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S. Kuno et al. / Tetrahedron Letters 55 (2014) 720–724
References and notes
6. Compound 1 or 1a was reacted with 1.8 equiv or 0.9 equiv, respectively, of aryl
bromides in the presence of 2 equiv or 1 equiv, respectively, of K2CO3 and
catalytic amounts of PdCl2(PPh3)2 (0.1 equiv or 0.05 equiv, respectively) in
EtOH/H2O (5/1) at 50 °C for 5 h (the base was removed in entries iii, v, and vii).
In entry viii, compound 1a was reacted with 0.9 equiv of 1-bromo-4-
methoxybenzene catalyzed by 0.05 equiv of Pd(OAc)2 in DMF/H2O (5/1) at rt
for 4 h.
15. To
a
suspension of 10 mg of 1-bromo-4-tert-butylbenzene (0.047 mmol),
(0.035 mmol,
8.6 mg of phenylboronic acid (0.070 mmol), 16 mg of
1
anhydride), and 9.7 mg of K2CO3 (0.070 mmol) in 1 mL of EtOH/H2O (4/1), 1.7 mg
of PdCl2(PPh3)2 (0.0024 mmol) in 0.2 mL of EtOH/H2O (4/1) was added. After
stirring at 50 °C for 3 h, 0.1 mL of the reaction suspension was centrifugally
evaporated. In total, 0.1 mL of sat. NaHCO3 aqueous solution and 0.3 mL of hexane/
EtOAc (9/1) were added to the residue, and the mixture was shaken vigorously and
centrifugedagain. Theorganicsupernatant(0.2 mL)wascollectedandcentrifugally
evaporated. The residue was dissolved in MeCN and was analyzed by HPLC.
7. As an example, the synthesis of compound
1 is described: scyllo-inositol
16. For entry i: compound
3
(50 mg, 0.076 mmol, tetrahydrate), 4-
(728 mg, 4.04 mmol), potassium hydroxide (413 mg, 7.36 mmol) and 4-
methylphenylboronic acid (1.00 g, 7.36 mmol) were suspended in 15 mL of
hot water. The resulting suspension was stirred under reflux for 1 h.
Subsequently, the solution became transparent and was cooled to room
temperature. In total, 150 mL of ethanol was added, and the solution was
vigorously stirred to precipitate the product. The precipitates were removed by
filtration, and the filtrate was concentrated at reduced pressure. The residue
was washed with toluene several times and was dried in vacuo. The resulting
white powder was dried at 150 °C in an oven until a constant mass was
achieved, yielding 1 (1.41 g, 84%) as an anhydrate. The weight of the anhydrate
gradually increased over time in air and became constant, producing the tri-
hydrate.
methoxyphenylboronic acid (46 mg, 0.30 mmol), K2CO3 (42 mg, 0.30 mmol),
and 6 mg of PdCl2(PPh3)2 (0.009 mmol) were suspended in 2 mL of degassed
EtOH/H2O (5/1) under a N2 atmosphere. After stirring at 50 °C for 4 h, 18 mL of
EtOH was added, and 2 mL of the suspension was collected and quenched with
0.2 mL of 1 M HCl. The suspension was evaporated, and the residue was
dissolved in 60% MeCN (aq), and was analyzed by HPLC with the previously
prepared sample. For entry iii: to a suspension of 50 mg of 5 (0.076 mmol,
tetrahydrate), 46 mg of 4-methoxyphenylboronic acid (0.30 mmol), and 42 mg
of K2CO3 (0.30 mmol) in 6 mL of degassed EtOH/H2O (5/1), 6.5 mg of
PdCl2(Amphos)2 (0.0092 mmol) in 0.1 mL of the same solvent was added
under a N2 atmosphere. After stirring at 50 °C for 5 h, 14 mL of EtOH was
added, and the suspension was worked up in the same manner as entry i and
analyzed by HPLC.
Characterization data for compound 1: 1H NMR (400 MHz, DMSO-d6): d 2.18 (s,
6H, Me), 3.73 (s, 6H, CH), 6.78 (d, 4H, Ph, J = 7.3 Hz), 7.24 (d, 4H, Ph, J = 7.8 Hz);
13C NMR (100 MHz, DMSO-d6): d 21.07, 70.64, 126.08, 131.52, 132.20 (C–B was
not observed); 11B NMR (128 MHz, DMSO-d6): d 2.03; HR-ESI-MS: 379.1538
(C20H21O6B2-, [Mꢁ2K+H]ꢁ; calcd 379.1530); elemental analysis: calcd (%) for
C
20H24O8B2K2 (as dihydrate): C 48.80, H 4.91; found: C 49.73, H 4.82. For
18. The procedure for entry v is shown as an example: compound 3 (150 mg,
compound 2: 1H NMR (400 MHz, DMSO-d6): d 3.77 (s, 6H, CH), 6.90 (tt, 2H, Ph,
J = 1.9, 7.3 Hz), 6.95–6.99 (m, 4H), 7.36 (dd, 4H, Ph, J = 1.6, 8.0 Hz); 13C NMR
(100 MHz, DMSO-d6): d 70.61, 123.75, 125.37, 132.18 (C–B was not observed);
11B NMR (128 MHz, DMSO-d6): d 2.42. For compound 3: 1H NMR (400 MHz,
0.228 mmol,
tetrahydrate),
2-methoxyphenylboronic
acid
(139 mg,
0.912 mmol), K2CO3 (126 mg, 0.912 mmol), and PdCl2(PPh3)2 (19 mg,
0.027 mmol) were placed in a flask under a N2 atmosphere. Degassed EtOH/
H2O (5/1; 3 mL) was added, and the reaction mixture was stirred at 50 °C for
4 h. The solvent was removed under reduced pressure. Hexane/EtOAc (1/1)
was added, and the residue was extracted with water. To the aqueous layer,
1 M HCl was added dropwise until the pH was approximately 2, and the
resulting mixture was extracted twice with EtOAc. The combined organic
layers were dried with Na2SO4 and concentrated in vacuo. The residue was
purified by silica gel column chromatography (hexane/EtOAc = 4/1?1/1) to
give 51 mg of the biaryl compound (49%). All of the products gave satisfactory
1H and 13C NMR data (see the Supplementary data).
DMSO-d6): d 3.73 (s, 6H, CH), 7.10–7.12 (m, 4H, Ph), 7.28–7.31 (m, 4H, Ph); 13
C
NMR (100 MHz, DMSO-d6): d 70.57, 117.31, 128.02, 134.54 (C–B was not
observed); 11B NMR (128 MHz, DMSO-d6):
d
2.19; HR-ESI-MS: 506.9439
(C18H15O6B2Br2-, [Mꢁ2K+H]-; calcd 506.9427); elemental analysis: calcd (%)
for C18H20O9B2Br2K2 (as trihydrate): C 33.78, H 3.15; found: C 33.64, H 2.96. For
compound 4: 1H NMR (400 MHz, DMSO-d6): d 3.75 (s, 6H, CH), 6.94 (t, 2H, Ph,
J = 7.3 Hz), 7.05–7.08 (m, 2H), 7.31 (d, 2H, Ph, J = 7.3 Hz), 7.47 (d, 2H, Ph,
J = 2.3 Hz); 13C NMR (100 MHz, DMSO-d6): d 70.60, 120.50, 126.30, 127.83,
130.71, 134.92 (C–B was not observed); 11B NMR (128 MHz, DMSO-d6): d 1.90.
For compound 5: 1H NMR (400 MHz, DMSO-d6): d 3.80 (s, 6H, CH), 6.82 (td, 2H,
Ph, J = 1.8, 7.4 Hz), 6.97 (td, 2H, Ph, J = 1.2, 7.2 Hz), 7.19 (dd, 2H, Ph, J = 0.9,
7.8 Hz), 7.47 (dd, 2H, Ph, J = 1.8, 7.3 Hz); 13C NMR (100 MHz, DMSO-d6): d
70.65, 124.36, 126.05, 128.75, 131.22, 135.52 (C–B was not observed); 11B NMR
(128 MHz, DMSO-d6): d 1.98. For compound 6: 1H NMR (400 MHz, DMSO-d6): d
3.73 (s, 6H, CH), 7.29 (t, 2H, Ph, J = 2.1 Hz), 7.42 (d, 4H, Ph, J = 1.8 Hz); 13C NMR
19. The reaction mixture containing compound
3 (300 mg, 0.456 mmol,
tetrahydrate), 4-methylphenylboronic acid (248 mg, 1.82 mmol), K2CO3
(251 mg, 1.82 mmol), and PdCl2(PPh3)2 (38 mg, 0.055 mmol) in EtOH/H2O (5/
1; 6 mL) was stirred at 50 °C for 4 h under a N2 atmosphere. After cooled to
room temperature, the solution was diluted with 50 mL of EtOH and passed
thorough celite and concentrated. Hexane/EtOAc (1/1) was added and
extracted with water twice. To the aqueous layer, 1 M HCl was added
dropwise until the pH was approximately 2, and the resulting suspension
was extracted twice with EtOAc. The combined organic layer was dried with
Na2SO4 and passed through a short pad of silica-gel and concentrated in vacuo.
To a suspension of the residue, K2CO3 (251 mg, 1.82 mmol) and Pd(PPh3)4
(100 MHz, DMSO-d6): d 70.56, 120.75, 128.20, 133.63 (C–B was not observed);
11B NMR (128 MHz, DMSO-d6): d 1.88; HR-ESI-MS: 662.7645 (C18H13O6B2Br4
[Mꢁ2K+H]ꢁ; calcd 662.7637).
,
-
8. The concentration of the alcoholic solvent to a minimal volume and storage at
room temperature also led to the precipitation of SABC.
(32 mg, 0.027 mmol) in degassed DME/H2O (9/1; 6 mL) under
a N2
9. Nearly all of the SABCs were stable after heating at 150 °C for several hours
(5 h); however, the SABC composed of phenylboronic acid (compound 2)
degraded slightly to scyllo-inositol and phenylboronic acid after heating at
150 °C for 4–5 h. Drying at 105 °C for a couple of hours did not affect the
complex.
10. CCDC 971419 contains the supplementary crystallographic data of 3. This data
can be obtained free of charge from the Cambridge Crystallographic Data
11. The use of Pd(OAc)2, a ligand-free palladium complex, slightly increased yields
of the coupling reaction between compound 1 and aryl bromides similar to the
trend between entry vii and viii in Table 1. This phenomenon is under
investigation.
atmosphere, bromobenzene (0.142 mL, 1.37 mmol) was added. After stirring
at reflux for 6 h, the reaction solution was cooled to room temperature, diluted
with EtOAc, and passed through celite. The filtrate was washed with water and
brine, dried with Na2SO4, and concentrated in vacuo. The residue was purified
by silica gel column chromatography (hexane?hexane/diethylether = 98/2) to
give 88 mg of 4-methyl-1,10:40,100-terphenyl (40% from 3 after 2 steps) as a
white powder. Mp: 205–207 °C (lit.20a 206–208 °C). The 1H and 13C NMR
spectra corresponded to literature data.20b