Palladium-catalyzed borylation of aryl iodides with 2,3-dihydro-1H-benzo[d] [1,3,2]diazaboroles

Article abstract of DOI:10.3987/COM-13-S(S)43

The palladium-catalyzed borylation of aryl iodides with 2,3-dihydro-1H-benzo[d][1,3,2]diazaboroles was achieved. The mild reaction conditions employed allowed for the inclusion of a wide variety of functional groups in aryl iodides to be tolerated. Additionally, the borylated products can be transformed into the corresponding boronic acids or their esters under acidic conditions.

Full text of DOI:10.3987/COM-13-S(S)43

Supporting Information
PALLADIUM-CATALYZED BORYLATION OFARYL IODIDES WITH
2,3-DIHYDRO-1H-BENZO[d][1,3,2]DIAZABOROLES
Miki Murata,* Nobuyoshi Hirai, Michihiro Okuyama,
Takeshi Namikoshi, and Shinji Watanabe
Department of Materials Science and Engineering, Kitami Institute of Technology,
165 Koen-cho, Kitami, Hokkaido 090-8507, Japan
muratamk@mail.kitami-it.ac.jp
General Considerations.
All experiments were carried out under a nitrogen atmosphere using oven-dried (120 °C) glassware. NMR
spectra were recorded on a JEOL JNM-A500 spectrometer (1H, 500 MHz; 13C, 125 MHz) or a JEOL
1
ECX-400 spectrometer (1H, 400 MHz; 13C, 100 MHz). Chemical shifts of H NMR and 13C NMR signals
reported δ ppm referenced to the solvent or an internal SiMe4. Mass spectra were obtained at an ionization
potential of 70 eV with a JEOL JMS-T100GCV spectrometer. GLC analyses were carried out with a
Shimadzu GC-14B equipped with a glass column (OV-17 on Chromosorb W, 2 m). GLC yields were
determined using suitable hydrocarbons as internal standards.
Materials.
Toluene and 1,4-dioxane were distilled from sodium benzophenone ketyl before use. Aryl halides 2,
Pd[P(t-Bu)3]2 (TCI Co., Inc.) and Et3N (Kanto Chemical Co., Inc.) were purchased from commercial
sources, and used without purification. 1,3,5,6-Tetramethyl-2,3-dihydro-1H-benzo[d][1,3,2]diazaborole (1)
was prepared by the literature methods.1 PdCl2(dtbpf) (DtBPF = 1,1′-bis(di-tert-butylphosphino)ferrocene)
was prepared by the treatment of PdCl2(MeCN)2 with DtBPF.2
Procedure for Arylboronate Synthesis (Tables 1 and 2)
In a glove box, 1 (0.375 mmol), 2 (0.25 mmol), and Pd catalyst (7.5 μmol), and Et3N (104 µL, 0.75 mmol)
were placed in a screw-capped vial containing a stir bar, and dissolved in 1.0 mL of solvent. The vial was
sealed with a cap equipped and removed from the glove box. The reaction mixture was then stirred at 80 °C
for 3–6 h, and then cooled to room temperature. Pinacol (35.4 mg, 0.3 mmol) and 6 M aq HCl (0.5 mL)
– S1 –

were added to the mixture. After stirring for 15 h at room temperature, the GC analysis of the resulting
mixture indicated the formation of the corresponding pinacol boronate esters.
Borylation of Electron-Rich Aryl Iodides  General Procedure A (Table 3)
In a glove box, 1 (65.3 mg, 0.375 mmol), 2 (0.25 mmol), and PdCl2(dtbpf) (4.9 mg, 7.5 μmol) were placed
in a screw-capped vial containing a stir bar, and dissolved in 1,4-dioxane (1.0 mL) and Et3N (104 µL, 0.75
mmol). The vial was sealed with a cap equipped and removed from the glove box. The reaction mixture
was then stirred at 80 °C for 6 h. The resulting mixture was allowed to cool to room temperature, diluted
with toluene, washed with brine, and dried over Na2SO4. The solvent was removed under reduced pressure,
and the residue was purified by silica gel chromatography to give the desired product 3.
Borylation of Electron-Deficient Aryl Iodides  General Procedure B (Table 3)
In a glove box, 1 (0.375 mmol), 2 (0.25 mmol), and Pd[P(t-Bu)3]2 (3.8 mg, 7.5 μmol) were placed in a
screw-capped vial containing a stir bar, and dissolved in toluene (1.0 mL) and Et3N (0.75 mmol). The vial
was sealed with a cap equipped and removed from the glove box. The reaction mixture was then stirred at
80 °C for 3 h. The resulting mixture was allowed to cool to room temperature, diluted with toluene, washed
with brine, and dried over Na2SO4. The solvent was removed under reduced pressure, and the residue was
purified by silica gel chromatography to give the desired product 3.
2-(4-Methoxyphenyl)-1,3,5,6-tetramethyl-2,3-dihydro-1H-benzo[d][1,3,2]diazaborole (3a). Following
the general procedure A, the title compound was prepared starting from 2a (57.7 mg, 0.247 mmol). Silica
gel chromatography afforded the analytically pure product (55.3 mg, 80% yield) as a white solid. 1H NMR
(500 MHz, CDCl3): δ = 2.35 (s, 6 H), 3.34 (s, 6 H), 3.87 (s, 3 H), 6.84 (s, 2 H), 7.02 (d, J = 8.5 Hz, 2 H),
7.54 (d, J = 9.0 Hz, 2 H). 13C NMR (CDCl3): δ = 19.96, 29.73, 55.03, 109.44, 113.61, 126.46, 135.43,
136.56, 159.91. HRMS (EI): m/z calcd for C17H21BN2O [M+]: 280.1747; found: 280.1740.
4-(1,3,5,6-Tetramethyl-1,3-dihydro-2H-benzo[d][1,3,2]diazaborol-2-yl)phenol (3c). Following the
general procedure A, the title compound was prepared starting from 2c (54.8 mg, 0.249 mmol). Silica gel
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chromatography afforded the analytically pure product (55.7 mg, 84% yield) as a white solid. H NMR
(CDCl3): δ = 2.35 (s, 6H), 3.33 (s, 6H), 5.01 (s, 1H), 6.84 (s, 2H), 6.91 (d, J = 8.5 Hz, 2H), 7.48 (d, J = 8.5
Hz, 2H). 13C NMR (CDCl3): δ = 19.96, 29.72, 109.47, 115.027, 126.502, 135.64, 136.54, 155.86. HRMS
(EI): m/z calcd for C16H19BN2O [M+]: 266.1590; found: 266.1556.
4-(1,3,5,6-tetramethyl-1,3-dihydro-2H-benzo[d][1,3,2]diazaborol-2-yl)aniline (3d). Following the
general procedure A, the title compound was prepared starting from 2d (54.0 mg, 0.247 mmol). Silica gel
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chromatography afforded the analytically pure product (55.6 mg, 85% yield) as a white solid. H NMR
(CDCl3): δ = 2.34 (s, 6H), 3.33 (s, 6H), 3.73 (s, 2H), 6.76 (d, J = 7.7 Hz, 2H), 6.82 (s, 2H), 7.40 (d, J = 7.7
Hz, 2H). 13C NMR (CDCl3): δ = 19.94, 29.74, 109.32, 114.62, 126.25, 135.33, 136.64, 146.74. HRMS (EI):
m/z calcd for C16H20BN3 [M+]: 265.1750; found: 265.1775.
1,3,5,6-Tetramethyl-2-phenyl-2,3-dihydro-1H-benzo[d][1,3,2]diazaborole (3e). Following the general
– S2 –

procedure B, the title compound was prepared starting from 2e (50.5 mg, 0.248 mmol). Silica gel
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chromatography afforded the analytically pure product (48.9 mg, 79% yield) as a white solid. H NMR
(CDCl3): δ = 2.35 (s, 6 H), 3.34 (s, 6 H), 6.85 (s, 2 H), 7.43 (d, J = 14.3 Hz, 2 H), 7.46 (t, J = 9.2 Hz, 1 H),
7.59 (d, J = 9.1 Hz, 2 H). 13C NMR (CDCl3): δ = 19.97, 29.72, 109.55, 109.62, 126.61, 127.88, 128.50,
134.02, 136.50. HRMS (EI): m/z calcd for C16H19BN2 [M+]: 250.1641; found: 250.1642.
Ethyl 4-(1,3,5,6-Tetramethyl-1,3-dihydro-2H-benzo[d][1,3,2]diazaborol-2-yl)benzoate (3b). Following
the general procedure B, the title compound was prepared starting from 2b (68.3 mg, 0.247 mmol). Silica
gel chromatography afforded the analytically pure product (55.0 mg, 69% yield) as a white solid. 1H NMR
(CDCl3): δ = 1.42 (t, J = 7.0 Hz, 3H), 2.36 (s, 6H), 3.34 (s, 6H), 4.42 (q, J = 7.1 Hz, 2H), 6.87 (s, 2H), 7.67
(d, J = 8.1 Hz, 2H), 8.12 (d, J = 8.3 Hz, 2H). 13C NMR (CDCl3): δ = 14.35, 19.98, 29.71, 60.95, 109.71,
123.95, 128.72, 130.30, 133.91, 136.36, 166.81. HRMS (EI): m/z calcd for C19H23BN2O2 [M+]: 322.1853;
found: 322.1848.
1-(4-(1,3,5,6-Tetramethyl-1,3-dihydro-2H-benzo[d][1,3,2]diazaborol-2-yl)phenyl)ethan-1-one
(3f).
Following the general procedure B, the title compound was prepared starting from 2f (65.8 mg, 0.267
mmol). Silica gel chromatography afforded the analytically pure product (61.7 mg, 79% yield) as a yellow
solid. 1H NMR (CDCl3): δ = 2.36 (s, 6H), 2.65 (s, 6H), 3.34 (s, 6H), 6.88 (s, 2H), 7.69 (d, J = 8.5 Hz, 2H),
8.03 (d, J = 8.5 Hz, 2H). 13C NMR (CDCl3): δ = 20.01, 26.65, 29.68, 109.66, 127.14, 127.63, 134.28,
136.52, 198.40. HRMS (EI): m/z calcd for C18H21BN2O [M+]: 292.1747; found: 292.1724.
4-(1,3,5,6-Tetramethyl-1,3-dihydro-2H-benzo[d][1,3,2]diazaborol-2-yl)benzaldehyde (3g). Following
the general procedure B, 2g (56.1 mg, 0.242 mmol) was allowed to react with 1 for 1 h at 80 °C. Silica gel
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chromatography afforded the analytically pure product (56.5 mg, 84% yield) as a yellow solid. H NMR
(CDCl3): δ = 2.36 (s, 6H), 3.33 (s, 6H), 6.88 (s, 2H), 7.76 (d, J=7.7 Hz 2H), 7.95 (d, J=6.8 Hz 2H), 10.08 (s,
1H). 13C NMR (CDCl3): δ = 6.34, 20.01, 29.68, 109.66, 124.60, 127.14, 134.28, 136.32, 192.61. HRMS
(EI): m/z calcd for C17H19BN2O [M+]: 278.1590; found: 278.1578.
3-(1,3,5,6-Tetramethyl-1,3-dihydro-2H-benzo[d][1,3,2]diazaborol-2-yl)benzonitrile (3h). Following the
general procedure B, the title compound was prepared starting from 2h (57.3 mg, 0.250 mmol). Silica gel
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chromatography afforded the analytically pure product (49.6 mg, 72% yield) as a yellow solid. H NMR
(CDCl3): δ = 2.36 (s, 6H), 3.33 (s, 6H), 6.85 (s, 2H), 7.56 (t, J = 7.8 Hz, 1H), 7.71 (d, J = 8.0 Hz, 1H), 7.80
(d, J = 7.5 Hz, 1H), 7.86 (s, 1H). 13C NMR (CDCl3): δ = 19.98, 29.69, 109.84, 112.18, 119.16, 127.22,
128.55, 131.92, 136.12, 137.32, 138.08. HRMS (EI): m/z calcd for C17H18BN3 [M+]: 275.1594; found:
275.1623.
1,3,5,6-Tetramethyl-2-(4-(trifluoromethyl)phenyl)-2,3-dihydro-1H-benzo[d][1,3,2]diazaborole
(3i).
Following the general procedure B, the title compound was prepared starting from 2i (66.9 mg, 0.246
mmol). Silica gel chromatography afforded the analytically pure product (64.9 mg, 83% yield) as a white
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solid. H NMR (CDCl3): δ = 2.36 (s, 6H), 3.33 (s, 6H), 6.88 (s, 2H), 7.69 (s, 4H). 13C NMR (CDCl3): δ =
19.99, 29.68, 109.79, 124.34 (q, J = 270.78 Hz), 124.49 (q, J = 3.81 Hz), 127.08, 130.44 (q, J = 32.42 Hz),
134.21, 136.31. HRMS (EI): m/z calcd for C17H18BF3N2 [M+]: 317.1437; found: 317.1431.
1,3,5,6-Tetramethyl-2-(4-nitrophenyl)-2,3-dihydro-1H-benzo[d][1,3,2]diazaborole (3j). Following the
– S3 –

general procedure B, the title compound was prepared starting from 2j (62.6 mg, 0.251 mmol). Silica gel
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chromatography afforded the analytically pure product (53.4 mg, 72% yield) as a yellow solid. H NMR
(CDCl3): δ = 2.37 (s, 6H), 3.34 (s, 6H), 6.90 (s, 6H), 7.76 (d, J = 9.0 Hz, 2H), 8.30 (d, J = 8.5 Hz, 2H). 13
C
NMR (CDCl3): δ = 20.01, 29.68, 109.86, 122.85, 127.44, 134.76, 136.32, 147.50. HRMS (EI): m/z calcd
for C16H18BN3O2 [M+]: 295.1492; found: 295.1487.
Procedure for Arylboronic Acid Synthesis (Scheme 2)
To a solution of 1,3,5,6-tetramethyl-2-phenyl-1,3,2-benzodiazaborole (62.8 mg, 0.251 mmol) in ether (1
mL) was added 6 M aq HCl (0.5 mL). After stirring for 15 h at room temperature, the organic extracts were
washed with 6 M aq HCl (3 × 0.5 mL), dried over Na2SO4 and concentrated. The crude product was dried
in vacuo overnight to yield phenyl boronic acid as a white solid (30.4 mg, 99% yield).
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2. T. Hayashi, M. Konishi, Y. Kobori, M. Kumada, T. Higuchi, K. Hirotsu, J. Am. Chem. Soc. 1984, 106,
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