Synthesis of B,O,N-Doped Adamantanes and Diamantanes by Condensation of Oximes with Boronic Acids

Article abstract of DOI:10.1021/acs.joc.5b00892

Condensation of oximes with boronic acids RB(OH)₂ or B(OH)₃ affords remarkably stable 2,4,10-trioxa-1,5,7-triaza-3-boroadamantanes via an unprecedented multicomponent process. The mechanism involves the reversible generation of unstable oxime cyclotrimers, which are readily intercepted by boronic acids.

Full text of DOI:10.1021/acs.joc.5b00892

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Article
Synthesis of B,O,N-Doped Adamantanes and Diamantanes
by Condensation of Oximes with Boronic Acids
Ivan S. Golovanov, Alexey Yu. Sukhorukov, Yulia V. Nelyubina,
Yulia A. Khomutova, Sema L. Ioffe, and Vladimir A. Tartakovsky
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 02 Jun 2015
Downloaded from http://pubs.acs.org on June 2, 2015
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Synthesis of B,O,NꢀDoped Adamantanes and Diamantanes by Condensation of Oximes
with Boronic Acids
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Ivan S. Golovanov,† Alexey Yu. Sukhorukov,*,† Yulia V. Nelyubina,‡ Yulia A. Khomutova,†
Sema L. Ioffe,† Vladimir A. Tartakovsky†
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†N.D. Zelinsky Institute of Organic Chemistry, Leninsky prospect 47, 119991, Moscow, Russia
‡A.N. Nesmeyanov Institute of Organoelement Compounds, Vavilov str. 28, 119991, Moscow,
Russia
* sukhorukov@ioc.ac.ru
ABSTRACT
Condensation of oximes with boronic acids RB(OH)2 or B(OH)3 affords remarkably stable
2,4,10ꢀtrioxaꢀ1,5,7ꢀtriazaꢀ3ꢀboroadamantanes via an unprecedented multiꢀcomponent process.
The mechanism involves the reversible generation of unstable oxime cyclotrimers, which are
readily intercepted by boronic acids.
INTRODUCTION
Adamantane derivatives find numerous applications in medicine, material sciences, as well
as in the rational design of functional molecules and nanosystems.1 Substitution of carbon atoms
for heteroatoms provides vast opportunities for tuning adamatane properties and thus creation of
substances and materials with predefined characteristics.2 Thus, incorporation of heteroatoms
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such as nitrogen, oxygen or boron in adamantane cage results in a significant enhancement of
pharmacological activity that led to development of highly potent heteroadamantaneꢀbased
antiviral drugs.2a Some other staggering applications of heteroadamantanes are known.
Polyazaadamantanes are used as precursors of highꢀenergy materials2b and biodegradable
polymers.2c Diamondoid molecules doped with oxygen atoms exhibit unusual electronic
properties.2d Incorporation of boron and nitrogen atoms in the diamond structure produces a
superhard and chemically inert material (“heterodiamond”) with improved characteristics
compared to diamond itself.2e
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Owing to a significant progress in the synthesis of cage systems in 1960−1980s
heteroadamantanes of various structures became available.3 However, not any combination of
heteroatoms in the adamantane skeleton leads to a stable cage structure.4 The reasons of extreme
stability of some heteroadamantanes and lability of other ones are still not completely understood
being probably a superposition of various factors such as stereoelectronic effects, 3D aromacity,
lone electron pair repulsion, electrostatic interactions, etc.4 In this context, basic studies of
structure, stability and reactivity of heterodiamondoid molecules are of high scientific interest.4,5
Unfortunately, traditional approaches to the construction of cage compounds seem to have
exhausted themselves, and thus many challenging heteroadamantane structures still remain
inaccessible.4 Among them are 2,4,10ꢀtrioxaꢀ1,5,7ꢀtriazaꢀ3ꢀheteroadamantanes (Scheme 1) none
of which are known in literature. Quantumꢀchemical calculations at G4 level of theory predict
thermodynamic stability of these heterocage systems over the corresponding isomeric
orthoesters6 (RꢀE(OꢀN=CH2)3) in case atom E is boron, carbon, phosphorous and some other pꢀ
elements. In the present work, the synthesis of 2,4,10ꢀtrioxaꢀ1,5,7ꢀtriazaꢀ3ꢀboroadamantanes 1 as
the first representatives of this unusual class of heteroadamantanes is reported.
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Scheme 1. Suggested approach to the synthesis of heteroadamantanes 1.
We assumed that the assembly of heteroadamantanes 1 can be achieved by a multiꢀ
component condensation of three oxime molecules with a boronic acid involving the formation
of three boronꢀoxygen bonds and cyclotrimerization of oxime groups (Scheme 1). This
previously unknown transformation does not have any close analogy in the chemistry of oximes
and resembles the oneꢀpot multiꢀcomponent synthesis of methenamine from six molecules of
formaldehyde and ammonia.7
RESULTS AND DISCUSSION
In our preliminary studies, phenylboronic acid was treated with an excess of formaldoxime
generated in situ from formaldehyde and hydroxylamine in aqueous methanol (Scheme 2). We
were pleased to find that the desired adamantane 1a did form in moderate yield. However,
product 1a proved to be a labile compound slowly decomposing in solution (DMSOꢀd6, see.
Supporting information) forming formaldoxime and an indecipherable product mixture. Based
on quantumꢀchemical calculations we reasoned, that the presence of a proton on the nitrogen
atom in product 1a may be the course of the instability of 2,4,10ꢀtrioxaꢀ1,5,7ꢀtriazaꢀ3ꢀ
boroadamantane cage. Indeed the adduct of 3ꢀpyridinylboronic acid with formaldehyde oxime
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(product 1b in Scheme 2) proved to be more stable and formed in higher yield, probably,
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because the proton is localized preferably on the nitrogen atom of pyridine ring (Scheme 2).
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Scheme 2. Interaction of formaldoxime with phenylꢀ and 3ꢀpyridinylboronic acids.
In a similar fashion reaction of formaldehyde oxime with PhB(OH)2 in presence of K2CO3
furnished potassium salt of 2,4,10ꢀtrioxaꢀ1,5,7ꢀtriazaꢀ3ꢀboroadamantane 1c (entry 1, Table 1),
for which XꢀRay analysis was performed.8 Product 1c is stable on air up to 250oC and unlike 1a
does not undergo any noticeable decomposition upon storage in DMSOꢀd6 solution within at
least two weeks. Treatment of salt 1c with an excess of HCl results in liberation of
phenylboronic acid (73% yield) demonstrating that protonation leads to decomposition of 2,4,10ꢀ
trioxaꢀ1,5,7ꢀtriazaꢀ3ꢀboroadamantane structure.
Using this protocol several stable potassium salts of heteroadamantanes 1сꢀh containing
various substituents at boron atom were obtained (entries 1−6, Table 1). Importantly, B(OH)3
and B(OCH3)3 also successfully entered the condensation with formaldehyde, hydroxylamine
and K2CO3 to yield potassium salt of adamantanes 1g and 1h in 86% and 85% yields,
respectively (entries 5 and 6, Table 1).
Condensation of acetaldehyde oxime with phenylboronic acid in presence of K2CO3 under
solventꢀfree conditions afforded potassium salt 1i in 73% yield as a mixture of diastereomers
eq,eq,eqꢀ1i and eq,eq,axꢀ1i in 2.0 : 1.0 ratio (entry 7, Table 1). Reaction with propionaldehyde
oxime under same conditions was less smooth and the desired adamantane salt 1j was formed in
10% yield (entry 8, Table 1). In case of a more bulky isobutyraldehyde oxime (Table 1, entry 9)
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the corresponding adamantane 1k was detected only in trace amounts by ESIꢀHRMS.
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Benzaldehyde and acetone oximes did not react with phenylboronic acid (entries 10,11, Table 1).
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Table 1. Synthesis of potassium salts of heteroadamantanes 1.
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Entry
1
c
d
e
f
R
R1
H
H
H
H
H
H
H
H
H
H
R2
H
H
H
H
H
H
Solvent
Yield, %a
1
Ph
CH3OH/H2O 99
CH3OH/H2O 92
CH3OH/H2O 79
CH3OH/H2O 97
2
3ꢀpyridinyl
transꢀCH=CHꢀPh
CH3
3
4
5
OH
H2O
86
g
h
i
b
6
OCH3
CH3OH/H2O 85
7
Ph
Ph
Ph
Ph
Ph
CH3 n.s.c
Et n.s.
iꢀPr n.s
Ph n.s.
73d,e
10d,f,g
traces
n.r.
8
j
9
k
l
10
11
CH3 CH3 CH3OH
n.r.
m
a
b
n.r. – no reaction observed within 24 h. Yields calculated on RB(OH)2. B(OCH3)3
c
d
was used. n.s. – no solvent, 5 equiv. of H2O were added. Eq and ax correspond to
positions of substituents R2 in triazine ring. d.r. eq,eq,eqꢀ1i/eq,eq,axꢀ1i = 2.0 : 1.0.
e
f Determined by H NMR with internal standard. Characterized in mixture with
1
g
potassium phenylborate, d.r. eq,eq,eqꢀ1j/eq,eq,axꢀ1j = 1.0 : 1.4.
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These results clearly demonstrate that the presence of substituents at the oxime group
complicates the formation of products 1. We supposed that the formation of heteroadamantane 1
could proceed easier if three oxime groups were tethered together. The only compounds of this
type available to date are tris(βꢀoximinoalkyl)amines 2 (Table 2).9
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Consequently we studied the interaction of various symmetrically and unsymmetrically
substituted trisꢀoximes 2aꢀj with boronic acids (Table 2). Most of trisꢀoximes 2 studied did react
with PhB(OH)2 to give in good to high yields stable diamantanes 3 containing 2,4,10ꢀtrioxaꢀ
1,5,7ꢀtriazaꢀ3ꢀboroadamantane fused with 1,4,6,10ꢀtetraazaadamantane cage (entries 1–5,8,10,
Table 2). Since basic tertiary nitrogen is present in trisꢀoximes 2 all reactions were performed
without an external base.
The nature of substituents at oxime groups mainly influenced the time needed for a full
conversion of reagents, i.e. more bulky trisꢀoximes 2 reacted slower (cf. entries 2−5, Table 2).
The exceptions were trisꢀoximes 2f bearing three phenyl groups (entry 6, Table 2), 2g with three
CO2Et substituents (entry 7, Table 2) and 2i bearing two phenyl and one benzyl group (entry 9,
Table 2). No conversion of these trisꢀoximes was observed. On the contrary, condensation of
PhB(OH)2 with trisꢀoxime 2h possessing two phenyl groups and a hydrogen at the oxime groups
produced the desired unsymmetrically substituted diamantane 3h in moderate yield (entry 8,
Table 2). Therefore, reaction of trisꢀoximes 2 with boronic acids proved to be much less sensitive
to the substitution at oxime groups as compared to monoꢀoximes. In particular, aldoximes as
well as ketoximes 2 bearing relatively bulky benzyl and phenyl groups afforded the
corresponding diamantanes 3 efficiently.
Various boronic acids were wellꢀtolerated in the reaction with trisꢀoximes 2 (entries 11ꢀ15,
Table 2). In addition to PhB(OH)2 diamantane adducts of trisꢀoxime 2b with methylꢀ,
cyclopropylꢀ, transꢀstyrylboronic acids as well as with В(ОН)3 were prepared in excellent yields
(entries 11−14, Table 2). 1,4ꢀPhenylenediboronic acid in reaction with two equivalents of trisꢀ
oxime 2b selectively produced a 1 : 2 adduct 3o in high yield (entry 15, Table 2).
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Table 2. Condensation of trisꢀoximes 2 with boronic acids.
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Entry
1
2
а
b
c
d
e
f
3
а
b
c
d
e
f
R
R1
R2
R3
H
H
H
H
H
H
H
Yield, %
70a,b
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
CH3
H
H
2
CH3
CH3
89b,c
3
Et
Et
83b,c
4
(CH2)2CO2CH3
(CH2)2CO2CH3
CH2Ph
Ph
78a,b
5
CH2Ph
76b,d
6
Ph
n.r.b,e
n.r.b,e
7
CO2Et
CO2Et
Ph
g
h
i
g
h
i
8
H
CH3 64a,b
9
CH2Ph
Ph
H
H
H
H
H
H
H
n.r.b,d
72b,c
93b,c
91b,c
91b,c
99c,f
10
11
12
13
14
15
(CH2)2CO2CH3
CH3
CH3
j
j
CH3
b
b
b
b
b
k
l
transꢀCH=CHꢀPh CH3
CH3
cyclopropyl
OH
CH3
CH3
CH3
CH3
m
n
CH3
4ꢀ(HO)2BꢀC6H4ꢀ
CH3
83b,c,g
o
a
b
c
d
e
f
g
n.r. – no reaction. 48 h. Solvent – CH3OH. 24 h. 72 h. 96 h. Solvent – H2O. 2 equiv. of 2b were used.
Product –
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Structures of diamantanes 3b and 3n were secured by singleꢀcrystal XꢀRay analysis
(Scheme 3).8 Interestingly, in the crystal of 3n the acidic proton is localized on nitrogen atom
N(1) (form A), while in 3b nitrogen N(2) is protonated (form B) (Scheme 3). In result, a
considerable distortion of triazine ring is observed in 3b due to the elongation of bonds C(4)–
N(2) and C(5)–N(2) (by 0.02–0.04 Å) and shortening of bonds C(4)–N(3) and C(5)–N(4) (by
0.02–0.03 Å) as compared to analogous bonds in 3n. Such distortion results from strong
lp(N)→σ*C–N(2) interactions in structure B leading to charge transfer from lone electron pairs of
nitrogens N(3) and N(4) to the σ* orbitals of C–N(2) bonds as confirmed by NBO analysis for
3b (Supporting information). Furthermore, the presence of a positive charge on nitrogen N(2) in
diamantane 3b leads to the expected shortening of N(2)+–O(1) bond (by 0.03 Å) and elongation
of B–O(1) bond (by 0.02–0.03 Å) as compared to the corresponding bonds with N(3) and N(4).
It is likely, that there is equilibrium between zwitterionic forms A and B in solution leading to
the observed widening of signals in NMR spectra in products 3.
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Scheme 3. Structures of diamantanes 3n and 3b. Methyl groups are omitted for clarity.
Two mechanisms can be proposed for the discovered condensation of oximes with boronic
acids (Scheme 4). The first pathway involves oxime cyclotrimerization furnishing allꢀcisꢀ1,3,5ꢀ
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trihydroxyꢀhexahydroꢀ1,3,5ꢀtriazines 4,10 which serve as matrix for the assembly of adamantanes
1 in reaction with RB(OH)2. The second pathway starts with condensation of three oxime
molecules with a boronic acid furnishing boronates 5, which then cyclize to adamantane 1. Both
routes involve as a key stage the cyclotrimerization of C=NꢀO fragments, which is nonꢀtypical
for oximes.
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Scheme 4. Possible mechanisms for the formation of heteroadamantanes 1.
In our experiments we never observed the formation of openꢀchain oxime ethers 5 neither in
methanol/H2O nor in toluene solutions. In those cases when adamantanes 1 or 3 were not formed
the initial oximes and boronic acids remained unchanged (according to 1H NMR, see Supporting
Information). On the other hand, stable 1,3,5ꢀtrihydroxyꢀ1,3,5ꢀtriazines 4a•HCl10 and 6b
(prepared from 2b9b) readily reacted with phenylboronic acid to give the corresponding
adamantanes 3b in quantitative yield (Scheme 5). Furthermore, strong correlation between
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oxime cyclotrimerization and the formation of corresponding boradamantanes is observed: trisꢀ
oximes 2f,g,i, which did not enter the intramolecular oxime cyclotrimerization,9b did not react
with boronic acids (entries 6,7,9, Table 2). These data suggest that pathway (1) involving oxime
trimers 4 or 6 as key intermediates is likely to be involved (Scheme 4). However, pathway (2)
can not be completely ruled out as a competitive route considering that boronate 5 cyclization to
heteroadamantane 1 should be thermodynamically favored according to G4 theory level
calculations (see Scheme 1 and Supporting Information).
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PhB(OH)2
Ph
K2CO3, 24 h
K
B
O
OH
N
OH
OH
O
O
N
CH3OH
N
N
(1)
H
N
85%
N
Cl
4a•HCl
1c
X-Ray8
Ph
B
PhB(OH)2
CH3OH
0.5 h
O
OH
O
AcOH
CH3OH
CH3
CH3
OH
O
N OH
CH3
N
N
N
H
H3C
H3C
N
N
(2)
2b
CH3
98%
95%
lit.9b
N
6b
N
3b (X-Ray8)
Scheme 5. Reaction of 1,3,5ꢀtrihydroxyꢀ1,3,5ꢀtriazines 4a•HCl and 6b with PhB(OH)2.
Pathway (1) explains why the formation of heteroadamantanes 1 from substituted oximes is
difficult (Table 1). Evidently, the reason is thermodynamic instability of oxime cyclotrimers
4.9b,10 In contrast to azomethines and carbonyl compounds,11 the intermolecular
cyclotrimerization of oximes has been reported only for formaldoxime.10 The resulting trimer 4a
is a kinetic product and decomposes to a monomer and polymer.10 Substitution at the oxime
group hampers its cyclotrimerization both in interꢀ and intramolecular variant that is wellꢀ
illustrated by highꢀlevel quantumꢀchemical calculations (see table in Scheme 4). Thus, we failed
to observe cyclotrimerization of acetaldehyde oxime by 1H NMR in a broad concentration range
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(0.2÷10M in CDCl3) indicating that the equilibrium concentration of the corresponding trimer 2
is very low. Apparently, cyclotrimerization of simple aldoximes takes place only to a very small
extent, however, the trimer 4 still can be intercepted by a boronic acid to give a stable
heteroadamantane anion 1. Therefore, reactions with boronic acids may serve as a convenient
tool to study oxime cyclotrimerization process.
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The suggested strategy for the synthesis of B,O,Nꢀdoped adamantanes may be useful in
the construction of pH responsible boronate linear polymers, dendrimers and supramolecular
systems.12 2,4,10ꢀtrioxaꢀ1,5,7ꢀtriazaꢀ3ꢀboroadamantanes of type 1 and 3 represent interest as
potential antiviral agents considering their structural similarity to bananins.2a,13 Furthermore,
boradamantane salts 1, which are readily prepared by mixing RB(OH)2 with formaldehyde,
hydroxylamine and K2CO3, may be considered as convenient thermoꢀ and airꢀstable forms of
boronic acids. Interestingly, unlike other boronates,14 adamantane 1c proved to be unreactive in
SuzukiꢀMiyaura (SM) coupling with 1ꢀbromoꢀ4ꢀnitrobenzene and 1ꢀbromoꢀ4ꢀmethoxybenzene at
ambient temperature. The formation of coupling product (4ꢀnitrobiphenyl) was observed only at
elevated temperatures and led to complete decomposition of heteroadamantane (Scheme 6).
Scheme 6. SM coupling with boradamantane 1c.
Similar behavior was recently reported by Kuno15 for adamantaneꢀlike boronates derived
from scylloꢀinosytol, which thus was suggested as an effective protective group for arylboronic
acids.14 In this context, boradamantanes 1 may be considered as an alternative to scylloꢀinosytol
complexes of boronic acids. Further studies on application of 2,4,10ꢀtrioxaꢀ1,5,7ꢀtriazaꢀ3ꢀ
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boroadamantanes 1 and 3 in other transition metalꢀcatalyzed crossꢀcoupling reactions are
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currently underway.
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CONCLUSIONS
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In summary, a straightforward synthesis of hitherto unknown 2,4,10ꢀtrioxaꢀ1,5,7ꢀtriazaꢀ3ꢀ
boroadamantanes and their fused derivatives has been achieved by an unprecedented multiꢀ
component condensation of oximes with boronic acids. The discovered process involves
uncommon cyclotrimerization of oximes to unstable 1,3,5ꢀtrihydroxyꢀ1,3,5ꢀtriazaadamantanes,
which react with boronic acids to give the desired heteroadamantanes.
EXPERIMENTAL SECTION
All reactions were performed in ovenꢀdried (150°C) glassware. 1D and 2D NMR spectra
were recorded at room temperature on a 300 MHz spectrometer with residual solvents peaks as
an internal standard.16 Chemical shifts in 11B are given in relative to BF3•Et2O. Multiplicities are
indicated by s (singlet), d (doublet), t (triplet), q (quartet), quint (quintet), m (multiplet), br
(broad). W values correspond to full width at half maximum of signal in Hz. Peaks in FTꢀIRꢀ
spectra data are reported in cmꢀ1 with the following relative intensities: s (strong), m (medium),
w (weak), br (broad), sh (shoulder). HRMS were measured on electrospray ionization (ESI)
instrument with a timeꢀofꢀflight (TOF) detector. Analytical thinꢀlayer chromatography was
performed on silica gel plates with QFꢀ254. Visualization was accomplished with UV light and
solution of ninhydrine/acetic acid in ethanol. CH3OH, EtOH and ethyl acetate were distilled
without drying agents. All inorganic reagents and boronic acids were commercial grade and were
used as received. Trisꢀoximes 2a,c,d,g,9b 2b,e,f,9a 2i,j9c and 1,4,6,10ꢀtetraazaadamantane 6b9b
were synthesized according to previously published protocols. Quantumꢀchemical calculations
were performed with the Gaussian 09 program.
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Synthesis of 3ꢀBoroꢀ2,4,10ꢀtrioxaꢀ1,5,7ꢀtriazaadamantanes 1aꢀg. To a stirred solution of
boronic acid or B(OH)3 (1.0 mmol) in 1.8 mL of CH3OH (for 1aꢀf) or water (for 1g) at 0oC was
added a 37% aqueous solution of formaldehyde (0.75 mL, 10 mmol) followed by a 50% aqueous
solution of hydroxylamine (0.61 mL, 10 mmol). The mixture was stirred for 10 min at 0oC,
warmed up to room temperature and stirred for 18 h followed by addition of potassium carbonate
(69 mg, 0.5 mmol, for the synthesis of 1cꢀg). After stirring for additional 5 h the reaction mixture
was diluted with water (5 mL) and the precipitate was centrifuged off and washed with water (5
mL) and CH3OH (5 mL) in centrifuge cups. Combined solutions were evaporated in vacuum at
45ꢀ50oC and the residue was dried in vacuum at 0.1 Torr until constant weight (unstable products
1a,b were dried at room temperature, products 1cꢀg were dried at 100oC).
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3ꢀPhenylꢀ2,4,10ꢀtrioxaꢀ1,5,7ꢀtriazaꢀ3ꢀboratricyclo[3.3.1.13,7]decanꢀ1ꢀiumꢀ3ꢀuide
(1a).
0.084 g (yield 38%). White solid, decomposes upon storage at r.t. or heating. Undergoes
decomposition at 149−150ºC to give crystalline triphenyl boroxine (Mp = 208−212ºC, lit.17
213−214ºC). 1H NMR (300 MHz, DMSOꢀd6): σ = 4.62 (d, J = 12.2 Hz, 3 H), 4.85 (d, J = 12.2
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Hz, 3 H), 7.12 (m, 3 H), 7.32 (d, J = 5.4 Hz, 2 H), 8.59 (br, NH). C NMR (75 MHz, DMSOꢀ
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d6): σ = 72.6, 126.1, 126.4 and 130.9, 146.1. B NMR: (96 MHz, DMSOꢀd6): σ = 6.6 (br, W =
480 Hz). FTꢀIR: 3406 (w, br), 3181 (m, br), 3013 (s), 2997 (s), 2936 (s, sh), 2759 (s, br), 2091
(w, br), 1633 (m), 1533 (w), 1434 (m), 1372 (w), 1297 (w), 1237 (s, sh), 1164 (s), 991 (m, sh),
945 (s), 932 (s), 909 (m), 877 (m), 844 (s), 809 (s), 744 (s), 710 (m), 680 (s), 537 (m), 438 (m,
sh). ESIꢀHRMS m/z: [MꢀH]ꢀ Calcd for C9H11BN3O3 220.0901; Found 220.0908.
3ꢀ(Pyridinꢀ3ꢀyl)ꢀ2,4,10ꢀtrioxaꢀ1,5,7ꢀtriazaꢀ3ꢀboratricyclo[3.3.1.13,7]decanꢀ1ꢀiumꢀ3ꢀuide (1b).
0.204 g (yield 92%). For analytical properties the product was recrystallized from CH3OHꢀ
AcOEtꢀEt2O = 1 : 1 : 1 to give 1b as сolorless needles. Mp 152−157ºC (with decomposition). 1H
NMR (300 MHz, D2O): σ = 4.70 (d, J = 13.0 Hz, 3 H), 4.74 (br s, NH and H2O), 5.05 (d, J =
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13.0 Hz, 3 H), 7.95 (t, J = 6.8 Hz, 1 H), 8.52 (d, J = 6.8 Hz, 1 H), 8.54 (s, 1 H), 8.61 (d, J = 6.8
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Hz, 1 H). C NMR (75 MHz, DEPT, D2O): σ = 72.5 (CH2), 126.6 and 140.0 (CH), 142.2 and
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149.0 (CH) (CꢀB not observed). B NMR: (96 MHz, DMSOꢀd6): σ = 5.6 (br, W = 96 Hz). FTꢀ
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IR: 3461 (s, br), 3122 (m), 3050 (m), 2997 (m), 2925 (m), 2526 (s, br), 2155 (s, br), 1649 (s, sh),
1467 (s), 1423 (m, sh), 1372 (s), 1252 (s), 1233 (s), 1164 (s, sh), 1058 (m), 999 (s), 959 (s), 944
(s), 902 (m), 816 (m), 786 (s), 691 (s, sh), 614 (s), 526 (w), 511 (w), 443 (s, sh). ESIꢀHRMS m/z:
[MꢀH]ꢀ Calcd for C8H10BN4O3 221.0853; Found 221.0857; [M+H]+ Calcd
for C8H12BN4O3 223.0998; Found 223.0994.
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Potassium 3ꢀphenylꢀ2,4,10ꢀtrioxaꢀ1,5,7ꢀtriazaꢀ3ꢀboratricyclo[3.3.1.13,7]decanꢀ3ꢀuide (1c).
0.256 g (yield 99%). White solid. Dec. 280ºC (without melting). 1H NMR (300 MHz, DMSOꢀ
d6): σ = 4.32 (d, J = 12.1 Hz, 3 H), 4.75 (d, J = 12.1 Hz, 3 H), 7.02 (m, 3 H), 7.29 (d, J = 6.8 Hz,
2 H). 13C NMR (75 MHz, DEPT, DMSOꢀd6): σ = 73.9 (CH2), 125.2, 125.9 and 131.2 (CH) (CꢀB
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not observed). B NMR: (96 MHz, DMSOꢀd6): σ = 6.3 (br, W = 288 Hz). FTꢀIR: 3420 (s, br),
3075 (w, sh), 3015 (w), 2978 (m), 2937 (m), 2230 (w, br), 1639 (m), 1441 (m, sh), 1420 (m),
1364 (m), 1259 (m), 1232 (s), 1159 (s), 1040 (m), 1026 (m), 993 (s), 940 (s, sh), 914 (m), 894
(m), 814 (m), 799 (w), 737 (m), 710 (m), 696 (s), 635 (m, br), 580 (s, br), 490 (w), 446 (w), 430
(w). ESIꢀHRMS m/z: [MꢀK]ꢀ Calcd for C9H11BN3O3 220.0901; Found 220.0901. Anal. Calcd for
C9H11BKN3O3: C, 41.72; H, 4.28; N, 16.22. Found: C, 41.54; H, 4.48; N, 16.12.
For XꢀRay diffraction analysis the compound was crystallized from CH3OH/H2O = 10 : 1
mixture to give crystal solvate 1с•3.25H2O•CH3OH.
Potassium 3ꢀ(pyridinꢀ3ꢀyl)ꢀ2,4,10ꢀtrioxaꢀ1,5,7ꢀtriazaꢀ3ꢀboratricyclo[3.3.1.13,7]decanꢀ3ꢀuide
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hydrate (1d). 0.247 g (yield 92%). White hydroscopic solid. Dec. 240ºC (without melting). H
NMR (300 MHz, DMSOꢀd6): σ = 4.38 (d, J = 11.9 Hz, 3 H), 4.77 (d, J = 11.9 Hz, 3 H), 7.04
(ddd, J = 7.4, 4.9, 0.9 Hz, 1 H), 7.57 (ddd, J = 7.4, 1.8, 1.8 Hz, 1 H), 8.21 (dd, J = 4.8, 1.8 Hz, 1
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H), 8.40 (dd, J = 1.8, 0.9 Hz, 1 H). 13C NMR (75 MHz, DEPT, DMSOꢀd6): σ = 74.0 (CH2),
122.1 and 138.6 (CH), 146.4 and 152.4 (CH) (CꢀB not observed). 11B NMR: (96 MHz, DMSOꢀ
d6): σ = 6.0 (br, W = 192 Hz). ESIꢀHRMS m/z: [MꢀK]ꢀ Calcd for C8H10BKN4O3 221.0853;
Found 221.0851. Anal. Calcd for 2C8H10BKN4O3•H2O: C, 35.71; H, 4.12; N, 20.82. Found: C,
35.95; H, 4.32; N, 21.11.
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Potassium
3ꢀ[(E)ꢀ2ꢀphenylethenyl]ꢀ2,4,10ꢀtrioxaꢀ1,5,7ꢀtriazaꢀ3ꢀ
boratricyclo[3.3.1.13,7]decanꢀ3ꢀuide (1e). 0.225 g (yield 79%). White solid. Dec. > 290ºC
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(without melting). H NMR (300 MHz, DMSOꢀd6): σ = 4.23 (d, J = 12.0 Hz, 3 H), 4.67 (d, J =
12.0 Hz, 3 H), 5.92 (d, J = 18.4 Hz, 1 H), 6.37 (d, J = 18.4 Hz, 1 H), 7.10 (m, 1 H), 7.23 (m, 4
H). 13C NMR (75 MHz, DEPT, DMSOꢀd6): σ = 74.0 (CH2), 125.3, 125.8, 128.2 (CH), 133.8
(CH), 139.1 (C), 140.3 (CH). 11B NMR: (96 MHz, DMSOꢀd6): σ = 5.8 (br, W = 288 Hz). FTꢀIR:
3420 (s, br), 3076 (m), 3022 (m), 2994 (m, sh), 2932 (m), 1638 (s, sh), 1493 (m), 1447 (s), 1422
(s), 1377 (s, sh), 1301 (m), 1242 (m), 1154 (s, sh), 1125 (s), 996 (m), 959 (s, sh), 931 (s), 883 (s),
823 (s), 783 (s), 733 (m), 691 (s), 670 (m), 554 (m), 521 (m), 495 (m), 451 (m). ESIꢀHRMS m/z:
[MꢀK]ꢀ Calcd for C11H13BN3O3 246.1057; Found 246.1060. Anal. Calcd for C11H13BKN3O3: C,
46.33; H, 4.60; N, 14.74. Found: C, 45.64; H, 4.54; N, 14.51.
Potassium 3ꢀmethylꢀ2,4,10ꢀtrioxaꢀ1,5,7ꢀtriazaꢀ3ꢀboratricyclo[3.3.1.13,7]decanꢀ3ꢀuide (1f).
0.191 g (yield 97%). White solid. Dec. > 290ºC (without melting). 1H NMR (300 MHz, D2O): σ
= ꢀ0.39 (s, 3 H), 4.60 (d, J = 13.1 Hz, 3 H), 4.94 (d, J = 13.1 Hz, 3 H). 13C NMR (75 MHz, D2O):
σ = 2.8 (CH3), 71.2 (CH2). 11B NMR: (96 MHz, D2O): σ = 8.1 (br, W = 192 Hz). FTꢀIR: 3343 (s,
br), 3236 (m, br), 3017 (w), 2965 (s), 2942 (s), 2929 (s), 1701 (w, br), 1604 (w, br), 1447 (m),
1432 (m), 1367 (m), 1307 (s), 1296 (s), 1163 (s, sh), 1105 (s), 997 (s), 982 (s), 967 (s), 930 (s),
889 (m), 814 (s), 743 (s), 687 (s), 617 (w, br), 564 (w), 482 (w), 430 (w). ESIꢀHRMS m/z: [Mꢀ
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K]ꢀ Calcd for C4H9BN3O3 158.0732; Found 158.0735. Anal. Calcd for C4H9BKN3O3: C, 24.38;
H, 4.60; N, 21.33. Found: C, 24.35; H, 4.62; N, 21.22.
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Potassium 3ꢀhydroxyꢀ2,4,10ꢀtrioxaꢀ1,5,7ꢀtriazaꢀ3ꢀboratricyclo[3.3.1.13,7]decanꢀ3ꢀuide (1g).
0.171 g (yield 86%). White solid. Dec. > 220ºC (without melting). 1H NMR (300 MHz, D2O): σ
= 4.54 (d, J = 13.2 Hz, 3 H), 4.72 (d, J = 13.2 Hz, 3 H), 4.79 (br, OH). 13C NMR (75 MHz,
DEPT, D2O): σ = 71.2 (CH2). 11B NMR: (96 MHz, D2O): σ = 2.1. FTꢀIR: 3407 (s, br), 2992 (m),
2940 (m), 1663 (m, sh), 1431 (m, sh), 1365 (m), 1267 (s, sh), 1160 (s), 945 (s), 911 (s), 890 (s),
818 (s), 796 (s), 692 (s), 563 (w), 483 (w), 437 (w). ESIꢀHRMS m/z: [MꢀK]ꢀ Calcd for
C3H7BN3O4 160.0536; Found 160.0539. Anal. Calcd for C3H7BKN3O4: C, 18.11; H, 3.55; N,
21.11. Found: C, 18.24; H, 3.56; N, 21.25.
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Synthesis of 3ꢀBoroꢀ2,4,10ꢀtrioxaꢀ1,5,7ꢀtriazaadamantane 1h. To a stirred solution of
B(OСH3)3 (0.112 mL, 1.0 mmol) in 1.8 mL of CH3OH at 0oC was added a 37% aqueous solution
of formaldehyde (0.75 mL, 10 mmol) followed by a 50% aqueous solution of hydroxylamine
(0.61 mL, 10 mmol). The mixture was stirred for 10 min at 0oC, warmed up to room temperature
and stirred for 18 h followed by addition of potassium carbonate (69 mg, 0.5 mmol). After
stirring for additional 5 h the reaction mixture was diluted with CH3OH (5 mL) and the
precipitate was centrifuged off and washed with CH3OH (2×5 mL) in centrifuge cups. Combined
solutions were evaporated in vacuum at 45ꢀ50oC to give a mixture of 1g and 1h (ratio 1.6 : 1.0).
The residue was dissolved in CH3OH (10 mL) and refluxed for 1 h to convert 1g to 1h and
evaporated in vacuum. The product was dried in vacuum at 0.1 Torr and 100oC until constant
weight to give analytically pure 1h as white solid (0.181 g, 85%). Dec. 230ºC (without melting).
1H NMR (300 MHz, DMSOꢀd6): σ = 3.07 (s, 3 H), 4.14 (d, J = 12.1 Hz, 3 H), 4.41 (d, J = 12.1
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Hz, 3 H). 13C NMR (75 MHz, DMSOꢀd6): σ = 47.9, 72.7. B NMR: (96 MHz, DMSOꢀd6): σ =
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2.7. ESIꢀHRMS m/z: [MꢀK]ꢀ Calcd for C4H9BN3O4 174.0694; Found 174.0692. Anal. Calcd for
C4H9BKN3O4: C, 22.55; H, 4.26; N, 19.72. Found: C, 22.52; H, 4.32; N, 19.65.
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Synthesis of 3ꢀBoroꢀ2,4,10ꢀtrioxaꢀ1,5,7ꢀtriazaadamantanes 1i,j. Phenylboronic acid (122 mg,
1.0 mmol), oxime (10 mmol) were placed in a vial, water (0.09 mL, 5.0 mmol) was added and
the resulting slurry was stirred for 5 min followed by addition of potassium carbonate (69 mg,
0.5 mmol). After stirring for 24 h at room temperature the reaction mixture was diluted with
Et2O (3 mL) and water (3 mL). The organic layer was separated, the aqueous layer was washed
with Et2O (3 × 2 mL) and the combined organic extracts were washed with water (2 mL). The
combined aqueous solutions were evaporated at in vacuum at 45ꢀ50oC and the residue was dried
in vacuum at 0.1 Torr and 100oC until constant weight.
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Potassium
6,8,9ꢀtrimethylꢀ3ꢀphenylꢀ2,4,10ꢀtrioxaꢀ1,5,7ꢀtriazaꢀ3ꢀ
boratricyclo[3.3.1.13,7]decanꢀ3ꢀuide hydrate (1i). 0.233 g (yield 73%). White hydroscopic
solid. Dec. 250ºC (without melting). Mixture of eq,eq,eqꢀ1i and eq,eq,axꢀ1i isomers (ratio 2.0 :
1.0). 1H NMR (300 MHz, DMSOꢀd6, COSY, HSQC, NOESY, eq,eq,eqꢀ1i): σ = 1.49 (d, J = 6.3
Hz, 9 H, CH3), 3.88 (q, J = 6.3 Hz, 3 H, CH), 6.96−7.06 (m, 3 H, mꢀ, pꢀC6H5), 7.30 (d, J = 7.7
Hz, 2 H, oꢀC6H5). 13C NMR (75 MHz, DMSOꢀd6, HSQC, eq,eq,eqꢀ1i): σ = 18.2 (CH3), 76.5
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(CH), 124.8, 125.7 and 131.1 (o, m, pꢀC6H5), 150.7 (CꢀB). H NMR (300 MHz, DMSOꢀd6,
COSY, HSQC, NOESY, eq,eq,axꢀ1i): σ = 1.16 (d, J = 7.3 Hz, 3 H, axꢀCH3), 1.47 (d, J = 6.3 Hz,
6 H, eqꢀCH3), 4.03 (q, J = 6.3 Hz, 2 H, axꢀCH), 5.00 (q, J = 7.3 Hz, 1 H, eqꢀCH), 6.96−7.06 (m,
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3 H, mꢀ, pꢀC6H5), 7.29 (d, J = 6.2 Hz, 2 H, oꢀC6H5). C NMR (75 MHz, DMSOꢀd6, HSQC,
eq,eq,axꢀ1i): σ = 16.3 (eqꢀCH3), 18.2 (axꢀCH3), 69.2 (axꢀCH), 78.3 (eqꢀCH), 124.8, 125.7 and
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131.2 (o, m, pꢀC6H5), 150.7 (CꢀB). B NMR: (96 MHz, DMSOꢀd6): σ = 4.6 (br, W = 288 Hz).
Characteristic 2DꢀNOESY correlations in eq,eq,axꢀ1i: axꢀCH/axꢀCH3. FTꢀIR: 3332 (s, br), 3067
(s), 3005 (s, sh), 2935 (s), 1648 (m, sh), 1432 (m, sh), 1369 (s), 1318 (m), 1244 (m, sh), 1225 (s),
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1163 (s), 1120 (m), 1085 (w), 1044 (s), 1002 (s, sh), 932 (s, sh), 914 (s, sh), 766 (s), 752 (s), 737
(s), 704 (s), 654 (w), 590 (w), 534 (w, sh), 409 (m). ESIꢀHRMS m/z: [MꢀK]ꢀ Calcd for
C12H17BN3O3 262.1360; Found 262.1374. Anal. Calcd for C12H17BKN3O3•H2O: C, 45.15; H,
6.00; N, 13.16. Found: C, 44.60; H, 6.49; N, 12.73.
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Potassium 6,8,9ꢀtriethylꢀ3ꢀphenylꢀ2,4,10ꢀtrioxaꢀ1,5,7ꢀtriazaꢀ3ꢀboratricyclo[3.3.1.13,7]decanꢀ
3ꢀuide (1j). Obtained and characterized in mixture with potassium phenylborate.18 Mixture of
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eq,eq,eqꢀ1j and eq,eq,axꢀ1j isomers (ratio 1.0 : 1.4). White hydroscopic solid. H NMR (300
MHz, D2O, COSY, HSQC, NOESY, eq,eq,eqꢀ1j): σ = 1.07 (t, J = 7.6 Hz, 9 H, CH2CH3), 2.24
(m, 6 H, CH2CH3), 3.96 (t, J = 6.3 Hz, 3 H, CH), 7.30−7.40 (m, 3 H, mꢀ, pꢀC6H5), 7.49 (br d, J =
6.7 Hz, 2 H, oꢀC6H5). 13C NMR (75 MHz, D2O, HSQC, eq,eq,eqꢀ1j): σ = 10.2 (CH3), 23.8
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(CH2), 82.7 (CH), 127.1, 127.6 and 130.8 (o, m, pꢀC6H5) (CꢀB not observed). H NMR (300
MHz, D2O, COSY, HSQC, NOESY, eq,eq,axꢀ1j): σ = 1.07 (t, J = 7.3 Hz, 3 H, axꢀCH2CH3),
1.12 (t, J = 7.6 Hz, 6 H, eqꢀCH2CH3), 1.78 (m, 2 H, axꢀCH2CH3), 2.09 and 2.29 (2 m, 4 H, eqꢀ
CH2CH3), 4.12 (t, J = 6.3 Hz, 2 H, axꢀCH), 5.06 (t, J = 6.8 Hz, 1 H, eqꢀCH), 7.30−7.40 (m, 3 H,
mꢀ, pꢀC6H5), 7.49 (br d, J = 6.7 Hz, 2 H, oꢀC6H5). 13C NMR (75 MHz, D2O, HSQC, eq,eq,axꢀ1j):
σ = 9.8 (eqꢀCH2CH3), 10.6 (axꢀCH2CH3), 23.0 (axꢀCH2CH3), 23.6 (eqꢀCH2CH3), 75.8 (axꢀCH),
84.1 (axꢀCH), 127.1, 127.6 and 131.0 (o, m, pꢀC6H5) (CꢀB not observed). Characteristic 2Dꢀ
NOESY correlations in eq,eq,axꢀ1j: axꢀCH/axꢀCH2CH3. ESIꢀHRMS m/z: [MꢀK]ꢀ Calcd for
C15H23BN3O3 304.1833; Found 304.1841.
Synthesis of 3ꢀBoroꢀ2,4,10ꢀtrioxaꢀ1,5,7ꢀtriazaadamantanes 3aꢀe,h,jꢀo from trisꢀoximes 2aꢀ
e,h. To a stirred solution of trisꢀoxime 2aꢀe,h,j (1.0 mmol) in 8 mL of CH3OH (for 3aꢀe,h,jꢀm,o)
or water (for 3n) was added boronic acid (1.0 mmol for 3aꢀe,h,jꢀn, 0.5 mmol for 3o). The
solution was kept at room temperature for time indicated in Table 2 and evaporated in vacuum.
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The residue was triturated with AcOEt and dried in vacuum (0.1 Torr and 100oC) until constant
weight.
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9ꢀPhenylꢀ8,10,13ꢀtrioxaꢀ1,4,7,11ꢀtetraazaꢀ9ꢀborapentacyclo[7.3.1.1⁴,¹².0²,⁷.0⁶,¹¹]tetradecanꢀ
1ꢀiumꢀ9ꢀuide (3a). 192 mg (yield 70%). White solid. Dec. c.a 200ºC (without melting). 1H NMR
(300 MHz, DMSOꢀd6): σ = 3.21 (s, 6 H), 3.27 (br, HN), 4.83 (s, 3H), 7.09−7.15 (m, 3 H), 7.33
(br d, J = 7.9 Hz, 2 H). 13C NMR (75 MHz, DEPT, DMSOꢀd6): σ = 53.2 (СH2), 72.3 (CH),
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126.3, 126.4 and 131.0 (CH), 144.8 (C). B NMR: (96 MHz, DMSOꢀd6): σ = 4.3 (br W = 384
Hz). ESIꢀHRMS m/z: [MꢀH]ꢀ Calcd for C12H14BN4O3 273.1167; Found 273.1168; [M+H]+ Calcd
for C12H16BN4O3 275.1312; Found 275.1322. Anal. Calcd for C12H15BN4O3: C, 52.59; H, 5.52;
N, 20.44. Found: C, 52.28; H, 5.69; N, 20.12.
2,6,12ꢀTrimethylꢀ9ꢀphenylꢀ8,10,13ꢀtrioxaꢀ1,4,7,11ꢀtetraazaꢀ9ꢀborapentacyclo
[7.3.1.1⁴,¹².0²,⁷.0⁶,¹¹]tetradecanꢀ1ꢀiumꢀ9ꢀuide dihydrate (3b). 313 mg (yield 89%). White
hydroscopic solid. For analytical purposes and XꢀRay diffraction analysis the sample was
crystallized from H2OꢀMeOH (1 : 1). Mp = 138−144 ºC (melting with dec.). 1H NMR (300 MHz,
DMSOꢀd6): σ = 1.60 (s 9 H), 3.05 (s, 6 H), 3.80−5.20 (br, H2O and HN), 7.09−7.20 (m, 3 H),
7.31−7.39 (m, 2 H).13C NMR (75 MHz, DMSOꢀd6): σ = 19.3, 59.1, 74.9, 126.5, 126.6, 130.0,
144.1. 11B NMR: (96 MHz, DMSOꢀd6): σ = 4.0 (br, W = 451 Hz). FTꢀIR: 3387 (s, br), 3075 (w),
3021 (w), 2942 (m), 2602 (m), 2550 (m), 1639 (w, br), 1439 (m), 1377 (m), 1328 (w), 1233 (s,
sh), 1202 (w), 1179 (w), 1081 (s), 1011 (s, sh), 948 (s ,sh), 892 (w), 849 (s), 775 (w), 745 (s),
706 (m), 626 (br), 563 (w), 526 (w), 496 (w), 462 (w), 420 (w). ESIꢀHRMS m/z: [MꢀH]ꢀ Calcd
for C15H20BN4O3 315.1637; Found 315.1631; [M+H]+ Calcd for C15H22BN4O3 317.1782; Found
317.1785. Anal. Calcd for C15H21BN4O3•2H2O: C, 51.15; H, 7.15; N, 15.91. Found: C, 50.90; H,
7.08; N, 15.86.
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2,6,12ꢀTriethylꢀ9ꢀphenylꢀ8,10,13ꢀtrioxaꢀ1,4,7,11ꢀtetraazaꢀ9ꢀborapentacyclo
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[7.3.1.1⁴,¹².0²,⁷.0⁶,¹¹]tetradecanꢀ1ꢀiumꢀ9ꢀuide (3c). 297 mg (yield 83%). White solid. Mp =
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140−147 ºC (melting with dec.). H NMR (300 MHz, DMSOꢀd6): σ = 0.92 (t, J = 6.8 Hz, 9 H),
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2.11−2.43 (br, 7 H), 3.05 (s, 6 H), 7.10−7.20 (m, 3 H), 7.26−7.42 (m, 2 H). 13C NMR (75 MHz,
DEPT, DMSOꢀd6): σ = 6.8 (CH3), 24.3 (CH2), 56.2 (CH2), 77.3 (C), 126.3, 126.4 and 131.0
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(CH), 145.3 (C). B NMR: (96 MHz, DMSOꢀd6): σ = 3.6 (br, W = 576 Hz). ESIꢀHRMS m/z:
[MꢀH]ꢀ Calcd for C18H26BN4O3 357.2107; Found 357.2092; [M+H]+ Calcd for C18H28BN4O3
359.2252; Found 359.2243. Anal. Calcd for C18H27BN4O3: C, 60.35; H, 7.60; N, 15.64. Found:
C, 60.37; H, 7.76; N, 15.51.
2,6,12ꢀTris(3ꢀmethoxyꢀ3ꢀoxopropyl)ꢀ9ꢀphenylꢀ8,10,13ꢀtrioxaꢀ1,4,7,11ꢀtetraazaꢀ9ꢀ
borapentacyclo[7.3.1.1⁴,¹².0²,⁷.0⁶,¹¹]tetradecanꢀ1ꢀiumꢀ9ꢀuide (3d). 415 mg (yield 78%).
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White solid. Mp = 153−155 ºC (melting with dec.). H NMR (300 MHz, DMSOꢀd6): σ =
2.41−2.55 (br, 12 H), 3.07 (br, 7 H), 3.59 (s, 9 H), 7.09−7.17 (m, 3 H), 7.28 (br d, J = 7.0 Hz, 2
13
H). C NMR (75 MHz, DEPT, DMSOꢀd6): σ = 26.5 and 26.9 (CH2), 51.3 (CH3), 56.1 (CH2),
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76.3 (C), 126.4, 126.5 and 130.9 (CH), 144.7 (br, C), 173.5 (C). B NMR: (96 MHz, DMSOꢀ
d6): σ = 4.0 (br, W = 96 Hz). FTꢀIR: 3422 (m, br), 3008 (m, br), 2362 (m, br), 1638 (w, br), 1426
(m, sh), 1359 (m, sh), 1315 (m), 1233 (s, sh), 1186 (m), 1151 (w), 1102 (m, sh), 1044 (s), 1005
(s, sh), 972 (s), 939 (s, sh), 841 (s, sh), 806 (m), 781 (s), 729 (s, sh), 703 (s), 656 (m), 619 (w),
527 (m, sh), 474 (m), 425 (m, sh). ESIꢀHRMS m/z: [MꢀH]ꢀ Calcd for C24H32BN4O9 531.2261;
Found 531.2265; [M+H]+ Calcd for C24H34BN4O9 533.2418; Found 533.2410. Anal. Calcd for
C24H33BN4O9: C, 54.15; H, 6.25; N, 10.52. Found C, 54.14; H, 6.25; N, 10.43.
2,6,12ꢀTribenzylꢀ9ꢀphenylꢀ8,10,13ꢀtrioxaꢀ1,4,7,11ꢀtetraazaꢀ9ꢀborapentacyclo
[7.3.1.1⁴,¹².0²,⁷.0⁶,¹¹]tetradecanꢀ1ꢀiumꢀ9ꢀuide (3e). 413 mg (yield 76%). White solid. Mp =
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141−142 ºC (melting with dec.). H NMR (300 MHz, HSQC, DMSOꢀd6): σ = 2.69 (s, 6 H,
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CH2N), 3.59 (br s, 7 H, CH2Ph and NH), 7.13−7.32 (m, 12 H, 4 m and pꢀC6H5), 7.42 (d, J = 6.9
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Hz, 6 H, 3 oꢀC6H5), 7.61 (d, J = 7.7 Hz, 2 H, oꢀC6H5ꢀB). C NMR (75 MHz, DEPT, HSQC,
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DMSOꢀd6): σ = 37.4 (CH2Ph), 56.0 (CH2N), 77.0 (br ,C), 126.4, 126.5, 126.8, 127.6, 130.9 and
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131.1 (o, m, pꢀC6H5), 135.0 (iꢀC6H5), 145.1 (br, CꢀB). B NMR (96 MHz, DMSOꢀd6): σ = 3.9
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(br, W = 864 Hz). ESIꢀHRMS m/z: [M+H]+ Calcd for C33H34BN4O3 545.2719; Found 545.2727;
[M+Na]+ Calcd for C33H33BN4O3Na 567.2538; Found 567.2537. Anal. Calcd for C33H33BN4O3:
C, 72.80; H, 6.11; N, 10.29. Found C, 72.91; H, 6.20; N, 10.28.
5ꢀMethylꢀ2,9,12ꢀtriphenylꢀ8,10,13ꢀtrioxaꢀ1,4,7,11ꢀtetraazaꢀ9ꢀborapentacyclo
[7.3.1.1⁴,¹².0²,⁷.0⁶,¹¹]tetradecanꢀ1ꢀiumꢀ9ꢀuide hydrate (3h). 293 mg (yield 64%). White
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hydroscopic solid. Mp = 146−152ºC (melting with dec.). H NMR (300 MHz, HSQC, DMSOꢀ
d6): σ = 1.48 (d, J = 6.4 Hz, 3 H, CH3), 3.08−3.55 (br m, CH2N, NH and H2O), 3.76 (br m, 1 H,
CHCH3), 5.38 (br m, 1 H, CHꢀN), 6.81−6.96, 7.19−7.51 and 7.80−7.91 (3 m, 5 H, 6 H and 4 H,
o, m, pꢀC6H5). 13C (75 MHz, HSQC, DMSOꢀd6): σ = 14.4 (CH3), 55.6 (CH2N), 57.1 (CHCH3),
62.0 (br, C), 78.1 (CHꢀN), 125.8, 126.6, 127.2, 127.4, 127.6 and 130.9 (o, m, pꢀC6H5), 133.9 (iꢀ
C6H5), 141.2 (br, CꢀB). 11B NMR (96 MHz, DMSOꢀd6): σ = 3.7 (br, W = 1824 Hz). ESIꢀHRMS
m/z: [MꢀH]ꢀ Calcd for C25H24BN4O3 439.1951; Found 439.1926; [M+H]+ Calcd for
C25H26BN4O3 441.2097; Found 441.2080; [M+K]+ Calcd for C25H25BN4O3K 479.1656; Found
479.1646. Anal. Calcd for C25H25BN4O3•H2O calcd: C, 65.52; H, 5.95; N, 12.22. Found C,
65.12; H, 5.75; N, 12.47.
2ꢀ(3ꢀMethoxyꢀ3ꢀoxopropyl)ꢀ6,12ꢀdimethylꢀ9ꢀphenylꢀ8,10,13ꢀtrioxaꢀ1,4,7,11ꢀtetraazaꢀ9ꢀ
borapentacyclo[7.3.1.1⁴,¹².0²,⁷.0⁶,¹¹]tetradecanꢀ1ꢀiumꢀ9ꢀuide (3j). 279 mg (yield 72%). White
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solid. Mp = 148−152ºC (melting with dec.). H NMR (300 MHz, HSQC, DMSOꢀd6): σ = 1.64
(s, 6 H, CH3), 2.36−2.60 (m, 4 H, CH2−CH2), 2.98−3.23 (m, 6 H, 3 CH2N), 3.60 (s, 3 H,
CO2CH3), 3.90−5.46 (br, 1 H, NH), 7.12−7.21 (m, 3 H, m and pꢀC6H5), 7.30−7.37 (br d, J = 7.0
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Hz, 2 H, oꢀC6H5). 13C NMR (75 MHz, HSQC, DMSOꢀd6): σ = 19.1 (CH3), 26.6 and 27.1
(CH2−CH2), 51.2 (CO2CH3), 56.8 (1 CH2N), 58.7 (2 CH2N), 75.1 and 75.5 (C), 126.4, 126.5 and
130.9 (o, m, pꢀC6H5), 145.0 (CꢀB), 173.4 (CO2CH3).11B NMR (96 MHz, DMSOꢀd6): σ = 3.9 (br,
W = 960 Hz). ESIꢀHRMS m/z: [MꢀH]ꢀ Calcd for C18H24BN4O5 387.1848; Found 387.1848;
[M+H]+ Calcd for C18H26BN4O5 389.1994; Found 389.1990. Anal. Calcd for C18H25BN4O5: C,
55.69; H, 6.49; N, 14.43. Found C, 55.16; H, 6.91; N, 14.10.
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2,6,9,12ꢀTetramethylꢀ8,10,13ꢀtrioxaꢀ1,4,7,11ꢀtetraazaꢀ9ꢀborapentacyclo[7.3.1.1⁴,¹².0²,⁷.0⁶,¹¹]
tetradecanꢀ1ꢀiumꢀ9ꢀuide (3k). 245 mg (yield 93%). White hydroscopic solid, oxidizes upon
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exposure to air. Mp = 147−150ºC (melting with dec.). H NMR (300 MHz, HSQC, DMSOꢀd6):
σ = ꢀ0.61 (s, 3 H, CH3B), 1.51 (s, 9 H, CH3), 2.98 (s, 6 H, CH2N), 4.6−6.2 (br, NH and H2O). 13C
NMR (75 MHz, DEPT, HSQC, DMSOꢀd6): σ = 2.3 (CH3B), 19.3 (CH3), 59.0 (CH2N), 74.4 (C).
11B NMR: (96 MHz, DMSOꢀd6): σ = 5.5 (br, W = 336 Hz ). ESIꢀHRMS m/z: [MꢀH]ꢀ Calcd for
C10H18BN4O3 253.1479; Found 253.1487; [M+H]+ Calcd for C10H20BN4O3 255.1625 Found
255.1623. Anal. Calcd for 2C10H19BN4O3•H2O calcd: C, 45.65; H, 7.66; N, 21.29. Found C,
45.31; H, 7.98; N, 20.83.
2,6,12ꢀTrimethylꢀ9ꢀ[(E)ꢀ2ꢀphenylethenyl]ꢀ8,10,13ꢀtrioxaꢀ1,4,7,11ꢀtetraazaꢀ9ꢀborapentacyclo
[7.3.1.1⁴,¹².0²,⁷.0⁶,¹¹]tetradecanꢀ1ꢀiumꢀ9ꢀuide (3l). 311 mg (yield 91%). White solid. Mp =
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160−163 ºC (melting with dec.). H NMR (300 MHz, HSQC, DMSOꢀd6): σ = 1.56 (s, 9 H,
CH3), 3.02 (s, 6 H, CH2N), 3.3−3.9 (br, NH), 5.93 (d, J = 18.4 Hz, 1 H, CH=CH), 6.53 (d, J =
18.4 Hz, 1 H, CH=CH), 7.16 (t, J = 7.0 Hz, 1 H, pꢀC6H5), 7.27 (dd, J = 7.6, 7.0 Hz, 2 H, mꢀ
C6H5), 7.35 (d, J = 7.6 Hz, 2 H, mꢀC6H5). 13C NMR (75 MHz, HSQC, DMSOꢀd6): σ = 19.4
(CH3), 59.1 (CH2N), 74.7 (C), 125.6, 126.6 and 128.3 (o, m, pꢀC6H5), 133.4 (br, HCꢀB), 136.1
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(=CH), 139.2 (iꢀC6H5). B NMR: (96 MHz, DMSOꢀd6): σ = 3.5 (br, W = 672 Hz). ESIꢀHRMS
m/z: [MꢀH]ꢀ Calcd for C17H22BN4O3 341.1794; Found 341.1791; [M+H]+ Calcd for
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C17H24BN4O3 343.1939; Found 343.1938. Anal. Calcd for C17H23BN4O3 calcd: C, 59.67; H,
6.77; N, 16.37; Found C, 59.45; H, 6.90; N, 16.48.
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[7.3.1.1⁴,¹².0²,⁷.0⁶,¹¹]tetradecanꢀ1ꢀiumꢀ9ꢀuide hydrate (3m). 271 mg (yield 91%). White
hydroscopic solid. For analytical purposes the sample was crystallized from H2OꢀMeOH. Mp =
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142−145ºC (melting with dec.). H NMR (300 MHz, DMSOꢀd6): σ = ꢀ0.85 (quint, J = 7.2 Hz,
1H), ꢀ0.03 (m, 4 H), 1.47 (s, 9 H), 2.95 (s, 6 H), 4.7−6.3 (br, NH and H2O). 13C NMR (75 MHz,
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DEPT, DMSOꢀd6): σ = ꢀ0.9 (CH), 0.0 (CH2), 19.1 (CH3), 59.0 (CH2), 74.5 (C). B NMR: (96
MHz, DMSOꢀd6): σ = 3.8 (br, W = 336 Hz). ESIꢀHRMS m/z: [MꢀH]ꢀ Calcd for C12H20BN4O3
279.1636; Found 279.1633; [M+H]+ Calcd for C12H22BN4O3 281.1782; Found 281.1790. Anal.
Calcd for C12H21BN4O3•H2O calcd: C, 48.34; H, 7.78; N, 18.79. Found: C, 48.30; H, 8.37; N,
18.93.
9ꢀHydroxyꢀ2,6,12ꢀtrimethylꢀ8,10,13ꢀtrioxaꢀ1,4,7,11ꢀtetraazaꢀ9ꢀborapentacyclo
[7.3.1.1⁴,¹².0²,⁷.0⁶,¹¹]tetradecanꢀ4ꢀiumꢀ9ꢀuide hydrate (3n). 271 mg (yield 99%). White
hydroscopic solid. For analytical purposes and XꢀRay diffraction analysis the sample was
crystallized from H2O. Mp = 158ºC (melting with dec.). 1H NMR (300 MHz, D2O): σ = 1.77 (s,
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9 H), 3.57 (s, 6 H), 4.79 (br s, NH, OH and H2O). C NMR (75 MHz, DEPT, D2O): σ = 19.6
(CH3), 57.4 (CH2), 72.6 (C).11B NMR: (96 MHz, D2O): σ = ꢀ0.13. FTꢀIR: 3193 (s, br), 2343 (w,
sh), 1444 (w, sh), 1405 (w, sh), 1366 (w), 1270 (w), 1176 (br, sh), 1057 (w), 1009 (s), 946 (m,
sh), 903 (m, sh), 766 (s), 714 (w), 649 (s), 570 (m), 463 (m), 423 (w). ESIꢀHRMS m/z: [MꢀH]ꢀ
Calcd for C9H16BN4O4 255.1272; Found 255.1269; [M+H]+ Calcd for C9H18BN4O4 257.1417;
Found 257.1406. Anal. Calcd for C9H17BN4O4•H2O: C, 39.44; H, 6.99; N, 20.44. Found C,
39.11; H, 7.36; N, 20.49.
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(3o). 505 mg (yield 83%). White hydroscopic solid. For analytical purposes the sample was
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crystallized from H2OꢀMeOH. Mp = 166−176 ºC (melting with dec.). H NMR (300 MHz,
DMSOꢀd6): σ = 1.59 (s, 18 H), 3.04 (s, 12 H), 3.32 (s, H2O), 7.14 (s, 4 H), 10.1−11.7 (br, 2 H,
13
NH). C NMR (75 MHz, DEPT, DMSOꢀd6): σ = 19.3 (CH3), 59.1 (CH2), 74.6 (br, C), 129.4
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(CH), 142.4 (C). B NMR: (96 MHz, DMSOꢀd6): σ = 3.7 (br, W = 960 Hz). ESIꢀHRMS m/z:
[MꢀH]ꢀ Calcd for C24H35B2N8O6
553.2880; Found 553.2880. Anal. Calcd for
C24H36B2N8O6•3H2O calcd: C, 47.39; H, 6.96; N, 18.42. Found C, 47.28; H, 7.07; N, 18.14.
Synthesis of 3ꢀBoroꢀ2,4,10ꢀtrioxaꢀ1,5,7ꢀtriazaadamantane 1c from formaldoxime trimer
hydrochloride 4a•HCl. To a stirred solution of hydrochloride 4a•HCl (172 mg, 1.0 mmol) and
phenylboronic acid (122 mg, 1.0 mmol) in CH3OH (7.5 mL) was stirred for 18 h. Then K2CO3
(69 mg, 0.5 mmol) was added and the mixture was stirred for additional 5 h. The resulting
mixture was filtered through syringe filter and evaporated in vacuum. The residue was dried in
vacuum until constant weight to give 221 mg (85%) of boradamantane 1c as white solid.
Synthesis of 3ꢀBoroꢀ2,4,10ꢀtrioxaꢀ1,5,7ꢀtriazaadamantane 3b from adamantane 6b. To a
stirred solution of adamantane 6b (115 mg, 0.5 mmol) in CH3OH (3.8 mL) was added
phenylboronic acid (61 mg, 0.5 mmol). The solution was stirred at room temperature until full
consumption of starting material (0.5 h, TLC control) and evaporated in vacuum. The residue
was triturated with AcOEt and dried in vacuum (0.1 Torr and 100oC) until constant weight to
give 155 mg (98%) of boroadamantane 3b as a white solid.
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Decomposition of boradamantane salt 1c under acidic conditions. To a solution of
boradamantane salt 1c (115 mg, 0.44 mmol) in 1 mL of water was added concentrated aqueous
solution of HCl (36% in water, 0.2 mL). The mixture was kept for 1 h and then extracted with
CHCl3 (8×5 mL). Combined organic extracts were dried (Na2SO4) and evaporated in vacuum to
give 39 mg (73%) of phenylboronic acid (Mp 212ꢀ214oC, lit. 214ꢀ219 oC (Alfa Aesar)).
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SM coupling of boradamantane salt 1c with 1ꢀbromoꢀ4ꢀnitrobenzene. To a solution of
Pd(OAc)2 (2 mg, 0.009 mmol) in 0.6 mL of DMF/H2O mixture (5 : 1) was added boradamantane
salt 1c (52 mg, 0.2 mmol) and 1ꢀbromoꢀ4ꢀnitrobenzene (36 mg, 0.18 mmol) under argon
atmosphere. The mixture was stirred at 100ºC for 5 h. After cooling the organic products were
extracted with Et2O (3×3 mL). Combined organic layers were washed with water, dried (MgSO4)
and evaporated in vacuum. Flashꢀchromatography (pentaneꢀEt2O = 10 : 1) of the residue
provided 26 mg (71%) of 4ꢀnitrobiphenyl (GCꢀMS) as white crystals (Mp 111ꢀ114oC, lit.19 112ꢀ
114 oC).
Synthesis of Nꢀ(2ꢀ{[2ꢀ(hydroxyimino)ꢀ2ꢀphenylethyl][1ꢀ(hydroxyimino)propanꢀ2ꢀyl]amino}ꢀ
1ꢀphenylethylidene)hydroxylamine (2h) (synthesized according to procedure used for 2i9c). To
a stirred solution of Nꢀ(2ꢀaminopropylidene)hydroxylamine9c (176 mg, 2.0 mmol) in 8 mL of
dioxane was added a 1 M solution of 2,2,6,6ꢀtetramethylꢀ4ꢀ(1ꢀphenylethenyl)ꢀ3,5ꢀdioxaꢀ4ꢀazaꢀ
2,6ꢀdisilaheptane20 in dry CH2Cl2 (4.4 mL, 4.4 mmol). After 24 h at room temperature 20 ml of
CH3OH was added and the mixture was kept for additional 5 h with stirring. Then the mixture
was evaporated in vacuum at 37 °C. The residue was preadsorbed on silica gel and purified by
flash chromatography (silica gel; EtOAc–hexane, 1:1 then EtOAc and EtOAc–CH3OH, 3:1). The
residue was triturated with CHCl3 and dried in vacuum (0.1 Torr, room temperature) until
constant weight to give 438 mg (61%) of oxime 2h as a yellowish solid. Mixture of three isomers
1
(ratio 2h’ : 2h’’ : 2h’’’ = 5.2 : 3.8 : 1.0). H NMR (300 MHz, DMSOꢀd6, HSQC, isomer 2h’):
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1.05 (d, J = 6.5 Hz, 3 H, CH3), 3.34 (m, 1 H, CH), 3.68 (d, J = 13.5 Hz, 2 H, CH2), 3.85 (d, J =
13.5, 3.4 Hz, 2 H, CH2), 7.11−7.46 (m, 11 H, 2 C6H5 and N=CH), 10.69, 10.96 and 11.45 (3 s, 3
5
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6
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H, 3 NOH). H NMR (300 MHz, DMSOꢀd6, HSQC, isomer 2h’’): 1.11 (d, J = 7.6 Hz, 3 H,
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9
CH3), 3.34 (m, 3 H, CH and CH2), 3.59 (d, J = 13.2 Hz, 2 H, CH2), 7.11−7.46 (m, 11 H, 2 C6H5
and N=CH), 10.73, 10.85 and 11.50 (3 s, 3 H, 3 NOH). 1H NMR (300 MHz, DMSOꢀd6, HSQC,
isomer 2h’’’): 0.97 (d, J = 6.6 Hz, 3 H, CH3), 3.19 (m, 1 H, CH), 3.46 (s, 4 H, CH2), 6.72 (d, J =
5.9 Hz, 1 H, N=CH), 7.11−7.46 (m, 10 H, 2 C6H5), 10.64, 10.94 and 11.41 (3 s, 3 H, 3 NOH).
13C NMR (75 MHz, DMSOꢀd6, HSQC, 2h’ and 2h’’): 11.8 and 12.0 (CH3), 42.8, 53.0, 53.2,
53.4, 53.9 (CH and CH2), 126.4, 127.4, 127.7, 127.8, 128.2, 128.3, 128.5 (o, m, pꢀC6H5), 135.5
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(iꢀC6H5), 150.1 and 154.1 (C=N). C NMR (75 MHz, DMSOꢀd6, HSQC, characteristic signals
of 2h’’’): 152.8 (C=N). ESIꢀHRMS m/z: [M+H]+ Calcd for C19H22N4O3 355.1765; Found
355.1758. [M+Na]+ Calcd for C19H22N4O3 377.1584; Found 377.1576.
SUPPORTING INFORMATION
Characterization data for all new compounds, NMR and GCꢀMS for known compounds, Xꢀray
data, Cartesian coordinates, absolute energies for all optimized geometries and NBO analysis
summary. This material is available free of charge via the Internet at http://pubs.acs.org.
ACKNOWLEDGMENTS
The support from Russian Foundation for Basic Research (grant # 14ꢀ03ꢀ00933ꢀa) and Russian
President’s Council for Grants (grant MKꢀ5957.2015.3) is greatly acknowledged.
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