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(101 MHz, [D6]DMSO): d=152.3, 148.7, 143.5, 130.7, 129.0, 127.8,
126.9 ppm.
The product was isolated as a colourless oil (880 mg, 85%).
1H NMR (400 MHz, CDCl3): d=7.76 (2H, d, J=7.5 Hz), 7.40 (2H, d,
J=7.5 Hz), 6.72 (1H, dd, J=17.5, 10.0 Hz), 5.81 (1H, d, J=17.5 Hz),
5.29 (1H, d, J=10.0 Hz), 1.34 ppm (12H, s); 13C NMR (101 MHz,
CDCl3): d=137.9, 136.1, 133.3, 126.4, 114.3, 88.1, 24.0 ppm.
Flow preparation of quinolin-8-ylboronic acid (12)[23]
The flow equipment was set-up and operated according to GP1,
with the following amendments: instead of using dry THF, a mix-
ture 4:1 toluene/THF was used, the concentration of aryl halide
was 0.25m. Stream A reagent quantities: 8-bromo-quinoline
(563 mg), triisopropyl borate (610 mg). To the collected material
was added cold 1m HCl, the organic layer was separated, and the
aqueous layer was then neutralised with sodium bicarbonate. 3-
Quinolineboronic acid precipitated and was filtered, washed and
dried to obtain a pale yellow solid (285 mg, 64% yield). M.p. 135–
Flow preparation of 4,4,5,5-tetramethyl-2-(4-(trifluoro meth-
yl)phenyl)-1,3,2-dioxaborolane (1) with in-line polymeric
acid workup
The flow equipment was set-up and operated according to GP1.
An omnifit column containing 5 g of QuadraPure Sulfonic acid (QP-
SA, 3.5–4.5 mmolgꢀ1) was added in-line at the output of the cryo-
flow reactor. Stream A reagent quantities: 1-bromo-4-(trifluorome-
thyl)benzene (900 mg) and 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-
dioxaborolane (818 mg). The product was isolated as a colourless
1
1378C; H NMR (400 MHz, [D6]DMSO): d=9.58 (2H, s), 8.72 (1H, s),
8.42 (1H, d, J=4.0 Hz), 8.48 (1H, d, J=8.5 Hz), 8.28 (1H, d, J=
7.0 Hz), 8.08 (1H, d, J=8.5 Hz), 7.65 (1H, t, J=7.0 Hz), 7.60 ppm
(1H, q, J=4.0 Hz); 13C NMR (101 MHz, [D6]DMSO): d=151.9, 149.8,
138.5, 138.1, 131.4, 128.1, 127.1, 121.7 ppm.
1
solid (900 mg, 83% yield). H NMR (400 MHz, CDCl3): d=7.90–7.93
(2H, m), 7.60–7.64 (2H, m), 1.36 ppm (12H, s); 13C NMR (101 MHz,
CDCl3): d=135.0, 132.9 (q, JC-F =32 Hz), 124.3 (q, JC-F =4 Hz), 124.2
(q, JC-F =269 Hz), 84.3, 24.9 ppm.
Flow preparation of 4,4,5,5-tetramethyl-2-(thiophen-3-yl)-
1,3,2-dioxaborolane (13)[24]
The flow equipment was set-up and operated according to GP1.
Stream A reagent quantities: 3-bromo-thiophene (817 mg) and 2-
isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (818 mg). The
product was isolated as a pale brown oil (828 mg, 95% yield).
1H NMR (400 MHz, CDCl3): d=7.92 (1H, s), 7.42 (1H, d, J=5.0 Hz),
7.33 (1H, m), 1.34 ppm (12H, s); 13C NMR (101 MHz, CDCl3): d=
136.5, 132.1, 125.3, 83.7, 24.9 ppm.
Flow preparation of potassium trifluoro(4-methoxyphenyl)-
borate (17)[25]
The flow equipment was set-up and operated according to GP1.
Following workup the reaction mixture was treated according to
the procedure reported by Aggarwal.[15d] Stream A reagent quanti-
ties: 1-bromo-4-methoxybenzene (748 mg) and 2-isopropoxy-
4,4,5,5-tetramethyl-1,3,2-dioxaborolane (818 mg). The product was
isolated as
a
colourless solid (471 mg, 55% yield). 1H NMR
Flow preparation of 2-(4-(difluoromethoxy)phenyl)-4.4.5.5-
tetramethyl-1,3,2-dioxaborolane (14)
(400 MHz, [D6]DMSO): d=7.21 (2H, d, J=7.0 Hz), 6.64 (2H, d, J=
7.0 Hz), 3.65 ppm (3H, s); 13C NMR (101 MHz, [D6]DMSO): d=157.5,
132.6, 112.2, 54.9 ppm.
The flow equipment was set-up and operated according to GP1.
Stream A reagent quantities: 1-bomo-4-(difluoromethoxy)benzene
(1110 mg) and 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
(818 mg). The product was isolated as a colourless oil (728 mg,
68%). 1H NMR (400 MHz, CDCl3): d=7.81 (2H, d, J=8.5 Hz), 7.09
(2H, d, J=8.5 Hz), 6.54 (1H, t, J=74.0 Hz), 1.34 ppm (12H, s);
Flow preparation of potassium trifluoro(4-(trifluoromethyl)-
phenyl)borate (18)[24]
13C NMR (101 MHz, CDCl3): d=153.7, 136.6, 118.2, 115.8 (t, JC-F
=
The flow equipment was set-up and operated according to GP1.
Following workup the reaction mixture was treated according to
the procedure reported by Aggarwal.[15d] Stream A reagent quanti-
ties: 1-bromo-4-(trifluoromethyl)benzene (900 mg) and 2-isopro-
poxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (818 mg). The product
was isolated as a colourless solid (856 mg, 85% yield). 1H NMR
(400 MHz, [D6]DMSO): d=7.52 (2H, m), 7.38 (2H, m), 3.65 ppm (3H,
s); 13C NMR (101 MHz, [D6]DMSO): d=131.8, 126.0 (q, JC-F =31 Hz),
125.2 (q, JC-F =271 Hz), 122.9 ppm (q, JC-F =4 Hz).
259 Hz), 83.9, 24.8 ppm; 19F NMR (376 MHz, CDCl3): d=ꢀ81.4 ppm;
HRMS (ES+) found 271.1309 for C13H1711BF2O3H+; calcd 271.1312.
Flow preparation of 4,4,5,5-tetramethyl-2-(3,4,5-trifluoro-
phenyl)-1,3,2-dioxaborolane (15)
The flow equipment was set-up and operated according to GP1.
Stream A reagent quantities: 5-bromo-1,2,3-trifluorobenzene
(1045 mg) and 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaboro-
lane (818 mg). The product was isolated as a colourless oil
(880 mg, 85%). 1H NMR (400 MHz, CDCl3): d=7.38 (2H, t, J=
7.0 Hz), 1.33 ppm (12H, s); 13C NMR (101 MHz, CDCl3): d=151.0
Configuration of equipment for sequential addition of
boron electrophile
(dd, JC-F =251, 8 Hz), 142.0 (dt, JC-F =255, 15 Hz), 118.2 (d, JC-F
=
16 Hz), 84.5, 24.6 ppm; 19F NMR (376 MHz, CDCl3): d=ꢀ136.0 (d,
J=20.0 Hz), ꢀ157.1 ppm (t, J=20.0 Hz); HRMS (ES+) found
259.1112 for C12H1411BF3O2H+; calcd 259.1112.
In addition to the set-up described in GP1, a tee-piece was added
to the end of the reactor coil, an input from a third pump (that
which would be delivering the 2-isopropoxy-4,4,5,5-tetramethyl-
1,3,2-dioxaborolane) was also plumbed into this tee-piece. The
output of which led into another mandrel, fixed with 2.44 mm
i.d.ꢁ3.26 mm o.d. (20 mL) PFA tubing, which was placed over the
cooled block. As the electrophile is relatively easy to remove,
excess was used and the timing of the third stream addition was
calculated manually and then a generous time buffer was added
to either side to circumvent issues arising from dispersion.
Flow preparation of 4,4,5,5-tetramethyl-2-(4-vinylphenyl)-
1,3,2-dioxaborolane (16)[20]
The flow equipment was set-up and operated according to GP1.
Stream A reagent quantities: 1-bromo-4-vinylbenzene (910 mg)
and 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (818 mg).
Chem. Eur. J. 2014, 20, 263 – 271
269
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