Method for Accessing Nitrogen-Containing, B-Heteroaryl-Substituted 2,1-Borazaronaphthalenes

Article abstract of DOI:10.1021/acs.joc.6b02574

The azaborine motif provides a mimic of aromatic systems through replacement of a C=C bond with a B-N bond. In particular, 2,1-borazaronaphthalenes, accessible through robust methods of synthesis and subsequent functionalization, afford an ideal platform to use for a variety of applications. However, the scope of substructures for this archetype has been limited by the lack of nitrogen-containing heteroaryls that can be incorporated within them. In this study, modified reaction conditions were developed to provide access to a wider range of substructures.

Full text of DOI:10.1021/acs.joc.6b02574

Article
pubs.acs.org/joc
Method for Accessing Nitrogen-Containing, B‑Heteroaryl-Substituted
2
,1-Borazaronaphthalenes
†
,§
†,‡,§
†
,†
Geraint H. M. Davies, Zhao-Zhao Zhou,
Matthieu Jouffroy, 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
‡
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, P.R. China
*
S Supporting Information
ABSTRACT: The azaborine motif provides a mimic of
aromatic systems through replacement of a CC bond with
a B−N bond. In particular, 2,1-borazaronaphthalenes, acces-
sible through robust methods of synthesis and subsequent
functionalization, afford an ideal platform to use for a variety of
applications. However, the scope of substructures for this
archetype has been limited by the lack of nitrogen-containing heteroaryls that can be incorporated within them. In this study,
modified reaction conditions were developed to provide access to a wider range of substructures.
7
INTRODUCTION
pyridyl styrenes in high yields. Furthermore, they reported
select examples of pyridyltrifluoroborates being successful in
the annulation under their conditions. Despite this recent
advance, we were interested in finding a widely applicable set of
conditions that would allow the incorporation of a variety of
nitrogen-containing heterocyclic substructures. Herein we
report conditions that enable the annulation of various nitrogen
heterocyclic trifluoroborates to prepare a range of 2,1-
borazaronaphthalene scaffold bearing having B-substituted N-
heterocycles.
■
With the well-documented value of isosteric replacements in
biological and material applications, the capacity to access
complementary systems that advance into new chemical space
1
would be beneficial. The azaborine motif, wherein a C−C
double bond is exchanged with a B−N bond, provides a class of
compound that mimics traditional aromatic systems both
2
structurally and electronically. Recently, the 2,1-borazaronaph-
thalene variant has been demonstrated to be a competent
bioisostere in direct comparison to all-carbon analogues of
3
a
propranolol, a well-known β-blocker, and phosphodiesterase
3
b
1
0A inhibitors. This specific class of azaborines has been
RESULTS AND DISCUSSION
■
investigated for their utility mainly because of the simple and
robust method for their synthesis, which begins with a highly
versatile condensation between 2-aminostyrenes and potassium
Using the standard reaction conditions previously developed by
our group for accessing the 2,1-borazaronaphthalene core,
4
4
initial attempts to condense nitrogen-containing trifluorobo-
rates with o-aminostyrene derivatives were met with no success.
To understand what caused nitrogen heterocyclic trifluorobo-
rates to be incompatible with the reported conditions, pyridine
was added in increasing amounts to the reaction of 2-
aminostyrene (1) with phenyltrifluoroborate (2) (Table 1).
As is evident from the results presented, pyridine has a marked
inhibitory effect on the reaction, which intensifies with
increasing amounts of this additive. With evidence in hand of
the direct inhibition caused by added pyridine in the formation
of 2-phenyl-2,1-borazaronaphthalene (3), we surmised that the
effect of Lewis basic sites in the nitrogen-containing,
heterocyclic trifluoroborates explained the previous lack of
success observed in using them as partners for azaborine
organotrifluoroborates. Furthermore, the myriad recent
methods for functionalizing this core extends the potential for
additional applications of the 2,1-borazaronaphthalene sub-
5
structure. However, one deficiency within the initial synthetic
scope for accessing the 2,1-borazaronaphthalene core was the
lack of nitrogen-containing heterocyclic functional units,
particularly substituted off of boron. Azaborine subunits
containing N-heterocyclic scaffolds at this position would be
of particular value, especially considering the diverse use of
heterocycles and their recognition as “privileged structures” for
modulation of biological systems. A recent solution to address
this problem was reported by Rombouts et al. using microwave
μW) conditions (eq 1), which allowed the annulation of
4
6
(
8
synthesis. It was therefore anticipated that increasing the
loading of SiCl would allow the reaction to proceed in the case
4
of heteroaryl-containing trifluoroborates.
Received: October 25, 2016
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.6b02574
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
Table 1. Effect of Pyridine on the Synthesis of 2,1-
Borazaronaphthalene
(5d compared to 5e), presumably caused by a combination of
electronic effects.
Various other N-substituted 2-aminostyrenes could also be
used in the annulation (Table 3). N-Methylated 2,1-
Table 3. 2,1-Borazaronaphthalene Annulation with
Nitrogen-Modified 2-Aminostyrene
a
added pyridine
0
prod:SM
full conversion
66:34
0.5
1.0
2.0
8:92
no reaction
a
Ratios determined by GCMS.
By adjusting the reaction conditions (Table 2, in bold), using
two equivalents of SiCl , exchanging cyclopentyl methyl ether
4
Table 2. Nitrogen-Containing B-Heterocyclic 2,1-
Borazaronaphthalenes from N-Benzyl-2-aminostyrene
borazaronaphthalenes could be synthesized (6a−i), but were
consistently lower yielding compared to N-benzyl systems.
Examples that had substituents more likely to disrupt π−π
interactions more effectively, such as morpholine (6f) or N-
methylated pyrazole (6i), demonstrated higher product
isolation. As previously mentioned, there was a consistent
effect of the substitution pattern off of pyridine when
comparing 6d and 6e to the corresponding benzylated
compounds 5d and 5e. Isoquinoline variants (6c,p) could
also be formed in modest yield using various N-alkylated 2-
aminostyrenes partners. Other substituents tolerated off of the
styrenyl nitrogen included 4-t-Bu-phenyl (6k), allyl (6l),
arylated alkyl (6n−p) as well as unsubstituted N−H (6m).
In addition, preinstalled functional groups could be
employed on the aminostyrene to develop more elaborated
cores (Table 4). Fluorinated motifs (7a−c), including
trifluoromethyl (7a) and trifluoromethyl ether (7b) were
tolerated, as well as isopropyl (7d) and nitrile (7e) substituents.
Typically those substrates incorporating substituents with more
(
CPME) for acetonitrile, and increasing both the dilution and
temperature to improve solubility, the substrate scope was
explored. In early condition development, it was observed that
some of the heteroaromatic 2,1-borazaronaphthalene cores
were observed to have poor solubility, most probably because
of the high tendency toward π stacking noticed in extended
9
aromatic systems. To mitigate this, substitutions off the
styrenyl nitrogen helped facilitate both the reaction progress
and purification by increasing the solubility of the resulting
compounds. Upon reaction completion, purification of
products was routinely done by initial filtration of solid
byproducts followed by column chromatography. With this
viable set of conditions to access isolatable products, we started
investigating the tolerability of scope for the N-benzyl-2-
aminostyrene precursor.
3
Under these conditions, quinolinyl- (5a,b), pyrimidinyl-
sp character tended to be isolated in higher yield, continuing
(
5c), and substituted pyridinyl- (5d−f) trifluoroborates were all
to suggest the influence of π interactions on the effectiveness of
tolerated in the cyclization process, as well as pyrazolyl- (5g),
isoxazolyl- (5h), and indolyl- (5i) derivatives. It was observed
that the substitution pattern of pyridine had an effect on yield
the reaction or isolation process. Aminopyridyl styrenes, similar
6
to those previously reported, were also amenable to these
conditions (7f−i).
B
DOI: 10.1021/acs.joc.6b02574
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The Journal of Organic Chemistry
Article
4
amination of 2-bromostyrene (P1) or Suzuki cross-coupling of 2-
bromoanilines (P2).
Table 4. Substituted 2-Aminostyrene Derivatives for B-
Heterocyclic 2,1-Borazaronaphthalenes
1
0
N-(4-(tert-Butyl)phenyl)-2-vinylaniline (6k Starting Material).
Synthesized following procedure P1. Obtained as a brown solid
1
(
2.31 g, 92%, 10.0 mmol scale); mp: 65−66 °C; H NMR (CDCl ,
3
5
3
1
5
00.4 MHz): δ 7.45−7.43 (dd, J = 7.7, 1.6 Hz, 1H), 7.31−7.21 (m,
H), 7.19−7.16 (dt, J = 8.0, 1.6 Hz, 1H), 6.98−6.95 (t, J = 7.5 Hz,
H), 6.94−6.91 (m, 2H), 6.91−6.85 (dd, J = 17.5, 11.0 Hz, 1H),
.70−5.66 (dd, J = 17.4, 1.5 Hz, 1H), 5.48 (br s, 1H), 5.33−5.30 (dd, J
11.0, 1.5 Hz, 1H), 1.31 (s, 9H) ppm; 13C { H} NMR (CDCl , 125.8
1
=
3
MHz): δ 143.7, 141.1, 140.7, 132.9, 129.1, 128.5, 127.2, 126.1, 121.7,
1
1
18.8, 117.6, 116.2, 34.1, 31.5 ppm; IR: ν = 3392, 2957, 1612, 1515,
−1
455, 1300, 1267, 824, 757, 738 cm ; HRMS (ESI) m/z calc. for
+
C H N [M + H] 252.1752, found 252.1756.
18
22
N-(3-Phenylpropyl)-2-vinylaniline (6n,o,p Starting Material).
Synthesized following procedure P1. Obtained as a yellow liquid
1
(
1.00 g, 66%, 6.4 mmol scale); H NMR (CDCl , 500.4 MHz): δ
3
7
.30−7.27 (td, J = 7.7, 2.0 Hz, 2H), 7.24−7.18 (m, 4H), 7.17−7.13
td, J = 7.7, 1.4 Hz, 1H), 6.71−6.65 (m, 2H), 6.60−6.59 (d, J = 8.1 Hz,
H), 5.60−5.56 (dd, J = 17.3, 1.6 Hz, 1H), 5.30−5.27 (dd, J = 11, 1.6
Hz, 1H), 3.76 (br s, 1H), 3.19−3.16 (t, J = 6.9 Hz, 2H), 2.77−2.73 (t,
(
1
1
3
1
J = 7.4 Hz, 2H), 2.02−1.96 (m, 2H) ppm; C { H} NMR (CDCl ,
3
1
1
2
25.8 MHz): δ 145.3, 141.6, 133.0, 128.9, 128.5, 128.4, 127.4, 126.0,
24.1, 117.1, 116.1, 110.6, 43.4, 33.5, 31.0 ppm; IR: ν = 3430, 3025,
934, 2856, 1622, 1601, 1576, 1506, 1455, 1258, 908, 742, 698 cm ;
−
1
+
HRMS (ESI) m/z calc. for C H N [M + H] 238.1596, found
17
20
CONCLUSION
The development of a new set of reaction conditions has
enabled a broad advance of substrate classes available for the
238.1596.
-(Trifluoromethoxy)-2-vinylaniline (7b Starting Material). Syn-
thesized following procedure P2. Obtained as a yellow liquid (1.49 g,
■
4
1
7
6
6
5
3%, 10 mmol scale); H NMR (CDCl , 500.4 MHz): δ 7.13 (s, 1H),
3
2
,1-borazaronaphthalene core isostere. Considering that the
.94−6.92 (d, J = 8.7 Hz, 1H), 6.69−6.64 (dd, J = 11.1, 17.4 Hz, 1H),
conditions were not optimized for each individual substrate, the
capacity to access such diversity affords a reliable method to
gain entry to versatile 2,1-borazaronaphthalene compounds. It
is important to note that many of these substructures, even
though quite simple, have no comparable analogues in the all-
carbon naphthalene isosteres, speaking volumes about the
ability of the method described to allow access to new chemical
space. The power to access nitrogen heterocyclic-substituted
azaborines thus allows the synthesis of more biologically
relevant core structures that can continue to propagate the
value of this class of isosteres.
.60−6.58 (d, J = 8.7 Hz, 1H), 5.63−5.60 (dd, J = 17.4, 1.2 Hz, 1H),
13
1
.36−5.34 (dd, J = 11.1, 1.1 Hz, 1H), 3.74 (br s, 2H) ppm; C { H}
NMR (CDCl , 125.8 MHz): δ 142.4, 141.5, 131.6, 124.7, 121.6,
3
19
1
120.71 (q, J = 255.8 Hz), 120.0, 117.0, 116.5 ppm; F { H} NMR
(CDCl , 470.8 MHz): δ −58.3 ppm; IR: ν = 3352, 2984, 1780, 1496,
435, 1247, 1221, 1203, 1046, 917, 873, 820 cm ; HRMS (ESI) m/z
3
−1
1
+
calc. for C H NOF [M + H] 204.0636, found 204.0623.
9
9
3
2
,4-Difluoro-6-vinylaniline (7c Starting Material). Synthesized
following procedure P2. Obtained as a yellow liquid (0.60 g, 39%, 10.0
1
mmol scale); H NMR (CDCl , 500.4 MHz): δ 6.85−6.82 (dt, J = 9.4,
3
2
1
.1 Hz, 1H), 6.75−6.69 (m, 2H), 5.68−5.64 (dd, J = 17.4, 0.9 Hz,
13 1
H), 5.41−5.39 (dd, J = 11.0 Hz, 1H), 3.64 (br s, 2H) ppm; C { H}
NMR (CDCl , 125.8 MHz): δ 155.0 (dd, J = 238.1, 12.6 Hz), 151.4
3
EXPERIMENTAL SECTION
General Considerations. All reactions were carried out under an
inert atmosphere of nitrogen or argon in oven-dried glassware, unless
otherwise noted. Toluene was dried using a J. C. Meyer solvent
■
(dd, J = 240.4, 12.5 Hz), 130.9 (dd, J = 3.7, 2.5 Hz), 128.3 (dd, J =
13.2, 2.9 Hz), 126.4 (dd, J = 13.2, 4.8 Hz), 117.5, ppm, 108.3 (dd, J =
22.5, 3.3 Hz), 102.8 (dd, J = 27.0, 23.4 Hz); 19F { H} NMR (CDCl
1
,
3
470.8 MHz): δ −124.3, −130.7 ppm; IR: ν = 3462, 3376, 3087, 1586,
−1
system. MeCN was purchased dry and used as received. Et N was
1482, 1294, 1111, 978, 919, 859, 587 cm ; HRMS (ESI) m/z calc. for
3
+
distilled prior to use and stored over activated molecular sieves. All
reagents were purchased commercially and used as received, unless
otherwise noted. Column chromatography was performed by
C H NF [M + H] 156.0625, found 156.0633.
8
8
2
4-Amino-3-vinylbenzonitrile (7e Starting Material). Synthesized
following procedure P2. Obtained as a yellow solid (0.61 g, 43%, 10.0
(
R)
(R)
1
Combiflash using RediSep Rf Gold Normal-Phase Silica columns
or Alumina Basic columns. Melting points (°C) are uncorrected. Mass
spectra (ESI- or CI-TOF) were recorded using CH Cl , MeCN, or
mmol scale); mp: 77−78 °C; H NMR (CDCl , 500.4 MHz): δ 7.48
3
(d, J = 1.8 Hz, 1H), 7.31−7.29 (dd, J = 8.4, 1.9 Hz, 1H), 6.67−6.61
(m, 2H), 5.65−5.61 (dd, J = 17.4, 1.0 Hz, 1H), 5.42−5.40 (dd, J =
2
2
11.0, 0.9 Hz, 1H), 2.04 (s, 2H) ppm; 13C { H} NMR (CDCl , 125.8
1
MeOH as the solvent. IR spectra were recorded using FTIR-ATR of
the neat oil or solid products. NMR spectra ( H, C { H}, B,
3
1
13
1
11
19
F
MHz): δ 147.7, 132.3, 131.5, 130.7, 123.6, 120.0, 117.9, 115.3, 100.1
ppm; IR: ν = 3465, 3369, 2215, 1631, 1599, 1558, 1499, 1425, 1307,
1
1
13
1
{
H}) were performed at 298 K. H (500.4 MHz) and C { H}
125.8 MHz) NMR chemical shifts are reported relative to internal
TMS (δ = 0.00 ppm) or to residual protiated solvent. Any observed
−
1
+
(
1282, 890, 815, cm ; HRMS (ESI) m/z calc. for C H N [M + H]
9 9 2
145.0766, found 145.0773.
13
1
13
19
11
splitting in the C { H} NMR spectra is due to C− F coupling.
B
General Procedure for Synthesis of Nitrogen-Containing
Heteroaryl-2,1-borazaronaphthalenes. Potassium heteroaryltri-
fluoroborate (1.0 equiv) was introduced into a microwave vial with
a stir bar. The vial was sealed with a Teflon-coated septum cap, then
128.4 MHz) and 19F { H} NMR (470.8 MHz) chemical shifts were
1
(
referenced to external BF ·Et O (0.0 ppm) and CFCl (0.0 ppm),
3
2
3
respectively. Data are presented as follows: chemical shift (ppm),
multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, sept =
septet, m = multiplet, br = broad), coupling constant J (Hz) and
integration.
evacuated and purged with N four times. An MeCN/toluene mixture
2
(0.25 M, 1:1, v/v) and 2-aminostyrene (1.2 equiv) were introduced via
syringe, followed by NEt (1.5 equiv) and SiCl (2.0 equiv). The
3
4
Procedure for Synthesis of 2-Aminostyrene Derivatives.
Previously unreported 2-aminostyene derivatives were synthesized
using known procedures established for the Buchwald−Hartwig
resulting suspension was heated to 80 °C under vigorous stirring for
18 h. The vial was then cooled to rt, and the reaction mixture was
neutralized by using saturated NaHCO3 aqueous solution. The
C
DOI: 10.1021/acs.joc.6b02574
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The Journal of Organic Chemistry
Article
1
9
1
resulting solid was filtered off and the remaining solution was extracted
(d, J = 3.8 Hz), 117.0, 52.6 ppm; F { H} NMR (CDCl , 470.8
3
11
with EtOAc/H O, dried (MgSO ), and concentrated under vacuum.
MHz): δ −58.1 ppm; B NMR (CDCl , 128.4 MHz): δ 35.1 ppm;
IR: ν = 1609, 1592, 1549, 1494, 1416, 1400, 1367, 1350, 1286, 1244,
1219, 1192, 962, 804, 764, 750, 744, 734, 706, 696 cm ; HRMS (ESI)
m/z calc. for C H BN FNa [M + Na] 337.1288, found 337.1285.
1-Benzyl-2-(4-(N,N-dimethylamino)pyridin-5-yl)-2,1-borazaro-
naphthalene (5f). Purified on silica gel and obtained as a pale yellow
2
4
3
The crude material was purified through a short plug of silica and
flushed with hexanes/EtOAc mixture (20 times solvent volume, 4:1, v/
v). Solvents were removed in vacuo to obtain a crude material that was
further purified by automated column chromatography on silica gel or
basic alumina, eluting with a gradient method of CH Cl and hexanes,
−1
+
20
16
2
2
2
1
starting at 100% hexanes to 10:90 hexanes/CH Cl .
solid (28.9 mg, 17%, 0.5 mmol scale); mp: 139−140 °C; H NMR
2
2
1
-Benzyl-2-(quinolin-6-yl)-2,1-borazaronaphthalene (5a). Puri-
(CDCl , 500.4 MHz): δ 8.43 (m, 1H), 8.09−8.07 (d, J = 11.4 Hz, 1H),
3
fied on silica gel and obtained as a white solid (131.0 mg, 76%, 0.5
7.67−7.65 (d, J = 8.4 Hz, 1H), 7.62−7.60 (dd, J = 8.6, 2.2 Hz, 1H),
7.31−7.27 (m, 4H), 7.23−7.20 (m, 1H), 7.17−7.14 (m, 3H), 7.09−
1
mmol scale); mp: 105−106 °C; H NMR (CDCl , 500.4 MHz): δ
3
8
.89−8.90 (m, 1H), 8.17−8.20 (d, J = 11.3 Hz, 1H), 8.02−8.06 (m, 2
7.07 (d, J = 11.4 Hz, 1H), 6.48−6.46 (dd, J = 8.6, 0.7 Hz, 1H), 5.47 (s,
2H), 3.07 (s, 6H) ppm; 13C { H} NMR (CDCl
1
, 125.8 MHz): δ
H), 7.95 (s, 1H), 7.86−7.88 (d, J = 8.4 Hz, 1H), 7.74−7.75 (d, J = 7.6
3
Hz, 1H), 7.30−7.39 (m, 5H), 7.22−7.26 (m, 2H), 7.10−7.15 (m, 3H),
159.0, 152.8, 145.0, 142.2, 141.5, 139.2, 130.2, 128.9, 128.4, 127.3,
126.9, 125.7, 120.8, 116.9, 105.4, 52.5, 37.9 ppm; B NMR (CDCl3,
128.4 MHz): δ 34.0 ppm; IR: ν = 1588, 1549, 1510, 1495, 1453, 1412,
1385, 1344, 1272, 1242, 1223, 1145, 953, 805, 765, 759, 737, 730, 694,
5
1
1
.46 (s, 2H) ppm; 13C { H} NMR (CDCl , 125.8 MHz): δ 150.4,
1
11
3
48.1, 145.7, 141.1, 139.0, 136.2, 133.4, 132.4, 130.4, 128.8, 128.8,
28.3, 127.8, 127.4, 127.0, 125.7, 121.3, 121.0, 117.0, 52.6 ppm; 11
B
−1
+
NMR (CDCl , 128.4 MHz): δ 36.7 ppm; IR: ν = 1605, 1588, 1547,
478 cm ; HRMS (ESI) m/z calc. for C H BN [M + H] 340.1985,
3
22 23 3
1
7
492, 1455, 1410, 1353, 1229, 1181, 1143, 1118, 982, 840, 814, 798,
found 340.1989.
−
1
65, 748, 698, 476, 465 cm ; HRMS (ESI) m/z calc. for
1-Benzyl-2-(1-methyl-1H-pyrazol-4-yl)-2,1-borazaronaphthalene
(5g). Purified on silica gel and obtained as a yellow solid (80.7 mg,
+
C H BN Na [M + Na] 369.1539, found 369.1547.
2
4
19
2
1
1
-Benzyl-2-(quinolin-3-yl)-2,1-borazaronaphthalene (5b). Puri-
54%, 0.5 mmol scale); mp: 116−117 °C; H NMR (CDCl
3
, 500.4
fied on silica gel and obtained as a white solid (140.8 mg, 81%, 0.5
MHz): δ 8.05−8.03 (d, J = 11.5 Hz, 1H), 7.69 (s, 1H), 7.65−7.64 (d, J
= 7.5 Hz, 1H), 7.46 (s, 1H), 7.33−7.30 (m, 4H), 7.26−7.24 (m, 1H),
1
mmol scale); mp: 94−95 °C; H NMR (CDCl , 500.4 MHz): δ 9.07
3
(
=
s, 1 H), 8.27 (s, 1H), 8.20−8.22 (d, J = 11.3 Hz, 1H), 8.07−8.09 (d, J
7.20−7.19 (d, J = 7.5 Hz, 2H), 7.17−7.11 (m, 2H), 5.51 (s, 2H), 3.88
(s, 3H) ppm; 13C { H} NMR (CDCl
1
, 125.8 MHz): δ 145.0, 144.8,
8.5 Hz, 1H), 7.75−7.76 (d, J = 7.6 Hz, 1H), 7.68−7.70 (m, 2H),
3
7
7
.48−7.51 (t, J = 8 Hz, 1H), 7.39−7.40 (m, 2H), 7.32−7.29 (m, 2H),
141.9, 138.6, 135.4, 130.1, 129.0, 128.5, 127.0, 127.0, 125.8, 120.7,
116.2, 52.6, 38.6 ppm; B NMR (CDCl
IR: ν = 1604, 1591, 1548, 1533, 1487, 1460, 1411, 1376, 1347, 1327,
1299, 1218, 1177, 934, 896, 808, 761, 730, 696, 674 cm ; HRMS
13
1
11
.26−7.23 (m, 2H), 7.15−7.12 (m, 3H), 5.48 (s, 2H) ppm; C { H}
3
, 128.4 MHz): δ 33.4 ppm;
NMR (CDCl , 125.8 MHz): δ 153.7, 147.7, 146.0, 141.2, 140.7, 138.7,
3
−1
130.5, 129.5, 129.2, 128.9 (2 × C), 128.0, 127.7, 127.4, 127.1, 126.4,
125.6, 121.5, 117.0, 52.6 ppm; B NMR (CDCl , 128.4 MHz): δ 36.1
11
+
(ESI) m/z calc. for C19H18BN Na [M + Na] 322.1491, found
3
3
ppm; IR: ν = 1608, 1593, 1550, 1491, 1452, 1415, 1347, 1282, 1226,
322.1470.
−1
9
43, 913, 856, 812, 789, 761, 731, 695, 477 cm ; HRMS (ESI) m/z
1-Benzyl-2-(3,5-dimethylisoxazole-4-yl)-2,1-borazaronaphtha-
lene (5h). Purified on silica gel and obtained as a pale yellow solid
+
calc. for C H BN Na [M + Na] 369.1539, found 369.1534.
24
19
2
1
1
-Benzyl-2-(pyrimidin-5-yl)-2,1-borazaronaphthalene (5c). Puri-
(83.0 mg, 53%, 0.5 mmol scale); mp: 110−111 °C; H NMR (CDCl
3
,
fied on silica gel and obtained as a brown solid (86.2 mg, 58%, 0.5
500.4 MHz): δ 8.14−8.12 (d, J = 11.3 Hz, 1H), 7.73−7.71 (d, J = 7.7
1
mmol scale); mp: 123−124 °C; H NMR (CDCl , 500.4 MHz): δ
Hz, 1H), 7.45−7.35 (m, 2H), 7.23−7.20 (m, 3H), 7.18−7.15 (m, 1H),
3
9
.18 (s, 1H), 8.82 (s, 2H), 8.21−8.23 (d, J = 11.3 Hz, 1H), 7.75−7.76
6.97−6.96 (d, J = 7.4 Hz, 2H), 6.93−6.91 (d, J = 11.3 Hz, 1H), 5.36 (s,
2H), 2.20 (s, 3H), 2.15 (s, 3H) ppm; 13C { H} NMR (CDCl
1
, 125.8
(
=
{
d, J = 7.5 Hz, 1H), 7.40 (m, 2H), 7.24−7.31 (m, 4H), 7.08−7.09 (d, J
3
1
3
7.5 Hz, 2H), 7.03−7.05 (d, J = 11.3 Hz, 1H), 5.40 (s, 2H) ppm;
C
MHz): δ 169.8, 162.0, 145.8, 141.1, 138.1, 130.4, 128.7, 128.6, 127.4,
127.0, 125.6, 121.5, 117.0, 52.2, 12.8, 12.2 ppm; B NMR (CDCl ,
128.4 MHz): δ 34.6 ppm; IR: ν = 1589, 1547, 1492, 1415, 1402, 1356,
1
11
H} NMR (CDCl , 125.8 MHz): δ 160.1, 158.2, 146.6, 140.9, 138.0,
3
3
1
1
1
30.6, 129.2, 129.0, 127.4, 127.3, 125.3, 121.8, 116.9, 52.5 ppm;
B
NMR (CDCl , 128.4 MHz): δ 34.9 ppm; IR: ν = 1611, 1592, 1568,
1288, 1259, 1209, 1133, 1055, 1028, 958, 896, 818, 769, 733, 697, 481,
3
−
1
O [M + H]+
1
7
543, 1493, 1452, 1403, 1354, 1280, 1251, 1218, 1138, 962, 810, 762,
468 cm ; HRMS (ESI) m/z calc. for C20H20BN
2
−1
25, 695, 638, 482, 463 cm ; HRMS (ESI) m/z calc. for C H BN
315.1669, found 315.1674.
1-Benzyl-2-(1-(phenylsulfonyl)-1H-indol-3-yl)-2,1-borazaronaph-
thalene (5i). Purified on silica gel and obtained as a white solid (53.4
19
17
3
+
[
M + H] 298.1516, found 298.1508.
-Benzyl-2-(6-fluoropyridin-3-yl)-2,1-borazaronaphthalene (5d).
1
1
Purified on silica gel and obtained as a brown solid (70.3 g, 45%, 0.5
mg, 23%, 0.5 mmol scale); mp: 74−75 °C; H NMR (CDCl
3
, 500.4
1
mmol scale); mp: 93−94 °C; H NMR (CDCl , 500.4 MHz): δ 8.34
MHz): δ 8.15−8.13 (d, J = 11.4 Hz, 1H), 8.03−8.01 (d, J = 8.3 Hz,
1H), 7.74−7.69 (m, 3H), 7.58−7.57 (d, J = 7.9 Hz, 1H), 7.49−7.46
(td, J = 7.5, 1.0 Hz, 1H), 7.41−7.38 (m, 3H), 7.35−7.32 (m, 5H),
7.30−7.27 (m, 1H), 7.24−7.20 (m, 2H), 7.14−7.11 (d, J = 11.3 Hz,
3
(
d, J = 1.85 Hz, 1H), 8.17−8.15 (d, J = 11.3 Hz, 1H), 7.88−7.84 (td, J
=
8.5, 2.1 Hz, 1H), 7.73−7.72 (d, J = 7.6 Hz, 1H), 7.37−7.36 (m, 2H),
7
7
2
.31−7.28 (t, J = 7.2 Hz, 2H), 7.25−7.21 (m, 2H), 7.09−7.08 (d, J =
1
3
1
.3 Hz, 2H), 7.02−7.00 (d, J = 11.3 Hz, 1H), 6.87−6.85 (dd, J = 8.2,
1H), 7.10−7.08 (d, J = 7.35 Hz, 2H), 5.41 (s, 2H) ppm; C { H}
NMR (CDCl , 125.8 MHz): δ 145.4, 141.6, 138.9, 138.3, 135.6, 134.5,
133.6, 130.4, 129.1, 128.9, 128.9, 128.7, 127.3, 127.1, 126.7, 125.6,
124.4, 123.3, 122.4, 121.3, 116.9, 113.5, 52.7 ppm; 11B NMR (CDCl
,
3
.3 Hz, 1H), 5.38 (s, 2H) ppm; 13C { H} NMR (CDCl , 125.8 MHz):
1
3
3
δ 163.8 (d, J = 239.7 Hz), 151.3 (d, J = 13.5 Hz), 146.1, 145.2 (d, J =
7
1
4
.3 Hz), 141.0, 138.4, 130.4, 129.0 (2 x C), 127.3, 127.1, 125.4, 121.5,
19
1
16.9, 108.8 (d, J = 35.3 Hz), 52.4 ppm; F { H} NMR (CDCl ,
128.4 MHz): δ 34.0 ppm; IR: ν = 1609, 1592, 1551, 1445, 1412, 1368,
3
11
70.8 MHz): δ −68.5 ppm; B NMR (CDCl , 128.4 MHz): δ 35.6
1175, 1130, 1087, 1021, 984, 809, 765, 746, 726, 686, 596, 587, 569,
3
−1
S [M + H]+
ppm; IR: ν = 1611, 1575, 1550, 1482, 1451, 1412, 1346, 1277, 1233,
551 cm ; HRMS (ESI) m/z calc. for C29H24BN O
2 2
−1
1
146, 1056, 964, 834, 805, 761, 727, 695, 645, 478, 463 cm ; HRMS
475.1652, found 475.1645.
1-Methyl-2-(quinolin-6-yl)-2,1-borazaronaphthalene (6a). Puri-
fied by basic alumina column and obtained as a pale yellow oil (48.0
mg, 36%, 0.5 mmol scale); H NMR (CDCl
1H), 8.44−8.43 (d, J = 5.9 Hz, 1H), 8.13−8.11 (d, J = 11.3 Hz, 1H),
7.99−7.98 (d, J = 8.2 Hz, 1H), 7.79−7.77 (t, J = 6.2 Hz, 2H), 7.68−
7.60 (m, 3H), 7.48−7.47 (d, J = 5.8 Hz, 1H), 7.35−7.32 (t, J = 7.6 Hz,
1H), 6.96−6.94 (d, J = 11.3 Hz, 1H), 3.54 (s, 3H) ppm; C { H}
NMR (CDCl , 125.8 MHz): δ 153.1, 145.0, 142.8, 142.2, 137.7, 134.4,
+
(
ESI) m/z calc. for C H BN F [M + H] 315.1469, found 315.1458.
20
17
2
1
-Benzyl-2-(2-fluoropyridin-3-yl)-2,1-borazaronaphthalene (5e).
1
Purified on silica gel and obtained as a yellow solid (122.3 mg, 78%,
3
, 500.4 MHz): δ 9.30 (s,
1
0
8
7
7
.5 mmol scale); mp: 108−109 °C; H NMR (CDCl , 500.4 MHz): δ
3
.18−8.19 (dd, J = 4.5, 2.0 Hz, 1H), 8.15−8.13 (d, J = 11.3 Hz, 1H),
.76−7.70 (m, 2H), 7.39−7.33 (m, 2H), 7.24−7.17 (m, 4H), 7.10−
.07 (m, 1H), 7.04−7.03 (d, J = 7.7 Hz, 2H), 7.00−6.98 (d, J = 11.3
1
3
1
13
1
Hz, 1H), 5.33 (s, 2H) ppm; C { H} NMR (CDCl , 125.8 MHz): δ
3
3
1
64.5 (d, J = 235.2 Hz), 147.7 (d, J = 14.5 Hz), 145.9, 144.7 (d, J = 8.5
130.4, 128.9, 128.4, 127.2, 127.0, 126.8, 121.7, 121.4, 115.1, 37.1 ppm;
11
Hz), 140.8, 138.2, 130.4, 128.8, 128.7, 127.4, 127.0, 125.5, 121.5, 121.0
B NMR (CDCl , 128.4 MHz): δ 36.6 ppm; IR: ν = 1608, 1590,
3
D
DOI: 10.1021/acs.joc.6b02574
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
−
1
1
1
549, 1455, 1409, 1336, 1289, 1266, 1238, 1215, 1174, 1135, 1101,
808, 785, 762, 728 cm ; HRMS (ESI) m/z calc. for C H BN O [M
18 21 3
−1
+
044, 830, 805, 760, 734, 674, 480 cm ; HRMS (ESI) m/z calc. for
+ H] 306.1778, found 306.1771.
1-Methyl-2-(pyrimidin-5-yl)-2,1-borazaronaphthalene (6g). Puri-
+
C H BN [M + H] 271.1407, found 271.1400.
1
8
16
2
1
-Methyl-2-(quinolin-3-yl)-2,1-borazaronaphthalene (6b). Puri-
fied by basic alumina column and obtained as a brown solid (44.5 mg,
1
fied by basic alumina column and obtained as a yellow solid (65.1 mg,
40%, 0.5 mmol scale); mp: 109−110 °C; H NMR (CDCl
3
, 500.4
1
4
8%, 0.5 mmol scale); mp: 101−102 °C; H NMR (CDCl , 500.4
MHz): δ 9.25 (s, 1H), 8.94 (s, 2H), 8.15−8.12 (d, J = 11.3 Hz, 1H),
3
MHz): δ 9.16 (s, 1H), 8.39 (s, 1H), 8.17−8.11 (m, 2H), 7.87−7.85 (d,
J = 8.1 Hz, 1H), 7.75−7.72 (m, 2H), 7.67−7.62 (m, 1H), 7.22−7.65
7.76−7.74 (d, J = 7.8 Hz, 1H), 7.70−7.62 (m, 2H), 7.35−7.32 (t, J =
1
3
6.8 Hz, 1H), 6.95−6.92 (d, J = 11.3 Hz, 1H), 3.75 (s, 3H) ppm;
C
1
(
m, 2H), 7.33−7.30 (m, 1H), 7.04−7.01 (d, J = 11.3 Hz, 1H), 3.78 (s,
{ H} NMR (CDCl
129.2, 127.0, 121.7, 115.2, 36.8 ppm; B NMR (CDCl , 128.4 MHz):
3
3
, 125.8 MHz): δ 160.6, 157.9, 145.9, 141.9, 130.5,
1
11
3
1
1
H) ppm; 13C { H} NMR (CDCl , 125.8 MHz): δ 154.2, 147.6,
3
45.3, 142.2, 141.1, 130.3, 129.4, 129.2, 128.9, 127.9, 127.8, 126.9,
δ 34.3 ppm; IR: ν = 1610, 1591, 1571, 1547, 1459, 1408, 1351, 1340,
26.4, 121.3, 115.1, 36.9 ppm; 11B NMR (CDCl , 128.4 MHz): δ 35.4
−1
1291, 1215, 1188, 1137, 1106, 980, 801, 754, 728, 647, 637, 484 cm ;
3
+
HRMS (ESI) m/z calc. for C H BN [M + H] 222.1203, found
ppm; IR: ν = 1608, 1590, 1549, 1483, 1409, 1343, 1316, 1288, 1215,
190, 1141, 1120, 1023, 947, 912, 807, 788, 753, 693, 484 cm ;
HRMS (ESI) m/z calc. for C H BN [M + H] 271.1407, found
13 13
3
−
1
2
22.1201.
1
+
1
-Methyl-2-(3,5-dimethylisoxazole-4-yl)-2,1-borazaronaphtha-
18
16
2
lene (6h). Purified by basic alumina column and obtained as a white
2
71.1409.
-(Isoquinolin-5-yl)-1-methyl-2,1-borazaronaphthalene (6c). Pu-
rified by basic alumina column and obtained as a yellow oil (43.1 mg,
1
solid (49.5 mg, 42%, 0.5 mmol scale); mp: 86−87 °C; H NMR
2
(
CDCl , 500.4 MHz): δ 8.06−8.04 (d, J = 11.3 Hz, 1H), 7.73−7.72 (d,
3
1
J = 7.7 Hz, 1H), 7.64−7.57 (m, 2H), 7.32−7.25 (td, J = 7.0, 1.2 Hz,
3
8
7
3
6
2%, 0.5 mmol scale); H NMR (CDCl , 500.4 MHz): δ 9.30 (s, 1H),
3
1
(
H), 6.87−6.84 (d, J = 11.3 Hz, 1H), 3.65 (s, 3H), 2.37 (s, 3H), 2.26
.44−8.43 (d, J = 5.8 Hz, 1H), 8.14−8.11 (d, J = 11.3 Hz, 1H), 8.00−
.98 (d, J = 8.2 Hz, 1H), 7.79−7.77 (t, J = 5.6 Hz, 2H), 7.68−7.60 (m,
H), 7.48−7.47 (d, J = 5.9 Hz, 1H), 7.35−7.32 (t, J = 7.0 Hz, 1H),
.96−6.94 (d, J = 11.3 Hz, 1H), 3.55 (s, 3H) ppm; C { H} NMR
CDCl , 125.8 MHz): δ 153.1, 145.0, 142.7, 142.2, 137.7, 134.4, 130.4,
28.9, 128.4, 127.2, 127.1, 126.8, 121.6, 121.4, 115.1, 37.1 ppm;
NMR (CDCl , 128.4 MHz): δ 36.5 ppm; IR: ν = 1608, 1590, 1550,
455, 1445, 1424, 1409, 1336, 1289, 1238, 1215, 1174, 1135, 1101,
044, 830, 805, 760, 739, 674 cm ; HRMS (ESI) m/z calc. for
C H BN [M + H] 271.1407, found 271.1389.
8
2
Purified by basic alumina column and obtained as a brown oil (21.5 g,
8%, 0.5 mmol scale); H NMR (CDCl , 500.4 MHz): δ 8.43 (s, 1H),
s, 3H) ppm; 13C { H} NMR (CDCl , 125.8 MHz): δ 170.3, 162.2,
1
3
1
45.0, 142.3, 130.3, 128.8, 126.9, 121.4, 115.1, 36.8, 12.9, 12.2 ppm;
1
1
13
1
B NMR (CDCl , 128.4 MHz): δ 33.7 ppm; IR: ν = 1591, 1551,
3
1
463, 1444, 1415, 1404, 1360, 1336, 1291, 1279, 1253, 1217, 1207,
(
1
3
−1
11
1131, 972, 891, 813, 767, 738, 485 cm ; HRMS (ESI) m/z calc. for
C H BN O [M + H] 239.1356, found 239.1354.
B
+
14 16
2
3
1
-Methyl-2-(1-methyl-1H-pyrazol-4-yl)-2,1-borazaronaphthalene
1
1
−1
(6i). Purified by basic alumina column and obtained as a brown solid
1
+
(67.4 mg, 61%, 0.5 mmol scale); mp: 82−83 °C; H NMR (CDCl
3
,
1
16
2
5
7
00.4 MHz): δ 7.94−7.92 (d, J = 11.3 Hz, 1H), 7.84 (s, 1H), 7.64−
-(6-Fluoropyridin-3-yl)-1-methyl-2,1-borazaronaphthalene (6d).
.61 (m, 2H), 7.54−7.48 (m, 2H), 7.23−7.18 (m, 1H), 6.98−6.95 (d, J
13
1
1
= 11.4 Hz, 1H), 3.96 (s, 3H), 3.79 (s, 3H) ppm; C { H} NMR
CDCl , 125.8 MHz): δ 144.7, 144.1, 142.6, 135.6, 129.9, 128.4, 126.5,
1
8
7
7
3
(
1
3
.10−8.08 (d, J = 11.3 Hz, 1H), 8.02−7.08 (td, J = 8.4, 2.1 Hz, 1H),
11
20.5, 114.7, 38.5, 36.5 ppm; B NMR (CDCl , 128.4 MHz): δ 31.9
3
.74−7.72 (d, J = 7.7 Hz, 1H), 7.65−7.58 (m, 2H), 7.32−7.29 (td, J =
ppm; IR: ν = 1608, 1590, 1552, 1531, 1495, 1460, 1438, 1409, 1361,
.8, 1.2 Hz, 1H), 7.02−7.00 (dd, J = 8.2, 2.6 Hz, 1H), 6.92−6.90 (d, J
−1
1
342, 1322, 1214, 1176, 1148, 1118, 940, 801, 757, 688, 677 cm ;
1
=
11.3 Hz, 1H), 3.72 (s, 3H) ppm; 13C { H} NMR (CDCl , 125.8
+
3
HRMS (ESI) m/z calc. for C H BN [M + H] 224.1359, found
13
15
3
MHz): δ 163.7 (d, J = 239.3 Hz), 151.7 (d, J = 13.3 Hz), 145.9 (d, J =
.1 Hz), 145.4, 142.1, 130.4, 129.0, 126.9, 121.4, 115.2, 108.9 (d, J =
5.3 Hz), 36.7 ppm; F { H} NMR (CDCl , 470.8 MHz): δ −68.9
ppm; B NMR (CDCl , 128.4 MHz): δ 35.0 ppm; IR: ν = 1608,
581, 1552, 1482, 1470, 1444, 1412, 1342, 1289, 1241, 1213, 1123,
84, 853, 830, 802, 763, 740, 633, 486 cm ; HRMS (ESI) m/z calc.
for C H BN F [M + H] 239.1156, found 239.1161.
2
24.1370.
7
3
1
-Methyl-2-(1-tosyl-1H-pyrrol-2-yl)-2,1-borazaronaphthalene
19
1
3
(6j). Purified by basic alumina column and obtained as a white solid
11
1
3
(57.9 mg, 32%, 0.5 mmol scale); mp: 122−123 °C; H NMR (CDCl ,
3
1
9
5
00.4 MHz): δ 8.00−7.98 (d, J = 11.3 Hz, 1H), 7.71−7.69 (d, J = 7.6
−1
Hz, 1H), 7.59−7.54 (m, 2H), 7.51−7.50 (d, J = 8.4 Hz, 2H), 7.46−
7.45 (dd, J = 3.1, 1.4 Hz, 1H), 7.28−7.25 (m, 1H), 7.17−7.15 (d, J =
+
14
13
2
2
-(3-Fluoropyridin-4-yl)-1-methyl-2,1-borazaronaphthalene (6e).
8
.4 Hz, 2H), 6.69−6.67 (d, J = 11.3 Hz, 1H), 6.40−6.38 (t, J = 3.2 Hz,
H), 6.30−6.29 (q, J = 1.5 Hz, 1H), 3.49 (s, 3H), 2.35 (s, 3H) ppm;
Purified by basic alumina column and obtained as a brown solid (65.1
1
1
mg, 55%, 0.5 mmol scale); mp: 97−98 °C; H NMR (CDCl , 500.4
13
1
3
C { H} NMR (CDCl , 125.8 MHz): δ 144.5, 144.0, 142.1, 136.3,
3
MHz): δ 8.49 (s, 1H), 8.47−8.46 (dd, J = 4.6, 2.3 Hz, 1H), 8.12−8.10
1
3
1
7
30.1, 129.5, 128.6, 127.0, 126.9, 123.8, 121.0, 120.2, 115.1, 113.7,
(
(
d, J = 11.3 Hz, 1H), 7.75−7.73 (dd, J = 7.7, 1.2 Hz, 1H), 7.66−7.64
d, J = 8.4 Hz, 1H), 7.62−7.59 (td, J = 6.9, 1.4 Hz, 1H), 7.39−7.37 (t,
11
7.3, 21.5 ppm; B NMR (CDCl , 128.4 MHz): δ 32.8 ppm; IR: ν =
3
612, 1594, 1554, 1456, 1411, 1359, 1293, 1168, 1058, 1034, 951, 807,
J = 4.8 Hz, 1H), 7.33−7.30 (td, J = 7.8, 0.8 Hz, 1H), 6.90−6.87 (d, J =
−1
56, 727, 701, 672, 588, 539, 489 cm ; HRMS (ESI) m/z calc. for
1
1
1.3 Hz, 1H), 3.63 (s, 3H) ppm; 13C { H} NMR (CDCl , 125.8
+
3
C H BN O S [M + H] 363.1339, found 363.1335.
20
20
2
2
MHz): δ 160.7 (d, J = 250.6 Hz), 145.7, 144.9 (d, J = 3.0 Hz), 141.8,
37.5 (d, J = 27.1 Hz), 130.4, 129.1, 128.3 (d, J = 5.6 Hz), 127.0,
1
-(4-(tert-Butyl)phenyl)-2-(quinolin-6-yl)-2,1-borazaronaphtha-
1
1
−
1
8
lene (6k). Purified by basic alumina column and obtained as a brown
19
1
1
21.6, 115.1, 37.1 ppm; F { H} NMR (CDCl , 470.8 MHz): δ
solid (167.8 mg, 87%, 0.5 mmol scale); mp: 157−158 °C; H NMR
3
118.8 ppm; 11B NMR (CDCl , 128.4 MHz): δ 33.2 ppm; IR: ν =
3
(CDCl , 500.4 MHz): δ 8.83 (s, 1H), 8.23−8.21 (d, J = 11.3 Hz, 1H),
3
611, 1586, 1552, 1442, 1410, 1346, 1282, 1237, 1202, 1054, 1001,
42, 798, 755, 664, 586, 574, 548, 525, 482 cm ; HRMS (ESI) m/z
calc. for C H BN F [M + H] 239.1156, found 239.1166.
7.93−7.92 (d, J = 7.9 Hz, 1H), 7.83−7.81 (d, J = 8.3 Hz, 1H), 7.75−
7.73 (d, J = 7.5 Hz, 1H), 7.67 (s, 1H), 7.51−7.50 (d, J = 8.3 Hz, 1H),
7.41−7.34 (m, 3H), 7.29−7.22 (m, 3H), 7.11−7.08 (m, 3H), 1.34 (s,
−1
+
14
13
2
9H) ppm; 13C { H} NMR (CDCl , 125.8 MHz): δ 150.5, 150.4,
1
1
-Methyl-2-(2-(morpholino)pyridin-3-yl)-2,1-borazaronaphtha-
3
lene (6f). Purified by basic alumina column and obtained as a colorless
147.9, 145.5, 142.8, 140.8, 136.2, 134.6, 134.4, 129.7, 128.8, 128.3,
1
11
oil (102.1 mg, 67%, 0.5 mmol scale); H NMR (CDCl , 500.4 MHz):
127.6, 127.3, 126.3, 126.1, 121.3, 120.6, 117.8, 34.6, 31.4 ppm;
B
3
δ 8.28−8.27 (dd, J = 4.9 2.0 Hz, 1H), 8.05−8.03 (d, J = 11.3 Hz, 1H),
NMR (CDCl , 128.4 MHz): δ 34.1 ppm; IR: ν = 1604, 1594, 1545,
3
7
(
(
.70−7.69 (dd, J = 7.7, 1.2 Hz, 1H), 7.61−7.55 (m, 3H), 7.29−7.25
1506, 1486, 1410, 1321, 1291, 1281, 1258, 1170, 1150, 894, 837, 807,
−
1
td, J = 7.8, 1.3 Hz, 1H), 6.94−6.92 (d, J = 11.3 Hz, 1H), 6.85−6.83
794, 770, 758, 581, 550 cm ; HRMS (ESI) m/z calc. for C H BN
27 26 2
dd, J = 7.1, 5.0 Hz, 1H), 3.60 (s, 7H), 3.27 (s, 4H) ppm; 13C { H}
1
+
[M + H] 389.2189, found 389.2201.
NMR (CDCl , 125.8 MHz): δ 156.3, 140.2, 138.3, 135.7, 135.1, 123.2,
1-Allyl-2-(quinolin-6-yl)-2,1-borazaronaphthalene (6l). Purified
3
11
1
21.8, 119.7, 114.1, 108.4, 107.9, 60.0, 42.9, 29.7 ppm; B NMR
by basic alumina column and obtained as a yellow solid (33.6 mg,
1
(
CDCl , 128.4 MHz): δ 34.7 ppm; IR: ν = 1609, 1590, 1572, 1551,
23%, 0.5 mmol scale); mp: 85−86 °C; H NMR (CDCl , 500.4
3
3
1
455, 1408, 1364, 1335, 1286, 1231, 1217, 1116, 980, 941, 925, 908,
MHz): δ 9.28 (s, 1H), 8.41−8.40 (d, J = 5.7 Hz, 1H), 8.14−8.11 (d, J
E
DOI: 10.1021/acs.joc.6b02574
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
−
1
=
11.3 Hz, 1H), 7.98−7.96 (d, J = 7.9 Hz, 1H), 7.77−7.76 (d, J = 6.8
Hz, 2H), 7.64−7.58 (m, 2H), 7.55−7.52 (t, J = 7.0 Hz, 1H), 7.49−
.48 (d, J = 5.9 Hz, 1H), 7.31−7.28 (t, J = 7.6 Hz, 1H), 6.95−6.93 (d,
J = 11.3 Hz, 1H), 5.93−5.86 (m, 1H), 5.11−5.09 (d, J = 10.6 Hz, 1H),
1042, 1030, 829, 805, 762, 740, 698, 675, 474 cm ; HRMS (ESI) m/z
+
calc. for C H BN [M + H] 375.2033, found 375.2025.
2-(Quinolin-6-yl)-7-(trifluoromethyl)-2,1-borazaronaphthalene
(7a). Purified by basic alumina column and obtained as a white solid
26
24
2
7
1
4
4
1
1
.91−4.88 (d, J = 17.3 Hz, 1H), 4.71−4.67 (dd, J = 15.2, 2.0 Hz, 1H),
(83.8 mg, 52%, 0.5 mmol scale); mp: 173−174 °C; H NMR (CDCl
3
,
13
1
.58−4.54 (dd, J = 17.2, 2.1 Hz, 1H) ppm; C { H} NMR (CDCl ,
500.4 MHz): δ 8.96−8.95 (dd, J = 4.2, 1.7 Hz, 1H), 8.43 (br s, 1H),
3
25.8 MHz): δ 153.0, 145.2, 142.6, 141.1, 137.6, 134.9, 133.5, 130.5,
8.38 (s, 1H), 8.24−8.19 (m, 4H), 7.79−7.77 (d, J = 8.1 Hz, 1H), 7.68
13
1
28.6, 128.4, 127.3, 127.1, 126.7, 121.7, 121.3, 116.6, 116.2, 51.0 ppm;
(s, 1H), 7.52−7.42 (m, 3H) ppm; C { H} NMR (CDCl , 125.8
3
1
1
B NMR (CDCl , 128.4 MHz): δ 37.1 ppm; IR: ν = 1608, 1590,
MHz): δ 151.1, 149.2, 145.1, 139.6, 136.5, 133.7, 132.6, 130.4, 130.2,
3
1
9
1
1
4
29.1, 128.1, 127.8, 121.4, 117.6, 115.5 ppm; F { H} NMR (CDCl ,
70.8 MHz): δ −62.2 ppm; B NMR (CDCl , 128.4 MHz): δ 32.7
ppm; IR: ν = 1619, 1571, 1459, 1358, 1329, 1249, 1219, 1167, 1150,
123, 1070, 924, 835, 772 cm ; HRMS (ESI) m/z calc. for
C H BN F [M + H] 325.1124, found 325.1121.
-(Quinolin-6-yl)-6-(trifluoromethoxy)-2,1-borazaronaphthalene
7b). Purified by basic alumina column and obtained as a white solid
1
9
547, 1455, 1409, 1358, 1333, 1283, 1245, 1219, 1174, 1134, 1049,
37, 918, 833, 809, 761, 675, 473 cm ; HRMS (ESI) m/z calc. for
3
11
−1
3
+
C H BN [M + H] 297.1563, found 297.1566.
2
0
18
2
−
1
1
2
-(Quinolin-6-yl)-2,1-borazaronaphthalene (6m). Purified by
+
basic alumina column and obtained as a white solid (84.6 mg, 66%,
18 13
2 3
1
2
0
.5 mmol scale); mp: 226−227 °C; H NMR (DMSO-d , 500.4
6
(
MHz): δ 10.7 (s, 1H), 8.94 (s, 1H), 8.69 (s, 1H), 8.48−8.44 (m, 2H),
1
(
51.4 mg, 30%, 0.5 mmol scale); mp: 204−205 °C; H NMR (DMSO-
8
7
7
1
1
.24−8.22 (d, J = 11.3 Hz, 1H), 8.12−8.10 (d, J = 8.2 Hz, 1H), 7.80−
d , 500.4 MHz): δ 10.9 (s, 1H), 8.97−8.96 (m, 1H), 8.71 (s, 1H),
.73 (m, 2H), 7.59−7.51 (m, 2H), 7.42−7.40 (d, J = 11.1 Hz, 1H),
6
13
1
8.48−8.45 (t, J = 8.0 Hz, 2H), 8.30−8.27 (d, J = 11.6 Hz, 1H), 8.14−
.22−7.21 (m, 1H) ppm; C { H} NMR (DMSO-d , 125.8 MHz): δ
6
8
.12 (d, J = 8.5 Hz, 1H), 7.91−7.89 (d, J = 8.9 Hz, 1H), 7.81 (s, 1H),
50.9, 148.5, 145.5, 140.9, 136.4, 134.3, 135.6, 129.1, 128.5, 128.0,
13 1
27.7, 125.2, 121.5, 120.8, 118.7 ppm; 11B NMR (Acetone-d , 128.4
7.60−7.51 (m, 3H) ppm;
1
1
C { H} NMR (DMSO-d , 125.8 MHz): δ
6
6
51.0, 148.6, 144.8, 141.9, 139.7, 136.4, 134.5, 133.5, 128.1, 127.7,
25.5, 121.8, 121.6, 120.7, 120.3 ppm; F { H} NMR (CDCl , 470.8
MHz): δ 32.7 ppm; IR: ν = 1615, 1597, 1568, 1496, 1456, 1448, 1346,
320, 1288, 1268, 1219, 1178, 1159, 872, 828, 802, 791, 765, 753
19
1
1
3
11
−1
+
MHz): δ −57.0 ppm; B NMR (CDCl , 128.4 MHz): δ 32.2 ppm;
cm ; HRMS (ESI) m/z calc. for C H BN [M + H] 257.1250,
3
17
14
2
IR: ν = 1572, 1457, 1251, 1225, 1205, 1177, 1156, 1123, 996, 975, 942,
found 257.1245.
-(3-Phenylpropyl)-2-(quinolin-6-yl)-2,1-borazaronaphthalene
6n). Purified by basic alumina column and obtained as a yellow oil
−1
8
99, 876, 832, 801, 767, 754, 740, 478, 463 cm ; HRMS (ESI) m/z
1
+
calc. for C H BN OF [M + H] 341.1073, found 341.1062.
,8-Difluoro-2-(quinolin-6-yl)-2,1-borazaronaphthalene (7c). Pu-
rified by basic alumina column and obtained as a white solid (27.2 mg,
(
(
18 13
2
3
1
6
39.1 mg, 21%, 0.5 mmol scale); H NMR (CDCl , 500.4 MHz): δ
3
9
1
.29 (s, 1H), 8.41−8.40 (d, J = 5.9 Hz, 1H), 8.10−8.07 (d, J = 11.2 Hz,
H), 7.98−7.96 (d, J = 8.1 Hz, 1H), 7.76−7.71 (m, 2H), 7.64−7.61 (t,
1
1
9%, 0.5 mmol scale); mp: 243−244 °C; H NMR (CDCl , 500.4
3
MHz): δ 8.95−8.94 (dd, J = 4.2, 1.7 Hz, 1H), 8.42 (br s, 1H), 8.34 (s,
J = 7.0 Hz, 1H), 7.53−7.50 (t, J = 7.1 Hz, 1H), 7.46−7.42 (m, 2H),
1
H), 8.23−8.18 (m, 3H), 8.07−8.05 (d, J = 11.6 Hz, 1H), 7.48−7.45
7
3
.30−7.27 (t, J = 7.5 Hz, 1H), 7.13−7.09 (m, 3H), 6.89−6.86 (m,
H), 4.10−4.04 (m, 1H), 3.90−3.84 (m, 1H), 2.40−2.37 (t, J = 7.4
(
(
d, J = 11.6 Hz, 1H), 7.43−7.40 (dd, J = 8.3, 4.3 Hz, 1H), 7.15−7.14
1
3
1
13
1
d, J = 8.8 Hz, 1H), 7.08−7.03 (td, J = 8.4, 2.6 Hz, 1H) ppm; C { H}
Hz, 2H), 2.03−1.94 (m, 2H) ppm; C { H} NMR (CDCl , 125.8
MHz): δ 153.0, 145.1, 142.5, 140.8, 140.7, 137.5, 133.6, 130.8, 128.7,
3
NMR (CDCl , 125.8 MHz): δ 155.9 (dd, J = 241.8, 11.7 Hz), 151.4
3
(
1
dd, J = 246.3, 13.1 Hz), 151.1, 149.2, 144.2 (t, J = 3.7, 3.1 Hz), 136.5,
33.6, 132.6, 129.1, 128.1, 126.9 (dd, J = 9.5, 4.5 Hz), 125.8 (d, J =
2.9 Hz), 121.3, 109.3 (dd, J = 21.5, 3.8 Hz), 103.1 (dd, J = 28.3, 22.3
1
4
28.4, 128.2, 128.0, 127.5, 127.0, 126.8, 125.9, 121.6, 121.2, 115.4,
7.9, 33.0, 31.3 ppm; B NMR (CDCl , 128.4 MHz): δ 37.0 ppm; IR:
1
1
3
1
ν = 1608, 1590, 1549, 1494, 1453, 1411, 1353, 1279, 1259, 1216, 1171,
19
1
−1
Hz) ppm; F { H} NMR (CDCl , 470.8 MHz): δ −119.8, −133.0
1
043, 1030, 830, 806, 763, 741, 698, 674, 475 cm ; HRMS (ESI) m/z
3
ppm; 11B NMR (CDCl , 128.4 MHz): δ 32.0 ppm; IR: ν = 1567,
+
calc. for C H BN [M + H] 375.2033, found 375.2031.
3
26
24
2
1
455, 1438, 1403, 1289, 1242, 1177, 1111, 1040, 978, 890, 829, 794,
769, 741, 707, 682, 647, 617, 594 cm ; HRMS (ESI) m/z calc. for
[M + H] 293.1062, found 293.1051.
6-Isopropyl-2-(quinolin-6-yl)-2,1-borazaronaphthalene (7d). Pu-
rified by basic alumina column and obtained as a white solid (85.3 mg,
1
-(3-Phenylpropyl)-2-(quinolin-3-yl)-2,1-borazaronaphthalene
−1
(
(
6o). Purified by basic alumina column and obtained as a colorless oil
65.3 mg, 35%, 0.5 mmol scale); H NMR (CDCl , 500.4 MHz): δ
1
+
C
H12BN
F
2
3
17
2
9
1
7
7
7
7
2
.10−9.09 (d, J = 1.3 Hz, 1H), 8.26 (s, 1H), 8.17−8.15 (d, J = 8.4 Hz,
H), 8.09−8.07 (d, J = 11.3 Hz, 1H), 7.82−7.80 (d, J = 8.1 Hz, 1H),
.76−7.71 (m, 2H), 7.58−7.55 (t, J = 7.6 Hz, 1H), 7.52−7.49 (t, J =
.3 Hz, 1H), 7.46−7.44 (d, J = 8.5 Hz, 1H), 7.27−7.23 (m, 1H),
.12−7.09 (m, 2H), 7.06−7.05 (d, J = 7.1 Hz, 1H), 7.02−7.01 (d, J =
.3 Hz, 2H), 6.95−6.93 (d, J = 11.2 Hz, 1H), 4.21−4.18 (m, 2H),
1
58%, 0.5 mmol scale); mp: 148−149 °C; H NMR (CDCl , 500.4
3
MHz): δ 8.92−8.91 (dd, J = 4.1, 1.7 Hz, 1H), 8.33 (m, 2H), 8.18−8.14
(m, 4H), 7.50 (s, 1H), 7.39−7.30 (m, 4H), 3.05−2.97 (m, 1H), 1.32
(s, 3H), 1.31 (s, 3H) ppm; 13C { H} NMR (CDCl
1
, 125.8 MHz): δ
3
13
1
.57−2.54 (t, J = 7.4 Hz, 2H), 2.16−2.10 (m, 2H) ppm; C { H}
150.7, 149.0, 145.8, 141.8, 138.4, 136.4, 133.2, 132.9, 128.8, 128.1,
127.4, 126.5, 125.7, 121.1, 118.2, 33.6, 24.2 ppm; 11B NMR (CDCl
,
3
128.4 MHz): δ 32.2 ppm; IR: ν = 1568, 1453, 1441, 1422, 1287, 1235,
NMR (CDCl , 125.8 MHz): δ 153.3, 147.5, 145.4, 140.7, 140.6, 140.0,
3
1
1
30.7, 129.3, 129.3, 128.8, 128.3, 128.1, 127.9, 127.9, 127.4, 126.4,
26.0, 121.2, 115.4, 47.5, 33.0, 31.5 ppm; 11B NMR (CDCl , 128.4
1223, 1187, 1176, 1123, 838, 830, 822, 810, 803, 777, 755, 725, 707,
3
−1
+
MHz): δ 34.9 ppm; IR: ν = 1608, 1591, 1549, 1486, 1453, 1412, 1347,
280, 1217, 1189, 1125, 1026, 949, 910, 808, 788, 763, 749, 698, 477
464 cm ; HRMS (ESI) m/z calc. for C20H20BN [M + H] 299.1720,
2
1
found 299.1723.
−1
+
cm ; HRMS (ESI) m/z calc. for C H BN [M + H] 375.2033,
found 375.2045.
2-(Quinolin-6-yl)-6-carbonitrile-2,1-borazaronaphthalene (7e).
Purified by basic alumina column and obtained as a white solid
26
24
2
1
2
-(Isoquinolin-5-yl)-1-(3-phenylpropyl)-2,1-borazaronaphtha-
(43.0 mg, 31%, 0.5 mmol scale); mp: 150−151 °C; H NMR (DMSO-
lene (6p). Purified by basic alumina column and obtained as a colorless
oil (29.3 mg, 17%, 0.5 mmol scale); H NMR (CDCl , 500.4 MHz): δ
d , 500.4 MHz): δ 11.0 (s, 1 H), 8.97 (s,1H), 8.73 (s, 1H), 8.47−8.46
6
1
(d, J = 7.5 Hz, 2H), 8.32 (s, 1H), 8.29−8.26 (d, J = 11.6 Hz, 1H),
8.14−8.12 (d, J = 8.3 Hz, 1H), 7.93−7.86 (q, J = 23.6, 8.3 Hz, 2H),
3
9
.29 (s, 1H), 8.41−8.40 (d, J = 5.8 Hz, 1H), 8.10−8.07 (d, J = 11.3 Hz,
13
1
1
H), 7.98−7.96 (d, J = 8.1 Hz, 1H), 7.76−7.71 (m, 2H), 7.64−7.61 (t,
7.60−7.54 (m, 2H) ppm; C { H} NMR (DMSO-d , 125.8 MHz): δ
6
J = 8.1 Hz, 1H), 7.53−7.50 (td, J = 8.5, 1.5 Hz, 1H), 7.46−7.41 (m,
151.2, 148.7, 144.7, 143.7, 136.5, 134.9, 134.4, 133.5, 130.7, 128.2,
2
H), 7.30−7.27 (t, J = 7.1 Hz, 1H), 7.13−7.09 (m, 3H), 6.89−6.86
127.7, 125.1, 121.6, 119.9, 119.4, 102.9 ppm; 11B NMR (CDCl , 128.4
3
(
m, 3H), 4.10−4.04 (m, 1H), 3.90−3.84 (m, 1H), 2.41−2.38 (t, J =
MHz): δ 33.2 ppm; IR: ν = 2221, 1613, 1597, 1576, 1461, 1343, 1321,
1298, 1244, 1212, 1180, 1171, 900, 877, 868, 832, 797, 770, 744, 574
cm ; HRMS (ESI) m/z calc. for C H BN [M + H] 282.1203,
13
1
7
.4 Hz, 2H), 2.04−1.94 (m, 2H) ppm; C { H} NMR (CDCl , 125.8
3
−1
+
MHz): δ 153.1, 145.1, 142.6, 140.8, 140.7, 137.5, 133.6, 130.8, 128.8,
18 13 3
1
4
28.5, 128.2, 128.0, 127.5, 127.0, 126.8, 125.9, 121.6, 121.2, 115.4,
found 282.1206.
1
1
8.0, 33.3, 31.3 ppm; B NMR (CDCl , 128.4 MHz): δ 36.6 ppm; IR:
2-(Quinolin-6-yl)-6,5-borazaroquinoline (7f). Purified by basic
alumina column and obtained as a white solid (45.1 mg, 35%, 0.5
3
ν = 1608, 1590, 1548, 1453, 1411, 1352, 1259, 1216, 1171, 1134, 1106,
F
DOI: 10.1021/acs.joc.6b02574
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
1
mmol scale); mp: 176−177 °C; H NMR (DMSO-d , 500.4 MHz): δ
6
ACKNOWLEDGMENTS
■
1
8
7
0.8 (br s, 1H), 8.95 (s, 1H), 8.72 (s, 1H), 8.54−8.46 (m, 3H), 8.33−
This research was supported by the NIH/NIGMS (R01 GM-
111465) and Eli Lilly. The China Scholarship Council and
Yong-Min Liang (Lanzhou University) are recognized for
support of Z.-Z.Z. Frontier Scientific is acknowledged for their
generous donation of potassium organotrifluoroborates. Dr.
Christopher B. Kelly (University of Pennsylvania) is acknowl-
edged for his support, discussions, and guidance.
.30 (d, J = 11.2 Hz, 1H), 8.16−8.11 (dd, J = 16.6, 7.3 Hz, 2H), 7.71−
13
1
.69 (d, J = 10.8 Hz, 1H), 7.59−7.53 (m, 2H) ppm; C { H} NMR
(
1
DMSO-d , 125.8 MHz): δ 151.1, 148.6, 146.6, 143.6, 142.3, 136.8,
6
11
36.5, 134.6, 133.5, 128.1, 127.7, 126.2, 123.3, 121.6 ppm; B NMR
CDCl , 128.4 MHz): δ 32.6 ppm; IR: ν = 1598, 1567, 1460, 1445,
374, 1353, 1321, 1264, 1240, 1219, 1194, 1182, 1116, 826, 791, 767,
41, 622, 588, 478 cm ; HRMS (ESI) m/z calc. for C H BN [M +
H] 258.1203, found 258.1198.
-(3,5-Dimethylisoxazole-4yl)-6,5-borazaroisoquinoline (7g). Pu-
rified by basic alumina column and obtained as a white solid (25.7 mg,
3%, 0.5 mmol scale); mp: 200−2017 °C; H NMR (CDCl , 500.4
MHz): δ 8.90 (s, 1H), 8.50 (d, J = 5.7 Hz, 1H), 8.14 (d, J = 11.6 Hz,
(
3
1
7
−1
16
13
3
+
2
REFERENCES
■
1
(1) For reviews on bioisosterism: (a) Patani, G. A.; LaVoie, E. J.
Chem. Rev. 1996, 96, 3147. (b) Meanwell, N. A. J. Med. Chem. 2011,
4, 2529. (c) Francotte, P.; Goffin, E.; Fraikin, P.; Graindorge, E.;
2
3
5
1
1
H), 8.06 (br s, 1H), 7.22 (d, J = 5.7 Hz, 1H), 7.15 (d, J = 11.7 Hz,
H), 2.60 (s, 3H), 2.46 (s, 3H) ppm; 1 C { H} NMR (CDCl , 125.8
3
1
Lestage, P.; Danober, L.; Challal, S.; Rogez, N.; Nosjean, O.; Caignard,
D. H.; Pirotte, B.; de Tullio, P. J. Med. Chem. 2013, 56, 7838.
(d) Pirotte, B.; de Tullio, P.; Florence, X.; Goffin, E.; Somers, F.;
Boverie, S.; Lebrun, P. J. Med. Chem. 2013, 56, 3247.
(2) For reviews on azaborine isosteres: (a) Bosdet, M. J. D.; Piers, W.
E. Can. J. Chem. 2009, 87, 8. (b) Campbell, P. G.; Marwitz, A. J. V.;
Liu, S.-Y. Angew. Chem., Int. Ed. 2012, 51, 6074. (c) Morgan, M. M.;
Piers, W. E. Dalton Trans. 2016, 45, 5920.
3) (a) Rombouts, F. J. R.; Tovar, F.; Austin, N.; Tresadern, G.;
Trabanco, A. A. J. Med. Chem. 2015, 58, 9287. (b) Vlasceanu, A.;
Jessing, M.; Kilburn, J. P. Bioorg. Med. Chem. 2015, 23, 4453.
4) Wisniewski, S. R.; Guenther, C. L.; Argintaru, O. A.; Molander,
G. A. J. Org. Chem. 2014, 79, 365.
5) Examples of functionalization of the 2,1-borazaronaphthalene
core: (a) Molander, G. A.; Wisniewski, S. R.; Amani, J. Org. Lett. 2014,
16, 5636. (b) Molander, G. A.; Wisniewski, S. R. J. Org. Chem. 2014,
3
MHz): δ 174.0, 162.1, 151.8, 147.7, 144.6, 143.5, 121.4, 112.7 ppm;
B NMR (CDCl , 128.4 MHz): δ 31.7 ppm; IR: ν = 3368, 3276,
1
1
3
−1
2
930, 1630, 1518, 1399, 1083, 967, 823, 798 cm ; HRMS (ESI) m/z
+
calc. for C H BN O [M + H] 226.1152, found 226.1150.
12
13
3
2
-(3-Fluorophenyl)-6,5-borazaroquinoline (7h). Purified by basic
alumina column and obtained as a white solid (30.9 mg, 27%, 0.5
1
mmol scale); mp: 246−247 °C; H NMR (CDCl , 500.4 MHz): δ
3
(
8
8
9
1
.61−8.59 (dd, J = 4.4, 1.4 Hz, 1H), 8.39−8.37 (d, J = 11.8 Hz, 1H),
.07 (br s, 1H), 7.70−7.67 (td, J = 7.9, 0.7 Hz, 2H), 7.59−7.58 (dd, J =
.6, 2.5 Hz, 1H), 7.53−7.51 (dd, J = 11.9, 2.2 Hz, 1H), 7.48−7.44 (m,
(
H), 7.41−7.38 (dd, J = 8.2, 4.4 Hz, 1H), 7.18−7.14 (m, 1H) ppm;
1
3
1
C { H} NMR (CDCl , 125.8 MHz): δ 163.0 (d, J = 245.1 Hz),
3
(
1
1
47.1, 144.0, 143.1, 135.8, 130.0 (d, J = 6.9 Hz), 128.3 (d, J = 3.2 Hz),
25.9, 123.0, 119.0 (d, J = 18.8 Hz), 116.8 (d, J = 20.3 Hz). F { H}
NMR (CDCl , 470.8 MHz): δ −113.5 ppm; B NMR (CDCl , 128.4
MHz): δ 31.7 ppm; IR: ν = 1596, 1568, 1445, 1418, 1377, 1323, 1289,
261, 1236, 1226, 1198, 1164, 880, 868, 825, 799, 786, 753, 746, 689
1
9
1
11
3
3
7
2
9, 6663. (c) Molander, G. A.; Amani, J.; Wisniewski, S. R. Org. Lett.
014, 16, 6024. (d) Molander, G. A.; Wisniewski, S. R.; Traister, K. T.
1
−1
+
Org. Lett. 2014, 16, 3692. (e) Amani, J.; Molander, G. A. Org. Lett.
015, 17, 3624. (f) Jouffroy, M.; Davies, G. H. M.; Molander, G. A.
Org. Lett. 2016, 18, 1606.
6) Reviews of N-heterocyclic influence on biological availability:
(a) Bua, R.; Shrivastava, S.; Sonwane, S. K.; Srivastava, S. K. Adv. Biol.
Res. 2011, 5, 120. (b) Welsch, M. E.; Snyder, S. A.; Stockwell, B. R.
Curr. Opin. Chem. Biol. 2010, 14, 347.
cm ; HRMS (ESI) m/z calc. for C H BN F [M + H] 225.0999,
13
11
2
2
found 225.1009.
2
-(Thiophen-3-yl)-6,5-borazaroisoquinoline (7i). Purified by basic
alumina column and obtained as a white solid (34.9 mg, 33%, 0.5
(
1
mmol scale); mp: 165−166 °C; H NMR (CDCl , 500.4 MHz): δ
3
8
(
.87 (s, 1H), 8.50−8.48 (d, J = 5.7 Hz, 1H), 8.13−8.06 (m, 2H), 7.99
dd, J = 2.5, 1.0 Hz, 1H), 7.58−7.57 (dd, J = 4.8, 1.0 Hz, 1H), 7.50−
(
́
7) Casado, M. R. S.; Jimenez, M. C.; Bueno, M. A.; Barriol, M.;
7
7
.49 (dd, J = 4.8, 2.7 Hz, 1H), 7.31−7.29 (dd, J = 11.6, 1.7 Hz, 1H),
13 1
Leenaerts, J. E.; Pagliuca, C.; Lamenca, C. M.; De Lucas, A. I.; García,
A.; Trabanco, A. A.; Rombouts, F. J. R. Eur. J. Org. Chem. 2015, 2015,
5221.
.21−7.20 (d, J = 5.7 Hz, 1H) ppm; C { H} NMR (CDCl , 125.8
3
MHz): δ 151.6, 147.5, 144.9, 143.3, 133.7, 130.3, 126.4, 121.9, 112.6
ppm; 1 B NMR (CDCl , 128.4 MHz): δ 31.1 ppm; IR: ν = 1623,
1
3
(
8) (a) Jolibois, H.; Doucet, A.; Dubry, J. L. J. Inorg. Nucl. Chem. Lett.
1976, 12, 759. (b) Rami, T.; Hensen, K. J. Inorg. Nucl. Chem. 1971, 33,
1
9
568, 1516, 1465, 1426, 1385, 1325, 1204, 1172, 1129, 1077, 1043,
76, 939, 911, 827.8, 786, 755, 693, 557 cm ; HRMS (ESI) m/z calc.
for C H BN S [M + H] 213.0658, found 213.0656.
−1
+
937.
(
(
11
10
2
9) Martinez, C. R.; Iverson, B. L. Chem. Sci. 2012, 3, 2191.
10) Ascic, E.; Buchwald, S. L. J. Am. Chem. Soc. 2015, 137, 4666.
ASSOCIATED CONTENT
Supporting Information
■
*
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.6b02574.
Copies of H, 13C, 11B, and 19F NMR spectra for all
1
compounds (PDF)
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: gmolandr@sas.upenn.edu
ORCID
Gary A. Molander: 0000-0002-9114-5584
Author Contributions
§
G.H.M.D. and Z.-Z.Z. contributed equally.
Notes
The authors declare no competing financial interest.
G
DOI: 10.1021/acs.joc.6b02574
J. Org. Chem. XXXX, XXX, XXX−XXX