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L.K. Mydock et al. / C. R. Chimie 14 (2011) 301–306
3.16 (d, 1H, OH), 3.52 (dd, 1H, CH2aOCH2Ph), 3.63 (dd, 1H,
CH2aOH), 3.70–3.77 (m, 5H, CH2bOCH2Ph, CH2bOH, OCH3),
4.34–4.43 (dd, 2H, OCH2Ph), 6.82 (d, 2H, aromatic), 7.22 (d,
3.27 (d, 1H, OH), 3.55 (dd, 1H, J = 3.9 Hz, J = 9.9 Hz,
CH2aOCH2Ph), 3.65–3.72 (m, 4H, OCH3, CH2bOCH2Ph),
4.02 (q, 2H, OCH2CH3), 4.39 (m, 3H, CHOH, CH2Ph), 6.77
2H, aromatic) ppm; 13C-n.m.r.:
d
, 28.2 (Â 3), 31.5, 49.8,
(d, 2H, aromatic), 7.14 (d, 2H, aromatic) ppm; 13C-n.m.r.:
d,
55.2, 64.0, 72.0, 73.2, 113.8 (Â 2), 129.2 (Â 2), 130.0,
159.2 ppm; HR-FAB MS [M + Na]+ calcd for C15H24O3Na+
275.1623, found 275.1616.
14.1, 28.7 (Â 3), 32.9, 42.7, 51.2, 55.0, 60.2, 67.7, 68.1, 72.8,
113.7 (Â 2), 129.1 (Â 2), 129.9, 159.1, 172.4 ppm; HR-FAB
MS [M + Na]+ calcd for C19H40O5Na+ 361.1991, found
361.1970.
2-tert-Butyl-3-p-methoxybenzyloxypropanal
(4).
Following a typical protocol [11] for the Swern oxidation,
a stirring solution of oxalyl chloride (4.25 mL, 48.8 mmol)
and anhydrous CH2Cl2 (100 mL) was flushed with argon
and cooled to À78 8C. A solution of DMSO (6.3 mL,
89.5 mmol) in anhydrous CH2Cl2 (6.3 mL) was added
dropwise and the resulting mixture was stirred for
30 min at À78 8C. A solution of compound 3 (8.2 g,
32.5 mmol) in anhydrous CH2Cl2 (15 mL) was added
dropwise, and resulting reaction mixture was stirred for
40 min at À78 8C. After that, Et3N (23.3 mL, 166.0 mmol)
was added and the resulting mixture was stirred for 1 h at
À78 8C, then allowed to warm to 0 8C and stirred for
additional 1 h. The mixture was then diluted with H2O
Analytical data for compound 5 [trans (syn)]: Rf = 0.43
(ethyl acetate/hexanes, 1/3, v/v); 1H-n.m.r.:
d, 0.89 (s, 9H,
C(CH3)3), 1.19 (t, 3H, OCH2CH3), 1.80–1.86 (m, 1H, CH),
2.44–2.47 (dd, 2H, CH2C = O), 3.43–3.50 (m, 2H, OH,
CH2aOCH2Ph), 3.62 (dd, 1H, J = 3.9 Hz, J = 11.4 Hz,
CH2bOCH2Ph), 3.72 (s, 3H, OCH3), 4.09 (q, 2H, OCH2CH3),
4.23–4.34 (m, 1H, CH2OH), 4.35 (s, 2H, CH2Ph), 6.80 (d, 2H,
aromatic), 7.21 (d, 2H, aromatic) ppm; 13C-n.m.r.:
d, 14.1,
29.0 (Â 3), 31.7, 39.5, 52.6, 55.0, 60.2, 68.8, 68.9, 72.9, 113.7
(Â 2), 129.2 (Â2), 129.6, 159.1, 172.7 ppm; HR-FAB MS
[M + Na]+ calcd for C19H40O5Na+ 361.1991, found
361.1997.
5-tert-Butyl-4-hydroxy-tetrahydro-2H-pyran-2-one
(6a and 6b). Similar to that of a published procedure [13],
to a stirring solution of the diastereomeric mixture of
compound 5 (5.48 g, 16.2 mmol) in wet CH2Cl2 (400 mL)
was added H2O (0.5 mL) followed by the portionwise
addition of trifluoroacetic acid (3 Â 1.2 mL, 48.6 mmol)
over the period of 1 h. The reaction was stirred for 16 h,
then neutralized with triethylamine and washed consecu-
tively with sat. aq. NaHCO3 (75 mL) and brine (75 mL). The
organic phase was separated, dried over Na2SO4, filtered
and concentrated in vacuo. The crude residue was
separated by column chromatography on silica gel (ethyl
acetate/hexane gradient elution) to afford 6b (15%, white
solid) and 6a (77%, white solid). Analytical data for
compound 6a [cis]: Rf = 0.42 (methanol/CH2Cl2, 1/19, v/
(200 mL),
and
extracted
with
dichloromethane
(4 Â 50 mL). The combined organic extract was washed
with sat. aq. NaHCO3 (50 mL) and brine (50 mL), then dried
over Na2SO4, filtered and concentrated in vacuo. The crude
residue was purified by column chromatography on silica
gel (ethyl acetate–hexane gradient elution) to allow the
title compound 4 in 90% yield as a colorless oil. Analytical
data for compound 4: Rf = 0.63 (ethyl acetate/hexanes, 1/3,
v/v); 1H-n.m.r.:
d, 0.87 (s, 9H, C(CH3)3), 2.24–2.30 (m, 1H,
CH), 3.51 (dd, 1H, 2J = 9.4 Hz, 3J = 4.0 Hz, CH2aOCH2Ph), 3.62
(s, 3H, OCH3), 3.75 (dd, 1H, 2J = 9.5 Hz, 3J = 9.5 Hz,
CH2bOCH2Ph), 4.24–4.32 (dd, CH2Ph), 6.72 (d, 2H, aromat-
ic), 7.08 (d, 2H, aromatic), 9.63 (d, 1H, HC = O) ppm; 13C-
n.m.r.:
d
, 28.3 (Â 3), 32.8, 55.2, 61.2, 66.4, 72.9, 113.8 (Â 2),
129.2 (Â 2), 130.1, 159.2, 204.9 ppm; HR-FAB MS [M + Na]+
v); 1H-n.m.r.:
d, 0.96 (s, 9H, C(CH3)3), 1.58 (dd, 1H,
calcd for C15H22O3Na+ 273.1467, found 273.1470.
3J = 12.0 Hz, 3J = 4.6 Hz, CH), 2.50–2.66 (m, 2H, CH2C = O),
2.95 (bs, 1H, OH), 4.30–4.36 (m, 2H, CHOH, CH2aO), 4.63
(dd, 1H, 2J = 10.8 Hz, 3J = 12.2 Hz, CH2aO) ppm; 13C-n.m.r.:
Ethyl 4-tert-butyl-3-hydroxy-5-p-methoxybenzylox-
ypentanoate (5). Following a reported general procedure
[12] for the Reformatsky reaction, BF3-Et2O (4.87 mL,
38.4 mmol) was added dropwise over a period of 1 h to a
stirring suspension of aldehyde 4 (4.8 g, 19.2 mmol), zinc
dust (6.24 g, 95.4 mmol), and ethyl bromoacetate (6.37 mL,
57.6 mmol) in anhydrous THF (51.2 mL) under argon.
During this period, the reaction mixture may warm up
rapidly, in which case immediately relieve pressure and
cool flask with a cold water bath before continuing the
addition of the remaining BF3-Et2O. Upon completion
(ꢀ 1 h), the solid was filtered off, and the filtrate was
concentrated in vacuo. The residue was redissolved in
dichloromethane (50 mL) and washed with sat. aq.
NaHCO3 (10 mL), 1 M aq. HCl (10 mL), and brine (10 mL).
The organic layer was then separated, dried, and concen-
trated in vacuo. The crude residue was purified by column
chromatography on silica gel (ethyl acetate–hexane
gradient elution) to afford the title compound 5 (cis: trans,
4.3:1) as a colorless oil in 79%. Analytical data for
compound 5 [cis (anti)]: Rf = 0.51 (ethyl acetate/hexanes,
d
, 28.6 (Â 3), 31.6, 41.5, 46.8, 63.9, 67.3, 171.3 ppm; HR-
FAB MS [M + H]+ calcd for C9H17O3 173.1178, found
173.1183.
+
Analytical data for compound 6b [trans]: Rf = 0.45
(methanol–CH2Cl2, 1/19, v/v); 1H-n.m.r.:
d, 0.92 (s, 9H,
C(CH3)3), 1.67–1.73 (m, 1H, CH), 2.51–2.64 (m, 2H,
CH2C = O), 3.35 (bs, 1H, OH), 3.95 (dd, 1H, 3J = 10.9 Hz,
2J = 11.3 Hz, CH2aO), 4.20 (m, 1H, CHOH), 4.31 (dd, 1H,
3J = 5.8 Hz, CH2aO) ppm; 13C-n.m.r.:
d
, 27.6 (Â 3), 31.9, 39.0,
51.8, 65.5, 67.6, 173.2 ppm; HR-FAB MS [M + H]+ calcd for
+
C9H17O3 173.1178, found 173.1179.
5-tert-Butyl-4-trimethylsilyloxy-tetrahydro-2H-py-
ran-2-one (7a, cis). A solution of lactone 6a (1.90 g,
11.4 mmol) in pyridine (20 mL) was flushed with argon
and cooled to 0 8C. Trimethylsilyl chloride (1.86 g,
17.1 mmol) was added and the resulting mixture was
stirred for 30 min. After that, the reaction mixture was
concentrated in vacuo, the residue was redissolved in
CH2Cl2 (50 mL) and washed with sat. aq. NaHCO3 (10 mL)
and brine (2 Â 10 mL). Organic phase was separated, dried
over Na2SO4, filtered and concentrated in vacuo. The crude
residue was purified by column chromatography on silica
1/3, v/v); 1H-n.m.r.:
d, 0.90 (s, 9H, C(CH3)3), 1.14 (t, 3H,
OCH2CH3), 1.22 (m, 1H, CH), 2.35 (dd, 1H, 3J = 4.8 Hz,
2J = 15.4 Hz, CH2aC = O), 2.64 (dd, 1H, 3J = 9.0 Hz, CH2bC = O),