The Journal of Organic Chemistry
Article
resulting residue was diluted with AcOEt (40 mL), and it was
successively washed with saturated aq NH4Cl, H2O, and brine. After
the general drying procedure, the crude product was purified by
column chromatography (57 g of SiO2, n-hexane/AcOEt = 4/1 to 3/
6H), 3.59−3.58 (m, 2H), 3.51 (s, 6H); 13C NMR (100 MHz, CDCl3)
δ 167.9 (s, 2C), 153.2 (s, 2C), 152.8 (s, 2C), 143.3 (s, 2C), 137.7 (s,
2C), 128.6 (s, 2C), 128.6 (d, 4C), 128.4 (d, 4C), 128.1 (d, 2C), 122.8
(s, 2C), 107.0 (d, 2C), 78.4 (d, 2C), 75.1 (t, 2C), 61.8 (t, 2C), 61.0 (q,
2C), 58.7 (q, 2C), 56.3 (q, 2C); ESIHRMS (m/z) calcd for
C38H40O12Na [M + Na]+ 711.2417, found 711.2398.
2) to afford 11 (2.28 g, 73% yield for two steps) as a yellow oil: [α]24
D
+33.3 (c 1.21, CHCl3); IR (ZnSe, thin film) 3032, 2982, 2878, 2828,
1734, 1592, 1497, 1455, 1366, 1331, 1246, 1196, 1157, 1096, 1013,
(2S,3S)-1,4-Dibenzyloxy-2,3-butandiyl Bis(4-O-benzylgal-
late) (14). (2S,3S)-1,4-Bis(benzyloxy)-2,3-butanediol (4) (1.00 g,
3.31 mmol) was azeotropically dried using C6H6 before use. It was
then dissolved in CH2Cl2 (10 mL). To the solution were added 6
(2.59 g, 7.44 mmol), (±)-camphor-10-sulfonic acid (384 mg, 1.65
mmol), EDC·HCl (2.54 g, 13.3 mmol), and DMAP (404 mg, 3.31
mmol) under an Ar atmosphere, and the mixture was stirred for 12 h
at rt. After addition of 1 M aq H3PO4 until pH of the mixture changed
to ∼2, the aq mixture was extracted with AcOEt. The combined
organic layer was successively washed with H2O, and brine. After the
general drying procedure, evaporation of the filtrate afforded crude
(2S,3S)-1,4-dibenzyloxy-2,3-butandiyl bis(4-O-benzyl-2,5-di-O -me-
1
978, 911, 847, 739, 696 cm−1; H NMR (400 MHz, acetone-d6) δ
7.60−7.58 (m, 4H), 7.46−7.38 (m, 10H), 7.28−7.27 (m, 6H), 7.22 (s,
2H), 7.18−7.16 (m, 6H), 7.01−6.99 (m, 4H), 5.28 (d, J = 16.6 Hz,
2H), 5.24 (d, J = 16.6 Hz, 2H), 5.03−4.96 (m, 6H), 4.80 (d, J = 10.8
Hz, 2H), 4.48 (d, J = 11.9 Hz, 2H), 4.23−4.20 (m, 2H), 3.66−3.64
(m, 2H), 3.49 (s, 6H); 13C NMR (100 MHz, acetone-d6) δ 168.4 (s,
2C), 153.5 (s, 2C), 153.0 (s, 2C), 145.2 (s, 2C), 138.9 (s, 2C), 138.8
(s, 2C), 138.0 (s, 2C), 130.5 (s, 2C), 129.4 (d, 4C), 129.1 (d, 8C),
129.0 (d, 6C), 128.9 (d, 4C), 128.8 (d, 4C), 128.7 (d, 2C), 128.4 (d,
2C), 124.2 (s, 2C), 109.7 (d, 2C), 78.7 (d, 2C), 76.1 (t, 2C), 75.6 (t,
2C), 71.9 (t, 2C), 61.7 (t, 2C), 58.0 (q, 2C); ESIHRMS (m/z) calcd
for C62H56O12Na [M + Na]+ 1015.3669, found 1015.3626.
thoxymethylgallate) as a colorless oil: [α]23 +12.1 (c 1.12, CHCl3);
D
IR (ZnSe, thin film) 3033, 2905, 1721, 1590, 1329, 1217, 1194, 1048,
(R)-4, 4′, 5, 5′, 6, 6′-Hexakis(benzyloxy)-2, 2′-bis-
(hydroxymethyl)-1,1′-biphenyl [(aR)-12]. To a stirred mixture of
LAH (9.1 mg, 0.24 mmol) in Et2O (1.0 mL) under an Ar atmosphere
was dropwise added a solution of 11 (80.3 mg, 80.9 μmol) in Et2O
(1.5 mL) at 0 °C. After being stirred at 0 °C to rt for 45 min, the
reaction mixture was cooled to 0 °C again. Additional LAH (7.7 mg,
0.20 mmol) was added to the mixture, and it was stirred at 0 °C to rt
for 45 min. The reaction mixture was diluted with Et2O (3.0 mL) and
quenched with H2O (minimal required amount). Anhydrous MgSO4
and Celite were added to the wet mixture, and it was filtered through a
cotton−Celite pad. After evaporation of the filtrate, the resulting
residue was purified by silica gel column chromatography (5.0 g of
SiO2, n-hexane/AcOEt = 9/1, then AcOEt only) to afford (aR)-12
(57.4 mg, 83% yield, >99% ee) and 3 (4.6 mg, 38% yield) both as a
colorless oil. Unidentified byproducts whose polarity was similar to
that of 3 decreased the isolation yield of 3. 1H NMR data for (aR)-12
were identical to the literature data.4 The ee value was determined by
HPLC with the chiral column (eluant: n-hexane/ethanol = 9/1, flow
1
758, 698 cm−1; H NMR (400 MHz, CDCl3) δ 7.49 (s, 4H), 7.46−
7.44 (m, 4H), 7.36−7.20 (m, 16H), 5.70−5.65 (m, 2H), 5.15 (d, J =
8.4 Hz, 4H), 5.13 (d, J = 8.4 Hz, 4H), 5.10 (s, 4H), 4.56 (d, J = 11.9
Hz, 2H), 4.47 (d, J = 11.9 Hz, 2H), 3.80−3.72 (m, 4H), 3.43 (s, 12H);
13C NMR (100 MHz, CDCl3) δ 165.3 (s, 2C), 151.0 (s, 4C), 143.5 (s,
2C), 137.9 (s, 2C), 137.5 (s, 2C), 128.5 (d, 4C), 128.4 (d, 8C), 128.2
(d, 2C), 127.9 (d, 4C), 127.8 (d, 2C), 125.5 (s, 2C), 112.6 (d, 4C),
95.7 (t, 4C), 75.4 (t, 2C), 73.5 (t, 2C), 72.2 (d, 2C), 68.4 (t, 2C), 56.5
(q, 4C); ESIHRMS (m/z) calcd for C54H58O16Na [M + Na]+
985.3623, found 985.3642.
To a solution of the crude (2S,3S)-1,4-dibenzyloxy-2,3-butandiyl
bis(4-O-benzyl-2,5-di-O-methoxymethylgallate) in THF (8 mL) was
added a mixture of i-PrOH containing 5 v/v% of concd hydrochloric
acid (25 mL), and it was stirred for 9 h at 50 °C. The mixture was
cooled to rt, and saturated aq NaHCO3 was added until the pH of the
mixture became ∼7. After removal of i-PrOH by evaporation, the aq
mixture was extracted with AcOEt. The combined organic layer was
successively washed with saturated aq NaHCO3, H2O, and brine. After
the general drying procedure, the mixture was purified by column
chromatography (100 g of SiO2, n-hexane/AcOEt = 6/1 to 1/1) to
afford 14 (2.41 g, 93% yield for two steps) as a colorless amorphous
solid: [α]25D +13.4 (c 1.52, CHCl3); IR (ZnSe, thin film) 3424, 1707,
rate: 1.0 mL/min, tR: 12.2 min). Data for (aR)-12: [α]25 −78.2 (c
D
0.85, CHCl3); IR (ZnSe, thin film) 3391, 3063, 2876, 1595, 1455,
1123, 1098, 696 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.53 (br d, J =
6.9 Hz, 4H), 7.46−7.34 (m, 10H), 7.31−7.24 (m, 6H), 7.21−7.12 (m,
6H), 7.06 (s, 2H), 6.83 (br d, J = 6.6 Hz, 4H), 5.25 (d, J = 11.7 Hz,
2H), 5.21 (d, J = 11.7 Hz, 2H), 5.07 (d, J = 10.8 Hz, 2H), 5.02 (d, J =
10.8 Hz, 2H), 4.98 (d, J = 11.0 Hz, 2H), 4.60 (d, J = 11.0 Hz, 2H),
4.19 (br s, 4H), 2.68 (br s, 2H); 13C NMR (100 MHz, acetone-d6) δ
153.5 (s, 2C), 151.5 (s, 2C), 141.8 (s, 2C), 139.0 (s, 2C), 138.7 (s,
2C), 138.2 (s, 2C), 137.8 (s, 2C), 129.3 (d, 4C), 129.1 (d, 4C), 128.9
(d, 4C), 128.8 (d, 4C), 128.7 (d, 2C), 128.6 (d, 2C), 128.5 (d, 4C),
128.1 (d, 2C), 128.1 (d, 4C), 122.9 (s, 2C), 110.1 (d, 2C), 75.8 (t,
2C), 75.2 (t, 2C), 71.5 (t, 2C), 62.8 (t, 2C); ESIHRMS (m/z): [M +
Na]+ calcd for C56H50O8 873.3403, found 873.3382.
1
1597, 1455, 1364, 1215, 1055, 754, 698 cm−1; H NMR (400 MHz,
CDCl3) δ 7.38−7.34 (m, 10H), 7.28−7.22 (m, 10H), 7.17 (s, 4H),
6.09 (br s, 4H), 5.65−5.62 (m, 2H), 5.11 (s, 4H), 4.53 (d, J = 12.1 Hz,
2H), 4.44 (d, J = 12.1 Hz, 2H), 3.70 (br d, J = 3.9 Hz, 4H); 13C NMR
(100 MHz, CDCl3) δ 165.9 (s, 2C), 149.2 (s, 4C), 137.9 (s, 2C),
137.5 (s, 2C), 136.7 (s, 2C), 129.0 (d, 6C), 128.8 (d, 4C), 128.6 (d,
4C), 128.1 (d, 4C), 128.0 (d, 2C), 125.4 (s, 2C), 110.1 (d, 4C), 75.6
(t, 2C), 73.5 (t, 2C), 71.9 (d, 2C), 68.3 (t, 2C); ESIHRMS (m/z)
calcd for C46H42O12Na [M + Na]+ 809.2574, found 809.2560.
(2S,3S)-Dimethoxy-1,4-Butandiyl (R)-5,5′-bis(benzyloxy)-
4,4′,6,6′-tetrakis(methyloxy)-1,1′-biphenyl-2,2′-dicarboxylate
(13). According to the procedure described in the synthesis of 10, 8
(200 mg, 0.315 mmol) was transformed to 10, which was used for the
next step without purification.52 To a solution of crude 10 in acetone
(9.5 mL) were added MeI (447 mg, 3.2 mmol) and K2CO3 (653 mg,
4.72 mmol) under an Ar atmosphere. The mixture was stirred for 14 h
at rt. It was then filtrated through a cotton−Celite pad and evaporated.
The residue was dissolved in CH2Cl2 (80 mL), and the solution was
successively washed with H2O and brine. After the general drying
procedure, the mixture was purified by preparative TLC (CHCl3/
MeOH = 30/1) to give 13 (106 mg, 49% yield for two steps) as a
yellow solid, which was recrystallized from a mixture of CH2Cl2 and n-
(2S,3S)-1,4-Dibenzyloxy-2,3-butandiyl (S)-5,5′-bis-
(benzyloxy)-4,4′,6,6′-tetrahydroxy-1,1′-biphenyl-2,2′-dicar-
boxylate (15). The substrate 14 (76.1 mg, 96.7 μmol) was
azeotropically dried using MeCN before use. It was then dissolved
in MeOH (3.0 mL). To the other flask were added CuCl2 (68.3 mg,
0.508 mmol) and n-BuNH2 (146 mg, 2.00 mmol) under a N2
atmosphere. To the mixture was added MeOH (7.0 mL), and it was
stirred for 20 min at rt to prepare a blue solution of CuCl2·n-BuNH2
complex. To this mixture was added the solution of 14 in MeOH. The
mixture was stirred for 1.5 h at rt. The reaction was quenched with 1
M hydrochloric acid and saturated aq NH4Cl. The aq mixture was
extracted by AcOEt. The combined organic layer was successively
washed with 1 M hydrochloric acid, saturated aq NaHCO3, H2O, and
brine. After the general drying procedure, evaporation of the filtrate
afforded crude 15 as a yellow amorphous solid. The isolated 15 was
unstable in air to prolonged storage, which was used for the next step
hexane to afford single crystals: mp 202.2−202.7 °C; [α]25 +101 (c
D
1.00, CHCl3); IR (ZnSe, thin film) 2961, 2936, 2851, 1736, 1593,
1497, 1485, 1395, 1337, 1206, 1103, 1059, 1026, 986, 754, 698 cm−1
;
1H NMR (400 MHz, CDCl3) δ 7.50−7.48 (m, 4H), 7.37−7.27 (m,
6H), 6.86 (s, 2H), 5.18 (d, J = 11.2 Hz, 2H), 5.10 (d, J = 11.2 Hz, 2H),
4.47 (br d, J = 11.9 Hz, 2H), 4.17−4.13 (m, 2H), 3.85 (s, 6H), 3.64 (s,
without purification. Data for 15: [α]25 +11.1 (c 0.19, CHCl3); IR
D
(ZnSe, thin film) 3063, 3032, 2923, 2361, 1750, 1607, 1584, 1497,
1
1455, 1368, 1177, 1132, 1061, 737, 700 cm−1; H NMR (400 MHz,
9716
dx.doi.org/10.1021/jo201750d|J. Org. Chem. 2011, 76, 9711−9719