Titanocene(II)-catalyzed hydroboration of carbonyl compounds

Article abstract of DOI:10.1021/om300828m

Titanocene bis(catecholborane), [Cp₂Ti(HBcat)₂] (1), catalyzes the room-temperature hydroboration of carbonyl compounds by pinacolborane (HBpin) rapidly, cleanly, and chemoselectively. Aryl aldehydes and ketones produced alkoxypinacolboronate esters in moderate to high yields in 2 h, and facile hydrolysis of alkoxypinacolboronate esters over silica occurred cleanly to afford alcohols in good yields. Complex 1 demonstrated a preference for C=O bonds over C=C bonds in both conjugated and nonconjugated enones. Kinetic studies of the catalytic hydroboration of a series of acetophenones showed that electron-poor substrates undergo the reaction more quickly than electron-rich substrates. This result is consistent with the proposed mechanism, in which stronger π-acids should undergo C=O bond cleavage more readily. Computational studies using benzophenone and benzaldehyde showed that the hydroboration is spontaneous and likely proceeds via intermediates that are best described as Ti metallacycles whose structures are not significantly altered by substrate steric differences. This result indicates that similarities in the electronic properties of benzophenone and benzaldehyde supersede their steric differences in determining reaction outcomes.

Full text of DOI:10.1021/om300828m

Article
pubs.acs.org/Organometallics
Titanocene(II)-Catalyzed Hydroboration of Carbonyl Compounds
Abdulafeez A. Oluyadi, Shuhua Ma, and Clare N. Muhoro*
Department of Chemistry, Fisher College of Science and Mathematics, Towson University, 8000 York Road, Towson, Maryland
21252, United States
S
* Supporting Information
ABSTRACT: Titanocene bis(catecholborane), [Cp2Ti(HBcat)2] (1), catalyzes the room-temperature hydroboration of
carbonyl compounds by pinacolborane (HBpin) rapidly, cleanly, and chemoselectively. Aryl aldehydes and ketones produced
alkoxypinacolboronate esters in moderate to high yields in 2 h, and facile hydrolysis of alkoxypinacolboronate esters over silica
occurred cleanly to afford alcohols in good yields. Complex 1 demonstrated a preference for CO bonds over CC bonds in
both conjugated and nonconjugated enones. Kinetic studies of the catalytic hydroboration of a series of acetophenones showed
that electron-poor substrates undergo the reaction more quickly than electron-rich substrates. This result is consistent with the
proposed mechanism, in which stronger π-acids should undergo CO bond cleavage more readily. Computational studies using
benzophenone and benzaldehyde showed that the hydroboration is spontaneous and likely proceeds via intermediates that are
best described as Ti metallacycles whose structures are not significantly altered by substrate steric differences. This result
indicates that similarities in the electronic properties of benzophenone and benzaldehyde supersede their steric differences in
determining reaction outcomes.
reports of carbonyl hydroboration with titanocene catalysts,
whose chiral ansa derivatives would be potentially useful in
enantioselective catalysis.30−32 This application would be
similar to asymmetric hydrosilylation of ketones, which has
been well-studied and is a valuable route to chiral secondary
alcohols.33−37
INTRODUCTION
■
The hydroboration of carbonyl compounds is an efficient
synthetic route to alcohols, and stoichiometric methods utilize
boranes1−6 to synthesize borates, which are then hydrolyzed to
alcohols. Metal-catalyzed hydroboration of ketones and
aldehydes has also been reported, and examples include
systems based on Ga,7 In,7 Mo(IV),8 Rh(I),9 Ru(II),10
Ti(IV),11−13 and Zn(II).14 Hill and co-workers very recently
reported a Mg alkyl catalyst that efficiently hydroborates
aldehydes and ketones.15 The Mg, Zn, and Ti systems
exemplify metal-catalyzed hydroboration reactions that do not
utilize costly and/or toxic mid to late transition metals.
Similarly, we seek to provide carbonyl hydroboration catalysts
based on earth-abundant, low-toxicity metals as cheaper and
environmentally benign alternatives to more expensive rare-
metal systems. In this regard, titanium is an attractive choice,
because it is the fourth most abundant metal in the earth’s crust
(0.86% by weight) after aluminum, iron, and magnesium.16 The
metal’s abundance, coupled with its vast catalytic utility, make
titanium a strong candidate for synthesizing versatile, cheap
catalysts.17−19
We have reported the use of titanocene(II) bis-
(catecholborane), [Cp2Ti(HBcat)2] (1), in the highly efficient
hydroboration of vinylphosphines to yield phosphanyl-
(organyl)boranes in short reaction times and under mild
conditions.38 This complex also performs rapid and high-
yielding anti-Markovnikov hydroboration of vinylarenes.39 The
mechanism of catalytic hydroboration of vinylarenes by
complex 1 is known to proceed via a two-step process (Scheme
1). Initial dissociation of catecholborane (HBcat) from complex
1 generates a mono(catecholborane) intermediate, the active
catalyst, which undergoes vinylarene coordination in the rate-
limiting step to generate an unobserved vinylarene−mono-
(catecholborane) intermediate. Rapid elimination of alkylca-
techolboronate ester occurs with concomitant coordination of
HBcat.
As part of our ongoing effort to explore the scope of the
catalytic chemistry of complex 1, we report on its hydro-
boration of carbonyl compounds with pinacolborane (HBpin)
Examples of titanium-catalyzed hydroboration of carbonyls
are limited to inorganic titanium(IV) oxides used in the
catalytic hydroboration of carbonyls with catecholborane.11−13
Titanium-catalyzed hydroboration of carbonyls using pinacol-
borane,20−29 a reagent more robust than catecholborane, is yet
unreported. Further, to our knowledge there have been no
Received: August 28, 2012
Published: December 19, 2012
© 2012 American Chemical Society
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Scheme 1. Mechanism of Catalytic Hydroboration of
Alkenes by Complex 1
Table 1. Scope of Carbonyl Hydroboration Catalyzed by
Complex 1
a
a
All reactions were performed using 5 mol % of complex 1, at room
as the hydroborating agent. Kinetic and computational studies
provide insight into the substrate preferences of complex 1. The
system reported herein is the first example of a titanium-based
organometallic catalyst used for the hydroboration of carbonyl
compounds.
temperature and in C6D6 solvent. NMR percent yields were
determined via H NMR spectroscopy of reaction mixtures after 2.5
h using Cp2Fe as internal standard. Other conditions: [substrate] = 2.4
× 10−1 M; [pinacolborane] = 2.4 × 10−1 M; [complex 1] = 1.2 × 10−2
M. Isolated products were obtained after 2 h of reaction time.
1
RESULTS AND DISCUSSION
The hydroboration reaction, when performed in tandem with
silica-promoted hydrolysis, furnishes alcohols in good yields.
Hydroboration reactions were conducted by mixing toluene/
pentane solutions of aryl ketones (1.4 M) with toluene/
pentane solutions of pinacolborane (1.4 M) and then
immediately adding the resultant mixture to solid complex 1
(5 mol %). Solutions were stirred at room temperature for 2 h,
and completion of the reactions was confirmed by 11B NMR
spectroscopy. Alkoxypinacolboronate esters were precipitated
from crude reaction mixtures by cooling to −30 °C overnight.
Pure hydroborated products were collected in moderate to
good yields as white crystalline solids. Secondary alcohols were
isolated in good yields via silica-promoted hydrolysis of
alkoxypinacolboronate esters. Hydrolysis was performed by
passing solutions of the alkoxypinacolboronate esters in
CH2Cl2 through a silica column, providing the benefit of
hydrolysis and purification in a single step.10 Scheme 2 shows
the results for a series of benzophenone substrates.
■
Titanocene bis(catecholborane), [Cp2Ti(HBcat)2] (1), cata-
lyzes the hydroboration of aldehydes and ketones by
pinacolborane (HBpin) selectively and rapidly at room
temperature to afford alkoxypinacolboronate esters. Although
catecholborane was previously used in vinylarene hydro-
borations by complex 1,40 pinacolborane afforded cleaner
reactions in our system, likely because HBpin is a weaker π-acid
than HBcat and thus has fewer side reactions.41−43
We surveyed the utility of complex 1 with a range of carbonyl
compounds, using HBpin as the sole hydroboration reagent. A
representative set of substrates, products, and yields is
presented in Table 1. Reactions were conducted by mixing
benzene-d6 solutions of the carbonyl substrate (1 equiv) and
pinacolborane (1 equiv) with 5 mol % of complex 1 at room
temperature. The resultant mixtures were analyzed by NMR
spectroscopy over the course of 24 h. In all cases, new peaks
were immediately observed in the 11B NMR spectra between 21
and 23 ppm only, within the spectral region characteristic of
alkoxyboronate esters.44 Both aldehydes and ketones under-
went catalysis cleanly without competing side reactions, and all
reactions went to completion within 6 h.
Catalyzed reactions proceeded significantly more quickly
than uncatalyzed reactions. For example, in the catalyzed
reaction, hydroboration of 4′-chloroacetophenone yielded 88%
alkoxypinacolboronate ester product after 2.5 h, while the
uncatalyzed reaction yielded less than 5% of the hydroborated
product over the same time period. Comparison with the only
other two cases of metal-catalyzed hydroboration using HBpin
shows that complex 1 is an improvement on Clark’s Ru(II)
catalyst10 but less efficient than Hill’s Mg catalyst.15 For
example, acetophenone yields 81% alkoxypinacolboronate ester
product after 2.5 h at 20 °C with 5 mol % of complex 1 in
C6D6, while Clark’s Ru(II) catalyst gave 50% product yield after
3 days at 70 °C with 4 mol % of catalyst in C6D6.10 Hill’s Mg
catalyst yielded 94% of the same product after 4 h at 25 °C with
1 mol % catalyst loading in C6D6.15
Catalyst selectivity for CO vs CC was compared using
unsaturated ketone substrates (Scheme 3). Reactions were
conducted by mixing benzene solutions of the carbonyl
substrate and pinacolborane with 5 mol % of complex 1 at
room temperature. The resultant mixtures were analyzed by 11
B
NMR spectroscopy after 24 h. The 11B NMR spectroscopic
Scheme 2. Alcohol Synthesis via Hydrolysis of
b
Alkoxyboronate Esters
b
Percent yields are isolated yields.
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Scheme 3. Hydroboration of Unsaturated Ketones Catalyzed
by Complex 1
Figure 1. Representative linear first-order decay plot for hydroboration
of 4′-methylacetophenone.
analysis of a reaction mixture of 3-cyclohexen-1-one and HBpin
in the presence of complex 1 revealed a single resonance at 18.9
ppm in the region characteristic of alkoxyboronate esters,
indicative of HBpin addition across CO.44 No peaks were
observed between 29 and 39 ppm, within the region typical of
alkylboronate esters, indicative of hydroboration across C
C.44 Similarly, a reaction mixture of 2-cyclohexen-1-one and
HBpin in the presence of complex 1 displayed a single peak at
1
18.3 ppm. The H NMR spectrum of the reaction mixture
revealed two new vinyl peaks at δ 5.89 and 5.64 in a 1:1 ratio,
consistent with the formation of a 1,2-addition product. Thus,
substrates bearing both conjugated and unconjugated CC
and CO bonds exclusively added HBpin across the CO
bond, demonstrating the chemoselectivity of this system. This
selectivity for the CO bond of nonconjugated enones differs
from the CC bond preference by Wilkinson’s catalyst
reported by Noth.45 Further, 1,2-hydroboration of conjugated
̈
enones by complex 1 offers an alternative to the Evans/Fu 1,4-
conjugate hydroborations of conjugated enones catalyzed by
Rh(I).46
The effects of carbonyl substrate electronic properties and
steric properties on hydroboration catalyzed by complex 1 were
investigated separately on a series of acetophenones and aryl
carbonyls, respectively. To systematically investigate the effect
of electronic properties, hydroboration rates of five para-
substituted acetophenones were measured and compared.
Benzene-d6 solutions of the acetophenone substrate, pinacol-
borane, and ferrocene internal standard were added to
preweighed complex 1 and 1H NMR spectra of reaction
mixtures acquired every 60 s for at least 3t1/2. Concentrations of
acetophenone reactant were determined by integration of
aromatic protons relative to ferrocene in the 1H NMR
spectrum. Pinacolborane was used in 5-fold excess concen-
tration for pseudo-first-order kinetic conditions. Linear first-
order plots were obtained and used to determine the observed
rate constants. A representative first-order linear plot for 4′-
methylacetophenone is shown in Figure 1.
Figure 2. Hammett plot for the hydroboration of arylketones by
complex 1 (5 mol %) at 20 °C. kR = rate constant for hydroboration of
4′-substituted acetophenone; kH = rate constant for hydroboration of
acetophenone.
with similar electron properties but dramatically different steric
properties: benzophenone and benzaldehyde. Benzene-d6
solutions of the carbonyl, pinacolborane (1 equiv), and
ferrocene internal standard were added to preweighed complex
1, and the reaction mixtures were analyzed by 1H NMR
spectroscopy at room temperature. Reactions were clean and
provided hydroborated products exclusively; percent yields
were equivalent to percent conversions. Surprisingly, despite
the structural difference between the two compounds, the
percent conversions of benzophenone (90%) and benzaldehyde
(86%) were comparable after 2.5 h at room temperature (Table
1). This result suggests that steric properties may be less
important than electronic properties in carbonyl hydroboration
by our system.
The data revealed that electron-poor ketones react more
quickly than electron-rich ketones, suggesting that a process
strongly influenced by electronics, such as π-bond cleavage,
may be involved in the rate-limiting step of the reaction. The
Hammett plot presented in Figure 2 illustrates the observed
trend.
The effect of substrate sterics on hydroboration was also
investigated by comparing the reactivity of two aryl carbonyls
A mechanism for the catalytic hydroboration of carbonyls by
complex 1, analogous to the reported vinylarene hydroboration
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Scheme 4. Postulated Mechanism for Catalytic Hydroboration of Carbonyls by Complex 1
pathway (Scheme 1), is postulated in Scheme 4.39 In the
precatalytic step, the monocatecholborane intermediate
([Cp2Ti(HBcat)]) is formed via HBcat dissociation from
complex 1. This intermediate then coordinates carbonyl and
eliminates alkoxycatecholboronate ester with concomitant
HBpin or HBcat coordination. Coordination by HBcat
regenerates [Cp2Ti(HBcat)], which again hydroborates the
carbonyl to provide a second alkoxycatecholboronate ester
molecule, thus furnishing a total of two catalytic equivalents of
alkoxycatecholboronate ester. Coordination by HBpin yields
[Cp2Ti(HBpin)], the active catalyst, and the rest of the catalysis
occurs with HBpin.
In the catalytic cycle proper, carbonyl substrate slowly
coordinates [Cp2Ti(HBpin)] (step 1), in agreement with our
observation of first-order kinetics with respect to carbonyl. As
with the vinylarene hydroboration mechanism pathway,39 the
intermediate generated in step 1 is most likely a resonance
structure between a Ti(II) η2-carbonyl complex and a Ti(IV)
metallacycle. Subsequent elimination of alkoxypinacolboronate
ester product from the intermediate (step 2) occurs rapidly
upon coordination of incoming pinacolborane.
In order to explain the observed trends in substrate reactivity,
we investigated factors influencing the formation and stability
of the unobserved Ti(II) η2-carbonyl/Ti(IV) metallacyclic
intermediate. Soft titanium(II) should bind carbonyls, as it is
well-known that transition-metal centers bind carbonyls in an
η2 fashion. The stability of the resultant complexes depends on
the degree of metal−ligand back-donation, with the extent of
back-donation regulated by the metal softness and/or ligand π-
acidity.47 For example, an early report by Erker et al.
demonstrated that benzophenone binds zirconocene to form
the isolable complex Cp2Zr(η2-Ph(CO)Ph), stabilized by back-
donation from the soft Zr(II) metal center.48 In addition,
Gladysz has shown that the Re(II) fluoro ketone complex
[Cp(NO)(PPh3)Re(CH2F(CO)CH2F)]+ is more stable than
the analogous chloro ketone complex [Cp(NO)(PPh3)Re-
(CH2ClCOCH2Cl)]+, presumably due to the enhanced π-
ligand acidity and back-donation in the former.49
compared the electronic and structural properties of the two
compounds. The initial structures of both compounds were
constructed with GaussView 5.0,50 and the geometries of both
compounds were optimized using the B3PW91 method from
the Gaussian 09 package.51 The 6-31G(d,p) basis set was
adopted in these computations. The atomic charges on the
optimized structures of benzophenone and benzaldehyde were
analyzed, and the negative charge was found to be highly
localized on the carbonyl oxygen atom in both molecules.52
The net charge on benzophenone’s carbonyl group was −0.113,
and that on benzaldehyde was −0.163, indicating a slightly
higher electron density in benzaldehyde. This result is
consistent with the experimentally determined 86% conversion
for the slightly more electron rich benzaldehyde vs 90%
conversion for benzophenone. Although these values are close,
they are consistent with the hypothesis that more electron rich
substrates undergo the reaction less readily.
The relative energies of the frontier molecular orbitals of the
two molecules further rationalize these findings, and Figure 3
depicts the orbital energies of both compounds. The LUMOs
are recipients of metal electron density in the CO bond
cleavage process, and their energies are virtually identical
(−1.80 eV in benzophenone and −1.81 eV in benzaldehyde),
Computational studies provided insight into the relative
importance of substrate electronic properties vs steric proper-
ties in the catalysis. The calculations optimized the structures of
benzophenone and benzaldehyde in the gas phase and
Figure 3. Frontier molecular orbital energies of benzophenone and
benzaldehyde.
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Figure 4. Optimized structures of [Cp2Ti(HBpin)(PhC(O)Ph)] (5), [Cp2Ti(HBpin)((R)-HC(O)Ph)] (6a), and [Cp2Ti(HBpin)((S)-HC(O)Ph)]
(6b).
demonstrating the similarity of the substrates’ electrophilic
nature.
distances (1.48−1.49 Å) are slightly longer than typical B−O
covalent bonds (1.36 Å).54
The Ti−H bonds (1.76−1.77 Å) are shorter than the TiII−H
bond in [Cp2Ti(η2-Ph2SiH2)(PMe3)] (1.81 Å58) and similar to
the TiIII−H bond distances in [Cp2TiSiH2Ph]2 (1.76 Å59) and
[Cp*{C5Me4CH2(C2H5MeN)}TiH] (1.70 Å57). The Ti−B
bonds (2.46−2.48 Å) are slightly longer than that in σ-complex
1 (2.34 Å).56 These data support the structure of intermediates
5 and 6a,b as five-membered rings bearing a Ti metal center
with a formal charge greater than +2 and are best described as
resonance hybrids of a Ti(IV) metallacycle and a Ti(II) η2-
carbonyl complex (Scheme 4). However, the intermediates may
more closely resemble the metallacyclic contributor, because
the C−O bond more closely resembles a single bond,54 the Ti−
C bond is similar to that in a crystallographically characterized
Ti(IV) carbonyl complex,55 and the Ti−B bond is longer than
that in titanocene σ-complexes.56
Computations were conducted to determine possible
structures for the intermediates generated from coordination
of benzophenone and benzaldehyde to [Cp2Ti(HBpin)]. The
B3PW91 method was able to reproduce experimental geo-
metries of titanocene borane complexes53 and was therefore
adopted in this work. The LanL2DZ basis set was used for Ti,
and the 6-31G(d,p) basis set was used for all the other atoms in
geometry optimizations of all the complexes.
The optimized structures of the benzophenone complex
[Cp2Ti(HBpin)(PhC(O)Ph)] (5), the pro-R benzaldehyde
complex [Cp2Ti(HBpin)((R)-HC(O)Ph)] (6a), and the pro-S
benzaldehyde complex [Cp2Ti(HBpin)((S)-HC(O)Ph)] (6b)
are shown in Figure 4, and the structural parameters of these
complexes are given in Table 2.
Table 2. Optimized Geometries of
Free energy calculations for the catalytic hydroboration of
benzophenone and benzaldehyde confirmed that, overall,
reactions were spontaneous, indicating that the proposed
intermediate structures were reasonable. The ΔG values of the
overall reactions show that hydroboration of benzaldehyde is
slightly favored over hydroboration of benzophenone (4 kcal/
mol for pro-R benzaldehyde and 2.38 kcal/mol for pro-S
benzaldehyde); the closeness of these values is in accord with
the similarity of experimentally determined conversions.
Computations on step 1 showed that coordination of
[Cp2Ti(HBpin)] by pro-R benzaldehyde to generate complex
6a is 1.39 kcal/mol higher than coordination by pro-S
benzaldehyde to form complex 6b, indicating that 6a is slightly
less stable than 6b. In step 2, formation of the hydroborated
product from the R intermediate 6a is favored over formation
of the hydroborated product fromthe S intermediate 6b by 3.01
kcal/mol. Overall, the reaction with pro-R benzaldehyde is 1.62
kcal/mol more favorable than that with pro-S benzaldehyde,
suggesting that the benzaldehyde complex may favor an R
configuration during the catalytic cycle.
[Cp2Ti(HBpin)(PhC(O)Ph)] (5), [Cp2Ti(HBpin)((R)-
HC(O)Ph)] (6a), and [Cp2Ti(HBpin)((S)-HC(O)Ph)](6b)
bond distance [Cp2Ti(HBpin)
[Cp2Ti(HBpin)
((R)-HC(O)Ph)]
(6a)
[Cp2Ti(HBpin)
((S)-HC(O)Ph)]
(6b)
(Å)/angle
(deg)
(PhC(O)Ph]
(5)
RTi−C
2.23
2.17
2.16
2.48
1.38
1.48
1.38
1.77
68.5
141.3
99.9
103.1
103.7
RTi−B
2.47
2.46
RC−O
1.40
1.39
RO−B
1.49
1.49
RB−H
1.36
1.36
RH−Ti
1.76
1.76
Ti−C−O
C−O−B
O−B−H
B−H−Ti
H−Ti−C
65.2
67.9
153.3
100.2
104.2
105.4
150.3
101.0
103.3
106.1
The data show that the calculated C−O bond distances in all
the intermediates are between 1.38 and 1.40 Å and thus more
closely resemble a C−O bond (1.43 Å) than a CO bond
(1.20 Å).54 Indeed, the titanium(IV) complex [Cp2Ti(PMe3)-
(PhC(O)Ph)], recently reported by Norton and co-workers to
display a characteristic C−O single bond, has a C−O distance
of 1.36 Å.55 The calculated Ti−C bond lengths of 2.16−2.23 Å
are also close to the crystallographically determined Ti−C bond
length of 2.25 Å in Norton’s Ti(IV) complex. The Ti−C bond
distance is slightly longer in the benzophenone complex (5,
2.23 Å) than in the benzaldehyde complexes (6a, 2.17 Å; 6b,
2.16 Å). This modest difference may be attributed to a more
negative charge on the CO group of benzaldehyde that may
strengthen and shorten the Ti−C bond in 6a,b. The B−H
bonds (1.36−1.38 Å) are longer than the B−H bonds (1.25 Å)
of HBcat in the σ-complex 1,56 while the B−O(carbonyl) bond
CONCLUSION
■
The catalytic hydroboration of carbonyls by complex 1 is
influenced strongly by substrate electronic factors and, to a
marginal extent, by their steric factors. All acetophenone
substrates had similar steric properties at CO but differed in
electronic properties at this same site; any difference in their
hydroboration rates can be attributed exclusively to differences
in electronic properties. We found that more electron poor
carbonyls underwent reactions more quickly, perhaps because
more electron poor carbonyls experience greater metal−
carbonyl π*-back-donation and, consequently, more facile
CO bond cleavage. Thus, electron-poor carbonyls may
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Table 3. Free Energies of Reactions (kcal/mol) in the Catalytic Cycle for the Hydroboration of Benzaldehyde and
Benzophenone
Synthesis of 2-(Diphenylmethoxy)pinacolborane (4a).
more easily generate thermodynamically accessible intermedi-
ates.
Computational studies on the intermediates generated in the
hydroboration of benzophenone and benzaldehyde indicate a
metallacyclic configuration, which is a resonance hybrid
structure of the metallacyclic Ti(IV) and the Ti(II) η2-carbonyl
contributors. The structure of the intermediates does not
appear to be significantly affected by the steric differences
between benzaldehyde and benzophenone. Calculations
showed that benzophenone and benzaldehyde have similar
electronic properties at C−O and that ΔG values for the two
overall reactions were similar. We conclude that, in this
reaction, the electronic similarities in benzaldehyde and
benzophenone override their steric differences, and the two
substrates behave virtually identically. Future studies will focus
on further extending the scope of the catalysis to other
heteroatomic substrates.
A vial was charged with benzophenone (1.00 g, 5.50 mmol) and a 3/1
toluene/pentane mixture (∼4 mL), forming a clear colorless solution.
Into a separate vial was weighed 5 mol % of Cp2Ti(HBcat)2 (1; 115
mg, 0.275 mmol), and in this vial was added a solution of
pinacolborane (800 μL, 5.50 mmol) in toluene (∼2 mL). The
benzophenone solution was added by pipet to the vial containing the
catalyst and pinacolborane, and the resultant mixture was stirred for 2
h at room temperature. After this time period, the reaction mixture was
layered with pentane (∼ 2 mL) and stored for 3 h at −30 °C. The
hydroboration product precipitated from solution as a white solid. The
product was collected via vacuum filtration using a precooled frit,
washed with cold pentane, and allowed to dry. A white flaky solid was
collected (1.36 g, 4.40 mmol, 80% yield).
EXPERIMENTAL SECTION
■
General Procedures. Unless otherwise noted, all experiments
were performed using oven-dried or flamed glassware and conducted
using standard Schlenk techniques or in a VAC OmniLab System
37897 inert-atmosphere glovebox (Vacuum Atmospheres Co.,
Hawthorne, CA) equipped with an oxygen sensor (working at <1
ppm) and a refrigeration unit (−30 °C).
1H NMR (C6D6, 400 MHz): δ 7.45 (d, J = 6.7 Hz, 2H), δ 7.08 (t, J
= 6.8 Hz, 2H), δ 6.99 (t, J = 7.3 Hz, 1H), δ 6.44 (s, 1H), δ 0.967 (s,
12H). 13C{1H} NMR (C6D6, 100 MHz): δ 143.7, 128.4, 127.4, 126.8,
82.6, 78.3, 24.4. 11B{1H} NMR (C6D6, 128 MHz): 22.5 (s).
Synthesis of 2-(1-(4-Methylphenyl)-1-phenylmethoxy))-
pinacolborane (4b).
Instrumentation. 1H, 13C, and 11B NMR spectra were obtained on
a JEOL-ECS 400 MHz NMR spectrometer operating at 399.78,
100.52, and 128.27 MHz, respectively, at 19.2 °C. All 13C and 11B
1
NMR signals reported were decoupled from proton resonances. H
NMR spectra were recorded relative to residual protiated solvent. 11B
NMR and 31P NMR spectra were recorded in units of parts per million
relative to BH3·Et2O and 85% H3PO4, respectively, as external
standards.
Materials. Unless specified otherwise, all reagents were purchased
from commercial suppliers and used without further purification.
Titanocene bis(catecholborane), [Cp2Ti(HBcat)2] (1), was prepared
via the literature procedure.39 All protiated solvents were purified and
distilled from VAC solvent purifier systems, sparging with nitrogen gas.
Deuterated solvents were refluxed and distilled by vacuum transfer
from purple solutions containing sodium benzophenone. Silica gel
(30−200 mesh) was used for hydrolysis of boronate ester products.
The procedure for the synthesis of 1,1-diphenylmethanol was repeated
using 4-methylbenzophenone (1.00 g, 5.10 mmol) instead of
benzophenone. The product was collected as a white flaky solid
(1.14 g, 3.52 mmol, 69% yield).
1H NMR (C6D6, 400 MHz): δ 7.48 (d, J = 8.0 Hz, 2H), 7.39 (d, J =
4.0 Hz, 2H), 7.10 (t, J = 8.0 Hz, 2H), 7.00 (t, J = 4.0 Hz, 1H), 6.92 (d,
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J = 8.0 Hz, 2H), 6.46 (s, 1H), 2.03 (s, 12 H). 13C{1H} NMR (C6D6,
100 MHz): 140.9, 136.7, 129.1, 128.4, 128.0, 127.7, 127.3, 126.8,
126.7, 82.6, 78.3, 24.4, 20.8. 11B{1H} NMR (C6D6, 128 MHz): 21.9
(s).
Synthesis of 2-(1-(4-Methoxyphenyl)-1-phenylmethoxy))-
pinacolborane (4c).
1H NMR (C6D6, 400 MHz): δ 7.34 (m, 4H), 7.26 (m, 3H), 6.85 (d,
J = 8.7 Hz, 2H), 5.81 (d, J = 2.2 Hz, 1H), 3.77 (s, 3H), 2.33 (d, J = 3.2
Hz, 1H). 13C{1H} NMR (C6D6, 100 MHz): δ 159.1, 144.1, 136.3,
126.5, 113.9, 77.5, 77.2, 76.9, 55.4.
Hydroboration of Acetophenone by Pinacolborane Cata-
lyzed by Complex 1. A vial was charged with acetophenone (56 μL,
0.478 mmol) in C6D6 (1 mL), and to the resultant solution were
added pinacolborane (69 μL, 0.478 mmol) and 200 μL of a 0.645 M
solution of Cp2Fe in C6D6 (internal standard). The resultant mixture
was transferred into a vial containing preweighed 5 mol % of complex
1 (10 mg, 0.00239 mg) and stirred at room temperature. The resultant
mixture was analyzed by NMR spectroscopy after 24 h. NMR yields
were determined by measuring the integrals of the product methyl
peaks or aromatic peaks and the cyclopentadienyl peaks of the internal
standard.
1H NMR (C6D6, 400 MHz): δ 7.35 (d, J = 7.3 Hz, 2H), 7.13 (t, J =
7.8 Hz, 2H), 7.03 (t, J = 7.3 Hz, 1H), 5.40 (q, J = 6.4 Hz, 1H), 1.44 (d,
J = 6.4 Hz, 3H), 1.00 (s, 6H), 1.01 (s, 6H). 11B{1H} NMR (C6D6): δ
25.8 (s).
The procedure for the synthesis of 1,1-diphenylmethanol was repeated
using 4-methoxybenzophenone (1.0 g, 4.71 mmol) instead of
benzophenone. The product was collected as a white flaky solid
(1.49 g, 4.10 mmol, 87% yield).
Hydroboration of 4′-Chloroacetophenone by Pinacolbor-
ane Catalyzed by Complex 1. A procedure identical with that
described for acetophenone was repeated using 4-chloroacetophenone
1H NMR (C6D6, 400 MHz): δ 7.48 (d, J = 8.0 Hz, 2H), 7.36 (d, J =
12 Hz, 2H), 7.12 (t, J = 8.0 Hz, 2H), 7.02 (t, J = 8.0 Hz, 1H), 6.70 (d,
J = 12 Hz, 2 H), 6.43 (s, 1H), 3.23 (s, 3H), 0.99 (s, 6H), 0.98 (s, 6H).
13C{1H} NMR (C6D6, 100 MHz): δ 158.9, 143.4, 135.6, 128.3, 128.0,
127.3, 126.4, 113.7, 83.0, 55.3, 31.0, 24.7. 11B{1H} NMR (C6D6, 128
MHz): 21.5 (s).
1
(62 μL, 0.478 mmol). H NMR (C6D6): δ 7.04 (s, 4H), 5.22 (q, J =
6.4 Hz, 1H), 1.32 (d, J = 6.4 Hz, 3H), 1.00 (s, 6H), 1.01 (s, 6H).
11B{1H} NMR (C6D6): δ 21.6 (s).
Hydroboration of 4′-Methylacetophenone by Pinacolbor-
ane Catalyzed by Complex 1. A procedure identical with that
described for acetophenone was repeated using 4-methylacetophenone
Synthesis of 1,1-Diphenylmethanol (5a).
1
(64 μL, 0.478 mmol). H NMR (C6D6): δ 7.30 (d, J = 7.8 Hz, 2H),
6.97 (d, J = 7.8 Hz, 2H), 5.42 (q, J = 6.4 Hz, 1H), 2.10 (s, 3H), 1.48
(d, J = 6.4 Hz, 3H), 1.00 (s, 6H), 1.02 (s, 6H). 11B{1H} NMR (C6D6):
δ 19.0 (s).
Hydroboration of 4′-(Trifluoromethyl)acetophenone by
Pinacolborane Catalyzed by Complex 1. A procedure identical
with that described for acetophenone was repeated using 4-
methoxyacetophenone (49 μL, 0.478 mmol). 1H NMR (C6D6): δ
7.30 (d, J = 8.2 Hz, 2H), 7.10 (d, J = 8.2 Hz, 2H), 5.26 (q, J = 6.4 Hz,
1H), 1.30 (d, J = 6.4 Hz, 3H), 0.985 (s, 6H), 1.02 (s, 6H). 11B{1H}
NMR (C6D6): δ 20.6 (s).
On the laboratory bench in air, 2-(diphenylmethoxy)pinacolborane
(0.577 g, 1.86 mmol) was dissolved in a vial with CH2Cl2 (∼4 mL)
and the solution passed through a silica plug. A clear colorless solution
was collected and excess solvent removed via rotary evaporation. A
white powdery solid was collected (0.260 g, 1.41 mmol, 76% yield).
1H NMR (C6D6, 400 MHz): δ 7.35 (m, 8H), 7.26 (m, 2H), 5.83 (d,
J = 4 Hz, 1 H), 2.26 (d, J = 4 Hz, 1 H). 13C{1H} NMR (C6D6, 100
MHz): δ 143.9, 77.5, 77.2, 76.7, 76.4.
Hydroboration of 2-Cyclohexen-1-one by Pinacolborane
Catalyzed by Complex 1. A vial was charged with 2-cyclohexen-1-
one (46 μL, 0.478 mmol) in C6D6 (1 mL), and to the resultant
solution was added pinacolborane (69 μL, 0.478 mmol). The resultant
mixture was transferred into a vial containing preweighed 5 mol % of
complex 1 (10 mg, 0.00239 mg), stirred at room temperature, and
Synthesis of 1-(4-Methylphenyl)-1-phenylmethanol (5b).
1
analyzed spectroscopically after 90 min. H NMR (C6D6): δ 5.89 (m,
1H), 5.64 (m, 1H), 4.76 (m, 1H), 2.17 (m, 2H), 1.63 (m, 2H), 1.39
(m, 2H), 1.00 (s, 12H). 11B{1H} NMR (C6D6): δ 18.3 (s).
The procedure for the synthesis of 1,1-diphenylmethanol was followed
using 2-(1-(4-methylphenyl)-1-phenylmethoxy))pinacolborane (0.267
g, 0.822 mmol) instead of 2-(diphenylmethoxy)pinacolborane, and 1-
(4-methylphenyl)-1-phenylmethanol formed as a colorless oil, which
subsequently solidified to a white powdery solid after 12 h at room
temperature (0.116 g, 0.584 mmol, 71% yield).
Kinetic Studies of Carbonyl Hydroboration Catalyzed by
Complex 1. A vial was charged with acetophenone (56 μL, 0.478
mmol) in C6D6 (2 mL), and to the resultant solution were added 5
equiv of pinacolborane (345 μL, 2.39 mmol) and 200 μL of a 0.645 M
solution of Cp2Fe in C6D6 (internal standard). The resultant mixture
was transferred into a vial containing preweighed 5 mol % of complex
1 (10 mg, 0.00239 mg) then transferred into an NMR tube; the tube
was then shaken to dissolve all solids. The NMR tube was loaded into
the NMR spectrometer quickly, and single-pulse experiments were
performed every 30 s over at least 3 half-lives using an automated
program. Rate measurements were performed by measuring the
integrals of the product methyl peaks or aromatic peaks and the
cyclopentadienyl peaks of the internal standard. Identical experiments
were performed using 4-chloro-, 4-methyl-, and 4-methoxyacetophe-
nones.
1H NMR (C6D6, 400 MHz): δ 7.17 (m, 4H), 7.08 (m, 3H), 6.98 (d,
J = 7.6 Hz), 5.63 (d, J = 1.8 Hz, 1H), 2.17 (s, 3H), 2.08 (d, J = 1.8 Hz,
1H). 13C{1H} NMR (C6D6, 100 MHz): δ 114.1, 141.2, 137.3, 129.3,
128.6, 127.6, 126.7, 126.6, 76.1, 21.3.
Synthesis of 1-(4-Methoxyphenyl)-1-phenylmethanol (5c).
Computational Details. The initial structures of benzophenone,
benzaldehyde, HBpin, Cp2Ti(HBpin), [Cp2Ti(HBpin)(PhC(O)Ph)]
(5), [Cp2Ti(HBpin)(HC(O)Ph)] (6a,b), and hydroborated products
were all built using GaussView 5.0.50 All the calculations were carried
out using the Gaussian 09 package.51 Since the B3PW91 method was
able to reproduce the experimental geometries of titanocene borane
complexes,53 it was adopted in this computational study. The 6-
The procedure for the synthesis of 1,1-diphenylmethanol was followed
using 2-(1-(4-methoxyphenyl)-1-phenylmethoxy))pinacolborane
(0.646 g, 1.89 mmol) instead of 2-(diphenylmethoxy)pinacolborane,
and 1-(4-methoxyphenyl)-1-phenylmethanol formed as a colorless oil,
which subsequently solidified to a white translucent solid after 12 h at
room temperature (0.365 g, 1.66 mmol, 88% yield).
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31G(d,p) basis set was employed in optimizing the geometries of
benzophenone, benzaldehyde, HBpin, and the final products. For
Cp2Ti(HBpin) and complexes 5 and 6a,b, the LanL2DZ basis set was
used for Ti, and the 6-31G(d,p) basis set was used for all the other
atoms in geometry optimizations.
(29) Waltz, K.; Hartwig, J. F. J. Am. Chem. Soc. 2000, 122, 11358.
(30) Bryliakov, K. P.; Babushkin, D. E.; Talsi, E. P.; Voskoboynikov,
A. Z.; Gritzo, H.; Schroder, L.; Damrau, H. R. H.; Wieser, U.; Schaper,
F.; Brintzinger, H. H. Organometallics 2005, 24, 894.
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ASSOCIATED CONTENT
* Supporting Information
■
S
Text, a figure, and tables giving details of the computations.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(34) Chakraborty, S.; Guan, H. R. Dalton Trans. 2010, 39, 7427.
(35) Diez-Gonzalez, S.; Nolan, S. P. Org. Prep. Proced. Int. 2007, 39,
523.
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6345.
AUTHOR INFORMATION
Corresponding Author
*E-mail: cmuhoro@towson.edu.
Notes
■
(37) Arena, C. G. Mini-Rev. Org. Chem. 2009, 6, 159.
(38) Thangavelu, S. G.; Hocker, K. E.; Cooke, S. R.; Muhoro, C. N. J.
Organomet. Chem. 2008, 693, 562.
(39) Hartwig, J. F.; Muhoro, C. N. Organometallics 2000, 19, 30.
(40) Muhoro, C. N.; He, X. M.; Hartwig, J. F. J. Am. Chem. Soc. 1999,
121, 5033.
(41) Vogels, C. M.; Hayes, P. G.; Shaver, M. P.; Westcott, S. A. Chem.
Commun. 2000, 51.
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Shaver, M. P.; Hayes, P. G.; Westcott, S. A. Can. J. Chem. 2001, 79,
1898.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
This research was supported by a Cottrell Science Grant Award
(CCSA 7820) from Research Corp.
■
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NOTE ADDED AFTER ASAP PUBLICATION
■
In the version of this paper published on December 19, 2012,
Tables 1 and 3 had some missing data. The version of this
paper that appears as of December 20, 2012, is correct.
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