Full Paper
B. H. Lipshutz et al.
18.2, -4.5, -5.1; HR-MS(ESI): calcd. for C22H37BO4NaSi (M+
now report that Miyaura borylations can be carried out
on bromoarenes under micellar conditions: in water at
room temperature.
Na+): 427.2452; found: 427.2444.
(E)-Ethyl 3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phe-
nyl)acrylate (14). Following the GP, using (E)-ethyl 3-(4-bromo-
phenyl)acrylate (128 mg, 0.5 mmol), Pd(PtBu3)2 (7.7 mg,
0.015 mmol), B2pin2 (140 mg, 0.55 mmol), and KOAc (147 mg,
1.5 mmol) in 2mL of 2% TPGS-750-M/H2O, GC/FID, and TLC
monitoring indicated complete conversion after an overall reac-
tion time of 6 h. Workup according to GP and flash column chro-
matography on silica (12 g, 2–10% EtOAc/hexanes) afforded 14
(116 mg, 77% yield) as a colorless oil. Rf =0.21 (10% EtOAc/
hexanes); 1H NMR (500 MHz, CDCl3) d=7.83 (d, J=8.0 Hz,
2H), 7.70 (d, J=16.1 Hz, 1H), 7.53 (d, J=8.2 Hz, 2H), 6.50 (d,
J=16.0 Hz, 1H), 4.27 (q, J=7.1 Hz, 2H), 1.36 (s, 12H), 1.34 (t,
J=7.0 Hz, 3H); 13C NMR (125 MHz, CDCl3) d=167.0, 144.6,
137.1, 135.4, 127.4, 119.3, 84.2, 60.7, 25.0, 14.5; HR-MS (ESI):
calcd. for C17H2310BO4 (M+): 301.1731; found: 301.1740.
2. Experimental Section
Unless otherwise noted, all reactions were performed under an
atmosphere of Argon. A 2% TPGS-750-M/H2O solution was
prepared by dissolving 4 g TPGS-750-M in 196 g degassed water
(HPLC grade). Pd(PtBu3)2 was generously supplied from Johnson
Matthey (catalog # Pd-116) and handled in a glove box under
Argon. Bis(pinacolato)diboron (B2pin2) was obtained from Fron-
tier Scientific (catalog # D6878). KOAc was freshly ground prior
use. 1H and 13C spectra were recorded at 228C on a Varian
UNITY INOVA Avance 400 MHz or a Varian UNITY INOVA
500 MHz. Chemical shifts in 1H NMR spectra are reported in
parts per million (ppm) on the d scale from an internal standard
of residual chloroform (7.26 ppm). Data are reported as follows:
chemical shift, multiplicity (s = singlet, d = doublet, t = triplet,
q = quartet, m = multiplet), coupling constant in hertz (Hz),
and integration. Chemical shifts of 13C NMR spectra are reported
in ppm from the central peak of CDCl3 (77.23 ppm) on the d
scale. High resolution mass analyses were obtained using a VG70
double-focusing magnetic sector instrument (VG Analytical) for
EI and a PE Sciex QStar Pulsar quadrupole/TOF instrument
(API) for ESI.
((1-(4-Bromophenyl)vinyl)oxy)(tert-butyl)dimethylsilane (22). A
250 mL round bottom flask was charged with 4-bromoacetophe-
none (1.99 g, 10.0 mmol), TBSCl (6.03 g, 40.0 mmol), and NaI
(6.00 g, 40 mmol). The flask was capped with a rubber septum
and placed under an atmosphere of Argon. After the addition of
200 mL MeCN, NEt3 (6.13 mL, 44.0 mmol) was introduced and
the reaction mixture was stirred for 16 h at rt until TLC monitor-
ing indicated complete conversion. The reaction mixture was
poured onto sat. NaHCO3 solution and extracted with EtOAc (3
ꢁ 40 mL). The combined organic extracts were washed with
brine, dried over anhydrous Na2SO4, and evaporated to yield a
brown slurry. Hexanes was added and the obtained heterogene-
ous mixture was filtered through a short plug of silica using hex-
anes to afford 22 (3.02 g, 96% yield) as a colorless oil. Rf =0.49
General Procedure for Borylations of Aryl Bromides in 2%
TPGS-750-M/water (GP)
1
(1% EtOc/hexanes); H NMR (500 MHz, CDCl3) d=7.47 (d, J=
A 10 mL glass vial containing a strong stir bar was charged with
Pd(PtBu3)2 (7.7 mg, 0.015 mmol), B2pin2 (140 mg, 0.55 mmol) and
KOAc (147 mg, 1.5 mmol). The vial was capped with a rubber
septum and placed under an Argon atmosphere, followed by the
addition of 1.0 mL of 2% TPGS-750-M/water. After 10 min of
vigorous stirring, the aryl bromide (0.5 mmol) was added, fol-
lowed by an additional 1.0 mL of solvent. Conversion was moni-
tored by GC/FID and/or TLC. After the indicated time, the reac-
tion was extracted with EtOAc (3 ꢁ 2 mL). The combined or-
ganic layers were filtered through a short plug of SiO2 and the
solvent was removed under reduced pressure. The residue was
purified by flash chromatography eluting with EtOAc/hexanes to
afford the product.
8.5 Hz, 2H), 7.44 (d, J=8.5 Hz, 2H), 4.88 (s, 1H), 4.44 (s, 1H),
1.00 (s, 9H), 0.21 (s, 6H); 13C NMR (125 MHz, CDCl3) d=155.2,
137.0, 131.4, 127.1, 122.4, 91.6, 26.0, 18.5, –4.4; HR-MS(ESI):
calcd. for C14H21OBrSi (M+): 312.0545; found: 312.0542.
tert-Butyldimethyl((1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-
2-yl)phenyl)vinyl)oxy)silane (23). Following the GP, using ((1-(4-
bromophenyl)vinyl)oxy)(tert-butyl)dimethylsilane; 22) (157 mg,
0.5 mmol), Pd(PtBu3)2 (7.7 mg, 0.015 mmol), B2pin2 (140 mg,
0.55 mmol), and KOAc (147 mg, 1.5 mmol) in 2 mL of 2%
TPGS-750-M/H2O, GC/FID, and TLC monitoring indicated com-
plete conversion after an overall reaction time of 2.5 h. Workup
according to GP and flash column chromatography on silica
(12 g, 3% EtOAc/hexanes) afforded 23 (153 mg, 77% yield) as a
Spectral data for the following compounds matched previously
reported data: 3,[8] 4,[9] 5,[10] 6,[8] 7,[8] 9,[8] 10,[6] 11,[8] 12,[6] 13,[11]
15,[10] 16,[10] 17.[6]
1
colorless oil. Rf =0.51 (10% EtOc/hexanes); H NMR (500 MHz,
CDCl3) d=7.77 (d, J=8.0 Hz, 2H), 7.60 (d, J=8.0 Hz, 2H), 4.95
(s, 1H), 4.47 (s, 1H), 1.35 (s, 12H), 1.00 (s, 9H), 0.20 (s, 6H);
13C NMR (125 MHz, CDCl3) d=156.1, 140.6, 134.8, 124.7, 84.0,
60.6, 26.0, 25.1, 18.5, –4.4; HR-MS (ESI): calcd. for
C20H3310BO3Si (M+): 359.2328; found: 359.2333.
(R)-4-((tert-Butyldimethylsilyl)oxy)-4-(4-(4,4,5,5-tetramethyl-
1,3,2-dioxaborolan-2-yl)phenyl)butan-2-one (8). Following the
general procedure (GP), using (R)-4-(4-bromophenyl)-4-((tert-
butyldimethylsilyl)oxy)butan-2-one (179 mg, 0.5 mmol), Pd-
(PtBu3)2 (7.7 mg, 0.015 mmol), B2pin2 (140 mg, 0.55 mmol), and
KOAc (147 mg, 1.5 mmol) in 2 mL of 2% TPGS-750-M/H2O,
GC/FID, and TLC monitoring indicated complete conversion
after an overall reaction time of 9 h. Workup according to the
GP and flash column chromatography on silica (12 g, 2–10%
EtOAc/hexanes) afforded 8 (165 mg, 82% yield) as a colorless
oil. Rf =0.25 (10% EtOAc/hexanes); 1H NMR (500 MHz,
CDCl3) d=7.73 (d, J=8.0 Hz, 2H), 7.31 (d, J=8.0 Hz, 2H), 5.13
(dd, J=9.0, 4.0 Hz, 1H), 2.89 (dd, J=14.5, 9.0 Hz, 1H), 2.48 (dd,
J=14.5, 4.0 Hz, 1H), 2.11 (s, 3H), 1.31 (s, 12H), 0.81 (s, 9H), –
0.03 (s, 3H), –0.22 (s, 3H); 13C NMR (125 MHz, CDCl3) d=
207.2, 147.8, 135.0, 125.3, 83.9, 72.1, 54.4, 32.0, 25.9, 25.1, 25.0,
4’-Methoxy-2-methyl-1,1’-biphenyl (26). Tandem 1-pot boryla-
tion-Suzuki–Miyaura cross-coupling in water: A 10 mL glass vial
containing a strong stir bar was charged with Pd(PtBu3)2 (5.7 mg,
0.011 mmol), B2pin2 (100 mg, 0.40 mmol), and KOAc (100 mg,
1.13 mmol). The vial was capped with a rubber septum and
placed under an Argon atmosphere, followed by the addition of
1.0 mL of 2% TPGS-750-M/water. After 10 min of vigorous stir-
ring, 2-bromo-toluene (46 mL, 0.38 mmol) was added, followed
by an additional 0.5 mL of solvent. After 3 h, GC/FID confirmed
the successful borylation. 4-Bromoanisole (34 mL, 0.25 mmol)
and KOH (42 mg, 0.75 mmol) were added followed by 0.5 mL of
solvent. The reaction was stirred for an additional 3 h and ex-
692
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Isr. J. Chem. 2010, 50, 691 – 695