Journal of the American Chemical Society
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Next, a suspension of IPrAuCl (16 mg, 0.025 mmol, 5.0 mol %) in
toluene (0.5 mL) was added to the reaction mixture at 25 °C, using
additional toluene as a rinse to aid in full transfer (1 × 0.5 mL
portion). The reaction mixture was then sealed with a ground glass
stopper and a PTFE sealing ring and placed in a preheated 50 °C
copper shot heating bath. The final concentration of the reaction
mixture was 0.1 M in 1a. After 24 h, analysis by TLC (20% EtOAc/
hexanes) indicated full consumption of boric ester intermediate 2a.
The reaction mixture was cooled to 25 °C, and a solution of PPh3 (13
mg, 0.050 mmol, 10 mol %) in toluene (0.5 mL) was added. The
resulting suspension was stirred for 22 h at 25 °C in order to quench
IPrAuTFA before proceeding. The quenched reaction mixture was
removed from the glovebox and filtered through a fiberglass filter to
remove the suspended solids. The filter was then rinsed with toluene
(3 × 3 mL), and the combined filtrates were concentrated in vacuo to
a pale yellow powder, which was suspended in acetone (4.5 mL) and
added to a stirring solution of KHF2 (140 mg, 1.8 mmol, 3.5 equiv) in
water (1.5 mL). The resulting mixture was stirred at 25 °C for 30 min,
and then concentrated in vacuo to remove the solvents. To this residue
was added 2 mL of Et2O and the solution was subsequently
concentrated at ca. 10 mTorr for 30 min in order to remove residual
acetone. The resulting pale yellow solid residue was washed with Et2O
(4 × 2 mL) and extracted with acetone (4 × 2 mL). The combined
acetone extracts were concentrated in vacuo, and the resulting residue
was subjected to an additional washing/extraction cycle to yield 4a as a
white powder (113 mg, 75% yield) after removing volatiles at 25 °C
and ca. 10 mTorr for 18 h. 1H NMR (DMSO-d6, 600 MHz): δ 8.10 (d,
J = 7.4 Hz, 2H), 7.88 (d, J = 7.7 Hz, 1H), 7.42 (d, J = 8.0 Hz, 1H),
7.38 (t, J = 7.6 Hz, 2H), 7.26 (t, J = 7.3 Hz, 1H), 7.13 (td, J = 6.5 Hz,
1.2 Hz, 1H), 7.08 (td, J = 7.4, 0.9 Hz, 1H). 13C NMR (DMSO-d6, 125
MHz): δ 154.7 (q, JC−F = 4.6 Hz), 153.8, 135.4, 133.3, 127.9, 126.8,
126.7 (q, JC−F = 2.3 Hz), 124.1 (q, JC−F = 2.8 Hz), 122.7, 109.6. [Note:
As with many organotrifluoroborates, the ipso carbon was not
detected, presumably due to broadening through coupling to the
11B nucleus. The quaternary carbon at the benzofuran 2 position was
100% Et2O to 100% MeCN. Removal of volatiles at 25 °C and ca. 10
mTorr for 18 h afforded MIDA boronate 4b as a white powder (101
mg, 58% yield). Crystals suitable for X-ray diffraction analysis were
prepared by slow diffusion of Et2O into a saturated solution of 4b in
Et2O/acetone at 25 °C over 3 days. TLC (10% MeCN/Et2O): Rf =
1
0.39. H NMR (CD3CN, 600 MHz): δ 7.72 (dd, J = 7.8 Hz, 0.8 Hz,
1H), 7.67−7.65 (m, 2H), 7.55 (d, J = 9.7 Hz, 1H), 7.47−7.44 (m,
3H), 7.35−7.31 (m, 1H), 7.29−7.26 (m, 1H), 3.97 (d, J = 17.1 Hz,
2H), 3.65 (d, J = 17.1 Hz, 2H), 2.56 (s, 3H). 13C NMR (CD3CN, 125
MHz): δ 169.0, 156.0, 133.6, 133.0, 130.6, 130.2, 129.3, 125.2, 123.9,
123.5, 111.8, 63.0, 48.2. [Note: no signals were observed for the
quaternary C−B ipso carbon or the quaternary carbon at the
benzofuran 2 position.] 11B NMR (CD3CN, 193 MHz): δ 11.3 (br
s). HRMS (ESI+): Calculated for C17H19BBrNO5 ([M + Na]+),
372.1023; found, 372.1016.
ASSOCIATED CONTENT
■
S
* Supporting Information
Full experimental procedures and characterization data,
including CIF data for 4b. This material is available free of
AUTHOR INFORMATION
■
Corresponding Author
Notes
The authors declare the following competing financial
interest(s): Provisional patent applications (no. 61/836,391
and no. 61/906,040) have been filed by the University of
California.
also not detected.] 11B NMR (DMSO-d6, 193 MHz): δ 3.2 (br s). 19
F
ACKNOWLEDGMENTS
■
NMR (DMSO-d6, 376 MHz): δ −131.9 (br s). HRMS (ESI-):
Calculated for C14H9BF3O ([M − K]−), 261.0701; found, 261.0706.
MIDA Boronate 4b. A solution of phenol 1a (97.0 mg, 0.500
mmol, 1.00 equiv) in 1.0 mL of toluene was added to a flame-dried 10-
mL Schlenk tube. To this stirring solution was added dropwise at 25
°C a suspension of NaH (92 wt % purity, 13.0 mg, 0.500 mmol, 1.00
equiv) in 0.5 mL of toluene over 2 min. A suspension of NaTFA (20
mg, 0.15 mmol, 30 mol %) in 0.5 mL of toluene was added next, and
the resulting suspension was stirred for 15 min to affect full
deprotonation. To the resulting stirring sodium phenoxide suspension
was added at 25 °C a solution of B-chlorocatecholborane (77.0 mg,
0.500 mmol, 1.00 equiv) in toluene (1.0 mL), using additional toluene
as a rinse to ensure full transfer (2 × 0.5 mL portions). The resulting
suspension was stirred vigorously for 30 min to allow for full
conversion to boric ester intermediate 2a. Next, a suspension of
IPrAuCl (16 mg, 0.025 mmol, 5.0 mol %) in toluene (0.5 mL) was
added to the reaction mixture at 25 °C, using additional toluene as a
rinse to aid in full transfer (1 × 0.5 mL portion). The reaction mixture
was then sealed with a ground glass stopper and a PTFE sealing ring
and placed in a preheated 50 °C copper shot heating bath. The final
concentration of the reaction mixture was 0.1 M in 1a. After 24 h,
analysis by TLC (20% EtOAc/hexanes) indicated full consumption of
boric ester intermediate 2a. The reaction mixture was cooled to 25 °C,
and a solution of PPh3 (13 mg, 0.050 mmol, 10 mol %) in toluene (0.5
mL) was added. The resulting suspension was stirred for 16 h at 25 °C
in order to quench IPrAuTFA before proceeding. Anhydrous DMSO
(2.0 mL) and H2MIDA (81 mg, 0.55 mmol, 1.1 equiv) were added to
the quenched alkoxyboration reaction mixture, and the resulting
suspension was stirred at 90 °C for 2 h. The reaction mixture was then
cooled to 25 °C and removed from the glovebox. Toluene was
removed in vacuo at 25 °C and ca. 10 Torr, then DMSO was removed
by Kugelrohr distillation at ca. 10 mTorr. The resulting semisolid
residue was adsorbed onto Celite from a MeCN suspension and
purified by silica gel chromatography using an elution gradient from
This work was supported by a grant from the NIH
(1R01GM098512-01) and by an NSF Graduate Fellowship to
J.J.H. (NSF-201015893). We thank Prof. David L. van Vranken
(University of California−Irvine) for helpful conversation. We
also thank Dr. Joseph W. Ziller and Ms. Jordan F. Corbey for
X-ray diffraction analysis, and Dr. Phillip R. Dennison for NMR
spectroscopy assistance.
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