A. Gillmore et al. / Tetrahedron 59 (2003) 4363–4375
4371
C(6a)H), 6.86 (1H, d, J¼8.3 Hz, C(5a)H), 7.01–7.04 (2H,
m, C(2b)H and C(6b)H), 7.05 (1H, d, J¼1.8 Hz, C(2a)H),
7.14 (1H, tt, J¼7.4, 1.0 Hz, C(4b)H), 7.33–7.45 (7H, m,
C(3b)H, C(5b)H and Phc); dC (100 MHz, CDCl3) 65.2 (C3),
73.3 (C1), 79.1 (C2), 114.2 (C2a), 118.6 (C2b and C6b),
118.6 (C5a and C6a), 123.9 (C4b), 127.7 (C2c and C6c),
128.8 (C3c and C5c), 128.9 (C4c), 137.1 (C1a), 138.2 (C1c),
143.4 (C4a), 147.4 (C3a), 156.4 (C1b); m/z (CI) 372
([MþNH42H2O, 37Cl]þ) 370 ([MþNH42H2O, 35Cl]þ)
(Found: [MþNH42H2O, 35Cl]þ, 370.12120. C21H21O3ClN
requires [MþNH42H2O, 35Cl]þ, 370.12100), 334, 232, 215
(100%).
residue. The crude material was purified by flash column
chromatography (SiO2; EtOAc/n-hexane, 1:3) to give the
title compound 15 as a pale cream gum (3 mg, 30%); Rf 0.60
(EtOAc/n-hexane, 1:1); [a]2D5¼þ93.3 (c¼0.3, CHCl3); nmax
(film, NaCl Plate)/cm21 3423 (bd, OH); dH (400 MHz,
CDCl3) 1.57 (3H, s, CH3), 1.61 (3H, s, CH3), 4.28 (1H, dd,
J¼5.3, 8.2 Hz, C(2)H), 4.78 (1H, d, J¼8.2 Hz, C(1)H), 4.89
(1H, d, J¼5.3 Hz, C(3)H), 5.53 (1H, bs, Ar-OH), 6.55 (1H,
dd, J¼8.2, 2.0 Hz, C(6a)H), 6.71 (1H, d, J¼8.2 Hz, C(5a)H),
6.83 (1H, d, J¼2.0 Hz, C(2a)H), 6.97 (2H, dd, J¼8.7,
0.9 Hz, C(2b)H and C(6b)H), 7.13 (1H, t, J¼7.3 Hz,
C(4b)H), 7.25–7.26 (3H, m, C(4c)H and 2£Hc), 7.31–7.37
(4H, m, C(3b)H, C(5b)H and 2£Hc); dC (100 MHz, CDCl3)
28.1 (CH3), 28.6 (CH3), 63.4 (CH, C2), 81.7 (CH, C1), 87.2
(CH, C3), 111.1 (Q, C(CH3)2), 115.8 (CH, C2a), 119.0
(2£CH, C2b and C6b), 119.9 (CH, C5a), 120.4 (CH, C6a),
124.8 (CH, C4b), 129.3 (2£CH), 129.6 (2£CH) and 131.0
(2£CH) (C2c, C6c, C3c, C5c, C3b, C5b), 129.9 (CH, C4c),
134.9 (Q, C1a), 139.0 (Q, C1c), 144.4 (Q, C4a), 148.5 (Q,
C3a), 157.7 (Q, C1b); m/z (CI) 412 ([M, 37Cl]þ), 410 ([M,
35Cl]þ). (Found: [M, 35Cl]þ, 410.12870. C24H23O4Cl
requires [M, 35Cl]þ, 410.12845), 372 ([MþNH4–
(CH3)2CO, 37Cl]þ), 370 ([MþNH4–(CH3)2CO, 35Cl]þ),
336 (100%, [MþNH4–Cl, –C3H5O]þ), 319 ([MþH, –Cl,
–C3H5O]þ), 256, 215 ([MþH–PhCHClCHOC(CH3)2]þ),
161, 91 ([C7H7]þ).
5.1.10. 5-{(4S,5S)-5-[(S)-Chloro(phenyl)methyl]-2,2-
dimethyl-1,3-dioxolan-4-yl}-2-phenoxyphenol
(14).
Dimethoxypropane (0.02 cm3, 0.18 mmol, 3.0 equiv.) and
p-toluenesulfonic acid (a few crystals) were added to a
solution of diol anti-11 (20 mg, 0.06 mmol) in dichloro-
methane (1 cm3) at rt. The mixture was stirred for 15 h and
was quenched by the addition of water (1 cm3). The organic
layer was separated, washed with brine (2 cm3), dried
(MgSO4), and the solvent was evaporated under reduced
pressure to afford a gummy residue (30 mg). The crude
product was purified by filtration through a short pad of
silica to give the pure acetonide 14 as a white solid (25 mg,
100%), mp 129–1308C; Rf 0.78 (EtOAc/n-hexane, 1:1);
[a]2D5¼283.3 (c¼1.9, CHCl3); nmax (film, NaCl Plate)/cm21
3420 (bd, OH), 3064 (m, Ar-H); dH (400 MHz, CDCl3) 1.55
(3H, s, CH3), 1.74 (3H, s, CH3), 4.64 (1H, d, J¼9.3 Hz,
C(3)H), 4.94 (1H, d, J¼6.9 Hz, C(1)H), 5.02 (1H, dd,
J¼6.9, 9.3 Hz, C(2)H), 5.46 (1H, bs, Ar-OH), 6.39 (1H, dd,
J¼2.0, 8.3 Hz, C(6a)H), 6.62 (1H, d, J¼8.3 Hz, C(5a)H),
6.66 (1H, d, J¼2.0 Hz, C(2a)H), 6.83 (2H, dd, J¼8.0,
1.4 Hz, C(2c)H and C(6c)H), 6.92 (2H, dd, J¼8.6, 1.0 Hz,
C(2b)H and C(6b)H), 7.06–7.12 (4H, m, C(3c)H, C(5c)H,
C(4b)H and C(4c)H), 7.28 (2H, t, J¼8.6 Hz, C(3b)H and
C(5b)H); dC (100 MHz, CDCl3) 23.7 (CH3), 25.9 (CH3),
61.1 (CH, C3), 78.2 (CH, C1), 80.7 (CH, C2), 108.1 (Q,
C(CH3)2), 114.7 (CH, C2a), 116.9 (2£CH, C2b and C6b),
117.3 (CH, C5a), 119.1 (CH, C5a), 122.7 (CH, C4b), 126.7
(2£CH, C2c and C6c), 127.4 (2£CH, C3c and C5c), 127.5
(CH, C4c), 128.9 (2£CH, C3b and C5b), 132.4 (Q, C1a),
137.0 (Q, C1c), 142.2 (Q, C4a), 146.1 (Q, C3a), 155.7 (Q,
C1b); m/z (CI) 430 ([MþNH4, 37Cl]þ), 428 ([MþNH4,
35Cl]þ) 413 ([MþH, 37Cl]þ), 411 ([MþH, 35Cl]þ). (Found:
[MþH, 35Cl]þ, 411.13608. C24H24O4Cl requires [MþH,
35Cl]þ, 411.13632), 412–410 ([M]þ), 372–370
([MþNH4–(CH3)2CO]þ), 317 (100%, [M2(CH3)2CO,
–Cl]þ), 256, 214 ([M2PhCHClCHOC(CH3)2]þ), 161;
nOe experiments: by the irradiation of the methyl signal at
d 1.55, nOes were observed at d 4.94 and d 5.02 for C(1)H
and C(2)H, respectively, whereas no nOes were observed
for the other methyl signal at d 1.74, confirming the syn-
relationship between C(1)H and C(2)H.
5.1.12. 5-{(S)-Hydroxy[(2S,3R)-3-phenyloxiran-2-
yl]methyl}-2-phenoxyphenol (16). Potassium carbonate
(25 mg, 0.18 mmol, 2.2 equiv.) was slowly added to a
solution of chlorohydrin anti-11 (30 mg, 0.081 mmol) in
methanol (2 cm3) at 08C. The mixture was allowed to warm
to rt and was stirred for 18 h. The reaction mixture was
quenched by the addition of water (2 cm3) and was extracted
with ethyl acetate (5£5 cm3). The combined organic
extracts were washed with brine (15 cm3), dried (MgSO4)
and the solvent was evaporated under reduced pressure to
give a creamy gum (35 mg). Flash column chromatography
(SiO2; EtOAc/n-hexane, 1:3) of the crude residue afforded
the title compound 16 as a pale cream gum (26 mg, 97%); Rf
0.50 (EtOAc/n-hexane, 1:1); [a]2D5¼2211 (c¼1, CHCl3);
n
max (film, NaCl Plate)/cm21 3423 (bd, OH); dH (400 MHz,
MeOD) 3.24 (1H, dd, J¼8.5, 3.9 Hz, C(2)H), 3.88 (1H, d,
J¼8.5 Hz, C(1)H), 4.18 (1H, d, J¼3.9 Hz, C(3)H), 6.79–
6.84 (4H, m, C(5a)H, C(6a)H, C(2b)H and C(6b)H), 6.90–
6.94 (1H, m, C(4b)H), 6.97 (1H, d, J¼1.5 Hz, C(2a)H),
7.16–7.35 (7H, m, C(3b)H, C(5b)H and Phc); dC (100 MHz,
MeOD) 59.8 (C3), 63.5 (C2), 70.2 (C1) 116.7 (C2a), 118.6
(C2b and C6b), 119.5 (C6a), 122.2 (C5a), 123.9 (C4b), 128.1,
129.3 and 129.7 (Phc), 130.9 (C3b and C5b), 136.8 (C1c),
141.3 (C1a), 144.9 (C4a), 150.5 (3a), 159.9 (C1b); m/z (CI)
352 ([MþNH4]þ). (Found: [MþNH4]þ, 352.15396.
C21H22O4N requires [MþNH4]þ, 352.15488), 335
([MþH]þ), 317, 232, 215 (100%), 91.
5.1.11. 5-{(4R,5S)-5-[(S)-Chloro(phenyl)methyl]-2,2-
5.1.13. 5-{(S)-Hydroxy[(2S,3S)-3-phenyloxiran-2-
yl]methyl}-2-phenoxyphenol (17). A solution of zinc
borohydride (0.13 M, 2.5 cm3, 0.31 mmol, 1 equiv.) was
added dropwise to a solution of epoxy ketone 9 (100 mg,
0.31 mmol) in anhydrous tetrahydrofuran (2 cm3), at 08C,
and under N2. The mixture was stirred for 2 h and was
quenched with water (5 cm3). The mixture was extracted
with ethyl acetate (5£10 cm3). The combined organic
dimethyl-1,3-dioxolan-4-yl}-2-phenoxyphenol
(15).
Dimethoxypropane (0.01 cm3, 0.081 mmol, 3.0 equiv.)
and p-toluenesulfonic acid (a few crystals) were added to
a solution of syn-13 (10 mg, 0.027 mmol) in dichloro-
methane (1 cm3) at rt under N2. The pale yellow solution
turned colourless and was stirred for 16 h. The solvent was
evaporated under reduced pressure to afford a brown