G
A. N. Ndimba et al.
Paper
Synthesis
Compound 18
IR (neat): 3059, 1614, 1590, 1506, 1463, 1321, 1296, 1260, 1208,
1188, 966, 950, 899, 884, 811, 747 cm–1
.
Obtained from 1 (200 mg, 1 equiv), purified by column chromatogra-
phy on silica gel using a mixture of petroleum ether/EtOAc (7:3 to
1:1) as eluent. Crystals suitable for X-ray diffraction study were
grown by slow diffusion of a CH2Cl2 solution layered with pentane.
1H NMR (300 MHz, CDCl3): δ = 8.00–7.89 (m, 3 H), 7.75 (d, J = 8.1 Hz,
1 H), 7.65–7.53 (m, 6 H), 7.48–7.40 (m, 3 H), 7.36–7.22 (m, 9 H), 7.13
(d, J = 8.4 Hz, 1 H), 7.05–6.89 (m, 4 H), 6.19–6.15 (m, 3 H).
20
13C NMR (75 MHz, CDCl3): δ = 147.0 (d, JCP = 11.5 Hz), 146.3 (d, JCP
=
Yield: 568 mg (83%); white solid; mp > 280 °C; [α]D +354 (c = 1;
CHCl3).
8.7 Hz), 145.9, 145.8, 145.7, 145.6 (d, JCP = 6.5 Hz), 134.5, 133.1, 132.7,
132.2, 132.0, 131.9 (d, JCP = 1.0 Hz), 131.6 (d, JCP = 1.0 Hz), 131.4, 131.0,
130.7, 130.2 (d, JCP = 4.0 Hz), 128.8, 128.6, 128.2, 127.8, 127.3, 127.2,
127.0, 127.0, 126.9, 126.8 (d, JCP = 2.6 Hz), 126.1, 125.9, 125.8, 125.6,
IR (neat): 3056, 1505, 1305, 1202, 1187, 965, 950 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 7.93 (d, J = 8.1 Hz, 2 H), 7.83 (d, J =
8.1 Hz, 2 H), 7.73 (d, J = 8.1 Hz, 2 H), 7.60–7.42 (m, 12 H), 7.39–7.25
(m, 8 H), 7.20–7.11 (m, 6 H), 6.51 (dd, J = 8.7, 0.9 Hz, 2 H), 5.94 (dd, J =
8.7, 0.9 Hz, 2 H).
125.4, 123.3 (d, JCP = 3.4 Hz), 121.4 (d, JCP = 2.2 Hz), 120.9 (d, JCP
=
4.4 Hz), 120.8, 120.7 (d, JCP = 3.1 Hz), 120.6 (d, JCP = 2.2 Hz), 119.5 (d,
JCP = 3.3 Hz), 118.8, 118.6, 112.7, 112.5, 112.4, 112.0 (d, JCP = 9.3 Hz).
31P NMR (202 MHz, CDCl3): δ = –3.55, –24.47.
ESI-HRMS: m/z [M + H]+ calcd. for C50H31O8P2: 821.1488; found:
821.1496.
13C NMR (75 MHz, CDCl3): δ = 146.9 (d, JCP = 11.6 Hz), 146.0 (d, JCP
=
5.9 Hz), 145.9 (d, JCP = 8.6 Hz), 133.2, 132.1 (d, JCP = 0.9 Hz), 131.9 (d,
JCP = 0.9 Hz), 131.7 (d, JCP = 1.0 Hz), 131.6 (d, JCP = 1.0 Hz), 131.1, 130.9,
130.8, 130.0, 128.8, 128.3, 128.2, 127.4, 127.2, 126.9, 126.6, 126.5,
126.0, 125.9, 125.8, 125.7, 121.6 (d, JCP = 8.1 Hz), 121.1 (d, JCP = 2.2 Hz),
120.4 (d, JCP = 2.2 Hz), 120.2 (d, JCP = 2.8 Hz), 119.3 (d, JCP = 3.2 Hz),
119.2.
31P NMR (202 MHz, CDCl3): δ = –3.58.
ESI-HRMS: m/z [M + Na]+ calcd. for C60H36O8P2Na: 969.1777; found:
Synthesis of Bisphosphate 20
Under an argon atmosphere, to a solution of 2 (150 mg, 1 equiv) in
anhydrous THF (0.3 M), NaH (2.5 equiv) was added at 0 °C and the
mixture was stirred at this temperature for 30 min before the addi-
tion of (S)-H8-BINOL phosphorochloridate 19 (2.1 equiv). The mixture
was stirred at r.t. for an additional 30 min, then hydrolyzed with H2O
and extracted with CH2Cl2. The organic phase was washed with an
aqueous 1N HCl solution and with H2O, then dried over anhydrous
MgSO4. The solvent was removed under vacuum and the residue was
purified by column chromatography on silica gel using a mixture of
petroleum ether/EtOAc (7:3 to 1:1) as eluent.
969.1780.
Compound 23
Obtained from 3 (85 mg, 1 equiv), purified by column chromatogra-
phy on silica gel using a mixture of petroleum ether/EtOAc (7:3) as
eluent.
Yield: 160 mg (73%); white solid; mp 165–167 °C; [α]D20 +141 (c = 1.1,
Yield: 438 mg (88%); white solid; mp 207–209 °C; [α]D20 +121 (c = 1.2,
CHCl3).
CHCl3).
IR (neat): 2927, 2857, 1589, 1464, 1307, 1210, 992, 956, 884, 811 cm–1
.
IR (neat): 3059, 1589, 1505, 1475, 1433, 1304, 1212, 1187, 1000, 965,
951, 886, 747 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 7.17 (d, J = 8.4 Hz, 2 H), 7.08 (d, J =
8.4 Hz, 2 H), 7.00 (d, J = 8.4 Hz, 2 H), 6.84 (d, J = 8.1 Hz, 2 H), 6.79 (dd,
J = 8.1, 1.2 Hz, 2 H), 5.98 (d, J = 8.1 Hz, 2 H), 2.78–2.73 (m, 12 H), 2.60–
2.42 (m, 6 H), 2.19–2.03 (m, 6 H), 1.74–1.72 (m, 18 H), 1.51–1.45 (m,
6 H).
1H NMR (300 MHz, CDCl3): δ = 7.95 (d, J = 9.3 Hz, 1 H), 7.87–7.77 (m,
6 H), 7.54–7.39 (m, 7 H), 7.35–7.30 (m, 3 H), 7.23–7.06 (m, 11 H), 7.01
(td, J = 8.1, 0.9 Hz, 1 H), 6.55 (dt, J = 8.1, 1.2 Hz, 1 H), 6.18 (d, J = 9.0 Hz,
1 H), 6.12 (d, J = 8.1 Hz, 1 H).
13C NMR (75 MHz, CDCl3): δ = 147.3 (d, JCP = 9.0 Hz), 147.2 (d, JCP
=
13C NMR (75 MHz, CDCl3): δ = 146.8 (d, JCP = 11.0 Hz), 146.0 (d, JCP
=
9.0 Hz), 146.9 (d, JCP = 11.2 Hz), 146.2 (d, JCP = 6.0 Hz), 146.2, 146.0 (d,
JCP = 6.0 Hz), 145.9, 133.3 (d, JCP = 9.8 Hz), 132.2 (d, JCP = 0.9 Hz), 131.9
(d, JCP = 0.9 Hz), 131.8, 131.5 (d, JCP = 1.0 Hz), 131.2, 131.1, 130.9,
130.8, 130.4, 130.0, 129.9 (d, JCP = 5.8 Hz), 129.4 (d, JCP = 2.5 Hz), 128.7,
128.5, 128.2, 128.0, 127.7 (d, JCP = 1.2 Hz), 127.6 (d, JCP = 1.2 Hz), 127.3
(d, JCP = 5.3 Hz), 127.2, 127.0, 126.7, 126.5, 126.2, 126.1, 125.8, 125.7
(d, JCP = 6.0 Hz), 125.7, 121.9 (d, JCP = 7.9 Hz), 121.3 (d, JCP = 2.3 Hz),
121.0 (d, JCP = 4.4 Hz), 120.8, 120.7, 120.5 (d, JCP = 2.9 Hz), 120.4 (d,
JCP = 2.3 Hz), 119.5, 119.2 (d, JCP = 3.2 Hz), 118.4.
6.5 Hz), 145.6 (d, JCP = 8.4 Hz), 138.4 (d, JCP = 1.4 Hz), 137.9, 137.7,
135.8 (d, JCP = 2.2 Hz), 135.0 (d, JCP = 2.2 Hz), 134.6, 130.2, 130.1, 129.5,
127.1 (d, JCP = 7.4 Hz), 126.2 (d, JCP = 6.9 Hz), 125.3 (d, JCP = 6.9 Hz),
118.6 (d, JCP = 3.4 Hz), 117.6 (d, JCP = 3.7 Hz), 117.3, 29.7, 29.3, 29.2,
27.9, 27.8, 27.4, 23.0, 22.9, 22.6, 22.5, 22.4.
31P NMR (202 MHz, CDCl3): δ = –4.63.
ESI-HRMS: m/z [M + Na]+ calcd. for C60H60O8P2Na: 993.3655; found:
993.3657.
31P NMR (202 MHz, CDCl3): δ = –3.46, –5.28.
ESI-HRMS: m/z [M + Na]+ calcd. for C52H32O8P2Na: 869.1464; found:
Synthesis of Bisphosphates 26
Under an argon atmosphere, to a solution of PCl3 (1 equiv) in toluene
(0.1 M), phenol (1.07 g, 2 equiv) and Et3N (5 equiv) were added at
0 °C. The mixture was stirred at 0 °C for 30 min before the addition of
1 (820 mg, 0.5 equiv). The reaction was stirred at r.t. for 1 h, then the
mixture was filtered over a pad of Celite and the solvent was removed
under vacuum. The crude was dissolved in EtOAc, washed with H2O,
an aqueous 5% NaOCl solution and brine, then dried over anhydrous
MgSO4. The solvent was removed under vacuum and the residue was
purified by column chromatography on silica gel using a mixture of
petroleum ether/EtOAc (3:1) as eluent. Crystals suitable for X-ray dif-
fraction study were grown by slow diffusion of a CH2Cl2 solution lay-
ered with heptane.
869.1464.
Compound 24
Obtained from 4 (80 mg, 1 equiv), purified by column chromatogra-
phy on silica gel using a mixture of petroleum ether/EtOAc (7:3) as
eluent. X-ray single quality crystals were grown by slow diffusion of
Et2O in CDCl3 solution.
Yield: 230 mg (56%); white solid; mp 171–173 °C; [α]D20 +112 (c = 1.2,
CHCl3).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–I