Photocatalytic Defluorinative Borylation of α-(Trifluoromethyl)styrenes

For Tatì

Abstract

The defluorinative radical borylation of α-(trifluoromethyl)styrenes is a novel access to diverse difluoroalkene-aminoboranes in good yields. Using the boryl radical precursor borobetaine gives the key boryl radical that reacts with the α-(trifluoromethyl)styrene forming the initial C–B bond. Then a radical-polar crossover mechanism releases fluoride to provide a difluoroalkene product bearing the aminoborane synthetic handle. The difluoroalkene motif is of interest as a potent carbonyl bioisostere that has been shown to enhance biological activity and reactivity. The presence of the aminoborane moiety allows further functionalization such as Suzuki–Miyaura cross-coupling of the borylated products, which is demonstrated using complex aryl bromides. Various post-functionalizations demonstrate difluoroalkene-aminoboranes to be valuable building blocks for the construction of complex, high-value molecules.

 

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Key word

boryl radicals - photoredox catalysis - radical-polar crossover - difluoroalkenes - borylation

The decoration of organic motifs with fluorine atoms is regularly employed to improve the properties of high-value molecules across pharmaceuticals, agrochemicals, and materials science.[1] [2] [3] gem-Difluoroalkenes specifically have emerged as valuable bioisosteres for ketones, playing key roles in molecular recognition and biological mimicry.[4] Two prominent examples of this are the difluoroalkene derivative of TDP-6-deoxy-l-lyxo-4-hexulose 1 demonstrating reverse regioselectivity of enzymatic reduction,[5] and improved antimalarial activity of CF₂-artemisinin 2 versus artemisinin (Scheme [1]A).[6]

While defluorinative functionalization of α-(trifluoromethyl)styrenes 3 to generate difluoroalkenes has been demonstrated by transition metal catalysis with B₂Pin₂ as a boron source,[7] [8] recent reports focused on photoredox initiated approaches instead. Most examples utilizing radical pathways, such as those by Molander, T. Wang, and Q. Wang, focus on the addition of carbon-centered radicals to α-(trifluoromethyl)styrenes 3 to give difluoroalkenes 5 (Scheme [1]B).[9] [10] [11] Heteroatomic radicals, such as boryl radicals, have been significantly less explored and have been limited entirely to NHC-ligated boranes 6. For these reactions, the key boryl radical is generated via hydrogen atom transfer (HAT), furnishing planar, π-radicals through the stabilizing effect of the NHC π-system.[12] Precisely this effect leads to stable products 7 that are too unreactive for direct participation in cross-coupling processes, hence they need to be derivatized further for engagement in such reactions.[13] As boron-bearing motifs are particularly interesting for the synthesis of complex organic scaffolds,[14] [15] their installation is most valuable as a synthetic handle for further derivatization, namely the Suzuki–Miyaura cross-coupling, which is among the most common reactions performed in medicinal chemistry.[16] Based on our previous work on the use of amine-ligated boryl radicals,[17] [18] we wanted to expand the borylation process to α-(trifluoromethyl)styrenes, forming difluoroalkenes bearing an aminoborane group, for direct further functionalization. To our knowledge, boryl radicals such as 9 have not previously been employed in the radical formation of difluoroalkenes.

Scheme 1 (A) Examples of difluoroalkenes 1 and 2 as ketone bioisosteres. (B) Precedent for the addition of carbon and boron-centered radicals to α-(trifluoromethyl)styrenes 3. (C) Boryl radical 9 generation from borobetaine 8 via oxidative decarboxylation.

An initial hit showed the defluorinative borylation was feasible with electron-donating group substituted 4-methoxy-α-(trifluoromethyl)styrene (10), a limitation in our previous work.[17] Encouraged by this finding, we began our endeavor using styrene 10 and boryl radical precursor borobetaine (8). Initial experiments revealed the organic photocatalyst 2,4,6-tris(diphenylamino)-3,5-difluorobenzonitrile (3DPA2FBN) to give the best yields of difluoroalkene 11 when compared to other photocatalysts screened, moving away from expensive metal-based photocatalysts. Importantly, control reactions omitting light (Table [1], entry 6) and photocatalyst (Table [1], entry 7) confirmed a photocatalytic process to be operative (see the Supporting Information for full details of the optimization).

Table 1 Selected Entries for the Optimization of Photocatalytic Borylation

Entry	Deviation from std conditions	Yielda (%)
1	–	64 (61b)
2	Cs2CO3 (2 equiv.)	54
3	4CzIPN	44
4	eosin Y	31
5	[Ir(ppy)3]	18
6	no light	0
7	no photocatalyst	0

^a NMR yield.

^b Isolated yield.

Having found conditions that provided us with good yield of the borylated difluoroalkenes, we examined the tolerance of the borylation to various other α-(trifluoromethyl)styrenes 3 bearing a range of functional groups (Scheme [2]). We observed very good yields of products for the borylation of α-(trifluoromethyl)styrenes 3 bearing para-substitutions such as ester 12, methyl and phenyl ethers 11 and 14, and methyl 13. Similarly meta-methoxy and meta-methyl provide good yields of difluoroalkenes 15 and 16. Disubstituted aryl substrates efficiently underwent borylation/defluorination providing products 17 and 18. An alkyne-containing α-(trifluoromethyl)styrene was successfully borylated to give 19 in 38% yield with no borylation or reduction of the alkyne group, therefore showing complete chemoselectivity for the desired radical addition. Substituted naphthyls also provided very good yields of 21, 22, and 23, with a lower yield observed for borylation, to give 2-styryl-naphthalene 24. α-(Trifluoromethyl)styrenes 3 bearing more complex heteroaromatic groups gave products such as pyridine 20, indole 25, benzofuran 26, benzothiophene 27, and indazole 28 thus demonstrating that a wide range of functionalities are conducive to the developed reaction. To further highlight the tolerance of this method, mecoprop derivative 29 was synthesized in 26% yield.

Scheme 2 Substrate scope for the photocatalytic borylation of α-(trifluoromethyl)styrenes screened

We propose that the developed defluorinative borylation of α-(trifluoromethyl)styrenes occurs via a radical-polar crossover mechanism (Scheme [3]). Excitation of 3DPA2FBN provides the excited state photocatalyst (PC*), this in turn undergoes single electron transfer (SET) with deprotonated borobetaine 30 as confirmed by Stern–Volmer quenching studies (see the Supporting Information). Control experiments show the requirement for light and photocatalyst. The measured potential for the deprotonated borobetaine ([30 ^–/9 ^•] = +0.38 V vs SCE) (see the Supporting Information) is within range of the reported excited state reduction potential of 3DPA2FBN ([PC*/PC^•–] = +0.92 V vs SCE).[19] Rapid decarboxylation furnishes the boryl radical 9 that undergoes addition to the α-(trifluoromethyl)styrene 10, to provide the stabilized benzylic radical 31. Reduction (by SET) of this intermediate radical occurs through concomitant oxidation of the photocatalyst radical anion (3DPA2FBN^•–). Literature reported reduction potentials of benzyl radicals depend on the substitution on the aromatic ring [–1.75 V (4-MeO) and –0.77 V (4-CN)],[20] however, they fall within range of the employed photocatalyst (3DPA2FBN [PC/PC^•–] = –1.92 V). Moreover, addition of TEMPO to the reaction inhibits product formation, indicative of a radical process being operative (see the Supporting Information). This mechanism is further supported by literature employing 3DPA2FBN in radical-polar crossover reactions, proceeding by reduction of the intermediate benzyl radical by the reduced form photocatalyst.[21] [22] Release of fluoride from the pendant trifluoromethyl group of the benzylic anion 32 furnishes the difluoroalkene product 11. Competitive protonation, seen with substrates lacking the trifluoromethyl substitution, is not presumably competitive with the unimolecular elimination observed for this process.[23]

With our process to furnish aminoborane bearing difluoroalkenes in hand, we wanted to explore further reactivity. Specifically, we wanted to investigate the cross-coupling using the alkyl aminoborane as a reaction partner with various aryl bromides.

Scheme 3 Mechanism of photocatalytic borylation of α-(trifluoromethyl)styrenes

Scheme 4 Suzuki–Miyaura cross-coupling of an aminoborane to afford bis-aryl alkenes

Traditionally the use of boryl radicals has focused on NHC-ligated boron species 7 that do not directly undergo cross-coupling but first require derivatization (vide supra). The Leonori group has demonstrated that both alkyl and aryl aminoboranes are effective reaction partners in the Suzuki–Miyaura cross-coupling owing to their hydrolysis to afford the highly reactive boronic acids in situ.[17] We were able to demonstrate the Suzuki–Miyaura cross-coupling of aminoborane 11 with a selected range of aryl bromides showing a high degree of complexity (Scheme [4]). In all cases, we observed the isomerization of the alkene to afford the difluoromethyl bis-arylated alkenes 33. Analogous products bearing the medicinally interesting difluoromethyl group have recently been synthesized through the use of Ni catalysis and bromodifluoromethane, or through a hydroboration/cross-coupling sequence of alkynes using dicyclohexylborane, a rather challenging-to-handle reagent.[24] [25] [26] As the interest towards the introduction of difluoromethyl and other fluorinated substitution patterns in biologically relevant molecules has risen due to their improved metabolic properties, we were pleased to access this substitution pattern with convenient and mild conditions.[27–29] Difluoroalkene-aminoborane 11 underwent cross-coupling in moderate to good yields, demonstrating the formation of simpler products, such as 34, but also using hetaryl bromides to give products containing oxazole 35, pyridine 36, and protected azaindole 37. Remarkably, we could also show cross coupling of aminoborane 11 with an example from the Merck informer library (X3) to afford complex Suzuki–Miyaura product 38 in a synthetically useful yield.[30]

To elaborate on the synthetic potential of these novel difluoroalkene-aminoboranes, substrate 12 was selected for a range of initial derivatization reactions to afford secondary products from the borylated substrates (Scheme [5]). Thus, the cross-coupling afforded a good yield of the Suzuki–Miyaura product 39, demonstrating that both electron-donating and electron-withdrawing groups in the borylated substrate are tolerated. The aminoborane moiety of 12 could be post-functionalized to give both the BPin 41 and BMIDA 43, providing alternative boron handles. Further, oxidation of aminoborane 12 provided the terminal alcohol 40. Finally, chlorination of the borane to furnish aminoborane 42 was demonstrated to be possible; attempts at fluorination returned the starting α-(trifluoromethyl)styrene 12.

Scheme 5 Post-functionalization of borylated product 12. ^a 1:1.4 mono/dichlorination

To conclude, we have demonstrated the photocatalytic borylation of α-(trifluoromethyl)styrenes using borobetaine (8) as the boryl radical precursor to afford difluoroalkene-aminoboranes 11–29. Further, we have shown these borylated products to undergo efficient Suzuki–Miyaura cross-coupling with various complex aryl bromides to deliver difluoromethyl bis-arylated alkenes 34–38. Additionally, we have shown that the novel difluoroalkene-aminoboranes can undergo a range of post-functionalization transformations, proving again their value as synthetic building blocks for academic and industry chemists alike.

All required fine chemicals were used directly without purification unless stated otherwise. All air and moisture sensitive reactions were carried out under N₂ atmosphere using standard Schlenk manifold technique. All solvents were bought from Acros as 99.8% purity and degassed by N₂ bubbling. ¹H and ¹³C NMR spectra were acquired at various field strengths as indicated and were referenced to CHCl₃ (δ = 7.27 and 77.16 for ¹H and ¹³C, respectively). ¹H NMR coupling constants are reported in Hertz and refer to apparent multiplicities and not true coupling constants. In the ¹H NMR measurements, the BH₂ hydrogens were usually not observed due to the broad character of the quartet (J _H–B ~ 90 Hz). In the ¹³C NMR, the carbon α-B was not always detected as consequence of the boron quadrupolar relaxation; when visible it is specified. The spectra measurements are specified when decoupled (e.g., ¹⁹F{¹H}). Proton assignment (determined by 2D NMR experiments: COSY, HSQC and HMBC) where possible. HRMS were obtained using a JEOL JMS-700 spectrometer or a Fissions VG Trio 2000 quadrupole mass spectrometer. Spectra were obtained using electron impact ionization (EI) and chemical ionization (CI) techniques, or positive electrospray (ESI). Analytical TLC: aluminum backed plates pre-coated (0.25 mm) with Merck Silica Gel 60 F254. Compounds were visualized by exposure to UV-light or by dipping the plates in permanganate (KMnO₄) stain followed by heating. Flash column chromatography was performed using Merck Silica Gel 60 (40–63 μm). The LEDs used are Kessil PR 160 440 nm. All the reactions were conducted in CEM 9-mL glass microwave tubes capped with a LABSOLUTE crimp seal with septum (PTFE/butyl) purchased from Th. Geyer.

Information on the synthesis of α-(trifluoromethyl)styrenes 3 and borobetaine (8), photographs of the photochemical reaction setup, and details of the chromatographic purification of the products and full yield data for 11–39 together with procedures and all relevant information for 40–43 are available in the Supporting Information.

 

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Borylation of α-(Trifluoromethyl)styrenes To Give Borane–Amine Complexes 11–29; General Procedure

A microwave vial equipped with a stirring bar was charged with Me₃N-BH₂CO₂H (8; 2.0 equiv.), base (4.0 equiv.), photocatalyst (5 mol%), and olefin 3 (1.0 equiv.). The tube was capped with a Supelco aluminum crimp seal with septum (PTFE/butyl), evacuated and refilled with N₂ (3 ×), then degassed DMF (1 mL, 0.1 M) was added. N₂ was bubbled through the reaction mixture for 10 s. The lid was sealed with parafilm and the vial was placed under blue LEDs. The light was switched on and the mixture was stirred under irradiation at r.t. for 16 h with a fan. The reaction was diluted with EtOAc and H₂O. The aqueous phase was washed with EtOAc (3 ×), and the organic layers were filtered through a layer of Celite and MgSO₄. The combined organic layers were concentrated in vacuo and then purified as specified (see the Supporting Information).

 

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Cross-Coupling of Amine–Boranes; General Procedure

A microwave vial equipped with a stirring bar was charged with the amine-borane (0.1 mmol, 1.0 equiv.), the aryl bromide (2.5 equiv., if solid), Cs₂CO₃ (98 mg, 0.3 mmol, 3.0 equiv.), XPhos (9.5 mg, 0.02 mmol, 20 mol%), and Pd₂dba₃ (2.3 mg, 0.003 mmol, 2.5 mol%). The tube was capped with a Supelco aluminum crimp seal with septum (PTFE/butyl), evacuated and refilled with N₂ (3 ×), then toluene (0.7 mL) was added. The aryl bromide (2.5 equiv., if liquid) was added, followed by H₂O (0.3 mL). The reaction was stirred at 90 °C for 16 h. The reaction was diluted with EtOAc and H₂O. The aqueous phase was washed with EtOAc (3 ×) and the organic layers were filtered through a layer of Celite and MgSO₄. The combined organic layers were concentrated in vacuo and purified by flash chromatography as specified.

 

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(3,3-Difluoro-2-(4-methoxyphenyl)allyl)borane–trimethylamine Complex (11)

Oil (31 mg, 0.12 mmol, 61%); R_f = 0.33 [30% EtOAc/pentane].

IR (film): 3419, 2951, 2347, 1813, 1714, 1607, 1511, 1247, 1030, 833 cm^–1.

¹H NMR (CDCl₃, 600 MHz): δ = 7.34 (d, J = 8.4 Hz, 2 H), 6.85 (d, J = 8.4 Hz, 2 H), 3.79 (s, 3 H), 2.55 (s, 9 H), 1.52 (s, 2 H).

¹³C NMR (CDCl₃, 151 MHz): δ = 158.0, 152.0 (dd, J _C–F = 286.4, 280.5 Hz), 129.5 (t, J _C–F = 3.6 Hz), 129.2 (dd, J _C–F = 3.4, 1.8 Hz), 113.5, 94.7 (dd, J _C–F = 23.6, 9.7 Hz), 55.3, 52.0, 16.2.

¹¹B NMR (CDCl₃, 193 MHz): δ = –3.55 (t, J = 99.1 Hz).

¹⁹F{¹H} NMR (CDCl₃, 565 MHz): δ = –96.00 (d, J = 57.9 Hz), –96.62 (d, J = 57.9 Hz).

HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₃H₂₀ONBF₂Na: 278.1498; found: 278.1492.

 

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Methyl 4-(3-Boranyl-1,1-difluoroprop-1-en-2-yl)benzoate–trimethylamine Complex (12)

Oil (46 mg, 0.17 mmol, 85%); R_f = 0.15 [20% EtOAc/cyclohexane].

IR (film): 2952, 2342, 2102, 1831, 1714, 1465, 1437, 1279, 1101, 986 cm^–1.

¹H NMR (CDCl₃, 600 MHz): δ = 7.97 (d, J = 8.4 Hz, 2 H), 7.48 (d, J = 8.4 Hz, 2 H), 3.89 (s, 3 H), 2.56 (s, 9 H), 1.55 (s, 2 H).

¹³C NMR (CDCl₃, 151 MHz): δ = 167.3, 152.5 (dd, J _C–F = 290.0, 283.4 Hz), 142.0 (t, J _C–F = 4.3 Hz), 129.3, 128.4 (t, J _C–F = 3.6 Hz), 127.9, 95.1 (dd, J _C–F = 24.5, 8.2 Hz), 52.1, 52.0, 16.0.

¹¹B NMR (CDCl₃, 193 MHz): δ = –3.70 (t, J = 98.6 Hz).

¹⁹F{¹H} NMR (CDCl₃, 565 MHz): δ = –92.58 (d, J = 49.2 Hz), –93.38 (d, J = 49.2 Hz).

HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₄H₂₀O₂NBF₂Na: 306.1447; found: 306.1449.

 

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(3,3-Difluoro-2-(p-tolyl)allyl)borane–trimethylamine Complex (13)

Oil (31 mg, 0.13 mmol, 65%); R_f = 0.21 [20% EtOAc/cyclohexane].

IR (film): 2924, 2691, 2117, 1994, 1812, 1715, 1608, 1512 cm^–1.

¹H NMR (CDCl₃, 600 MHz): δ = 7.30 (d, J = 7.8 Hz, 2 H), 7.12 (d, J = 7.8 Hz, 2 H), 2.56 (s, 9 H), 2.33 (s, 3 H), 1.54 (s, 2 H).

¹³C NMR (CDCl₃, 151 MHz): δ = 152.1 (dd, J _C–F = 287.0, 280.4 Hz), 135.9, 133.9 (dd, J _C–F = 5.5, 3.6 Hz), 128.8, 128.3 (t, J _C–F = 3.3 Hz), 95.1 (dd, J _C–F = 23.3, 9.4 Hz), 52.0, 21.3, 16.2.

¹¹B NMR (CDCl₃, 193 MHz): δ = –3.57 (t, J = 97.7 Hz).

¹⁹F NMR (CDCl₃, 565 MHz): δ = –95.60 (d, J = 56.2 Hz), –96.14 (d, J = 56.2 Hz).

HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₃H₂₀NBF₂Na: 262.1549; found: 262.1541.

 

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(3,3-Difluoro-2-(4-phenoxyphenyl)allyl)borane–trimethylamine Complex (14)

Oil (45 mg, 0.14 mmol, 71%); R_f = 0.39 [30% EtOAc/pentane].

IR (film): 2920, 2340, 1713, 1588, 1486, 1232, 1093, 995, 840 cm^–1.

¹H NMR (CDCl₃, 600 MHz): δ = 7.39 (d, J = 8.3 Hz, 2 H), 7.33 (t, J = 7.5 Hz, 2 H), 7.09 (t, J = 7.5 Hz, 1 H), 7.03 (d, J = 7.5 Hz, 2 H), 6.95 (d, J = 8.3 Hz, 2 H), 2.57 (s, 9 H), 1.54 (s, 2 H).

¹³C NMR (CDCl₃, 151 MHz): δ = 157.4, 155.5, 152.2 (dd, J _C–F = 287.0, 281.0 Hz), 131.9 (dd, J _C–F = 5.4, 3.7 Hz), 129.8, 129.7 (dd, J _C–F = 4.3, 3.8 Hz), 123.2, 119.0, 118.4, 94.7 (dd, J _C–F = 23.6, 9.1 Hz), 52.0, 16.4.

¹¹B NMR (CDCl₃, 193 MHz): δ = –3.54 (t, J = 93.3 Hz).

¹⁹F{¹H} NMR (CDCl₃, 565 MHz): δ = –95.10 (d, J = 56.0 Hz), –95.80 (d, J = 56.0 Hz).

HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₈H₂₂ONBF₂Na: 340.1655; found: 340.1653.

 

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(3,3-Difluoro-2-(3-methoxyphenyl)allyl)borane–trimethylamine Complex (15)

Oil (27 mg, 0.11 mmol, 53%); R_f = 0.29 [20% EtOAc/cyclohexane].

IR (film): 2941, 2337, 2092, 1581, 1483, 1230, 1103, 998 cm^–1.

¹H NMR (CDCl₃, 600 MHz): δ = 7.22 (t, J = 7.8 Hz, 1 H), 7.01 (t, J = 7.8 Hz, 1 H), 6.99 (s, 1 H), 6.75 (d, J = 8.1 Hz, 1 H), 3.80 (s, 3 H), 2.56 (s, 9 H), 1.53 (s, 2 H).

¹³C NMR (CDCl₃, 151 MHz): δ = 159.4, 152.3 (dd, J _C–F = 287.9, 281.3 Hz), 138.5 (td, J _C–F = 5.4, 3.2 Hz), 128.8, 121.2 (t, J _C–F = 3.9 Hz), 114.5 (t, J _C–F = 3.4 Hz), 111.9, 95.3 (dd, J _C–F = 23.6, 9.7 Hz), 55.3, 52.1, 16.2.

¹¹B NMR (CDCl₃, 193 MHz): δ = –3.52 (t, J = 94.8 Hz).

¹⁹F NMR (CDCl₃, 565 MHz): δ = –94.65 (d, J = 54.2 Hz), –95.01 (d, J = 54.2 Hz).

HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₃H₂₀ONBF₂Na: 278.1498; found: 278.1497.

 

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(3,3-Difluoro-2-(m-tolyl)allyl)borane–trimethylamine Complex (16)

Oil (30 mg, 0.13 mmol, 63%); R_f = 0.30 [20% EtOAc/cyclohexane].

IR (film): 3025,2955, 2924, 2687, 2115, 1996, 1835, 1722, 1606, 1481 cm^–1.

¹H NMR (CDCl₃, 600 MHz): δ = 7.24–7.15 (m, 3 H), 7.10–6.97 (m, 1 H), 2.56 (s, 9 H), 2.34 (s, 3 H), 1.54 (s, 2 H).

¹³C NMR (CDCl₃, 151 MHz): δ = 152.1 (dd, J _C–F = 287.0, 281.0 Hz), 137.4, 136.9 (dd, J _C–F = 5.4, 3.1 Hz), 129.3 (t, J _C–F = 3.3 Hz), 127.9, 127.2, 125.6 (t, J _C–F = 3.3 Hz), 95.3 (dd, J _C–F = 23.3, 9.4 Hz), 52.1, 21.7, 16.5.

¹¹B NMR (CDCl₃, 193 MHz): δ = –3.57 (t, J = 95.9 Hz).

¹⁹F NMR (CDCl₃, 565 MHz): δ = –95.36 (d, J = 55.2 Hz), –95.96 (d, J = 56.2 Hz).

HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₃H₂₀NBF₂Na: 262.1549; found: 262.1543.

 

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(3,3-Difluoro-2-(4-fluoro-2-methylphenyl)allyl)borane–trimethylamine Complex (17)

Oil (27 mg, 0.11 mmol, 53%); R_f = 0.27 [20% EtOAc/cyclohexane].

IR (film): 2921, 2337, 1995, 1915, 1733, 1586, 1494, 1231, 1144, 1090, 997 cm^–1.

¹H NMR (CDCl₃, 400 MHz): δ = 7.15 (dd, J = 8.4, 6.1 Hz, 1 H), 6.90–6.78 (m, 2 H), 2.53 (s, 9 H), 2.28 (s, 3 H), 1.40 (s, 2 H).

¹³C NMR (CDCl₃, 101 MHz): δ = 161.7 (d, J _C–F = 244.1 Hz), 151.0 (dd, J _C–F­ = 282.8, 280.7 Hz), 139.1 (ddd, J _C–F = 7.7, 2.4, 1.2 Hz), 132.7 (ddd, J _C–F = 5.7, 3.1, 1.1 Hz), 131.3 (ddd, J _C–F = 8.0, 3.4, 1.2 Hz), 116.3 (d, J _C–F = 21.1 Hz), 112.1 (d, J _C–F = 21.1 Hz), 93.0 (dd, J _C–F = 24.0, 14.5 Hz), 54.3, 52.0, 17.9.

¹¹B NMR (CDCl₃, 193 MHz): δ = –3.97 (t, J = 100.1 Hz).

¹⁹F NMR (CDCl₃, 565 MHz): δ = –94.95 (d, J = 58.2 Hz), –98.99 (d, J = 57.2 Hz), –117.07 (ddd, J = 15.6, 9.6, 6.1 Hz).

HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₃H₁₉NBF₃Na: 280.1455; found: 280.1455.

 

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(3,3-Difluoro-2-(3-fluoro-4-methoxyphenyl)allyl)borane–trimethylamine Complex (18)

Oil (28 mg, 0.1 mmol, 50%); R_f = 0.21 [20% EtOAc/cyclohexane].

IR (film): 2939, 2336, 2111, 1832, 1714, 1517, 1464, 1272, 1223, 1130, 1024, 840 cm^–1.

¹H NMR (CDCl₃, 600 MHz): δ = 7.18 (dd, J = 13.1, 1.5 Hz, 1 H), 7.14–7.09 (m, 1 H), 6.89 (t, J = 8.8 Hz, 1 H), 3.87 (s, 3 H), 2.57 (s, 9 H), 1.49 (s, 2 H).

¹³C NMR (CDCl₃, 151 MHz): δ = 152.2 (dd, J _C–F = 287.8, 281.4 Hz), 152.1 (d, J _C–F = 243.4 Hz), 146.0 (d, J _C–F = 10.3 Hz), 130.0, 124.2 (q, J _C–F = 3.3 Hz), 116.2 (dt, J _C–F = 19.0, 3.8 Hz), 112.9 (d, J _C–F = 1.9 Hz), 94.2 (dd, J _C–F = 23.8, 9.8 Hz), 56.4, 52.1, 15.9.

¹¹B NMR (CDCl₃, 193 MHz): δ = –3.64 (t, J = 97.4 Hz).

¹⁹F NMR (CDCl₃, 565 MHz): δ = –94.69 (d, J = 55.2 Hz), –95.32 (d, J = 55.2 Hz), –136.29 (dd, J = 13.6, 8.5 Hz).

HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₃H₁₉ONBF₃Na: 296.1404; found: 296.1402.

 

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(3,3-Difluoro-2-(4-(phenylethynyl)phenyl)allyl)borane–trimethylamine Complex (19)

Oil (25 mg, 0.08 mmol, 38%); R_f = 0.50 [30% EtOAc/pentane].

IR (film): 3440, 2920, 2337, 2253, 1712, 1461, 1383, 1225, 1028, 908, 733, 650 cm^–1.

¹H NMR (CDCl₃, 600 MHz): δ = 7.53 (d, J = 7.5 Hz, 2 H), 7.47 (d, J = 8.0 Hz, 2 H), 7.41 (d, J = 8.0 Hz, 2 H), 7.36–7.30 (m, 3 H), 2.56 (s, 9 H), 1.55 (s, 2 H).

¹³C NMR (CDCl₃, 151 MHz): δ = 152.3 (dd, J _C–F = 289.1, 282.5 Hz), 137.1 (dd, J _C–F = 5.7, 4.0 Hz), 131.7, 131.3, 128.4, 128.4 (dd, J _C–F = 4.4, 3.6 Hz), 128.2, 123.7, 121.0, 95.1 (dd, J _C–F = 24.0, 8.6 Hz), 89.9, 89.2, 52.0, 15.9.

¹¹B NMR (CDCl₃, 193 MHz): δ = –3.64 (t, J = 92.1 Hz).

¹⁹F NMR (CDCl₃, 565 MHz): δ = –93.43 (d, J = 51.2 Hz), –94.11 (d, J = 52.2 Hz).

HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₀H₂₂NBF₂Na: 348.1706; found: 348.1699.

 

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3-(4-(3-Boranyl-1,1-difluoroprop-1-en-2-yl)phenyl)pyridine–trimethylamine Complex (20)

Oil (36 mg, 0.12 mmol, 60%); R_f = 0.33 [EtOAc].

IR (film): 3001, 2923, 2855, 2340, 2088, 1914, 1708, 1475, 1220, 1097, 997, 842 cm^–1.

¹H NMR (CDCl₃, 400 MHz): δ = 8.87 (br s, 1 H), 8.57 (br s, 1 H), 7.88 (t, J = 7.7 Hz, 1 H), 7.54 (s, 4 H), 7.35 (dd, J = 7.7, 4.8 Hz, 2 H), 2.59 (s, 9 H), 1.58 (br s, 4 H).

¹³C NMR (CDCl₃, 101 MHz): δ = 152.3 (dd, J = 288.3, 282.1 Hz), 148.3, 136.9 (dd, J = 5.4, 3.7 Hz), 136.6, 135.6, 134.3, 129.1 (t, J = 3.8 Hz), 126.7, 123.6, 94.9 (dd, J = 24.0, 8.7 Hz), 52.0, 16.0.

¹¹B NMR (CDCl₃, 128 MHz): δ = –3.60 (t, J = 90.2 Hz).

¹⁹F{¹H} NMR (CDCl₃, 565 MHz): δ = –93.84 (d, J = 53.2 Hz), –94.68 (d, J = 53.2 Hz).

HRMS (ESI): m/z [M + H]⁺ calcd for C₁₇H₂₂N₂BF₂: 303.1834; found: 303.1837.

 

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(3,3-Difluoro-2-(naphthalen-1-yl)allyl)borane–trimethylamine Complex (21)

Oil (50 mg, 0.18 mmol, 91%); R_f = 0.30 [20% EtOAc/cyclohexane].

IR (film): 2916, 2340, 1731, 1590, 1481, 1223, 1127, 1075, 990, 907 cm^–1.

¹H NMR (CDCl₃, 400 MHz): δ = 8.04 (dd, J = 8.0, 1.1 Hz, 1 H), 7.84 (dd, J = 8.1, 1.6 Hz, 1 H), 7.76 (d, J = 2.8 Hz, 1 H), 7.55–7.38 (m, 4 H), 2.49 (s, 9 H), 1.61 (br s, 2 H).

¹³C NMR (CDCl₃, 101 MHz): δ = 151.6 (dd, J _C–F = 283.3, 281.6 Hz), 135.1 (dd, J _C–F = 5.8, 1.1 Hz), 133.8, 132.0, 131.9, 128.4, 127.3, 126.0, 125.7, 125.5, 125.4, 93.1 (dd, J _C–F = 24.2, 14.4 Hz), 52.0, 18.3.

¹¹B{¹H} NMR (CDCl₃, 193 MHz): δ = –3.80.

¹⁹F{¹H} NMR (CDCl₃, 565 MHz): δ = –93.89 (d, J = 57.2 Hz), –97.85 (d, J = 57.2 Hz).

HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₆H₂₀NBF₂Na: 298.1549; found: 298.1551.

 

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(3,3-Difluoro-2-(4-methoxynaphthalen-1-yl)allyl)borane–trimethylamine Complex (22)

Oil (45 mg, 0.15 mmol, 74%); R_f = 0.12 [20% EtOAc/pentane].

IR (film): 3343, 2300, 1878, 1597, 1460, 1028, 843, 780 cm^–1.

¹H NMR (CDCl₃, 600 MHz): δ = 8.27 (dd, J = 8.3, 0.7 Hz, 1 H), 7.96 (d, J = 8.3 Hz, 1 H), 7.50 (ddd, J = 8.2, 6.8, 1.4 Hz, 1 H), 7.45 (ddd, J = 8.2, 6.8, 1.4 Hz, 1 H), 7.32 (d, J = 7.9 Hz, 1 H), 6.80 (d, J = 7.9 Hz, 1 H), 3.99 (s, 3 H), 2.49 (s, 9 H).

¹³C NMR (CDCl₃, 151 MHz): δ = 154.7, 151.9 (dd, J _C–F = 283.6, 280.8 Hz), 132.8 (d, J _C–F = 2.8 Hz), 127.2 (dd, J _C–F = 3.5, 1.0 Hz), 126.2, 125.8, 125.8, 124.9, 122.3, 103.4, 92.9 (dd, J _C–F = 24.0, 14.3 Hz), 55.5, 52.0, 18.2.

¹¹B NMR (CDCl₃, 193 MHz): δ = –3.68 (t, J = 89.6 Hz).

¹⁹F{¹H} NMR (CDCl₃, 565 MHz): δ = –94.44 (d, J = 57.2 Hz), –97.99 (d, J = 57.2 Hz).

HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₇H₂₂ONBF₂Na: 328.1655; found: 328.1569.

 

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(3,3-Difluoro-2-(4-fluoronaphthalen-1-yl)allyl)borane–trimethylamine Complex (23)

Solid (41 mg, 0.14 mmol, 70%); R_f = 0.44 [25% EtOAc/pentane]; mp 85–87 °C.

IR (film): 3343, 2923, 1878, 1597, 1460, 1028, 843, 780 cm^–1.

¹H NMR (CDCl₃, 600 MHz): δ = 8.10 (d, J = 8.0 Hz, 1 H), 8.00 (d, J = 8.0 Hz, 1 H), 7.56–7.49 (m, 2 H), 7.35–7.31 (m, 1 H), 7.13–7.06 (m, 1 H), 2.50 (s, 9 H), 1.54 (s, 2 H).

¹³C NMR (CDCl₃, 151 MHz): δ = 158.1 (d, J _C–F = 251.0 Hz), 151.8 (dd, J _C–F = 282.8, 282.2 Hz), 133.2, 131.0 (t, J _C–F = 4.8 Hz), 127.0 (ddd, J _C–F = 3.2, 2.3, 1.2 Hz), 126.7, 126.0 (d, J _C–F = 2.8 Hz), 125.9 (d, J _C–F = 2.0 Hz), 123.9 (d, J _C–F = 16.3 Hz), 120.8 (d, J _C–F = 5.4 Hz), 109.0 (d, J _C–F = 19.4 Hz), 92.6 (dd, J _C–F = 24.8, 13.9 Hz), 52.0, 18.4.

¹¹B NMR (CDCl₃, 193 MHz): δ = –3.81 (t, J = 98.8 Hz).

¹⁹F NMR (CDCl₃, 565 MHz): δ = –93.79 (d, J = 55.2 Hz), –97.56 (d, J = 56.2 Hz), –124.92 (dd, J = 11.0, 5.0 Hz).

HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₆H₁₉NBF₃Na: 316.1455; found: 316.1448.

 

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(3,3-Difluoro-2-(naphthalen-2-yl)allyl)borane–trimethylamine Complex (24)

Oil (20 mg, 0.07 mmol, 36%); R_f = 0.21 [20% EtOAc/cyclohexane].

IR (film): 3016, 2946, 2351, 1829, 1715, 1484, 1247, 1078, 985, 823, 750 cm^–1.

¹H NMR (CDCl₃, 400 MHz): δ = 7.85 (s, 1 H), 7.82–7.76 (m, 3 H), 7.59–7.53 (m, 1 H), 7.46–7.39 (m, 2 H), 2.57 (s, 9 H), 1.65 (br s, 2 H).

¹³C NMR (CDCl₃, 151 MHz): δ = 152.4 (dd, J _C–F = 287.6, 281.6 Hz), 134.5 (dd, J _C–F = 5.5, 3.6 Hz), 133.5, 132.3, 128.1, 127.6, 127.4, 127.3 (t, J _C–F = 3.6 Hz), 127.0 (t, J _C–F = 3.3 Hz), 125.8, 125.5, 95.5 (dd, J _C–F = 23.6, 9.1 Hz) 52.1, 16.2.

¹¹B NMR (CDCl₃, 193 MHz): δ = –3.56 (t, J = 94.8 Hz).

¹⁹F NMR (CDCl₃, 565 MHz): δ = –94.47 (d, J = 53.2 Hz), –95.44 (d, J = 54.2 Hz).

HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₆H₂₀NBF₂Na: 298.1549; found: 298.1548.

 

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tert-Butyl 3-(3-Boranyl-1,1-difluoroprop-1-en-2-yl)-1H-indole-1-carboxylate–trimethylamine Complex (25)

Oil (50 mg, 0.14 mmol, 70%); R_f = 0.23 [20% EtOAc/cyclohexane].

IR (film): 2979, 2931, 2364, 1831, 1729, 1453, 1371, 1249, 1153, 1074, 988 cm^–1.

¹H NMR (CDCl₃, 400 MHz): δ = 8.13 (d, J = 6.8 Hz, 1 H), 7.60 (s, 1 H), 7.57 (d, J = 7.9 Hz, 1 H), 7.29 (ddd, J = 8.4, 7.1, 1.4 Hz, 1 H), 7.24–7.17 (m, 1 H), 2.55 (s, 9 H), 1.66 (s, 9 H), 1.58 (s, 2 H).

¹³C NMR (CDCl₃, 101 MHz): δ = 152.0 (dd, J _C–F = 286.1, 282.1 Hz), 149.9, 135.3, 129.9, 124.4 (dd, J _C–F = 4.7, 1.3 Hz), 124.1, 122.5, 120.7 (d, J _C–F = 4.4 Hz), 117.0 (dd, J _C–F = 5.6, 1.8 Hz), 115.3, 87.7 (dd, J _C–F = 27.2, 12.0 Hz), 83.6, 52.1, 28.4, 16.9.

¹¹B{¹H} NMR (CDCl₃, 128 MHz): δ = –3.70.

¹⁹F NMR (CDCl₃, 376 MHz): δ = –91.63 (d, J = 55.4 Hz), –95.88 (d, J = 53.6 Hz).

HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₉H₂₇O₂N₂BF₂Na: 387.2026; found: 387.2022.

 

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(2-(Benzofuran-5-yl)-3,3-difluoroallyl)borane–trimethylamine Complex (26)

Oil (31 mg, 0.12 mmol, 59%); R_f = 0.19 [30% EtOAc/pentane].

IR (film): 2919, 2328, 2096, 1942, 1718, 1466, 1304, 1212, 1096, 997, 840, 739 cm^–1.

¹H NMR (CDCl₃, 600 MHz): δ = 7.61 (s, 1 H), 7.58 (s, 1 H), 7.43 (d, J = 8.6 Hz, 1 H), 7.34 (d, J = 8.6 Hz, 1 H), 6.73 (s, 1 H), 2.56 (s, 9 H), 1.59 (s, 2 H).

¹³C NMR (CDCl₃, 151 MHz): δ = 153.9, 151.5 (dd, J _C–F = 285.9, 280.2 Hz), 145.1, 131.7 (dd, J _C–F = 5.4, 2.9 Hz), 127.3, 125.2, 121.2, 110.8, 106.9, 95.4 (dd, J _C–F = 23.5, 9.7 Hz), 52.1, 17.3.

¹¹B NMR (CDCl₃, 193 MHz): δ = –3.86 (t, J = 102.2 Hz).

¹⁹F NMR (CDCl₃, 565 MHz): δ = –96.18 (d, J = 58.2 Hz), –96.97 (d, J = 58.2 Hz).

HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₄H₁₈ONBF₂Na: 278.1342; found: 288.1340.

 

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(2-(Benzo[b]thiophen-5-yl)-3,3-difluoroallyl)borane–trimethylamine Complex (27)

Oil (22 mg, 0.08 mmol, 79%); R_f = 0.66 [40% EtOAc/pentane].

IR (film): 3420, 2922, 2342, 2093, 1829, 1715, 1480, 1440, 1220, 1052, 989, 702 cm^–1.

¹H NMR (CDCl₃, 600 MHz): δ = 7.84 (s, 1 H), 7.80 (d, J = 8.4 Hz, 1 H), 7.43–7.35 (m, 2 H), 7.30 (d, J = 5.3 Hz, 1 H), 2.56 (s, 9 H), 1.61 (s, 2 H).

¹³C NMR (CDCl₃, 151 MHz): δ = 152.2 (dd, J _C–F = 286.3, 280.9 Hz), 139.7, 137.9, 133.2 (dd, J _C–F = 5.8, 3.5 Hz), 126.3, 125.2 (t, J _C–F = 3.3 Hz), 124.2, 123.6 (d, J _C–F = 3.6 Hz), 121.9, 95.3 (dd, J _C–F = 23.9, 9.4 Hz), 52.1, 16.6.

¹¹B NMR (CDCl₃, 193 MHz): δ = –3.87 (t, J = 102.4 Hz).

¹⁹F NMR (CDCl₃, 565 MHz): δ = –95.33 (d, J = 56.2 Hz), –96.17 (d, J = 56.2 Hz).

HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₄H₁₈NSBF₂Na: 304.1119; found: 304.1107.

 

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(3,3-Difluoro-2-(2-methyl-2H-indazol-6-yl)allyl)borane–trimethylamine Complex (28)

Oil (37 mg, 0.13 mmol, 66%); R_f = 0.21 [40% EtOAc/pentane].

IR (film): 2999, 2924, 2336, 1715, 1631, 1464, 1208, 994, 840 cm^–1.

¹H NMR (CDCl₃, 600 MHz): δ = 7.79 (s, 1 H), 7.70 (s, 1 H), 7.54 (d, J = 8.7 Hz, 1 H), 7.16 (d, J = 8.7 Hz, 1 H), 4.17 (s, 3 H), 2.54 (s, 9 H), 1.60 (s, 2 H).

¹³C NMR (CDCl₃, 151 MHz): δ = 152.2 (dd, J _C–F = 287.3, 281.5 Hz), 149.5, 134.8 (dd, J _C–F = 5.0, 3.4 Hz), 123.6 (dd, J _C–F = 3.6, 3.6 Hz), 123.3, 121.0, 119.0, 116.4 (dd, J _C–F = 3.7, 3.7 Hz), 95.8 (dd, J _C–F = 23.2, 9.5 Hz), 52.0, 40.3, 16.7.

¹¹B NMR (CDCl₃, 193 MHz): δ = –3.58 (t, J = 99.8 Hz).

¹⁹F{¹H} NMR (CDCl₃, 565 MHz): δ = –94.90 (d, J = 54.3 Hz), –95.20 (d, J = 55.1 Hz).

HRMS (ESI): m/z [M + H]⁺ calcd for C₁₄H₂₁N₃BF₂: 278.1791; found: 278.1793.

 

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N-(4-(3-boraneyl-1,1-difluoroprop-1-en-2-yl)phenyl)-2-(4-chloro-2-methylphenoxy)propanamide–trimethylamine Complex (29)

Oil (23 mg, 0.05 mmol, 26%); R_f = 0.29 [40% EtOAc/pentane].

IR (film): 2924, 2339, 1686, 1593, 1522, 1485, 1404, 1293, 1238, 1186, 1094, 1039, 996, 839 cm^–1.

¹H NMR (CDCl₃, 600 MHz): δ = 8.07 (s, 1 H), 7.40 (d, J = 8.5 Hz, 2 H), 7.30 (d, J = 8.5 Hz, 2 H), 7.11 (d, J = 2.5 Hz, 1 H), 7.03 (dd, J = 8.7, 2.5 Hz, 1 H), 6.68 (d, J = 8.7 Hz, 1 H), 4.63 (q, J = 6.8 Hz, 1 H), 2.47 (s, 9 H), 2.24 (s, 3 H), 1.57 (d, J = 6.8 Hz, 3 H), 1.45 (s, 2 H).

¹³C NMR (CDCl₃, 151 MHz): δ = 169.9, 155.1, 153.7, 152.2 (dd, J _C–F = 287.6, 281.4 Hz), 135.1, 133.5 (dd, J _C–F = 5.5, 3.6 Hz), 131.2, 129.3, 129.2 (t, J _C–F = 3.7 Hz), 127.1, 119.5, 114.5, 94.7 (dd, J _C–F = 23.8, 9.2 Hz), 76.3, 52.0, 18.8, 16.5, 16.1.

¹¹B NMR (CDCl₃, 193 MHz): δ = –3.69 (t, J = 81.1 Hz).

¹⁹F{¹H} NMR (CDCl₃, 565 MHz): δ = –94.90 (d, J = 55.2 Hz), –95.51 (d, J = 54.4 Hz).

HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₂H₂₈O₂NBClF₂Na: 459.1793; found: 459.1796.

 

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4,4′-(3,3-Difluoroprop-1-ene-1,2-diyl)bis(methoxybenzene) (34)

Oil (19 mg, 0.07 mmol, 65%); R_f = 0.26 [cyclohexane].

IR (film): 2935, 2838, 2109, 1609, 1511, 1246, 1178, 1028, 988 cm^–1.

¹H NMR (CDCl₃, 600 MHz): δ = 7.43 (d, J = 9.0 Hz, 2 H), 7.27 (d, J = 8.9 Hz, 2 H), 6.89 (d, J = 9.0 Hz, 2 H), 6.80 (d, J = 8.9 Hz, 2 H), 5.65 (s, 1 H), 5.58 (s, 1 H), 3.81 (s, 3 H), 3.78 (s, 3 H).

¹³C NMR (CDCl₃, 151 MHz): δ = 160.8, 159.6, 145.0 (t, J _C–F = 26.3 Hz), 129.5, 129.1, 128.9 (t, J _C–F = 27.9 Hz), 127.6 (t, J _C–F = 5.4 Hz), 120.8 (t, J _C–F = 241.6 Hz), 118.0 (t, J _C–F = 7.9 Hz), 113.7, 113.7, 55.4, 55.3.

¹⁹F{¹H} NMR (CDCl_3, 565 MHz): δ = –89.30.

HRMS (EI): m/z [M]⁺ calcd for C₁₇H₁₆O₂F₂: 290.1112; found: 290.1113.

 

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5-(4-(3,3-Difluoro-2-(4-methoxyphenyl)prop-1-en-1-yl)phenyl)isoxazole (35)

Oil (15 mg, 0.05 mmol, 47%); R_f = 0.14 [10% EtOAc/pentane].

IR (film): 2926, 2322, 1740, 1603, 1509, 1458, 1290, 1239, 1183, 1029, 836, 793 cm^–1.

¹H NMR (CDCl₃, 600 MHz): δ = 8.31 (d, J = 1.8 Hz, 1 H), 7.82 (d, J = 8.1 Hz, 2 H), 7.60 (d, J = 8.3 Hz, 2 H), 7.29–7.25 (m, 2 H), 6.83–6.79 (m, 2 H), 6.57 (d, J = 1.9 Hz, 1 H), 5.71 (s, 1 H), 5.62 (s, 1 H), 3.79 (s, 3 H).

¹³C NMR (CDCl₃, 151 MHz): δ = 168.6, 159.7, 151.0, 144.6 (t, J _C–F = 25.5 Hz), 138.4 (t, J _C–F = 28.3 Hz), 129.5, 128.7, 128.6, 126.8 (t, J _C–F = 5.5 Hz), 125.9, 120.2 (t, J _C–F = 242.3 Hz), 118.5 (t, J _C–F = 8.2 Hz), 113.8, 99.6, 55.4.

¹⁹F{¹H} NMR (CDCl₃, 565 MHz): δ = –91.86.

HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₉H₁₅O₂NF₂Na: 350.0963; found: 350.0966.

 

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5-(3,3-Difluoro-2-(4-methoxyphenyl)prop-1-en-1-yl)-2-(trifluoromethyl)pyridine (36)

Oil (16 mg, 0.05 mmol, 48%); R_f = 0.48 [10% EtOAc/pentane].

IR (film): 2936, 2307, 1738, 1608, 1512, 1335, 1251, 1139, 1034, 989, 837 cm^–1.

¹H NMR (CDCl₃, 600 MHz): δ = 8.81 (s, 1 H), 7.94 (dd, J = 8.2, 1.1 Hz, 1 H), 7.68 (d, J = 8.2 Hz, 1 H), 7.24 (d, J = 8.9 Hz, 2 H), 6.82 (d, J = 8.8 Hz, 2 H), 5.75 (s, 1 H), 5.64 (s, 1 H), 3.79 (s, 3 H).

¹³C NMR (CDCl₃, 151 MHz): δ = 160.0, 149.5 (q, J _C–F = 35.9 Hz), 147.9 (t, J _C–F = 6.1 Hz), 143.8 (t, J _C–F = 24.7 Hz), 135.4, 135.3, 129.6, 127.7, 121.5 (q, J = 273.1 Hz), 120.1 (q, J _C–F = 2.7 Hz), 119.3 (t, J _C–F = 8.3 Hz), 119.1 (t, J _C–F = 242.0 Hz), 114.1, 55.4.

¹⁹F{¹H} NMR (CDCl₃, 565 MHz): δ = –68.11, –92.57.

HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₆H₁₂ONF₅Na: 352.0731; found: 352.0732.

 

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tert-Butyl 5-(3,3-Difluoro-2-(4-methoxyphenyl)prop-1-en-1-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (37)

Oil (18 mg, 0.05 mmol, 46%); R_f = 0.30 [20% Et₂O/pentane].

IR (film): 2980, 2083, 1732, 1608, 1514, 1375, 1319, 1252, 1157, 1029, 838, 736 cm^–1.

¹H NMR (CDCl₃, 600 MHz): δ = 8.61 (d, J = 2.1 Hz, 1 H), 8.00 (d, J = 2.2 Hz, 1 H), 7.68 (d, J = 4.1 Hz, 1 H), 7.26 (d, J = 8.7 Hz, 2 H), 6.77 (d, J = 8.9 Hz, 2 H), 6.52 (d, J = 4.0 Hz, 1 H), 5.73 (s, 1 H), 5.62 (s, 1 H), 3.76 (s, 3 H), 1.66 (s, 9 H).

¹³C NMR (CDCl₃, 151 MHz): δ = 159.7, 148.8, 147.9, 144.7 (t, J _C–F = 25.5 Hz), 143.4 (t, J _C–F = 5.6 Hz), 129.5, 128.5, 128.0, 127.5 (t, J _C–F = 27.9 Hz), 127.1 (d, J _C–F = 5.8 Hz), 122.4, 120.4 (t, J _C–F = 242.7 Hz), 118.5 (t, J = 8.0 Hz), 113.8, 104.8, 84.7, 55.3, 28.2.

¹⁹F{¹H} NMR (CDCl₃, 565 MHz): δ = –89.61.

HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₂H₂₂O₃N₂F₂Na: 423.1491; found: 423.1491.

 

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3-((5-(3,3-Difluoro-2-(4-methoxyphenyl)prop-1-en-1-yl)pyridin-2-yl)oxy)-5,5-dimethyl-4-(4-(methylsulfonyl)phenyl)furan-2(5H)-one (38)

Oil (25 mg, 0.05 mmol, 45%); R_f = 0.36 [50% EtOAc/pentane].

IR (film): 2934, 2306, 2088, 1769, 1603, 1513, 1479, 1313, 1241, 1150, 1094, 1030, 838, 771 cm^–1.

¹H NMR (CDCl₃, 600 MHz): δ = 8.26 (d, J = 1.3 Hz, 1 H), 7.99 (d, J = 8.5 Hz, 2 H), 7.77 (dd, J = 8.6, 2.5 Hz, 1 H), 7.70 (d, J = 8.5 Hz, 2 H), 7.26 (d, J = 8.9 Hz, 2 H), 6.98 (d, J = 8.6 Hz, 1 H), 6.82 (d, J = 8.8 Hz, 2 H), 5.65 (s, 1 H), 5.60 (s, 1 H), 3.79 (s, 3 H), 3.06 (s, 3 H), 1.75 (s, 6 H).

¹³C NMR (CDCl₃, 151 MHz): δ = 165.7, 162.1, 159.9, 149.2, 145.8 (t, J _C–F = 6.1 Hz), 144.3, 144.1, 141.7, 138.0 (t, J _C–F = 4.9 Hz), 137.6, 134.9, 129.5, 129.0, 128.7 (t, J _C–F = 29.2 Hz), 128.2 (t, J _C–F = 26.2 Hz), 128.1, 119.7 (t, J _C–F = 244.7 Hz), 119.0 (t, J _C–F = 8.0 Hz), 113.9, 110.8, 84.6, 55.4, 44.5, 26.4.

¹⁹F{¹H} NMR (CDCl₃, 565 MHz): δ = –90.32.

HRMS (ESI): m/z [M + Na]⁺ calcd for C₂₈H₂₅O₆NF₂SNa: 564.1263; found: 564.1260.

 

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Methyl 4-(3,3-Difluoro-1-(4-methoxyphenyl)prop-1-en-2-yl)benzoate (39)

Oil (20 mg, 0.06 mmol, 62%); R_f = 0.31 [20% EtOAc/cyclohexane].

IR (film): 2953, 2323, 2087, 2009, 1929, 1721, 1610, 1514, 1436, 1278, 1180, 1107, 1033, 988 cm^–1.

¹H NMR (CDCl₃, 600 MHz): δ = 7.93 (d, J = 8.4 Hz, 2 H), 7.40 (t, J = 8.1 Hz, 4 H), 6.88 (d, J = 8.9 Hz, 2 H), 5.79 (s, 1 H), 5.68 (s, 1 H), 3.90 (s, 3 H), 3.81 (s, 3 H).

¹³C NMR (151 MHz, CDCl₃): δ = 166.7, 160.8, 145.0 (t, J _C–F = 26.9 Hz), 141.1, 129.7, 129.4, 128.2, 127.4 (t, J _C–F = 5.4 Hz), 120.4 (t, J _C–F = 242.2 Hz), 120.2 (t, J _C–F = 7.9 Hz), 113.7, 55.3, 52.1.

¹⁹F{¹H} NMR (565 MHz, CDCl₃): δ = –89.50.

HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₈H₁₆O₃F₂Na: 341.0960; found: 341.0954.

 

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Methyl 4-(1,1-Difluoro-3-hydroxyprop-1-en-2-yl)benzoate (40)

Oil (15 mg, 0.041 mmol, 41%); R_f = 0.14 [20% acetone/cyclohexane].

IR (film): 3440, 2954, 2329, 2091, 1709, 1610, 1437, 1281, 1191, 1108, 1010, 900 cm^–1.

¹H NMR (CDCl₃, 600 MHz): δ = 8.05 (d, J = 8.4 Hz, 2 H), 7.54 (d, J = 8.4 Hz, 2 H), 4.66–4.40 (m, 2 H), 3.93 (s, 3 H).

¹³C NMR (151 MHz, CDCl₃): δ = 166.8, 155.4 (dd, J _C–F = 298.5, 292.8 Hz), 137.0, 130.0, 129.5, 128.2 (t, J _C–F = 3.6 Hz), 93.1 (dd, J _C–F = 11.4, 8.7 Hz), 59.0 (dd, J _C–F = 4.8, 2.4 Hz), 52.3.

¹⁹F NMR (CDCl₃, 565 MHz): δ = –85.67 (dt, J = 28.1, 2.6 Hz), –85.81 (d, J = 28.1 Hz).

HRMS (EI): m/z [M]⁺ calcd for C₁₁H₁₀O₃F₂: 228.0593; found: 228.0593.

 

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Methyl 4-(1,1-Difluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)prop-1-en-2-yl)benzoate (41)

Colorless oil (10 mg, 0.03 mmol, 42%); R_f = 0.45 [20% EtOAc/cyclohexane].

IR (film): 2981, 2316, 2095, 1930, 1815, 1719, 1610, 1437, 1350, 1277, 1105, 961 cm^–1.

¹H NMR (CDCl₃, 600 MHz): δ = 7.99 (d, J = 8.3 Hz, 2 H), 7.43 (d, J = 8.3 Hz, 2 H), 3.91 (s, 3 H), 1.97 (s, 2 H), 1.14 (s, 12 H).

¹³C NMR (151 MHz, CDCl₃): δ = 167.0, 153.7 (dd, J _C–F = 292.2, 286.7 Hz), 140.3, 129.6, 128.6, 127.9 (t, J _C–F = 3.9 Hz), 88.8 (dd, J _C–F = 24.2, 13.9 Hz), 83.9, 52.2, 24.7, 11.5.

¹¹B{¹H} NMR (193 MHz, CDCl₃): δ = 32.90.

¹⁹F NMR (CDCl₃, 565 MHz): δ = –88.05 (d, J = 40.2 Hz), –89.53 (d, J = 39.2 Hz).

HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₇H₂₁O₄BF₂Na: 361.1393; found: 361.1390.

 

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Methyl 4-(3-(Chloro(trimethylamino)-λ⁴-boranyl)-1,1-difluoroprop-1-en-2-yl)benzoate (42)

Oil (22 mg, 0.07 mmol, 69%, mixture 1:1.4 mono- and disubstituted); R_f = 0.41 [50% EtOAc/pentane].

IR (film): 2952, 2923, 2424, 2094, 1718, 1609, 1438, 1282, 1230, 1110, 836 cm^–1.

¹H NMR (CDCl₃, 600 MHz): δ = 7.98 (d, J = 8.5 Hz, 2 H), 7.45 (d, J = 7.1 Hz, 2 H), 3.90 (s, 3 H), 2.65 (s, 9 H), 1.73 (s, 1 H).

¹³C NMR (CDCl₃, 151 MHz): δ = 167.2, 153.2 (dd, J _C–F = 289.2, 284.3 Hz), 141.1 (d, J _C–F = 3.9 Hz), 129.4, 128.7 (t, J _C–F = 3.6 Hz), 128.3, 93.3 (dd, J _C–F = 23.1, 12.1 Hz), 52.1, 49.8.

¹¹B NMR (CDCl₃, 193 MHz): δ = 4.33 (d, J = 122.9 Hz).

¹⁹F{¹H} NMR (CDCl₃, 565 MHz): δ = –91.37 (d, J = 46.2 Hz), –92.58 (d, J = 46.6 Hz).

HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₄H₁₉O₂NBClF₂Na: 340.1058; found: 340.1062.

 

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Methyl 4-(1,1-Difluoro-3-(4-methyl-2,6-dioxotetrahydro-2H-4λ⁴,8λ⁴-[1,3,2]oxazaborolo[2,3-b][1,3,2]oxazaborol-8-yl)prop-1-en-2-yl)benzoate (43)

Solid (23 mg, 0.06 mmol, 63%); mp 206–208 °C.

IR (film): 2961, 1748, 1706, 1605, 1437, 1278, 1231, 1100, 1033, 956, 863, 777 cm^–1.

¹H NMR (DMSO-d ₆, 600 MHz): δ = 7.91 (d, J = 8.1 Hz, 2 H), 7.51 (d, J = 8.0 Hz, 2 H), 4.15 (d, J = 17.0 Hz, 2 H), 3.97 (d, J = 17.0 Hz, 2 H), 3.84 (s, 3 H), 2.87 (s, 3 H), 1.80 (s, 2 H).

¹³C NMR (DMSO-d ₆, 151 MHz): δ = 168.5, 166.0, 153.2 (t, J _C–F = 288.3 Hz), 139.9 (d, J _C–F = 1.9 Hz), 129.0, 128.6 (t, J _C–F = 3.4 Hz), 128.1, 90.7 (d, J _C–F = 12.6 Hz), 90.6 (d, J _C–F = 12.3 Hz), 61.6, 52.1, 45.5.

¹⁹F NMR (DMSO-d ₆, 565 MHz): δ = –89.87 (d, J = 44.0 Hz), –91.56 (d, J = 43.8 Hz).

HRMS (ESI): m/z [M + Na]⁺ calcd for C₁₆H₁₆BF₂NO₆Na: 390.0936; found: 390.0932.

 

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Conflict of Interest

The authors declare no conflict of interest.

Acknowledgment

We want to thank Prof Daniele Leonori for the opportunity to publish in the Synthesis special edition on boryl radicals. Dedicated to Prof. Maria Rita Cratassa, a philosophy enthusiast with an adventurous character. An example of tenacity, resolve and wit, and a model of humility and compassion. Thank you Tatì.

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Publication History

Received: 25 September 2024

Accepted after revision: 28 November 2024

Accepted Manuscript online:
12 December 2024

Article published online:
20 January 2025