pd catalyst = 1.6 mol% Pd2(dba)3/3.2 mol% P(2-biphenyl)Cy2;
deprotection: K3PO4/n-BuOH; Yield: 52%.
Fig. 1 Synthesis of Ti(NMe2)2(NHMe2)(pyr3,5-CF3)2 (1) and structure from
single crystal X-ray diffraction. Ellipsoids are at the 50% probability level.
The dimethylamine nitrogen is labelled N(5). One of the CF3 groups
had a disorder t◦hat was modelled (not shown). Selected bond distances
and 4,4¢-di-tert-butyl-2,2¢-bipyridine (Butbpy) led to the formation
of 3-BPin-N-BOC-pyrrole in excellent yield (generally >85%).13
The 3-borylated pyrrole was readily converted to 3-aryl-N-
BOC-pyrroles via Suzuki–Miyaura coupling (Scheme 2). For 3,5-
bis(trifluoromethyl)-1-bromobenzene and pentafluorobromoben-
zene, coupling was accomplished using 0.5–1 mol% Pd(PPh3)4. For
2,4,6-trifluoro-1-bromobenzene, however, a more active catalyst
system, based on the work of Buchwald and coworkers,14 was
chosen. The best conditions found used Pd2(dba)3 as the palladium
source with P(2-biphenyl)(cyclohexyl)2 as the ancillary. Removal
of the BOC group was accomplished by heating under a flow of
nitrogen at 170 ◦C for 20 min or by heating to 100 ◦C in the
presence of K3PO4 and n-butanol.
We prepared a simple bis(pyrrolyl)titanium complex via
transamination between Hpyr3,5-CF3 and Ti(NMe2)4 in a 2 : 1
ratio. The product, Ti(NMe2)2(NHMe2)(pyr3,5-CF3)2 (1), was iso-
lated in a 76% yield (Fig. 1). This composition can be con-
trasted with that of the titanium complex bearing two 2-(3,5-
bis(trifluoromethyl)phenyl)pyrrolyl ligands reported previously,
Ti(NMe2)2(2-Ar-pyrrolyl)2.4 The 2-aryl derivative, unlike this 3-
aryl compound, does not retain dimethylamine when prepared
through the same route.
˚
(A) and angles ( ): Ti-N(1) 2.098(4), Ti–N(2) 2.050(5), Ti–N(3) 1.861(5),
Ti–N(4) 1.872(5), Ti–N(5) 2.247(4), N(1)–Ti–N(2) 87.8(2), N(2)–Ti–N(3)
116.7(2), N(3)–Ti–N(4) 112.0(2), N(4)–Ti–N(5) 90.3(2), N(2)–Ti–N(4)
130.8(2), N(2)–Ti–N(5) 81.6(2), N(3)–Ti–N(5) 91.4(2), N(1)–Ti–N(3)
99.0(2), N(1)–Ti–N(4) 91.9(2), N(1)–Ti–N(5) 167.7(2).
Using the same route used for 1, we attempted to prepare
Ti(NMe2)2(NHMe2)(pyrC6F5)2 by transamination on Ti(NMe2)4.
However, a complex mixture of products resulted. Similar to the
results for complex 1, the spectra are suggestive of rapidly inter-
changing complexes of formula Ti(NMe2)x(pyrC6F5
)4-x(NHMe2)y.
Attempted hydroamination of 1-phenylpropyne by aniline using
1 as the catalyst (see Table 1 for conditions) only went to ~10%
completion after 10 h. The cause for this poor activity is unknown.
However, it could be related to the fast ligand exchange processes
that seem to be occurring in solutions of 1.
In an attempt to stop these exchange processes within these
pyrrolyl complexes, we prepared a sterically more substantial com-
pound with aromatic groups in both the 2- and 4-positions of the
pyrrole. The synthesis of the compound is shown in Scheme 3. We
started with the known 2-(3,5-bis(trifluoromethyl)phenyl)pyrrole
available through palladium-catalyzed coupling of pyrrole and
the aryl bromide using the method established by Sadighi and
coworkers.15 The nitrogen was protected with a BOC group, and
the pyrrole was borylated in the 4-position using the iridium-
catalyzed procedure.13 Suzuki–Miyaura coupling and deprotec-
tion readily afforded HpyrAr/Ar¢, albeit in a low overall yield.
Treatment of a solution of Ti(NMe2)4 with HpyrAr/Ar¢ gave
Ti(NMe2)3(pyrAr/Ar¢) (2) in a high yielding transamination (Fig.
2, Scheme 3). Adding additional equivalents of this much larger
pyrrolyl ligand did not lead to further substitution of dimethy-
lamido ligands. Also, addition of Li(pyrAr/Ar¢) to Ti(NMe2)2Cl2 did
Single crystal X-ray diffraction on 1 (Fig. 1) shows a titanium
center that is very nearly trigonal bipyramidal with the axis
occupied by the dimethylamine donor and one of the two pyrrolyl
substituents (ESI†).
However, this structure is apparently not retained in solution as
the major peaks in the 1H NMR suggest a single set of resonances
corresponding to the pyrrolyl ligand hydrogens (ESI†). In addi-
tion, there are smaller peaks in the spectrum at room temperature
that become more prominent at lower temperatures in a reversible
fashion. The spectrum can not be assigned to simple slow exchange
of a single isomer, and we suspect that ligand scrambling can
occur to give multiple Ti(NMe2)x(pyr3,5-CF3
solution, which are complicating the low temperature spectra.
)4-x(NHMe2)y species in
This journal is
The Royal Society of Chemistry 2011
Dalton Trans., 2011, 40, 7762–7768 | 7763
©

Table 1 Hydroamination rate constants for several titanium catalysts
Catalyst
Temp (◦C)
kobs (¥ 10-7 s-1)
100
7366 2002
100
3888 764a
75
75
1976 130a
866 94a
Ti(NMe2)4
75
6963 582
Scheme 3 Synthesis of Ti(pyrAr/Ar¢)(NMe2)3 (2).
75
6225 614
Fig. 2 Structure of Ti(NMe2)3(pyrAr/Ar¢) (2) from single crystal X-ray
diffraction with thermal ellipsoids at 50% probability level. The asym-
metric unit contains a chemically identical second molecule. Selected
a Rate constants from reference 4
◦
˚
bond distances (A) and angles ( ): Ti–N(1) 1.865(4), Ti–N(2) 1.860(4),
Ti–N(3) 1.866(4), Ti–N(4) 2.073(4), N(1)–Ti–N(2) 106.4(2), N(2)–Ti–N(3)
108.2(2), N(3)–Ti–N(4) 117.1(2), N(2)–Ti–N(4) 110.4(2), N(1)–Ti–N(4)
106.5(2).
not lead to observable formation of Ti(NMe2)2(pyrAr/Ar¢)2; instead,
low yields of 2 were observed. As a result, it seems that formation
of titanium complexes with multiple pyrAr/Ar¢ substituents is highly
unfavorable. Consistent with this, NMR spectra of 2 suggest a
single species is in solution.
order conditions relative to a previously reported catalyst,
Ti(NMe2)2(2-mesitylpyrrolyl)2,4 at 100 ◦C under the conditions
shown in Table 1. The mono(pyrrolyl) complex 2 with two different
electron-withdrawing groups in the pyrrolyl ring was found to be
The ability of 2 to catalyze the hydroamination of 1-
phenylpropyne by aniline was investigated under pseudo-first
7764 | Dalton Trans., 2011, 40, 7762–7768
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©

about 2 times faster for this application than the bis(pyrrolyl)
compound.
3-aryl substituted dipyrrolylmethane compounds and titanium
complexes
In past studies, the dipyrrolylmethane-based complexes have
proven to be somewhat less active when substituents were added
to the open a-positions of the pyrroles; this was attributed to
steric inhibition of the reactions by the addition of these large
substituents.4 It was hoped that addition of electron-withdrawing
groups to the b-position, away from the metal binding site on the
nitrogen, would increase the catalysis rates relative to the parent
dipyrrolylmethane derived from unmodified pyrrole and acetone
(Scheme 1).
Two dipyrrolylmethane ligands were prepared using Hpyr3,5-CF3
and HpyrF3 in Scheme 2 as starting materials. The parent
compound, H2dpm, is prepared using excess pyrrole with acetone
and a catalytic Brønsted acid, trifluoroacetic acid.6 However,
condensations with the 3-aryl-pyrroles were more amenable to
Lewis acid catalysis using InCl3. In these ligand syntheses, again
in contrast to the H2dpm synthesis, an excess of acetone was used
(Scheme 4) rather than an excess of pyrrole.
Fig. 3 Structure of Ti(NMe2)2(NHMe2)(dpm3,5-CF3) (3) from single crystal
X-ray diffraction. Ellipsoids are at the 50% probability level. The dimethy-
lamine nitrogen is labelled N(3). The structure has disordered amido
ligands and the parameters for t◦hem may have significant errors. Selected
˚
bond distances (A) and angles ( ): Ti–N(1) 1.967(11), Ti–N(2) 1.821(12),
Ti–N(3) 2.159(9), Ti–N(4) 2.064(6), Ti–N(5) 2.064(6), N(1)–Ti–N(2)
108.7(5) N(2)–Ti–N(3) 102.1(5), N(3)–Ti–N(4) 84.8(5), N(4)–Ti–N(5)
82.3(4), N(2)–Ti–N(4) 108.8(6), N(2)–Ti–N(5) 102.8(5), N(3)–Ti–N(5)
158.4(6), N(1)–Ti–N(3) 84.4(3), N(1)–Ti–N(4) 137.6(4), N(1)–Ti–N(5)
92.4(4).
Second, the complex retains dimethylamine, which is consistent
with a more Lewis acidic titanium center in 3 than in the parent
dpm complex, which was prepared through the same route.
The kinetics of hydroamination with these two new dipyrrolyl-
methane titanium complexes were investigated using the condi-
tions shown in Table 1. These reactions were run at the slightly
lower temperature of 75 ◦C relative to pyrrolyl 2, which was
necessary to get reasonable accuracy for these faster reactions.
For comparison, included in the table are the rate constants for
reactions catalyzed by Ti(NMe2)2(dpm) and Ti(NMe2)4.
The electron-withdrawing aryl derivatives 3 and 4 exhibited
rate constants that were the same as each other within the
99% confidence interval. The parent complex Ti(dpm)(NMe2)2,
previously the fastest catalyst we had investigated for these
reactions, was ~3 times slower than 3 and 4 for this hydroamination
reaction. The starting material Ti(NMe2)4, itself a hydroamination
catalyst with a somewhat limited scope,17 was around 8 times
slower than these new substituted dipyrrolylmethane catalysts.
Conclusions
Scheme 4 Synthesis of dipyrrolylmethanes H2dpm3,5-CF3 and H2dpmF3
and titanium complexes Ti(NMe2)2(NHMe2)(dpm3,5-CF3
)
(3) and
A previous study on dipyrrolylmethane titanium systems has
suggested that the active species in alkyne hydroamination reac-
tions contained an h ,h -dpm ligand.7 In addition, we have found
Ti(NMe2)2(NHMe2)(dpmF3) (4).
1
1
1
5
The reactions of the 3,3¢-diaryl-5,5-dimethyl-dipyrrolylmethane
compounds H2dpm3,5-CF3 and H2dpmF3 to Ti(NMe2)4 provided the
5-coordinate complexes Ti(NMe2)2(NHMe2)(dpm3,5-CF3) (3) and
Ti(NMe2)2(NHMe2)(dpmF3) (4) in good yields. Complex 3 has
been characterized by single crystal X-ray diffraction, and an
ORTEP diagram is shown in Fig. 3.
evidence that the hapticity change from the h ,h -dpm to the active
1 1
h ,h -dpm conformation was not rate determining.5 The barrier
for that isomerization for Ti(NMe2)2(dpm) is around 10 kcal mol-1,
and that barrier is reduced in cases where the pyrrolyl rings are
substituted.4 All this considered, we do not believe the h ,h -dpm
conformation in compounds 3 and 4 is what is leading to the
enhanced catalytic activity over unsubstituted Ti(NMe2)2(dpm).
Instead, we suggest that the increased rate constants for these
compounds are due to lower electron density at the titanium center,
which is consistent with previous results on pyrrolyl titanium
complexes where electron-withdrawing groups increased catalysis
rates.4 The combination of electron-withdrawing groups and a
small steric profile in these 3-aryl substituted dpm complexes led
1
1
These new dipyrrolylmethane compounds, 3 and 4, have a
couple of glaring differences with the dpm parent complex
5
Ti(NMe2)2(dpm).7,16 First, the parent dpm complex has one h -
1
5
1
pyrrolyl and one h -pyrrolyl (Scheme 1). This h ,h -dpm structure
was also retained in the structurally characterized 2-aryl variants
and in derivatives prepared from a variety of different ketones.5
1
1
However, 3-aryl 3 has an h ,h -dpm structure in the solid state.
This journal is The Royal Society of Chemistry 2011
Dalton Trans., 2011, 40, 7762–7768 | 7765
©

to the fastest rates for alkyne hydroamination we have observed
thus far.
Studies on increasing the activity in these types of systems
continue in the hope that this will lead to improved cat-
alysts for titanium-catalyzed heterocyclic synthesis and other
applications.8–12
Preparative details and characterization
3-(3,5-bis(trifluoromethyl)phenyl)-1H-pyrrole
(Hpyr3,5-CF3).
Under an atmosphere of dry N2, Pd(PPh3)4 (0.817 g, 0.07 mmol)
was loaded into a 20 mL scintillation vial in DME (5 mL). To
the same vial was added 3,5-bis(trifluoromethyl)bromobenzene
(4.0 g, 13.7 mmol), and the solution was stirred for 10 min before
being transferred to a Schlenk tube. To the solution was added
3-(pinacolboryl)-N-BOC-pyrrole (3.9 g, 13.3 mmol) in DME
(10 mL). Finally, K3PO4 (5.31 g, 20.0 mmol) was added. The tube
was capped, taken out the dry box, and heated at 100 ◦C in an
oil bath for 24 h. When the reaction was complete as judged by
GC-FID, the solution was transferred to a separatory funnel.
The tube was rinsed with OEt2 (30 mL) and H2O (30 mL). The
solution was extracted with OEt2 (2 ¥ 50 mL). The combined
organic layers were dried over MgSO4. Volatiles were removed
in vacuo to yield a viscous oil, which was placed under a
continuous flow of N2 and heated in an oil bath at 170 ◦C and left
to stir for ~20 min. The black solution was then run through a
plug of silica gel with methylene chloride (500 mL) as the eluent.
The volatiles were removed in vacuo to yield a white solid (2.81 g,
76%). M.p. 106–109 ◦C. 1H NMR (CDCl3, 500 MHz): 8.37 (br s,
1H), 7.90 (s, 2H), 7.65 (s, 1H), 7.18 (m, 1H), 6.87 (q, 1H), 6.58
Experimental
General considerations
All manipulations of air sensitive compounds were carried out in
an MBraun drybox under a purified nitrogen atmosphere. Anhy-
drous ether was purchased from Columbus Chemical Industries
Inc. Pentane and toluene were purchased from Spectrum Chemical
Mfg. Corp. These were purified by sparging with dry N2, then
dried by running through activated alumina systems purchased
from Solv-Tek. Hexanes and ethyl acetate were purchased from
Mallinckodt Baker Inc. Pinacolborane was donated by BASF
and was used as received. N-BOC-pyrrole was vacuum distilled
and stored under a purified nitrogen atmosphere over molecular
sieves. Di-tert-butyl-dicarbonate, (BOC)2O, was purchased from
Oakwood Chemical and was used as received. Aniline was pur-
chased from Matheson, Coleman, and Bell Mfg. and was distilled
twice from calcium hydride under vacuum. 1-phenylpropyne was
purchased from GFS Chemical, distilled under vacuum, and then
passed over two columns of neutral alumina. Ti(NMe2)4,18 2-[3,5-
bis(trifluoromethyl)phenyl]-1H-pyrrole,15 and 3-pinacolboryl-N-
BOC-pyrrole13 were synthesized according to literature methods.
Deuterated solvents were dried over purple sodium benzophenone
ketyl (C6D6) or phosphoric anhydride (CDCl3) then distilled under
a nitrogen atmosphere. Deuterated toluene was dried by passing
it through two columns of neutral alumina. Other compounds
were purchased from commercial sources and used as received.
1H and 13C spectra were recorded on Inova-300 or VXR-500
spectrometers. All spectra were referenced internally to residual
protiosolvent (1H) or solvent (13C) resonances.
1
(m, 1H). 13C{ H} NMR (CDCl3, 125 MHz): 138.04, 131.81 (q,
JCF = 31.51 Hz), 124.85 (dd), 123.77 (q, JCF = 277.72 Hz), 122.53,
119.78, 118.77 (sept, JCF = 4.63 Hz), 115.74, 106.63. Elemental
Anal. (Found) Calcd: C, (51.63) 51.29; H, (2.53) 2.33; N, (5.02)
5.03.
3-(perfluorophenyl)-1H-pyrrole (HpyrC6F5). Under an atmo-
sphere of dry N2, Pd(PPh3)4 (0.107 g, 0.092 mmol) was loaded
into a 20 mL scintillation vial in DME (5 mL). To the same
vial was added pentafluorobromobenzene (2.2 g, 8.9 mmol), and
the solution was stirred for 10 min before being transferred
to a Schlenk tube. To the tube was added 3-(pinacolboryl)-N-
BOC-pyrrole (2.63 g, 8.98 mmol) in DME (10 mL). Finally,
K3PO4 (3.58 g, 13.5 mmol) was added. The tube was capped, the
◦
headspace was evacuated, and the vessel was placed in a 100 C
oil bath for 8 d. When the reaction was complete as judged by GC-
FID, the tube was rinsed with OEt2 (30 mL) and H2O (30 mL).
The solution was transferred to a separatory funnel and extracted
with OEt2 (2 ¥ 50 mL). The combined organic layers were collected
and dried over MgSO4. Volatiles were removed in vacuo to yield a
viscous oil, which was placed under a continuous flow of N2 and
heated in an oil bath at 170 ◦C and left to stir for ~20 min. The black
solution was then run through a plug of silica gel with methylene
chloride (500 mL) as the eluent. The volatiles wer◦e removed in
vacuo to yield a white solid (1.1 g, 53%). M.p 48–51 C. 1H NMR
(CDCl3, 500 MHz): 8.46 (s, 1H), 7.29 (s, 1H), 6.89 (app s, 1H), 6.68
General procedure for kinetics
All manipulations were done in an inert atmosphere drybox.
In a 2 mL volumetric flask was loaded the catalyst (10 mol%,
0.1 mmol), aniline (0.931 g, 911 mL, 10 mmol), 1-phenylpropyne
(0.116 g, 125 mL, 1 mmol), and ferrocene (0.056 g, 0.3 mmol) as an
internal standard. The solution was then diluted to 2 mL with
deuterated toluene. An ample amount of solution (~0.75 mL)
was put into a threaded J. Young tube that was sealed with
a cap and then wrapped with Teflon tape. The tube was then
removed from the drybox and heated at 75 or 100 ◦C in the
NMR spectrometer. The relative 1-phenylpropyne versus ferrocene
concentration was monitored as a function of time. The fits are to
the exponential decay of the starting material using the scientific
graphing programs Origin or KaleidaGraph. The exact expression
used to fit the data was
1
(app s, 1H). 13C { H} NMR (CDCl3, 125 MHz) d 145.10–144.08
(m), 143.05–142.98 (m), 139.41–139.29 (m), 138.99–138.88 (m),
137.41–137.29 (m), 137.18–36.93 (m), 119.48 (t, JCF = 6.81 Hz),
118.43, 111.23–110.01 (m), 109.34 (t, JCF = 5.98 Hz). Elemental
Anal. (Found) Calcd: C, (51.37) 51.52; H, (1.72) 1.73; N, (5.85)
6.01.
k
t
obs
Yt = Y• + (Y0 - Y•)exp
3-(2,4,6-trifluorophenyl)-1H-pyrrole (HpyrF3). Under an atmo-
sphere of dry N2 a 200 mL Schlenk tube was loaded with
3-(pinacolboryl)-N-BOC-pyrrole (4.16 g, 14.2 mmol), K3PO4
(anhydrous) (2.81 g, 13.2 mmol), Pd2(dba)3 (0.156 g, 0.173 mmol),
where Y = [1-phenylpropyne] at time = t (Yt), infinity (Y•), or at
the start of the reaction (Y0). The variables Y•, Y0, and kobs were
optimized in the fits.19
7766 | Dalton Trans., 2011, 40, 7762–7768
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The Royal Society of Chemistry 2011
©

di(cyclohexyl)(2-biphenyl)phosphine (0.119 g, 0.346 mmol) and
a stirbar. The Schlenk tube was capped and removed from the
drybox. Under N2, a solution of t-amyl alcohol (30 mL) and
2-bromo-1,3,5-trifluorobenzene (2.0 g, 9.5 mmol) was added via
syringe, and the solution was heated at 100 ◦C for 18 h. Once
the reaction was complete as judged by GC-FID, K3PO4 (2.0 g,
9.4 mmol) and BunOH (8 mL) were added. The reaction mixture
was heated for an additional 2 h at 100 ◦C. After deprotection,
the resulting solution was poured into a separatory funnel with
H2O (50 mL) and ethyl acetate (50 mL). The water layer was
extracted with ethyl acetate (3 ¥ 75 mL). The combined organic
layers were dried over MgSO4. The volatiles were removed in vacuo
to give a viscous red oil. The product was purified by column
chromatography on silica gel using CH2Cl2 : hexanes (7 : 3) as
the elutant. A second column on silica gel with hexanes : ethyl
acetate (4 : 1) as elutant gave the product as an off-white solid,
33.9 Hz), 129.79, 123.18 (q, JCF = 276 Hz), 123.8–123.58 (m),
122.12, 122.14–121.9 (m), 120.19–119.5 (m), 111.88, 110.9–110.05
(m), 109.1–108.85 (m). Elemental Anal. (Found) Calcd: C, (48.11)
48.56; H, (1.27) 1.36; N, (3.22) 3.15.
5,5-dimethyl-3,3¢-bis(3,5-bis(trifluoromethyl)phenyl)-dipyrrolyl-
methane (H2dpm3,5-CF3). A pressure tube was loaded with 3-(3,5-
bis(trifluromethylphenyl-1H-pyrrole) (2.33 g, 8.35 mmol), acetone
(13 mL, 10.3 g, 176 mmol), and a stirbar. With stirring, InCl3
(0.3 g, 1.3 mmol) was added. The tube was sealed and placed in
an oil bath at 40 ◦C for 24 h. Once the reaction was complete
as judged by 1H NMR spectroscopy, the solution was transferred
to a 250 mL round bottom flask, and the volatiles were removed
in vacuo. The resulting solid was dissolved with hexanes : CH2Cl2
(7 : 3) (~35 mL). A column was made using silica gel and the
same solvents. Once the crude mixture was loaded, the column
was flashed with hexanes until impurities began to appear in
the solvent eluting off the column as judged by TLC. At this
point, the eluent was changed to hexanes : CH2Cl2 (7 : 3). Once
the desired product was observed in the eluting solvent by TLC,
the solvent was changed to CH2Cl2. The fractions containing
product were collected, and the volatiles were removed in vacuo.
1
(0.958 g, 52%). H NMR (CDCl3, 500 MHz): 8.38 (br s, 1H),
1
7.28–7.27 (m, 1H), 6.90–6.78 (m, 1H), 6.77–6.71 (m, 3H). 13C { H}
NMR (CDCl3, 125 MHz): 161.14–160.65 (m), 159.16–158.69 (m),
118.74 (app t), 117.89, 110.76, 109.40 (app t), 100.54–100.09 (m).
Elemental Anal. (Found) Calcd: C, (60.50) 60.92; H, (3.14) 3.07;
N, (6.84) 7.10.
1
The product obtained was a white solid, (1.9 g, 76%) H NMR
(CDCl3, 500 MHz): 8.03 (br s, 2H), 7.87 (s, 4H), 7.62 (s, 2H),
2-(3,5-bis(trifluoromethyl)phenyl)-4-(pentafluorophenyl)pyrrole
(HpyrAr/Ar¢). Under an atmosphere of dry N2, [Ir(OMe)(COD)]2
(0.1 g, 0.151 mmol) was loaded into a 20 mL scintillation vial
with hexane (4 mL) and HBpin (1.92 g, 15 mmol); this was
stirred for 10 min, and Butbpy (0.081 g, 0.302 mmol) was
added. After an additional 10 min of stirring, N-BOC-2-(3,5-
bis(trifluoromethyl)phenyl)pyrrole (3.8 g, 10 mmol) in hexane
(5 mL) was added to the iridium solution. The resulting reaction
mixture was transferred to a Schlenk tube, sealed, and heated
while being stirred at 60 ◦C in an oil bath for 36 h. After
the reaction was complete by GC-FID, the crude mixture was
run through two plugs of silica gel on a fritted filter with
methylene chloride. The volatiles were removed in vacuo to
yield a clear oil. Trituration with pentane provided N-BOC-2-
(3,5-bis(trifluoromethyl)phenyl)-4-pinacolboryl-pyrrole as a white
solid, which was used without further purification.
Under an atmosphere of dry N2, a 20 mL scintillation
vial was loaded with Pd(PPh3)4 (0.140 g, 0.120 mmol) in
DME (5 mL), BrC6F5 (0.632 g, 2.57 mmol), and N-BOC-
2-(3,5-bis(trifluoromethyl)phenyl)-4-pinacolboryl-pyrrole (1.18 g,
2.33 mmol). The solution was transferred to a Schlenk tube, sealed,
and removed from the dry box. Under a continuous flow of N2,
K3PO4 was added to the vessel. The headspace in the Schlenk tube
was evacuated, and the tube was heated in an oil bath at 100 ◦C for
8 d. The reaction mixture was transferred to a separatory funnel.
The tube was rinsed with H2O (30 mL) and EtOAc (30 mL), and
the solution was extracted with EtOAc (3 ¥ 30 mL). The combined
organic layers were dried over MgSO4. The volatiles were removed
in vacuo, and the resulting oil was placed in a 165 ◦C oil bath for
10 min under a continuous flow of N2. After 10 min the crude
mixture was run through a plug of silica gel on a fritted filter
with CH2Cl2 (500 mL). The volatiles were again removed in vacuo.
Crystallization from pentane y◦ielded the product as a pale pink
solid (0.2, 19%). M.p 146–149 C. 1H NMR (500 MHz, CDCl3):
1
7.06 (q, 2H), 6.45 (q, 2H), 1.74 (s, 6H). 13C { H} NMR (CDCl3,
125 MHz): 140.67, 138.13, 132.09 (q, JCF = 32.14 Hz), 124.88,
123.77 (q, JCF = 272.73 Hz), 122.46, 118.99 (pent., JCF = 4.11 Hz),
115.61, 102.73, 35.85, 29.19. Elemental Anal. (Found) Calcd: C,
(53.88) 54.14; H, (3.31) 3.03; N, (4.51) 4.68.
5,5-dimethyl-3,3¢-bis(2,4,6-trifluorophenyl)-dipyrrolylmethane
(H2dpmF3). A threaded pressure tube was charged with InCl3
(0.107 g, 0.0484 mmol), 3-(2,4,6-trifluorophenyl)-1H-pyrrole
(0.952 g, 0.483 mmol), acetone (2.80 g, 3.55 mL, 4.83 mmol),
and a stirbar. The tube was capped and placed in a 40 ◦C oil
1
bath for 18 h. Once the reaction was complete as judged by H
NMR spectroscopy, the solution was transferred to a 100 mL
round bottom flask, where the volatiles were removed in vacuo to
yield a viscous orange oil. The product was purified by column
chromatography on silica gel using hexanes : ethyl acetate (85 : 15)
as elutant. The product was obtained as an off white solid,
(0.450 g, 43%). 1H NMR (500 MHz, CDCl3): 7.09 (s, 2H), 7.07–
1
7.06 (m, 2H), 6.75–6.65 (m, 4H), 6.55–6.53 (m, 2H). 13C { H}
NMR (125 MHz, CDCl3): 161.12–160.67 (m), 159.12–158.72 (m),
138.68, 118.37 (t), 110.42, 110.05–109.83 (m), 105.12–105.01 (m),
100.63–100.15 (m), 35.35, 28.96. Elemental Anal. (Found) Calcd:
C, (63.11) 63.60; H, (3.58) 3.31; N, (6.17) 6.48.
Ti(NMe2)2(NHMe2)(pyr3,5-CF3)2 (1). Under an atmosphere of
dry N2, 3-Hpyr3,5–CF3 (0.283 g, 1.01 mmol) was loaded into a
20 mL scintillation vial in OEt2 (3 mL). In a separate vial was
loaded Ti(NMe2)4 (0.113 g, 0.506 mmol) in OEt2 (3 mL). The
two vials were capped and put into a liquid nitrogen cooled
cold well, where they sat until frozen. The thawing solution
of 3-Hpyrr3,5–CF3 was added to the vial containing Ti(NMe2)4,
and the reaction was allowed to warm to room temperature
where it was left to stir for 6 h. After 6 h the solution was
concentrated in vacuo to yield a red oil. The oil was triturated
with pentane to yield a red solid, which was crystallized from
pentane to yield Ti(NMe2)2(NHMe2)(pyrr3,5–CF3)2 (0.285 g, 38%)
9.01 (br s, 1H), 7.90 (s, 2H), 7.72 (s, 1H), 7.42 (s, 1H), 7.06 (s,
1
1H). 13C { H} NMR (125 MHz, CDCl3): 133.75, 132.52 (q, JCF
=
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The Royal Society of Chemistry 2011
Dalton Trans., 2011, 40, 7762–7768 | 7767
©

by X-ray diffraction. The 1H and 13C NMR spectra are consistent
with multiple isomers and/or Ti(NMe2)x(pyr3,5-CF3
4-x(NHMe2)y
very appreciative of BASF for their generous gift of pinacol
borane.
)
species. See the ESI for the room temperature spectra in
CDCl3.†
Notes and references
Ti(NMe2)3(pyrAr/Ar¢) (2). Under an atmosphere of dry N2,
Ti(NMe2)4 (0.05 g, 0.223 mmol) was loaded into a 20 mL scin-
tillation vial in OEt2 (2 mL). In a separate vial was loaded 2-(3,5-
bis(trifluoromethyl)phenyl)-4-pentafluorophenyl-pyrrole (0.1 g,
0.223 mmol) in OEt2 (2 mL). The vials were placed in a liquid
nitrogen cooled cold well where they sat until frozen. The thawing
solution of HpyrrAr/Ar¢ was added to the thawing solution of
Ti(NMe2)4. The reaction was allowed to warm to RT and was left
to stir for 18 h. The volatiles were removed in vacuo. Crystallization
from OEt2/pentane yielded the title compound as a yellow solid
1 For some recent reviews on hydroamination catalysis see: (a) T. E.
Muller, K. C. Hultzsch, M. Yus, F. Foulelo and M. Tada, Chem. Rev.,
2008, 108, 3795; (b) T. E. Mu¨ller and M. Beller, Chem. Rev., 1998, 98,
675; (c) R. Severin and S. Doye, Chem. Soc. Rev., 2007, 36, 1407; (d) A.
V. Lee and L. L. Schafer, Eur. J. Inorg. Chem., 2007, 2243; (e) A. L.
Odom, Dalton Trans., 2005, 225. See also this recent review on Group
2 chemistry that includes many hydroamination examples; A. G. M.
Barrett, M. R. Crimmin, M. S. Hill and P. A. Procopiou, Proc. R. Soc.
London, Ser. A, 2010, 466, 927.
2 For some recent, representative examples of titanium-catalyzed hy-
droamination see (a) K. Weitershaus, B. D. Ward, R. Kubiak, C. Mu¨ller,
H. Wadepohl, S. Doye and L. H. Gade, Dalton Trans., 2009, 4586; (b) K.
Gra¨be, F. Pohlki and S. Doye, Eur. J. Org. Chem., 2008, 4815; (c) E.
Smolensky, M. Kapon and M. S. Eisen, Organometallics, 2007, 26,
4510; (d) M. A. Esteruelas, A. M. Lo´pez, A. Concepcio´n Mateo and E.
On˜ate, Organometallics, 2006, 25, 1448; (e) N. Vujkovic, J. L. Fillol, B.
D. Ward, H. Wadepohl, P. Mountford and L. H. Gade, Organometallics,
2008, 27, 2518; (f) L. Ackermann, R. G. Bergman and R. N. Loy, J.
Am. Chem. Soc., 2003, 125, 11956; (g) L. Ackermann, R. Sandmann
and L. T. Kaspar, Org. Lett., 2009, 11, 2031; (h) B. Lian, T. P. Spaniol, P.
Horrillo-Mart´ınez, K. C. Hultzsch and J. Okuda, Eur. J. Inorg. Chem.,
2009, 429.
◦
1
(0.12 g, 86%). M.p 76–79 C. H NMR (500 MHz, CDCl3) 7.85
(2H, s), 7.70 (1H, s), 7.37 (1H, s), 6.80 (1H, s), 3.13 (18H, s).13C
1
{ H} NMR (125 MHz, CDCl3): 145.1–144.80 (m), 142.98–142.5
(m), 138.45, 139.05–138.73 (m), 137.51– 136.97 (m), 131.46 (q,
JCF = 33 Hz), 131.47–131.25 (m), 126.88 (q, JCF = 3.5 Hz), 126.75,
123.55 (q, JCF = 273 Hz), 119.41–119.21 (m), 111.60–111.49 (m),
110.82–110.67 (m), 43.74. Elemental Anal. (Found) Calcd: C,
(46.25) 46.17; H, (3.73) 3.71; N, (8.86) 8.97.
3 For some recent studies on related zirconium catalysts see (a) D. C.
Leitsch, C. S. Turner and L. L. Schafer, Angew. Chem., Int. Ed., 2010,
49, 6382; (b) D. V. Gribkov and K. C. Hultzsch, Angew. Chem., 2004,
116, 5659; (c) P. D. Knight, I. Munslow, P. N. O’Shaughnessy and P.
Scott, Chem. Commun., 2004, 894; (d) B. D. Stubbert and T. J. Marks,
J. Am. Chem. Soc., 2007, 129, 6149; (e) D. C. Leitch, P. R. Payne, C.
R. Dunbar and L. L. Schafer, J. Am. Chem. Soc., 2009, 131, 18246;
(f) D. A. Watson, M. Chiu and R. G. Bergman, Organometallics, 2006,
25, 4731; (g) S. Majumder and A. L. Odom, Organometallics, 2008,
27, 1174; (h) A. L. Reznichenko and K. C. Hultzsch, Organometallics,
2010, 29, 24; (i) L. E. N. Allan, G. J. Clarkson, D. J. Fox, A. L. Gott
and P. Scott, J. Am. Chem. Soc., 2010, 132, 15308; (j) A. L. Gott, A. J.
Clarke, G. J. Clarkson and P. Scott, Chem. Commun., 2008, 1422.
4 D. L. Swartz and A. L. Odom, Organometallics, 2006, 25, 6125.
5 D. L. Swartz and A. L. Odom, Dalton Trans., 2008, 4254.
6 B. J. Littler, M. A. Miller, C.-H. Hung, R. W. Wagner, D. F. O’Shea, P.
D. Boyle and J. S. Lindsey, J. Org. Chem., 1999, 64, 1391.
7 Y. Shi, C. Hall, J. T. Ciszewski, C. Cao and A. L. Odom, Chem.
Commun., 2003, 586.
Ti(NMe2)2(NHMe2)(dpm3,5-CF3) (3). Under an atmosphere of
purified N2, a vial was loaded with H2dpm3,5–CF3 (0.503 g,
0.841 mmol) in OEt2 (3 mL). A separate vial was loaded with
Ti(NMe2)4 (0.188 g, 0.840 mmol) in OEt2 (3 mL). The two vials
were placed in a liquid nitrogen cooled cold well where they
sat until frozen. To the thawing solution of 3-H2dpm3,5-CF3 was
added to the Ti(NMe2)4 solution. The reaction was allowed to
warm to room temperature and left to stir overnight. The volatiles
were removed under reduced pressure to give a red oil, which
was triturated with pentane three times to give the product as a
bright orange solid. The solid was crystallized from OEt2/pentane
(0.602 g, 92%). 1H NMR (CDCl3, 500 MHz): 7.83 (s, 4H), 7.53 (s,
2H), 7.07 (s, 2H), 6.40 (s, 2H), 3.37 (s, 12H), 2.61 (br s, 6H), 1.72 (s,
1
6H). 13C { H} NMR (CDCl3, 125 MHz): 154.05 (m), 138.8, 131.5
8 (a) C. Cao, Y. Li, Y. Shi and A. L. Odom, Chem. Commun., 2004, 2002;
(b) B. Ramanathan, A. J. Keith, D. Armstrong and A. L. Odom, Org.
Lett., 2004, 6, 2957.
(q, JCF = 34 Hz), 124.4, 123.8 (q, JCF = 270 Hz), 122.2, 121.8, 117.6,
100.9, 46.8, 40.5, 38.2, 31.1. Elemental Anal. (Found) Calcd: C,
(50.75) 50.98; H, (4.89) 4.54; N, (9.04) 9.01.
9 C. Cao, Y. Shi and A. L. Odom, J. Am. Chem. Soc., 2003, 125, 2880.
For a related reaction involving hydrazines in place of amines see; S.
Banerjee, Y. Shi, C. Cao and A. L. Odom, J. Organomet. Chem., 2005,
690, 5066.
Ti(NMe2)2(NHMe2)(dpmF3) (4). Under an atmosphere of puri-
fied N2, a vial was loaded with 3-H2dpmC6F3 (0.130 g, 0.30 mmol) in
OEt2 (3 mL). A separate vial was loaded with Ti(NMe2)4 (0.067 g,
0. mmol) in OEt2 (3 mL). The two vials were placed in a liquid
nitrogen cooled cold well, where they sat until frozen. To the
thawing solution of 3-H2dpmC6F3 was added to the Ti(NMe2)4
solution. The reaction was allowed to warm and left to stir
overnight. The volatiles were removed under reduced pressure to
give a red oil, which was triturated with pentane three times to give
the product as a bright orange solid. The solid was crystallized
10 S. Majumder, K. R. Gipson and A. L. Odom, Org. Lett., 2009, 11,
4720.
11 S. Majumder, K. R. Gipson, R. J. Staples and A. L. Odom, Adv. Synth.
Catal., 2009, 351, 2013.
12 S. Majumder and A. L. Odom, Tetrahedron, 2010, 66, 3152.
13 V. A. Kallepalli, F. Shi, S. Paul, E. N. Onyeozili, R. E. Maleczka Jr. and
Milton R. Smith III, J. Org. Chem., 2009, 74, 9199.
14 For a review see R. Martin and S. L. Buchwald, Acc. Chem. Res., 2008,
41, 1461.
15 R. D. Reith, N. P. Mankad, E. Calimano and J. P. Sadighi, Org. Lett.,
2004, 6, 3981.
◦
1
from OEt2/pentane (0.157 g, 86%). M.p 110–112 C. H NMR
(CDCl3, 500 MHz): 7.32 (s, 2H), 6.72–6.64 (m, 6H), 6.63 (s, 2H),
3.24 (s, 12H), 2.49 (br s, 6H), 1.73 (s, 6H).
16 A. Novak, A. J. Blake, C. Wilson and J. B. Love, Chem. Commun., 2002,
2796.
17 Y. Shi, J. T. Ciszewski and A. L. Odom, Organometallics, 2001, 20, 3967.
For intramolecular alkene hydroamination with the same complex see;
J. A. Bexrud, J. D. Beard, D. C. Leitch and L. L. Schafer, Org. Lett.,
2005, 7, 1959.
Acknowledgements
18 D. C. Bradley and I. M. Thomas, J. Chem. Soc., 1960, 3859.
19 J. H. Espensen, Chemical Kinetics and Reaction Mechanisms, McGraw
Hill, New York, 2nd Ed, 2002.
The authors thank the National Science Foundation of the
United States (CHE-1012537) for financial support. We are also
7768 | Dalton Trans., 2011, 40, 7762–7768
This journal is
The Royal Society of Chemistry 2011
©