Group 4 Diarylmetallocenes as Bespoke Aryne Precursors for Titanium-Catalyzed [2 + 2 + 2] Cycloaddition of Arynes and Alkynes

Article abstract of DOI:10.1021/acs.inorgchem.9b01082

Despite the ubiquity of reports describing titanium (Ti)-catalyzed [2 + 2 + 2] cyclotrimerization of alkynes, the incorporation of arynes into this potent manifold has never been reported. The in situ generation of arynes often requires fluoride, which instead will react with the highly fluorophilic Ti center, suppressing productive catalysis. Herein, we describe the use of group 4 diarylmetallocenes, Cp^R₂MAr₂ (Cp^R = C₅H₅, C₅Me₅; M = Ti, Zr), as aryne precursors for the Ti-catalyzed synthesis of substituted naphthalenes via coupling with 2 equiv of an alkyne. Fair-to-good yields of the desired naphthalene products could be obtained with 1% catalyst loadings, which is roughly an order of magnitude lower than similar reactions catalyzed by palladium or nickel. Additionally, naphthalenes find broad applications in the electronics, photovoltaics, and pharmaceutical industries, urging the discovery of more economic syntheses. These results indicate that aryne transfer from a Cp^R₂M(?²-aryne) complex to another metal is a viable route for the introduction of aryne fragments into organometallic catalytic processes.

Full text of DOI:10.1021/acs.inorgchem.9b01082

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Cite This: Inorg. Chem. XXXX, XXX, XXX−XXX
Group 4 Diarylmetallocenes as Bespoke Aryne Precursors for
Titanium-Catalyzed [2 + 2 + 2] Cycloaddition of Arynes and Alkynes
Benjamin R. Reiner and Ian A. Tonks*
Department of Chemistry, University of MinnesotaTwin Cities, 207 Pleasant Street SE, Minneapolis, Minnesota 55455, United
States
S
* Supporting Information
ABSTRACT: Despite the ubiquity of reports describing
titanium (Ti)-catalyzed [2 + 2 + 2] cyclotrimerization of
alkynes, the incorporation of arynes into this potent manifold
has never been reported. The in situ generation of arynes often
requires fluoride, which instead will react with the highly
fluorophilic Ti center, suppressing productive catalysis. Herein,
we describe the use of group 4 diarylmetallocenes, CpR MAr2
2
(CpR = C5H5, C5Me5; M = Ti, Zr), as aryne precursors for the
Ti-catalyzed synthesis of substituted naphthalenes via coupling
with 2 equiv of an alkyne. Fair-to-good yields of the desired
naphthalene products could be obtained with 1% catalyst
loadings, which is roughly an order of magnitude lower than
similar reactions catalyzed by palladium or nickel. Additionally, naphthalenes find broad applications in the electronics,
photovoltaics, and pharmaceutical industries, urging the discovery of more economic syntheses. These results indicate that
aryne transfer from a CpR M(η2-aryne) complex to another metal is a viable route for the introduction of aryne fragments into
2
organometallic catalytic processes.
INTRODUCTION
■
Titanium (Ti) is an attractive substitute to expensive noble
metals owing to its natural abundance, low toxicity, and high
activity in a number of synthetically relevant bond-forming
reactions.1−3 Our laboratory has an ongoing interest in
leveraging the reactivity of multiple valence states of Ti toward
the modular assembly of complex small molecules.4−13 While
TiII intermediates have been invoked in a multitude of catalytic
and stoichiometric transformations, historically the chemistry
of low-valent Ti species is weighted toward alkyne cyclo-
addition reactions such as alkyne cyclotrimerization.14 Alkyne
cyclotrimerization is a powerful synthetic tool that allows the
rapid construction of aromatic hydrocarbons through the
formation of three bonds in one pot.
Figure 1. Examples of naphthalene cores in drug molecules.
Naphthalenes and phenanthrenes have important applica-
tions in pharmaceuticals,15 photovoltaics,16 and the design of
functional electronic materials.17 Moreover, substituted naph-
techniques for the in situ generation of arynes have turned
toward fluoride-based activators, which enjoy mild reaction
thalenes exhibit a myriad of biologically relevant activities
including anticancer, antidepressant, antiinflammatory, anti-
conditions and easily accessible aryne precursors (Figure 2,
viral, and antihypertensive activities.15 For example, Naproxen,
marketed as Aleve, is a nonsteroidal antiinflammatory drug
(NSAID) that is very commonly prescribed for the treatment
of arthritis (Figure 1).
top).18 These methods avoid the use of strong reductants such
as magnesium(0) or organolithiums, synthetically elaborate
aryne precursors such as those employed in the hexadehydro
The synthesis of naphthalenes via formal [2 + 2 + 2]
cycloaddition requires the engagement of key metallacyclic
intermediates with an in situ generated reactive aryne
substrate. Fast generation and capture of a stoichiometric
aryne reagent is essential for selective trimerization. Modern
Special Issue: Celebrating the Year of the Periodic Table: Emerging
Investigators in Inorganic Chemistry
Received: April 13, 2019
© XXXX American Chemical Society
A
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The aryne intermediate can be stabilized via the addition of L-
type ligands33 or C−H activation of the cyclopentadienyl
ligands.32,34 Given this rich chemistry, we hypothesized that
this putative benzyne adduct could serve as an aryne coupling
partner via transfer from the metallocene fragment to a
catalytic metal center. Unlike other aryne generation methods,
we speculated that this simple and safe thermal generation of
arynes would be compatible with Ti-mediated catalysis.
Herein, we report the investigation of group 4 diary-
lmetallocenes as aryne precursors for the catalytic synthesis of
substituted naphthalenes (Figure 2, bottom). Good yields of
naphthalene products could be obtained with catalyst loadings
as low as 1%, which is an order of magnitude lower than similar
reactions catalyzed by Pd21−23 or Ni.24 Overall, our experi-
ments demonstrate that aryne transfer from a CpR M(η2-
2
aryne) complex to another metal is a viable route for the
introduction of aryne fragments into organometallic catalytic
processes.
RESULTS AND DISCUSSION
Model Reactions. We began our investigation by choosing
a suitable model reaction (Table 1). Diphenylacetylene was
■
a
Table 1. Screening of Reaction Conditions
Figure 2. Modern methods of in situ aryne generation.
Diels−Alder (HDDA) reaction,19 or thermally activated
substrates such as diazonium salts, which can pose serious
operational hazards.20
b
c
d
entry
CpR2M
catalyst
% yield 2
% yield 3
While catalytic synthesis of naphthalenes and phenanthrenes
has been achieved using palladium (Pd),21−23 nickel (Ni),24
and rhodium25 (Figure 2, middle), analogous reactivity with Ti
has never been reported. The prohibitive fluorophilicity of Ti
[Ti−F bond dissociation energy (BDE) = 138 kcal/mol],26,27
which makes in situ aryne generation with fluoride
incompatible with most potential Ti catalysts, likely contrib-
utes to this conspicuous absence. Considering the ubiquity of
Ti-mediated trimerization reactions and the high catalytic
activity reported therein, we were inspired to design aryne
precursors that could be safely activated under conditions
compatible with Ti.
The thermolysis and prolific ensuing insertion chemistry of
group 4 diarylmetallocenes is well-established (Figure 3).28,29
This chemistry is proposed to proceed via a putative aryne−
metallocene adduct, which is formed via β-abstraction under
relatively mild conditions (∼80 °C). This aryne adduct can
then be intercepted by a variety of unsaturated small molecules
including alkynes, alkenes, nitriles, CO2, N2O, and N2.30−32
e
f
1
2
3
4
5
6
7
8
9
Cp2Ti
Cp2Ti
TiI4(THF)2
TiI4(THF)2
TiI4(THF)2
TiI4(THF)2
TiI4(THF)2
>95
0
0
71
55
trace
trace
0
0
>95
0
0
0
0
0
0
0
Cp*2Ti
Cp*2Zr
Cp*2Zr
Cp*2Zr
Cp*2Zr
Cp*2Zr
Cp*2Zr
TiBr4(THF)2
TiCl4(THF)2
g
TiI4(THF)2
none
0
a
Reaction conditions: metallocene (0.05 mmol), diphenylacetylene
(0.05 mmol), catalyst (0.05−0.0005 mmol of Ti), Zn0 (0.05−0.0005
b
mmol), 0.5 mL of C6H5Br, 115 °C, 3 h. Cp = cyclopentadiene; Cp*
c
= pentamethylcyclopentadiene. Determined by quantitative GC-FID
with respect to an internal standard (1,3,5-trimethoxybenzene).
d
Determined by 1H NMR with respect to an internal standard
e
(1,3,5-trimethoxybenzene). Reaction conducted with 100 mol %
f
TiI4(THF)2. Reaction conducted with 0.1 mmol of diphenylacety-
g
lene. Reaction conducted in the absence of Zn0.
chosen as the alkyne coupling partner owing to the low
proclivity toward self-cyclotrimerization and the high symme-
try expected for the desired naphthalene products. Diphenylti-
tanocene was chosen as an initial benzyne precursor owing to
its ease of synthesis. All reactions were carried out in the
presence of stoichiometric or catalytic amounts of titanium
tetrahalide catalyst precursors and zinc(0) (Zn0), along with
equimolar amounts of diphenylacetylene and a metallocene
benzyne precursor. Access to the active TiII catalytic species is
proposed to occur via the initial reduction of titanium
tetrahalide to TiIII by Zn0 followed by disproportionation to
TiII and TiIV.35 The product yields were determined by
quantitative gas chromatography flame ionization detection
Figure 3. Group 4 diarylmetallocenes undergo β-hydrogen
abstraction, leading to aryne adducts that can be intercepted via
insertion.
B
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(GC-FID) with respect to an internal standard (trimethox-
ybenzene).
partner. We hypothesized that only alkynes with sufficient
steric bulk could engage in productive catalysis by avoiding the
formation of parasitic metalloindane species. A simple
structure−activity relationship was developed in order to
qualitatively correlate the alkyne steric size to reactivity. While
several models for substituent size have been developed,40−45
A values proved sufficient. The A values for both alkyne
substituents were summed to give a “composite A value” and
plotted against the total yield of naphthalene products formed
under catalytic conditions (Figure S20).
Under stoichiometric conditions, diphenyltitanocene served
as a suitable benzyne precursor and generated 1,2,3,4-
tetraphenylnaphthalene (2) in near-quantitative yields (Table
1, entry 1). However, under catalytic conditions, the
quantitative formation of metalloindane species 3 was observed
(Table 1, entry 2). This suggests that interception of the
putative metallocene−benzyne adduct with diphenylacetylene
is kinetically competitive to productive catalysis. Prolonged
thermolysis of metalloindane 3 in the presence of additional
diphenylacetylene does not afford naphthalene 2, demonstrat-
ing that 3 is likely an off-cycle thermodynamic sink. We
considered that increasing the steric bulk of the Cp rings (Cp =
cyclopentadiene) on the titanocene might suppress the
formation of parasitic metalloindane species such as 3.
However, the substitution of Cp2TiPh2 for Cp*2TiPh2 (Cp*
= pentamethylcyclopentadiene) led to no product formation
(Table 1, entry 3). Cp*2TiPh2 is known to favor Ti−C bond
homolysis to form phenyl radical rather than β-abstraction to
afford the desired benzyne adduct and benzene.36
Alkynes with composite A values of below 4 delivered
naphthalene products in zero or very poor yield (Table 2,
a
Table 2. Alkyne Partner Substrate Scope
Bearing in mind that the zirconium (Zr)−phenyl (Ph)
bonds in Cp*2ZrPh2 (BDE ∼ 75 kcal/mol) have a higher BDE
than analogous Ti−Ph bonds (BDE ∼ 67 kcal/mol),37 we
were prompted to consider Cp*2ZrPh2 as a benzyne precursor
in the hopes of promoting β-abstraction over extrusion of the
phenyl radical. Indeed, using Cp*2ZrPh2 as the benzyne
precursor, 2 was delivered in 71% yield with no detectable
amount of 3 (Table 1, entry 4). Reactions using a 1:2
stoichiometry of Cp*2ZrPh2 and diphenylacetylene afforded 2
in slightly lower yields, likely owing to decomposition of the
incipient Zr−benzyne complex (entry 5). Control reactions
conducted in the absence of catalytic Ti or Zn (Table 1, entries
8 and 9) showed no formation of 2. Other TiX4 precatalysts
(Table 1, entries 6 and 7) only afforded trace amounts of 2,
demonstrating the importance of iodide ligands to catalysis.
We have previously observed that TiI4-based precatalysts are
significantly more productive for alkyne trimerization than
TiCl4-based precatalysts,7 likely due to the decreased donor
ability of iodide (I−) compared to chloride (Cl−).38 Reactions
performed at lower temperatures (80 or 100 °C) afforded no
naphthalene product; however, evolution of stoichiometric
amounts of benzene signaled that β-hydrogen abstraction of
Cp*2ZrPh2 did occur. Moreover, low-valent Ti is competent
for trimerization under mild conditions.39 Thus, the high
reaction temperature may be more readily associated with the
barrier for the generation of an active TiII species. Notably, 2 is
furnished in good yield at 1 mol % catalyst loading, while
similar reactions employing Ni or Pd catalysts require 10 mol
% catalyst loading to achieve comparable yields. This highlights
the inherent advantage of utilizing Ti-based catalyst systems.
1H NMR spectra of catalytic reactions show decomposition
of Cp*2ZrII to multiple ill-defined species. In order to ascertain
whether any of these species are catalytically competent, the
cycloaddition of tetraphenylnaphthalene was attempted using
catalytic amounts of Cp*2ZrCl2/Zn. This system did not afford
tractable amounts of naphthalene product. Similarly, attempts
to catalyze the cyclotrimerization of 3-hexyne with Cp*2ZrCl2/
Zn were also unsuccessful. These observations suggest that
Cp*2ZrII-borne species are likely not involved in promoting
cycloaddition catalysis.
% yield
b
% yield
% yield
d
A
c
e
R1, R2
4:5:6
7
trimer
value
1a
1b
1c
1d
1e
1f
1g
1h
1i
Et, Et
5
4
86
88
8
9
3.5
3.6
2.5
3.0
3.9
4.7
4.8
6.0
6.0
6.0
nPr, Pr
TMS, H
Ph, H
n
0
0
0
>95
>95
>95
>95
19
0
0
0
0
0
0
iPr, Me
Ph, Me
Ph, Bu
Ph, Ph
p-CF3Ph,p-CF3Ph
0
0
n
0:4:10
71
64
78
16
24
19
15
1j
p-OMe-Ph,p-OMe-
Ph
1k
1l
p-tBuPh,p-tBuPh
76
0
0
0
0
22
0
0
6.0
5.5
4.3
6.6
Ph, TMS
8:14:26
0:34:31
0
1m nBu, TMS
t
1n
Me, Bu
0
a
Reaction conditions: metallocene (0.05 mmol), alkyne (0.05 mmol),
catalyst (0.0005 mmol of Ti), Zn0 (0.0005 mmol), 0.5 mL of C6H5Br,
b
115 °C, 3 h. Cp* = pentamethylcyclopentadiene. Determined by
quantitative GC-FID with respect to an internal standard (1,3,5-
trimethoxybenzene). Determined by H NMR with respect to an
c
1
d
internal standard (1,3,5-trimethoxybenzene). % yield of all alkyne
cyclotrimer regioisomers; determined by 1H NMR with respect to an
e
internal standard (1,3,5-trimethoxybenzene). Sum of both alkyne
substituent A values.
alkynes 1a−1f). These reactions were dominated by formation
of the corresponding metalloindanes 7a−7f. In the cases of 3-
hexyne (Table 1, alkyne 1a) and 4-octyne (Table 1, alkyne 2a),
alkylated benzenes formed via alkyne trimerization were
observed in low yields (∼10%).
Composite A values between 4 and 6 appear necessary but
are not sufficient to furnish naphthalene products 4−6 in
acceptable yields (Table 2, alkynes 1f−1m). The product
selectivity for asymmetric alkynes appears entirely substrate-
biased in accordance with literature precedent.21−24 Notably,
Alkyne Scope. With optimized reaction conditions in
hand, we set out to explore the scope of the alkyne coupling
C
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slight changes to the steric profile of the alkyne coupling
partner can substantially affect the catalytic performance.
While phenylpropyne affords the metalloindane complex 7f as
the exclusive product (Table 2, alkyne 1f), phenylhexyne
furnished the metalloindane complex 7g in a substantially
lower yield and produced both naphthalene and trimer
products in comparable yields (∼15%; Table 2, alkyne 1g).
The difference in the A values between Me and nBu is only 0.1
kcal/mol, illustrating how even small steric perturbations can
manifest in observable differences in the catalytic performance.
A substrate screen utilizing para-substituted diarylalkynes
shows a slight yield dependence on the electronic character of
the alkyne (Table 2, alkynes 1i−1k). More electron-rich alkyne
coupling partners deliver naphthalene products in higher
yields. Alkynes with composite A values exceeding 6 did not
convert under the reaction conditions (Table 2, alkyne 1n)
likely owing to the steric strain associated with the formation
of metallacyclic intermediates. While limited in overall scope,
the reactivity of the alkyne coupling partners appears to be
more closely governed by the steric rather than electronic
properties of the alkyne. Although the reaction yields delivered
by productive alkynes are moderate, the relatively high
turnover numbers are encouraging, and current work is
directed toward developing more robust catalytic systems.
Only trace amounts of benzyne homocoupled products
could be detected in the reactions with any alkynes.
Thermolysis of Cp*2ZrPh2 in the absence of alkyne or catalyst
also only affords trace yields of benzyne homocoupling
products. This stands in contrast to other synthetically relevant
metal−benzyne adducts of ruthenium,46 Pd,21−23 and Ni,24
where benzyne coupling products such as biphenylene or
triphenylene are furnished in more substantial yields. Addi-
tionally, Ti species generated during catalysis do not appear to
promote the formation of metalloindane byproducts. The
propensity of alkynes to form metalloindanes is identical in the
presence or absence of catalytic Ti.
Proposed Mechanism. Synthetic success with a fairly
unusual benzyne precursor prompted us to consider the
mechanistic aspects of the ensuing catalytic reaction. The most
likely pathway for naphthalene synthesis is as follows (Figure
4): after generation of an active TiII species (I) by the Zn
reductant, 2 equiv of alkyne undergo oxidative coupling to
yield a titanacyclopentadiene (II). Next, the titanacyclopenta-
diene reacts with the in situ generated Zr−benzyne adduct,
either via transmetalation of the benzyne to Ti or direct [4 + 2]
cycloaddition of Zr−benzyne to the diene fragment. The
resulting bound arene can either then dissociate to regenerate
the reduced TiII species I or undergo associative displacement
by alkyne to generate II. We favor II over titanaindane (Figure
4a) formation owing to the observed product and byproduct
selectivity: catalysis results in the formation of only
naphthalenes and a small amount of hexasubstituted benzene
as a consequence of alkyne cyclotrimerization. In principle, a
titanaindane intermediate (or a Ti−benzyne adduct) could
result in the formation of phenanthrene or triphenylene
byproducts, neither of which are observed.
Figure 4. Plausible mechanism for the formation of naphthalene
products from aryne/alkyne cyclization.
Conducting the coupling reaction with equimolar amounts of
Cp*2ZrPh2 and PhCCPh in the presence of 10% py3TiI2(NPh)
and 3-hexyne afforded naphthalene 2 in 60% yield (Figure 5).
Figure 5. Zn-free reactions yield significant amounts of 2, indicating
that Zn is not critically important for catalysis.
3-Hexyne was chosen as a sacrificial alkyne owing to its high
reactivity in the formation of the requisite pyrrole catalyst
activation product. The formation of 2 in in the absence of Zn
demonstrates that Zn is “innocent”not likely participating as
a transmetalation agent or Lewis acid during the catalytic
synthesis of naphthalenes.
Thus, benzyne incorporation into titanacyclopentadiene II
likely occurs via direct engagement of the Zr−benzyne adduct
with Ti, through either transmetalation (Figure 4c) or direct [4
+ 2] cycloaddition with II (Figure 4d). Thermolysis of
Cp*2ZrPh2 in the presence of furan and cyclohexadiene as
benzyne traps yielded no products from free benzyne capture
We were prompted to interrogate the role of Zn during
catalysis because the ZnX2 byproduct of Ti reduction could
facilitate either transmetalation or act as a Lewis acidin
either case possibly impacting how naphthalenes are formed.
We previously reported the generation of TiII trimerization
catalysts through the alkyne-triggered reduction of titanium
imidos7 instead of Zn reduction of titanium halides.
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(Figure 4c). Instead, only the tuck-in complex V (Figure 6)
was observed. Identical benzyne trap experiments were
substituted analogues of V (Figure S21), demonstrating that
isomerization is energetically facile and not dictated by Cp*
ring sterics. This isomerization behavior is consistent with the
observed reactivity of the analogous Cp2Zr(tolyl)2 complex.47
Overall, the mechanistic data are most consistent with the
direct engagement of a Zr−aryne adduct with a titanocyclo-
pentadiene to afford the observed naphthalene products.
Future work is focused on elucidating the fine details of this
transmetalation event and how it may affect or effect product
selectivity.
Figure 6. Free benzyne trap experiments led only to formation of the
tuck-in complex V.
CONCLUSIONS
■
Cp*2ZrPh2 was employed as a benzyne precursor in a Ti-
catalyzed formal [2 + 2 + 2] cycloaddition of arynes and
alkynes to form highly substituted naphthalene products. Bulky
Cp* rings were required to suppress the formation of parasitic
metalloindane byproducts. A screen of potential alkyne
coupling partners showed that formation of the desired
naphthalene products is best correlated to alkyne steric rather
than electronic properties. The product selectivity toward
naphthalenes over other potential coupling products including
triphenylenes or phenanthrenes suggests a mechanism in
which a titanacyclopentadiene is intercepted by a Zr−benzyne
adduct. An isomerization probe substrate, 8, was designed to
interrogate this possibility. The product distribution arising
from this substrate implicates isomerization through a Zr−
aryne adduct during productive catalysis.
While the yields of naphthalene products are modest, the
relatively low catalyst loadingnearly an order of magnitude
lower than comparable systems with Ni or Pdis encouraging.
The high oxo- and fluorophilicity of Ti could be circumvented
with an unusual aryne precursor, demonstrating a novel way to
introduce aryne fragments into organometallic catalytic
processes. Future work is directed toward expanding the
scope of reactions that incorporate these metallocene-born
arynes in the hopes of assembling more complex small
molecules and understanding the mechanistic implications of
aryne transmetalation in catalysis.
conducted with Cp2TiPh2, which cannot form a tuck-in
complex, but still no products assignable to free benzyne
capture were detected. Notably, the Zr tuck-in complex V does
not exhibit evidence of interconversion to the benzyne adduct
IV up to 90 °C;32 however, a small yet reactive population of
the benzyne adduct may be responsible for direct trans-
metalation from Zr to Ti. How the bulky zironocene fragment
may hinder formation of the requisite transition state(s)
needed for transmetalation remains a lingering question.
In order to determine whether the Cp*2Zr benzyne adduct
IV is indeed a relevant species during catalysis, we examined
substituted aryne coupling partner 8 as an isomerization probe
to detect the intermediacy of an aryne complex (Figure 7).
Metallocene aryne complexes that can be stabilized via C−H
activation of the Cp* ring (as in V) are expected to “proton
walk” via the successive protonation of an incipient aryne
intermediate (Figure 7).34 By measurement of the product
distribution, the aryne adduct isomer of Cp*2Zr(C6H3Me) can
be implicated as an on-cycle species in catalysis if isomerization
occurs. Indeed, after complex 8 was subjected to the catalytic
reaction conditions, a ∼2:1 mixture of 6-methyl-1,2,3,4-
tetraphenylnaphthalene (9) and 5-methyl-1,2,3,4-tetraphenyl-
naphthalene (10) was afforded in 64% yield. The formation of
naphthalene 10 can only arise following isomerization via an
aryne adduct and thus implicates the intermediacy of a
complex such as IV during catalysis (Figure 6). Notably,
thermolysis of 8 shows almost immediate scrambling of the
tolyl group to an equimolar mixture of ortho-, meta-, and para-
EXPERIMENTAL SECTION
General Considerations. All air- and moisture-sensitive com-
pounds were manipulated in a glovebox under a N2 atmosphere.
■
Figure 7. Formation of 10 implicating isomerization through a Zr−aryne adduct.
E
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Benzene, pentane, diethyl ether (Et2O), tetrahydrofuran (THF), and
toluene were sparged with ultrahigh-purity argon and dried via
passage through drying columns using a solvent purification system
from Pure Process Technologies. All solvents were stored over 4 Å
molecular sieves. C6D5Br was dried over CaH2 and distilled before
use. All high-boiling liquid reagents were freeze−pump−thawed three
times, brought into the glovebox, diluted in hexanes or Et2O, passed
through activated basic alumina, pumped dry in vacuo, and checked
by 1H NMR in CDCl3 to ensure the dryness. 1,2-Bis(4-tert-
butylphenyl)ethyne,48 bis(4-methoxyphenyl)ethyne,49 bis(4-
trifluoromethylphenyl)ethyne,50 Cp2TiPh2,36 Cp*2TiPh2,36
Cp*2ZrPh2,32 and p-tolyllithium51 were prepared according to
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: itonks@umn.edu.
ORCID
Ian A. Tonks: 0000-0001-8451-8875
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
1
reported procedures. H and 13C NMR spectra were collected on a
Financial support was provided by the National Institutes of
Health (Grant 1R35GM119457) and the Alfred P. Sloan
Foundation (I.A.T. is a 2017 Sloan Fellow). Equipment for the
Chemistry Department NMR facility was supported through a
grant from the National Institutes of Health (Grant
S10OD011952) with matching funds from the University of
Minnesota.
Bruker Avance III HD NanoBay 400 MHz spectrometer. Chemical
shifts are reported with references of the residual protiosolvent
impurity: 1H (s, 7.26 ppm for CHCl3), 13C (t, 77.16 ppm for CDCl3).
GC-FID was performed using an Agilent 7890 series gas chromato-
graph system (HP-5 column, 30 m length, 0.32 mm inside diameter,
0.25 μm film thickness; temperature program = 50 °C for 1.5 min, 20
°C/min to 290 °C, and held for 6.5 min) equipped with a Polyarc
reactor for quantitative C detection.
General Procedure for Catalytic Reactions. In an N2-filled
glovebox, a vial was charged with Cp*2ZrPh2 (25.8 mg, 0.05 mmol, 1
equiv), alkyne (0.05 mmol, 1 equiv), TiI4(THF)2 (0.350 mg, 0.0005
mmol, 0.01 equiv), C6D5Br (0.5 mL), and trimethoxybenzene (8.4
mg, 0.05 mmol, 1 equiv) as an internal standard. The reaction mixture
was transferred into an NMR tube charged with Zn (0.1−0.3 mg,
0.0015−0.0030 mmol, 0.03−0.05 equiv). The reaction was heated at
115 °C for 3 h in a preheated oil bath outside the glovebox. After
being cooled to ambient temperature, the reaction was concentrated
in vacuo, and the resulting residue was dissolved in ethyl acetate
(EtOAc) and passed over a plug of silica. Reactions using
tetramethylsilane−alkynes that afforded naphthalene products were
concentrated in vacuo and mixed with 10 mL of 2 M HCl in
methanol. After the mixture was stirred for 2 h, it was diluted by 20
mL of deionized water and extracted by EtOAc (3 × 15 mL). The
organic layer was washed with brine and dried by MgSO4. All
reactions were analyzed by 1H NMR in a CDCl3 solvent, and spectra
containing naphthalene products were compared to literature
examples.24,52−58 NMR samples were then diluted with dichloro-
methane (CH2Cl2) and analyzed by GC-FID. Product yields were
determined by quantitative GC-FID.
Synthesis of 8. A solution of p-tolyllithium (68 mg, 0.69 mmol, 3
equiv) in THF (2 mL) was added dropwise to a stirring solution of
Cp*2ZrCl2 (100 mg, 0.23 mmol, 1 equiv) in Et2O (5 mL) at −30 °C.
The reaction was allowed to warm to room temperature and stirred
for 6 h, affording a hazy orange solution. CH2Cl2 (0.5 mL) was added
dropwise to quench the remaining organolithium species. The
reaction solvent was removed in vacuo, and the resulting residue
was extracted into Et2O and filtered over Celite. The solution was
concentrated to quarter volume and left to stand in the freezer
overnight. The resulting white precipitate was collected and washed
with hexanes (3 × 2 mL). 8 was isolated as a white microcrystalline
powder (yield: 78 mg, 63%). 1H NMR (400 MHz, CDCl3): δ 7.11 (d,
2H, t, 3JH−H = 7.4 Hz, tolyl H), 6.97−6.91 (m, 6H), 2.26 (s, 6H, tolyl
Me), 1.64 (s, 30H, Cp*-Me). 13C{1H} NMR (101 MHz, CDCl3): δ
189.1 (s, 2C, Zr C), 136.7 (s, 2C, tolyl Me), 134.11 (s, 2C, o-tolyl C),
133.0 (s, 2C, o-tolyl C), 126.9 (s, 1C, m-tolyl C), 126.6 (s, 1C, m-tolyl
C), 120.3 (s, 2C, m-tolyl C), 21.3 (s, 2C, tolyl Me), 12.3 (s, 10C, Cp*
Me). Anal. Calcd for C34H44Zr: C, 75.08; H, 8.15. Found: C, 75.38;
H, 8.21.
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ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.inorg-
chem.9b01082.
■
S
Spectroscopic (NMR) and quantitative GC-FID data
(PDF)
F
DOI: 10.1021/acs.inorgchem.9b01082
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