Page 7 of 11
The Journal of Organic Chemistry
NMR (CDCl3, 400 MHz) δ 7.58 (d, 1H, J=8.1), 7.46 (t, 1H,
cooled to rt, concentrated to an oil, and precipitated with hex-
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3
4
5
6
7
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anes. The mixture was concentrated again and the solid was
subject to column chromatography (SiO2, 4:1 EtOAc:hexanes
with 1% triethylamine) to afford 9d (298 mg, 85%). Pale yellow
J=7.7), 7.31 (s, 2H), 7.27 (d, 1H, J=7.8), 7.21 (d, 1H, J=7.6),
7.02 (d, 1H, J=8.3), 6.88 (t, 1H, J=7.7), 5.18 (d, 1H, J=13.9),
5.03 (d, 1H, J=13.9), 4.63 (s, 2H), 3.08 (s, 3H), 2.57 (s, 3H).
13C{1H} NMR (CDCl3, 100 MHz) δ 170.2, 159.2, 148.6, 138.9,
136.3, 127.9, 127.2, 127.0, 120.8, 120.6, 118.6, 117.2, 71.8,
65.9, 37.0, 16.3. 11B NMR (CDCl3, 128 MHz) δ 8.7. HRMS
(MAII) m/z: calc. for C17H19BNO3 [M+H]+ 296.1453, found
296.1446.
1
solid; mp 175-178ºC; H NMR (CDCl3, 400 MHz) δ 8.23 (s,
1H), 8.19 (s, 1H), 8.15 (d, 1H, J=8.2), 7.54 (t, 1H, J=7.8), 7.35
(t, 2H, J=6.9), 7.00 (d, 1H, J=8.4), 6.93 (t, 1H, J=7.6), 5.24 (d,
1H, J=15.5), 5.09 (d, 1H, J=15.5), 3.19 (s, 3H). 13C{1H} NMR
(CDCl3, 100 MHz) δ 163.3, 159.7, 156.2, 147.6, 138.1, 131.1,
123.8, 123.5, 121.4, 119.6, 119.4, 71.9, 42.7. 11B NMR (CDCl3,
128 MHz) δ 8.4. HRMS (MAII) m/z: calc. for C15H14BN2O4
[M+H]+ 297.1041, found 297.1058.
9
Protection of 6-nitrobenzoxaborole with 2-[1-(me-
thylimino)ethyl]phenol (10d). A round-bottom flask was
charged with a stir bar, 4d (184 mg, 1.23 mmol), 3 (203 mg,
1.12 mmol), and toluene (25 mL). The flask was fitted with a
Dean-Stark trap and the mixture was brought to reflux for 5 h.
The reaction was then cooled to rt, concentrated to a minimum
amount of toluene (1-2 mL), and hexane (30 mL) was added.
The resulting precipitate was filtered, washed with cold hexanes
(3 x ~10 mL), and dried in vacuo to afford 10d (288 mg, 83%).
The compound was analytically pure and did not require further
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Protection
of
benzoxaborole
with
2-[1-(me-
thylimino)ethyl]phenol (10a). A round-bottom flask was
charged with a stir bar, 4a (910 mg, 6.81 mmol), 3 (1.22 g, 8.17
mmol) and toluene (10 mL). The flask was fitted with a Dean-
Stark trap and the suspension was brought to reflux for 5 h. The
reaction was then cooled to rt, concentrated to a minimum
amount of toluene (1-2 mL), and hexane (30 mL) was added.
The resulting precipitate was filtered, washed with cold hexanes
(3 x ~10 mL), and dried in vacuo to afford 10a (1.0 g, 55%).
The compound was analytically pure and did not require further
purification. Off-white solid; mp 159-161ºC; 1H NMR (CDCl3,
400 MHz) δ 7.58 (d, 1H, J=8), 7.45 (t, 1H, J=7.9), 7.30 (m, 2H),
7.19 (m, 2H), 7.03 (d, 1H, J=8.3), 6.88 (t, 1H, J=7.6), 5.20 (d,
1H, J=13.8), 5.04 (d, 1H, J=13.8), 3.09 (s, 3H), 2.57 (s, 3H).
13C{1H} NMR (CDCl3, 100 MHz) δ 170.0, 159.3, 148.8, 136.2,
128.3, 127.9, 127.6, 126.4, 120.6, 118.5, 117.3, 72.0, 37.0, 16.3.
11B NMR (CDCl3, 128 MHz) δ 8.7. HRMS (MAII) m/z: calc.
for C16H17BNO2 [M+H]+ 266.1347, found 266.1371.
1
purification. Yellow solid; mp 249-251ºC; H NMR (CDCl3,
400 MHz) δ 8.14 (2 x s, 2H), 7.62 (d, 1H, J=8.0), 7.49 (t, 1H,
J=7.8), 7.33 (d, 1H, J=8.2), 7.01 (d, 1H, J=8.4), 6.93 (t, 1H,
J=7.6), 5.24 (d, 1H, J=15.5), 5.10 (d, 1H, J=15.5), 3.09 (s, 3H),
2.62 (s, 3H). 13C{1H} NMR (CDCl3, 100 MHz) δ 158.7, 156.1,
136.9, 128.1, 123.7, 123.3, 121.4, 120.4, 119.1, 71.6, 36.9, 16.4.
11B NMR (CDCl3, 128 MHz) δ 8.2. HRMS (MAII) m/z: calc.
for C16H16BN2O4 [M+H]+ 311.1198, found 311.1190.
DIBAL-H reduction of nitrile (6). To a round-bottom flask
containing 5b (212 mg, 0.865 mmol) was added DCM (7 mL)
º
and the solution was cooled to -78 C. DIBAL-H (1M in Hex-
Protection of 6-cyanobenzoxaborole with 2-[1-(me-
thylimino)ethyl]phenol (10b). A round-bottom flask was
charged with a stir bar, 4b (150 mg, 0.940 mmol), 3 (196 mg,
1.32 mmol), and toluene (10 mL). The flask was fitted with a
Dean-Stark trap and the suspension was brought to reflux for 5
h. The reaction was then cooled to rt, concentrated to a mini-
mum amount of toluene (1-2 mL), and hexane (30 mL) was
added. The resulting precipitate was filtered, washed with cold
hexanes (3 x ~10 mL), and dried in vacuo to afford 10b (100
mg, 36%). The compound was analytically pure and did not re-
quire further purification. Yellow solid; mp 235-239ºC; 1H
NMR (CDCl3, 400 MHz) δ 7.60 (d, 1H, J=8.1), 7.58 (s, 1H),
7.54 (d, 1H, J=7.8), 7.49 (t, 1H, J=7.8), 7.29 (d, 1H, J=7.8),
7.01 (d, 1H, J=8.3), 6.93 (t, 1H, J=7.7), 5.21 (d, 1H, J=15.1),
5.07 (d, 1H, J=15.1), 3.07 (s, 3H), 2.60 (s, 3H), 13C{1H} NMR
(CDCl3, 100 MHz) δ 171.0, 158.8, 154.0, 136.8, 132.7, 131.4,
128.1, 121.5, 120.5, 120.1, 119.1, 117.1, 110.2, 71.8, 36.9, 16.4,
11B NMR (CDCl3, 128 MHz) δ 8.3. HRMS (MAII) m/z: calc.
for C17H16BN2O2 [M+H]+ 291.1299, found 291.1325.
ane, 1.3 mL, 1.3 mmol) was added dropwise via syringe over
15 min. After addition, the reaction was stirred for 30 min at -
º
78 C and then warmed to rt over 8 h. The reaction was
quenched with EtOAc (12 mL) and 1M HCl (8 mL), which also
promoted deprotection. The mixture was transferred to a sepa-
ratory funnel with additional EtOAc (~15 mL) and water (5
mL). The mixture was extracted and the aqueous layer was
treated with additional EtOAc (2 x 15 mL). The combined or-
ganics were washed with brine, dried over Na2SO4, and filtered.
Concentration afforded 6 (111 mg, 79%) which was analyti-
cally pure and did not require further purification. Off-white
solid; 1H NMR (DMSO-d6, 400 MHz) δ 10.06 (s, 1H), 9.45 (s,
1H, B-OH), 8.27 (s, 1H), 8.00 (d, 1H, J=7.8), 7.63 (d, 1H,
J=7.8), 5.08 (s, 2H). 13C{1H} NMR (DMSO-d6, 100 MHz) δ
193.6, 160.7, 135.8, 132.8, 132.0, 122.8, 70.5. 11B NMR
(DMSO-d6, 128 MHz) δ 31.6. HRMS (MAII) m/z: calc. for
C8H8BO3 [M+H]+ 163.0561, found 163.0568. All spectra match
those reported.19
Oxidation of alcohol with MnO2 (6). In a round-bottom flask,
5c (211 mg, 0.850 mmol) was dissolved in dry DCM (6 mL)
and MnO2 (1.2 g, 13.8 mmol) was added at rt. The mixture was
stirred for 32 h at rt, filtered over celite, and the filter cake was
washed with EtOAc (3 x 15 mL). The filtrate was transferred to
a separatory funnel and washed with 1M HCl (~20 mL) to pro-
mote deprotection. The organic layer was dried over Na2SO4,
filtered, and concentrated to afford 6 (99 mg, 72%) which did
not require further purification. Off-white solid. Characteriza-
tion exactly matches the previous procedure for 6.
Protection of 6-hydroxymethylbenzoxaborole with 2-[1-
(methylimino)ethyl]phenol (10c). A round-bottom flask was
charged with a stir bar, 4c (403 mg, 2.45 mmol), 3 (435 mg,
2.91 mmol), and toluene (10 mL). The flask was fitted with a
Dean-Stark trap and the suspension was brought to reflux for 5
h. The reaction was then cooled to rt and hexane (30 mL) was
added. The resulting precipitate was filtered, washed with cold
hexanes (3 x ~10 mL), and dried in vacuo to afford 10c (723
mg, 87%). The compound was analytically pure and did not re-
quire further purification. White, fluffy solid; mp 178-181ºC; 1H
7
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