Lewis base activation of Lewis acids: Group 13. in situ generation and reaction of borenium ions

Article abstract of DOI:10.1021/om400582k

A variety of Lewis bases were combined with 9-BBN-NTf₂ to establish the requirements for the generation of borenium cations. Five different types of behaviors were found, but the most interesting was the combination of Et₃N, DABCO, 2,6-lutidine, or Ph₃P=S, which formed borenium ions exclusively even in sub- or superstoichiometric quantities. The 9-BBN borenium ion complex of 2,6-lutidine rapidly catalyzes the hydrosilylation of a variety of ketones in the presence of Et₃SiH. Preliminary mechanistic experiments suggest that the reduction involves borenium ion activation of Et₃SiH and not the ketone.

Full text of DOI:10.1021/om400582k

Communication
pubs.acs.org/Organometallics
Lewis Base Activation of Lewis Acids: Group 13. In Situ Generation
and Reaction of Borenium Ions
Scott E. Denmark* and Yusuke Ueki
Roger Adams Laboratory, Department of Chemistry, University of Illinois, Urbana, Illinois 61801, United States
S
* Supporting Information
ABSTRACT: A variety of Lewis bases were combined with 9-
BBN-NTf2 to establish the requirements for the generation of
borenium cations. Five different types of behaviors were found,
but the most interesting was the combination of Et3N, DABCO,
2,6-lutidine, or Ph3PS, which formed borenium ions exclusively
even in sub- or superstoichiometric quantities. The 9-BBN
borenium ion complex of 2,6-lutidine rapidly catalyzes the hydrosilylation of a variety of ketones in the presence of Et3SiH.
Preliminary mechanistic experiments suggest that the reduction involves borenium ion activation of Et3SiH and not the ketone.
oregoing studies from these laboratories have provided
extensive preparative and mechanistic illustration of the
in arene and alkane borylation).10 On the other hand, the main
focus in borenium cation catalysis has been the development of
oxaazaborolidine catalysts and other application methods are
very rare.11 Very recently, borenium ion catalyzed hydro-
genation and hydroboration have been reported. In 2012,
Crudden and co-workers reported a novel, metal-free, catalytic
method for the reduction of imines using air-stable, non-
hazardous boranes. The catalysts for this process are discrete,
well-characterized borenium salts derived from pinacolbor-
ane.12a In addition, Curran, Vedejs, and co-workers reported a
borenium ion catalyzed hydroboration of alkenes with N-
heterocyclic carbene−boranes,12b Stephan and co-workers
described hydrogenation of imines with 9-BBN−NHC
F
counterintuitive concept of Lewis base activation of Lewis
acids.1 The majority of the early investigations focused on the
activation of silicon tetrachloride with chiral bisphosphoramides
to generate a highly reactive, chiral trichlorosiliconium ion
complex that catalyzed the diastereo- and enantioselective aldol
additions of enoxysilanes derived from aldehydes, ketones,
esters, amides, and nitriles.2 In recent years, our attention has
turned to the Lewis base activation of Lewis acidic reagents in
group 16 (selenium3 and sulfur4) as well as group 17 (bromine5
and chlorine6) to effect enantioselective cyclofunctionalizations
of unactivated alkenes. Despite the dramatic difference in the
chemical transformations involved, the underlying principle of
catalysis is the same: namely, the electronic redistribution in
donor−acceptor complexes first articulated by Gutmann
(Figure 1).7 To date, all of our mechanistic studies have
demonstrated that the ionization of the dative complexes into
highly electrophilic, cationic species is required for catalysis.
borenium ion complexes,12c and Jakle recently described the
̈
preparation of chiral borenium ions that effected asymmetric
hydrosilylation of a ketone.12d
To develop a catalytic method for the generation of
borenium ions presented far greater challenges than those
encountered with group 14, 16, and 17 elements in previous
endeavors, such as (1) the design features for Lewis base
activation are entirely different in view of the high affinity of the
Lewis acidic elements in this group, (2) the intrinsic Lewis
acidity of any precursors presents a major problem for
suppression of background reactions, (3) ionization of a labile
ligand is essential (at least for boron) to provide the
coordinative unsaturation needed for catalysis, and (4) there
is a lack of an established suite of known reactions of borenium
ions for which (asymmetric) catalysis would be useful. Thus, we
viewed this exercise as an exploratory investigation to learn the
rules for the catalytic generation of borenium ions to enable the
discovery of new reaction chemistry of these novel species.
Figure 1. Gutmann formulation of Lewis base activation of Lewis
acids.
In continuation of these investigations, we were drawn to the
possibility of activating Lewis acids in group 13, in view of the
recent interest in the chemistry of tricoordinate cationic boron
species (borenium ions).8 Many different methods for
borenium ion generation are on record,9 and these highly
reactive species have been used as stoichiometric reagents (e.g.,
Special Issue: Applications of Electrophilic Main Group Organo-
metallic Molecules
Received: June 19, 2013
© XXXX American Chemical Society
A
dx.doi.org/10.1021/om400582k | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Communication
The first phase of the study required the identification of a
suitable boron precursor and its behavior in the presence of a
wide range of Lewis bases. The structures of the possible
adducts in Scheme 1 could be identified by 11B, 19F, and 31P
NMR spectroscopy. From the pioneering work of Vedejs, we
chose 9-borabicyclo[3.3.1]nonane bis(triflimide) (9-BBN-
NTf2, 1). Vedejs demonstrated that 1 was effective for the
generation of borenium and boronium cations with amine
Lewis bases owing to the excellent nucleofugality of the
bis(triflimide) group.13
containing fragment as a cation. With this information in
hand, DABCO, pyridine, 2,4-lutidine, 2,6-lutidine, HMPA,
Ph3PO, n-Bu3PO, Ph3PS, (Me2N)3PS, pyridine N-
oxide, DMSO, n-Bu3P, and benzophenone were used as Lewis
bases and the structures of the 9-BBN−Lewis base complexes
were assigned by 11B and 19F NMR spectroscopy titration
experiments. Analysis of the results revealed that these Lewis
bases could be broadly classified into five different groups: (1)
type I, in which weak coordination formed a boronate complex
only at all loadings of Lewis base (benzophenone), (2) type II,
in which strong coordination formed a boronate complex which
spontaneously ionized and bound a second Lewis base to form
a boronium ion at all loadings of Lewis base (2,4-lutidine, n-
Bu3P), (3) type III, in which strong coordination led to
ionization to form borenium ions at all loadings of Lewis base
(Et3N, DABCO, 2,6-lutidine, Ph3PS), (4) type IV, in which
strong coordination led to ionization to form borenium ions
with 1.0 equiv and then boronium ions with 2.0 equiv of Lewis
base (HMPA, Ph3PO, n-Bu3PO, (Me2N)3PS, pyridine
N-oxide, DMSO), and (5) type V, in which strong coordination
led to ionization to form only boronium ions at all loadings of
Lewis base (pyridine, Proton Sponge). Notably, for type III
Lewis bases, boronium cations were not formed even with 2.0
equiv of Lewis base. Furthermore, with 1.0 equiv of type IV
Lewis bases, a borenium cation was formed predominantly
together with a small amount of the boronium cation.
With a reliable method for the efficient, in situ generation of
borenium−Lewis base complexes, the next phase involved the
identification of a reaction to evaluate the catalytic potential of
these species. The hydrosilylation reaction of ketones was
selected as a model reaction, inspired by the imine hydro-
silylation.12a By analogy to the proposed catalytic cycle, ketones
would be activated by the borenium complex to give the
corresponding boronium complex A. Subsequent hydride
transfer from triethylsilane would afford borinate complex B,
which could be exchanged by Et3SiNTf2 to regenerate the
borenium−Lewis base complex catalyst (Mechanism I)
(Scheme 2).
Scheme 1
Initially, 11B and 19F NMR spectroscopic analysis of isolated,
purified 1 was performed in CH2Cl2 (0.1 M) at room
temperature and sharp singlets were observed at 58.9 and
−70.0 ppm, respectively. To assay the potential of Lewis bases
to generate borenium cations from 1, 0.5, 1.0, and 2.0 equiv of
each Lewis base were titrated to the 0.1 M solution of 1 and
analyzed by NMR spectroscopy (Table 1). The 19F NMR
resonance at ca. −80.0 ppm is characteristic of bis(triflimide)
anion13 and thus allowed the assignment of the boron-
Table 1. Titration Experiments with 1 and Various Lewis
a
Bases: 11B NMR Data
Scheme 2
Initial experiments to probe this hypothesis were conducted
by treating 4-methylbenzophenone (5a) with Et3SiH (1.5
equiv) in the presence of various boron reagents. It was first
established that Et3SiH does not reduce 5a at room
temperature after 6 h (Table 2, entry 1). However, in the
presence of 9-BBN-NTf2 (1; 0.1 equiv) only over-reduced
product 6a was obtained in 69% yield in 10 min (entry 2).
Whereas no reaction took place in the presence of 0.1 equiv of
complex 3b (entry 3), 0.1 equiv of complex 3e afforded the
a
11B NMR spectra were recorded at 128 MHz (CH2Cl2) with proton
decoupling. Chemical shifts are reported in ppm from BF3·OEt2 (0.0
b
ppm) as the external standard. Data in parentheses are from ref 13.
c
d
1,8-Bis(dimethylamino)naphthalene. 2.0 equiv of Lewis base.
B
dx.doi.org/10.1021/om400582k | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Communication
generation of intermediates A and B and subjecting them to the
reaction conditions. However, the combination of 3e and
benzophenone in CH2Cl2 revealed no interaction by 11B NMR
spectroscopic analysis of the mixture.
Table 2. Hydrosilylation of Ketones Catalyzed by Various
Boron Reagents
a
The preparation of intermediate B was attempted by
treatment of boronate 9a14 with N-(trimethylsilyl)bis-
(trifluoromethylsulfonyl)imide (TMSNTf2) and 2,6-lutidine.
However, 9a was not converted to either silyl ether 7a or over-
reduced product 6a; instead, it slowly converted to the
corresponding lutidinium salt 10a. In addition, 10a was also
observed in the presence of Et3SiH (Scheme 3). These
experiments suggest that the hydrosilylation reaction catalyzed
by 3e does not proceed via Mechanism I.15
b
b
Lewis base
(amt
amt of
Et3SiH
(equiv)
yield
of 6a
(%)
yield
amt of 1
of 7a
(%)
entry (equiv)
(equiv))
time
6 h
1
2
3
0
1.5
1.5
1.0
0
69
0
0
0
0
0.1
0.1
10 min
12 h
DABCO
(0.1)
4
5
0.1
2,6-lutidine
(0.1)
1.5
1.5
30 min
20 h
<5
<5
95
69
Scheme 3
0.05
2,6-lutidine
(0.05)
a
Reactions were performed at room temperature in an NMR tube (see
b
the Supporting Information for details). Yields determined by
integration of product signals versus Cl3CCH2Cl as an internal
standard.
expected reduction product 7a in 95% yield (entry 4).
Remarkably, lowering the loading of 2,6-lutidine to 0.05
equiv in the presence of 0.05 equiv of 1 still afforded exclusively
7a, albeit much more slowly, such that after 20 h only a 69%
yield was obtained (entry 5). Clearly, two different mechanisms
are operative for the different catalysts, 1 and 3e.
The scope of the borenium cation catalyzed hydrosilylation
was explored with various ketones 5, and the results are
summarized in Table 3. Generally, the use of 0.1 equiv of 3e
In a different mechanism for the borenium ion catalyzed
ketone hydrosilylation reaction, hydride abstraction from
Et3SiH by the borenium cation could generate 9-BBN-
hydride-2,6-lutidine complex 11 as the active reducing reagent
(Scheme 4). To investigate this possibility required the
independent preparation of 11. However, 11 did not form
from 9-BBN-dimer and 2,6-lutidine.16 Instead, the existence of
11 was probed indirectly by a 11B NMR experiment between 3e
and Et3SiH. Although 11 was not detected via 11B NMR
spectroscopy, 3e was slowly converted to 9-BBN-H dimer.
Furthermore, on mixing 9-BBN-H dimer with TMSNTf2 in the
presence of 2,6-lutidine, 9-BBN-H dimer was also slowly
converted to 3e. Thus, the equilibrium between 3e and 9-BBN-
H dimer and the ability of 3e to activate triethylsilane toward
hydrogen transfer were confirmed (Scheme 4).
a
Table 3. Substrate Scope
b
entry
R
ketone
time (min)
yield (%)
alcohol
1
2
3
4
5
6
7
4-Me-C6H4
3-Me-C6H4
4-MeO-C6H4
4-Br-C6H4
1-naphthyl
2-furyl
5a
5b
5c
5d
5e
5f
30
10
92
90
91
93
86
82
83
77
8a
8b
8c
8d
8e
8f
Scheme 4
180
10
60
10
2-thiophene
isopropyl
5g
5h
60
8g
8h
c
8
60
a
Unless otherwise noted, reactions were performed on a 0.1 mmol
b
scale with 1.5 equiv of Et3SiH in dichloromethane (1.0 mL). Yield of
isolated, purified product. 0.2 equiv of 3e was used as catalyst.
c
and 1.5 equiv of triethylsilane was sufficient for a smooth
reaction and, after treatment of the mixture with catalytic
amounts of FeCl3 in methanol to remove the silyl protecting
group, alcohols 8 were obtained in high yield. Both electron-
deficient and electron-rich aryl ketones were compatible with
the reduction conditions (entries 1−4). In addition, fused
aromatic and heteroaromatic substituents had no negative
influence (entries 5 and 7). A secondary alkyl group was also
nicely accommodated (entry 8).
Although 3e functioned as a catalyst for the hydrosilylation
of ketones as described above, the reaction mechanism
remained unclear. Several control experiments were carried
out to provide mechanistic insight. First, the operation of
Mechanism I (Scheme 2) was probed by the attempted
With this information in hand, two plausible catalytic cycles
can be constructed; one catalyzed by borenium ion 3e
(Mechanism II) and one catalyzed by Et3SiNTf2 (Mechanism
III) (Scheme 5). Mechanism II (borenium ion activation of
Et3SiH followed by carbonyl activation via silyl transfer (path a)
to form silyloxycarbenium ion D and consummated by hydride
transfer to regenerate 3e) finds excellent precedent in the Piers
mechanism for (C6F5)3B-catalyzed hydrosilylation of ketones.17
Mechanism III involves the Tf2N−-assisted activation of Et3SiH
to form Et3SiNTf2 (path b) that in turn forms ion D, which is
reduced by Et3SiH.
C
dx.doi.org/10.1021/om400582k | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Communication
Scheme 5
ACKNOWLEDGMENTS
■
Y.U. thanks the Japan Society for the Promotion of Science for
a postdoctoral fellowship. We are grateful to the National
Institutes of Health for generous financial support (R01
GM85235).
REFERENCES
■
(1) Denmark, S. E.; Beutner, G. L. Angew. Chem., Int. Ed. 2008, 47,
1560−1638.
(2) (a) Beutner, G. L.; Denmark, S. E. Angew. Chem., Int. Ed. 2013,
DOI: 10.1002/anie.201302084. (b) Beutner, G. L.; Denmark, S. E.
Top. Organomet. Chem. 2013, 44, 55−89. (c) Denmark, S. E.; Fujimori,
S. In Modern Aldol Reactions; Mahrwald, R., Ed.; Wiley-VCH:
Weinheim, Germany, 2004; Vol. 2, Chapter 7. (d) Denmark, S. E.;
Stavenger, R. A. Acc. Chem. Res. 2000, 33, 432−440.
(3) (a) Denmark, S. E.; Kalyani, D.; Collins, W. R. J. Am. Chem. Soc.
2010, 132, 15752−15765. (b) Denmark, S. E.; Collins, W. R. Org. Lett.
2007, 9, 3801−3804.
(4) (a) Denmark, S. E.; Jaunet, A. J. Am. Chem. Soc. 2013, 135,
6419−6422. (b) Denmark, S. E.; Kornfilt, D. J. P.; Vogler, T. J. Am.
Chem. Soc. 2011, 133, 15308−15311. (c) Denmark, S. E.; Collins, W.
R.; Cullen, M. D. J. Am. Chem. Soc. 2009, 131, 3490−3492.
(d) Denmark, S. E.; Vogler, T. Chem. Eur. J. 2009, 15, 11737−11745.
(5) (a) Denmark, S. E.; Burk, M. T. Org. Lett. 2012, 14, 256−259.
(b) Denmark, S. E.; Burk, M. T. Proc. Natl. Acad. Sci. U.S.A. 2010, 107,
20655−20660.
To differentiate between these two catalytic cycles, control
experiments were conducted. Mechanism III posits that the
reduction involves Et3SiNTf2 as the activator and Et3SiH as the
reducing agent but does not require 9-BBN-H. Accordingly, 5a,
Et3SiH, and 0.1 equiv each of TMSNTf2 and 2,6-lutidine were
combined in CH2Cl2 at rt. The reaction required 6 h to reach
full conversion and afforded 7a in 92% yield. In contrast, an
identical reaction containing 0.1 equiv of 9-BBN-H dimer was
complete within 10 min to afford 7a in 96% yield. Thus,
although Mechanism III is viable, it does not compete with
Mechanism II under the established reaction conditions.
In a final set of experiments, the stability of silyl ether 7a in
the presence of Et3SiH and both catalysts was tested.
Treatment of 7a with 1 resulted in the formation of 6a in
99% yield after 10 min. However, 7a did not react with
borenium cation 3e even after 24 h. These results further
support the operation of Mechanism II and also explain the
formation of the reduced product 6a in the reaction without
2,6-lutidine.
In conclusion, the interaction of various Lewis bases with 9-
BBN-NTf2 has been investigated. The stable borenium cation
complex 3e catalyzed the hydrosilylation of ketones. Mecha-
nistic studies revealed that this reaction takes place via a
hydride abstraction pathway similar to that for (C6F5)3B-
catalyzed hydrosilylation of ketones. Further studies on this
concept, including the development of other activation modes
and asymmetric reactions, will be reported in due course.
(6) Burk, M. T. Ph.D. Thesis, University of Illinois, Urbana-
Champaign, IL, 2012.
(7) (a) Gutmann, V. The Donor-Acceptor Approach to Molecular
Interactions; Plenum Press: New York, 1978. (b) Gutmann, V. Coord.
Chem. Rev. 1975, 15, 207−237.
(8) (a) De Vries, T. S.; Prokofjevs, A.; Vedejs, E. Chem. Rev. 2012,
112, 4246−4282. (b) Piers, W. E.; Bourke, S. C.; Conroy, K. D. Angew.
Chem., Int. Ed. 2005, 44, 5016−5036. (c) Kolle, P.; Noth, H. Chem.
̈
̈
Rev. 1985, 85, 399−418.
(9) Interestingly, one of the very early methods described for the
generation of borenium ions termed “nucleophilic addition” by Noth
̈
or “nucleophilic addition-heterolysis” by Vedejs is, in fact, Lewis base
activation of the boron Lewis acid.
(10) (a) Del Grosso, A.; Singleton, P. J.; Muryn, C. A.; Ingleson, M. J.
Angew. Chem., Int. Ed. 2011, 50, 2102−2106. (b) Genaev, A. M.; Nagy,
S. M.; Salnikov, G. E.; Shubin, V. G. Chem. Commun. 2000, 1587−
1588. (c) De Vries, T. S.; Prokofjevs, A.; Harvey, J. N.; Vedejs, E. J.
Am. Chem. Soc. 2009, 131, 14679−14687.
(11) Corey, E. J. Angew. Chem., Int. Ed. 2009, 48, 2100−2117.
(12) (a) Eisenberger, P.; Bailey, A. M.; Crudden, C. M. J. Am. Chem.
Soc. 2012, 134, 17384−17387. (b) Prokofjevs, A.; Boussonnier
̀
e, A.; Li,
L.; Bonin, H.; Lacote, E.; Curran, D. P.; Vedejs, E. J. Am. Chem. Soc.
̂
2012, 134, 12281−12288. (c) Farrell, J. M.; Hatnean, J. A; Stephan, D.
W. J. Am. Chem. Soc. 2012, 134, 15728−15731. (d) Chen, J.;
Lalancette, R. A; Jakle, F. Chem. Commun. 2013, 4893−4895.
̈
(13) Prokofjevs, A.; Kampf, J. W.; Vedejs, E. Angew. Chem., Int. Ed.
2011, 50, 2098−2101.
(14) Boronate 9a was prepared by reaction of 9-BBN-H with
authentic carbinol 8a; see the Supporting Information.
(15) Hydrosilylation of imines with neutral boranes proceeds by a
different mechanism than that by borenium ions: Mewald, M.;
Oestreich, M. Chem. Eur. J. 2012, 18, 14079−14084.
(16) 9-BBN-H dimer was treated with 2,6-lutidine in CH2Cl2 at
room temperature. After 24 h, 11B NMR analysis showed no change.
(17) (a) Piers, W. E.; Marwitz, A. J. V.; Mercier, L. G. Inorg. Chem.
2011, 50, 12252−12262. (b) Parks, D. J.; Blackwell, J. M.; Piers, W. E.
J. Org. Chem. 2000, 65, 3090−3098. (c) Parks, D. J.; Piers, W. E. J. Am.
Chem. Soc. 1996, 118, 9440−9441. (d) Rendler, S.; Oestreich, M.
Angew. Chem., Int. Ed. 2008, 47, 5997−6000.
ASSOCIATED CONTENT
* Supporting Information
Text, figures, and tables giving experimental procedures and
characterization data. This material is available free of charge via
the Internet at http://pubs.acs.org.
■
S
AUTHOR INFORMATION
Corresponding Author
*E-mail for S.E.D.: sdenmark@illinois.edu.
■
Notes
The authors declare no competing financial interests.
D
dx.doi.org/10.1021/om400582k | Organometallics XXXX, XXX, XXX−XXX