Borenium-Catalyzed Reduction of Pyridines through the Combined Action of Hydrogen and Hydrosilane

Article abstract of DOI:10.1021/acs.orglett.1c01892

Mesoionic carbene-stabilized borenium ions efficiently reduce substituted pyridines to piperidines in the presence of a hydrosilane and a hydrogen atmosphere. Control experiments and deuterium labeling studies demonstrate reversible hydrosilylation of the pyridine, enabling full reduction of the N-heterocycle under milder conditions. The silane is a critical reaction component to prevent adduct formation between the piperidine product and the borenium catalyst.

Full text of DOI:10.1021/acs.orglett.1c01892

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Letter
Borenium-Catalyzed Reduction of Pyridines through the Combined
Action of Hydrogen and Hydrosilane
Joshua J. Clarke, Yuuki Maekawa, Masakazu Nambo, and Cathleen M. Crudden*
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ABSTRACT: Mesoionic carbene-stabilized borenium ions effi-
ciently reduce substituted pyridines to piperidines in the presence
of a hydrosilane and a hydrogen atmosphere. Control experiments
and deuterium labeling studies demonstrate reversible hydro-
silylation of the pyridine, enabling full reduction of the N-
heterocycle under milder conditions. The silane is a critical
reaction component to prevent adduct formation between the
piperidine product and the borenium catalyst.
Scheme 1. Borenium-Catalyzed Hydroboration of Imines
and Pyridines
itrogen-containing heterocycles are key functional
groups in pharmaceutical science, with 59% of drugs
N
containing at least one N-heterocycle and piperidines being the
most common ring structure.1 Transition-metal-catalyzed
hydrogenation of pyridines is a common route to piperidines,2
but it may require pretreatment with acid or protecting groups
and can result in metal contamination.3 Hydroboration/
hydrosilylation of pyridines and other heterocycles represents
an alternative to direct hydrogenation and has been reported
with frustrated Lewis pair (FLP) catalysts.4,5
Stephan reported the first example of the use of B(C6F5)3 to
hydrogenate quinoline6 and other heterocycles, including
lutidine as a single pyridyl example.7,8 Chang’s group reported
the use of B(C6F5)3 to catalyze the reductive hydrosilylation of
quinolines with turnover numbers of up to 10009 and also
described the hydrosilylation of pyridines in which different
levels of reduction were observed depending on the
substitution pattern of the pyridine.10 Du described catalytic
hydrogenation using a catalyst derived from the reaction of
HB(C6F5)2 and alkenes, which included a selected pyridine
reduction.11 Wang12 reported a combined hydrosilylation/
transfer hydrogenation in the hydrogenation of a wide variety
of pyridines. Despite requiring excesses of both the silane and
proton sources, the reaction is highly effective for the reduction
of a variety of pyridines.
Our group and others have employed borenium ions in FLP-
catalyzed hydrogenation reactions and organic transforma-
tions.13−18 Borenium ions are isoelectronic with neutral
boranes, but their full positive charge negates the need for
multiple perfluorinated aromatic substituents. Recently, our
group showed that borenium ions stabilized by electron-
donating mesoionic carbenes (MICs) are effective reduction
catalysts (Scheme 1A). Sterically encumbered imines were
reduced at room temperature and H2 at atmospheric pressure,
and quinolines were also reduced at higher hydrogen pressures.
Pyridines could be reduced but required more forcing
conditions and reacted in poor to moderate yields. Inspired
by the concept of using mixed reducing agents, we report the
facile reduction of even monosubstituted pyridines with
borenium ion 1+ in combination with silanes and hydrogen,
illustrating the important role of the silane in preventing
catalyst decomposition.
We began our studies with precatalyst 1-H (eq 1), which
was previously shown to be the optimal catalyst for imine
Received: June 7, 2021
https://doi.org/10.1021/acs.orglett.1c01892
© XXXX American Chemical Society
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reduction of fluorinated pyridines with rhodium catalysts,21
pyridines with titanium catalysts22 and α,β-unsaturated ketones
with a B(C6F5)3/phosphine intermolecular FLP.23
In the event, introducing PhSiH3 into the reaction mixture
dramatically improved the reduction of 2-phenyl-6-methylpyr-
idine (7a) (Table 1).24 Adding 2 equiv of PhSiH3 to the
hydrogenation because of the electron-donating triazolylidene
and the decreased steric hindrance provided by the presence of
one C−H bond adjacent to the nascent borenium ion. In situ
activation of this precatalyst is accomplished by hydride
Table 1. Optimization of the Reaction Conditions for 2,6-
Disubstituted Pyridine 7a
a
−
abstraction with Ph3C+B(C6F5)4 . The high reactivity of the
borenium ion generated in this manner requires the use of
solvents with low coordinating ability, such as 1,2-dichloro-
ethane (DCE) or toluene (Table S1). With these preliminary
activation parameters in hand, we investigated the hydro-
genation of 2,6-diphenylpyridine (3), which is a bulky Lewis
base known to form FLPs with Lewis acids such as B(C6F5)3
(eq 1).19
b
equiv of
silane
pressure
(bar)
temp.
yield
entry
solvent
(°C)
(conv)
c
1
2
3
4
5
6
7
0
0
DCM
DCE
DCE
103
90
50
50
50
50
50
RT
90
90
RT
RT
RT
40
33
40 (41)
84 (100)
52 (61)
52 (69)
67 (65)
87 (96)
Reaction of 3 with catalyst 1+ under a high pressure of
hydrogen gave the desired piperidine product 4 in 36−48%
yield (see the Supporting Information for details). Increasing
the temperature, catalyst loading, or reaction time did not
significantly increase the yield of the product, suggesting issues
with product inhibition or catalyst decomposition. To test this
2.0
1.5
1.1
1.5
1.5
DCE
PhMe
PhMe
PhMe
a
All of the reactions were carried out on a 0.125 mmol scale of 7a
over 19 h. Yields are based on H NMR analysis in the presence of
b
1
i
hypothesis, we treated 1+ with Pr2NH as a surrogate for the
c
an internal standard. Entry 1 was taken from ref 16.
reaction product (Scheme 2A). Heating this mixture at 90 °C
Scheme 2. Borenium Ion Deactivation Pathway
reaction mixture resulted in complete conversion to piperidine
8a in 84% yield and full conversion (entry 3), compared with
only 40% yield without silane (entry 2), while decreasing the
required dihydrogen pressure by almost half (90 bar vs 50 bar).
Even at room temperature with a lower number of equivalents
of silane (entry 6), we were able to achieve 67% yield at 50 bar
H2. Increasing the temperature to 40 °C gave our optimal
conditions, resulting in 87% yield of the product with 96%
conversion (entry 7).
for 4 days resulted in complete decomposition of 1+. A broad
With viable conditions in hand, we examined the scope of
this transformation. Electron-neutral and electron-rich sub-
strates were reduced in excellent yields (7a−c), but electron-
deficient pyridines required elevated temperatures. Heating to
90 °C was sufficient for the reduction of trifluoromethylated
substrate 7d and chlorinated arylpyridine 7e. It is important to
note that for 7d we did not observe hydrodefluorination, which
has been observed with highly electrophilic silicon and
aluminum cations.25 π-Extended derivative 7f was reduced
without concomitant reduction of the naphthyl group. Less
sterically demanding 2,6-lutidine (7g) was also reduced to give
8g in 47% yield, and 50% of 7g was recovered. Unfortunately,
pyridine substrates containing very large substituents such as
2,4,6-triisopropylphenyl in 7h or lacking steric protection
around nitrogen as in 7i are not amenable to reduction with
the current protocol. In the case of 7h, the starting material
was recovered largely intact, with only trace protodebromina-
singlet at 47.8 ppm in the 11B NMR spectrum is assigned to
1
amino borane 5. A singlet at 8.95 ppm in the H NMR
spectrum of the crude reaction mixture indicates the presence
of triazolium salt 6. The presence of both 5 and 6 in the
reaction mixture was confirmed by high-resolution mass
spectrometry (HRMS).
Although our group has not previously observed catalyst
decomposition of this type, this reactivity is not unprece-
dented. Bourissou and co-workers reported C−B bond
protonolysis in a phosphine-stabilized borenium ion in the
presence of Ph2NH.20 A two-step mechanism was proposed, in
which coordination of the amine to the boron center takes
place, followed by boron−carbon bond scission.
To decrease the likelihood of amine-promoted catalyst
decomposition, we examined a combined hydrosilylation and
hydrogenation approach. We envisioned two possible
beneficial effects of the silane. First, the weaker, more polarized
Si−H bond might be more easily activated by the FLP,
resulting in a milder process. Second, the silyl group would
increase the steric bulk of the Lewis basic product, deterring
adduct formation with the catalyst, facilitating catalyst
turnover, and decreasing catalyst decomposition.
1
tion detected by H NMR spectroscopy.
The reaction was found to be highly diastereoselective in all
cases, giving the cis-2,6-arylmethylpiperidine products with
typically greater than 97:3 selectivity (Scheme 3). DFT
calculations by Li et al. indicated that this high degree of
stereoselectivity is a result of a lower energy barrier for the final
hydrogenation step as well as the stability of the final product,
in which both the methyl and phenyl substituents occupy
equatorial positions.26
The concept of dearomatization/hydrogenation cascades has
been explored with other catalysts and has been shown to be a
useful tool for sensitive or difficult substrates, including the
B
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a
and pressure (90 bar) to reduce these substrates. However,
successful reduction was achieved under these conditions.
More highly substituted silanes were employed to disrupt
potential product/catalyst complexes. Thus, PhMe2SiH gave a
better yield of 2-phenylpiperidine (10a) (Table 2, entry 6)
compared with less-substituted PhSiH3 or Ph2SiH2. Interest-
ingly, Ph3SiH showed no reactivity, indicating the importance
of properly tuning the steric parameters of the silane (entry 7).
The reduction of 9a did not take place without PhMe2SiH,
showing the importance of the silane additive in 2-substituted
pyridine reductions (entry 8).
Scheme 3. Substrate Scope for 2,6-Disubstituted Pyridines
Under these optimized conditions, phenyl, m-tolyl, and p-
trifluorotolyl-substituted 2-arylpyridines gave the desired
products in excellent yields (Scheme 4).27 The highly
a
Scheme 4. Substrate Scope for 2-Substituted Pyridines
a
All of the reactions were carried out on a 0.125 mmol scale of 9 over
1
19 h. Isolated yields are reported, with yields obtained by crude H
a
NMR analysis with an internal standard shown in parentheses.
All of the reactions were carried out on a 0.125 mmol scale of 7 over
19 h (except the reaction with 7b, which was run on a 0.25 mmol
scale). Yields are of isolated products after purification, with 1H NMR
yields given in parentheses.
electron-deficient 3,5-bis(trifluoromethyl)-substituted pyridine
9d gave the desired product 10d in a moderate yield of 48%.
Once again, our catalyst leaves the CF3 functional group intact.
Currently there is only one reported example of the
hydrogenation of 2-arylpyridines by FLPs,11 reflecting the
difficulty in reducing these sterically unencumbered substrates,
where strong binding of the product to the catalyst (Lewis acid
or metal) has the potential to inhibit catalysis.
As a more stringent test of the reduction procedure,
monosubstituted 2-arylpyridines were examined (Table 2).
The diminished steric demands of 2-substituted pyridines do
affect their reactivity, requiring a higher temperature (90 °C)
Table 2. Optimization of the Reaction Conditions for
Reduction of 2-Phenylpyridine
Finally, we demonstrated a half-gram-scale reduction of 9a
with 2.5 mol % 1-H using less solvent than under the
optimized conditions to give 11a in 86% yield (eq 2).
a
b
equiv of
silane
pressure
(bar)
yield
entry
silane
solvent
DCE
DCE
PhMe/
DCE
(conv.)
c
1
PhSiH3
PhSiH3
PhSiH3
1.1
1.1
1.5
47
47
90
NR
2
3
33 (44)
64 (70)
To investigate the mechanism of this transformation, several
control experiments were performed. To examine the potential
involvement of silylium ion catalysis,28 which would result
from hydride abstraction from silane by Ph3C+, we carried out
the reaction by mixing PhMe2SiH with 10 mol % [Ph3C][B-
(C6F5)4] in toluene in the absence of borenium precatalyst 1-
H (Scheme 5A). Immediate decoloration of the solution
occurred, suggesting successful hydride abstraction by Ph3C+
to form Ph3CH and the silylium ion. Under our typical
conditions, [Ph3C][B(C6F5)4] is mixed with a slight excess of
1-H before the addition of silane or pyridine to promote
borenium formation over silylium formation. 2-Phenylpyridine
4
5
6
7
8
PhSiH3
Ph2SiH2
PhMe2SiH
Ph3SiH
none
1.5
1.5
1.5
1.5
0
PhMe
PhMe
PhMe
PhMe
PhMe
90
90
90
90
90
73 (68)
68 (75)
85 (86)
NR
NR
a
All of the reactions were carried out on a 0.125 mmol scale of 7a
b
over 19 h at 100 °C. 1H NMR yields obtained with an internal
c
standard. NR = no reaction. The reaction was conducted at room
temperature.
C
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intermediate dihydropyridines but that full reduction of the
ring is not possible without H2 (Scheme 5D).10 This result is
aligned with observations made by Wang,12 who showed that
when 1.2 equiv of silane was used with B(C6F5)3 as the
catalyst, 1,4-hydrosilylation of a 3-substitued pyridine was
observed. When dihydrogen was added to the PhMe2SiD
reduction, the expected piperidine was observed with
deuterium incorporated at the 2-, 4-, and 6-positions (Scheme
5E).
Scheme 5. Mechanistic Studies
In conclusion, we have discovered that the presumed
thermally stable triazolylidene-stabilized borenium ion 1+
undergoes protolytic cleavage in the presence of bulky
secondary amines at elevated temperatures. This decom-
position pathway has consequences for the hydrogenation of
pyridine substrates, in which only low yields for the
hydrogenation of substituted pyridines were obtained in the
presence of dihydrogen and 1+. The addition of hydrosilane, a
more soluble and stronger reducing agent, mitigates the
deactivation of 1+ with the production of a N−Si bond over a
N−H bond. Furthermore, the N-silyl group deters Lewis acid−
Lewis base adduct formation between the product and the
Lewis acid catalyst, as the product piperidine is more basic
than the starting pyridine, allowing the reaction to be
performed at lower pressure and temperature while giving
rise to substituted piperidines in good yields. Deuterium
labeling experiments demonstrated the reversible reduction of
pyridine by the hydrosilane at the ortho and para positions,
providing insight into the mechanism of this transformation.
The hydrosilane−dihydrogen tandem system may find
important uses in other fields in which adduct formation
with basic heteroatoms remain problematic.
ASSOCIATED CONTENT
* Supporting Information
■
sı
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.1c01892.
(9a) was added to the mixture with silylium ion, which was
then heated to 100 °C under H2 gas at 90 bar. After 19 h, no
Experimental details and NMR spectra (PDF)
1
reduced product 10a was formed as determined by H NMR
analysis, providing strong evidence against silylium ion
catalysis in this reaction.
AUTHOR INFORMATION
Corresponding Author
■
Next, to confirm that the reduction is catalyzed by the
borenium Lewis acid rather than the hydride sources, a
reaction was undertaken without the addition of [Ph3C][B-
(C6F5)4] (Scheme 5B). Here we observed no conversion to the
piperidine product 10a, once again affirming the necessity of
1+ in the reduction process.
Cathleen M. Crudden − Department of Chemistry, Queen’s
University, Kingston, Ontario, Canada K7L 3N6; Institute of
Transformative Bio-Molecules (WPI-ITbM), Nagoya
University, Nagoya 464-8602, Japan; orcid.org/0000-
0003-2154-8107; Email: cruddenc@chem.queensu.ca
For more insight into the fate of the silane, we hydrogenated
9a under the optimized conditions and analyzed the crude
Authors
1
reaction mixture by H and 13C NMR spectroscopy before
Joshua J. Clarke − Department of Chemistry, Queen’s
University, Kingston, Ontario, Canada K7L 3N6
Yuuki Maekawa − Department of Chemistry, Queen’s
University, Kingston, Ontario, Canada K7L 3N6; Institute of
Transformative Bio-Molecules (WPI-ITbM), Nagoya
University, Nagoya 464-8602, Japan
Masakazu Nambo − Institute of Transformative Bio-Molecules
(WPI-ITbM), Nagoya University, Nagoya 464-8602, Japan;
orcid.org/0000-0003-0153-3178
workup (Scheme 5C). As shown in Scheme 3C, N-silylated
piperidine 11a was obtained in 86% NMR yield, providing
evidence for either hydrosilylation of the pyridine over the
course of the reaction or a dehydrocoupling reaction with the
penultimate N−H product.
Next, we carried out the reaction with PhMe2SiD in the
presence of 1+ without dihydrogen. After 19 h at 100 °C, no
reduced product was observed by 1H NMR analysis before the
reaction workup. Upon the purification of the crude mixture,
deuterium exchange at the 4- and 6-positions of the pyridine
Complete contact information is available at:
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1
ring was confirmed by H NMR spectroscopy. Under typical
conditions (in the presence of dihydrogen), an 85% yield of
product was observed (Table 2, entry 6). This suggests that
hydrosilylation of the pyridine takes place to generate
Notes
The authors declare no competing financial interest.
D
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with Mesoionic Carbene-Stabilized Borenium Catalysts. Angew.
Chem., Int. Ed. 2015, 54 (8), 2467−2471.
ACKNOWLEDGMENTS
■
We acknowledge the Natural Sciences and Engineering
Research Council of Canada (NSERC) and the Canada
Foundation for Innovation (CFI) for funding of the work
described in this article. J.J.C. is a recipient of the Ontario
Graduate Scholarship Award, and the Government of Ontario
is acknowledged for funding of this research. Y.M. is a recipient
of a JSPS Postdoctoral Fellowship. JSPS and NU are
acknowledged for funding of this research through the World
Premier International Research Center Initiative (WPI)
Program. This work was partially supported by a Grant in
Aid for Specially Promoted Research from MEXT
(17H06091).
(17) Del Grosso, A.; Singleton, P. J.; Muryn, C. A.; Ingleson, M. J.
Pinacol Boronates by Direct Arene Borylation with Borenium
Cations. Angew. Chem., Int. Ed. 2011, 50 (9), 2102−2106.
(18) Lawson, J. R.; Clark, E. R.; Cade, I. A.; Solomon, S. A.;
Ingleson, M. J. Haloboration of Internal Alkynes with Boronium and
Borenium Cations as a Route to Tetrasubstituted Alkenes. Angew.
Chem., Int. Ed. 2013, 52 (29), 7518−7522.
(19) Geier, S. J.; Gille, A. L.; Gilbert, T. M.; Stephan, D. W. From
Classical Adducts to Frustrated Lewis Pairs: Steric Effects in the
Interactions of Pyridines and B(C6F5)3. Inorg. Chem. 2009, 48 (21),
10466−10474.
(20) Devillard, M.; Mallet-Ladeira, S.; Bouhadir, G.; Bourissou, D.
Diverse Reactivity of Borenium Cations with > N-H Compounds.
Chem. Commun. 2016, 52 (57), 8877−8880.
(21) Nairoukh, Z.; Wollenburg, M.; Schlepphorst, C.; Bergander, K.;
Glorius, F. The Formation of All-Cis-(Multi)Fluorinated Piperidines
by a Dearomatization−Hydrogenation Process. Nat. Chem. 2019, 11
(3), 264−270.
REFERENCES
■
(1) Vitaku, E.; Smith, D. T.; Njardarson, J. T. Analysis of the
Structural Diversity, Substitution Patterns, and Frequency of Nitrogen
Heterocycles among U.S. FDA Approved Pharmaceuticals. J. Med.
Chem. 2014, 57 (24), 10257−10274.
(22) Harrod, J. F.; Shu, R.; Woo, H. G.; Samuel, E. Titanocene(III)
Catalyzed Homogeneous Hydrosilation-Hydrogenation of Pyridines.
Can. J. Chem. 2001, 79 (5−6), 1075−1085.
(2) Baumann, M.; Baxendale, I. R. An Overview of the Synthetic
Routes to the Best Selling Drugs Containing 6-Membered Hetero-
cycles. Beilstein J. Org. Chem. 2013, 9, 2265−2319.
(23) Greb, L.; Ona-Burgos, P.; Kubas, A.; Falk, F. C.; Breher, F.;
̃
Fink, K.; Paradies, J. [2.2] Paracyclophane Derived Bisphosphines for
the Activation of Hydrogen by FLPs: Application in Domino
Hydrosilylation/Hydrogenation of Enones. Dalt. Trans. 2012, 41
(30), 9056−9060.
(3) Wang, D. S.; Chen, Q. A.; Lu, S. M.; Zhou, Y. G. Asymmetric
Hydrogenation of Heteroarenes and Arenes. Chem. Rev. 2012, 112
(4), 2557−2590.
(4) Oestreich, M.; Hermeke, J.; Mohr, J. A Unified Survey of Si-H
and H-H Bond Activation Catalysed by Electron-Deficient Boranes.
Chem. Soc. Rev. 2015, 44 (8), 2202−2220.
(24) Redistribution of silyl ligands is possible with PhSiH3 to form
SiH4. See: Feigl, A.; Chiorescu, I.; Deller, K.; Heidsieck, S. U. H.;
Buchner, M. R.; Karttunen, V.; Bockholt, A.; Genest, A.; Rösch, N.;
Rieger, B. Metal-Free Polymerization of Phenylsilane: Tris-
(Pentafluorophenyl)Borane- Catalyzed Synthesis of Branched Poly-
silanes at Elevated Temperatures. Chem. - Eur. J. 2013, 19 (37),
12526−12536. However, under our reaction conditions we did not
see generation of SiH4.
(25) Stahl, T.; Klare, H. F. T.; Oestreich, M. Main-Group Lewis
Acids for C-F Bond Activation. ACS Catal. 2013, 3 (7), 1578−1587.
(26) Zhao, J.; Wang, G.; Li, S. Mechanistic insights into the full
hydrogenation of 2,6-substituted pyridine catalyzed by the Lewis acid
C6F5(CH2)2B(C6F5)2. Dalton Trans 2015, 44, 9200−9208.
(27) The decrease in isolated yield for 10c is due to issues with
chromatography, not defluorination.
(5) Park, S.; Chang, S. Catalytic Dearomatization of N-Heteroarenes
with Silicon and Boron Compounds. Angew. Chem., Int. Ed. 2017, 56
(27), 7720−7738.
(6) Geier, S. J.; Chase, P. A.; Stephan, D. W. Metal-Free Reductions
of N-Heterocycles via Lewis Acid Catalyzed Hydrogenation. Chem.
Commun. 2010, 46 (27), 4884−4886.
(7) Mahdi, T.; Del Castillo, J. N.; Stephan, D. W. Metal-Free
Hydrogenation of N -Based Heterocycles. Organometallics 2013, 32
(6), 1971−1978.
(8) Erös, G.; Nagy, K.; Mehdi, H.; Pápai, I.; Nagy, P.; Király, P.;
Tárkányi, G.; Soos, T. Catalytic Hydrogenation with Frustrated Lewis
̃
Pairs: Selectivity Achieved by Size-Exclusion Design of Lewis Acids.
Chem. - Eur. J. 2012, 18 (2), 574−585.
(9) Gandhamsetty, N.; Joung, S.; Park, S. W.; Park, S.; Chang, S.
Boron-Catalyzed Silylative Reduction of Quinolines: Selective Sp3 C-
Si Bond Formation. J. Am. Chem. Soc. 2014, 136 (48), 16780−16783.
(10) Gandhamsetty, N.; Park, S.; Chang, S. Selective Silylative
Reduction of Pyridines Leading to Structurally Diverse Azacyclic
Compounds with the Formation of Sp 3 C-Si Bonds. J. Am. Chem. Soc.
2015, 137 (48), 15176−15184.
(11) Liu, Y.; Du, H. Metal-Free Borane-Catalyzed Highly Stereo-
selective Hydrogenation of Pyridines. J. Am. Chem. Soc. 2013, 135
(35), 12968−12971.
(12) Liu, Z. Y.; Wen, Z. H.; Wang, X. C. B(C6F5)3-Catalyzed
Cascade Reduction of Pyridines. Angew. Chem., Int. Ed. 2017, 56 (21),
5817−5820.
(28) Denmark, S. E.; Ueki, Y. Lewis Base Activation of Lewis Acids:
Group 13. in Situ Generation and Reaction of Borenium Ions.
Organometallics 2013, 32 (22), 6631−6634.
(13) Farrell, J. M.; Posaratnanathan, R. T.; Stephan, D. W. A Family
of N-Heterocyclic Carbene-Stabilized Borenium Ions for Metal-Free
Imine Hydrogenation Catalysis. Chem. Sci. 2015, 6 (3), 2010−2015.
(14) Farrell, J. M.; Hatnean, J. A.; Stephan, D. W. Activation of
Hydrogen and Hydrogenation Catalysis by a Borenium Cation. J. Am.
Chem. Soc. 2012, 134 (38), 15728−15731.
(15) Lam, J.; Gunther, B. A. R.; Farrell, J. M.; Eisenberger, P.;
̈
Bestvater, B. P.; Newman, P. D.; Melen, R. L.; Crudden, C. M.;
Stephan, D. W. Chiral Carbene-Borane Adducts: Precursors for
Borenium Catalysts for Asymmetric FLP Hydrogenations. Dalt. Trans.
2016, 45 (39), 15303−15316.
(16) Eisenberger, P.; Bestvater, B. P.; Keske, E. C.; Crudden, C. M.
Hydrogenations at Room Temperature and Atmospheric Pressure
E
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