Synthesis and catalytic reactivity of bis(amino)cyclopropenylidene carbene-borane adducts

Article abstract of DOI:10.1021/acs.organomet.6b00654

The first reported neutral boron(III) adducts of bis(amino)cyclopropenylidene carbenes (BAC carbenes) have been synthesized, structurally characterized, and applied in homogeneous reaction chemistry. These air-stable adducts have been prepared by the combination of a BAC carbene lithium tetrafluoroborate adduct with borane dimethyl sulfide, boron trifluoride etherate, or dicyclohexylborane. A borenium cation derived in situ from the dicyclohexylborane adduct catalytically reduces unhindered benzyl ketimines, a class of substrate that cannot be reduced by prior borenium catalysts, at room temperature, employing 20 atm of hydrogen gas as the terminal reductant.

Full text of DOI:10.1021/acs.organomet.6b00654

Communication
pubs.acs.org/Organometallics
Synthesis and Catalytic Reactivity of Bis(amino)cyclopropenylidene
Carbene−Borane Adducts
†
†
‡
‡
Blake S. N. Huchenski, Matt R. Adams, Robert McDonald, Michael J. Ferguson,
,
†
and Alexander W. H. Speed*
†Department of Chemistry, Dalhousie University, 6274 Coburg Road, P.O. Box 15000, Halifax, Nova Scotia, Canada B3H 4R2
‡X-ray Crystallography Laboratory, Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2G2
*
S Supporting Information
ABSTRACT: The first reported neutral boron(III) adducts of
bis(amino)cyclopropenylidene carbenes (BAC carbenes) have
been synthesized, structurally characterized, and applied in
homogeneous reaction chemistry. These air-stable adducts have
been prepared by the combination of a BAC carbene lithium
tetrafluoroborate adduct with borane dimethyl sulfide, boron
trifluoride etherate, or dicyclohexylborane. A borenium cation
derived in situ from the dicyclohexylborane adduct catalytically
reduces unhindered benzyl ketimines, a class of substrate that
cannot be reduced by prior borenium catalysts, at room
temperature, employing 20 atm of hydrogen gas as the terminal reductant.
dducts of carbenes and boranes have recently emerged as
powerful reducing reagents. The most common type of
alkylcarbene (CAAC)−boron trifluoride adduct 2a could be
2
c
A
isolated, the corresponding borane adduct 2b was not isolable.
adduct employs N-heterocyclic carbenes (NHCs): for example,
Notwithstanding the above difficulties, changing the identity of
the carbene has allowed development of enhanced reactivity;
mesoionic carbene (MIC)−borane adducts such as 3 have been
shown to be more potent reducing reagents than the
1
adduct 1 (Figure 1). These neutral adducts are remarkably
2
stable stoichiometric reductants, frequently being stable to
3
silica gel chromatography, despite their capacity to reduce
4
corresponding NHC adducts. In addition to stoichiometric
carbonyl and imine compounds and hydroborate olefins in the
presence of activating reagents. Not all carbenes can form stable
adducts with borane; for example, while the cyclic amino-
reactivity, carbene−borane adducts have recently been used to
generate borenium cations that serve as the Lewis acid
component in frustrated Lewis pair based hydrogenation
5
catalysts. As an example, NHC-supported borenium cation 4
represents the most active NHC−borane-based hydrogenation
catalyst, capable of reducing tert-butyl or phenyl ketimines and
6
hindered enamines at 5 mol % loading under 102 atm of H2.
In a further demonstration of the importance of exploring
different carbene motifs, MIC-supported borenium cation 5
represents the most active borenium-based hydrogenation
catalyst reported to date, capable of hydrogenating tert-butyl
or phenyl imines and sterically encumbered nitrogen-
containing heterocycles at pressures of hydrogen varying from
7
1
to 102 atm at 10 mol % loading.
Bis(amino)cyclopropenylidene carbenes (BAC carbenes)
represent an alternative and emerging carbene architecture.
The first example of an isolated BAC carbene was disclosed by
Bertrand and co-workers in 2006 as a highly air and moisture
8
sensitive crystalline solid. Since that time, catalysts based on
BAC carbenes have been used to promote Stetter and benzoin
9
reactions and have been used as ligands in a nickel-catalyzed
10
reductive vinylation. The aforementioned work in nickel-
Figure 1. Various adducts of boron and carbenoids (DiPP = 2,6-
diisopropylphenyl).
Received: August 14, 2016
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.organomet.6b00654
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Organometallics
Communication
catalyzed reactions has shown that BAC carbenes possess
In an attempt to develop a more general synthesis of BAC
carbene−borane adducts, we added crystalline BAC carbene 10
to borane dimethyl sulfide or 9-BBN in ethereal solvents or
toluene (Scheme 2). Each of these trials resulted in the
reactivity characteristic of having a steric profile smaller than
10
that of N-heterocyclic carbenes. We anticipated that this
decreased steric demand would enhance reactivity in
stoichiometric and catalytic reactions employing BAC car-
bene−borane adducts. Also, BAC carbene precursors are
readily and inexpensively synthesized, being accessible from
commercially available pentachlorocyclopropane in a single-pot
operation on a multigram scale, unlike current lengthier routes
Scheme 2. Synthesis and Structures of BAC Carbene−BH
3
a
(6) and −BF (12) Adducts
3
4
,11
to MIC precursors.
This present work discloses the
synthesis, stoichiometric carbonyl reduction, and catalytic
imine reduction with BAC carbene−borane adducts 6 and 7.
Disclosure of BAC carbene adducts with main-group
elements preceded the isolation of the parent BAC carbene,
12
and examples including tin, germanium, and lead, phospho-
1
3
14
rus, and arsenic adducts have been synthesized. Additional
complexes of BAC carbenes and metals include copper, silver,
1
5
rhodium, iridium, and palladium. To the best of our
knowledge, BAC carbenes have not been employed in the
16
formation of adducts with neutral boranes.
Our initial attempt to synthesize adduct 6 involved heating
BAC carbene precursor 8a at reflux in toluene for 20 h with
sodium borohydride (Scheme 1). While we undertook this
Scheme 1. Synthesis and Structure of BAC Carbene−
a
Triphenylborane Adduct 9
a
The thermal ellipsoids are scaled at the 30% probability level.
Selected interatomic distances (Å): 6, C1−B1 1.608(5); 12, C1−B1
1
.641(3).
formation of intractable tacky red mixtures exhibiting complex
1
11
H and B NMR spectra. Despite these initial setbacks, our
attention turned to the use of the BAC carbene−lithium
19
tetrafluoroborate adduct 11 (the Weiss−Yoshida reagent).
This reagent was crystallized and characterized by Bertrand
and co-workers as a polymeric material consisting of a BAC
carbene−lithium adduct with a 5:4 lithium tetrafluoroborate to
BAC carbenenoid stoichiometry. In our hands, deprotonation
of 8b with butyllithium in diethyl ether, in the presence of 0.25
equiv of lithium tetrafluoroborate, followed by concentration
and pentane trituration under a dry nitrogen atmosphere gives
a 93% yield of a free-flowing white powder (11) that was used
in subsequent reactions without additional purification. Mixture
of this reagent with borane dimethyl sulfide or boron trifluoride
etherate complexes in toluene, followed by evaporation and
extraction of the resulting residue with dichloromethane,
resulted in clean formation of the desired adducts 6 and 12.
Adducts 6 and 12 can be stored indefinitely in air without
decomposition (>4 months); however, some decomposition of
6 is noted with silica gel chromatography.
a
The thermal ellipsoids are scaled at the 30% probability level.
Hydrogen atoms are omitted for clarity. Selected interatomic distances
(
Å); C1−B1 1.6394(15), C1−C3 1.3871(15), C2−C3 1.3892(14),
N1−C2 1.3267(14).
operation with the hope of directly synthesizing target BAC−
borane adduct 6 with concomitant loss of hydrogen and
sodium tetraphenylborate, in analogy to known chemistry with
imidazolium iodides, we instead observed clean formation of
a crystalline, air-stable product exhibiting a broad singlet at
17
1
1
−
9.4 ppm in the proton-coupled B NMR spectrum.
1
Integration of the phenyl and isopropyl signals in the H
NMR spectrum suggested the formation of 9, which was
verified on the basis of a single-crystal X-ray crystallography
experiment (Scheme 1). Compound 9 features a boron to
carbon interatomic distance of 1.6394(15) Å. This is similar to
the 1.666(3) Å boron to carbon interatomic distance reported
The structures of 6 and 12 were confirmed on the basis of
NMR spectroscopy and single-crystal X-ray diffraction data.
Compound 6 features a C−B interatomic distance of 1.608(5)
Å, while compound 12 features a C−B interatomic distance of
18
1
by Ong and co-workers for an NHC−triphenylboron adduct.
1.641(3) Å. A quartet is observed at −35.1 ppm with JBH = 86
Hz in the 11B NMR spectrum of 6, and a quartet is also
The presence of an ionic additive proved necessary for the
formation of 9, as 8a was stable for 24 h in refluxing toluene
without any additional additive. Sodium tetrafluoroborate also
promoted the formation of 9 from 8a.
11
observed in the B NMR spectrum of 12 at −0.4 ppm, with
1
J
BF = 34 Hz. These metrics are comparable to those of
4
,20
previously reported carbene−borane adducts.
B
DOI: 10.1021/acs.organomet.6b00654
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Organometallics
Communication
The ability of adduct 6 to serve as a source of hydride was
investigated (Scheme 3). While no reaction occurred when 0.5
Scheme 4. Hydrogenations of Benzyl Imines Catalyzed by
Borenium Cation 20
Scheme 3. Reduction of Carbonyl Compounds using 0.5
equiv of 6 in the Presence of Silica Gel
a
Conditions: 0.5 equiv of 6, 0.2 M substrate in CH Cl , 15 mg of
2
2
b
silica/mg of aldehyde. NMR yield; all other yields are isolated yields.
equiv of 6 was mixed with 4-cyanobenzaldehyde (13a),
addition of silica gel, a precedented activator for carbonyl
2
reduction by NHC−boranes, resulted in clean reduction to
alcohol 14a in only 1 h.
Electron-rich anisaldehyde (13b) and 2-naphthaldehyde (15)
were also reduced under the same conditions. A slightly higher
yield of 2-naphthylmethanol (16) was attributed to decreased
product volatility. Acetophenone (13c) proved a more
challenging substrate, with only 60% conversion observed
after 6 h. Cinnamaldehyde (17) was cleanly reduced in a 1,2-
fashion, with cinnamyl alcohol (18) as the only product; no
1
1
02 atm H pressure for 4, and “trace” conversion reported at
2
6,7
02 atm H for 5). Since the benzyl and PMB groups are
2
some of the most commonly used protecting groups for
amines, the work disclosed herein represents an advance in
borenium-catalyzed hydrogenation reactions, enabled by the
use of BAC carbene−borane complexes.
In conclusion, we have developed a reliable and high-yielding
synthesis of crystallographically characterized BAC carbene−
borane adducts, where success was dependent on the use of
lithium tetrafluoroborate adducts of BAC carbenes rather than
the free carbene. We have shown BAC carbene−borane
adducts are capable of stoichiometric reduction of carbonyl
compounds and catalytic reductions of benzyl imines, a
challenging class of substrate for catalytic reduction by
borenium catalysts. Preparation of additional BAC carbene−
borane adducts to increase reaction efficiency, expand substrate
scope, and effect asymmetric imine hydrogenations is underway
and will be reported in due course.
1
,4-addition product was observed. These reaction times are
2
faster than those reported for NHC−boranes4 and are
comparable to those observed for MIC−borane 3.
Our methodology was extended to a borane bearing both
hydride and alkyl groups. Addition of dicyclohexylborane to
reagent 11 in diethyl ether gave adduct 7 in 84% yield as an air-
21
stable beige solid that is unstable to silica gel chromatography.
While we could not obtain a single crystal suitable for X-ray
analysis, NMR and MS data corroborate the structure of 7
depicted in Scheme 4. As a diagnostic feature, a doublet is
1
11
observed at −12.1 ppm with J = 71 Hz in the B NMR
BH
spectrum of 7.
Combination of adduct 7 with trityl tetrakis[3,5-
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the
ACS Publications Web site. The Supporting Information is
available free of charge on the ACS Publications website at
DOI: 10.1021/acs.organomet.6b00654.
■
(
trifluoromethyl)phenyl]borate 19 in dry CDCl resulted in
3
*
S
hydride transfer and formation of putative borenium cation 20,
identified by the disappearance of the doublet at −12.1 ppm
and the appearance of a broad signal at 81.0 ppm in the 11
B
NMR spectrum (a range comparable to that of adduct 4, 82.9
6
ppm). One equivalent of triphenylmethane also appeared in
1
General considerations, solvents, reagents, crystallo-
graphic solution and refinement details, ORTEP
drawings for compounds 6, 9, and 12, synthetic
procedures, references, and NMR spectra of boron
adducts and reduction products (PDF)
Crystallographic data for 6 (CIF)
Crystallographic data for 9 (CIF)
the H spectrum of the reaction. Since borenium cations 4 and
5
are hydrogenation catalysts, we explored the application of 7
to catalytic hydrogenation. A 10 mol % combination of 7 and
9 in trifluorotoluene was able to effect the hydrogenation of
benzyl imines 21 and 23 and p-methoxybenzyl (PMB) imine
5 to the corresponding amines with high conversion under 20
1
2
atm of H at ambient temperature. The hydrogenation was
2
Crystallographic data for 12 (CIF)
conducted in a Parr bomb, with 99.999% purity grade
22
hydrogen, which was otherwise used as received. Importantly,
benzyl imines have not been substrates for previously reported
AUTHOR INFORMATION
Corresponding Author
*E-mail for A.W.H.S.: aspeed@dal.ca.
■
23
borenium-based hydrogenation catalysts. Catalysts 4 and 5
cannot hydrogenate substrate 21 (0% conversion reported at
C
DOI: 10.1021/acs.organomet.6b00654
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Organometallics
Communication
Notes
was unstable to concentration or isolation and was not otherwise
characterized.
The authors declare no competing financial interest.
(22) The equipment we had access to was limited to a maximum
pressure of 20 atm. Higher pressures of hydrogen gas will be explored
in due course. Trifluorotoluene was an optimal solvent in ref 7.
Dichloromethane provides inferior conversions in our chemistry (34%
for 21).
ACKNOWLEDGMENTS
■
Financial support in the form of start-up funding from
Dalhousie University is gratefully acknowledged. Dr. Mike
Lumsden and Mr. Xiao Feng are thanked for assistance with
NMR spectroscopy and mass spectrometry, respectively.
(23) A single example of hydrogenation of the benzyl imine of
benzophenone, employing a MIC carbene supported borenium cation,
with 99% conversion at 102 atm was reported in the Supporting
Information of ref 7. Presumably the steric bulk of this substrate
prevents product inhibition, as the same catalyst provided only trace
hydrogenation of less bulky 21 under the same conditions.
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D
DOI: 10.1021/acs.organomet.6b00654
Organometallics XXXX, XXX, XXX−XXX