Palladium-Catalyzed Hiyama Cross-Coupling of Aryltrifluorosilanes with Aryl and Heteroaryl Chlorides

Abstract

An efficient, palladium-catalyzed Hiyama cross-coupling reaction of aryltrifluorosilanes with aryl chlorides has been developed. A wide variety of functionalized biaryl derivatives were isolated in good to excellent yields. The scope of this reaction has also been extended to heteroaryl chlorides, affording the corresponding heterobiaryl compounds in high yields.

Metal-mediated cross-coupling reactions are among the most powerful methods of creating carbon-carbon bonds in organic chemistry. In the past forty years, organomagnesium (Kumada-Corriu), organoboron (Suzuki-Miyaura), organotin (Stille), organozinc (Negishi) and organosilane (Hiyama) derivatives have been developed as nucleophilic partners for cross-coupling reactions.^1–5 Each of these classes has its own limitations, often because of the instability or toxicity of the reagent. In this context, organosilicon derivatives, known to be easy to handle, stable (toward air and moisture), and less toxic compared to other organometallic reagents such as organostannanes, appeared as interesting partners for the development of cross-coupling reactions.⁵

Previously, silane derivatives have been seen as poor cross-coupling partners because of the weak polarization of the carbon-silicon bond. This limitation has been overcome through the generation of a pentacoordinate silicon intermediate in situ,² using a fluoride activator⁷ such as tetra-n-butylammonium fluoride (TBAF) or an inorganic base.^8–12 Subsequently, efficient partners for Hiyama cross-coupling such as organo(trialkoxy)silanes,^13–19 organosilanolates,^20–23 organobis(catechol)silicates,²⁴ organosilatranes,²⁵ and organohalosilanes^26–32 have been developed.

Among these types of organosilanes, organotrifluorosilanes are interesting because of their stability to heat, air and moisture, easy handling, and facile accessibility from commercially available trichlorosilanes.³³ Surprisingly, although they have been used in a wide range of metal-mediated reactions as efficient partners,^34–39 only a few examples of Hiyama cross-coupling reactions of trifluorosilanes have been reported. The first report came from Hiyama and coworkers, who achieved the cross-coupling reaction of alkyltrifluorosilanes with a variety of aryl iodides and bromides using a catalytic amount of Pd(PPh₃)₄, but a large excess of TBAF.^29–30 More recently, Fu has developed a nickel-catalyzed Hiyama cross-coupling of aryltrifluorosilanes with secondary alkyl halides (iodides, bromides and chlorides).^31–32 To the best of our knowledge, there are no examples of aryltrifluorosilane cross-couplings with aryl chlorides. Therefore, we were intrigued to see if they could be suitable partners for this transformation.

Herein, we describe an efficient palladium-catalyzed Hiyama cross-coupling of aryltrifluorosilanes with both aryl- and heteroaryl chlorides for the synthesis of biaryls and heterobiaryls. The catalytic system was first optimized on a model reaction between phenyltrifluorosilane 1a and 4-chloroanisole in the presence of 2.5 mol % Pd(OAc)₂ as catalyst. After a ligand screen with various ligands (Figure 1) was performed in t-BuOH as solvent (Table 1, entries 1–3), XPhos emerged as the most efficient, yielding 2a in 71% yield.

Figure 1.

Ligands utilized in optimization studies.

TABLE 1.

Optimization

entry	1a equiv	ligand	additive (equiv)	solvent	% isoltd yield
1	1	SPhos	TBAF (2)	t-BuOH	53
2	1	CatacXiumA	TBAF (2)	t-BuOH	38
3	1	XPhos	TBAF (2)	t-BuOH	71
4	1	XPhos	TBAF (2)	THF	51
5	1	XPhos	TBAF (2)	toluene	47
6	1	XPhos	CsF (3)	t-BuOH	0
7	1	XPhos	NaOH (3)	t-BuOH	0
8	1	XPhos	KF (3)	t-BuOH	0
9	1	XPhos	TBAF (2)	t-BuOH	73
10	1.5	XPhos	TBAF (2.5)	t-BuOH	78

Other solvents were tested (Table 1, entries 4–5), but all of them led to a decrease in reaction yield. When TBAF was replaced with various inorganic bases (Table 1, entries 6–8), no reaction occurred. Finally, the ratio of aryltrifluorosilane 1a and TBAF was studied, and 2a was isolated in 78% yield by employing 1.5 equivalents of 1a and 2.5 equivalents of TBAF at 60 °C.

We then chose to investigate the electrophile compatibility in this palladium-catalyzed Hiyama cross-coupling reaction under the conditions previously optimized. The iodide, bromide and triflate provided the desired product in 95, 88 and 86% yields, respectively (Table 2, entries 1, 2, and 4). The aryl chloride afforded a slightly lower yield (78%) (Table 2, entry 3). On the other hand, the tosylate and mesylate were not effective coupling partners under these conditions, affording the cross-coupled product in low yields. Given the low price and wide range of commercially available aryl chlorides, we used them as the electrophiles of choice.

TABLE 2.

Electrophile Compatibility

entry	X	% isoltd yield
1	I	95
2	Br	88
3	Cl	78
4	OTf	86
5	OTs	16
6	OMs	24

We were pleased to find that a wide variety of substituted aryl chlorides provided the expected biaryl derivatives in good to excellent yields (Table 3). Even the hindered 1-chloro-4-methoxy-2,6-dimethylbenzene could be used with phenyltrifluorosilane 1a to give the coupling product 2d with an excellent yield of 97% by simply increasing the temperature to 100 °C (Table 3, entry 4). We were delighted to observe the compatibility of this reaction with both electron-rich (Table 3, entries 1–5) and electron-poor (Table 3, entries 6–12) aryl chlorides. Notably, a large functional group array including ether, amine, nitrile, nitro, ester, aldehyde and ketone functional groups was tolerated. Substituted 3-methoxy- and 4-methylbenzenetrifluorosilanes 1b and 1c were also suitable partners in this process, affording the corresponding products 2k and 2n in 80 and 81% yields, respectively (Table 3, entries 13–14). Interestingly, scaling the reaction up to 6.4 mmol of 4-chloroacetophenone allowed a reduction in the catalyst loading to 2 mol % of palladium and 4 mol % of ligand, yielding the biaryl 2m in 96% yield.

TABLE 3.

Scope of Aryl Chlorides

entry	silane	Ar-Cl	product	%isoltd yield
1	1a		2a	78
2	1a		2b	90
3	1a		2c	70
4	1a		2d	97a
5	1a		2e	90
6	1a		2f	75
7	1a		2g	89
8	1a		2h	73
9	1a		2i	91
10	1a		2j	98
11	1a		2k	85
12	1a		2l	86 (96)b
13	1b		2m	80
14	1c		2n	81

^a100 °C;

^bReaction performed on a 6.4 mmol scale using 2 mol % of Pd(OAc)₂, 4 mol % of XPhos, 1.5 equiv of 1a and 2.5 equiv of TBAF.

To expand the scope of this transformation even further, heteroaryl chlorides were next examined. 3-Arylpyridines 3a, 3b, 3c, 3d and 3e were obtained in yields ranging from 74 to 94% (Table 4, entry 1–5). 4-Chloroquinaldine was coupled with phenyltrifluorosilane 1a, providing the corresponding heterobiaryl 3f in moderate yield (Table 4, entry 6). Thienyl and furanyl chlorides also reacted, affording coupled products 3g and 3h in 90 and 74% yields, respectively (Table 4, entries 7 and 8). As before, sensitive functional groups such as aldehydes were tolerated under the reaction conditions. In addition, 6-chloroisoquinoline gave the desired heterobiaryl derivatives 3i and 3j in good yields, although it required a higher temperature to cross-couple (Table 3, entries 9 and 10). Moreover, substituted trifluorosilanes 1b and 1c performed as efficient partners in Hiyama cross-coupling with heteroaryls, leading to the expected products 3b and 3e with good yields (Table 4, entries 2 and 5).

TABLE 4.

Scope of Heteroaryl Chlorides

entry	silane	HetAr-Cl	product	% isoltd yield
1	1a		3a	74
2	1b		3b	76
3	1a		3c	78
4	1a		3d	84
5	1c		3e	94
6	1a		3f	65
7	1a		3g	90
8	1a		3h	74
9	1a		3i	85a
10	1b		3j	71a

^a100 °C.

In summary, we have demonstrated that aryltrifluorosilanes can be cross-coupled with a wide variety of substituted aryl and heteroaryl chlorides. The corresponding cross-coupled products were obtained in good to excellent yields.

Experimental Section

General Considerations

All reactions were carried out under an argon atmosphere. Pd(OAc)₂, XPhos and TBAF were used as received. Phenyltrichlorosilane and trichloro(4-methylphenyl)silane were purchased and used as received. Trichloro(3-methoxyphenyl)silane was prepared as described in the literature.⁴⁰ Solvents were degassed with argon each time prior to use. Standard benchtop techniques were employed for handling air-sensitive reagents. Melting points (°C) are uncorrected. NMR spectra were recorded on a 500 MHz spectrometer. Data are presented as follows: chemical shift (ppm), multiplicity (s = singlet, d = doublet, t = triplet, m = multiplet, br = broad), coupling constant J (Hz) and integration. Analytical thin-layer chromatography (TLC) was performed on TLC silica or alumina gel plates (0.25 mm) precoated with a fluorescent indicator. Standard flash chromatography procedures were followed using 32–63 μm silica gel. Visualization was effected with ultraviolet light.

General procedure for preparation of organotrifluorosilanes

The organotrichlorosilane (1 equiv) and Na₂SiF₆ (2 equiv) were heated to 200 °C for 1 h.³³ After cooling to rt, the crude mixture was purified by distillation, affording the desired organotrifluorosilane.

Phenyltrifluorosilane (1a).³¹

Following the general procedure for preparation of organotrifluorosilane, 1a was obtained as a colorless oil (2.95 g, 59%). ¹H NMR (500 MHz, CDCl₃): δ = 7.52 (t, J = 7.5 Hz, 2 H), 7.64–7.67 (m, 1 H), 7.76–7.78 (m, 2 H). ¹³C NMR (125 MHz, CDCl₃): δ = 120.3, 128.8, 133.5, 134.7. ¹⁹F NMR (471 MHz, CDCl₃): δ = − 141.1. IR (neat): ν̃_max = 1537, 1589, 3078 cm⁻¹.

Trifluoro(3-methoxyphenyl)silane (1b).⁴⁰

Following the general procedure for preparation of organotrifluorosilane, 1b was obtained as a colorless oil (1.29 g, 45%). ¹H NMR (500 MHz, CDCl₃): δ = 3.84 (s, 3 H), 7.15–7.17 (m, 1 H), 7.22–7.23 (m, 1 H), 7.30–7.32 (m, 1 H), 7.41–7.45 (m, 1 H). ¹³C NMR (125 MHz, CDCl₃): δ = 55.4, 119.4, 119.6, 121.4, 126.8, 130.3, 159.6. ¹⁹F NMR (471 MHz, CDCl₃): δ = − 141.0. IR (neat): ν̃_max = 1267, 1507, 1567, 3089 cm⁻¹.

Trifluoro(para-tolyl)silane (1c).³¹

Following the general procedure for preparation of organotrifluorosilane, 1c was obtained as a colorless oil (2.06 g, 42%). ¹H NMR (500 MHz, CDCl₃): δ = 2.43 (s, 3 H), 7.33 (d, J = 8.0 Hz, 2 H), 7.65 (d, J = 8.0 Hz, 2 H). ¹³C NMR (125 MHz, CDCl₃): δ = 21.9, 116.8, 117.0, 129.6, 133.3, 134.7, 144.2. ¹⁹F NMR (471 MHz, CDCl₃): δ = − 140.9. IR (neat): ν̃_max = 1540, 1609, 3056 cm⁻¹.

General procedure for Hiyama cross-coupling with aryltrifluorosilanes

Pd(OAc)₂ (0.17 mmol, 3.9 mg) and XPhos (0.35 mmol, 17 mg) were added under argon to a soln of aryltrifluorosilane 1a–c (1.05 mmol) in t-BuOH (1 mL) in a Biotage microwave vial. TBAF was added, and the vial sealed with a cap lined with a disposable Teflon septum. After stirring for 5 min at rt, a soln of aryl chloride (0.7 mmol) in t-BuOH (1 mL) was added, and the reaction mixture heated conventionally to 60 °C overnight. After cooling to rt, the crude mixture was filtered through a pad of silica, concentrated in vacuo, and purified by flash column chromatography using a gradient mixture of hexanes and EtOAc as eluent.

4-Methoxybiphenyl (2a).⁴¹

Following the general procedure for Hiyama cross-coupling with aryltrifluorosilanes, 2a was obtained as a white solid directly from the chromatographic solvent, mp 84–86 °C, (100 mg, 78%). ¹H NMR (500 MHz, CDCl₃): δ = 3.86 (s, 3 H), 6.69 (d, J = 8.5 Hz, 2 H), 7.32 (t, J = 7.2 Hz, 1 H), 7.43 (t, J = 7.5 Hz, 2 H), 7.54–7.58 (m, 4 H). ¹³C NMR (125 MHz, CDCl₃): δ = 55.4, 114.3, 126.7, 126.8, 128.2, 128.8, 133.9, 140.9, 159.2. IR (neat): ν̃_max = 1290, 1579, 3098 cm⁻¹. HRMS: calcd for C₁₃H₁₃O [M+H]⁺: 185.0966; found: 185.0970.

3,5-Dimethoxybiphenyl (2b).⁴²

Following the general procedure for Hiyama cross-coupling with aryltrifluorosilanes, 2b was obtained as a yellow oil (135 mg, 90%). ¹H NMR (500 MHz, CDCl₃): δ = 3.85 (s, 6 H), 6.48 (t, J = 2.0 Hz, 1 H), 6.75 (d, J = 2.0 Hz, 2 H), 7.34–7.36 (m, 1 H), 7.42–7.45 (m, 2 H), 7.58–7.59 (m, 2 H). ¹³C NMR (125 MHz, CDCl₃): δ = 55.5, 99.4, 105.6, 127.3, 127.6, 128.8, 141.3, 143.6, 161.1. IR (neat): ν̃_max = 1167, 1534, 1589, 3045 cm⁻¹. HRMS: calcd for C₁₄H₁₅O₂ [M+H]⁺: 215.1072; found: 215.1077.

2-Methoxybiphenyl (2c).⁴¹

Following the general procedure for Hiyama cross-coupling with aryltrifluorosilane, 2c was obtained as a colorless oil (90 mg, 70%). ¹H NMR (500 MHz, CDCl₃): δ = 3.82 (s, 3 H), 6.99–7.01 (m, 1 H), 7.04 (t, J = 7.5 Hz, 1 H), 7.32–7.35 (m, 3 H), 7.42 (t, J = 7.5 Hz, 2 H), 7.55 (d, J = 7.5 Hz, 2 H). ¹³C NMR (125 MHz, CDCl₃): δ = 55.6, 111.3, 120.9, 127.7, 128.1, 128.7, 129.6, 130.8, 131.0, 138.6, 156.5. IR (neat): ν̃_max = 1178, 1508, 1567, 3029 cm⁻¹. HRMS: calcd for C₁₃H₁₂O [M]⁺: 184.0888; found: 184.0889.

2-Phenyl-5-methoxy-1,3-dimethylbenzene (2d)

Following the general procedure for Hiyama cross-coupling with aryltrifluorosilane, 2d was obtained as a colorless oil (143 mg, 97%). ¹H NMR (500 MHz, CDCl₃): δ = 2.12 (s, 6 H), 3.90 (s, 3 H), 6.78 (s, 2 H), 7.23 (d, J = 7.5 Hz, 2 H), 7.40 (t, J = 7.5 Hz, 1 H), 7.49 (t, J = 7.5 Hz, 2 H). ¹³C NMR (125 MHz, CDCl₃): δ = 21.2, 55.1, 112.6, 126.5, 128.4, 129.7, 134.6, 137.4, 140.9, 158.3. IR (neat): ν̃_max = 1234, 1567, 1590, 3028 cm⁻¹. HRMS: calcd for C₁₅H₁₆O [M]⁺: 212.1201; found: 212.1210.

4-Phenyl-1H-benzopyrrole (2e)

Following the general procedure for Hiyama cross-coupling with aryltrifluorosilanes, 2e was obtained as a white solid directly from the chromatographic solvent, mp 185–186 °C, (139 mg, 90%). ¹H NMR (500 MHz, CDCl₃): δ = 6.39 (t, J = 2.0 Hz, 2 H), 7.15 (t, J = 2.0 Hz, 2 H), 7.38 (t, J = 7.5 Hz, 1 H), 7.46–7.49 (m, 4 H), 7.62 (d, J = 8.0 Hz, 2 H), 7.66 (d, J = 8.0 Hz, 2 H). ¹³C NMR (125 MHz, CDCl₃): δ = 110.6, 119.3, 120.7, 126.9, 127.4, 128.2, 128.9, 138.5, 139.9, 140.2. IR (neat): ν̃_max = 1123, 1597, 1690, 3043, cm⁻¹. HRMS: calcd for C₁₆H₁₄N [M+H]⁺: 220.1126; found: 220.1126.

1-Phenylnaphthalene (2f).⁴³

Following the general procedure for Hiyama cross-coupling with aryltrifluorosilanes, 2f was obtained as a colorless oil (107 mg, 75%). ¹H NMR (500 MHz, CDCl₃): δ = 7.44–7.47 (m, 3 H), 7.50–7.57 (m, 6 H), 7.89 (d, J = 8.5 Hz, 1 H), 7.94 (d, J = 9.0 Hz, 2 H). ¹³C NMR (125 MHz, CDCl₃): δ = 125.4, 125.8, 126.1 (2C), 127.0, 127.3, 127.7, 128.3, 130.1, 131.7, 133.9, 140.3, 140.8. IR (neat): ν̃_max = 1578, 1590, 3067, 3090 cm⁻¹. HRMS: calcd for C₁₆H₁₃ [M+H]⁺: 205.1017; found: 205.1012.

4-(Trifluoromethyl)biphenyl (2g).⁴⁴

Following the general procedure for Hiyama cross-coupling with aryltrifluorosilanes, 2g was obtained as a white solid directly from the chromatographic solvent, mp 65–67 °C, (138 mg, 89%). ¹H NMR (500 MHz, CDCl₃): δ = 7.43–7.46 (m, 1 H), 7.51 (t, J = 7.5 Hz, 2 H), 7.63 (d, J = 7.5 Hz, 2 H), 7.70–7.74 (m, 4 H). ¹³C NMR (125 MHz, CDCl₃): δ = 123.4 (q, J = 272.1 Hz), 125.8 (q, J = 3.7 Hz), 127.4, 127.5, 128.3, 128.8, 129.1 (q, J = 32.2 Hz), 139.9, 144.9. ¹⁹F NMR (471 MHz, CDCl₃): δ = − 62.3. IR (neat): ν̃_max = 1545, 1607, 3067 cm⁻¹. HRMS: calcd for C₁₃H₉F₃ [M]⁺: 222.0656; found: 222.0648.

4-Phenylbenzonitrile (2h).⁴¹

Following the general procedure for Hiyama cross-coupling with aryltrifluorosilanes, 2h was obtained as a white solid directly from the chromatographic solvent, mp 85–87 °C, (91 mg, 73%). ¹H NMR (500 MHz, CDCl₃): δ = 7.41–7.44 (m, 1 H), 7.47–7.50 (m, 2 H), 7.58–7.59 (m, 2 H), 7.66–7.72 (m, 4 H). ¹³C NMR (125 MHz, CDCl₃): δ = 110.8, 118.9, 127.2, 127.7, 128.7, 129.1, 132.6, 139.1, 145.6. IR (neat): ν̃_max = 1567, 1601, 2307, 3110 cm⁻¹. HRMS: calcd for C₁₃H₉N (M)⁺: 179.0735; found: 179.0743.

4-Nitrobiphenyl (2i).⁴⁵

Following the general procedure for Hiyama cross-coupling with aryltrifluorosilanes, 2i was obtained as a yellow solid directly from the chromatographic solvent, mp 100–102 °C, (127 mg, 91%). ¹H NMR (500 MHz, CDCl₃): δ = 7.43–7.46 (m, 1 H), 7.49–7.52 (m, 2 H), 7.63 (d, J = 8.0 Hz, 2 H), 7.72–7.74 (m, 2 H), 8.28–8.30 (m, 2 H). ¹³C NMR (125 MHz, CDCl₃): δ = 124.2, 127.4, 127.8, 129.0, 129.2, 138.8, 147.1, 147.7. IR (neat): ν̃_max = 1343, 1508, 1643, 3078 cm⁻¹. HRMS: calcd for C₁₂H₉NO₂ [M]⁺: 199.0633; found: 199.0639.

3-Phenylmethylbenzoate (2j).⁴⁶

Following the general procedure for Hiyama cross-coupling with aryltrifluorosilanes, 2j was obtained as a colorless oil (146 mg, 98%). ¹H NMR (500 MHz, CDCl₃): δ = 3.94 (s, 3 H), 7.36–7.39 (m, 1 H), 7.44–7.53 (m, 3 H), 7.61–7.63 (m, 2 H), 7.78–7.79 (m, 1 H), 8.02 (d, J = 7.5 Hz, 1 H), 8.28 (s, 1 H). ¹³C NMR (125 MHz, CDCl₃): δ = 52.3, 127.3, 127.8, 128.4 (2C), 128.9, 129.0, 130.8, 131.6, 140.2, 141.6, 167.2. IR (neat): ν̃_max = 1234, 1576, 1705, 3090 cm⁻¹. HRMS: calcd for C₁₄H₁₃O₂ [M+H]⁺: 213.0916; found: 213.0911.

Biphenyl-4-carboxaldehyde (2k).⁴³

Following the general procedure for Hiyama cross-coupling with aryltrifluorosilanes, 2k was obtained as a yellow solid directly from the chromatographic solvent, mp 182–184 °C, (108 mg, 85%). ¹H NMR (500 MHz, CDCl₃): δ = 7.40–7.43 (m, 1 H), 7.46–7.49 (m, 2 H), 7.62–7.64 (m, 2 H), 7.73–7.74 (m, 2 H), 7.93–7.95 (m, 2 H), 10.05 (s, 1 H). ¹³C NMR (125 MHz, CDCl₃): δ = 127.3, 127.6, 128.5, 129.0, 130.2, 135.2, 139.7, 147.1, 191.8. IR (neat): ν̃_max = 1527, 1604, 1689, 3087 cm⁻¹. HRMS: calcd for C₁₃H₁₀O [M]⁺: 182.0732; found: 182.0732.

4-Acetylbiphenyl (2l).⁴¹

Following the general procedure for Hiyama cross-coupling with aryltrifluorosilanes, 2l was obtained as a white solid directly from the chromatographic solvent, mp 118–120 °C, (118 mg, 86%). ¹H NMR (500 MHz, CDCl₃): δ = 2.62 (s, 3 H), 7.38–7.41 (m, 1 H), 7.46 (t, J = 7.5 Hz, 2 H), 7.62 (d, J = 7.5 Hz, 2 H), 7.67 (d, J = 8.0 Hz, 2 H), 8.02 (d, J = 8.0 Hz, 2 H). ¹³C NMR (125 MHz, CDCl₃): δ = 26.6, 127.1, 127.2, 128.2, 128.8, 128.9, 135.8, 139.7, 145.6, 197.6. IR (neat): ν̃_max = 1549, 1579, 1721, 3023 cm⁻¹. HRMS: calcd for C₁₄H₁₃O [M+H]⁺: 197.0966; found: 197.0968.

3-(3-Methoxybenzene)-methylbenzoate (2m)

Following the general procedure for Hiyama cross-coupling with aryltrifluorosilanes, 2m was obtained as a yellow oil (136 mg, 80%). ¹H NMR (500 MHz, CDCl₃): δ = 3.86 (s, 3 H), 3.94 (s, 3 H), 6.91–6.93 (m, 1 H), 7.16 (s, 1 H), 7.21 (d, J = 8.0 Hz, 1 H), 7.37 (t, J = 7.7 Hz, 1 H), 7.49 (t, J = 7.7 Hz, 1 H), 7.77 (d, J = 7.5 Hz, 1 H), 8.03 (d, J = 7.5 Hz, 1 H), 8.29 (s, 1 H). ¹³C NMR (125 MHz, CDCl₃): δ = 52.1, 55.3, 112.9, 113.1, 119.6, 128.2, 128.5, 128.8, 129.9, 130.6, 131.5, 141.3, 141.6, 160.0, 167.0. IR (neat): ν̃_max = 1178, 1230, 1567, 1609, 1715, 3067 cm⁻¹. HRMS: calcd for C₁₅H₁₅O₃ [M+H]⁺: 243.1021; found: 243.1015.

4-(4-Methyl)-acetylbiphenyl (2n).⁴⁷

Following the general procedure for Hiyama cross-coupling with aryltrifluorosilanes, 2n was obtained as a white solid directly from the chromatographic solvent, mp 116–118 °C, (120 mg, 81%). ¹H NMR (500 MHz, CDCl₃): δ = 2.41 (s, 3 H), 2.62 (s, 3 H), 7.28 (d, J = 7.5 Hz, 2 H), 7.53 (d, J = 7.5 Hz, 2 H), 7.66 (d, J = 7.5 Hz, 2 H), 8.01 (d, J = 7.5 Hz, 2 H). ¹³C NMR (125 MHz, CDCl₃): δ = 21.1, 26.5, 126.8, 127.0, 128.8, 129.6, 135.5, 136.8, 138.1, 145.6, 197.6. IR (neat): ν̃_max = 1534, 1605, 1708, 3026 cm⁻¹. HRMS: calcd for C₁₅H₁₅O [M+H]⁺: 211.1123; found: 211.1126.

3-Phenylpyridine (3a).⁴¹

Following the general procedure for Hiyama cross-coupling with aryltrifluorosilanes, 3a was obtained as a colorless oil (80 mg, 74%). ¹H NMR (500 MHz, CDCl₃): δ = 7.33–7.38 (m, 1 H), 7.39–7.41 (m, 1 H), 7.45–7.48 (m, 2 H), 7.56–7.58 (m, 2 H), 7.85 (d, J = 8.0 Hz, 1 H), 8.59 (d, J = 5.0 Hz, 1 H), 8.85 (s, 1 H). ¹³C NMR (125 MHz, CDCl₃): δ = 123.6, 127.2, 128.1, 129.1, 134.4, 136.6, 137.9, 148.4, 148.5. IR (neat): ν̃_max = 1534, 1569, 3089 cm⁻¹. HRMS: calcd for C₁₁H₁₀N [M+H]⁺: 156.0813; found: 156.0811.

3-(3-Methoxyphenyl)pyridine (3b).⁴⁸

Following the general procedure for Hiyama cross-coupling with aryltrifluorosilanes, 3b was obtained as a yellow oil (98 mg, 76%). ¹H NMR (500 MHz, CDCl₃): δ = 3.82 (s, 3 H), 6.91 (d, J = 7.5 Hz, 1 H), 7.07 (s, 1 H), 7.12 (d, J = 7.0 Hz, 1 H), 7.29–7.31 (m, 1 H), 7.35 (t, J = 8.0 Hz, 1 H), 7.81 (d, J = 7. 5 Hz, 1 H), 8.56 (s, 1 H), 8.82 (s, 1 H). ¹³C NMR (125 MHz, CDCl₃): δ = 55.2, 112.9, 113.3, 119.5, 123.4, 130.1, 134.3, 136.4, 139.2, 148.3, 148.5, 160.1. IR (neat): ν̃_max = 1178, 1549, 1590, 3034 cm⁻¹. HRMS: calcd for C₁₂H₁₂NO [M+H]⁺: 186.0919; found: 186.0911.

6-Methoxy-3-phenylpyridine (3c).⁴¹

Following the general procedure for Hiyama cross-coupling with aryltrifluorosilanes, 3c was obtained as a yellow oil (100 mg, 78%). ¹H NMR (500 MHz, CDCl₃): δ = 3.99 (s, 3 H), 6.82 (d, J = 8.5 Hz, 1 H), 7.34–7.37 (m, 1 H), 7.45 (t, J = 8.2 Hz, 2 H), 7.52–7.54 (m, 2 H), 7.79 (dd, J = 8.5, 2.5 Hz, 1 H), 8.40–8.41 (m, 1 H). ¹³C NMR (125 MHz, CDCl₃): δ = 53.5, 110.8, 126.7, 127.3, 129.0, 130.1, 137.5, 137.9, 145.0, 163.6. IR (neat): ν̃_max = 1290, 1508, 1567, 3045 cm⁻¹. HRMS: calcd for C₁₂H₁₂NO [M+H]⁺: 186.0919; found: 186.0914.

6-Fluoro-3-phenylpyridine (3d)

Following the general procedure for Hiyama cross-coupling with aryltrifluorosilanes, 3d was obtained as a yellow oil (101 mg, 84%). ¹H NMR (500 MHz, CDCl₃): δ = 7.00 (dd, J = 8.5, 2.5 Hz, 1 H), 7.39–7.42 (m, 1 H), 7.47 (t, J = 7.5 Hz, 2 H), 7.52–7.53 (m, 2 H), 7.96 (dt, J = 8.0, 2.5 Hz, 1 H), 8.41 (s, 1 H). ¹³C NMR (125 MHz, CDCl₃): δ = 109.3, 109.6, 127.1, 128.2, 129.2, 134.9, 136.7, 139.7, 145.8, 162.2, 164.1. ¹⁹F NMR (471 MHz, CDCl₃): δ = − 71.06. IR (neat): ν̃_max = 1567, 3089 cm⁻¹. HRMS: calcd for C₁₁H₈FN [M]⁺: 173.0641; found: 173.0640.

3-(4-Methylbenzene)-6-fluoropyridine (3e)

Following the general procedure for Hiyama cross-coupling with aryltrifluorosilanes, 3e was obtained as a white solid directly from the chromatographic solvent, mp 55–57 °C, (122 mg, 94%). ¹H NMR (500 MHz, CDCl₃): δ = 2.41 (s, 3 H), 6.97–6.99 (m, 1 H), 7.28 (d, J = 7.5 Hz, 2 H), 7.43 (d, J = 6.5 Hz, 2 H), 7.92–7.96 (m, 1 H), 8.40 (s, 1 H). ¹³C NMR (125 MHz, CDCl₃): δ = 21.2, 109.3, 109.6, 127.0, 129.9, 133.9, 134.9, 138.2, 139.6, 145.7, 162.1, 164.0. ¹⁹F NMR (471 MHz, CDCl₃): δ = − 71.0. IR (neat): ν̃_max = 1569, 1607, 3032 cm⁻¹. HRMS: calcd for C₁₂H₁₁NF [M+H]⁺: 188.0876; found: 188.0879.

4-Phenyl-2-methoxyquinoline (3f).⁴⁹

Following the general procedure for Hiyama cross-coupling with aryltrifluorosilanes, 3f was obtained as a yellow oil (100 mg, 65%). ¹H NMR (500 MHz, CDCl₃): δ = 2.76 (s, 3 H), 7.20 (s, 1 H), 7.40 (t, J = 7.5 Hz, 1 H), 7.46–7.50 (m, 5 H), 7.66 (t, J = 7.5 Hz, 1 H), 7.84 (d, J = 8.0 Hz, 1 H), 8.10 (d, J = 8.0 Hz, 1 H). ¹³C NMR (125 MHz, CDCl₃): δ = 25.3, 122.2, 125.1, 125.6, 125.7, 128.3, 128.5, 129.0, 129.3, 129.5, 138.1, 148.4, 148.5, 158.5. IR (neat): ν̃_max = 1567, 1609, 3065, 3089 cm⁻¹. HRMS: calcd for C₁₆H₁₄N [M+H]⁺: 220.1126; found: 220.1130.

5-Phenylthiophene-2-carboxaldehyde (3g).⁴¹

Following the general procedure for Hiyama cross-coupling with aryltrifluorosilanes, 3g was obtained as an orange solid directly from the chromatographic solvent, mp 92–94 °C, (118 mg, 90%). ¹H NMR (500 MHz, CDCl₃): δ = 7.36–7.41 (m, 4 H), 7.62–7.64 (m, 2 H), 7.70 (d, J = 4.0 Hz, 1 H), 9.86 (s, 1 H). ¹³C NMR (125 MHz, CDCl₃): δ = 124.1, 126.3, 129.1, 129.4, 132.9, 137.5, 142.3, 154.1, 182.8. IR (neat): ν̃_max = 1534, 1609, 1789, 3023 cm⁻¹. HRMS: calcd for C₁₁H₉OS [M+H]⁺: 189.0374; found: 189.0383.

5-Phenylfuran-2-carboxaldehyde (3h).⁵⁰

Following the general procedure for Hiyama cross-coupling with aryltrifluorosilanes, 3h was obtained as a yellow oil (89 mg, 74%). ¹H NMR (500 MHz, CDCl₃): δ = 6.80 (d, J = 3.5 Hz, 1 H), 7.28 (d, J = 3.5 Hz, 1 H), 7.35–7.42 (m, 3 H), 7.78 (m, 2 H), 9.60 (s, 1 H). ¹³C NMR (125 MHz, CDCl₃): δ = 107.7, 125.2, 128.9, 129.6, 151.9, 159.3, 177.2. IR (neat): ν̃_max = 1567, 1602, 1712, 3078 cm⁻¹. HRMS: calcd for C₁₁H₉O₂ [M+H]⁺: 173.0603; found: 173.0607.

6-Phenylisoquinoline (3i)

Following the general procedure for Hiyama cross-coupling with aryltrifluorosilanes, 3i was obtained as a colorless oil (122 mg, 85%). ¹H NMR (500 MHz, CDCl₃): δ = 7.45–7.53 (m, 5 H), 7.67 (d, J = 4.5 Hz, 2 H), 7.73 (d, J = 5.5 Hz, 1 H), 7.99 (t, J = 4.5 Hz, 1 H), 8.49 (d, J = 6.0 Hz, 1 H), 9.31 (s, 1 H). ¹³C NMR (125 MHz, CDCl₃): δ = 126.9, 127.2, 127.9, 128.6, 129.9, 131.0, 134.2, 139.1, 139.3, 143.5, 153.0. IR (neat): ν̃_max = 1589, 1609, 3034 cm⁻¹. HRMS: calcd for C₁₅H₁₂N [M+H]⁺: 206.0970; found: 206.0971.

6-(3-Methoxybenzene)isoquinoline (3j)

Following the general procedure for Hiyama cross-coupling with aryltrifluorosilanes, 3j was obtained as a yellow solid directly from the chromatographic solvent, mp 71–73 °C, (117 mg, 71%). ¹H NMR (500 MHz, CDCl₃): δ = 3.81 (s, 3 H), 6.96–7.02 (m, 3 H), 7.38 (t, J = 7.7 Hz, 1 H), 7.57–7.62 (m, 2 H), 7.73 (d, J = 6.0 Hz, 1 H), 7.92 (d, J = 7.5 Hz, 1 H), 8.46 (d, J = 6.0 Hz, 1H), 9.27 (s, 1 H). ¹³C NMR (125 MHz, CDCl₃): δ = 55.2, 113.1, 115.5, 118.5, 122.2, 126.7, 127.1, 128.9, 129.5, 130.7, 134.0, 139.0, 140.3, 143.3, 152.8, 159.6. IR (neat): ν̃_max = 1230, 1524, 1589, 3078 cm⁻¹. HRMS: calcd for C₁₆H₁₄NO [M+H]⁺: 236.1075; found: 236.1079.