1,2-Nucleophilic addition of 2-(picolyl)organoboranes to nitrile, aldehyde, ketone, and amide

Article abstract of DOI:10.1039/c2ob25518a

A series of 2-(picolyl)borane molecules were synthesized as products of the reaction between 2-(picolyl)lithium and R₂BOMe (R = ethyl, 9-BBN, phenyl, 9-borafluorenyl). The 2-(picolyl)boranes were dimeric; whereas, monomers coordinated to LiOMe could be isolated when the synthesis was carried out in the presence of TMEDA and THF. The 2-(picolyl)boranes undergo reaction with nitriles, ketones, aldehydes, and amides with apparent 1,2-addition of the B-C(picolyl) bond to the unsaturated bond. Theoretical models reveal the presence of a donor orbital on the 2-(picolyl)borane with significant electron density at the benzylic carbon that we conclude was involved in nucleophilic attack on the electrophilic center of unsaturated organic functional groups.

Full text of DOI:10.1039/c2ob25518a

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PAPER
1,2-Nucleophilic addition of 2-(picolyl)organoboranes to nitrile, aldehyde,
ketone, and amide†
Jung-Ho Son and James D. Hoefelmeyer*
Received 9th March 2012, Accepted 21st June 2012
DOI: 10.1039/c2ob25518a
A series of 2-(picolyl)borane molecules were synthesized as products of the reaction between 2-(picolyl)-
lithium and R2BOMe (R = ethyl, 9-BBN, phenyl, 9-borafluorenyl). The 2-(picolyl)boranes were dimeric;
whereas, monomers coordinated to LiOMe could be isolated when the synthesis was carried out in the
presence of TMEDA and THF. The 2-(picolyl)boranes undergo reaction with nitriles, ketones, aldehydes,
and amides with apparent 1,2-addition of the B–C(picolyl) bond to the unsaturated bond. Theoretical
models reveal the presence of a donor orbital on the 2-(picolyl)borane with significant electron density at
the benzylic carbon that we conclude was involved in nucleophilic attack on the electrophilic center of
unsaturated organic functional groups.
A 1,2-borylphosphinoethene with bulky phosphine and highly
electrophilic –B(C6F5)2 group was found to undergo 1,2-addition
Introduction
Frustrated Lewis pairs (FLPs) have received much attention
recently. For instance, they have been shown to activate H2,
CO2, RSSR, participate in hydrogenation and carboboration reac-
tions, etc.1,2 Theoretical investigation even points out the poten-
tial for heterolytic cleavage of the methane C–H bond in the
presence of a highly preorganized active site.3 Catalysis
mediated by FLPs could offer new opportunities for catalyst
design and optimization. An early example is the catalytic
hydrolysis of 2-chloroalcohols in the presence of 8-quinoline
boronic acid.4
Recently, Bourissou and co-workers reported the synthesis of
2-(picolyl)dicyclohexylborane, (2-(picolyl)BCy2).5 The mol-
ecule was found to exist in equilibrium between monomeric and
dimeric forms. Addition of dichlororuthenium(II)cymene dimer
to 2-(picolyl)BCy2 led to dissociation of the dimer and for-
mation of ruthenium–nitrogen and boron–chlorine dative bonds.
No reactions with other substrates have been reported for
2-(picolyl)BCy2. In particular, the preorganized nature of the
monomeric FLP could allow their utilization as active site for
activation of polar unsaturated organic molecules. Examples
already exist in which a preorganized FLP forms a chelate struc-
ture (I) with polar unsaturated bond (Scheme 1).
to unsaturated substrates trans-cinnamic aldehyde and norbor-
nene.6 Interestingly, a similar bifunctional activation could be
involved in the reaction of bis(pentafluorophenyl)borinic acid,
(C6F5)2BOH, with nitriles that led to six-member BOBOCN
rings.7 Reaction of 2-pyridylaminodiorganoborane with isocya-
nate led to a chelate structure in which the pyridine N-atom was
donor to the isocyanate C-atom, and a boron–oxygen bond was
formed that completed the six-member ring.8,9 Balueva and co-
workers reported 1,2-borylphosphinoethene reacted with small
polar molecules such as ketene, diazo compounds,10 keteni-
mine,11 carbodiimide, isothiocyanate,12 acetyl chloride,13 alde-
hyde,14,15
oxygen,
carbon
disulfide,16
isocyanate,17
thiocyanate,18 sulfur and selenium;19 though, it was unreactive
toward nitriles and ketones.
Department of Chemistry, University of South Dakota, 414 E. Clark St.,
Vermillion, SD 57069, USA. E-mail: James.Hoefelmeyer@usd.edu
†Electronic supplementary information (ESI) available: Experimental
data for 1a, 2a, 2b and reactions of 1–4 with ketones, aldehydes, amine,
and nitriles, Ortep drawings, and Cartesian coordinates of atomic pos-
itions from DFT calculations. CCDC 871057–871077. For ESI and
crystallographic data in CIF or other electronic format see DOI:
10.1039/c2ob25518a
Scheme 1 Activation of polar unsaturated organic molecules in the
presence of preorganized FLP to form chelate structures (I), and starting
model for interaction of 2-(picolyl)boranes with polar unsaturated
bonds (II).
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We synthesized a family of 2-(picolyl)boranes, 2-(picolyl)-
BR2 (R = Et, Ph; BR2 = 9-borafluorenyl, 9-borabicyclononane
(BBN)). The molecules were combined with several types of
polar unsaturated molecules: nitriles, aldehydes, ketones, and
amide. The 2-(picolyl)boranes do not form adducts with the
polar unsaturated functional group with dual coordination (II,
Scheme 1). Instead we observed the product of an apparent 1,2-
nucleophilic addition (1,2-carboboration) of the 2-(picolyl)-
borane to the unsaturated organic molecules (Scheme 2). Reac-
tions with alkyl side-chains at the 2- or 6- position of a pyridine
ring are well known due to the stabilization of the conjugated
enaminate.20–22 The additional boron atom enhances the stability
of the enaminate. Therefore, the role of the 2-(picolyl)boranes as
bifunctional catalysts in the activation of polar unsaturated bonds
is diminished.
can adopt non-superimposable clock-wise or counter clock-wise
mirror images (Scheme 4). According to X-ray data, the isomer-
ism in 1 and 3 was found to be opposite of 2 and 4; however, we
cannot so far rule out whether the four molecules could adopt
either isomer. We note that boracycles (2 and 4) have opposite
conformations than diorganoboryl with two free groups (1 and
3), and interestingly the 2-(picolyl)dicyclohexylborane dimer
has like isomerism with 1 and 3. The chair conformation has not
been observed.
The boat shape 8-membered ring geometry is rigid in solution
without flipping, as evidenced by NMR. Two well-separated
doublets (1: 3.54 and 2.39 ppm) assigned to inequivalent
1
benzylic protons were observed in the H NMR spectrum. NOE
experiments show the resonance at 3.54 ppm belongs to the
inner ring proton and the resonance at 2.39 ppm to the outer ring
proton. The rigidity of the dimer differentiates axial and equator-
ial ethyl groups (1), resulting in four different multiplets from
each proton of ethyl CH2 and two different triplets from ethyl
CH3. A sharp 11B NMR peak at 0.77 ppm was found, and is
within the chemical shift range for tetracoordinate boron. Negli-
Results and discussion
The molecule 2-picoline was deprotonated in the presence of
n-butyllithium, and addition of diorganomethoxyborane led to
formation of 2-(picolyl)organoboranes 1–4 (Scheme 3). Isolation
of the molecules required an additional step, as the initial crude
product was the lithium methoxide adduct. Further treatment
with BF3OEt2 or B(OEt)3 produced [2-(picolyl)BR2]2 dimer
without alkoxide. Alternatively, lithiation in the presence of
N,N,N′,N′-tetramethylethylenediamine (TMEDA) followed by
addition of the boron source led to clean formation of mono-
meric 2-(picolyl)borane as adduct with lithium methoxide.
The structures of 1–4 were determined with X-ray crystallo-
graphy (structural parameters can be found in the ESI†) and are
shown in Fig. 1. In all cases the molecule is found in dimeric
form wherein the central 8-member ring adopts a boat confor-
mation (similar to the shape of cyclooctatetraene). Stereoisomer-
ism is possible in the dimer structure, and the 8-membered ring
1
gible changes were seen in the H and 11B VT NMR spectra (in
C6D6) up to 80 °C, suggesting that the rigidity of the boat shape
8-membered ring is retained even at elevated temperature and
that there is no dissociation into monomer. NMR data of 1–4
show similar features: two different doublets from the benzylic
protons and differentiated axial and equatorial diorganoborane
groups. The dimers have different dihedral angles between the
pyridine rings, depending on the group attached to boron: 1,
64.02(4)°; 2, 43.34(9)°; 3, 89.22(5)°; 4, 86.91(8)°. In contrast,
2-(picolyl)BCy2 has a wide dihedral angle between the pyridine
rings (113.05°). This dihedral angle may be symptomatic of the
degree of sp2 hybridization at the benzylic carbon and boron
atoms.
A solution of 1 in acetonitrile was nearly colorless, but upon
heating, the solution gradually turned deep yellow and finally
Scheme 2 Reaction products formed from 2-(picolyl)boranes and nitrile, amide, ketone, or aldehyde.
Scheme 3 Synthesis of 2-(picolyl)boranes 1 (R = Et), 2 (BR2 = 9-BBN), 3 (R = Ph), 4 (BR2 = 9-borafluorenyl).
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Fig. 2 Structure of 6 in the crystal. Thermal ellipsoids are shown at
50% probability. Hydrogen atoms are omitted.
doublets from the benzylic protons of 1 disappeared and a broad
peak at 3.85 ppm and a doublet at 4.42 ppm emerged. The oily
nature of the product prevented it from structural characteriz-
ation; however, the nature of the product was revealed by the
reaction of 1 with benzonitrile, which produced orange–red crys-
tals after recrystallization from CH2Cl2. Upon crystal structure
determination a new product (6) was identified (Fig. 2) that
apparently formed as a result of 1,2-addition of the B–C bond to
the nitrile. The product was an aminoborane with intramolecular
coordination of the pyridine nitrogen to form a 6-member ring.
Due to the presence of a conjugated double bond in the ring, it is
almost planar; whereas, boron is displaced from the plane. The
11B NMR peak at 1.4 ppm is indicative of tetracoordinate boron.
Inspired by the nitrile insertion product, the reactivity of 1–4
with nitriles, aldehyde, ketone, and amide was also examined.
The reactions were carried out in toluene with 1 : 2 stoichio-
metric ratio of dimer : unsaturated group (except acetonitrile and
N,N-dimethylacetamide). Analogous 1,2-addition of the B–C
(picolyl) bond to the unsaturated bond occurred, except that 4
proved unreactive. Reaction with dicyanobenzenes led to 1,2-
addition with two equivalents of 2-(picolyl)borane. Aldehydes
and ketones appeared to react more readily than nitriles. In con-
trast to the orange–red colored nitrile insertion products, the pro-
ducts from addition of aldehyde or ketone were nearly colorless
due to the lack of conjugation in the new 6-member ring. The
reaction of 1, 2, or 3 with N,N-dimethylacetamide gave rise to
another type of product. The structure showed the insertion of
the carbonyl group and absence of the dimethylamino group. As
a result, the product has a conjugated 6-member ring in addition
to the picoline ring, similar to the nitrile insertion product. The
reactions with nitrile, ketone, aldehyde, and amide are summar-
ized in Table 1 with experimental details in the ESI.†
Fig. 1 Structures of 1–4 (descending from top to bottom) from single
crystal X-ray diffraction data. Thermal ellipsoids are shown at 50% prob-
ability. Hydrogen atoms except benzylic protons are omitted.
The monomers, as LiOMe adducts, undergo reaction with
nitriles in 1 : 1 stoichiometry to form a 1,2-insertion product
identical to that formed from reaction of nitriles with dimeric
species. The reaction of 1-Li(OMe)(TMEDA), 1a, with aceto-
nitrile occurs at room temperature over about one hour; whereas,
the reaction with dimeric 1 required elevated temperature.
Compound 2 appears slightly less reactive than the monomeric
LiOMe adducts.
Scheme 4 Conformations and isomerism of the central 8-member ring
of 2-(picolyl)borane dimers.
1
became orange. The H NMR of the oily product after solvent
removal indicated complete conversion to a new product, 5. Two
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Table 1 Reaction conditions and yields for products 5–24
Borane
Electrophile
T (°C)
Time (h)
Isolated yield
Product
1
1a
1
Acetonitrile
Acetonitrile
Benzonitrile
70
25
60
12
1
3
99
100a
29
5
5
6
1
1
1
1
1
1
1
1
1,2-Dicyanobenzene
1,3-Dicyanobenzene
1,4-Dicyanobenzene
Benzophenone
2-Chloroacetophenone
4-Chlorobenzaldehyde
4-Nitrobenzaldehyde
p-Trifluorotolualdehyde
p-Trifluorotolualdehyde
Crotonaldehyde
70
60
60
60
80
85
80
80
25
70
50
60
25
50
25
60
4
96
79
96
76
47
90
51
7
8
9
12
12
3
12
12
1
3
0.3
3
10
11
12
13
14
14
15
16
17
n/a
18
19
20
21
22
23
24
n/a
69
1a
1
1
100a
100
85
Heptaldehyde
2
3
1
N,N-Dimethylacetamide
N,N-Dimethylacetamide
Benzonitrile
4-Chlorobenzaldehyde
N,N-Dimethylacetamide
Acetonitrile
38
1a
2b
2b
2
3
3
3
3
4
dec.a
44
3
12
2
12
3
2
3
81
94
98
72
89
70
0
100
100
100
100
110
Benzonitrile
4-Chlorobenzaldehyde
N,N-Dimethylacetamide
Benzonitrile
12
a NMR Yield.
The reaction of 2-pyridylaminodiorganoborane (or 2-amino-
thiazoledialkylborane) with nitrile, carbonyl, or acetylene
resulted in 1,2-addition of the B–N bond to the unsaturated
bond.23–25 This is in contrast to its reaction with isocyanate,
which formed the chelated structures.8,9 Theoretically, the 1,2-
addition of the B–N bond to unsaturated bonds could proceed
via 4-member or 6-member cyclic transition states. In the
former, the 2° amine participates in SN2 reaction with the elec-
trophilic carbon of the substrate (nitrile, etc.); whereas, in the
latter borotropic rearrangement to form a conjugated imine–
aminoborane presents an imine nucleophile to the unsaturated
substrate (Scheme 5). It is possible that the interaction of the 2°
amine with the electrophile induces concerted weakening of the
B–N bond that leads to a borotropic shift.
Neutral 2-pyridylaminoborane is isoelectronic with deproto-
nated (at the benzylic carbon) 2-(picolyl)borane, and suggests
the mode of reactivity toward polar unsaturated bonds in the
latter. Furthermore, Hamana and Sugasawa showed that addition
of R2B+ (as triflate) to 2-picoline sufficiently stabilized the enam-
inate that it subsequently participated in nucleophilic addition to
aldehydes.21 Related to this, addition of chiral R2B+ to oxazoline
stabilized azaenolates led to a stereochemically selective aldol
reaction.26 Carboranyldibutylborane was found to undergo 1,2-
addition with nitrile and aldehyde in basic solvent.27,28 Base
coordination to boron led to polarization of the B–C(carboranyl)
bond and subsequent nucleophilic addition was proposed to
occur through a 4-member cyclic transition state.
could stabilize the adjacent resonance stabilized carbanion upon
deprotonation (to form a structure isoelectronic with 2-pyridyl-
aminodiorganoborane). Furthermore, a borotropic shift would
lead to a reactive conjugated tetraene intermediate. The obser-
vation that acetylene reacts with 2-pyridylaminodiorganoborane
even suggests a Diels–Alder type mechanism. However, the con-
jugated tetraene is a resonance form of the N-boronium stabilized
2-picolyl anion. We propose that dimeric 2-(picolyl)boranes are
susceptible to B–C bond breaking within the 8-member core due
to the dual donation of electron density from nitrogen to boron.
We note the observation of 1,2-addition to carboranyldibutylbor-
ane was promoted by Lewis base, and conclude that the dimer is
source of N-boronium stabilized 2-picolyl anion that could par-
ticipate in 1,2-addition to polar unsaturated bonds via 6-member
cyclic transition state.
Computational study
Dimeric compounds. The origin of reactivity of dimeric 1–4
toward polar unsaturated bonds in organic molecules can be
understood upon inspection of their molecular orbitals. The
orbital analysis of the dimeric species is important since the
NMR data shows no evidence of monomeric species in solution
at elevated temperatures. Therefore, we propose that dimeric
species are reactants in the apparent 1,2-carboboration of polar
unsaturated substrates. We performed DFT calculations using the
B3LYP/6-31G* basis set. The optimized geometry of 1–4 is
approximately C2 in symmetry. The energies and orbital surfaces
(HOMO − 9 through LUMO + 1) were calculated with isovalue
of 0.032 e− au−3. Our analysis will focus on the filled MOs that
have significant probability at the benzylic carbon, with attention
We attempt to rationalize the observation of apparent 1,2-
addition of the B–C bond of 2-(picolyl)boranes to polar unsatu-
rated bonds in an explanation that incorporates all of the above
findings (Scheme 6). Noting the stability of the 2-picolyl anion,
2-(picolyl)borane is simply a borylated form wherein boron
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Scheme 5 Proposed (4- or 6-member) cyclic transition states on the approach of polar unsaturated bond to 2-pyridylaminodiorganoborane to form
the 1,2-addition product versus type I chelate structure.
to the C(picoline)–C(benzylic)–B interactions. The LUMO of all
dimers 1–4 is localized on the pyridine rings, and we conclude
that the electron rich atom of the polar unsaturated substrate does
not form a dative bond to boron initially. Furthermore, as we
have no evidence to support dissociation of the dimer 1–4 to
monomeric species, we do not conclude type I chelate structures
are possible. Among the (HOMO through HOMO − 9) orbitals,
three types of MOs are conserved in compounds 1–4 that will be
called pic(π*)C(σ)B, pic(π)C(σ)B, and C(σ)B as shown in
Scheme 7.
The orbital representations in Scheme 7 are only a simplified
picture, as the complete wavefunctions have additional contri-
butions throughout the molecule. The C(σ)B and pic(π)C(σ)B
MOs are lower in energy than pic(π*)C(σ)B due to the stronger
bonding interactions. The pic(π*)C(σ)B MO is antibonding
between the picoline ring and the benzylic carbon and bonding
between the benzylic carbon and boron. A loss of electron
density from the MO would give rise to a weakening B–
MO. Experiments show that 4 is extremely sluggish in reactions
with polar unsaturated bonds; whereas 1 and 2 undergo the same
reactions within hours or minutes.
The proposed mechanism of the reaction is that electron
density from the benzylic carbon attacks an electrophilic carbon
atom in a polar unsaturated bond in an SN2 reaction. In this
elementary step, a C–C bond forms due to donation of electron
density from the pic(π*)C(σ)B type MO to the electrophilic
carbon atom of a polar unsaturated bond. Donation of electron
density from this orbital will lead to weakening of the B–C
bond, which should be accompanied by charge buildup on the
more electronegative member of the unsaturated bond. The
newly concentrated electron density contributes to a bond-
making step with boron. The result is the apparent 1,2-carbo-
boration reaction of the B–C(benzylic) bond to a polar unsaturated
bond and formation of a 6-member ring.
Monomeric compounds as Li-base adducts. Faster reaction
rates of 1,2-addition with polar unsaturated bonds were observed
with monomeric counterparts. The molecules 1a, 2a, and 2b
(ESI†) have a high-lying HOMO that is mostly boron–oxygen
(π*) in character; however, we do not observe products from
nucleophilic addition of methoxide to electrophilic centers. The
HOMO − 1 is a pic(π*)C(σ)B type MO deemed responsible for
the 1,2-addition reaction. The calculated HOMO − 1 of 1a, 2a,
and 2b is higher in energy than the pic(π*)C(σ)B type MO in
1–4. The same addition products were observed starting from 1
or 1a, or from 2, 2a, or 2b. We propose an identical reaction
mechanism based on the MO analysis. The highest lying pic(π*)-
C(σ)B type MO coincides with the fastest reactant in the 1,2-
addition reaction. Whether the reactant is a 2-(picolyl)borane
dimer or lithium methoxide adduct to the monomer, the mo-
lecules feature a reactive benzylic carbon with significant elec-
tron density in a high-lying frontier orbital. In both cases, the B–
C
(benzylic) bond and more stable C(picoline)–C(benzylic) bond.
The energies of (HOMO through HOMO − 9) were compared
with attention to the pic(π*)C(σ)B type MOs (Chart 1). Mo-
lecules 3 and 4 include additional π-bonding MOs due to the
presence of conjugated ring systems. While at first it may appear
counter-intuitive that the energies of (HOMO through HOMO −
9) are increasing as the electron withdrawing power of the
organic groups on boron is increasing, this can be understood
given the additional π-bonding MOs that originate from phenyl
and borafluorene groups. It is more instructive to view the trend
of energy of a conserved MO type. Here, the attention will be
focused on the pic(π*)C(σ)B type MOs because we propose
these are the source of electron density that initiates the 1,2-
nucleophilic addition reaction. In Fig. 3, the HOMO of 1 is
shown, which is representative of the pic(π*)C(σ)B type MOs.
Interestingly, the energy of the pic(π*)C(σ)B type MO shows
two consistent trends. First, as the electron withdrawing power of
the organic groups attached to boron increases, the energy of the
pic(π*)C(σ)B type MO decreases. Second, the (qualitative) rate
of reaction is fastest with a higher energy pic(π*)C(σ)B type
C
(benzylic) bond is activated by the presence of a base coordinated
to boron. This type of activation was also observed in the polar-
ization of B–C(carboranyl) bonds that led to 1,2-addition to nitrile
or aldehyde.27,28
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Scheme 6 Formation of the N-boronium stabilized 2-picolyl anion upon dissociation of the 2-(picolyl)borane dimer via Lewis base induced dis-
sociation of the B–C(benzylic) bond is the proposed route to the apparent 1,2-nucleophilic addition to polar unsaturated bonds.
Scheme 7 Frontier MOs of 1–4 with significant probability at the
benzylic carbon.
Chart 1 Calculated bonding orbital energies (HOMO through HOMO
− 9) of compounds 1–4 are shown. In bold are the orbitals proposed to
be involved in the first step of the 1,2-addition; SN2 attack of the
benzylic carbon to an electrophilic unsaturated carbon. The heavy dotted
line marks the calculated boron–carbon bond distances in 1–4.
Conclusion
Reaction of 2-(picolyl)lithium with R2BX reagents led to
2-(picolyl)boranes. The molecules were found to be dimeric;
however monomers coordinated to lithium alkoxide could be
isolated. Members of the 2-(picolyl)boranes feature four-coordi-
nate boron, and were found to undergo 1,2-nucleophilic addition
(1,2-carboboration) to unsaturated bonds of nitrile, aldehyde,
ketone, and amide. In theoretical models, a high-lying filled
molecular orbital with significant electron density at the benzylic
carbon was found and presumed responsible for the carbobora-
tion reaction. The orbital energy of the 2-(picolyl)borane
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n-BuLi solution in hexane was added slowly and kept at −78 °C
for 30 min. Diethylmethoxyborane (6.4 g, 64.0 mmol) in 20 mL
THF was added via cannula. The contents were allowed to warm
to room temperature overnight. Then the contents were again
cooled to −78 °C and BF3·OEt2 (9.1 g, 64.1 mmol) in 20 mL of
THF was added via cannula. The solution was allowed to warm
to room temperature overnight. The solvent was removed under
vacuum, and an orange–brown oil remained in the flask. Purifi-
cation was performed by acetonitrile–hexane extraction. The
acetonitrile portion was dark, and the hexane portion was light
orange color. The hexane portion was kept, and evaporation of
the solvent in vacuo gave an orange oil that crystallized in a
glovebox. Analytically pure product was obtained by extraction
of the product with pentane. Large prism crystals (up to 1 cm)
were obtained upon slow evaporation of pentane in the glovebox.
Yield: 4.72 g (45%). Mp: 76–78 °C. δH (200 MHz; C6D6;
C6H6): 0.39–0.56 (1 H, m, CH2CH3, H8), 0.81 (3 H, t, J 7.2,
CH2CH3, H11a–c), 0.88–1.11 (2 H, m, CH2CH3, H8 and H10),
1.15–1.33 (1 H, m, CH2CH3, H10), 1.31 (3 H, t, J 7.4, CH2CH3,
H9a–c), 2.39 (1 H, d, J 11.4, H7out), 3.54 (1 H, d, J 11.4, H7in),
6.03 (1 H, dt, J 7.2 and 1.8, H3), 6.70 (1 H, dt, J 7.0 and 1.6,
H4), 6.81 (1 H, td, J 7.0 and 1.2, H5), 7.74 (1 H, d, J 6.2, H2).
δC (50 MHz; CDCl3; CHCl3) 9.6 (C11), 10.9 (C9), 13.2 (br, C8
and C10), 33.9 (br, C7), 117.8 (C3), 126.5 (C5), 136.9 (C4),
143.6 (C2), 169.6 (C6). δB (128 MHz; C6D6; BF3OEt2) 0.77.
Found: C, 74.26; H, 10.16; N, 8.79. C10H16BN requires C,
74.58; H, 10.01; N, 8.70%.
Fig. 3 Highest occupied molecular orbital (HOMO) of 1 from DFT
calculation using B3LYP/6-31G* basis set.
nucleophile depends on the groups bound to boron and correlates
qualitatively with the rate of reaction with unsaturated substrates.
Similarly, the dimeric 2-(picolyl)borane can be viewed as source
of N-boronium stabilized picolyl anion due to the destabilization
of the B–C(benzylic) bond at the four-coordinate boron. A more
detailed theoretical investigation into the specific reaction
pathway may be an opportunity for future study. Potentially, as
demonstrated in other studies, a chiral organoborane moiety
could be substituted in order to create stereochemically selective
reactions with aldehydes or asymmetric ketones, which may be a
direction for future work.
(2-Picolyl)borabicyclononane dimer (2)
Experimental section
2-Picoline (2.0 g, 21.5 mmol) was dissolved in 30 mL THF and
cooled to −78 °C. To this solution n-BuLi (1.6 M in hexane,
14 mL, 22.4 mmol) was added via cannula and kept cold for 1 h
after which 9-methoxy-9-BBN (1.0 M in hexane, 21 mL,
21.0 mmol) was added via cannula. The reaction was allowed to
warm to room temperature overnight. Solvent was removed
in vacuo and the product was dissolved in 20 mL of CH2Cl2.
BF3·OEt2 (3.0 g, 21.1 mmol) in 10 mL of THF was added via
cannula. Solvent was removed in vacuo and the product was
extracted with CH2Cl2. Crystals formed by slow evaporation of
the solvent. The product could be further purified by extraction
with toluene. Yield: 1.8 g (39%). Mp: 126–128 °C. δH
(200 MHz; CDCl3; CHCl3): 0.90–1.14 (3 H, br m, BBN),
1.53–1.87 (10 H, br m, BBN), 2.34 (1 H, br s, BBN), 2.74 (1 H,
d, J 11.4, H7out), 3.24 (1 H, d, J 11.2, H7in), 6.56 (1 H, dt, J 6.8
and 1.6, H3), 6.94 (1 H, d, J 8.2, H5), 7.35 (1 H, dt, J 7.6 and
1.6, H4), 7.63 (1 H, d, J 6.2, H2). δC (50 MHz; CDCl3; CHCl3)
22.8, 24.0, 30.8, 31.6, 34.8, 117.1(C3), 125.5(C5), 136.8(C4),
144.7 (C2), 171.7(C6). HRMS (ESI) m/z calcd for (2 + H3O+)
C28H43B2N2O: 445.356148, found: 445.35704.
General procedures
All procedures were carried out using standard Schlenk line tech-
nique or in a glovebox under N2 or Ar atmosphere. 2-Picoline
was distilled over CaH2. THF, dichloromethane, acetonitrile,
hexane and pentane were obtained from solvent dryer system
(Puresolv). Diethylmethoxyborane, 9-methoxy-9-BBN (1.0 M in
hexane), n-butyllithium (1.6 M in hexanes), benzonitrile, benzo-
phenone and N,N-dimethylacetamide were purchased from
Aldrich. Benzonitrile and N,N-dimethylacetamide was dried over
4 Å molecular sieve. Diphenylmethoxyborane29 and 9-methoxy-
9-borafluorene30 were synthesized according to the literature. 1H,
13C and 11B NMR spectra, VT NMR, as well as 2D-COSY,
HMQC and 1D-NOE experiments, were obtained using
Varian 200 MHz Mercury-plus NMR spectrometer or
400 MHz JEOL ECS-400 NMR spectrometer. Elemental
analysis was carried out using an Exeter CE-440 Elemental
Analyzer or performed by Atlantic Microlab, Inc. HRMS
data were obtained using Bruker Daltonics ESI FTICR MS at
the South Dakota State University Mass Spectrometry facility.
Experimental data for 1a, 2a, 2b and 5–24 can be found in
the ESI.†
(2-Picolyl)diphenylborane dimer (3)
2-Picoline (1.0 g, 10.7 mmol) was dissolved in 15 mL THF and
cooled to −78 °C. To this solution n-BuLi (1.6 M in hexane,
7 mL, 11.2 mmol) was added and kept cold for 30 min. Diphe-
nylmethoxyborane (2.1 g, 10.7 mmol) in 10 mL THF was added
via cannula, and the contents were allowed to warm to room
(2-Picolyl)diethylborane dimer (1)
2-Picoline (6.0 g, 64.4 mmol) was dissolved in 40 mL THF and
cooled to −78 °C. To this 41.6 mL (66.6 mmol) of 1.6 M
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temperature overnight. The solvent was removed in vacuo and
the product was dissolved in 40 mL of dichloromethane.
BF3·OEt2 (1.6 g, 11.0 mmol) was added via cannula. After
30 min, solvent was removed in vacuo and the product was
washed with 95% ethanol until white product remained. The
product was sonicated in distilled water and the remaining white
powder was filtered and washed with ethanol. Yield: 1.0 g
(36%). Mp: >300 °C. δH (200 MHz; CDCl3; CH2Cl2): 2.39 (1
H, d, J 11.8, CH2), 3.81 (1 H, d, J 12.0, CH2), 6.56 (1 H, dd, J
7.7 and 1.1, H5), 6.78–6.82 (2 H, br m, o-Heq), 6.97–7.04 (3 H,
br m, H3 and o-Hax), 7.12–7.25 (6 H, br m, H-m and H-p), 7.59
(1 H, dt, J 7.6 and 1.6, H4), 8.54 (1 H, d, J 6.4 and 1.4, H2). δC
(50 MHz; CDCl3; CDCl3) 119.0 (C3), 125.1 (C-p), 125.3 (C-p),
126.9 (C-m), 127.4 (C-m), 130.8 (C5), 132.1 (o-Cax), 134.2
(o-Ceq), 137.8 (C4), 147.4 (C2), 168.8 (C6). δB (64 MHz;
CDCl3; BF3OEt2) 2.45 (br). HRMS (ESI) m/z calcd for (3+)
C36H32B2N2: 514.275158, found: 514.27789. Found: C, 83.08;
H, 6.34; N, 5.45. C18H16BN requires C, 84.08; H, 6.27; N,
5.45%.
Acknowledgements
We thank Mr. Brandon Gustafson in the Department of Chem-
istry, Augustana College (Sioux Falls, SD) for assistance with
NMR experiments performed on the 400 MHz instrument (sup-
ported by NSF/EPSCOR (0903804), NIH Grant Number 2 P20
RR016479 from the INBRE Program of the National Center for
Research Resources, the state of South Dakota, and the Roland
Wright Chemistry Equipment Endowment, Augustana College).
This work was supported by the U.S. Department of Energy
under Contract Nos. DE-FG02-08ER64624 and DE-EE0000270,
NSF EPSCOR 0903804, South Dakota 2010 Initiative ‘Center
for Research and Development of Light-Activated Materials’,
and startup funds from the University of South Dakota. Purchase
of the single crystal X-ray diffractometer and glovebox was
made possible by the National Science Foundation
(EPS-0554609). The instrumentation in the SDSU Campus Mass
Spectrometry Facility used in this study was obtained with
support from the National Science Foundation/EPSCoR (Grant
No. 0091948) and the State of South Dakota.
9-(2-Picolyl)-9-borafluorene dimer (4)
References
2-Picoline (1.0 g, 10.7 mmol) was dissolved in 20 mL of THF
and cooled to −78 °C. To this solution n-BuLi (1.6 M in hexane,
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(1 H, d, J 7.4, C15), 8.13 (1 H, dd, J 6.5 and 1.3, H2). δC
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(4 + H+) C36H29B2N2: 511.251683, found: 511.24775.
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