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M. G. Banwell et al. / Tetrahedron: Asymmetry 16 (2005) 1645–1654
compound 9 (380 mg, 72%) as a white, crystalline solid:
mp 68–70 ꢁC; [a]D = ꢀ14 (c 1.0, CHCl3); IR: mmax 3422
(broad), 2940, 1595, 1462, 1422, 1357, 1235, 1189,
1176, 1126, 967, 815cm ꢀ1; 1H NMR (300 MHz, CDCl3):
d 7.75(d, J = 8.2 Hz, 2H, ArH), 7.34 (d, J = 8.2 Hz, 2H,
ArH), 6.57 (s, 2H, ArH), 5.09 (s, 2H), 4.63 (d, J = 6.2 H,
1H), 4.04–3.86 (m, 3H), 3.82 (s, 6H), 3.58 (s, 3H), 2.60
(broad s, 2H, OH), 2.44 (s, 3H); 13C NMR (75MHz,
CDCl3): d 153.4 (C), 145.2 (C), 135.7 (C), 134.1 (C),
132.3 (C), 129.9 (CH), 127.9 (CH), 103.3 (CH), 98.0
extracted with ethyl acetate (4 · 20 mL). The combined
organic extracts were then dried over Na2SO4, filtered,
and concentrated under reduced pressure. The residue
thus obtained was subjected to flash chromatography
(7:3 v/v diethyl ether/hexane elution) to afford, after con-
centration of the appropriate fractions (Rf 0.5), a white
solid. Recrystallization (ethanol) of this material gave
the title compound 1119 (320 mg, 39%) as colorless crys-
tals: mp 120–121 ꢁC (lit.19b mp 121–122 ꢁC); IR: mmax
3210 (broad), 2870, 1674, 1605, 1580, 1513, 1344,
1
(CH2), 73.6 (CH), 73.5(CH), 70.1 (CH ), 57.1 (OCH3),
2
1288, 1259, 1117, 1016, 1008, 812, 728 cmꢀ1; H NMR
56.0 (OCH3), 21.6 (CH3); MS (EI, 70 eV): m/z 442
(M+Å, <1%), 410 (7), 380 (4), 227 (20), 208 (22), 183
(25), 155 (48), 167 (65), 91 (92), 45 (100); HRMS: M+Å
calcd for C20H26O9S: 442.1298; found: 442.1293.
(300 MHz, CD3COCD3): d 9.83 (s, 1H, CHO), 8.40
(broad s, 1H, OH), 7.53 (dm, J = 8.2 Hz, 1H), 7.45–
7.32 (complex m, 6H, ArH), 7.24 (d, J = 8.2 Hz, 1H),
5.26 (s, 2H); 13C NMR (75MHz, CD 3COCD3): d
190.9 (CHO), 152.3 (C), 147.6 (C), 136.6 (C), 131.1
(C), 128.7 (CH), 128.4 (CH), 128.3 (CH), 124.3 (CH),
114.4 (CH), 112.7 (CH), 70.8 (CH2); MS (EI, 70 eV):
m/z 228 M+Å, 17%, 137 (3), 109 (3), 91 (100), 81 (6), 65
(21); HRMS: M+Å calcd for C14H12O3: 228.0786; found:
228.0789.
4.1.7. (1R,2R)-2,3-Epoxy-1-(30,50-dimethoxy-40-methoxy-
methoxyphenyl)propanol 10. A solution of tosylate 9
(301 mg, 0.7 mmol) in dry methanol (20 mL) was treated
with K2CO3 (98 mg of anhydrous material, 0.7 mol) and
the resulting suspension stirred vigorously at 18 ꢁC under
an atmosphere of nitrogen for 3 h, then poured into
water (20 mL) and extracted with ethyl acetate
(3 · 20 mL). The combined organic phases were washed
with brine (1 · 30 mL), dried over Na2SO4, filtered, and
concentrated under reduced pressure to give a light-yel-
low oil. Subjection of this material to flash chromatogra-
phy (7:3 v/v ethyl acetate/hexane elution) gave, after
concentration of the appropriate fractions [Rf 0.3(5)],
an off-white solid. Recrystallization (DCM–hexane) of
this material then afforded title compound 10 (160 mg,
88%) as a white, crystalline solid, mp 71–73 ꢁC, in
>95% ee (as determined by chiral HPLC analysis using
CHIRALPAKꢂ AS-H 250 · 4.6 mm column, 1:3 v/v iso-
propyl alcohol/hexane elution at a solvent flow rate of
1 mL/min and with UV peak detection at 254 nm, tR
16.1 min): [a]D = ꢀ5.4 (c 1.3, CHCl3); IR: mmax 3433
(broad), 2940, 1593, 1505, 1462, 1420, 1331, 1230,
4.1.9.
(10S,20R)-4-Benzyloxy-3-[20,30-epoxy-10-(300,500-
dimethoxy-400-methoxymethoxyphenyl)-propoxy]-benzal-
dehyde 12. A magnetically stirred solution of aldehyde
11 (111 mg, 0.5mmol) and DIAD (98 lL, 0.5mmol) in
dry toluene (10 mL) maintained at 18 ꢁC under an atmo-
sphere of nitrogen was treated, dropwise, with a solution
of PPh3 (130 mg, 0.5mmol) and epoxide 10 (101 mg,
0.4 mmol) in dry THF–toluene (2 mL of a 1:1 v/v mix-
ture). The ensuing mixture was stirred at 18 ꢁC for
24 h and then solvent removed under reduced pressure.
Subjection of the residue thus obtained to flash chroma-
tography (3:2 v/v ethyl acetate/hexane elution) then
gave, after concentration of the appropriate fractions
(Rf 0.3), title compound 12 (99 mg, 60%) as a white,
crystalline solid, mp 50–52 ꢁC, in >95% ee (as deter-
mined by chiral HPLC analysis using CHIRALPAKꢂ
AS-H 250 · 4.6 mm column, 1:3 v/v isopropyl alcohol/
hexane elution at a solvent flow rate of 0.8 mL/min
and with UV peak detection at 254 nm, tR 39.9 min):
[a]D = +11.9 (c 0.6, CHCl3); IR: mmax 2939, 2840, 1687,
1596, 1507, 1462, 1436, 1337, 1272, 1128, 967, 739,
1
1155, 1126, 1078, 969, 924 cmꢀ1; H NMR (300 MHz,
CDCl3): d 6.63 (s, 2H), 5.11 (s, 2H), 4.40 (d,
J = 4.9 Hz, 1H), 3.85(s, 6H), 3.95 (s, 3H), 3.20 (m,
1H), 2.84 (m, 2H), 2.56 (broad s, 1H, OH); 13C NMR
(75MHz, CDCl 3): d 153.5 (C), 136.3 (C), 134.1 (C),
103.2 (CH), 98.1 (CH2), 74.4 (CH), 57.1 (CH), 56.0
(OCH3), 55.8 (OCH3), 45.4 (CH2); MS (EI, 70 eV): m/z
1
698 cmꢀ1; H NMR (300 MHz, CDCl3): d 9.77 (s, 1H,
CHO), 7.48–7.34 (complex m, 7H, ArH), 7.02 (d,
J = 8.7 Hz, 1H, ArH), 6.68 (s, 2H, ArH), 5.24–5.14
(complex m, 3H), 5.10 (s, 2H), 3.77 (s, 6H), 3.58 (s,
3H), 3.34 (m, 1H), 2.89 (dd, J = 5.2 and 2.6 Hz, 1H),
2.80 (dd, J = 5.2 and 3.8 Hz, 1H); 13C NMR (75MHz,
CDCl3): d 190.5 (CHO), 154.8 (C), 153.5 (C), 147.8
(C), 136.0 (C), 134.4 (C), 133.2 (C), 130.1 (C), 128.6
(CH), 128.2 (CH), 127.1 (CH), 115.8 (CH), 113.0
(CH), 103.7 (CH), 98.1 (CH2), 80.3 (CH), 70.7 (CH2),
57.1 (CH), 56.0 (OCH3), 54.2 (OCH3), 45.1 (CH2) (one
signal obscured or overlapping); MS (EI, 70 eV): m/z
270 (M+Å, 27%), 240 (10), 197 (16), 195(17), 177 (23),
+Å
165(32), 109 (12), 45(100); HRMS: M
calcd for
C13H18O6: 270.1103; found: 270.1102. Anal. Calcd for
C13H18O6: C, 57.77; H, 6.71. Found: C, 57.90; H, 7.00.
4.1.8. 4-Benzyloxy-3-hydroxybenzaldehyde 11. A mag-
netically stirred suspension of NaH (160 mg, 60% sus-
pension washed free of oil with hexane, 4.0 mmol) in
DMSO (5mL) maintained at 18 ꢁC under an atmo-
sphere of nitrogen was treated, in portions over
10 min, with 3,4-dihydroxybenzaldehyde (499 mg,
3.6 mmol). The resulting mixture was stirred at 18 ꢁC
for 1 h then benzyl chloride (410 lL, 3.6 mmol) was
added dropwise to the reaction mixture. Stirring was
continued for 18 h then the ensuing mixture diluted with
water (15mL) and the basic solution washed with
diethyl ether (3 · 10 mL). The aqueous phase was acid-
ified with HCl (0.5M aqueous solution) to pH ꢁ4 then
480 (M+Å, 7%), 450 (6), 272 (11), 253 (96), 223 (27),
+Å
195(47), 91 (9)5, 45(100); HRMS: M
calcd for
C27H28O8: 480.1784; found: 480.1777. Anal. Calcd for
C27H28O8: C, 67.49; H, 5.87. Found: C, 67.07; H, 5.66.
4.1.10.
(1S,2R)-4-Hydroxy-3-[20,300-epoxy-10-(300,500-
dimethoxy-400-methoxymethoxyphenyl)-propoxy]-benzal-
dehyde 13. A solution of compound 12 (60 mg,