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

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.

Introduction

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 would be beneficial.[1] 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 structurally and electronically.[2] Recently, the 2,1-borazaronaphthalene variant has been demonstrated to be a competent bioisostere in direct comparison to all-carbon analogues of propranolol,[3a] a well-known β-blocker, and phosphodiesterase 10A inhibitors.[3b] This specific class of azaborines has been 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 organotrifluoroborates.[4] Furthermore, the myriad recent methods for functionalizing this core extends the potential for additional applications of the 2,1-borazaronaphthalene substructure.[5] 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.[4] 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.[6] A recent solution to address this problem was reported by Rombouts et al. using microwave (μW) conditions (eq ), which allowed the annulation of pyridyl styrenes in high yields.[7] 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.

Results and Discussion

Using the standard reaction conditions previously developed by our group for accessing the 2,1-borazaronaphthalene core,[4] initial attempts to condense nitrogen-containing trifluoroborates with o-aminostyrene derivatives were met with no success. To understand what caused nitrogen heterocyclic trifluoroborates to be incompatible with the reported conditions, pyridine was added in increasing amounts to the reaction of 2-aminostyrene (1) with phenyltrifluoroborate (2) (Table ). 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 synthesis.[8] It was therefore anticipated that increasing the loading of SiCl4 would allow the reaction to proceed in the case of heteroaryl-containing trifluoroborates.

Table 1

Effect of Pyridine on the Synthesis of 2,1-Borazaronaphthalene

added pyridine	prod:SMa
0	full conversion
0.5	66:34
1.0	8:92
2.0	no reaction

Ratios determined by GCMS.

By adjusting the reaction conditions (Table , in bold), using two equivalents of SiCl4, exchanging cyclopentyl methyl ether (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 aromatic systems.[9] 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.

Table 2

Nitrogen-Containing B-Heterocyclic 2,1-Borazaronaphthalenes from N-Benzyl-2-aminostyrene

Under these conditions, quinolinyl- (5a,b), pyrimidinyl- (5c), and substituted pyridinyl- (5d–f) trifluoroborates were all 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 (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 ). N-Methylated 2,1-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).

Table 3

2,1-Borazaronaphthalene Annulation with Nitrogen-Modified 2-Aminostyrene

In addition, preinstalled functional groups could be employed on the aminostyrene to develop more elaborated cores (Table ). 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 sp3 character tended to be isolated in higher yield, continuing to suggest the influence of π interactions on the effectiveness of the reaction or isolation process. Aminopyridyl styrenes, similar to those previously reported,[6] were also amenable to these conditions (7f–i).

Table 4

Substituted 2-Aminostyrene Derivatives for B-Heterocyclic 2,1-Borazaronaphthalenes

Conclusion

The development of a new set of reaction conditions has enabled a broad advance of substrate classes available for the 2,1-borazaronaphthalene core isostere. Considering that the 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.

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 system. MeCN was purchased dry and used as received. Et3N was 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 Combiflash(R) using RediSep Rf Gold Normal-Phase Silica(R) columns or Alumina Basic columns. Melting points (°C) are uncorrected. Mass spectra (ESI- or CI-TOF) were recorded using CH2Cl2, MeCN, or MeOH as the solvent. IR spectra were recorded using FTIR-ATR of the neat oil or solid products. NMR spectra (1H, 13C {1H}, 11B, 19F {1H}) were performed at 298 K. 1H (500.4 MHz) and 13C {1H} (125.8 MHz) NMR chemical shifts are reported relative to internal TMS (δ = 0.00 ppm) or to residual protiated solvent. Any observed splitting in the 13C {1H} NMR spectra is due to 13C–19F coupling. 11B (128.4 MHz) and 19F {1H} NMR (470.8 MHz) chemical shifts were referenced to external BF3·Et2O (0.0 ppm) and CFCl3 (0.0 ppm), 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.

Procedure for Synthesis of 2-Aminostyrene Derivatives

Previously unreported 2-aminostyene derivatives were synthesized using known procedures established for the Buchwald–Hartwig amination of 2-bromostyrene (P1)4 or Suzuki cross-coupling of 2-bromoanilines (P2).[10]

N-(4-(tert-Butyl)phenyl)-2-vinylaniline (6k Starting Material)

Synthesized following procedure P1. Obtained as a brown solid (2.31 g, 92%, 10.0 mmol scale); mp: 65–66 °C; 1H NMR (CDCl3, 500.4 MHz): δ 7.45–7.43 (dd, J = 7.7, 1.6 Hz, 1H), 7.31–7.21 (m, 3H), 7.19–7.16 (dt, J = 8.0, 1.6 Hz, 1H), 6.98–6.95 (t, J = 7.5 Hz, 1H), 6.94–6.91 (m, 2H), 6.91–6.85 (dd, J = 17.5, 11.0 Hz, 1H), 5.70–5.66 (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 {1H} NMR (CDCl3, 125.8 MHz): δ 143.7, 141.1, 140.7, 132.9, 129.1, 128.5, 127.2, 126.1, 121.7, 118.8, 117.6, 116.2, 34.1, 31.5 ppm; IR: ν = 3392, 2957, 1612, 1515, 1455, 1300, 1267, 824, 757, 738 cm–1; HRMS (ESI) m/z calc. for C18H22N [M + H]+ 252.1752, found 252.1756.

N-(3-Phenylpropyl)-2-vinylaniline (6n,o,p Starting Material)

Synthesized following procedure P1. Obtained as a yellow liquid (1.00 g, 66%, 6.4 mmol scale); 1H NMR (CDCl3, 500.4 MHz): δ 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, 1H), 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, J = 7.4 Hz, 2H), 2.02–1.96 (m, 2H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 145.3, 141.6, 133.0, 128.9, 128.5, 128.4, 127.4, 126.0, 124.1, 117.1, 116.1, 110.6, 43.4, 33.5, 31.0 ppm; IR: ν = 3430, 3025, 2934, 2856, 1622, 1601, 1576, 1506, 1455, 1258, 908, 742, 698 cm–1; HRMS (ESI) m/z calc. for C17H20N [M + H]+ 238.1596, found 238.1596.

4-(Trifluoromethoxy)-2-vinylaniline (7b Starting Material)

Synthesized following procedure P2. Obtained as a yellow liquid (1.49 g, 73%, 10 mmol scale); 1H NMR (CDCl3, 500.4 MHz): δ 7.13 (s, 1H), 6.94–6.92 (d, J = 8.7 Hz, 1H), 6.69–6.64 (dd, J = 11.1, 17.4 Hz, 1H), 6.60–6.58 (d, J = 8.7 Hz, 1H), 5.63–5.60 (dd, J = 17.4, 1.2 Hz, 1H), 5.36–5.34 (dd, J = 11.1, 1.1 Hz, 1H), 3.74 (br s, 2H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 142.4, 141.5, 131.6, 124.7, 121.6, 120.71 (q, J = 255.8 Hz), 120.0, 117.0, 116.5 ppm; 19F {1H} NMR (CDCl3, 470.8 MHz): δ −58.3 ppm; IR: ν = 3352, 2984, 1780, 1496, 1435, 1247, 1221, 1203, 1046, 917, 873, 820 cm–1; HRMS (ESI) m/z calc. for C9H9NOF3 [M + H]+ 204.0636, found 204.0623.

2,4-Difluoro-6-vinylaniline (7c Starting Material)

Synthesized following procedure P2. Obtained as a yellow liquid (0.60 g, 39%, 10.0 mmol scale); 1H NMR (CDCl3, 500.4 MHz): δ 6.85–6.82 (dt, J = 9.4, 2.1 Hz, 1H), 6.75–6.69 (m, 2H), 5.68–5.64 (dd, J = 17.4, 0.9 Hz, 1H), 5.41–5.39 (dd, J = 11.0 Hz, 1H), 3.64 (br s, 2H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 155.0 (dd, J = 238.1, 12.6 Hz), 151.4 (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 {1H} NMR (CDCl3, 470.8 MHz): δ −124.3, −130.7 ppm; IR: ν = 3462, 3376, 3087, 1586, 1482, 1294, 1111, 978, 919, 859, 587 cm–1; HRMS (ESI) m/z calc. for C8H8NF2 [M + H]+ 156.0625, found 156.0633.

4-Amino-3-vinylbenzonitrile (7e Starting Material)

Synthesized following procedure P2. Obtained as a yellow solid (0.61 g, 43%, 10.0 mmol scale); mp: 77–78 °C; 1H NMR (CDCl3, 500.4 MHz): δ 7.48 (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 = 11.0, 0.9 Hz, 1H), 2.04 (s, 2H) ppm; 13C {1H} NMR (CDCl3, 125.8 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, 1282, 890, 815, cm–1; HRMS (ESI) m/z calc. for C9H9N2 [M + H]+ 145.0766, found 145.0773.

General Procedure for Synthesis of Nitrogen-Containing Heteroaryl-2,1-borazaronaphthalenes

Potassium heteroaryltrifluoroborate (1.0 equiv) was introduced into a microwave vial with a stir bar. The vial was sealed with a Teflon-coated septum cap, then evacuated and purged with N2 four times. An MeCN/toluene mixture (0.25 M, 1:1, v/v) and 2-aminostyrene (1.2 equiv) were introduced via syringe, followed by NEt3 (1.5 equiv) and SiCl4 (2.0 equiv). The 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 resulting solid was filtered off and the remaining solution was extracted with EtOAc/H2O, dried (MgSO4), and concentrated under vacuum. 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 CH2Cl2 and hexanes, starting at 100% hexanes to 10:90 hexanes/CH2Cl2.

1-Benzyl-2-(quinolin-6-yl)-2,1-borazaronaphthalene (5a)

Purified on silica gel and obtained as a white solid (131.0 mg, 76%, 0.5 mmol scale); mp: 105–106 °C; 1H NMR (CDCl3, 500.4 MHz): δ 8.89–8.90 (m, 1H), 8.17–8.20 (d, J = 11.3 Hz, 1H), 8.02–8.06 (m, 2 H), 7.95 (s, 1H), 7.86–7.88 (d, J = 8.4 Hz, 1H), 7.74–7.75 (d, J = 7.6 Hz, 1H), 7.30–7.39 (m, 5H), 7.22–7.26 (m, 2H), 7.10–7.15 (m, 3H), 5.46 (s, 2H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 150.4, 148.1, 145.7, 141.1, 139.0, 136.2, 133.4, 132.4, 130.4, 128.8, 128.8, 128.3, 127.8, 127.4, 127.0, 125.7, 121.3, 121.0, 117.0, 52.6 ppm; 11B NMR (CDCl3, 128.4 MHz): δ 36.7 ppm; IR: ν = 1605, 1588, 1547, 1492, 1455, 1410, 1353, 1229, 1181, 1143, 1118, 982, 840, 814, 798, 765, 748, 698, 476, 465 cm–1; HRMS (ESI) m/z calc. for C24H19BN2Na [M + Na]+ 369.1539, found 369.1547.

1-Benzyl-2-(quinolin-3-yl)-2,1-borazaronaphthalene (5b)

Purified on silica gel and obtained as a white solid (140.8 mg, 81%, 0.5 mmol scale); mp: 94–95 °C; 1H NMR (CDCl3, 500.4 MHz): δ 9.07 (s, 1 H), 8.27 (s, 1H), 8.20–8.22 (d, J = 11.3 Hz, 1H), 8.07–8.09 (d, J = 8.5 Hz, 1H), 7.75–7.76 (d, J = 7.6 Hz, 1H), 7.68–7.70 (m, 2H), 7.48–7.51 (t, J = 8 Hz, 1H), 7.39–7.40 (m, 2H), 7.32–7.29 (m, 2H), 7.26–7.23 (m, 2H), 7.15–7.12 (m, 3H), 5.48 (s, 2H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 153.7, 147.7, 146.0, 141.2, 140.7, 138.7, 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; 11B NMR (CDCl3, 128.4 MHz): δ 36.1 ppm; IR: ν = 1608, 1593, 1550, 1491, 1452, 1415, 1347, 1282, 1226, 943, 913, 856, 812, 789, 761, 731, 695, 477 cm–1; HRMS (ESI) m/z calc. for C24H19BN2Na [M + Na]+ 369.1539, found 369.1534.

1-Benzyl-2-(pyrimidin-5-yl)-2,1-borazaronaphthalene (5c)

Purified on silica gel and obtained as a brown solid (86.2 mg, 58%, 0.5 mmol scale); mp: 123–124 °C; 1H NMR (CDCl3, 500.4 MHz): δ 9.18 (s, 1H), 8.82 (s, 2H), 8.21–8.23 (d, J = 11.3 Hz, 1H), 7.75–7.76 (d, J = 7.5 Hz, 1H), 7.40 (m, 2H), 7.24–7.31 (m, 4H), 7.08–7.09 (d, J = 7.5 Hz, 2H), 7.03–7.05 (d, J = 11.3 Hz, 1H), 5.40 (s, 2H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 160.1, 158.2, 146.6, 140.9, 138.0, 130.6, 129.2, 129.0, 127.4, 127.3, 125.3, 121.8, 116.9, 52.5 ppm; 11B NMR (CDCl3, 128.4 MHz): δ 34.9 ppm; IR: ν = 1611, 1592, 1568, 1543, 1493, 1452, 1403, 1354, 1280, 1251, 1218, 1138, 962, 810, 762, 725, 695, 638, 482, 463 cm–1; HRMS (ESI) m/z calc. for C19H17BN3 [M + H]+ 298.1516, found 298.1508.

1-Benzyl-2-(6-fluoropyridin-3-yl)-2,1-borazaronaphthalene (5d)

Purified on silica gel and obtained as a brown solid (70.3 g, 45%, 0.5 mmol scale); mp: 93–94 °C; 1H NMR (CDCl3, 500.4 MHz): δ 8.34 (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), 7.31–7.28 (t, J = 7.2 Hz, 2H), 7.25–7.21 (m, 2H), 7.09–7.08 (d, J = 7.3 Hz, 2H), 7.02–7.00 (d, J = 11.3 Hz, 1H), 6.87–6.85 (dd, J = 8.2, 2.3 Hz, 1H), 5.38 (s, 2H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 163.8 (d, J = 239.7 Hz), 151.3 (d, J = 13.5 Hz), 146.1, 145.2 (d, J = 7.3 Hz), 141.0, 138.4, 130.4, 129.0 (2 x C), 127.3, 127.1, 125.4, 121.5, 116.9, 108.8 (d, J = 35.3 Hz), 52.4 ppm; 19F {1H} NMR (CDCl3, 470.8 MHz): δ −68.5 ppm; 11B NMR (CDCl3, 128.4 MHz): δ 35.6 ppm; IR: ν = 1611, 1575, 1550, 1482, 1451, 1412, 1346, 1277, 1233, 1146, 1056, 964, 834, 805, 761, 727, 695, 645, 478, 463 cm–1; HRMS (ESI) m/z calc. for C20H17BN2F [M + H]+ 315.1469, found 315.1458.

1-Benzyl-2-(2-fluoropyridin-3-yl)-2,1-borazaronaphthalene (5e)

Purified on silica gel and obtained as a yellow solid (122.3 mg, 78%, 0.5 mmol scale); mp: 108–109 °C; 1H NMR (CDCl3, 500.4 MHz): δ 8.18–8.19 (dd, J = 4.5, 2.0 Hz, 1H), 8.15–8.13 (d, J = 11.3 Hz, 1H), 7.76–7.70 (m, 2H), 7.39–7.33 (m, 2H), 7.24–7.17 (m, 4H), 7.10–7.07 (m, 1H), 7.04–7.03 (d, J = 7.7 Hz, 2H), 7.00–6.98 (d, J = 11.3 Hz, 1H), 5.33 (s, 2H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 164.5 (d, J = 235.2 Hz), 147.7 (d, J = 14.5 Hz), 145.9, 144.7 (d, J = 8.5 Hz), 140.8, 138.2, 130.4, 128.8, 128.7, 127.4, 127.0, 125.5, 121.5, 121.0 (d, J = 3.8 Hz), 117.0, 52.6 ppm; 19F {1H} NMR (CDCl3, 470.8 MHz): δ −58.1 ppm; 11B NMR (CDCl3, 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–1; HRMS (ESI) m/z calc. for C20H16BN2FNa [M + Na]+ 337.1288, found 337.1285.

1-Benzyl-2-(4-(N,N-dimethylamino)pyridin-5-yl)-2,1-borazaronaphthalene (5f)

Purified on silica gel and obtained as a pale yellow solid (28.9 mg, 17%, 0.5 mmol scale); mp: 139–140 °C; 1H NMR (CDCl3, 500.4 MHz): δ 8.43 (m, 1H), 8.09–8.07 (d, J = 11.4 Hz, 1H), 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), 7.09–7.07 (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 {1H} NMR (CDCl3, 125.8 MHz): δ 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; 11B 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, 478 cm–1; HRMS (ESI) m/z calc. for C22H23BN3 [M + H]+ 340.1985, found 340.1989.

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, 54%, 0.5 mmol scale); mp: 116–117 °C; 1H NMR (CDCl3, 500.4 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), 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 {1H} NMR (CDCl3, 125.8 MHz): δ 145.0, 144.8, 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; 11B NMR (CDCl3, 128.4 MHz): δ 33.4 ppm; IR: ν = 1604, 1591, 1548, 1533, 1487, 1460, 1411, 1376, 1347, 1327, 1299, 1218, 1177, 934, 896, 808, 761, 730, 696, 674 cm–1; HRMS (ESI) m/z calc. for C19H18BN3Na [M + Na]+ 322.1491, found 322.1470.

1-Benzyl-2-(3,5-dimethylisoxazole-4-yl)-2,1-borazaronaphthalene (5h)

Purified on silica gel and obtained as a pale yellow solid (83.0 mg, 53%, 0.5 mmol scale); mp: 110–111 °C; 1H NMR (CDCl3, 500.4 MHz): δ 8.14–8.12 (d, J = 11.3 Hz, 1H), 7.73–7.71 (d, J = 7.7 Hz, 1H), 7.45–7.35 (m, 2H), 7.23–7.20 (m, 3H), 7.18–7.15 (m, 1H), 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 {1H} NMR (CDCl3, 125.8 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; 11B NMR (CDCl3, 128.4 MHz): δ 34.6 ppm; IR: ν = 1589, 1547, 1492, 1415, 1402, 1356, 1288, 1259, 1209, 1133, 1055, 1028, 958, 896, 818, 769, 733, 697, 481, 468 cm–1; HRMS (ESI) m/z calc. for C20H20BN2O [M + H]+ 315.1669, found 315.1674.

1-Benzyl-2-(1-(phenylsulfonyl)-1H-indol-3-yl)-2,1-borazaronaphthalene (5i)

Purified on silica gel and obtained as a white solid (53.4 mg, 23%, 0.5 mmol scale); mp: 74–75 °C; 1H NMR (CDCl3, 500.4 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, 1H), 7.10–7.08 (d, J = 7.35 Hz, 2H), 5.41 (s, 2H) ppm; 13C {1H} NMR (CDCl3, 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 (CDCl3, 128.4 MHz): δ 34.0 ppm; IR: ν = 1609, 1592, 1551, 1445, 1412, 1368, 1175, 1130, 1087, 1021, 984, 809, 765, 746, 726, 686, 596, 587, 569, 551 cm–1; HRMS (ESI) m/z calc. for C29H24BN2O2S [M + H]+ 475.1652, found 475.1645.

1-Methyl-2-(quinolin-6-yl)-2,1-borazaronaphthalene (6a)

Purified by basic alumina column and obtained as a pale yellow oil (48.0 mg, 36%, 0.5 mmol scale); 1H NMR (CDCl3, 500.4 MHz): δ 9.30 (s, 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; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 153.1, 145.0, 142.8, 142.2, 137.7, 134.4, 130.4, 128.9, 128.4, 127.2, 127.0, 126.8, 121.7, 121.4, 115.1, 37.1 ppm; 11B NMR (CDCl3, 128.4 MHz): δ 36.6 ppm; IR: ν = 1608, 1590, 1549, 1455, 1409, 1336, 1289, 1266, 1238, 1215, 1174, 1135, 1101, 1044, 830, 805, 760, 734, 674, 480 cm–1; HRMS (ESI) m/z calc. for C18H16BN2 [M + H]+ 271.1407, found 271.1400.

1-Methyl-2-(quinolin-3-yl)-2,1-borazaronaphthalene (6b)

Purified by basic alumina column and obtained as a yellow solid (65.1 mg, 48%, 0.5 mmol scale); mp: 101–102 °C; 1H NMR (CDCl3, 500.4 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 (m, 2H), 7.33–7.30 (m, 1H), 7.04–7.01 (d, J = 11.3 Hz, 1H), 3.78 (s, 3H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 154.2, 147.6, 145.3, 142.2, 141.1, 130.3, 129.4, 129.2, 128.9, 127.9, 127.8, 126.9, 126.4, 121.3, 115.1, 36.9 ppm; 11B NMR (CDCl3, 128.4 MHz): δ 35.4 ppm; IR: ν = 1608, 1590, 1549, 1483, 1409, 1343, 1316, 1288, 1215, 1190, 1141, 1120, 1023, 947, 912, 807, 788, 753, 693, 484 cm–1; HRMS (ESI) m/z calc. for C18H16BN2 [M + H]+ 271.1407, found 271.1409.

2-(Isoquinolin-5-yl)-1-methyl-2,1-borazaronaphthalene (6c)

Purified by basic alumina column and obtained as a yellow oil (43.1 mg, 32%, 0.5 mmol scale); 1H NMR (CDCl3, 500.4 MHz): δ 9.30 (s, 1H), 8.44–8.43 (d, J = 5.8 Hz, 1H), 8.14–8.11 (d, J = 11.3 Hz, 1H), 8.00–7.98 (d, J = 8.2 Hz, 1H), 7.79–7.77 (t, J = 5.6 Hz, 2H), 7.68–7.60 (m, 3H), 7.48–7.47 (d, J = 5.9 Hz, 1H), 7.35–7.32 (t, J = 7.0 Hz, 1H), 6.96–6.94 (d, J = 11.3 Hz, 1H), 3.55 (s, 3H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 153.1, 145.0, 142.7, 142.2, 137.7, 134.4, 130.4, 128.9, 128.4, 127.2, 127.1, 126.8, 121.6, 121.4, 115.1, 37.1 ppm; 11B NMR (CDCl3, 128.4 MHz): δ 36.5 ppm; IR: ν = 1608, 1590, 1550, 1455, 1445, 1424, 1409, 1336, 1289, 1238, 1215, 1174, 1135, 1101, 1044, 830, 805, 760, 739, 674 cm–1; HRMS (ESI) m/z calc. for C18H16BN2 [M + H]+ 271.1407, found 271.1389.

2-(6-Fluoropyridin-3-yl)-1-methyl-2,1-borazaronaphthalene (6d)

Purified by basic alumina column and obtained as a brown oil (21.5 g, 18%, 0.5 mmol scale); 1H NMR (CDCl3, 500.4 MHz): δ 8.43 (s, 1H), 8.10–8.08 (d, J = 11.3 Hz, 1H), 8.02–7.08 (td, J = 8.4, 2.1 Hz, 1H), 7.74–7.72 (d, J = 7.7 Hz, 1H), 7.65–7.58 (m, 2H), 7.32–7.29 (td, J = 7.8, 1.2 Hz, 1H), 7.02–7.00 (dd, J = 8.2, 2.6 Hz, 1H), 6.92–6.90 (d, J = 11.3 Hz, 1H), 3.72 (s, 3H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 163.7 (d, J = 239.3 Hz), 151.7 (d, J = 13.3 Hz), 145.9 (d, J = 7.1 Hz), 145.4, 142.1, 130.4, 129.0, 126.9, 121.4, 115.2, 108.9 (d, J = 35.3 Hz), 36.7 ppm; 19F {1H} NMR (CDCl3, 470.8 MHz): δ −68.9 ppm; 11B NMR (CDCl3, 128.4 MHz): δ 35.0 ppm; IR: ν = 1608, 1581, 1552, 1482, 1470, 1444, 1412, 1342, 1289, 1241, 1213, 1123, 984, 853, 830, 802, 763, 740, 633, 486 cm–1; HRMS (ESI) m/z calc. for C14H13BN2F [M + H]+ 239.1156, found 239.1161.

2-(3-Fluoropyridin-4-yl)-1-methyl-2,1-borazaronaphthalene (6e)

Purified by basic alumina column and obtained as a brown solid (65.1 mg, 55%, 0.5 mmol scale); mp: 97–98 °C; 1H NMR (CDCl3, 500.4 MHz): δ 8.49 (s, 1H), 8.47–8.46 (dd, J = 4.6, 2.3 Hz, 1H), 8.12–8.10 (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, J = 4.8 Hz, 1H), 7.33–7.30 (td, J = 7.8, 0.8 Hz, 1H), 6.90–6.87 (d, J = 11.3 Hz, 1H), 3.63 (s, 3H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 160.7 (d, J = 250.6 Hz), 145.7, 144.9 (d, J = 3.0 Hz), 141.8, 137.5 (d, J = 27.1 Hz), 130.4, 129.1, 128.3 (d, J = 5.6 Hz), 127.0, 121.6, 115.1, 37.1 ppm; 19F {1H} NMR (CDCl3, 470.8 MHz): δ −118.8 ppm; 11B NMR (CDCl3, 128.4 MHz): δ 33.2 ppm; IR: ν = 1611, 1586, 1552, 1442, 1410, 1346, 1282, 1237, 1202, 1054, 1001, 842, 798, 755, 664, 586, 574, 548, 525, 482 cm–1; HRMS (ESI) m/z calc. for C14H13BN2F [M + H]+ 239.1156, found 239.1166.

1-Methyl-2-(2-(morpholino)pyridin-3-yl)-2,1-borazaronaphthalene (6f)

Purified by basic alumina column and obtained as a colorless oil (102.1 mg, 67%, 0.5 mmol scale); 1H NMR (CDCl3, 500.4 MHz): δ 8.28–8.27 (dd, J = 4.9 2.0 Hz, 1H), 8.05–8.03 (d, J = 11.3 Hz, 1H), 7.70–7.69 (dd, J = 7.7, 1.2 Hz, 1H), 7.61–7.55 (m, 3H), 7.29–7.25 (td, J = 7.8, 1.3 Hz, 1H), 6.94–6.92 (d, J = 11.3 Hz, 1H), 6.85–6.83 (dd, J = 7.1, 5.0 Hz, 1H), 3.60 (s, 7H), 3.27 (s, 4H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 156.3, 140.2, 138.3, 135.7, 135.1, 123.2, 121.8, 119.7, 114.1, 108.4, 107.9, 60.0, 42.9, 29.7 ppm; 11B NMR (CDCl3, 128.4 MHz): δ 34.7 ppm; IR: ν = 1609, 1590, 1572, 1551, 1455, 1408, 1364, 1335, 1286, 1231, 1217, 1116, 980, 941, 925, 908, 808, 785, 762, 728 cm–1; HRMS (ESI) m/z calc. for C18H21BN3O [M + H]+ 306.1778, found 306.1771.

1-Methyl-2-(pyrimidin-5-yl)-2,1-borazaronaphthalene (6g)

Purified by basic alumina column and obtained as a brown solid (44.5 mg, 40%, 0.5 mmol scale); mp: 109–110 °C; 1H NMR (CDCl3, 500.4 MHz): δ 9.25 (s, 1H), 8.94 (s, 2H), 8.15–8.12 (d, J = 11.3 Hz, 1H), 7.76–7.74 (d, J = 7.8 Hz, 1H), 7.70–7.62 (m, 2H), 7.35–7.32 (t, J = 6.8 Hz, 1H), 6.95–6.92 (d, J = 11.3 Hz, 1H), 3.75 (s, 3H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 160.6, 157.9, 145.9, 141.9, 130.5, 129.2, 127.0, 121.7, 115.2, 36.8 ppm; 11B NMR (CDCl3, 128.4 MHz): δ 34.3 ppm; IR: ν = 1610, 1591, 1571, 1547, 1459, 1408, 1351, 1340, 1291, 1215, 1188, 1137, 1106, 980, 801, 754, 728, 647, 637, 484 cm–1; HRMS (ESI) m/z calc. for C13H13BN3 [M + H]+ 222.1203, found 222.1201.

1-Methyl-2-(3,5-dimethylisoxazole-4-yl)-2,1-borazaronaphthalene (6h)

Purified by basic alumina column and obtained as a white solid (49.5 mg, 42%, 0.5 mmol scale); mp: 86–87 °C; 1H NMR (CDCl3, 500.4 MHz): δ 8.06–8.04 (d, J = 11.3 Hz, 1H), 7.73–7.72 (d, J = 7.7 Hz, 1H), 7.64–7.57 (m, 2H), 7.32–7.25 (td, J = 7.0, 1.2 Hz, 1H), 6.87–6.84 (d, J = 11.3 Hz, 1H), 3.65 (s, 3H), 2.37 (s, 3H), 2.26 (s, 3H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 170.3, 162.2, 145.0, 142.3, 130.3, 128.8, 126.9, 121.4, 115.1, 36.8, 12.9, 12.2 ppm; 11B NMR (CDCl3, 128.4 MHz): δ 33.7 ppm; IR: ν = 1591, 1551, 1463, 1444, 1415, 1404, 1360, 1336, 1291, 1279, 1253, 1217, 1207, 1131, 972, 891, 813, 767, 738, 485 cm–1; HRMS (ESI) m/z calc. for C14H16BN2O [M + H]+ 239.1356, found 239.1354.

1-Methyl-2-(1-methyl-1H-pyrazol-4-yl)-2,1-borazaronaphthalene (6i)

Purified by basic alumina column and obtained as a brown solid (67.4 mg, 61%, 0.5 mmol scale); mp: 82–83 °C; 1H NMR (CDCl3, 500.4 MHz): δ 7.94–7.92 (d, J = 11.3 Hz, 1H), 7.84 (s, 1H), 7.64–7.61 (m, 2H), 7.54–7.48 (m, 2H), 7.23–7.18 (m, 1H), 6.98–6.95 (d, J = 11.4 Hz, 1H), 3.96 (s, 3H), 3.79 (s, 3H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 144.7, 144.1, 142.6, 135.6, 129.9, 128.4, 126.5, 120.5, 114.7, 38.5, 36.5 ppm; 11B NMR (CDCl3, 128.4 MHz): δ 31.9 ppm; IR: ν = 1608, 1590, 1552, 1531, 1495, 1460, 1438, 1409, 1361, 1342, 1322, 1214, 1176, 1148, 1118, 940, 801, 757, 688, 677 cm–1; HRMS (ESI) m/z calc. for C13H15BN3 [M + H]+ 224.1359, found 224.1370.

1-Methyl-2-(1-tosyl-1H-pyrrol-2-yl)-2,1-borazaronaphthalene (6j)

Purified by basic alumina column and obtained as a white solid (57.9 mg, 32%, 0.5 mmol scale); mp: 122–123 °C; 1H NMR (CDCl3, 500.4 MHz): δ 8.00–7.98 (d, J = 11.3 Hz, 1H), 7.71–7.69 (d, J = 7.6 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 = 8.4 Hz, 2H), 6.69–6.67 (d, J = 11.3 Hz, 1H), 6.40–6.38 (t, J = 3.2 Hz, 1H), 6.30–6.29 (q, J = 1.5 Hz, 1H), 3.49 (s, 3H), 2.35 (s, 3H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 144.5, 144.0, 142.1, 136.3, 130.1, 129.5, 128.6, 127.0, 126.9, 123.8, 121.0, 120.2, 115.1, 113.7, 37.3, 21.5 ppm; 11B NMR (CDCl3, 128.4 MHz): δ 32.8 ppm; IR: ν = 1612, 1594, 1554, 1456, 1411, 1359, 1293, 1168, 1058, 1034, 951, 807, 756, 727, 701, 672, 588, 539, 489 cm–1; HRMS (ESI) m/z calc. for C20H20BN2O2S [M + H]+ 363.1339, found 363.1335.

1-(4-(tert-Butyl)phenyl)-2-(quinolin-6-yl)-2,1-borazaronaphthalene (6k)

Purified by basic alumina column and obtained as a brown solid (167.8 mg, 87%, 0.5 mmol scale); mp: 157–158 °C; 1H NMR (CDCl3, 500.4 MHz): δ 8.83 (s, 1H), 8.23–8.21 (d, J = 11.3 Hz, 1H), 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, 9H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 150.5, 150.4, 147.9, 145.5, 142.8, 140.8, 136.2, 134.6, 134.4, 129.7, 128.8, 128.3, 127.6, 127.3, 126.3, 126.1, 121.3, 120.6, 117.8, 34.6, 31.4 ppm; 11B NMR (CDCl3, 128.4 MHz): δ 34.1 ppm; IR: ν = 1604, 1594, 1545, 1506, 1486, 1410, 1321, 1291, 1281, 1258, 1170, 1150, 894, 837, 807, 794, 770, 758, 581, 550 cm–1; HRMS (ESI) m/z calc. for C27H26BN2 [M + H]+ 389.2189, found 389.2201.

1-Allyl-2-(quinolin-6-yl)-2,1-borazaronaphthalene (6l)

Purified by basic alumina column and obtained as a yellow solid (33.6 mg, 23%, 0.5 mmol scale); mp: 85–86 °C; 1H NMR (CDCl3, 500.4 MHz): δ 9.28 (s, 1H), 8.41–8.40 (d, J = 5.7 Hz, 1H), 8.14–8.11 (d, J = 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), 7.49–7.48 (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), 4.91–4.88 (d, J = 17.3 Hz, 1H), 4.71–4.67 (dd, J = 15.2, 2.0 Hz, 1H), 4.58–4.54 (dd, J = 17.2, 2.1 Hz, 1H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 153.0, 145.2, 142.6, 141.1, 137.6, 134.9, 133.5, 130.5, 128.6, 128.4, 127.3, 127.1, 126.7, 121.7, 121.3, 116.6, 116.2, 51.0 ppm; 11B NMR (CDCl3, 128.4 MHz): δ 37.1 ppm; IR: ν = 1608, 1590, 1547, 1455, 1409, 1358, 1333, 1283, 1245, 1219, 1174, 1134, 1049, 937, 918, 833, 809, 761, 675, 473 cm–1; HRMS (ESI) m/z calc. for C20H18BN2 [M + H]+ 297.1563, found 297.1566.

2-(Quinolin-6-yl)-2,1-borazaronaphthalene (6m)

Purified by basic alumina column and obtained as a white solid (84.6 mg, 66%, 0.5 mmol scale); mp: 226–227 °C; 1H NMR (DMSO-d6, 500.4 MHz): δ 10.7 (s, 1H), 8.94 (s, 1H), 8.69 (s, 1H), 8.48–8.44 (m, 2H), 8.24–8.22 (d, J = 11.3 Hz, 1H), 8.12–8.10 (d, J = 8.2 Hz, 1H), 7.80–7.73 (m, 2H), 7.59–7.51 (m, 2H), 7.42–7.40 (d, J = 11.1 Hz, 1H), 7.22–7.21 (m, 1H) ppm; 13C {1H} NMR (DMSO-d6, 125.8 MHz): δ 150.9, 148.5, 145.5, 140.9, 136.4, 134.3, 135.6, 129.1, 128.5, 128.0, 127.7, 125.2, 121.5, 120.8, 118.7 ppm; 11B NMR (Acetone-d6, 128.4 MHz): δ 32.7 ppm; IR: ν = 1615, 1597, 1568, 1496, 1456, 1448, 1346, 1320, 1288, 1268, 1219, 1178, 1159, 872, 828, 802, 791, 765, 753 cm–1; HRMS (ESI) m/z calc. for C17H14BN2 [M + H]+ 257.1250, found 257.1245.

1-(3-Phenylpropyl)-2-(quinolin-6-yl)-2,1-borazaronaphthalene (6n)

Purified by basic alumina column and obtained as a yellow oil (39.1 mg, 21%, 0.5 mmol scale); 1H NMR (CDCl3, 500.4 MHz): δ 9.29 (s, 1H), 8.41–8.40 (d, J = 5.9 Hz, 1H), 8.10–8.07 (d, J = 11.2 Hz, 1H), 7.98–7.96 (d, J = 8.1 Hz, 1H), 7.76–7.71 (m, 2H), 7.64–7.61 (t, J = 7.0 Hz, 1H), 7.53–7.50 (t, J = 7.1 Hz, 1H), 7.46–7.42 (m, 2H), 7.30–7.27 (t, J = 7.5 Hz, 1H), 7.13–7.09 (m, 3H), 6.89–6.86 (m, 3H), 4.10–4.04 (m, 1H), 3.90–3.84 (m, 1H), 2.40–2.37 (t, J = 7.4 Hz, 2H), 2.03–1.94 (m, 2H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 153.0, 145.1, 142.5, 140.8, 140.7, 137.5, 133.6, 130.8, 128.7, 128.4, 128.2, 128.0, 127.5, 127.0, 126.8, 125.9, 121.6, 121.2, 115.4, 47.9, 33.0, 31.3 ppm; 11B NMR (CDCl3, 128.4 MHz): δ 37.0 ppm; IR: ν = 1608, 1590, 1549, 1494, 1453, 1411, 1353, 1279, 1259, 1216, 1171, 1043, 1030, 830, 806, 763, 741, 698, 674, 475 cm–1; HRMS (ESI) m/z calc. for C26H24BN2 [M + H]+ 375.2033, found 375.2031.

1-(3-Phenylpropyl)-2-(quinolin-3-yl)-2,1-borazaronaphthalene (6o)

Purified by basic alumina column and obtained as a colorless oil (65.3 mg, 35%, 0.5 mmol scale); 1H NMR (CDCl3, 500.4 MHz): δ 9.10–9.09 (d, J = 1.3 Hz, 1H), 8.26 (s, 1H), 8.17–8.15 (d, J = 8.4 Hz, 1H), 8.09–8.07 (d, J = 11.3 Hz, 1H), 7.82–7.80 (d, J = 8.1 Hz, 1H), 7.76–7.71 (m, 2H), 7.58–7.55 (t, J = 7.6 Hz, 1H), 7.52–7.49 (t, J = 7.3 Hz, 1H), 7.46–7.44 (d, J = 8.5 Hz, 1H), 7.27–7.23 (m, 1H), 7.12–7.09 (m, 2H), 7.06–7.05 (d, J = 7.1 Hz, 1H), 7.02–7.01 (d, J = 7.3 Hz, 2H), 6.95–6.93 (d, J = 11.2 Hz, 1H), 4.21–4.18 (m, 2H), 2.57–2.54 (t, J = 7.4 Hz, 2H), 2.16–2.10 (m, 2H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 153.3, 147.5, 145.4, 140.7, 140.6, 140.0, 130.7, 129.3, 129.3, 128.8, 128.3, 128.1, 127.9, 127.9, 127.4, 126.4, 126.0, 121.2, 115.4, 47.5, 33.0, 31.5 ppm; 11B NMR (CDCl3, 128.4 MHz): δ 34.9 ppm; IR: ν = 1608, 1591, 1549, 1486, 1453, 1412, 1347, 1280, 1217, 1189, 1125, 1026, 949, 910, 808, 788, 763, 749, 698, 477 cm–1; HRMS (ESI) m/z calc. for C26H24BN2 [M + H]+ 375.2033, found 375.2045.

2-(Isoquinolin-5-yl)-1-(3-phenylpropyl)-2,1-borazaronaphthalene (6p)

Purified by basic alumina column and obtained as a colorless oil (29.3 mg, 17%, 0.5 mmol scale); 1H NMR (CDCl3, 500.4 MHz): δ 9.29 (s, 1H), 8.41–8.40 (d, J = 5.8 Hz, 1H), 8.10–8.07 (d, J = 11.3 Hz, 1H), 7.98–7.96 (d, J = 8.1 Hz, 1H), 7.76–7.71 (m, 2H), 7.64–7.61 (t, J = 8.1 Hz, 1H), 7.53–7.50 (td, J = 8.5, 1.5 Hz, 1H), 7.46–7.41 (m, 2H), 7.30–7.27 (t, J = 7.1 Hz, 1H), 7.13–7.09 (m, 3H), 6.89–6.86 (m, 3H), 4.10–4.04 (m, 1H), 3.90–3.84 (m, 1H), 2.41–2.38 (t, J = 7.4 Hz, 2H), 2.04–1.94 (m, 2H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 153.1, 145.1, 142.6, 140.8, 140.7, 137.5, 133.6, 130.8, 128.8, 128.5, 128.2, 128.0, 127.5, 127.0, 126.8, 125.9, 121.6, 121.2, 115.4, 48.0, 33.3, 31.3 ppm; 11B NMR (CDCl3, 128.4 MHz): δ 36.6 ppm; IR: ν = 1608, 1590, 1548, 1453, 1411, 1352, 1259, 1216, 1171, 1134, 1106, 1042, 1030, 829, 805, 762, 740, 698, 675, 474 cm–1; HRMS (ESI) m/z calc. for C26H24BN2 [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 (83.8 mg, 52%, 0.5 mmol scale); mp: 173–174 °C; 1H NMR (CDCl3, 500.4 MHz): δ 8.96–8.95 (dd, J = 4.2, 1.7 Hz, 1H), 8.43 (br s, 1H), 8.38 (s, 1H), 8.24–8.19 (m, 4H), 7.79–7.77 (d, J = 8.1 Hz, 1H), 7.68 (s, 1H), 7.52–7.42 (m, 3H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 151.1, 149.2, 145.1, 139.6, 136.5, 133.7, 132.6, 130.4, 130.2, 129.1, 128.1, 127.8, 121.4, 117.6, 115.5 ppm; 19F {1H} NMR (CDCl3, 470.8 MHz): δ −62.2 ppm; 11B NMR (CDCl3, 128.4 MHz): δ 32.7 ppm; IR: ν = 1619, 1571, 1459, 1358, 1329, 1249, 1219, 1167, 1150, 1123, 1070, 924, 835, 772 cm–1; HRMS (ESI) m/z calc. for C18H13BN2F3 [M + H]+ 325.1124, found 325.1121.

2-(Quinolin-6-yl)-6-(trifluoromethoxy)-2,1-borazaronaphthalene (7b)

Purified by basic alumina column and obtained as a white solid (51.4 mg, 30%, 0.5 mmol scale); mp: 204–205 °C; 1H NMR (DMSO-d6, 500.4 MHz): δ 10.9 (s, 1H), 8.97–8.96 (m, 1H), 8.71 (s, 1H), 8.48–8.45 (t, J = 8.0 Hz, 2H), 8.30–8.27 (d, J = 11.6 Hz, 1H), 8.14–8.12 (d, J = 8.5 Hz, 1H), 7.91–7.89 (d, J = 8.9 Hz, 1H), 7.81 (s, 1H), 7.60–7.51 (m, 3H) ppm; 13C {1H} NMR (DMSO-d6, 125.8 MHz): δ 151.0, 148.6, 144.8, 141.9, 139.7, 136.4, 134.5, 133.5, 128.1, 127.7, 125.5, 121.8, 121.6, 120.7, 120.3 ppm; 19F {1H} NMR (CDCl3, 470.8 MHz): δ −57.0 ppm; 11B NMR (CDCl3, 128.4 MHz): δ 32.2 ppm; IR: ν = 1572, 1457, 1251, 1225, 1205, 1177, 1156, 1123, 996, 975, 942, 899, 876, 832, 801, 767, 754, 740, 478, 463 cm–1; HRMS (ESI) m/z calc. for C18H13BN2OF3 [M + H]+ 341.1073, found 341.1062.

6,8-Difluoro-2-(quinolin-6-yl)-2,1-borazaronaphthalene (7c)

Purified by basic alumina column and obtained as a white solid (27.2 mg, 19%, 0.5 mmol scale); mp: 243–244 °C; 1H NMR (CDCl3, 500.4 MHz): δ 8.95–8.94 (dd, J = 4.2, 1.7 Hz, 1H), 8.42 (br s, 1H), 8.34 (s, 1H), 8.23–8.18 (m, 3H), 8.07–8.05 (d, J = 11.6 Hz, 1H), 7.48–7.45 (d, J = 11.6 Hz, 1H), 7.43–7.40 (dd, J = 8.3, 4.3 Hz, 1H), 7.15–7.14 (d, J = 8.8 Hz, 1H), 7.08–7.03 (td, J = 8.4, 2.6 Hz, 1H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 155.9 (dd, J = 241.8, 11.7 Hz), 151.4 (dd, J = 246.3, 13.1 Hz), 151.1, 149.2, 144.2 (t, J = 3.7, 3.1 Hz), 136.5, 133.6, 132.6, 129.1, 128.1, 126.9 (dd, J = 9.5, 4.5 Hz), 125.8 (d, J = 12.9 Hz), 121.3, 109.3 (dd, J = 21.5, 3.8 Hz), 103.1 (dd, J = 28.3, 22.3 Hz) ppm; 19F {1H} NMR (CDCl3, 470.8 MHz): δ −119.8, −133.0 ppm; 11B NMR (CDCl3, 128.4 MHz): δ 32.0 ppm; IR: ν = 1567, 1455, 1438, 1403, 1289, 1242, 1177, 1111, 1040, 978, 890, 829, 794, 769, 741, 707, 682, 647, 617, 594 cm–1; HRMS (ESI) m/z calc. for C17H12BN2F2 [M + H]+ 293.1062, found 293.1051.

6-Isopropyl-2-(quinolin-6-yl)-2,1-borazaronaphthalene (7d)

Purified by basic alumina column and obtained as a white solid (85.3 mg, 58%, 0.5 mmol scale); mp: 148–149 °C; 1H NMR (CDCl3, 500.4 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 {1H} NMR (CDCl3, 125.8 MHz): δ 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 (CDCl3, 128.4 MHz): δ 32.2 ppm; IR: ν = 1568, 1453, 1441, 1422, 1287, 1235, 1223, 1187, 1176, 1123, 838, 830, 822, 810, 803, 777, 755, 725, 707, 464 cm–1; HRMS (ESI) m/z calc. for C20H20BN2 [M + H]+ 299.1720, found 299.1723.

2-(Quinolin-6-yl)-6-carbonitrile-2,1-borazaronaphthalene (7e)

Purified by basic alumina column and obtained as a white solid (43.0 mg, 31%, 0.5 mmol scale); mp: 150–151 °C; 1H NMR (DMSO-d6, 500.4 MHz): δ 11.0 (s, 1 H), 8.97 (s,1H), 8.73 (s, 1H), 8.47–8.46 (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), 7.60–7.54 (m, 2H) ppm; 13C {1H} NMR (DMSO-d6, 125.8 MHz): δ 151.2, 148.7, 144.7, 143.7, 136.5, 134.9, 134.4, 133.5, 130.7, 128.2, 127.7, 125.1, 121.6, 119.9, 119.4, 102.9 ppm; 11B NMR (CDCl3, 128.4 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–1; HRMS (ESI) m/z calc. for C18H13BN3 [M + H]+ 282.1203, found 282.1206.

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 mmol scale); mp: 176–177 °C; 1H NMR (DMSO-d6, 500.4 MHz): δ 10.8 (br s, 1H), 8.95 (s, 1H), 8.72 (s, 1H), 8.54–8.46 (m, 3H), 8.33–8.30 (d, J = 11.2 Hz, 1H), 8.16–8.11 (dd, J = 16.6, 7.3 Hz, 2H), 7.71–7.69 (d, J = 10.8 Hz, 1H), 7.59–7.53 (m, 2H) ppm; 13C {1H} NMR (DMSO-d6, 125.8 MHz): δ 151.1, 148.6, 146.6, 143.6, 142.3, 136.8, 136.5, 134.6, 133.5, 128.1, 127.7, 126.2, 123.3, 121.6 ppm; 11B NMR (CDCl3, 128.4 MHz): δ 32.6 ppm; IR: ν = 1598, 1567, 1460, 1445, 1374, 1353, 1321, 1264, 1240, 1219, 1194, 1182, 1116, 826, 791, 767, 741, 622, 588, 478 cm–1; HRMS (ESI) m/z calc. for C16H13BN3 [M + H]+ 258.1203, found 258.1198.

2-(3,5-Dimethylisoxazole-4yl)-6,5-borazaroisoquinoline (7g)

Purified by basic alumina column and obtained as a white solid (25.7 mg, 23%, 0.5 mmol scale); mp: 200–2017 °C; 1H NMR (CDCl3, 500.4 MHz): δ 8.90 (s, 1H), 8.50 (d, J = 5.7 Hz, 1H), 8.14 (d, J = 11.6 Hz, 1H), 8.06 (br s, 1H), 7.22 (d, J = 5.7 Hz, 1H), 7.15 (d, J = 11.7 Hz, 1H), 2.60 (s, 3H), 2.46 (s, 3H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 174.0, 162.1, 151.8, 147.7, 144.6, 143.5, 121.4, 112.7 ppm; 11B NMR (CDCl3, 128.4 MHz): δ 31.7 ppm; IR: ν = 3368, 3276, 2930, 1630, 1518, 1399, 1083, 967, 823, 798 cm–1; HRMS (ESI) m/z calc. for C12H13BN3O [M + H]+ 226.1152, found 226.1150.

2-(3-Fluorophenyl)-6,5-borazaroquinoline (7h)

Purified by basic alumina column and obtained as a white solid (30.9 mg, 27%, 0.5 mmol scale); mp: 246–247 °C; 1H NMR (CDCl3, 500.4 MHz): δ 8.61–8.59 (dd, J = 4.4, 1.4 Hz, 1H), 8.39–8.37 (d, J = 11.8 Hz, 1H), 8.07 (br s, 1H), 7.70–7.67 (td, J = 7.9, 0.7 Hz, 2H), 7.59–7.58 (dd, J = 9.6, 2.5 Hz, 1H), 7.53–7.51 (dd, J = 11.9, 2.2 Hz, 1H), 7.48–7.44 (m, 1H), 7.41–7.38 (dd, J = 8.2, 4.4 Hz, 1H), 7.18–7.14 (m, 1H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 163.0 (d, J = 245.1 Hz), 147.1, 144.0, 143.1, 135.8, 130.0 (d, J = 6.9 Hz), 128.3 (d, J = 3.2 Hz), 125.9, 123.0, 119.0 (d, J = 18.8 Hz), 116.8 (d, J = 20.3 Hz). 19F {1H} NMR (CDCl3, 470.8 MHz): δ −113.5 ppm; 11B NMR (CDCl3, 128.4 MHz): δ 31.7 ppm; IR: ν = 1596, 1568, 1445, 1418, 1377, 1323, 1289, 1261, 1236, 1226, 1198, 1164, 880, 868, 825, 799, 786, 753, 746, 689 cm–1; HRMS (ESI) m/z calc. for C13H11BN2F [M + H]+ 225.0999, 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 mmol scale); mp: 165–166 °C; 1H NMR (CDCl3, 500.4 MHz): δ 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), 7.50–7.49 (dd, J = 4.8, 2.7 Hz, 1H), 7.31–7.29 (dd, J = 11.6, 1.7 Hz, 1H), 7.21–7.20 (d, J = 5.7 Hz, 1H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 151.6, 147.5, 144.9, 143.3, 133.7, 130.3, 126.4, 121.9, 112.6 ppm; 11B NMR (CDCl3, 128.4 MHz): δ 31.1 ppm; IR: ν = 1623, 1568, 1516, 1465, 1426, 1385, 1325, 1204, 1172, 1129, 1077, 1043, 976, 939, 911, 827.8, 786, 755, 693, 557 cm–1; HRMS (ESI) m/z calc. for C11H10BN2S [M + H]+ 213.0658, found 213.0656.