Notes
J . Org. Chem., Vol. 61, No. 23, 1996 8319
Exp er im en ta l Section 16
δ C 169.2, 137.4; CH 129.1, 128.3, 126.4, 99.3, 93.2, 71.8; CH2
37.4; CH3 21.4, 21.1. Anal. Calcd for C13H16O4: C, 66.09; H,
6.83. Found: C, 65.86; H, 6.72.
Sta n d a r d P r oced u r e for th e On e-P ot DIBALH Red u c-
tion a n d Acetyla tion of a n Ester . To 25 mL flame-dried, two-
neck flask equipped with a low-temperature thermometer and
an N2 inlet was added a solution of the starting ester (1.0 mmol)
in 5 mL of dry CH2Cl2. After the mixture was cooled to -78 °C,
DIBALH (1.0 M in cyclohexane, 1.1 mL, 1.1 mmol, 1.1 equiv)
was added dropwise (on a larger scale, a syringe pump was used
for the slow addition). After being stirred for 2 h (TLC showed
no ester) the reaction mixture was treated with pyridine (237
mg, 0.24 mL, 3.0 mmol, 3.0 equiv), and then a solution of DMAP
(134 mg, 1.1 mmol, 1.1 equiv) in 2 mL of dry CH2Cl2 was slowly
added by cannula. Finally, Ac2O (408 mg, 0.38 mL, 4.0 mmol,
4.0 equiv) was added dropwise, the reaction vessel was packed
in a Dewar flask containing dry ice, and the mixture was stirred
under an N2 atmosphere. After 12 h, the mixture was warmed
to -20 °C and the reaction was quenched by adding saturated
NH4Cl (5 mL) solution. The reaction mixture was stirred for
30 min, allowed to warm to room temperature, and then
extracted with CH2Cl2 (×4). If the Al salts formed emulsions,
they were disrupted by adding a saturated solution of Rochelle’s
salt with vigorous stirring. The combined CH2Cl2 extracts were
washed with ice-cold 1 N NaHSO4 (×2), saturated NaHCO3 (×3),
and brine (×1). After drying (anhydrous Na2SO4) and evapora-
tion of CH2Cl2 extracts, the residue obtained was purified by
flash chromatography on silica gel.
2-Acetoxy-1-oxa cycloh exa d eca n e (16). The reduction and
acetylation of lactone 15 (962 mg, 4.00 mmol) was carried out
in toluene to give 809 mg (71.1%, 2.84 mmol) of 16 as a colorless
viscous oil after purification on silica gel (3% EtOAc/hexanes):
1
IR (neat) 2928, 2858, 1738 cm-1; H NMR (300 MHz, CDCl3) δ
5.78 (dd, J ) 3.3, 7.7 Hz, 2 H), 3.80-3.75 (m, 1 H), 3.46-3.39
(m, 1 H), 2.06 (s, 3 H), 1.72-.22 (m, 25 H); 13C NMR (75 MHz,
CDCl3) δ 171.0, 99.3, 69.5, 34.1, 29.0, 27.2 (2), 27.1, 27.0, 26.6,
26.1, 26.0 (2), 25.8, 25.0, 23.0, 21.3; MS (HRCI-isobutane) calcd
for C17H33O3 (M + H) 285.2429, found 285.2432. Anal. Calcd
for C17H32O3: C, 71.79; H, 11.34. Found: C, 72.02; H, 11.27.
cis,cis-4,6-Dia cet oxy-2-p h en yl-1,3-d ioxa n e (18). Com-
pound 178 (770 mg, 4.00 mmol) gave 840 mg (75.5%, 3.02 mmol)
of 18 as a yellow oil after chromatography on silica gel (20%
EtOAc/hexanes): IR (neat) 3068, 3039, 2987, 1767, 1620 cm-1
;
1H NMR (500 MHz, CDCl3) δ 7.52-7.48 (m, 2 H), 7.39-7.35 (m,
3 H), 6.16 (dd J ) 3.1, 10.1 Hz, 1 H), 5.75 (s, 1 H), 2.18 (s, 3 H),
2.03-1.96 (m, 2 H); 13C NMR (75 MHz, CDCl3) δ 168.8, 135.7,
129.4, 128.3, 126.3, 96.2, 91.2, 89.5, 34.8, 21.0; MS (HRCI-
isobutane) calcd for C14H15O6 (M - H) 279.0869, found 279.0873.
Anal. Calcd for C14H16O6: C, 60.00; H, 5.75. Found: C, 59.89;
H, 5.70.
cis-2,4-Diacetoxy-1,5-dioxaspir o[5.5]u n decan e (20). Com-
pound 199 (1.84 g, 10.00 mmol) gave 1.83 g (67.3%, 6.73 mmol)
of 20 as a pale yellow oil after purification on silica gel (20%
EtOAc/hexanes). The pale yellow oil solidified on standing: mp
48-51 °C; IR (neat) 2941, 2864, 1761, 1447 cm-1; 1H NMR (500
MHz, CDCl3) δ 6.21 (dd, J ) 4.0, 8.0 Hz, 2 H), 2.21-2.07 (m, 1
H), 2.11 (s, 6 H), 1.87-1.79 (m, 5 H), 1.62-1.53 (m, 4 H), 1.42-
1.38 (m, 2 H); 13C NMR (125 MHz, CDCl3) δ 169.2, 101.0, 87.4,
38.0, 33.7, 32.6, 25.1, 22.3, 22.1, 21.1; MS (HREI) calcd for
For malonates 17 and 19 the DIBALH reduction time was 4
h, and the quantities of the other reagents were doubled
(2S*,4R*,6S*)-4-Acetoxy-2-h exyl-6-m eth yl-1,3-dioxan e (10).
Compound 97b (610 mg, 3.00 mmol) gave 670 mg (91.4%, 2.74
mmol) of 10 as a colorless oil after purification on silica gel (5%
EtOAc/hexanes): IR (neat) 2955, 2930, 2860, 1762 cm-1 1H
;
NMR (300 MHz, CDCl3) δ 5.83 (dd, J ) 2.7, 9.9 Hz, 1 H), 4.62
(t, J ) 5.2 Hz, 1 H), 3.80-3.71 (m, 1 H), 2.08 (s, 3 H), 1.77-1.14
C
C
13H20O6 (M+) 272.1260, found 272.1260. Anal. Calcd for
13H20O6: C, 57.34; H, 7.40. Found: C, 57.52; H, 7.44.
1-Meth oxy-2-p h en eth yl Aceta te (22). Ester 21 (601 mg,
(m, 12 H), 1.23 (d, J ) 6.1 Hz, 3 H), 0.83 (t, J ) 6.5 Hz, 3 H); 13
C
NMR (50 MHz, CDCl3, DEPT) δ C 169.2; CH 100.0, 93.0, 71.1;
CH2 37.4, 34.6, 31.7, 29.1, 23.9, 22.6; CH3 21.3, 21.1, 14.1. Anal.
Calcd for C13H24O4: C, 63.91; H, 9.90. Found: C, 63.73; H, 9.69.
(4R*,6S*)-4-Acetoxy-2,2,6-tr im eth yl-1,3-dioxan e (12). Com-
pound 117c (288 mg, 2.00 mmol) gave 228 mg (60.6%, 1.21 mmol)
of 12 as a volatile colorless oil after purification on silica gel
(10% EtOAc/hexanes, chromic acid stain used for visualization
4.00 mmol) gave 590 mg (75.9%, 3.04 mmol) of 22 as a colorless
oil after purification on silica gel (3% EtOAc/hexanes): IR (neat)
1
3065, 3031, 3002, 2938, 1740, 1684, 1653, 1606 cm-1; H NMR
(300 MHz, CDCl3) δ 7.32-7.21 (m, 5 H), 5.89 (t, J ) 5.6 Hz, 1
H), 3.39 (s, 3 H), 3.01-2.94 (m, 2 H), 2.05 (s, 3 H); 13C NMR (75
MHz, CDCl3) δ 170.8, 135.4, 129.7, 128.3, 126.7, 99.7, 56.9, 40.9,
21.1. Anal. Calcd for C11H14O3: C, 68.02; H, 7.27. Found: C,
68.00; H, 7.50.
of the TLC plate): IR (neat) 2992, 2938, 2880, 1759 cm-1 1H
;
NMR (300 MHz, CDCl3) δ 6.09 (dd, J ) 3.0, 9.9 Hz, 1 H), 4.07-
3.97 (m, 1 H), 2.06 (s, 3 H), 1.82-1.75 (m, 1 H), 1.47 (s, 3 H),
1.42 (s, 3 H), 1.45-1.33 (m, 1 H), 1.19 (d, J ) 6.1 Hz, 3 H); 13C
NMR (50 MHz, CDCl3, DEPT) δ C 169.4; CH 100.5, 89.4, 64.5,
CH2 37.5; CH3 29.9, 21.8, 21.2, 20.8. Anal. Calcd for C9H16O4:
C, 57.43; H, 8.57. Found: C, 57.18; H, 8.72.
1-(1-P h en yleth oxy)-1-octyl Aceta te (24). Ester 23 was
prepared by the reaction of octanoic acid with 2-phenylethanol
in presence of DCC and DMAP. Reduction and acetylation of
compound 23 (1.99 g, 8.00 mmol) gave 1.92 g (82.0%, 6.56 mmol)
of 24 as a colorless oil after chromatography on silica gel (3%
EtOAc/hexanes, phosphomolybdic acid stain used for visualiza-
tion of the TLC plate): IR (neat) 3032, 2956, 2928, 1739, 1494
(2S *,4R *,6S *)-4-Ace t oxy-6-m e t h yl-2-p h e n yl-1,3-d iox-
a n e (14). Compound 137c (384 mg, 2.00 mmol) gave 372 mg
(78.8%, 1.57 mmol) of 14 as a pale yellow oil after purification
on silica gel (10% EtOAc/hexanes, chromic acid stain used for
visualization of the TLC plate): IR (neat) 3067, 3037, 2976, 1761
1
cm-1; H NMR (300 MHz, CDCl3, mixture of isomers) δ 7.37-
7.22 (m, 10 H), 6.04 (t, J ) 5.6 Hz, 1 H), 5.66 (t, J ) 5.6 Hz, 1
H), 4.70-4.63 (m, 2 H), 2.09 (s, 3 H), 1.81-1.20 (m, 25 H), 1.59
(s, 3 H), 1.47 (d, J ) 4.5 Hz, 3 H), 0.91-0.83 (m, 6 H); 13C NMR
(75 MHz, CDCl3, mixture of isomers) δ 170.8, 143.8, 142.7, 128.4,
128.1, 127.8, 127.2, 126.6, 126.0, 97.8, 96.7, 78.0, 76.0, 34.8, 34.6,
31.7, 29.2, 29.1, 28.6, 24.1, 24.0, 23.9, 23.6, 22.6, 21.3, 20.7, 14.0.
Anal. Calcd for C18H28O3: C, 73.93; H, 9.65. Found: C, 73.80;
H, 9.49.
cm-1; H NMR (300 MHz, CDCl3) δ 7.53-7.50 (m, 2 H), 7.39-
1
7.30 (m, 3 H), 6.09 (dd, J ) 2.7, 9.0 Hz, 1 H), 5.65 (s, 1 H), 4.08-
3.98 (m, 1 H) 2.11 (s, 3 H), 1.89-1.83 (m, 1 H), 1.77-1.62 (m, 1
H), 1.35 (d, J ) 6.2 Hz, 3 H); 13C NMR (50 MHz, CDCl3, DEPT)
(15) Berger, D.; Overman, L. E.; Renhowe, P. A. J . Am. Chem. Soc.
1993, 115, 9305-6.
(4R*,6S*)-4-(P h en ylth io)-2,2,6-tr im eth yl-1,3-dioxan e (25).
Acetate 12 (94 mg, 0.50 mmol) was dissolved in 5 mL of dry
CH2Cl2, and thiophenol (110 mg, 1.0 mmol, 2.0 equiv) was added.
After being cooled to -78 °C, the reaction mixture was treated
with BF3‚Et2O (85 mg, 71 µL, 0.6 mmol, 1.2 equiv). After being
stirred for 1 h, the reaction was quenched by adding 1 N NaOH
(5 mL) at -78 °C. The mixture was warmed to room temper-
ature and extracted with CH2Cl2 (×3). The combined CH2Cl2
extracts were washed with 1 N NaOH (×2), brine (×1) and dried
over anhydrous Na2SO4. Evaporation of solvent followed by
chromatography (SiO2, 50% CH2Cl2/hexanes then 10% EtOAc/
hexanes) gave 110 mg (0.46 mmol, 92.4%) of 25 as a colorless
oil: IR (neat) 3075, 2990, 2913, 1584, 1457, 1440 cm-1; 1H NMR
(500 MHz, CDCl3) δ 7.52-7.44 (m, 2 H), 7.32-7.22 (m, 3 H),
5.26 (dd, J ) 2.6, 12.1 Hz, 1 H), 4.05 (ddddd, J ) 2.4, 6.1, 5.9,
5.9, 11.6 Hz, 1 H), 1.80 (td, J ) 2.5 , 13.1 Hz , 1 H), 1.56-1.45
(m, 1 H), 1.50 (s, 3 H), 1.49 (s, 3 H), 1.17 (d, J ) 5.8 Hz, 3 H);
(16) Gen er a l. IR spectra were recorded on a Prospect IR. NMR
spectra were recorded on a IBM NR-200 AF, an IBM NR-300AF,
Varian VXR-500, or a GN Omega 500 MHz instrument. Chemical shifts
of the 1H NMR spectra were referenced to residual chloroform at 7.26
ppm. Chemical shifts of the 13C spectra were referenced to CDCl3 at
77.0 ppm. Carbon multiplicities were determined by use of the DEPT
pulse sequence. Capillary GC analysis was performed on a Hewlett
Packard Model 5890 A instrument with a 30 m PhMe-Silicon column,
a flame ionization detector and a Hewlett Packard 3390 A integrator.
Combustion analysis were performed by M-H-W Laboratories, Phoenix,
AZ. Mass spectra were determined on an AE2-MS 30 instrument or a
PG 7070E-HF instrument. Liquid chromatography was performed
using forced flow (flash chromatography) of the indicated solvent
system on EM reagent silica gel 60 (230-400 mesh). Moisture sensitive
reactions were carried out under atmosphere of N2 using oven dried
glassware and standard syringe/septa techniques. DIBALH (1.0 M in
cyclohexane), compounds 15 and 21 were purchased from Aldrich
Chemical Co.