Azaborininones: Synthesis and Structural Analysis of a Carbonyl-Containing Class of Azaborines

Article abstract of DOI:10.1021/acs.joc.7b00747

An approach to access azaborininones (carbonyl-containing, boron-based heterocyclic scaffolds) using simple reagents and conditions from both organotrifluoroborates and boronic acids is described. An inexpensive, common reagent, SiO₂, was found to serve as both a fluorophile and desiccant to facilitate the annulation process across three different azaborininone platforms. Computational analysis of some of the cores synthesized in this study was undertaken to compare the azaborininones with the analogous carbon-based heterocyclic systems. Computationally derived pK_a values, NICS aromaticity calculations, and electrostatic potential surfaces revealed a unique isoelectronic/isostructural relationship between these azaborines and their carbon isosteres that changed based on boron connectivity. Correlation to experimentally derived data supports the computational findings.

Full text of DOI:10.1021/acs.joc.7b00747

Article
pubs.acs.org/joc
Azaborininones: Synthesis and Structural Analysis of a Carbonyl-
Containing Class of Azaborines
Geraint H. M. Davies,† Asma Mukhtar,†,‡ Borna Saeednia,†,§ Fatemeh Sherafat,†,∥
Christopher B. Kelly,† and Gary A. Molander*,†
†Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia,
Pennsylvania 19104-6323, United States
‡Institute of Chemistry, University of the Punjab, Lahore-54590, Pakistan
§Laboratory of Organic Synthesis and Natural Products, Department of Chemistry, Sharif University of Technology, Azadi Street,
P.O. Box 111559516, Tehran, Iran
∥School of Chemistry, College of Science, University of Tehran, P.O. Box 141556455, Tehran, Iran
S
* Supporting Information
ABSTRACT: An approach to access azaborininones (carbonyl-
containing, boron-based heterocyclic scaffolds) using simple
reagents and conditions from both organotrifluoroborates and
boronic acids is described. An inexpensive, common reagent,
SiO2, was found to serve as both a fluorophile and desiccant to
facilitate the annulation process across three different
azaborininone platforms. Computational analysis of some of
the cores synthesized in this study was undertaken to compare
the azaborininones with the analogous carbon-based hetero-
cyclic systems. Computationally derived pKa values, NICS
aromaticity calculations, and electrostatic potential surfaces
revealed a unique isoelectronic/isostructural relationship
between these azaborines and their carbon isosteres that
changed based on boron connectivity. Correlation to
experimentally derived data supports the computational findings.
unique modes of bioactivity, and recent studies on 2,1-
borazaronaphthalenes indicate a strong correlation to known
bioactive compounds.4d,8 Thus, methods to construct new or
unexplored boron heterocyclic species would dramatically
improve the quality of drug discovery libraries.
INTRODUCTION
■
The preparation of boron-based heteroaromatic species has
long fascinated synthetic chemists. Such ring systems greatly
expand the library of heterocyclic structures and redefine the
reactivity profile of these conjugated systems.1 Although
historically studied as a means to understand aromaticity,2
boron-based aromatic systems have been recognized as viable,
emerging platforms for expanding molecular diversity.3
Particularly privileged among these boron-based cores is the
azaborine scaffold, in which a B−N bond is integrated into the
aromatic system.4 The B−N bond serves as a surrogate for a
CC bond in arenes or heteroarenes, providing structural
mimicry with unique electronic properties (and hence chemical
reactivity). The unique disconnections, wholly unavailable in
the corresponding carbon analogues, provide opportunities for
dissonant synthetic routes to bicyclic systems. Additionally, the
interchange between B−N and CC bonds is particularly
attractive for drug discovery, as it greatly enhances available
structural diversity, and the trivalent nature of boron provides
alternative electrostatic contacts for enzymatic targets.5 Taken
together, not only could this enhance potency of existing
scaffolds, but it could also lead to new pharmacons. Indeed,
oxaboroles6 and benzodiazaborines7 have been shown to have
Recently, our group has engaged in highly successful
programs to access azaborinyl cores from potassium organo-
trifluoroborates (R-BF3Ks) via in situ generated dihaloboranes,
resulting in rapid access to both the 2,1-borazaronaphthalene9a
and 1,3,2-benzodiazaborole9b scaffolds. Although exploration of
methods to functionalize these unique cores is being
continued,10 it is also of interest to expand into new
polyheteroatom-based azaborinyl systems. Of particular interest
was the azaborininone family (Figure 1). These underexplored,
carbonyl-bearing, boron-heterocyclic scaffolds chelate a boron
atom between a carboxylate or an amide and a secondary point
(either an aryl hydroxyl or amino group), thus establishing a
6,6-bicyclic ring system. The three resulting classes of
azaborininones have been very sporadically explored11 and
have shown applications as boron protecting/directing groups
Received: March 30, 2017
© XXXX American Chemical Society
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in the context of organotrifluoroborates,12 this reagent was
considered as an alternative to BF3·NH2Et in enabling mild,
defluorinative annulation. Not only would this mitigate the
requirement of an excess of a harsh, boron trifluoride-based
reagent, but it would also employ an extraordinarily
inexpensive, readily available reagent already found in virtually
any organic laboratory.
A brief screen of alternative additives in conjunction with 3a
and potassium phenyltrifluoroborate revealed SiO2 to be the
optimal fluorophile (Table 1). Importantly, these same
Table 1. Fluorophilic Reagent Optimization
Figure 1. Azaborininones, their possible isosteric counterparts, and
their requisite starting points.
for C−H activation,11e−g as well as potential promise as
therapeutics given their known abilities as insect chemo-
sterilants.11h Development of a concise, robust synthetic
method applicable to the entire family of azaborininones
would be highly attractive. In addition to overcoming a
synthetic challenge, the three core systems provide future
opportunities to explore the reactivity of an entirely new library
of boron-containing compounds. In parallel to these synthetic
studies, a computational investigation of the azaborininone
family would provide further understanding as to how the
substitution of O−B and N−B affect the structural and
electronic properties.
a
1
Conversion determined by H NMR spectroscopy.
conditions could be extended to both anthranilic acid and
salicylamide without modification. Upon further study of SiO2
as a fluorophile, oven-dried SiO2 was determined to be more
effective and allowed the reaction temperature to be lowered to
60 °C. In addition to being a fluorophilic species, SiO2 can
further convert organotrifluoroborates to their corresponding
boronic acids,12 suggesting a potential reaction intermediate.
Exposure of phenylboronic acid in place of phenyltrifluoro-
borate (Scheme 2) to the optimized conditions resulted in the
RESULTS AND DISCUSSION
■
Early synthetic efforts centered on accessing 1,3,2-benzodiaza-
borininones derived from anthranilamide 3a. Using the
conditions established from the prior work with the similar
3,1,2-benzodiazaboroles,9b the defluorinative annulation with
phenyltrifluoroborate was met with success (Scheme 1a).
Scheme 1. Attempts at Preparing Various Azaborininones
via Defluorinative Annulation: (a) Success with 1,3,2-
Benzodiazaborininones; (b and c) Failed Attempts at
Extension to the Mixed N,O-Azaborininone Classes
Scheme 2. Successful Annulation Using a Boronic Acid
Mediated by SiO2
near-identical yield of 4a (conditions b, Table 2). This finding
also explains the benefit observed with dried SiO2, as this
improved the ability for the SiO2 to act as a desiccant in the
annulation (whose byproduct is H2O). This indicates two
viable mechanisms: one proceeding through a difluoro-
organoborane and the other via a SiO2-mediated boronate
species. Both may be operative under SiO2-mediated
annulation, but only the former is possible when using the
anhydrous BF3·NH2Et conditions.
Substrate Scope. With two complementary conditions in
hand, the scope of each approach was assessed. In the case of
the 1,3,2-benzodiazaborininones (Table 2), derived from
anthranilamide and the corresponding potassium organo-
trifluoroborates, a variety of annulated products could be
accessed using either protocol. Typically, the BF3·NH2Et
conditions outperformed SiO2-mediated cyclizations (compare
yields for 4a, 4b, 4e, 4f, 4p−4r). Various functional groups
were amenable to the annulation process, including ethers (4f,
4m), amines (4h), esters (4i), and cyano groups (4j).
Unfortunately, the fluorophile used (BF3·NH2Et) to facilitate
the cyclization proved unsuccessful in reactions with anthranilic
acid, 3b, or salicylamide, 3c (Scheme 1b and 1c), likely because
the strong Lewis acidity of BF3 diminished the already weak
nucleophilicity of these systems. Thus, although the boron
trifluoride based approach would grant access to one core,
alternative conditions were required to access the remaining
two cores reliably. Given the known affinity of SiO2 for fluoride
B
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Table 2. Synthesis of 1,3,2-Benzodiazaborininones via Defluorinative Annulation
a
Yield on 7 mmol scale (see Experimental Section for full reaction conditions).
Furthermore, polycyclic (4l) and multiple heterocyclic (4n, 4o)
species could be accessed, as well as nonaryl organotrifluoro-
borates (4p−4r). Finally, the BF3·NH2Et conditions were
readily scalable to furnish gram quantities of 4b. Stability
studies of 4a indicate that it is quite sensitive to an aqueous
base, but is rather insensitive to aqueous acid or neutral pH
solutions. Little to no hydrolysis was observed even after 18 h
in aqueous DMSO (see Supporting Information for aqueous
stability studies).
Table 3. Synthesis of 3,1,2-Benzoxazaborininones via
Defluorinative Annulation
Utilization of the SiO2-based conditions enabled initial entry
to the mixed N,O-azaborininone classes. Starting from
anthranilic acid (3b), a variety of 1,3,2-benzoxazaborininones
could be synthesized (Table 3). A range of potassium
organotrifluoroborates were quite competent in the synthesis
of this class of oxazaborininone, and functional group tolerance
remained high. In addition to retaining the functional group
tolerance seen with 1,3,2-benzodiazaborininones, additional
substrates containing ketones (5e) and indoles (5i) were
demonstrated to be amenable to cyclization. Alkenyl- (5j) and
alkyl-3,1,2-benzoxazaborinine substrates (5k, 5l) could also
readily be prepared. One difficulty encountered was incon-
sistent conversion observed upon isolation of the products.
Oftentimes, 3b would remain even after purification by silica
plug, suggestive of a reversible process (via hydrolysis). Using
1H NMR spectroscopy, these compounds were determined to
be very intolerant to water and rapidly hydrolyzed to the
corresponding boronic acid and 3b in a quantifiable manner
(see Supporting Information for stability studies).11e,13
However, apart from hydrolysis, these systems were found to
be stable in organic solutions even at elevated temperatures.
With this in mind, supplementary conditions involving boronic
acids were considered, capitalizing on azeotropic water removal
to drive cyclization.11e,14 These conditions (denoted conditions
b) provide an alternative route that in many cases gives equal to
superior yields, likely because of the now nonreversible
annulation. Although not the focus of this study, considering
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the practical benefits of trifluoroborates,15 this approach was
useful for systems prone to hydrolysis (5a−5c, 5f−5i, 5l).
The isomeric 1,3,2-benzoxaborininones (Table 4) could also
be accessed from salicylamide (3c). These substrates were
was used to glean insight. All calculations were carried out using
Gaussian 09,16 and the structures were visualized via
WebMO.17 Geometry optimizations were performed in the
gas phase at the B3LYP/6-311+G(2d,p) level of theory.18 The
method used for calculations involving thermochemical values
(e.g., computed pKa) of the various systems involved (i)
geometry optimization and vibrational frequency calculations in
the gas phase at the B3LYP/6-311+G(2d,p) level of theory and
(ii) geometry optimization and vibrational frequency calcu-
lations in implicit water (H2O) using PCM19 at the B3LYP/6-
311+G(2d,p) level of theory. Stationary points were charac-
terized by frequency analysis at 298.15 K, with structures at
energy minima showing no imaginary frequencies. To probe
the ring current in these systems, nuclear independent chemical
shift (NICS) values were determined at the GIAO-B3LYP/6-
311+G(2d,p) level of theory at distances of 0.0 Å [A(0) and
B(0)] and 1 Å [A(1) and B(1)] from each ring system as well
as from the center of the bicyclic systems [Center(1)] in the
perpendicular direction.20
Table 4. Synthesis of 1,3,2-Benzoxazaborininones via
Defluorinative Annulation
Initial computational investigations focused on the truncated
cores (i.e., without functionalization on boron) to explore the
structural and electronic features in comparison to isostructural
compounds (Table 5). Looking at the 1,3,2-benzodiaza-
borininones, isoquinolinone 10 and quinolinone 11 were
identified as likely isosteres. A pictorial comparison of the
electrostatic potential maps of these isosteres with the
truncated 1,3,2-benzodiazaborininone 7 seemed to indicate
that this system was a hybrid of both structures, with 7 having
comparable A ring electrostatic potential to 11 and B ring
similarity to 10. This is not altogether surprising given that
nitrogen is well-known to participate in electron donation to
boron. Indeed, the B−N bond lengths in the 1,3,2-benzodiaza-
borininone are quite uniform despite the nitrogen atoms being
in vastly different electronic environments. This is corroborated
in the slight contraction seen in the CO bond as compared
to isoquinolinone (10), indicating diminished nitrogen
participation in the carbonyl π system. NICS calculations,
which provide a quantitative correlation for electron delocaliza-
tion using “theoretical nuclei” at the center of a π-system to
probe electron shielding, were used for further elucidations.21
Specifically, NICS(1) values were highlighted based on their
improved ability to observe a π-delocalized aromatic ring
current. NICS studies indicated that, relative to its isosteres,
1,3,2-benzodiazaborininone 7 has less aromatic character in its
B ring. This finding is in agreement with prior work by our
group and others, wherein boryl-based aromatic systems display
diminished aromatic character when compared to their indole
counterparts.9b,20a This effect is less pronounced in the
adjoined carbon ring but is still observed. NICS values between
the two possible isosteres of this system are relatively similar,
with 11 having slightly less aromatic character in its B ring and
thus more similarity to 7. Because of the aforementioned
inherent stability issues of these systems, experimentally derived
pKa values were unobtainable, and thus theoretical values were
pursued.21 The computed pKa’s of 7 are quite uniform,
indicative of a strong electron donation to boron by both
nitrogen atoms. The pKa’s are notably higher than their
isosteres, a consequence of the competitive donation by both
nitrogen atoms into boron and the lack of complete resonance
stabilization around the B ring to delocalize negative charge.
Moving to 3,1,2-benzoxazaborininone 8 and 1,3,2-benzoxaza-
borininones 9, similar trends were observed. As a whole these
mixed N,O systems displayed less electron delocalization and
typically the lowest-yielding members of the azaborininone
family. This can be attributed to the diminished nucleophilicity
of the amidyl nitrogen relative to aniline, combined with the
lability of O-borylated phenols. In this case, a significant
difference in yield exists between the SiO2 conditions (a) and
the Dean−Stark condensation (b). This likely relates to the
unique electronics of this azaborininone class, which is more
prone to degradation via hydrolysis. Similar to 5a, 6a
underwent rapid hydrolysis in aqueous DMSO to give 3c and
phenylboronic acid. Despite this sensitivity, many, if not all, of
the boryl substitution patterns tolerated with other members of
the azaborininone family could be accessed with this more
sensitive core. Not surprisingly, the azeotropic protocol fared
far better with these systems. Indeed, in some cases, such as the
acetophenone derivative 6e, azeotropic condensation was the
only way to effect annulation.
COMPUTATIONAL EVALUATION
■
In parallel to developing a user-friendly synthesis of this
underexplored azaborine class, we sought to evaluate their
electronic properties. More specifically, we hoped to discern
what, if any, isostructural (or isoelectronic) character these
systems possessed. Indeed, many possible isosteres were
envisioned, such as isochromones for 3,1,2-benzoxaza-
borininones or isoquinolinones for 1,3,2-benzodiazaborole.
The compounds compared were considered on an isostructural
basis, focusing on the structural similarities, comparing B−N/
CC and the analogous B−O/CN. Given the prior
successes in analyzing the 1,3,2-benzodiazaborole core using
quantum mechanical calculations,9b computational modeling
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a
Table 5. Comparison of the Azaborininone Family with Their Probable Isosteres
a
All distances given in angstroms (Å), and the electrostatic potentials range from +31.38 to −31.38 kcal mol−1. NICS(1) values are given in ppm
where a more negative NICS value indicates greater electron shielding via a stronger ring current and more π-electron delocalization (thus greater
aromatic character).
were more acidic. This increased acidity can be attributed to
diminished π-orbital overlap with boron by the secondary
heteroatom (in this case oxygen). The lower participation of
electron donation by oxygen likely also relates to the observed,
less negative, NICS values for the B rings of these systems.
However, the isosteric character of these two systems was not
as uniform. Using electrostatic potentials, 8 more closely
resembles isochromone 12, whereas 9 appears to be more of a
hybrid of 14 and 15. These trends are also borne out in the
NICS analysis of the B rings of 8 and 9, wherein 9 has slightly
more aromatic character than 8, indicating more oxygen
participation in the ring system and thus provides further
plausibility to B−O/CN mimicry.22 Additionally, the CN
resonance contribution of amides renders the system more
aromatic. The relatively longer B−N bond seen in 9 also is in
line with enhanced oxygen participation. However, the NICS
value for the B ring of 9 more closely aligns with the B ring of
15. The exact opposite is true for the A ring, thus supporting
the notion that 9 is a hybrid of the two systems.
prepared during the synthetic studies to allow correlative
studies. In general, adding a B-aryl group led to diminished
aromatic character in both the A and B rings for all members of
the azaborininone family, as the boron is in favorable π-orbital
overlap with the external ring. In particular, the 1,3,2-
benzoxazaborininones showed the most significant disparity
in the NICS values of the B ring from its truncated system.
Ultimately, this increase may relate to their observed
experimental instability. Electronically, the 1,3,2-benzodiaza-
borininones were the least sensitive to electronic changes,
suggesting the overriding participation of both nitrogen atoms
in this core. The 3,1,2-benzoxazaborininones seemed to be
most influenced by electronic changes and appeared to gain
aromatic character in both the A and B rings with more
electron-deficient B-arenes.
As a means of correlating some of the observed computa-
tional trends with experimental data, NICS calculations were
compared with some possible values that could be
experimentally derived. Although pKa’s would have been
ideal, the instability of these systems to strongly basic
environments prohibited such a correlative study. Instead, IR
and NMR spectroscopy were used as a means of quantitatively
comparing calculations to experiment. Initially, the computed
To probe the role of electronics in these systems further,
substitution on boron was next explored (Table 6). Four
representative B-aryl groups were selected that not only
provided a range of electronic environments but also were
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Table 6. NICS Analysis of Electronically Disparate Azaborininones Divided by Class
Figure 2. Plots of computed CO IR stretch vs NICS values for both the A and B rings of various azaborininones.
IR values were compared against the NICS values for both
rings, to determine if the double bond character of the carbonyl
would be influenced by the aromatic character of the rings and
the relative electron-donation propensity of the adjacent
heteroatom with boron. It was observed that, whereas the
amide-containing 1,3,2-benzoxazaborininones and 1,3,2-
benzodiazaborininones were readily comparable, the 3,1,2-
benzoxazaborininones did not trend with the other members of
the azaborininone class (Figure 2). This is not altogether that
surprising given the pseudo-α,β-unsaturated character of the
structures (via B−N/CC isosterism) possible with the
former two systems that are not possible in the latter. This
trend is also in agreement with the findings of the truncated
systems. Whereas the amide-based systems usually are hybrid
structures and very much electronically related, the ester-like
3,1,2-benzoxazaborininones are more like their isochromenone
isosteres. Comparison of the experimental values for these
systems provided some level of correlation, but because of their
complex IR spectrum, the correlations were less than ideal (see
Supporting Information for details). For a more precise
correlation, 13C NMR was used, which would be quite sensitive
to electronic changes. Experimental NMR values correlated
well with NICS(1) values in both rings, indicating the
electronic shielding trends observed computationally may
indeed occur in these systems experimentally (Figure 3). In
general, the distribution of these values was self-consistent
within each structural class (i.e., bimodal for the two classes
plotted). Moreover, although the B rings show aromatic
character, the values observed for the A ring are more
analogous to aromatic systems [NICS(1) value of benzene is
−10.20].20b This is similarly reflected in these studies, with the
A ring showing a stronger correlation than the B ring. Thus,
this provides some level of experimental validation of the trends
observed in the NICS studies.
CONCLUSIONS
■
In summary, a modular approach to the synthesis of the
underexplored azaborininone family of azaborines is presented.
A set of simple conditions enables various organotrifluoro-
borates to undergo facile defluorinative annulation facilitated by
two inexpensive fluorophiles. Alternatively, boronic acids also
succumb to annulation via a more classical condensation route.
Three classes, 1,3,2-benzodiazaborininones, 1,3,2-benzoxaza-
borininones, and 3,1,2-benzoxazaborininones, can be prepared
using these varying approaches. These classes were further
studied using computational methods, revealing some sim-
ilarities to possible carbon isosteres. Whereas 1,3,2-benzodiaza-
borininones and 3,1,2-benzoxazaborininones appear to repre-
sent a hybrid between their plausible isosteres, the 1,3,2-
benzoxazaborininones seem to align closely with isochrome-
nones. Correlations between computed NICS values and
experimentally derived trends provide support for these
computed trends.
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Figure 3. Plots of experimental 13C NMR values vs computed NICS values for both the A and B rings of various 1,3,2-benzoxazaborininones and
1,3,2-benzodiazaborininones.
3245, 1635, 1612, 1526, 1484, 1270, 747, 686 cm−1; HRMS (CI) m/z
EXPERIMENTAL SECTION
■
calcd for C13H12BN2O [M + H]+ 223.1043, found 223.1043.
General Considerations. All reactions were carried out under an
2-(o-Tolyl)-1,3,2-benzodiazaborininone (4b). Obtained as a white
inert atmosphere of nitrogen or argon in oven-dried glassware, unless
solid by procedure A after recrystallization from EtOAc (1.43 g, 87%,
otherwise noted. Toluene and cyclopentyl methyl ether (CPME) were
7.0 mmol scale) and procedure B-1 (132 mg, 56%, 1.0 mmol scale);
dried using a J. C. Meyer solvent system. SiO2 was dried in a
1
mp: 168−169 °C; H NMR (CDCl3, 500.4 MHz): δ 8.25 (d, J = 7.9
laboratory oven at 160 °C. All reagents were purchased commercially
Hz, 1H), 7.55 (t, J = 7.6 Hz, 1H), 7.45 (d, J = 7.2 Hz, 1H), 7.34 (t, J =
and used as received, unless otherwise noted. Melting points (°C) are
7.5 Hz, 1H), 7.30 (s, 1H), 7.23 (d, J = 6.1 Hz, 2H), 7.18 (t, J = 7.6 Hz,
uncorrected. Mass spectra (ESI- or EI-TOF) were recorded using
1H), 7.07 (d, J = 8.1 Hz, 1H), 6.72 (s, 1H), 2.48 (s, 3H) ppm; 13C
CH2Cl2 or MeCN as the solvent. IR spectra were recorded using
{1H} NMR (CDCl3, 125.8 MHz): δ 166.5, 144.4, 140.9, 134.0, 132.7,
FTIR-ATR of the neat oil or solid products. NMR spectra (1H, 13C
130.1, 130.1, 129.3, 125.6, 122.1, 119.0, 117.7, 22.6 ppm; 11B NMR
{1H}, 11B, 19F {1H}) were performed at 298 K. H (500.4 MHz) and
(CDCl3, 128.4 MHz): δ 30.7 ppm; IR: ν = 3385, 3210, 1614, 1516,
13C {1H} (125.8 MHz) NMR chemical shifts are reported relative to
1484, 1455, 745, 723 cm−1; HRMS (ES+) m/z calcd for C14H14BN2O
1
internal TMS (δ = 0.00 ppm) or to residual protonated solvent. Any
[M + H]+ 237.1199, found 237.1193.
observed splitting in the 13C {1H} NMR spectra is due to 13C−19F
2-(2,6-Fluorophenyl)-1,3,2-benzodiazaborininone (4c). Obtained
coupling. 11B (128.4 MHz) chemical shifts were referenced to external
BF3·Et2O (0.0 ppm). Data are presented as follows: chemical shift
as a beige solid by procedure A after recrystallization from EtOAc (150
1
mg, 58%, 1.0 mmol scale); mp: 164−165 °C; H NMR (acetone-d6,
(ppm), multiplicity (s = singlet, d = doublet, t = triplet, q = quartet,
500.4 MHz): δ 8.59 (s, 1H), 8.55 (s, 1H), 8.15 (d, J = 7.9 Hz, 1H),
sept = septet, m = multiplet, br = broad), coupling constant J (Hz),
7.64−7.50 (m, 2H), 7.42 (d, J = 8.1 Hz, 1H), 7.18 (t, J = 7.5 Hz, 1H),
and integration.
7.05 (t, J = 7.8 Hz, 2H) ppm; 13C {1H} NMR (DMSO-d6, 125.8
Procedure A: Cyclization of Potassium Organotrifluoro-
MHz): δ 165.9, 164.8 (dd, J = 244.6, 13.7 Hz), 145.4, 133.9, 133.1 (t, J
borates Activated with BF3·EtNH2 To Form 1,3,2-Benzodiaza-
= 10.1 Hz), 128.4, 121.8, 119.4, 118.5, 111.6 (dd, J = 22.7, 5.3 Hz)
borininones. To a microwave vial with a stir bar were added
ppm; 19F {1H} NMR (acetone-d6, 470.8 MHz): δ −103.6 ppm; 11B
anthranilamide (1.0 equiv) and the appropriate potassium organo-
NMR (acetone-d6, 128.4 MHz): δ 28.0 ppm; IR: ν = 3438, 3362,
trifluoroborate (1.05 equiv) along with BF3·EtNH2 (3.0 equiv). The
1666, 1616, 1454, 982, 762, 750, 720 cm−1; HRMS (ES+) m/z calcd
reaction vessel was capped and purged with argon, upon which CPME
and toluene were added in a 1:1 mixture (3 mL/mmol). The reaction
was then heated at 80 °C for 16 h. Upon cooling to rt, the reaction
mixture was washed with an aqueous solution of NaHCO3, extracted
with EtOAc, and dried (MgSO4), before being concentrated to afford
the azaborininone product. If needed, the product was further purified
by passage of the crude matter through a short pad of silica, using a 9:1
mixture of hexane/EtOAc as eluent.
Procedure B-1: Cyclization of Potassium Organotrifluoro-
borates Activated with SiO2 To Form Azaborininones. To a
microwave vial with a stir bar were added anthranilamide, anthranilic
acid, or salicylamide (1.0 equiv) and potassium organotrifluoroborates
(1.05 equiv) along with oven-dried SiO2 (100 mg/mmol). The
reaction vessel was capped and purged with argon, upon which CPME
and toluene were added in a 1:1 mixture (3 mL/mmol). The reaction
was then heated at 60 °C for 16 h. Upon cooling to rt, the reaction
mixture was filtered through a short pad of Celite and flushed with
MeOH, before being concentrated. If needed, the solid was further
washed with EtOAc for purification to afford the azaborininone
product.
2-Phenyl-1,3,2-benzodiazaborininone (4a). Obtained as a white
solid by procedure A (195 mg, 88%, 1.0 mmol scale) and procedure B-
1 (113 mg, 51%, 1.0 mmol scale); mp: 206−208 °C; 1H NMR
(CDCl3, 500.4 MHz): δ 8.27 (d, J = 7.9 Hz, 1H), 7.70 (d, J = 7.5 Hz,
2H), 7.61−7.44 (m, 5H), 7.18 (t, J = 7.6 Hz, 1H), 7.12 (d, J = 8.1 Hz,
1H), 6.81 (s, 1H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ
166.9, 144.4, 134.1, 132.0, 131.2, 129.4, 128.7, 122.1, 119.1, 117.8
ppm; 11B NMR (CDCl3, 128.4 MHz): δ 29.4 ppm; IR: ν = 3347,
for C13H10BN2OF2 [M + H]+ 259.0854, found 259.0862.
2-(p-Tolyl)-1,3,2-benzodiazaborininone (4d). Obtained as a white
solid by procedure A (177 mg, 75%, 1.0 mmol scale); mp: 255−256
1
°C; H NMR (CDCl3, 500.4 MHz): δ 8.26 (d, J = 7.8 Hz, 1H), 7.61
(d, J = 7.8 Hz, 2H), 7.56 (t, J = 7.7 Hz, 1H), 7.51 (s, 1H), 7.31 (d, J =
7.6 Hz, 2H), 7.18 (t, J = 7.6 Hz, 1H), 7.11 (d, J = 8.1 Hz, 1H), 6.76 (s,
1H), 2.43 (s, 3H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ
166.7, 144.5, 141.6, 134.0, 132.0, 129.6, 129.4, 122.0, 119.1, 117.7, 21.8
ppm; 11B NMR (CDCl3, 128.4 MHz): δ 29.5 ppm; IR: ν = 3321,
3247, 1635, 1615, 1486, 1364, 1342, 1272, 752, 719, 477 cm−1; HRMS
(EI) m/z calcd for C14H13BN2O [M]+ 236.1121, found 236.1136.
2-(4-Methoxyphenyl)-1,3,2-benzodiazaborininone (4e). Obtained
as a white solid by procedure A (82 mg, 65%, 0.5 mmol scale) and
1
procedure B-1 (58 mg, 68%, 0.5 mmol scale); mp: 215−217 °C; H
NMR (CDCl3, 500.4 MHz): δ 8.26 (d, J = 7.9 Hz, 1H), 7.65 (d, J =
8.5 Hz, 2H), 7.56 (dt, J = 7.8, 1.5 Hz, 1H), 7.52 (s, 1H), 7.17 (t, J =
7.6 Hz, 1H), 7.10 (d, J = 8.1 Hz, 1H), 7.02 (d, J = 8.5 Hz, 2H), 6.73 (s,
1H), 3.88 (s, 3H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ
166.8, 162.2, 144.6, 134.0, 133.7, 129.4, 121.9, 119.0, 117.6, 114.4, 55.4
ppm; 11B NMR (CDCl3, 128.4 MHz): δ 29.2 ppm; IR: ν = 3352,
3290, 1640, 1602, 1507, 1487, 1242, 1179, 753 cm−1; HRMS (ES+)
m/z calcd for C14H1410BN2O2 [M + H]+ 252.1185, found 252.1187.
2-(4-(Trifluoromethyl)phenyl)-1,3,2-benzodiazaborininone (4f).
Obtained as a white solid by procedure A (270 mg, 93%, 1.0 mmol
scale) and procedure B-1 (197 mg, 68%, 1.0 mmol scale); mp: >260
1
°C; H NMR (DMSO-d6, 500.4 MHz): δ 9.80 (s, 1H), 9.45 (s, 1H),
8.23 (d, J = 7.5 Hz, 2H), 8.04 (d, J = 7.7 Hz, 1H), 7.77 (d, J = 7.6 Hz,
G
DOI: 10.1021/acs.joc.7b00747
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The Journal of Organic Chemistry
Article
2H), 7.57 (t, J = 7.4 Hz, 1H), 7.43 (d, J = 7.9 Hz, 1H), 7.11 (t, J = 7.7
Hz, 1H) ppm; 13C {1H} NMR (DMSO-d6, 125.8 MHz): δ 166.7,
145.6, 134.3, 133.8, 130.9 (q, J = 31.7 Hz), 128.3, 124.6 (q, J = 272.2
Hz), 124.6 (q, J = 3.4 Hz), 121.5, 119.3, 118.6 ppm; 19F {1H} NMR
(DMSO-d6, 470.8 MHz): δ −63.1 ppm; 11B NMR (CDCl3, 128.4
MHz): δ 28.5 ppm; IR: ν = 3333, 3245, 1630, 1616, 1316, 1110, 1066,
763, 526 cm−1; HRMS (ES+) m/z calcd for C14H11BN2OF3 [M + H]+
291.0917, found 291.0916.
2-(4-Bromophenyl)-1,3,2-benzodiazaborininone (4g). Obtained
as a white solid by modification to procedure A, as 4g was not
particularly soluble in EtOAc. As a result, some product could be
collected as a precipitate from the aqueous workup (273 mg, 91%, 1.0
mmol scale); mp: >260 °C; 1H NMR (DMSO-d6, 500.4 MHz): δ 9.73
(s, 1H), 9.36 (s, 1H), 8.04−7.95 (m, 3H), 7.65 (d, J = 8.3 Hz, 2H),
7.60−7.53 (m, 1H), 7.40 (d, J = 8.0 Hz, 1H), 7.10 (t, J = 7.3 Hz, 1H)
ppm; 13C {1H} NMR (DMSO-d6, 125.8 MHz): δ 166.6, 145.7, 135.8,
133.8, 131.1, 128.3, 125.0, 121.3, 119.2, 118.5 ppm; 11B NMR (THF,
128.4 MHz): δ 29.4 ppm; IR: ν = 3331, 3240, 1615, 1486, 1269, 753,
717, 528 cm−1; HRMS (ES+) m/z calcd for C13H11BN2OBr [M + H]+
301.0148, found 301.0157.
2-(4-(Naphthalen-1-yl)phenyl)-1,3,2-benzodiazaborininone (4l).
Obtained as a beige solid by procedure A (247 mg, 71%, 1.0 mmol
1
scale); mp: 255−256 °C; H NMR (DMSO-d6, 500.4 MHz): δ 9.76
(s, 1H), 9.42 (s, 1H), 8.20 (d, J = 7.8 Hz, 2H), 8.01 (t, J = 8.7 Hz,
2H), 7.96 (d, J = 8.2 Hz, 1H), 7.82 (d, J = 8.3 Hz, 1H), 7.61−7.52 (m,
5H), 7.52−7.43 (m, 3H), 7.10 (t, J = 7.4 Hz, 1H) ppm; 13C {1H}
NMR (DMSO-d6, 125.8 MHz): δ 166.8, 146.0, 142.5, 139.7, 133.9,
133.8, 133.8, 131.1, 129.6, 128.8, 128.3, 128.2, 127.3, 126.8, 126.3,
125.9, 125.5, 121.2, 119.2, 118.6 ppm; 11B NMR (THF, 128.4 MHz):
δ 29.9 ppm; IR: ν = 3320, 1657, 1316, 1533, 1511, 1485, 1358, 798,
774, 760, 716 cm−1; HRMS (ES-) m/z calcd for C23H16BN2O [M −
H]− 347.1356, found 347.1357.
2-(4-(Benzyloxy)phenyl)-1,3,2-benzodiazaborininone (4m). Ob-
tained as a white solid by procedure A (265 mg, 81%, 1.0 mmol scale);
mp: 249−251 °C; 1H NMR (DMSO-d6, 500.4 MHz): δ 9.57 (s, 1H),
9.20 (s, 1H), 8.07−7.94 (m, 3H), 7.54 (t, J = 7.6 Hz, 1H), 7.46 (d, J =
7.7 Hz, 2H), 7.43−7.37 (m, 3H), 7.33 (t, J = 7.3 Hz, 1H), 7.11−7.03
(m, 3H), 5.17 (s, 2H) ppm; 13C {1H} NMR (DMSO-d6, 125.8 MHz):
δ 166.7, 160.8, 146.0, 137.3, 135.5, 133.7, 128.8, 128.3, 128.2, 128.0,
120.9, 118.9, 118.4, 114.7, 69.4 ppm; 11B NMR (THF, 128.4 MHz): δ
29.6 ppm; IR: ν = 3404, 3302, 1645, 1622, 1604, 1486, 1214, 996, 759,
721 cm−1; HRMS (ES+) m/z calcd for C20H18BN2O2 [M + H]+
329.1461, found 329.1458.
2-(3-Aminophenyl)-1,3,2-benzodiazaborininone (4h). Obtained
as a tan solid by modification to procedure A, as 4h was minimally
soluble in EtOAc. As a result, the product could be collected directly as
a precipitate from the aqueous workup (173 mg, 73%, 1.0 mmol
2-(Furan-3-yl)-1,3,2-benzodiazaborininone (4m). Obtained as a
1
light brown solid by procedure A (172 mg, 81%, 1.0 mmol scale); mp:
scale); mp: 210−213 °C; H NMR (DMSO-d6, 500.4 MHz): δ 9.38
1
190−192 °C; H NMR (CDCl3, 500.4 MHz): δ 8.25 (d, J = 7.9 Hz,
(s, 1H), 9.17 (s, 1H), 7.99 (d, J = 7.9 Hz, 1H), 7.61−7.50 (m, 1H),
7.42 (d, J = 8.2 Hz, 1H), 7.19−7.12 (m, 2H), 7.12−7.04 (m, 2H), 6.70
(d, J = 7.7 Hz, 1H), 4.92 (s, 2H) ppm; 13C {1H} NMR (DMSO-d6,
125.8 MHz): δ 166.6, 148.3, 146.0, 133.6, 128.7, 128.2, 121.5, 121.0,
119.1, 118.5, 116.6, 99.9 ppm; 11B NMR (MeCN, 128.4 MHz): δ 30.1
ppm; IR: ν = 3395, 3292, 3211, 1657, 1608, 1526, 1484, 757, 509
cm−1; HRMS (ES+) m/z calcd for C13H12BN3ONa [M + Na]+
260.0971, found 260.0984.
1H), 8.00 (s, 1H), 7.90 (s, 1H), 7.60 (s, 1H), 7.55 (t, J = 8.2 Hz, 1H),
7.27 (s, 1H), 7.17 (t, J = 7.5 Hz, 1H), 7.09 (d, J = 8.1 Hz, 1H), 6.68 (s,
1H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 167.0, 148.6,
144.5, 144.1, 134.0, 129.3, 121.9, 119.1, 117.5, 111.7 ppm; 11B NMR
(EtOAc, 128.4 MHz): δ 28.2 ppm; IR: ν = 3347, 3250, 1636, 1610,
1516, 1487, 1150, 754, 732, 668, 527 cm−1; HRMS (ES+) m/z calcd
for C11H10BN2O2 [M + H]+ 213.0835, found 213.0836
2-(Thiophen-2-yl)-1,3,2-benzodiazaborininone (4n). Obtained as
a white solid by procedure A (169 mg, 74%, 1.0 mmol scale); mp:
211−213 °C; 1H NMR (DMSO-d6, 500.4 MHz): δ 9.71 (s, 1H), 9.26
(s, 1H), 7.99 (dd, J = 11.2, 2.5 Hz, 2H), 7.92 (d, J = 4.6 Hz, 1H), 7.55
(td, J = 7.8, 1.5 Hz, 1H), 7.41 (d, J = 8.1 Hz, 1H), 7.29 (dd, J = 4.6, 3.5
Hz, 1H), 7.09 (t, J = 7.5 Hz, 1H) ppm; 13C {1H} NMR (DMSO-d6,
125.8 MHz): δ 166.4, 145.8, 136.7, 133.8, 132.8, 129.0, 128.3, 121.2,
119.2, 118.5 ppm; 11B NMR (EtOAc, 128.4 MHz): δ 27.7 ppm; IR: ν
= 3315, 3240, 1614, 1530, 1486, 1264, 1025, 753, 698, 687, 474 cm−1;
HRMS (ES+) m/z calcd for C11H10BN2OS [M + H]+ 229.0607, found
229.0618.
(E)-2-(Prop-1-en-1-yl)-1,3,2-benzodiazaborininone (4o). Obtained
as an off-white solid by procedure A (166 mg, 89%, 1.0 mmol scale)
and procedure B-1 (156 mg, 84%, 1.0 mmol scale); mp: 142−143 °C;
1H NMR (DMSO-d6, 500.4 MHz): δ 9.25 (s, 1H), 8.91 (s, 1H), 7.93
(d, J = 7.8 Hz, 1H), 7.55−7.45 (m, 1H), 7.22 (d, J = 8.2 Hz, 1H), 7.02
(t, J = 7.5 Hz, 1H), 6.77 (dq, J = 18.7, 6.3 Hz, 1H), 5.69 (dd, J = 17.9,
1.7 Hz, 1H), 1.86 (d, J = 6.3 Hz, 3H) ppm; 13C {1H} NMR (DMSO-
d6, 125.8 MHz): δ 166.4, 145.9, 145.7, 133.5, 128.3, 120.7, 119.1,
118.1, 22.1 ppm; 11B NMR (EtOAc, 128.4 MHz,): δ 28.4 ppm; IR: ν =
3315, 3201, 1608, 1517, 1485, 1362, 986, 754 cm−1; HRMS (ES+) m/
z calcd for C10H12BN2O [M + H]+ 187.1043, found 187.1048.
2-Methyl-1,3,2-benzodiazaborininone (4p). Obtained as a white
solid by procedure A after purifying via a plug of silica gel with EtOAc/
hexane (1:1) as eluent (86 mg, 54%, 1.0 mmol scale) and procedure B-
1 (86 mg, 62%, 1.0 mmol scale); mp: 181−182 °C; 1H NMR (CDCl3,
500.4 MHz): δ 8.20 (d, J = 6.8 Hz, 1H), 7.50 (t, J = 6.8 Hz, 1H), 7.12
(t, J = 7.2 Hz, 2H), 6.98 (d, J = 7.3 Hz, 1H), 6.40 (s, 1H), 0.59 (s, 3H)
ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 166.5, 144.4, 133.8,
129.2, 121.6, 118.7, 117.2 ppm; 11B NMR (CDCl3, 128.4 MHz): δ
32.3 ppm; IR: ν = 3267, 3190, 1609, 1519, 1486, 1364, 909, 749 cm−1;
HRMS (CI) m/z calcd for C8H9BN2O [M]+ 160.0808, found
160.0808.
2-(3-(Methoxycarbonyl)phenyl)-1,3,2-benzodiazaborininone (4i).
Obtained as a white solid by modification to procedure A, as 4i was
not particularly soluble in EtOAc. As a result some product was also
collected as a precipitate from the aqueous workup (258 mg, 92%, 1.0
mmol scale); mp: 234−235 °C; 1H NMR (DMSO-d6, 500.4 MHz): δ
9.82 (s, 1H), 9.48 (s, 1H), 8.63 (s, 1H), 8.27 (d, J = 7.4 Hz, 1H), 8.05
(d, J = 7.8 Hz, 1H), 8.01 (d, J = 7.8 Hz, 1H), 7.63−7.54 (m, 2H), 7.44
(d, J = 8.1 Hz, 1H), 7.10 (t, J = 7.5 Hz, 1H), 3.89 (s, 3H) ppm; 13C
{1H} NMR (DMSO-d6, 125.8 MHz): δ 166.9, 166.6, 145.8, 138.5,
134.5, 133.8, 131.4, 129.7, 128.6, 128.3, 121.3, 119.3, 118.6, 52.5 ppm;
11B NMR (THF, 128.4 MHz): δ 29.5 ppm; IR: ν = 3320, 3226, 2951,
1716, 1623, 1487, 1289, 749, 690 cm−1; HRMS (ES+) m/z calcd for
C15H14BN2O3 [M + H]+ 281.1097, found 281.1092.
2-(3-Cyanophenyl)-1,3,2-benzodiazaborininone (4j). Obtained as
a white solid by procedure A after purifying via plug of silica gel with
EtOAc/hexane (1:1) as eluent (138 mg, 56%, 1.0 mmol scale); mp:
1
>260 °C; H NMR (DMSO-d6, 500.4 MHz): δ 9.84 (s, 1H), 9.47 (s,
1H), 8.48 (s, 1H), 8.35 (t, J = 6.6 Hz, 1H), 8.01 (d, J = 7.5 Hz, 1H),
7.93 (d, J = 6.9 Hz, 1H), 7.66 (t, J = 7.5 Hz, 1H), 7.58 (d, J = 7.1 Hz,
1H), 7.40 (d, J = 7.1 Hz, 1H), 7.16−7.03 (m, 1H) ppm; 13C {1H}
NMR (DMSO-d6, 125.8 MHz): δ 166.6, 145.6, 138.2, 137.3, 134.1,
133.9, 129.2, 128.3, 121.5, 119.4, 119.3, 118.6, 111.6 ppm; 11B NMR
(THF, 128.4 MHz): δ 29.3 ppm; IR: ν = 3365, 3197, 2230, 1651,
1619, 1485, 760, 699, 687 cm−1; HRMS (ES+) m/z calcd for
C14H11BN3O [M + H]+ 248.0995, found 248.0991.
2-(3-Nitrophenyl)-1,3,2-benzodiazaborininone (4k). Obtained as a
beige solid by procedure A (123 mg, 92%, 0.5 mmol scale); mp: >260
1
°C; H NMR (DMSO-d6, 500.4 MHz): δ 9.97 (s, 1H), 9.62 (s, 1H),
8.92 (s, 1H), 8.46 (d, J = 7.4 Hz, 1H), 8.31 (dd, J = 8.2, 1.4 Hz, 1H),
8.02 (d, J = 7.9 Hz, 1H), 7.74 (t, J = 7.8 Hz, 1H), 7.63−7.55 (m, 1H),
7.44 (d, J = 8.1 Hz, 1H), 7.13 (t, J = 7.5 Hz, 1H) ppm; 13C {1H} NMR
(DMSO-d6, 125.8 MHz): δ 166.6, 148.1, 145.6, 140.3, 140.3, 133.9,
129.7, 128.3, 125.4, 121.6, 119.3, 118.6 ppm; 11B NMR (THF, 128.4
MHz): δ 29.1 ppm; IR: ν = 3325, 1614, 1515, 1484, 1345, 1269, 763,
679 cm−1; HRMS (ES-) m/z calcd for C13H9BN3O3 [M − H]−
266.0737, found 266.0747.
2-Cyclopropyl-1,3,2-benzodiazaborininone (4q). Obtained as a
white solid by procedure A (121 mg, 65%, 1.0 mmol scale) and
1
procedure B-1 (108 mg, 58%, 1.0 mmol scale); mp: 186−188 °C; H
NMR (DMSO-d6, 500.4 MHz): δ 8.98 (s, 1H), 8.50 (s, 1H), 7.90 (dd,
H
DOI: 10.1021/acs.joc.7b00747
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Article
J = 7.9, 1.4 Hz, 1H), 7.47 (td, J = 7.8, 1.6 Hz, 1H), 7.17 (d, J = 8.0 Hz,
1H), 6.99 (t, J = 7.5 Hz, 1H), 0.68 (dt, J = 9.2, 2.5 Hz, 2H), 0.65−0.59
(m, 2H), 0.05 (ddd, J = 9.2, 6.5, 2.9 Hz, 1H) ppm; 13C {1H} NMR
(DMSO-d6, 125.8 MHz): δ 166.2, 145.8, 133.4, 128.2, 120.4, 118.7,
117.8, 5.4 ppm; 11B NMR (EtOAc, 128.4 MHz): δ 30.4 ppm; IR: ν =
3380, 3308, 3189, 1615, 1557, 1488, 1393, 1254, 752 cm−1; HRMS
(ES+) m/z calcd for C10H12BN2O [M + H]+ 187.1043, found
187.1048.
Procedure C: Condensation of Boronic Acids To Form
Oxazaborininones. To a round-bottomed flask with a stir bar were
added the appropriate boronic acid (1 equiv) and either anthranilic
acid or salicylamide (1 equiv) followed by toluene (4 mL/mmol). The
flask was equipped with a Dean−Stark trap, and the reaction was
heated to reflux. The reaction was stirred at this temperature
overnight. After this time, the solvent was removed in vacuo by rotary
evaporation, giving a crude solid. The resulting solid was further
purified by washing with hexane/EtOAc (1:1), affording the desired,
pure oxazaborininone.
198.7, 162.0, 146.5, 139.2, 136.1, 134.1, 130.3, 128.0, 122.3, 118.3,
115.1, 27.5 ppm; 11B NMR (acetone-d6, 128 MHz): δ 27.6 ppm; IR: ν
= 3308, 1668, 1614, 1484, 1399, 1261, 1233, 760, 628 cm−1; HRMS
(ES+) m/z calcd for C15H13BNO3 [M + H]+ 266.0988, found
266.0983.
2-(3-Cyanophenyl)-3,1,2-benzoxazaborininone (5f). Obtained as
an off-white solid by procedure B-1 (136 mg, 55%, 1.0 mmol scale)
1
and procedure C (677 mg, 91%, 3.0 mmol scale); mp: >260 °C; H
NMR (DMSO-d6, 500.4 MHz): δ 9.33 (s, 1H), 8.26 (s, 1H), 8.15 (d, J
= 7.5 Hz, 1H), 7.90 (d, J = 7.6 Hz, 2H), 7.64 (t, J = 7.6 Hz, 1H), 7.59
(t, J = 7.5 Hz, 1H), 7.21 (d, J = 8.1 Hz, 1H), 7.06 (t, J = 7.5 Hz, 1H)
ppm; 13C {1H} NMR (DMSO-d6, 125.8 MHz): δ 162.1, 146.8, 138.1,
137.2, 136.0, 134.5, 130.4, 129.6, 121.8, 119.5, 118.1, 114.8, 111.8
ppm; 11B NMR (acetone-d6, 128 MHz): δ 27.1 ppm; IR: ν = 3313,
2235, 1694, 1621, 1526, 1483, 1279, 753, 688, 524 cm−1; HRMS (ES
+) m/z calcd for C14H10BN2O2 [M + H]+ 249.0835, found 249.0836.
2-(2-Nitrophenyl)-3,1,2-benzoxazaborininone (5g). Obtained as a
light yellow solid by procedure B-1 (81 mg, 30%, 1.0 mmol scale) and
1
2-Phenyl-3,1,2-benzoxazaborininone (5a). Obtained as a white
solid by procedure B-1 (367 mg, 83%, 2.0 mmol scale) and procedure
C (650 mg, 93%, 3.0 mmol scale); mp: 211−212 °C; 1H NMR
(CDCl3, 500.4 MHz): δ 8.21 (d, J = 7.8 Hz, 1H), 7.95 (d, J = 6.9 Hz,
2H), 7.64−7.59 (m, 1H), 7.58−7.53 (m, 1H), 7.48 (t, J = 7.4 Hz, 2H),
7.20 (t, J = 7.5 Hz, 1H), 7.09 (d, J = 8.1 Hz, 1H), 6.89 (s, 1H) ppm;
13C {1H} NMR (DMSO-d6, 125.8 MHz): δ 161.8, 146.1, 135.8, 133.8,
procedure C (498 mg, 93%, 2.0 mmol scale); mp: 210−211 °C; H
NMR (DMSO-d6, 500.4 MHz): δ 9.43 (s, 1H), 8.25 (d, J = 8.2 Hz,
1H), 7.98 (d, J = 7.8 Hz, 1H), 7.92−7.85 (m, 2H), 7.76 (t, J = 7.3 Hz,
1H), 7.65 (t, J = 7.5 Hz, 1H), 7.19−7.13 (m, 2H) ppm; 13C {1H}
NMR (DMSO-d6, 125.8 MHz): δ 161.8, 151.3, 146.5, 136.3, 135.1,
134.3, 131.6, 130.4, 123.8, 122.5, 118.2, 114.8 ppm; 11B NMR
(methanol-d4, 128 MHz): δ 27.0 ppm; IR: ν = 3348, 1698, 1510, 1484,
1342, 1266, 756, 724, 695 cm−1; HRMS (ES+) m/z calcd for
C13H10BN2O4 [M + H]+ 269.0734, found 269.0741.
131.8, 130.1, 128.3, 122.2, 118.1, 114.9 ppm; 11B NMR (CDCl3, 128.4
MHz): δ 28.9 ppm; IR: ν = 3315, 1685, 1613, 1484, 1431, 1271, 1227,
750, 692 cm−1; HRMS (ES+) m/z calcd for C13H11BNO2 [M + H]+
224.0883, found 224.0904.
2-(Thiophen-3-yl)-3,1,2-benzoxazaborininone (5h). Obtained as
an off-white solid by procedure B-1 (147 mg, 64%, 1.0 mmol scale)
and procedure C after washing with t-BuOH (400 mg, 87%, 3.0 mmol
scale); mp: 227−229 °C; 1H NMR (CDCl3, 500.4 MHz): δ 8.19 (d, J
= 7.9 Hz, 1H), 8.13 (s, 1H), 7.60 (t, J = 7.7 Hz, 1H), 7.53 (d, J = 4.8
Hz, 1H), 7.49−7.43 (m, 1H), 7.19 (t, J = 7.6 Hz, 1H), 7.07 (d, J = 8.1
Hz, 1H), 6.77 (s, 1H) ppm; 13C {1H} NMR (DMSO-d6, 125.8 MHz):
δ 161.7, 146.1, 136.7, 135.9, 131.6, 130.1, 127.0, 122.2, 118.0, 114.9
ppm; 11B NMR (CDCl3, 128.4 MHz): δ 27.0 ppm; IR: ν = 3295,
1694, 1619, 1524, 1483, 1273, 1096, 695, 658, 521 cm−1; HRMS (ES
+) m/z calcd for C11H9BNO2S [M + H]+ 230.0447, found 230.0445.
2-(1-Methyl-1H-indol-5-yl)-3,1,2-benzoxazaborininone (5i). Ob-
tained as a white solid by procedure B-1 (138 mg, 50%, 1.0 mmol
scale) and procedure C (524 mg, 95%, 2.0 mmol scale); mp: >260 °C;
1H NMR (DMSO-d6, 500.4 MHz): δ 9.65 (s, 1H), 8.28 (s, 1H), 7.95
(d, J = 7.8 Hz, 1H), 7.79 (d, J = 8.3 Hz, 1H), 7.64 (t, J = 8.3 Hz, 1H),
7.53 (d, J = 8.3 Hz, 1H), 7.38−7.34 (m, 2H), 7.12 (t, J = 7.5 Hz, 1H),
6.53 (d, J = 2.8 Hz, 1H), 3.81 (s, 3H) ppm; 13C {1H} NMR (DMSO-
d6, 125.8 MHz): δ 161.9, 146.4, 138.8, 135.8, 130.6, 130.1, 128.3,
127.6, 126.4, 122.0, 118.0, 114.7, 109.8, 101.5, 32.9 ppm; 11B NMR
(acetone-d6, 128 MHz): δ 28.7 ppm; IR: ν = 3285, 1693, 1612, 1520,
1485, 1293, 1268, 1175, 753, 717, 697 cm−1; HRMS (ES+) m/z calcd
for C16H14BN2O2 [M + H]+ 277.1148, found 277.1147.
2-Vinyl-3,1,2-benzoxazaborininone (5j). Obtained as an off-white
solid by procedure B-1 (142 mg, 41%, 2.0 mmol scale); mp: 140−141
°C; 1H NMR (CDCl3, 500.4 MHz): 8.14 (d, J = 8.6 Hz, 1H), 7.55 (td,
J = 7.7, 1.5 Hz, 1H), 7.15 (t, J = 7.6 Hz, 1H), 6.98 (d, J = 8.1 Hz, 1H),
6.51 (s, 1H), 6.41 (dd, J = 19.1, 3.6 Hz, 1H), 6.16 (dd, J = 13.6, 3.4
Hz, 1H), 6.07 (dd, J = 19.1, 13.6 Hz, 1H) ppm; 13C {1H} NMR
(CDCl3, 125.8 MHz): δ 161.8, 144.2, 137.2, 135.5, 131.1, 122.9, 117.1,
115.6 ppm; 11B NMR (CDCl3, 128.4 MHz): δ 27.6 ppm; IR: ν =
3265, 1706, 1618, 1516, 1486, 1351, 1283, 1175. 755, 694 cm−1;
HRMS (ES+) m/z calcd for C9H9BNO2 [M + H]+ 174.0726, found
174.0730.
2-(p-Tolyl)-3,1,2-benzoxazaborininone (5b). Obtained as an off-
white solid by procedure B-1 (408 mg, 86%, 2.0 mmol scale) and
1
procedure C (230 mg, 97%, 2.0 mmol scale); mp: 220−221 °C; H
NMR (DMSO-d6, 500.4 MHz): δ 9.66 (s, 1H), 7.94 (d, J = 7.9 Hz,
1H), 7.88 (d, J = 7.8 Hz, 2H), 7.67−7.62 (m, 1H), 7.33 (d, J = 8.1 Hz,
1H), 7.29 (d, J = 7.6 Hz, 2H), 7.13 (t, J = 7.6 Hz, 1H), 2.35 (s, 3H)
ppm; 13C {1H} NMR (DMSO-d6, 125.8 MHz): δ 161.4, 145.7, 141.3,
135.5, 133.6, 129.7, 128.7, 121.8, 117.7, 114.4, 21.3 ppm; 11B NMR
(MeCN, 128.4 MHz): δ 29.2 ppm; IR: ν = 3307, 1701, 1613, 1485,
1280, 756, 695, 626 cm−1; HRMS (ES+) m/z calcd for C14H13BNO2
[M + H]+ 238.1039, found 238.1033.
2-(4-Methoxyphenyl)-3,1,2-benzoxazaborininone (5c). Obtained
as a white solid by procedure B-1 (154 mg, 61%, 1.0 mmol scale) and
procedure C after an additional wash with t-BuOH (364 mg, 72%, 2.0
1
mmol scale); mp: 205−206 °C; H NMR (CDCl3, 500.4 MHz): δ
8.18 (d, J = 7.8 Hz, 1H), 7.88 (d, J = 8.5 Hz, 2H), 7.61−7.54 (m, 1H),
7.16 (t, J = 7.5 Hz, 1H), 7.04 (d, J = 8.1 Hz, 1H), 6.99 (d, J = 8.6 Hz,
2H), 6.75 (s, 1H), 3.87 (s, 3H) ppm; 13C {1H} NMR (CDCl3, 125.8
MHz): δ 162.5, 161.8, 146.2, 135.9, 135.8, 130.1, 122.1, 118.0, 114.7,
114.1, 55.5 ppm; 11B NMR (CDCl3, 128.4 MHz): δ 28.6 ppm; IR: ν =
3340, 1698, 1599, 1428, 1281, 1251, 1224, 1180, 753, 693 cm−1;
HRMS (ES+) m/z calcd for C14H13BNO3 [M + H]+ 254.0988, found
254.0984.
2-(4-(Trifluoromethyl)phenyl)-3,1,2-benzoxazaborininone (5d).
Obtained as a white solid by procedure B-1 (226 mg, 78%, 1.0
mmol scale); mp: >260 °C; 1H NMR (DMSO-d6, 500.4 MHz): δ 9.50
(s, 1H), 8.12 (d, J = 7.8 Hz, 2H), 7.93 (d, J = 7.7 Hz, 1H), 7.81 (d, J =
7.9 Hz, 2H), 7.62 (t, J = 7.4 Hz, 1H), 7.28 (d, J = 8.1 Hz, 1H), 7.09 (t,
J = 7.5 Hz, 1H) ppm; 13C NMR (DMSO-d6, 126 MHz): δ 162.1,
146.7, 136.0, 134.5, 131.4 (q, J = 31.4 Hz), 130.4, 124.9 (q, J = 272
Hz), 125.0 (q, J = 3.5 Hz), 122.0, 118.2, 115.0 ppm; 19F {1H} NMR
(DMSO-d6, 470.8 MHz): δ −61.3 ppm; 11B NMR (EtOAc, 128.4
MHz): δ 28.8 ppm; IR: ν = 3307, 1686, 1615, 1326, 1265, 1149, 1108,
1071, 759, 635 cm−1; HRMS (ES+) m/z calcd for C14H10BNO2F3 [M
+ H]+ 292.0757, found 292.0753.
2-Phenethyl-3,1,2-benzoxazaborininone (5k). Obtained as a
yellow solid by procedure B-1 (377 mg, 75%, 2.0 mmol scale); mp:
1
100−102 °C; H NMR (CDCl3, 500.4 MHz): δ 8.12 (d, J = 7.9 Hz,
2-(4-Acetylphenyl)-3,1,2-benzoxazaborininone (5e). Obtained as
a white solid by procedure B-1 (313 mg, 59%, 2.0 mmol scale); mp:
252−253 °C; 1H NMR (DMSO-d6, 500.4 MHz): δ 9.64 (s, 1H), 8.09
(d, J = 7.9 Hz, 2H), 8.03 (d, J = 7.9 Hz, 2H), 7.96 (d, J = 7.8 Hz, 1H),
7.65 (t, J = 7.5 Hz, 1H), 7.32 (d, J = 8.1 Hz, 1H), 7.13 (t, J = 7.5 Hz,
1H), 2.62 (s, 3H) ppm; 13C {1H} NMR (DMSO-d6, 125.8 MHz): δ
1H), 7.52 (td, J = 8.2, 1.5 Hz, 1H), 7.30 (t, J = 7.5 Hz, 2H), 7.26−7.23
(m, 2H), 7.22−7.17 (m, 1H), 7.13 (t, J = 7.6 Hz, 1H), 6.84 (d, J = 8.0
Hz, 1H), 6.23 (s, 1H), 2.91 (t, J = 8.0 Hz, 2H), 1.50 (t, J = 8.0 Hz, 2H)
ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 161.9, 144.1, 143.6,
135.5, 131.0, 128.7, 128.1, 126.1, 122.8, 116.8, 115.2, 29.8 ppm; 11B
NMR (CDCl3, 128.4 MHz): δ 32.7 ppm; IR: ν = 3118, 1689, 1619,
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1520, 1489, 1276, 1131, 757, 693 cm−1; HRMS (ES+) m/z calcd for
C15H15BNO2 [M + H]+ 252.1196, found 252.1196.
cm−1; HRMS (ES+) m/z calcd for C14H10BNO2F3 [M + H]+
292.0757, found 292.0750.
2-Cyclopropyl-3,1,2-benzoxazaborininone (5l). Obtained as a
beige solid by procedure B-1 after washing with 5:1 hexane/EtOAc
instead of straight EtOAc (137 mg, 73%, 1.0 mmol scale) and
2-(4-Acetylphenyl)-1,3,2-benzoxazaborininone (6e). Obtained as
a white solid by procedure C (398 mg, 75%, 2.0 mmol scale); mp:
236−238 °C; 1H NMR (CDCl3, 500.4 MHz): δ 8.21 (dd, J = 7.8, 1.7
Hz, 1H), 8.06 (dd, J = 10.3, 8.5 Hz, 4H), 7.91 (s, 1H), 7.69 (td, J =
7.8, 1.7 Hz, 1H), 7.42 (d, J = 8.2 Hz, 1H), 7.34 (t, J = 7.5 Hz, 1H),
2.67 (s, 3H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 197.9,
164.7, 155.6, 139.7, 135.1, 133.5, 128.5, 127.8, 124.0, 119.4, 119.1, 26.7
ppm; 11B NMR (THF, 128.4 MHz): δ 31.4 ppm; IR: ν = 3158, 3100,
2985, 1687, 1673, 1402, 1258, 864, 753, 619 cm−1; HRMS (ES+) m/z
calcd for C15H13BNO3 [M + H]+ 266.0988 found 266.0990.
2-(2-Methoxyphenyl)-1,3,2-benzoxazaborininone (6f). Obtained
as a white solid by procedure B-2 after further washing with acetone
(89 mg, 35%, 1.0 mmol scale) and procedure C (454 mg, 90%, 2.0
1
procedure C (516 mg, 92%, 3.0 mmol scale); mp: 155−156 °C; H
NMR (CDCl3, 500.4 MHz): δ 8.07 (d, J = 7.8 Hz, 1H), 7.52 (t, J = 7.7
Hz, 1H), 7.08 (t, J = 7.6 Hz, 1H), 6.94 (d, J = 8.1 Hz, 1H), 6.58 (s,
1H), 0.82−0.71 (m, 4H), 0.02 (tt, J = 8.7, 6.6 Hz, 1H) ppm; 13C {1H}
NMR (CDCl3, 125.8 MHz): δ 162.1, 144.4, 135.3, 130.7, 122.0, 116.5,
114.8, 5.0 ppm; 11B NMR (CDCl3, 128.4 MHz): δ 32.3 ppm; IR: ν =
3270, 1699, 1615, 1515, 1486, 1442, 1163, 755 cm−1; HRMS (ES+)
m/z calcd for C10H1110BNO2 [M + H]+ 187.0919, found 187.0925.
Procedure B-2: Cyclization of Potassium Trifluoroborates
Activated with Silica Gel To Form 1,3,2-Benzoxaza-
borininones. To a microwave vial with a stir bar were added
salicylamide (1.0 equiv) and the appropriate potassium organo-
trifluoroborates (1.05 equiv) along with oven-dried silica gel (100 mg/
mmol). The reaction vessel was capped and purged with argon, and
subsequently dry MeOH was added (3 mL/mmol). The reaction was
then heated at 60 °C for 16 h. Upon cooling to rt, the reaction mixture
was filtered through a short pad Celite and flushed with additional
MeOH. Removal of the solvent in vacuo afforded the desired 1,3,2-
benzoxazaborininone product.
1
mmol scale); mp: 169−171 °C; H NMR (THF-d8, 500.4 MHz): δ
8.59 (s, 1H), 8.12 (dd, J = 7.8, 1.6 Hz, 1H), 8.06 (dd, J = 7.4, 1.6 Hz,
1H), 7.67−7.62 (m, 1H), 7.56−7.46 (m, 1H), 7.38 (dd, J = 8.3, 0.6
Hz, 1H), 7.27 (t, J = 7.5 Hz, 1H), 7.06 (t, J = 7.4 Hz, 2H), 3.97 (s, 3H)
ppm; 13C {1H} NMR (THF-d8, 125.8 MHz): δ 165.2, 163.0, 155.9,
135.6, 134.0, 133.4, 127.9, 123.0, 120.2, 118.6, 110.2, 54.6 ppm; 11B
NMR (THF-d8, 128.4 MHz): δ 31.4 ppm; IR: ν = 3397, 1694, 1598,
1468, 1420, 1365, 1243, 767, 752 cm−1; HRMS (ES+) m/z calcd for
C14H13BNO3 [M + H]+ 254.0988, found 254.0981.
2-Phenyl-1,3,2-benzoxazaborininone (6a). Obtained as a white
solid by procedure B-2 after recrystallization from CHCl3 (123 mg,
55%, 1.0 mmol scale) and procedure C (2.75 g, 81%, 10.0 mmol
2-(Thiophen-3-yl)-1,3,2-benzoxazaborininone (6g). Obtained as a
white solid by procedure B-2 after further washing with acetone (44
mg, 19%, 1.0 mmol scale) and procedure C (408 mg, 89%, 2.0 mmol
scale); mp: 215−217 °C; 1H NMR (CDCl3, 500.4 MHz): δ 8.24−8.18
(m, 2H), 8.11 (s, 1H), 7.70−7.63 (m, 1H), 7.60 (dd, J = 4.8, 0.9 Hz,
1H), 7.50 (dd, J = 4.8, 2.7 Hz, 1H), 7.38 (d, J = 8.3 Hz, 1H), 7.31 (t, J
= 7.5 Hz, 1H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 165.3,
155.9, 136.5, 134.9, 130.7, 128.4, 126.4, 123.6, 119.4, 119.0 ppm; 11B
NMR (CDCl3, 128.4 MHz): δ 29.7 ppm; IR: ν = 3163, 3102, 1679,
1469, 1385, 1263, 1244, 760, 662 cm−1; HRMS (ES+) m/z calcd for
C11H9BNO2S [M + H]+ 230.0447, found 230.0463.
2-(1-Methyl-1H-indol-5-yl)-1,3,2-benzoxazaborininone (6h). Ob-
tained as a beige solid by procedure B-2 after recrystallization from
CHCl3 (41 mg, 15%, 1.0 mmol scale) and procedure C (528 mg, 95%,
2.0 mmol scale); mp: 244−246 °C; 1H NMR (CDCl3, 500.4 MHz): δ
8.27 (s, 1H), 8.19 (dd, J = 7.8, 1.7 Hz, 1H), 7.75 (d, J = 8.3 Hz, 1H),
7.70−7.62 (m, 2H), 7.43 (dd, J = 12.4, 8.3 Hz, 2H), 7.28 (t, J = 7.5 Hz,
1H), 7.12 (d, J = 3.1 Hz, 1H), 6.61 (s, 1H), 3.85 (s, 3H) ppm; 13C
{1H} NMR (CDCl3, 125.8 MHz): δ 165.0, 156.1, 139.0, 134.7, 129.5,
128.5, 128.3, 127.4, 125.8, 123.3, 119.4, 119.0, 109.2, 101.9, 32.8 ppm;
11B NMR (CDCl3, 128.4 MHz): δ 29.9 ppm; IR: ν = 3210, 2185,
3097, 1680, 1601, 1372, 1242, 1184, 1177, 759, 622, 598 cm−1; HRMS
(ES+) m/z calcd for C16H14BN2O2 [M + H]+ 277.1148, found
277.1157.
1
scale); mp: 195−196 °C; H NMR (CDCl3, 500.4 MHz): δ 8.25 (s,
1H), 8.22 (dd, J = 7.8, 1.6 Hz, 1H), 8.01 (d, J = 6.8 Hz, 2H), 7.70−
7.64 (m, 1H), 7.61−7.56 (m, 1H), 7.52 (t, J = 7.3 Hz, 2H), 7.41 (d, J =
8.2 Hz, 1H), 7.32 (t, J = 7.5 Hz, 1H) ppm; 13C {1H} NMR (CDCl3,
125.8 MHz): δ 165.3, 155.8, 134.8, 133.3, 132.1, 128.4, 128.3, 123.7,
119.5, 119.1 ppm; 11B NMR (128.4 MHz, CDCl3): δ 32.2 ppm; IR: ν
= 3202, 3101, 1688, 1471, 11373, 1276, 1245, 758, 629 cm−1; HRMS
(ES+) m/z calcd for C13H11BNO2 [M + H]+ 224.0883, found
224.0880.
2-(p-Tolyl)-1,3,2-benzoxazaborininone (6b). Obtained as a white
solid by procedure B-2 after recrystallization from CHCl3 (156 mg,
66%, 1.0 mmol scale) and procedure C (1.32 g, 90%, 5.0 mmol scale);
mp: 200−202 °C; 1H NMR (CDCl3, 500.4 MHz): δ 8.20 (dd, J = 7.8,
1.7 Hz, 1H), 7.97 (s, 1H), 7.87 (d, J = 7.9 Hz, 2H), 7.66 (td, J = 7.8,
1.7 Hz, 1H), 7.39 (d, J = 8.3 Hz, 1H), 7.34−7.28 (m, 3H), 2.44 (s,
3H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 165.1, 155.9,
142.6, 134.8, 133.3, 129.1, 128.3, 123.6, 119.4, 119.1, 21.7 ppm; 11B
NMR (CDCl3, 128.4 MHz): δ 30.7 ppm; IR: ν = 3210, 3098, 1667,
1609, 1454, 1372, 1276, 860, 760 cm−1; HRMS (ES+) m/z calcd for
C14H13BNO2 [M + H]+ 238.1039, found 238.1031.
2-(4-Methoxyphenyl)-1,3,2-benzoxazaborininone (6c). Obtained
as a white solid by procedure B-2 after recrystallization from CHCl3
(106 mg, 42%, 1.0 mmol scale) and procedure C (466 mg, 92%, 2.0
2-Phenethyl-1,3,2-benzoxazaborininone (6i). Obtained as a white
solid by procedure B-2 after further washing with acetone (75 mg,
1
1
mmol scale); mp: 231−233 °C; H NMR (CDCl3, 500.4 MHz): δ
30%, 1.0 mmol scale); mp: 115−116 °C; H NMR (CDCl3, 500.4
8.19 (d, J = 8.2 Hz, 1H), 7.89 (d, J = 8.3 Hz, 2H), 7.66 (t, J = 7.7 Hz,
1H), 7.58 (s, 1H), 7.38 (d, J = 8.3 Hz, 1H), 7.30 (t, J = 7.3 Hz, 1H),
7.03 (d, J = 8.3 Hz, 2H), 3.90 (s, 3H) ppm; 13C {1H} NMR (CDCl3,
125.8 MHz): δ 164.8, 162.9, 155.9, 135.1, 134.8, 128.4, 123.5, 119.3,
119.0, 113.9, 55.1 ppm; 11B NMR (THF, 128.4 MHz): δ 31.2 ppm;
IR: ν = 3203, 1680, 1471, 1454, 1373, 1334, 1247, 756, 708 cm−1;
HRMS (ES+) m/z calcd for C14H13BNO3 [M + H]+ 254.0991, found
254.0991.
MHz): δ 8.13 (dd, J = 7.8, 1.6 Hz, 1H), 7.65−7.59 (m, 1H), 7.40 (s,
1H), 7.33−7.25 (m, 6H), 7.21 (t, J = 7.2 Hz, 1H), 2.93 (t, J = 8.1 Hz,
2H), 1.53 (t, J = 8.1 Hz, 2H) ppm; 13C {1H} NMR (CDCl3, 125.8
MHz): δ 164.6, 155.7, 143.2, 134.7, 128.4, 128.3, 127.8, 125.9, 123.5,
119.3, 118.8, 29.4 ppm; 11B NMR (acetonitrile, 128.4 MHz): δ 32.7
ppm; IR: ν = 3105, 2928, 1688, 1468, 1373, 1348, 752, 731, 699 cm−1;
HRMS (CI) m/z calcd for C15H15BNO2 [M + H]+ 252.1196, found
252.1194.
2-(4-(Trifluoromethyl)phenyl)-1,3,2-benzoxazaborininone (6d).
Obtained as a white solid by procedure B-2 after recrystallization
from CHCl3 (167 mg, 57%, 1.0 mmol scale); mp: 245−246 °C; H
ASSOCIATED CONTENT
1
■
S
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.7b00747.
NMR (CDCl3, 500.4 MHz): δ 8.21 (dd, J = 7.8, 1.6 Hz, 1H), 8.08 (d, J
= 8.0 Hz, 2H), 7.97 (s, 1H), 7.76 (d, J = 8.2 Hz, 2H), 7.69 (td, J = 7.6,
1.5 Hz, 1H), 7.42 (d, J = 8.3 Hz, 1H), 7.34 (t, J = 7.6 Hz, 1H) ppm;
13C {1H} NMR (CDCl3, 125.8 MHz): δ 165.0, 155.8, 135.4, 134.0 (q,
J = 32.5 Hz), 133.8, 128.7, 125.2 (q, J = 3.7 Hz), 124.3, 124.0 (d, J =
272.5 Hz), 119.7, 119.4 ppm; 19F {1H} NMR (CDCl3, 470.8 MHz): δ
−63.2 ppm; 11B NMR (MeCN, 128.4 MHz): δ 31.6 ppm; IR: ν =
3172, 3100, 1683, 1614, 1323, 1108, 1097, 1069, 865, 835, 755, 636
Aqueous stability studies, computed properties for
azaborininones and isosteres, methods and data for
computational pKa evaluation, geometry optimized
Cartesian coordinates for computed molecules, along
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DOI: 10.1021/acs.joc.7b00747
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with 1H, 13C, 19F, and 11B NMR spectra for all
compounds (PDF)
(d) Mahdavi, M.; Asadi, M.; Saeedi, M.; Tehrani, M. H.; Mirfazli, S.
S.; Shafiee, A.; Foroumadi, A. Synth. Commun. 2013, 43, 2936.
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(f) Ihara, H.; Ueda, A.; Suginome, M. Chem. Lett. 2011, 40, 916.
(g) Koyanagi, M.; Eichenauer, N.; Ihara, H.; Yamamoto, T.; Suginome,
M. Chem. Lett. 2013, 42, 541. (h) Settepani, J. A.; Stokes, J. B.;
Borkovec, A. J. Med. Chem. 1970, 13, 128. (i) Kaupp, G.; Naimi-Jamal,
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(14) Murugan, K.; Chinnapattu, M.; Khan, F.-R. N.; Lyer, P. S. RSC
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AUTHOR INFORMATION
Corresponding Author
*E-mail: g molandr@sas.upenn.edu.
ORCID
Geraint H. M. Davies: 0000-0002-5986-0756
Christopher B. Kelly: 0000-0002-5530-8606
Gary A. Molander: 0000-0002-9114-5584
■
Notes
The authors declare no competing financial interest.
(15) Molander, G. A. J. Org. Chem. 2015, 80, 7837.
(16) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.;
Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci,
B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H.
P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.;
Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima,
T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J. A., Jr.;
Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin,
K. N.; Staroverov, V. N.; Kobayashi, R.; Normand, J.; Raghavachari, K.;
Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega,
N.; Millam, J. M.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.;
Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.;
Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.;
Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.;
ACKNOWLEDGMENTS
■
This research was supported by the NIH/NIGMS (R01 GM-
111465). C.B.K. is grateful for funding from an NIH NRSA
postdoctoral fellowship (F32 GM117634). A.M. is grateful for
financial assistance granted by the HEC (Higher Education
Commission, 1-8/HEC/HRD/2015/4044) of Pakistan under
the IRSIP (International Research Support Initiative Program).
Frontier Scientific is acknowledged for their generous donation
of potassium organotrifluoroborates. Dr. George Furst and Dr.
Jun Gu (University of Pennsylvania) are thanked for their help
in the NMR elucidations.
̈
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DOI: 10.1021/acs.joc.7b00747
J. Org. Chem. XXXX, XXX, XXX−XXX