Suzuki–Miyaura Cross-Coupling of Brominated 2,1-Borazaronaphthalenes with Potassium Alkenyltrifluoroborates

Abstract

Conditions have been developed for the palladium-catalyzed cross-coupling of 3-bromo-2,1-borazaronaphthalenes with potassium alkenyltrifluoroborates. Twenty-seven alkenyl-substituted azaborines have been synthesized through this method, providing access to a family of 2,1-borazaronaphthalenes with alkenyl substitution at the C3 position.

Introduction

2,1-Borazaronaphthalenes serve as versatile isosteres of all-carbon naphthalene substructures, which allows facile emplacement of a variety of substituents about the ring in an efficient and selective manner. Because of electronic desymmetrization brought about by the incorporation of a B—N bond in these aromatic systems, borazines have proven to be far more easily elaborated than naphthalenes themselves. Previous studies have focused on decorating these ring systems by utilizing arylation reactions. Alkenylation reactions are herein examined as a means to elaborate brominated 2,1-borazaronaphthalenes.

2-Alkenylnaphthalenes can be synthesized through a variety of transition-metal-catalyzed transformations, including Heck,¹ Mizoroki–Heck,² Hiyama,³ and Suzuki–Miyaura⁴ reactions. However, installation of an alkenyl substituent on a functionalized naphthalene is more challenging and often requires four or five steps.⁵ One method to afford alkenyl-substituted naphthalenes is to perform free-radical bromination of a methyl-substituted derivative followed by a Wittig olefination.⁶ Aside from the generation of a stoichiometric amount of difficult-to-remove phosphine oxide waste, additional substitution on the naphthalene can affect regiochemical control of free-radical bromination. Similarly, titanium-mediated carbonylation with dichloromethyl methyl ether followed by Wittig olefination afforded 2-alkyl-3-alkenylnaphthalene in moderate yield over two steps.⁷ In addition to the drawbacks described above, the use of a strong Lewis acid limits functional group tolerability in this approach. Further, there is only one example demonstrating the installation of an alkenyl substituent on a 2-arylnapthalene through the cross-coupling of naphthyl iodide and alkenylboronic acid, which provides 2-aryl-3-alkenylnaphthalene in good yield.⁸ The naphthyl iodide in this case was synthesized through gold-catalyzed cyclization/iodination, which required preparation of the requisite starting material (1-arylalka-2,3-dienyl acetate). Additionally, to the best of our knowledge, installation of an alkenyl substituent at the C3 position of a 1,2-disubstituted naphthalene has not been reported.

Accessing 2,1-borazaronaphthalenes, a class of azaborines⁹ that are BN-isosteres of naphthalene, with alkenyl substituents at the C3 position under mild reaction conditions would therefore serve as an example of how functionalized azaborines could be prepared more efficiently than their corresponding all-carbon analogues. Recently, we reported the bromination of 2,1-borazaronaphthalenes in high yield under mild reaction conditions with complete regiochemical control.¹⁰ Because of the inherent reactivity of azaborine, bromination occurs selectively at the C3 position of the azaborine in the presence of alkyl/aryl substituents on boron and nitrogen. We therefore envisioned these brominated azaborines as prefunctionalized electrophilic components in Suzuki–Miyaura cross-coupling reactions¹¹ with potassium alkenyltrifluoroborates¹² as a route to C3-alkenyl-substituted 2,1-borazaronaphthalenes, a compound class that has not been previously reported.

Results and Discussion

Optimization of the reaction of 3-bromo-2-methyl-2,1-borazaronaphthalene 1 with functionalized alkenyltrifluoroborate 2 was carried out by screening palladium sources, solvents, and bases. Side products represent the sum of homocoupling of the azaborine, protodebromination of the azaborine, and unidentifiable side products. Conditions for the cross-coupling of potassium aryltrifluoroborates with brominated 2,1-borazaronaphthalenes did not afford the desired product in appreciable yield (Table 1, entry 1). Therefore, several other ligands were screened in this reaction (entries 2–4 and 7). Of the ligands tested, triphenylphosphine (PPh₃) and 1,1′-bis(diphenylphosphino)ferrocene (dppf) provided the highest conversions to products. Several solvents/ratios were tested for these ligands, and the best result was obtained using toluene as the cosolvent and Pd(dppf)Cl₂ as the palladium source (entry 7). Attempts to lower palladium loading resulted in incomplete conversion of the starting material.

Table 1. Optimization of Cross-Coupling with Potassium Alkenyltrifluoroborates.

entry	palladium source (loading)	base	solvent	P:SPa
1	XPhos-Pd-G2 (4 mol %)	Cs2CO3	1:1 CPME/H2O	trace product
2	SPhos-Pd-G2 (4 mol %)	K2CO3	1:1 CPME/H2O	trace product
3	Pd2dba3/cataCXium A (4 mol %)	Cs2CO3	1:1 CPME/H2O	0.50:1.0
4	(Ph3P)2PdCl2 (6 mol %)	Cs2CO3	1:1 CPME/H2O	2.57:1.0
5	(Ph3P)2PdCl2 (6 mol %)	Cs2CO3	1:1 toluene/H2O	2.00:1.0
6	(Ph3P)2PdCl2 (6 mol %)	Cs2CO3	9:1 toluene/H2O	2.50:1.0
7	Pd(dppf)Cl2(6 mol %)	Cs2CO3	1:1 toluene/H2O	3.10:1.0
8	Pd(dppf)Cl2 (6 mol %)	Cs2CO3	1:1 CPME/H2O	1.85:1.0

^aProduct:side products.

A representative set of potassium alkenyltrifluoroborates were subjected to the developed reaction conditions with 3-bromo-2-methyl-2,1-borazaronaphthalene as the electrophilic partner (Table 2). Cyclic alkenyltrifluoroborates were successful nucleophiles in the reaction by providing the desired product in yields up to 90% (entries 5, 6, 8, and 10). Alkenyltrifluoroborates with alkyl substituents afforded the desired product in high yields (entries 2, 3, and 9). Vinyltrifluoroborate was a suitable nucleophile for the reaction because the azaborine was obtained in 70% yield (entry 7). Most importantly, cis-1-propenyltrifluoroborate was successfully employed in the reaction, affording the product in high yield without isomerization of the alkene (entry 3). The scalable nature of the cross-coupling reaction was demonstrated by performing the coupling on a 4.5 mmol scale (1 g of azaborine) with one-third palladium loading (2 mol %), which provided the desired product in similar yield (entry 8).

Table 2. Scope of the Cross-Coupling with Potassium Alkenyltrifluoroborates^c.

^aAlkenyltrifluoroborate ratio of 94:6 cis/trans employed in this reaction.

^bReaction completed on a 4.5 mmol scale with 2.0 mol % Pd(dppf)Cl₂.

^cReaction conditions (unless otherwise noted): 1.0 equiv of 3-bromo-2-methyl-2,1-borazaronaphthalene, 1.1 equiv of potassium alkenyltrifluoroborate, 6.0 mol % Pd(dppf)Cl₂, 3.0 equiv of base, 1:1 toluene/H₂O, and 60 °C for 18 h.

The developed reaction conditions were extended to cross-coupling of 3-bromo-2-phenyl-2,1-borazaronaphthalene with an array of potassium alkenyltrifluoroborates to demonstrate that azaborine can also be substituted with an aryl group on the boron. Six different alkenyltrifluoroborates were employed in the coupling and provided the desired product in yields up to 90%. The mild reaction conditions of the coupling were demonstrated in the successful coupling of an alkenyltrifluoroborate with an alkyl chloride substituent, affording the desired product in 90% yield (Table 3, entry 2). Cyclic alkenyltrifluoroborates were successfully engaged in the reaction as the desired products were obtained in high yields (entries 3, 4, and 6).

Table 3. Scope of the Cross-Coupling of Brominated B-Phenyl 2,1-Borazaronaphthalenes^a.

^aReaction conditions (unless otherwise noted): 1.0 equiv of 3-bromo-2-phenyl-2,1-borazaronaphthalene, 1.1 equiv of potassium alkenyltrifluoroborate, 6.0 mol % Pd(dppf)Cl₂, 3.0 equiv of base, 1:1 toluene/H₂O, and 60 °C for 18 h.

To demonstrate the versatility of this method, an array of brominated 2,1-borazaronaphthalenes were synthesized and subjected to the developed reaction conditions with 1-decenyltrifluoroborate as the nucleophile in the reaction. The cross-coupled products were obtained with secondary cyclic and acyclic groups on boron in yields up to 90% (Table 4, entries 1 and 2). Azaborines with various substitution patterns on the arene of boron were suitable electrophiles for coupling as the cross-coupled products were isolated in high yield (entries 3–5). Substitution on the nitrogen of the 2,1-borazaronaphthalenes did not affect the coupling as reactions with both N-allyl and N-benzyl substituents provided the desired product in high yields (entries 6 and 7).

Table 4. Scope of the Cross-Coupling with Various Brominated 2,1-Borazaronaphthalenes^a.

^aReaction conditions (unless otherwise noted): 1.0 equiv of 3-bromo-2,1-borazaronaphthalene, 1.1 equiv of potassium alkenyltrifluoroborate, 6.0 mol % Pd(dppf)Cl₂, 3.0 equiv of base, 1:1 toluene/H₂O, and 60 °C for 18 h.

To demonstrate that the developed reaction conditions can be directly applied to the functionalization of other azaborines, 6-bromo-2-methyl-3-phenyl-2,1-borazaronaphthalene was subjected to the reaction (eq 1). The desired product was obtained in 83% yield to afford C6-alkenyl-substituted 2,1-borazaronaphthalenes, examples of which are absent in the literature.

1

The reaction conditions were then extended to cross-coupling of 3,6-dibrominated 2,1-borazaronaphthalene. The addition of 2.2 equiv of 1-propenyltrifluoroborate provides a doubly cross-coupled product in 76% yield (eq 2).

2

In conclusion, a general method for Suzuki–Miyaura cross-coupling of brominated 2,1-borazaronaphthalenes with potassium alkenyltrifluoroborates has been developed. Azaborines with alkyl and aryl groups on boron and with or without substitution on nitrogen are suitable reagents for the coupling. Through this route, functionalized 2,1-borazaronaphthalenes with alkenyl substituents can be easily accessed for the first time.

Experimental Section

General Considerations

Toluene was dried over activated alumina. Standard benchtop techniques were employed for handling air-sensitive reagents. Melting points (°C) are uncorrected. NMR spectra were recorded on a 400 or 500 MHz spectrometer. ¹¹B NMR spectra were obtained on a spectrometer equipped with the appropriate decoupling accessories. All ¹¹B NMR chemical shifts were referenced to external BF₃·OEt₂ (0.0 ppm) with a negative sign indicating an upfield shift. Data are presented as follows: chemical shift (ppm), multiplicity (s = singlet, d = doublet, t = triplet, q = quadruplet, m = multiplet, br = broad), coupling constant J (Hz), and integration. Analytical thin-layer chromatography (TLC) was performed on TLC silica gel plates (0.25 mm) precoated with a fluorescent indicator. Visualization of the TLC plates was effected with ultraviolet light. Standard flash chromatography procedures were followed using 100–200 mesh silica gel. HRMS data were obtained by either ESI or CI using a TOF mass spectrometer.

Spectral Information of 2,1-Borazaronaphthalenes

2,1-Borazaronaphthalenes were synthesized¹³ and brominated¹⁰ according to methods previously described in the literature.

3-Bromo-2-(4-trifluoromethylphenyl)-2,1-borazaronaphthalene

The title compound was obtained as a white solid in 90% yield (1.0 mmol scale, 316.7 mg): mp 98–103 °C; ¹H NMR (500 MHz, CDCl₃) δ 8.49 (s, 1H), 8.07 (s, 1H), 7.98 (d, J = 7.8 Hz, 2H), 7.72 (d, J = 7.8 Hz, 2H), 7.64 (d, J = 7.9 Hz, 1H), 7.51–7.49 (m, 1H), 7.34 (d, J = 8.1 Hz, 1H), 7.30–7.27 (m, 1H); ¹³C NMR (125.8 MHz, CDCl₃) δ 147.3, 139.0, 133.6, 131.2 (d, J = 32.5 Hz), 129.7, 129.2, 126.5 (q, J = 275.8 Hz), 125.3, 124.6 (q, J = 3.6 Hz), 122.5, 118.4; ¹¹B NMR (128.38 MHz, CDCl₃) δ 32.9; IR (neat) 3367, 2923, 1556, 1427, 1120, 1070 cm^–1; HRMS (CI) m/z [M + H]⁺ calcd for C₁₅H₁₁BNF₃Br 352.9825, found 352.9802.

General Procedure for the Palladium-Catalyzed Cross-Coupling Reaction of Potassium Alkenyltrifluoroborates with Brominated 2,1-Borazaronaphthalenes

To a Biotage 10 mL microwave vial equipped with a magnetic stir bar were added 3-bromo-2,1-alkenyltrifluoroborate (1.1 mmol, 1.1 equiv), Cs₂CO₃ (3.0 mmol, 977 mg), Pd(dppf)Cl₂ (6.0 mol %, 42 mg), and potassium alkenyltrifluoroborate (1.0 mmol, 1.0 equiv). The vial was sealed with a cap, lined with a Teflon septum, and evacuated and purged with argon gas three times. Anhydrous degassed toluene (1.0 mL) and deionized H₂O (1.0 mL) were added under argon gas. The reaction mixture was heated at 60 °C for 18 h. After cooling to rt, the reaction mixture was extracted with EtOAc (3 × 10 mL) and dried (MgSO₄). After being concentrated in vacuo, the product was isolated by flash column chromatography and eluted with a gradient of EtOAc in hexanes (0 to 10% EtOAc).

N-(3-(2-Methyl-2,1-borazaronaphth-2-yl)allyl)morpholine (3a)

The title compound was obtained as a yellow solid in 88% yield (235.8 mg): mp 89–93 °C; ¹H NMR (500 MHz, CDCl₃) δ 7.79 (s, 1H), 7.72 (s, 1H), 7.58 (d, J = 7.5 Hz, 1H), 7.34–7.37 (m, 1H), 7.18 (d, J = 8.1 Hz, 1H), 7.15–7.12 (m, 1H), 5.24–5.23 (m, 1H), 5.12 (d, J = 2.5 Hz, 1H), 3.67 (t, J = 4.6 Hz, 4H), 3.31 (s, 2H), 2.48 (br, 4H), 0.79 (s, 3H); ¹³C NMR (125.8 MHz, CDCl₃) δ 149.0, 140.1, 129.6, 128.1, 125.0, 121.0, 117.4, 114.2, 67.3, 64.8, 53.9; ¹¹B NMR (128.38 MHz, CDCl₃) δ 36.7; IR (neat) 3319, 2928, 1566, 1434, 1109, 891 cm^–1; HRMS (ESI+) m/z [M + H]⁺ calcd for C₁₆H₂₂BN₂O 269.1825, found 269.1820.

2-Methyl-3-((E)-1-propen-1-yl)-2,1-borazaronaphthalene (3b)

The title compound was obtained as a yellow solid in 98% yield (179.3 mg): mp 69–75 °C; ¹H NMR (500 MHz, CDCl₃) δ 7.76 (s, 1H), 7.65 (s, 1H), 7.56 (d, J = 7.8 Hz, 1H), 7.36–7.29 (m, 1H), 7.16 (d, J = 8.0 Hz, 1H), 7.13–7.10 (m, 1H), 6.59 (d, J = 15.6 Hz, 1H), 6.19–6.12 (m, 1H), 1.91 (dd, J = 6.6, 1.5 Hz, 3H), 0.85 (s, 3H); ¹³C NMR (125.8 MHz, CDCl₃) δ 139.5, 138.7, 134.8, 129.3, 127.6, 126.5, 125.6, 121.0, 117.4, 19.4; ¹¹B NMR (128.38 MHz, CDCl₃) δ 37.2; IR (neat) 3364, 2924, 1614, 1457, 1343 cm^–1; HRMS (CI) m/z [M]⁺ calcd for C₁₂H₁₄BN 183.1219, found 183.1216.

2-Methyl-3-((Z)-1-propen-1-yl)-2,1-borazaronaphthalene (3c)

The title compound was obtained as a brown solid in 87% yield (159.2 mg): mp 98–103 °C; ¹H NMR (500 MHz, CDCl₃) δ 7.42 (s, 1H), 7.68 (s, 1H), 7.59 (d, J = 7.8 Hz, 1H), 7.37–7.34 (m, 1H), 7.19 (d, J = 8.0 Hz, 1H), 7.18–7.13 (m, 1H), 6.57–6.54 (m, 1H), 5.72–5.79 (m, 1H), 1.85 (dd, J = 7.0, 1.8 Hz, 3H), 0.74 (s, 3H); ¹³C NMR (125.8 MHz, CDCl₃) δ 140.8, 139.6, 132.1, 129.4, 127.8, 125.3, 125.0, 121.0, 117.6, 14.8; ¹¹B NMR (128.38 MHz, CDCl₃) δ 37.3; IR (neat) 3364, 2925, 1611, 1560, 1454 cm^–1; HRMS (CI) m/z [M]⁺ calcd for C₁₂H₁₄BN 183.1219, found 183.1213.

3-(Isopropen-1-yl)-2-methyl-2,1-borazaronaphthalene (3d)

The title compound was obtained as a yellow oil in 69% yield (126.2 mg). ¹H NMR (500 MHz, CDCl₃) δ 7.80 (s, 1H), 7.68 (s, 1H), 7.62 (d, J = 7.7 Hz, 1H), 7.39–7.36 (m, 1H), 7.19–7.15 (m, 2H), 5.21–5.11 (m, 1H), 5.07 (d, J = 1.9 Hz, 1H), 2.16 (s, 3H), 0.87 (s, 3H); ¹³C NMR (125.8 MHz, CDCl₃) δ 148.4, 139.6, 139.2, 129.6, 128.0, 125.1, 121.0, 117.4, 113.0, 23.9; ¹¹B NMR (128.38 MHz, CDCl₃) δ 36.9; IR (neat) 3368, 2933, 1567, 1462, 1453 cm^–1; HRMS (CI) m/z [M]⁺ calcd for C₁₂H₁₄BN 183.1219, found 183.1220.

4-(2-Methyl-2,1-borazaronaphthyl)-3,6-dihydro-2H-pyran (3e)

The title compound was obtained as a yellow oil in 82% yield (184.5 mg). ¹H NMR (500 MHz, CDCl₃) δ 7.75 (s, 1H), 7.73 (s, 1H), 7.59 (d, J = 7.8 Hz, 1H), 7.34–7.38 (m, 1H), 7.18 (d, J = 8.1 Hz, 1H), 7.16–7.13 (m, 1H), 5.83–5.82 (m, 1H), 4.36–4.35 (m, 2H), 3.97 (t, J = 5.4 Hz, 2H), 2.52–2.49 (m, 2H), 0.84 (s, 3H); ¹³C NMR (125.8 MHz, CDCl₃) δ 138.6, 137.6, 137.5, 128.5, 127.0, 124.1, 121.9, 120.1, 116.4, 65.2, 63.9, 28.1; ¹¹B NMR (128.38 MHz, CDCl₃) δ 36.7; IR (neat) 3325, 2923, 1572, 1458, 1032 cm^–1; HRMS (CI) m/z [M]⁺ calcd for C₁₄H₁₆BNO 225.1325, found 225.1336.

8-[3-(2-Methyl-2,1-borazaronaphthyl)]-1,4-dioxaspiro[4.5]dec-7-ene (3f)

The title compound was obtained as a white solid in 81% yield (227.6 mg): mp 83–88 °C; ¹H NMR (500 MHz, CDCl₃) δ 7.73 (s, 1H), 7.69 (s, 1H), 7.54–7.56 (m, 1H), 7.32–7.35 (m, 1H), 7.16 (d, J = 8 Hz, 1H), 7.13–7.10 (m, 1H), 5.66–5.65 (m, 1H), 4.05–4.02 (m, 4H), 2.63–2.59 (m, 2H), 2.50–2.49 (m, 2H), 1.93 (t, J = 6.5 Hz, 2H), 0.81 (s, 3H); ¹³C NMR (125.8 MHz, CDCl₃) δ 140.9, 139.5, 138.7, 129.4, 127.8, 125.2, 121.1, 120.9, 117.3, 108.3, 64.7, 36.5, 31.8, 28.7; ¹¹B NMR (128.38 MHz, CDCl₃) δ 37.0; IR (neat) 3308, 2927, 1609, 1460, 1047 cm^–1; HRMS (CI) m/z [M]⁺ calcd for C₁₇H₂₀BNO₂ 281.1587, found 281.1593.

2-Methyl-3-vinyl-2,1-borazaronaphthalene (3g)

The title compound was obtained as a light yellow solid in 70% yield (118.3 mg): mp 52–56 °C; ¹H NMR (500 MHz, CDCl₃) δ 7.70 (s, 1H), 7.64 (s, 1H), 7.55 (d, J = 7.8 Hz, 1H), 7.33–7.30 (m, 1H), 7.15 (d, J = 8.0 Hz, 1H), 7.10–7.08 (m, 1H), 6.73–6.66 (m, 1H), 5.87–5.85 (m, 1H), 5.74–5.71, (m, 1H), 0.70 (s, 3H); ¹³C NMR (125.8 MHz, CDCl₃) δ 140.7, 140.3, 139.9, 129.6, 128.2, 125.3, 121.2, 117.5, 114.8; ¹¹B NMR (128.38 MHz, CDCl₃) δ 37.2; IR (neat) 3365, 2927, 1610, 1457 cm^–1; HRMS (CI) m/z [M]⁺ calcd for C₁₁H₁₂BN 169.1063, found 169.1063.

3-(4,4-Difluoro-1-cyclohexen-1-yl)-2-methyl-2,1-borazaronaphthalene (3h)

The title compound was obtained as a white solid in 90% yield (233.1 mg): mp 72–76 °C; ¹H NMR (500 MHz, CDCl₃) δ 7.73 (s, 1H), 7.69 (s, 1H), 7.60 (d, J = 8.0 Hz, 1H), 7.41–7.37 (m, 1H), 7.20–7.15 (m, 2H), 5.59–5.56 (m, 1H), 2.78–2.72 (m, 2H), 2.67–2.64 (m, 2H), 2.25–2.17 (m, 2H), 0.82 (s, 3H); ¹³C NMR (125.8 MHz, CDCl₃) δ 140.8, 139.5, 139.1, 129.4, 128.0, 124.9, 123.3 (t, J = 239.6 Hz), 121.0, 118.2 (t, J = 4.9 Hz), 117.3, 35.3 (t, J = 26.4 Hz), 31.0 (t, J = 24.4 Hz), 27.8 (t, J = 5.2 Hz); ¹¹B NMR (128.38 MHz, CDCl₃) δ 36.2; IR (neat) 3397, 2936, 1613, 1560, 1425, 1058, cm^–1; HRMS (CI) m/z [M]⁺ calcd for C₁₅H₁₆BNF₂ 259.1344, found 259.1327.

3-[(E)-1-Decen-1-yl]-2-methyl-2,1-borazaronaphthalene (3i)

The title compound was obtained as a yellow solid in 75% yield (210.7 mg): mp 58–62 °C; ¹H NMR (500 MHz, CDCl₃) δ 7.79 (s, 1H), 7.65 (s, 1H), 7.57 (d, J = 7.75 Hz, 1H), 7.34–7.31 (m, 1H), 7.16–7.11 (m, 2H), 6.58 (d, J = 15.5 Hz, 1H), 6.18–6.12 (m, 1H), 2.26–2.22 (m, 2H), 1.53–1.47 (m, 2H), 1.40–1.28 (m, 10H), 0.92 (t, J = 6.9 Hz, 3H), 0.86 (s, 3H); ¹³C NMR (125.8 MHz, CDCl₃) δ 139.5, 138.8, 133.4, 132.2, 129.3, 127.6, 125.6, 121.0, 117.4, 34.0, 32.2, 30.0, 29.9, 29.7, 29.6, 23.0, 14.4; ¹¹B NMR (128.38 MHz, CDCl₃) δ 37.1; IR (neat) 3366, 2921, 1556, 1463, 977 cm^–1; HRMS (CI) m/z [M]⁺ calcd for C₁₉H₂₈BN 281.2315, found 281.2328.

tert-Butyl-4-[3-(2-methyl-2,1-borazaronaphthyl)]-3,6-dihydropyridine-1-(2H)-carboxylate (3j)

The title compound was obtained as a white solid in 65% yield (210.6 mg): mp 83–87 °C; ¹H NMR (500 MHz, CDCl₃) δ 7.75 (s, 1H), 7.69 (s, 1H), 7.57 (d, J = 7.7 Hz, 1H), 7.36–7.33 (m, 1H), 7.17 (d, J = 8.0 Hz, 1H), 7.14–7.11 (m, 1H), 5.71 (br, 1H), 4.07 (br, 2H), 3.64 (t, J = 5.5 Hz, 2H), 4.47 (br, 2H), 1.52 (s, 9H), 0.80 (s, 3H); ¹³C NMR (125.8 MHz, CDCl₃) δ 155.3, 139.9, 139.6, 138.7, 129.5, 128.0, 125.1, 121.1, 120.7, 117.4, 79.7, 44.3, 40.1, 34.9, 29.4, 28.8; ¹¹B NMR (128.38 MHz, CDCl₃) δ 32.0; IR (neat) 3327, 2975, 1677, 1563, 1423, 1163 cm^–1; HRMS (CI) m/z [M + H]⁺ calcd for C₁₉H₂₆BN₂O₂ 325.2087, found 325.2080.

2-Methyl-3-[(Z)-4-phenyl-1-buten-1-yl]-2,1-borazaronaphthalene (3k)

The title compound was obtained as a yellow solid in 83% yield (226.5 mg): mp 74–77 °C; ¹H NMR (500 MHz, CDCl₃) δ 7.66 (s, 1H), 7.59 (s, 1H), 7.55 (d, J = 7.7 Hz, 1H), 7.38–7.36 (m, 1H), 7.35–7.31 (m, 2H), 7.22–7.13 (m, 5H), 6.58 (dd, J = 11.5, 1.4 Hz, 1H), 5.69 (dt, J = 11.5, 7.2 Hz, 1H), 2.79 (t, J = 7.7 Hz, 2H), 2.70–2.45 (m, 2H), 0.73 (s, 3H); ¹³C NMR (125.8 MHz, CDCl₃) δ 142.3, 140.6, 139.7, 132.1, 129.9, 129.5, 128.9, 128.6, 127.9, 126.1, 125.3, 121.0, 117.5, 36.7, 30.6; ¹¹B NMR (128.38 MHz, CDCl₃) δ 37.4; IR (neat) 3373, 2925, 1556, 1452, 746, 703 cm^–1; HRMS (CI) m/z [M]⁺ calcd for C₁₉H₂₀BN 273.1689, found 273.1683.

3-[(E)-1-Decen-1-yl]-2-phenyl-2,1-borazaronaphthalene (4a)

The title compound was obtained as a white oil in 73% yield (250.3 mg). ¹H NMR (500 MHz, CDCl₃) δ 8.05 (s, 1H), 7.91 (s, 1H), 7.77–7.75 (m, 2H), 7.69 (d, J = 8.0 Hz, 1H), 7.51–7.47 (m, 3H), 7.42–7.39 (s, 1H), 7.26 (d, J = 8.0 Hz, 1H), 7.22 (t, J = 7.5 Hz, 1H), 6.70 (d, J = 15.5 Hz, 1H), 6.07 (dt, J = 15.4, 7.0 Hz, 1H), 2.21 (q, J = 7.0 Hz, 2H), 1.50–1.45 (m, 2H), 1.40–1.35 (m, 10H), 0.96 (t, J = 7.0 Hz, 3H); ¹³C NMR (125.8 MHz, CDCl₃) δ 139.8, 139.6, 133.2, 132.7, 132.3, 129.5, 128.8, 128.2, 128.0, 125.9, 121.0, 118.0, 33.7, 32.2, 29.9, 29.8, 29.7, 29.6, 23.0, 14.4; ¹¹B NMR (128.38 MHz, CDCl₃) δ 34.4; IR (neat) 3370, 2923, 2852, 1421, 749 cm^–1; HRMS (CI) m/z [M + Na]⁺ calcd for C₂₄H₃₀BNNa 366.2369, found 366.2375.

3-(6-Chloro-1-hexen-1-yl)-2-phenyl-2,1-borazaronaphthalene (4b)

The title compound was obtained as a brown oil in 90% yield (288.9 mg). ¹H NMR (500 MHz, CDCl₃) δ 8.03 (s, 1H), 7.92 (s, 1H), 7.72 (dd, J = 7.25, 1.5 Hz, 2H), 7.68 (d, J = 7.5 Hz, 1H), 7.50–7.46 (m, 3H), 7.42–7.39 (m, 1H), 7.26 (d, J = 8 Hz, 1H), 7.23–7.20 (m, 1H), 6.68 (d, J = 15.5 Hz, 1H), 6.00 (dt, J = 15.4, 7.0 Hz, 1H), 3.57 (t, J = 6.5 Hz, 2H), 2.23–2.19 (m, 2H), 1.86–1.83 (m, 2H), 1.62–1.58 (m, 2H); ¹³C NMR (125.8 MHz, CDCl₃) δ 140.1, 139.6, 133.4, 133.1, 131.1, 129.5, 128.8, 128.2, 128.1, 125.7, 121.7, 118.0, 45.3, 32.7, 32.3, 27.0; ¹¹B NMR (128.38 MHz, CDCl₃) δ 35.0; IR (neat) 3373, 2933, 1558, 1421, 969, 752 cm^–1; HRMS (CI) m/z [M]⁺ calcd for C₂₀H₂₁BNCl 321.1456, found 321.1463.

3-(1-Cyclohexen-1-yl)-2-phenyl-2,1-borazaronaphthalene (4c)

The title compound was obtained as a yellow solid in 79% yield (225.1 mg): mp 88–92 °C; ¹H NMR (500 MHz, CDCl₃) δ 7.95 (s, 1H), 7.85 (s, 1H), 7.79–7.7.78 (m, 2H), 7.66 (d, J = 7.5 Hz, 1H), 7.45–7.39 (m, 4H), 7.28 (d, J = 8.0 Hz, 1H), 7.22–7.19 (m, 1H), 5.73–5.71 (m, 1H), 2.19–2.13 (m, 4H), 1.66–1.65 (m, 4H); ¹³C NMR (125.8 MHz, CDCl₃) δ 142.3, 140.5, 139.6, 132.8, 129.5, 128.9, 128.1, 128.0, 125.6, 124.2, 121.5, 117.9, 29.9, 26.1, 23.5, 22.6; ¹¹B NMR (128.38 MHz, CDCl₃) δ 34.0; IR (neat) 3375, 2920, 1558, 1451, 751 cm^–1; HRMS (CI) m/z [M]⁺ calcd for C₂₀H₂₀BN 285.1689, found 285.1705.

4-(2-Phenyl-2,1-borazaronaphthyl)-3,6-dihydro-2H-pyran (4d)

The title compound was obtained as a white solid in 86% yield (246.8 mg): mp 112–115 °C; ¹H NMR (500 MHz, CDCl₃) δ 8.02 (s, 1H), 7.91 (s, 1H), 7.76–7.68 (m, 2H), 7.69 (d, J = 7.5 Hz, 1H), 7.47–7.42 (m, 4H), 7.29 (d, J = 8.1 Hz, 1H), 7.24–7.21 (m, 1H), 5.75–5.73 (m, 1H), 4.31–4.29 (m, 2H), 3.84 (t, J = 5.5 Hz, 2H), 2.30 (td, J = 5.3, 2.7 Hz, 2H); ¹³C NMR (125.8 MHz, CDCl₃) δ 140.9, 139.7, 139.4, 132.7, 129.6, 128.9, 128.4, 128.2, 125.3, 122.8, 121.7, 118.0, 66.2, 64.9, 29.5; ¹¹B NMR (128.38 MHz, CDCl₃) δ 34.0; IR (neat) 3287, 2930, 1564, 1455, 1229, 758 cm^–1; HRMS (CI) m/z [M]⁺ calcd for C₁₉H₁₈BNO 287.1481, found 287.1487.

2-Phenyl-3-(isopropen-1-yl)-2,1-borazaronaphthalene (4e)

The title compound was obtained as a brown oil in 76% yield (186.2 mg). ¹H NMR (500 MHz, CDCl₃) δ 7.96 (br, 2H), 7.92–7.81 (m, 2H), 7.70 (d, J = 7.5 Hz, 1H), 7.47–7.43 (m, 4H), 7.29 (d, J = 8.0 Hz, 1H), 7.25–7.22 (m, 1H), 5.06–5.02 (m, 2H), 1.99 (s, 3H); ¹³C NMR (125.8 MHz, CDCl₃) δ 149.2, 140.9, 139.5, 132.6, 129.5, 128.7, 128.2, 128.0, 125.2, 121.5, 117.8, 113.0, 24.1; ¹¹B NMR (128.38 MHz, CDCl₃) δ 33.6; IR (neat) 3367, 2925, 1573, 1463, 757 cm^–1; HRMS (CI) m/z [M]⁺ calcd for C₁₇H₁₆BN 245.1376, found 245.1377.

8-(2-Phenyl-2,1-borazaronaphthyl)-1,4-dioxaspiro[4.5]dec-7-ene (4f)

The title compound was obtained as a white solid in 81% yield (277.8 mg): mp 108–112 °C; ¹H NMR (500 MHz, CDCl₃) δ 7.98 (s, 1H), 7.90 (s, 1H), 7.80–7.78 (m, 2H), 7.65 (d, J = 7.5 Hz, 1H), 7.45–7.39 (m, 4H), 7.28 (d, J = 8.0 Hz, 1H), 7.21–7.18 (m, 1H), 6.62–5.60 (m, 1H), 4.05–3.98 (m, 4H), 2.47–2.46 (m, 2H), 2.38 (td, J = 6.3, 1.6 Hz, 2H), 1.79 (t, J = 6.5 Hz, 2H); ¹³C NMR (125.8 MHz, CDCl₃) δ 141.9, 141.1, 139.6, 132.7, 129.4, 128.9, 128.1, 128.1, 125.3, 121.5, 121.1, 117.8, 108.2, 64.5, 36.4, 31.6, 29.0; ¹¹B NMR (128.38 MHz, CDCl₃) δ 34.4; IR (neat) 3326, 1560, 1421, 1112, 755 cm^–1; HRMS (CI) m/z [M]⁺ calcd for C₂₂H₂₂BNO₂ 343.1744, found 343.1756.

2-Isopropyl-3-[(E)-1-decen-1-yl]-2,1-borazaronaphthalene (5a)

The title compound was obtained as a colorless oil in 81% yield (247.8 mg). ¹H NMR (500 MHz, CDCl₃) δ 7.92 (s, 1H), 7.67 (s, 1H), 7.62 (d, J = 7.8 Hz, 1H), 7.39–7.35 (m, 1H), 7.24 (d, J = 8.0 Hz, 1H), 7.18–7.15 (m, 1H), 6.69 (dd, J = 15.6, 0.4 Hz, 1H), 6.13–6.18 (m, 1H), 2.31–2.26 (m, 2H), 1.96–1.92 (m, 1H), 1.57–1.54 (m, 2H), 1.43–1.35 (m, 10H), 1.23 (d, J = 7.3 Hz, 6H), 0.97 (t, J = 6.9 Hz, 3H); ¹³C NMR (125.8 MHz, CDCl₃) δ 139.6, 138.4, 132.2, 131.1, 129.3, 127.6, 125.7, 121.2, 117.7, 33.8, 32.2, 30.0, 29.9, 29.7, 29.6, 23.0, 19.6, 14.4; ¹¹B NMR (128.38 MHz, CDCl₃) δ 38.8; IR (neat) 3424, 2924, 1560, 1427, 969 cm^–1; HRMS (CI) m/z [M]⁺ calcd for C₂₁H₃₂BN 309.2628, found 309.2633.

2-Cyclopropyl-3-[(E)-1-decen-1-yl]-2,1-borazaronaphthalene (5b)

The title compound was obtained as a yellow solid in 90% yield (276.3 mg): mp 51–55 °C; ¹H NMR (500 MHz, CDCl₃) δ 7.92 (s, 1H), 7.56 (d, J = 7.7 Hz, 1H), 7.32–7.29 (m, 1H), 7.18 (s, 1H), 7.11 (t, J = 7.9 Hz, 2H), 6.69 (d, J = 15.6 Hz, 1H), 6.38–6.24 (m, 1H), 2.25 (q, J = 7.2 Hz, 2H), 1.52–1.48 (m, 2H), 1.39–1.28 (m, 10H), 0.92–0.89 (m, 5H), 0.66–0.55 (m, 3H); ¹³C NMR (125.8 MHz, CDCl₃) δ 139.5, 138.5, 132.8, 132.4, 129.3, 127.6, 125.5, 121.0, 117.4, 34.0, 32.2, 30.0, 29.9, 29.7, 29.6, 23.0, 14.4, 6.0; ¹¹B NMR (128.38 MHz, CDCl₃) δ 37.1; IR (neat) 3374, 3010, 2920, 1557, 1428, 1105 cm^–1; HRMS (CI) m/z [M]⁺ calcd for C₂₁H₃₀BN 307.2471, found 307.2484.

3-[(E)-1-Decen-1-yl]-2-(4-fluorophenyl)-2,1-borazaronaphthalene (5c)

The title compound was obtained as a yellow oil in 88% yield (317.6 mg). ¹H NMR (500 MHz, CDCl₃) δ 8.01 (s, 1H), 7.85 (s, 1H), 7.71–7.65 (m, 3H), 7.41–7.37 (m, 1H), 7.25 (d, J = 8.5 Hz, 1H), 7.22–7.19 (m, 1H), 7.17–7.14 (m, 2H), 6.62 (dd, J = 15.6, 0.7 Hz, 1H), 6.01 (dt, J = 15.5, 7.0 Hz, 1H), 2.17 (qd, J = 7.3, 1.3 Hz, 2H), 1.48–1.49 (m, 2H), 1.36–1.29 (m, 10H), 0.92 (t, J = 7.0 Hz, 3H); ¹³C NMR (125.8 MHz, CDCl₃) δ 163.6 (d, J = 252 Hz), 139.8, 139.3, 134.9 (d, J = 7.4 Hz), 132.4, 132.3, 129.3, 127.9, 125.7, 121.6, 117.8, 115.1 (d, J = 19.6 Hz), 33.5, 32.0, 29.7, 29.6, 29.5, 29.4, 22.8, 14.2; ¹¹B NMR (128.38 MHz, CDCl₃) δ 33.9; IR (neat) 3375, 2923, 1595, 1224, 832 cm^–1; HRMS (CI) m/z [M]⁺ calcd for C₂₄H₂₉BNF 361.2377, found 361.2368.

3-[(E)-1-Decen-1-yl]-2-(3-methoxyphenyl)-2,1-borazaronaphthalene (5d)

The title compound was obtained as a colorless oil in 81% yield (302.1 mg). ¹H NMR (500 MHz, CDCl₃) δ 8.04 (s, 1H), 7.94 (s, 1H), 7.68 (d, J = 7.7 Hz, 1H), 7.43–7.40 (m, 2H), 7.32 (d, J = 7.2 Hz, 1H), 7.29–7.27 (m, 2H), 7.22 (t, J = 7.5 Hz, 1H), 7.01 (dd, J = 8.2, 2.7 Hz, 1H), 6.68 (d, J = 15.6 Hz, 1H), 6.10–6.04 (m, 1H), 3.89 (s, 3H), 2.21–2.16 (m, 2H), 1.47–1.43 (m, 2H), 1.36–1.28 (m, 10H), 0.93 (t, J = 6.9 Hz, 3H); ¹³C NMR (125.8 MHz, CDCl₃) δ 159.4, 139.8, 139.5, 132.5, 132.3, 129.5, 129.4, 128.0, 125.9, 125.5, 121.7, 118.3, 118.0, 114.4, 55.4, 33.7, 32.2, 29.9, 29.8, 29.6, 29.6, 23.0, 14.4; ¹¹B NMR (128.38 MHz, CDCl₃) δ 34.8; IR (neat) 3366, 2924, 1558, 1451, 1236, 971, 761 cm^–1; HRMS (CI) m/z [M + H]⁺ calcd for C₂₅H₃₃BNO 374.2655, found 374.2661.

3-[(E)-1-Decen-1-yl]-2-(4-trifluorophenyl)-2,1-borazaronaphthalene (5e)

The title compound was obtained as a light brown oil in 83% yield (341.3 mg). ¹H NMR (500 MHz, CDCl₃) δ 8.03 (s, 1H), 7.91 (s, 1H), 7.80 (d, J = 7.7 Hz, 2H), 7.70–7.68 (m, 3H), 7.42–7.39 (m, 1H), 7.27 (d, J = 8.1 Hz, 1H), 7.22–7.21 (m, 1H), 6.56 (dd, J = 15.6, 1.0 Hz, 1H), 5.60–5.94 (m, 1H), 2.14 (m, 2H), 1.42–1.39 (m, 2H), 1.27–1.32 (m, 10H), 0.90 (t, J = 5.1 Hz, 3H); ¹³C NMR (125.8 MHz, CDCl₃) δ 140.1, 139.1, 133.1, 132.8, 131.9, 130.4 (d, J = 32.3 Hz), 129.4, 128.1, 126.3 (q, J = 272.2 Hz), 125.8, 124.6 (q, J = 3.7 Hz), 121.9, 117.9, 33.5, 32.0, 29.6, 29.5, 29.3, 22.8, 14.2; ¹¹B NMR (128.38 MHz, CDCl₃) δ 34.5; IR (neat) 3395, 2924, 1559, 1323, 969, 836 cm^–1; HRMS (CI) m/z [M]⁺ calcd for C₂₅H₂₉BNF₃ 411.2345, found 411.2353.

1-Allyl-3-[(E)-1-decen-1-yl]-2-methyl-2,1-borazaronaphthalene (5f)

The title compound was obtained as a light yellow oil in 62% yield (199.0 mg). ¹H NMR (500 MHz, CDCl₃) δ 7.84 (s, 1H), 7.61 (d, J = 7.0 Hz, 1H), 7.39 (dd, J = 4.7, 1.2 Hz, 2H), 7.17–7.13 (m, 1H), 6.66 (dd, J = 15.5, 1.0 Hz, 1H), 6.10–6.01 (m, 2H), 5.15 (dd, J = 10.5, 1.4 Hz, 1H), 4.99 (dd, J = 17.2, 1.3 Hz, 1H), 4.72 (dd, J = 4.1, 2.0 Hz, 2H), 2.27–2.22 (m, 2H), 1.54–1.49 (m, 2H), 1.41–1.27 (m, 10H), 0.93–0.89 (m, 6H); ¹³C NMR (125.8 MHz, CDCl₃) δ 141.2, 137.7, 134.7, 132.7, 131.3, 130.2, 127.8, 126.7, 120.8, 115.9, 115.5, 49.8, 33.8, 32.2, 30.1, 29.9, 29.7, 29.6, 23.0, 14.4; ¹¹B NMR (128.38 MHz, CDCl₃) δ 38.7; IR (neat) 2923, 1556, 1405, 1212, 968 cm^–1; HRMS (CI) m/z [M]⁺ calcd for C₂₂H₃₂BN 321.2628, found 321.2633.

1-Benzyl-3-[(E)-1-decen-1-yl]-2-methyl-2,1-borazaronaphthalene (5g)

The title compound was obtained as a light brown oil in 90% yield (333.9 mg). ¹H NMR (500 MHz, CDCl₃) δ 7.97 (s, 1H), 7.68 (d, J = 7.0 Hz, 1H), 7.35–7.27 (m, 5H), 7.19–7.16 (m, 3H), 6.78 (dd, J = 15.6, 0.6 Hz, 1H), 6.19 (dt, J = 15.5, 6.9 Hz, 1H), 5.38 (s, 2H), 2.36–2.37 (m, 2H), 1.63–1.57 (m, 2H), 1.50–1.39 (m, 10H), 1.00–0.98 (m, 6H); ¹³C NMR (125.8 MHz, CDCl₃) δ 141.3, 138.8, 138.02, 132.7, 131.4, 130.2, 129.0, 127.9, 127.1, 126.9, 126.1, 120.9, 115.9, 51.4, 33.8, 32.2, 30.1, 29.9, 29.8, 29.7, 23.0, 14.4; ¹¹B NMR (128.38 MHz, CDCl₃) δ 39.0; IR (neat) 2924, 2853, 1610, 1492, 1402, 1360, 967 cm^–1; HRMS (CI) m/z [M]⁺ calcd for C₂₆H₃₄BN 371.2784, found 371.2791.

3-[(E)-1-Decen-1-yl]-2-(4-methylphenyl)-2,1-borazaronaphthalene (5h)

The title compound was obtained as a light yellow oil in 80% yield (285.6 mg). ¹H NMR (500 MHz, CDCl₃) δ 8.04 (s, 1H), 7.91 (s, 1H), 7.68 (d, J = 7.5 Hz, 1H), 7.57–7.52 (m, 2H), 7.42–7.37 (m, 2H), 7.29–7.25 (m, 2H), 7.21 (t, J = 7.5 Hz, 1H), 6.68 (d, J = 15.5 Hz, 1H), 6.07 (dt, J = 15.4, 7.0 Hz, 1H), 2.47 (s, 3H), 2.20 (q, J = 6.9 Hz, 2H), 1.49–1.46 (m, 2H), 1.39–1.33 (m, 10H), 0.94 (t, J = 6.9 Hz, 3H); ¹³C NMR (125.8 MHz, CDCl₃) δ 139.7, 137.5, 133.9, 132.7, 132.2, 130.3, 129.5, 128.1, 128.0, 125.9, 121.6, 117.9, 33.7, 32.2, 30.0, 29.9, 29.7, 29.6, 23.0, 21.9, 14.4; ¹¹B NMR (128.38 MHz, CDCl₃) δ 34.7; IR (neat) 3369, 2923, 2852, 1612, 1557, 1450, 969 cm^–1; HRMS (CI) m/z [M]⁺ calcd for C₂₅H₃₂BN 357.2628, found 357.2632.

6-[(E)-1-Decen-1-yl]-2-methyl-3-phenyl-2,1-borazaronaphthalene (6)

The title compound was obtained as a brown oil in 83% yield (296.3 mg). ¹H NMR (500 MHz, CDCl₃) δ 7.85 (s, 1H), 7.77 (s, 1H), 7.57 (d, J = 1.5 Hz, 1H), 7.47–7.41 (m, 5H), 7.33–7.31 (m, 1H), 7.16 (d, J = 8.5 Hz, 1H), 6.46 (d, J = 16.0 Hz, 1H), 6.23 (dt, J = 15.7, 6.9 Hz, 1H), 2.27–2.22 (m, 2H), 1.52–1.48 (m, 2H), 1.39–1.28 (m, 10H), 0.92 (t, J = 7.0 Hz, 3H), 0.83 (s, 3H); ¹³C NMR (125.8 MHz, CDCl₃) δ 145.1, 141.8, 139.0, 131.3, 130.0, 129.6, 128.5, 128.4, 127.2, 126.3, 126.0, 125.3, 117.7, 33.4, 32.2, 29.8, 29.8, 29.6, 29.6, 23.0, 14.4; ¹¹B NMR (128.38 MHz, CDCl₃) δ 36.4; IR (neat) 3372, 2924, 2853, 1617, 1577, 1456, 962, 762 cm^–1; HRMS (CI) m/z [M]⁺ calcd for C₂₅H₃₂BN 357.2628, found 357.2621.

2-Methyl-3,6-di[(E)-1-propen-1-yl]-2,1-borazaronaphthalene (7)

The title compound was obtained as a yellow solid in 76% yield (169.4 mg): mp 106–110 °C; ¹H NMR (500 MHz, CDCl₃) δ 7.75 (s, 1H), 7.60 (s, 1H), 7.48 (d, J = 1.5 Hz, 1H), 7.38 (dd, J = 8.3, 1.9 Hz, 1H), 7.07 (d, J = 8.4 Hz, 1H), 6.62 (dd, J = 15.7, 0.7 Hz, 1H), 6.48 (dd, J = 15.7, 1.5 Hz, 1H), 6.26–6.14 (m, 2H), 1.95–1.93 (m, 6H), 0.86 (s, 3H); ¹³C NMR (125.8 MHz, CDCl₃) δ 137.4, 137.6, 133.9, 130.1, 130.0, 125.7, 125.4, 124.5, 124.3, 123.1, 116.6, 18.3, 17.8; ¹¹B NMR (128.38 MHz, CDCl₃) δ 37.2; IR (neat) 3371, 2957, 2910, 1610, 1557, 1436 cm^–1; HRMS (CI) m/z [M]⁺ calcd for C₁₅H₁₈BN 223.1532, found 223.1532.

Supporting Information Available

Copies of ¹H, ¹³C, and ¹¹B NMR spectra for all compounds. This material is available free of charge via the Internet at http://pubs.acs.org.

The authors declare no competing financial interest.

Funding Statement

National Institutes of Health, United States