PAPER
Enantioselective Synthesis of Biaryl Compounds
681
7′-Butoxy-7-(trifluoromethylsulfonyloxy)-8,8′-biquinolyl (6)
A stirred solution of phenol 5 (1.00 g, 2.90 mmol) in anhydrous pyr-
idine (12 mL) at 0 °C under argon was treated dropwise with neat
Tf2O (1.43 mL, d = 1.677, 2.40 g, 8.50 mmol). The mixture was al-
lowed to warm to r.t. and stirred for 71 h and then concentrated in
vacuo. The residue was purified by column chromatography (SiO2,
eluting with 3–5% MeOH in CH2Cl2) to afford triflate 6 (1.29 g,
2.71 mmol, 93%) as a yellow solid; mp 117–119 °C (CHCl3).
Efforts to structurally characterize Pd and other metal
complexes derived from 8,8′-biquinoyl phosphine 2 and
related quinoline containing biaryl molecules are in prog-
ress. This work and investigations of further applications
of axially chiral heterocyclic biaryls in asymmetric syn-
thesis will be reported in due course.
IR (KBr): 2961, 1613, 1503, 1418, 1213, 1143, 964, 847 cm–1.
Preparative chromatographic separations were performed on silica
gel 60 (35–75 μm) and reactions followed by TLC analysis using
silica gel 60 plates (2–25 μm) with fluorescent indicator (254 nm)
and visualized by UV or phosphomolybdic acid (PMA). All com-
mercially available reagents were used as received (Aldrich). Anhy-
drous solvents were obtained from a Pure Process Technologies
solvent purification system and dispensed under argon.25 Melting
points were recorded on a Mel-Temp melting point apparatus and
are uncorrected. IR spectra were recorded on a PerkinElmer Spec-
trum II FT-IR using KBr discs for solids or a thin film between
NaCl plates for oils. NMR spectra were recorded on Bruker Avance
spectrometers at the field strength specified from 5 mm diameter
tubes. Chemical shift in ppm is quoted relative to residual solvent
signals calibrated as follows for CDCl3: δH (CHCl3) = 7.26,
δC = 77.2 ppm. Numbers in parentheses following carbon atom
chemical shifts refer to the number of attached hydrogen atoms as
revealed by the DEPT spectral editing technique. Low- (MS) and
high-resolution (HRMS) mass spectra were obtained using electro-
spray (ES), electron impact (EI), or chemical ionization (CI) tech-
niques. Ion mass/charge (m/z) ratios are reported as values in atomic
mass units. Chiral stationary phase (CSP) high performance liquid
chromatography (HPLC) was executed on an Agilent 1100 series
modular HPLC system equipped with standard Daicel Industries
chiral columns as indicated. Circular dichroism (CD) spectra were
recorded on a Jasco J-815 instrument at a scan rate of 100 nm min–1
from MeOH solutions in a cell with 1 mm path length.
1H NMR (400 MHz, CDCl3): δ = 8.84 (dd, J = 4.0, 1.2 Hz, 1 H),
8.71 (dd, J = 4.1, 1.4 Hz, 1 H), 8.26 (dd, J = 8.4, 1.4 Hz, 1 H), 8.15
(dd, J = 8.0, 1.0 Hz, 1 H), 7.99 (d, J = 8.9 Hz, 1 H), 7.97 (d, J = 9.0
Hz, 1 H), 7.65 (d, J = 9.0 Hz, 1 H), 7.49 (d, J = 9.1 Hz, 1 H), 7.42
(dd, J = 8.2, 4.1 Hz, 1 H), 7.23 (dd, J = 8.2, 4.2 Hz, 1 H), 4.05 (t,
J = 6.5 Hz, 2 H), 1.42 (quint, J = 7.0 Hz, 2 H), 0.99 (sext, J = 7.4
Hz, 2 H), 0.66 (t, J = 7.4 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 157.7 (0), 151.4 (1), 151.1 (1),
148.2 (0), 148.1 (0), 148.0 (0), 136.3 (1), 136.1 (1), 130.5 (1), 129.5
(1), 127.7 (0), 123.6 (0), 121.6 (1), 120.4 (1), 120.0 (0), 119.0 (1),
117.7 (0), 114.8 (1), 68.8 (2), 31.2 (2), 18.8 (2), 13.6 (3) (CF3 not
distinguishable).
MS (ES+): m/z (%) = 477 (100, [M + H+]).
HRMS (ES+): m/z calcd for C23H20F3N2O4S: 477.1096; found:
477.1094.
7′-Butoxy-7-(diphenyloxyphosphino)-8,8′-biquinolyl (7)
A 30 mL thick-walled glass reaction tube equipped with a Teflon
screw-fitting stopper (a ‘sealed tube’ apparatus) was opened to air
and charged with a stir bar, triflate 6 (566 mg, 1.19 mmol),
tris(dibenzylideneactone)dipalladium (Pd2dba3, 53 mg, 0.058
mmol, 5 mol%), and 1,1′-bis(diphenylphosphino)ferrocene (dppf,
71 mg, 0.128 mmol, 11 mol%). Et3N (0.24 mL, d = 0.726, 174 mg,
1.73 mmol), Ph2PH (0.22 mL, d = 1.07, 235 mg, 1.26 mmol), and
DMF (12 mL) were then added and the Teflon stopper screwed back
into place to create a tight seal. Stirring was initiated to effect disso-
lution and the tube partially submerged in a 100 °C oil bath above a
magnetic stirrer-hotplate (note: the entire apparatus was set-up be-
hind a large plastic blast shield). The contents of the sealed tube
were stirred in this manner for 47 h and then allowed to cool to r.t.
before the stopper was cautiously removed. The reaction mixture
was filtered and the solids washed with EtOAc (2 × 5 mL). The fil-
trate and combined washings were partitioned between EtOAc (20
mL) and H2O (30 mL) and the layers separated. The aqueous phase
was extracted with EtOAc (3 × 20 mL) and the combined organic
phases washed with sat. aq NH4Cl (3 × 40 mL), brine (20 mL), then
dried (Na2SO4), and concentrated in vacuo. The residue was further
purified by column chromatography (SiO2, eluting with 3–5%
MeOH in CHCl2) to afford the racemic phosphine oxide (±)-7 (577
mg, 1.09 mmol, 92%) as a viscous yellow-brown oil that solidified
on standing. Recrystallization from toluene gave pale yellow plates
suitable for X-ray diffraction analysis9 (Figure 2); mp 136–138 °C
(toluene).
7′-Butoxy-7-hydroxy-8,8′-biquinolyl (5)
A stirred suspension of 7,7´-dihydroxy-8,8′-biquinolyl (4;6 1.48 g,
5.13 mmol), Ph3P (1.88 g, 7.18 mmol), and n-BuOH (2.40 mL,
d = 0.810, 1.94 g, 26.2 mmol) in THF (52 mL) was treated with di-
ethyl azodicarboxylate (DEAD, 3.10 mL, 40 wt% in toluene,
d = 0.956, 1.19 g, 6.81 mmol) at r.t. The resulting mixture was
stirred for 4 h at r.t. and then concentrated in vacuo. The residue was
taken up in 2.0 M aq HCl (10 mL) and H2O (20 mL) and the acidic
aqueous solution of biquinolyl hydrochloride salts washed with
EtOAc (3 × 30 mL). The pH of the aqueous phase was adjusted to
7.0 with 30 wt% aq KOH and the free bases of the biquinolyl com-
ponents were extracted with EtOAc (4 × 40 mL). The combined or-
ganic extracts were dried (Na2SO4) and concentrated in vacuo. The
residue was purified by column chromatography (SiO2, eluting with
1–2% MeOH in CH2Cl2) to afford the monoether 5 (1.35 g, 3.92
mmol, 76%) as a yellow solid; mp 136–138 °C.
IR (KBr): 2933, 1610, 1501, 1428, 1307, 1085 cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.82 (dd, J = 4.3, 1.8 Hz, 1 H),
8.68 (dd, J = 4.3, 1.8 Hz, 1 H), 8.23 (dd, J = 8.2, 1.8 Hz, 1 H), 8.11
(dd, J = 8.1, 1.8 Hz, 1 H), 7.97 (d, J = 9.0 Hz, 1 H), 7.82 (d, J = 8.8
Hz, 1 H), 7.53 (d, J = 9.0 Hz, 1 H), 7.46 (d, J = 8.9 Hz, 1 H), 7.31
(dd, J = 8.3, 4.3 Hz, 1 H), 7.19 (dd, J = 8.1, 4.2 Hz, 1 H), 6.80–6.30
(br s, OH), 4.04–3.91 (m, 2 H), 1.30–1.20 (m, 2 H), 0.86 (sext,
J = 7.1 Hz, 2 H), 0.63 (t, J = 7.3 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 159.2 (0), 155.2 (0), 151.1 (1),
149.9 (1), 148.7 (0), 147.8 (0), 137.4 (1), 136.1 (1), 129.9 (1), 129.0
(1), 124.1 (0), 124.0 (0), 120.5 (1), 119.3 (0), 119.0 (1), 118.6 (0),
118.4 (1), 116.4 (1), 69.1 (2), 31.2 (2), 18.7 (2), 13.7 (3).
IR (KBr): 2926, 1611, 1502, 1437, 1308, 1273, 1175, 1116 cm–1.
1H NMR (400 MHz, CDCl3): δ = 8.71 (dd, J = 4.1, 1.7 Hz, 1 H),
8.45 (dd, J = 4.2, 1.7 Hz, 1 H), 8.18 (dd, J = 8.3, 1.7 Hz, 1 H), 8.00
(dd, J = 11.3, 8.6 Hz, 1 H), 7.92 (dd, J = 8.6, 2.7 Hz, 1 H), 7.85 (dd,
J = 8.2, 1.7 Hz, 1 H), 7.62–7.55 (m, 3 H), 7.37 (dd, J = 8.3, 4.2 Hz,
1 H), 7.32 (tm, J = 7.5 Hz, 1 H), 7.25–7.17 (m, 5 H), 7.08 (d, J = 9.0
Hz, 1 H), 7.05–7.00 (m, 3 H), 3.95–3.90 (m, 1 H), 3.88–3.81 (m, 1
H), 1.43–1.35 (m, 2 H), 0.98–0.85 (m, 2 H), 0.62 (t, J = 7.4 Hz, 3
H).
13C NMR (100 MHz, CDCl3): δ = 157.5 (0), 150.8 (1), 150.0 (1),
148.5 (0), 147.7 (0, d, J = 14 Hz), 142.6 (0, d, J = 8 Hz), 136.0 (1),
135.6 (1), 133.7 (0, d, J = 103 Hz), 133.2 (0, d, J = 104 Hz), 132.2
(1, d, J = 10 Hz, 2 C), 131.7 (1, d, J = 10 Hz, 2 C), 131.1 (1, d, J = 2
Hz), 130.8 (1, d, J = 2 Hz), 129.9 (0, d, J = 3 Hz), 129.8 (1, d, J = 11
MS (ES+): m/z (%) = 345 (100, [M + H+]).
HRMS (ES+): m/z calcd for C22H21N2O2: 345.1603; found:
345.1586.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 678–685