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chloride (0.88 cm3, 10.0 mmol) in anhydrous dichloromethane (10 cm3)
at –70°C under a nitrogen atmosphere. After stirring for 20 min at this
temperature, a solution of the alcohol (12) (633 mg, 2.00 mmol) in dry
dichloromethane (8 cm3) was added dropwise and the stirring continued
for 15 min. Dry triethylamine (3.30 cm3, 23.8 mmol) was then added
dropwise and, after a further 5 min at –70°C, the mixture was allowed
to warm to room temperature. Water was then added and the organic
layer separated. The aqueous phase was extracted with
dichloromethane . The combined organic extracts were washed succes-
sively with dilute hydrochloric acid solution, water, saturated sodium
hydrogencarbonate solution, water and brine, and then dried and evap-
orated to give an orange oil (702 mg). The crude product was purified
by column chromatography (hexane–10% ethyl acetate–hexane/0.5%
Et3N) to afford the aldehyde (13) as a pale yellow oil (502 mg, 80%).
Further chromatography and distillation furnished a colourless oil, b.p.
175–185°C/0.3 mmHg (Kugelrohr) (Found: C, 72.3; H, 6.9. C19H22O4
requires C, 72.6; H, 7.0%). [α]D –75.9° (c, 0.5 in CHCl3). νmax (thin
film) 1733, 1586, 1498, 1479, 1455 cm–1. δH 1.22 d, J 7.0 Hz, 2-CH3;
1.50, d, J 6.4 Hz, α´-CH3; 3.71 dq, J 2.0 and 7.0 Hz, H 2; 3.83, s, OCH3;
5.01, q, J 6.4 Hz, H α´; 5.11, s, OCH2; 6.90, t, J 7.8 Hz, H 5´; 7.04–7.06,
m, H 4´, 6´; 7.30–7.47, m, C6H5; 9.72, d, J 2.0 Hz, H 1. δC 15.9, C 3;
23.5, ArCH H3; 60.9, OCH3; 70.7, CH2; 71.3, Cα´; 77.8, C 2; 113.2,
C 6´;a 118.5, C 5´;a 124.3, C 4´;a 127.3, C 2´´, C 6´´;b 128.0, C 4´´; 128.6,
C 3´´, C 5´´;b 136.6, C 1´; 136.9, C 1´´; 146.9, C 3´;c 151.5, C 2´;c 204.2,
C 1. m/z 314 (M, 29%), 241 (100), 137 (14), 107 (7).
benzyl ether (13), to afford the phenol (17) as a yellow oil (112 mg,
91%) which was used immediately for subsequent reactions. νmax
(thin film) 3406, 1732, 1593, 1472 cm–1. δH 1.29, d, J 6.8 Hz, 2-CH3;
1.53, d, J 6.4 Hz, α´-CH3; 3.75, dq, J 1.7 and 6.8 Hz, H 2; 3.79, s,
OCH3; 4.98, q, J 6.4 Hz, H α´; 5.60, br s, OH; 6.88, dd, J 2.0 and 7.8
Hz, H 4´; 7.02–7.05, m, H 5´, 6´; 9.45, d, J 1.7 Hz, H 1. δC 15.2, C 3;
23.2, ArCH H3; 62.0, OCH3; 70.2, C α´; 78.2, C 2; 115.4, C 6´;a
118.6, C 4´;a 125.6, C 5´;a 135.9, C 1´; 144.9, C 3´;b 148.7, C 2´;b
203.3, C 1. m/z 224 (M, 61%), 151 (100), 136 (20), 107( 8), 91 (8),
77 (4).
(1S,3S,4R)- and (1S,3S,4S)-8-Methoxy-1,3-dimethylisochroman-4,7-
diols (21) and (23)
The crude phenol (14) (110 mg, 0.49 mmol) was subjected to
column chromatography on silica gel with 5–50% ethyl
acetate–hexane/trace Et3N as eluent to provide the cyclized product
(76 mg, 69%) as a mixture of inseparable diastereomers (21) and (23)
in a ratio of approximately 1.3 : 1. νmax (thin film) 3352, 1607, 1590,
1493 cm–1. δH (major diastereomer (21)) 1.32, d, J 6.3 Hz, 3-CH3;
1.55, d, J 6.6 Hz, 1-CH3; 2.90, br s, 4-OH; 3.77, s, OCH3; 3.84, dq, J
7.4, 6.3 Hz, H 3; 4.24, d, J 7.4 Hz, H 4; 5.04, q, J 6.6 Hz, H 1; 5.86, br
s, 7-OH; 6.80–6.85, m, H 5, 6. δH (minor diastereomer (23)) 1.35, d, J
6.4 Hz, 3-CH3; 1.50, d, J 6.7 Hz, 1-CH3; 2.70, br s, 4-OH; 3.76, s,
OCH3; 4.08, dq, J 1.6 and 6.4 Hz, H 3; 4.15, d, J 1.6 Hz, H 4; 5.10, q,
J 6.7 Hz, H 1; 5.75, br s, 7-OH; 7.03, 7.13, d, J 8.3 Hz, H 6, 5. δC
(mixture of two diastereomers) 17.0, 18.0, 3-CH3; 19.0, 20.2, 1-CH3;
60.3, OCH3; 66.5, 69.4, C 3;a 67.8, C 1;a 68.80, 70.7, C 4;a 123.6,
128.2, C 6;b 126.5, 128.6, C 5;b 132.3, C 8a;c 133, C 4a;c 142.3, C 7;d
142.5, C 8.d
(α ´R,2S)-2-(3 ´-Benzyloxy-2´-methoxy-α ´-
methylbenzyloxy)propanal (16)
Utilizing the procedure described above for the preparation of the
aldehyde (13) from alcohol (12), the alcohol (15) (295 mg, 0.93 mmol)
was transformed into the aldehyde (16), which was isolated as an
orange oil (298 mg). Purification of this crude oil by column chro-
matography (hexane–10% ethyl acetate–hexane/0.5% Et3N) provided
the aldehyde (16) as a pale yellow oil (226 mg, 77%). Further chro-
matography and distillation yielded the pure product as a colourless oil,
b.p. 155–167°C/0.3 mmHg (Kugelrohr) (Found: C, 72.2; H, 7.0.
C19H22O4 requires C, 72.6; H, 7.0%). [α]D +17.5°. νmax (thin film) 1734,
1583, 1479, 1456 cm–1. δH 1.29, d, J 6.8 Hz, 2-CH3; 1.49, d, J 6.4 Hz,
α´-CH3; 3.76, dq, J 1.5 and 6.8 Hz, H 2; 3.87, s, OCH3; 5.09, q, J 6.4
Hz, H α´; 5.10, s, OCH2; 6.89, dd, J 2.0 and 7.8 Hz, H 4´; 7.04, t, J 7.8
Hz, H 5´; 7.09, dd, J 2.0 and 7.8 Hz, H 6´; 7.30–7.47, m, C6H5; 9.51, d,
J 1.5 Hz, H 1. δC 15.1, C 3; 23.3, ArCH H3; 61.0, OCH3; 70.2, Cα´;
70.7, CH2; 78.2, C 2; 113.3, C 6´;a 118.9, C 4´;a 124.4, C 5´;a 127.3,
C 2´´, C 6´´;b 128.0, C 4´; 128.6, C 3´´, C 5´´;b 136.6, C 1´; 136.9, C 1´´;
146.9, C 3´;c 151.5, C 2´;c 203.5, C 1. m/z 314 (M, 65%), 241 (100), 151
(45), 137 (21), 135 (21), 107 (12), 91 (100), 63 (27).
(1S,3S,4R)- and (1S,3S,4S)-4,7-Diacetoxy-8-methoxy-1,3-
dimethylisochromans (22) and (24)
The crude mixture of the diols (76 mg, 0.34 mmol) was immedi-
ately dissolved in dry pyridine (2 cm3) and acetic anhydride (2 cm3)
and stirred at room temperature for 20 h. Water and ether were added
and stirring was continued (3 h). The organic layer was separated and
then washed with water, dilute hydrochloric acid, water and then
brine, dried and concentrated to give the diacetates as a yellow oil (83
mg, 79% combined crude yield). Examination of the crude product by
t.l.c. and 1H n.m.r. spectroscopy showed two major products (similar
RF by t.l.c.) and no other material. Separation of the two diacetates
was achieved by column chromatography (10% ethyl
acetate–hexane/0.5% Et3N) followed by p.l.c. (20% ethyl
acetate–hexane) to yield:
(i) The higher RF (0.32, 30% ethyl acetate–hexane) product (22) (35
mg, 33%) as a pale yellow oil (Found: C, 62.6; H, 6.8%; M+, 308.1248.
C16H20O6 requires C, 62.3; H, 6.5%; M+, 308.1260). [α]D –66.3° (c, 0.7
in CHCl3). νmax (thin film) 1772, 1742, 1490 cm–1. δH 1.25, d, J 6.3 Hz,
3-CH3; 1.59, J 6.6 Hz, 1-CH3; 2.16, s, 4-OCOCH3; 2.34, s, 7-OCOCH3;
3.81, s, OCH3; 4.06, dq, J 7.4 and 6.3 Hz, H3; 5.07, q, J 6.6 Hz, H1;
5.70, d, J 7.4 Hz, H 4; 6.93–6.98, m, H 5, 6. δC 18.1, 3-CH3; 20.0, 1-
CH3; 20.9, 4-OCO H3;a 21.2, 7-OCO H3;a 60.7, OCH3; 66.5, C 4;b
67.8, C 3;b 71.2, C 1;b 122.3, C 5; 123.3, C 6; 131.1, C 8a;c 134.7, C 4a;c
142.6, C 8; 147.1, C 7; 168.8, 4-O OCH3;d 171.1, 7-O OCH3. m/z 308
(M, 16%), 293 (11), 266 (11), 264 (9), 248 (20), 233 (42), 222 (16), 206
(60), 191 (85), 180 (100), 163 (12), 149 (24).
(ii) The lower RF (0.29, 30% ethyl acetate–hexane) diacetate (22)
(27 mg, 26%) as a pale yellow oil (Found: C, 62.3; H, 6.9%; M+,
308.1265. C16H20O6 requires C, 62.3; H, 6.5%; M, 308.1260). [α]D
+122.5° (c, 0.6 in CHCl3). νmax (thin film) 1773, 1742, 1593, 1462 cm–1.
δH 1.27, d, J 6.4 Hz, 3-CH3; 1.53, d, J 6.7 Hz, 1-CH3; 2.11, s, 4-
OCOCH3; 2.34, s, 7-OCOCH3; 3.83, s, OCH3; 4.21, dq, J 2.0 and 6.4
Hz, H3; 5.20, q, J 6.7 Hz, H1; 5.77, d, J 2.0 Hz, H 4; 6.98, d, J 8.4 Hz,
H6; 7.14, d, J 8.4 Hz, H 5. δC 16.8, 3-CH3; 18.9, 1-CH3; 20.9, 4-
OCO H3;a 21.1, 7-OCO H3;a 60.7, OCH3; 64.8, C 4;b 67.6, C 3;b 68.6,
C 1;b 122.5, C 5; 126.0, C 6; 130.5, C 8a;c 134.4, C 4a;c 143.2, C 7;
147.2, C 8; 168.8, 4-O OCH3;d 171.0, 7-O OCH3.d m/z 264
[(M–CH3CHO), 21%], 248 (13), 233 (24), 206 (13), 191 (41), 180
(100), 163 (18), 149 (19), 113 (11).
(α ´S,2S)-2-(3 ´-Hydroxy-2´-methoxy-α ´-
methylbenzyloxy)propanal (14)
A stirred suspension of the benzyl ether (13) (435 mg, 1.39 mmol)
and 10% palladium on carbon catalyst (560 mg) in ethyl acetate (10
cm3) was subjected to an atmosphere of hydrogen for 2 h. The catalyst
was then removed by filtration through a pad of Celite, a further amount
of catalyst (560 mg) added and the suspension subjected to a hydrogen
atmosphere for a further 2 h. Filtration through Celite and concentration
of the filtrate furnished the unstable phenol (14) as a yellow oil (290
mg, 93%) which was used immediately for subsequent reactions. νmax
(thin film) 3413, 1732, 1591, 1475, 1440 cm–1. δH 1.21, d, J 7.0 Hz, 2-
CH3; 1.53, d, J 6.4 Hz, α´-CH3; 3.70, dq, J 2.0 and 7.0 Hz, H2; 3.75, s,
OCH3; 4.92, q, J 6.4 Hz, H α´; 5.81, br s, OH; 6.89, dd, J 1.8 and 7.8
Hz, H4´; 6.97, dd, J 1.8 and 7.8 Hz, H6´; 7.05, t, J 7.8 Hz, H5´; 9.70,
d, J 2.0 Hz, H 1. δC 15.8, C 3; 23.5, ArCH H3; 61.8, OCH3; 71.0, Cα´;
77.7, C 2; 115.3, C 6´;a 118.2, C 4´;a 125.4, C 5´;a 136.0, C 1´; 144.9,
C 3´;b 148.8, C 2´;b 204.0, C 1. m/z 224 (M, 10%), 151 (100), 136 (35),
107 (6), 91 (14), 77 (6).
(α ´R,2S)-2-(3 ´-Hydroxy-2´-methoxy-α ´-
methylbenzyloxy)propanal (17)
The benzyl ether (16) (173 mg, 0.55 mmol) was subjected to
hydrogenolysis, according to the method described above for the