Studies of Acyl Nitrene Insertions
J . Org. Chem., Vol. 64, No. 3, 1999 743
butyldimethylsilyl trifluoromethanesulfonate (6.2 g, 23 mmol).
After 15 min, saturated aqueous NaHCO3 (15 mL) was added,
and the reaction mixture was diluted with Et2O and washed
with saturated aqueous CuSO4 (×1). The aqueous phase was
extracted with Et2O (×2), and the combined organic layers
were dried (Na2SO4), filtered, and concentrated. The residue
was chromatographed (10 f 50% EtOAc/hexanes, 250 g of
SiO2), providing silyl ether 24b as an oil (6.8 g, 89% from
δ-lactone 20): Rf ) 0.61 (5% THF/CH2Cl2); [R]25 -53.6° (c )
D
2.20, CHCl3); FTIR (neat) 1734, 1624 cm-1; 1H NMR (400 MHz,
CDCl3) δ 6.35 (d, J ) 2.7 Hz, 1H), 5.00 (d, J ) 2.7 Hz, 1H),
4.41 (d, J ) 1.9 Hz, 1H), 4.24 (m, 1H), 4.05 (m, 1H), 3.67 (s,
3H), 3.65 (m, 1H), 3.49 (m, 1H), 2.10 (m, 1H), 2.00-1.60 (m,
2H), 1.38 (s, 3H), 1.36 (s, 3H), 1.33 (s, 3H), 0.89 (s, 9H), 0.75
(d, J ) 6.7 Hz, 3H), 0.06 (s, 3H), 0.04 (s, 3H); 13C NMR (101
MHz, CDCl3) δ 174.93 (s), 146.26 (d), 108.13 (s), 106.27 (d),
89.56 (d), 72.56 (d), 71.88 (d), 69.97 (t), 55.06 (s), 51.97 (q),
39.31 (d), 36.63 (t), 27.40 (q), 26.89 (q), 25.87 (q), 18.01 (s),
8.57 (q), -4.28 (q), -4.98 (q); HRMS m/e calcd for C22H41O6Si
(M+ + 1) 429.2673, found 429.2671. Anal. Calcd for C22H40O6-
Si: C, 61.65; H, 9.41. Found: C, 61.50; H, 9.51.
and the residue purified by column chromatography (80%
EtOAc/hexanes, 2 g of SiO2), providing lactols 36 (5 mg, 75%):
Rf ) 0.25 (80% EtOAc/hexanes); FTIR (neat) 3364, 1726 cm-1
;
1H NMR (400 MHz, CDCl3) indicated ca. 2:1 mixture of
anomers. Data for major anomer: δ 5.40 (br s, 1H), 5.22 (br d,
J ) 9.1 Hz, 1H), 4.55 (dd, J ) 9.3, 4.7 Hz, 1H), 4.39 (m, 1H),
4.20-4.00 (m, 4H), 3.82 (d, J ) 9.7 Hz, 1H), 3.59 (t, J ) 7.8
Hz, 1H), 3.27 (broad, 1H), 2.08-1.92 (m, 2H), 1.82 (m, 1H),
1.41 (s, 3H), 1.41 (s, 3H), 1.35 (s, 3H), 1.27 (t, J ) 7.4 Hz, 3H),
1.13 (d, J ) 6.5 Hz, 3H); HRMS m/e calcd for C18H30NO8 (M+
+ 1) 388.1972, found 388.1978.
[3S-[3R,3a R,6â(R*),7R,7a R]]-[6-[(2,2-Dim eth yl-1,3-d iox-
ola n -4-yl)m eth yl]h exa h yd r o-3a ,7-d im eth yl-2,4-d ioxo-4H-
fu r o[3,2-c]p yr a n -3-yl]ca r ba m ic a cid E t h yl E st er (23b ).
F r om h em ia ceta ls 36: A solution of hemiacetals 36 (5 mg,
0.013 mmol) and pyridinium dichromate (19 mg, 0.051 mmol)
in CH2Cl2 (2.5 mL) was heated at reflux 90 min, recooled to
ambient temperature, filtered through Celite, and concen-
trated. The residue was purified by column chromatography
(50% EtOAc/hexanes, 2 g of SiO2), providing bis-lactone 23b
(4 mg, 80%). F r om ep im er iza tion of bis-la cton e 23a : Bis-
lactone 23a (14 mg, 0.036 mmol) in THF (1 mL) was added to
a -78 °C solution of LDA (0.55 mL of a freshly prepared 0.33
M solution in THF, 0.18 mmol), giving a yellow color. After
10 min, acetic acid (22 mg, 0.36 mmol) was added, followed
by saturated aqueous NH4Cl. The mixture was warmed to
ambient temperature, diluted with Et2O, and washed with
H2O. The organic phase was dried (MgSO4), filtered, and
concentrated. The residue was purified by column chromatog-
raphy (60% EtOAc/hexanes, 2 g of SiO2), providing the
epimeric bis-lactone 23b (7 mg, 50%): Rf ) 0.40 (60% EtOAc/
[3aS-[3aR,5R[1R*,2S*,3(R*)],6R,6aR]]-5-[3-(2,2-Dim eth yl-
1,3-d ioxola n -4-yl)-2-[[(1,1-d im eth yleth yl)d im eth ylsilyl]-
oxy]-1-m et h ylp r op yl]-2-et h oxy-3a ,5,6,6a -t et r a h yd r o-6-
m eth yl-fu r o[3,2-d]oxazole-6-car boxylic Acid Meth yl Ester
(25) a n d (2S,3S)-1,4-An h yd r o-2,3,5,7-tetr a d eoxy-6-O-[(1,1-
dim eth yleth yl)dim eth ylsilyl]-2-[(eth oxycar bon yl)am in o]-
1-h yd r oxy-3-(m et h oxyca r b on yl)-3,5-d im et h yl-8,9-O-(1-
m eth yleth ylid en e)-D-a ltr o-n on itol (26). A solution of vinyl
ether 24b (3.4 g, 7.9 mmol) in CH2Cl2 (160 mL) was degassed
with an argon stream for 15 min, ethyl azidoformate (3.4 g,
30 mmol) was added, and the solution was photolyzed for 3 h
with a 400 W Hanovia Hg-vapor lamp through a Vycor filter.
An aliquot (8 mL) of the yellow reaction mixture was concen-
trated and the residue was chromatographed (2.5 f 3.5% THF/
CH2Cl2), providing oxazoline 25 (165 mg) as a colorless oil. To
the bulk of the reaction mixture was added additional ethyl
azidoformate (1.1 g, 9.6 mmol), and photolysis was continued
1 h. The solution was concentrated, and the residue was stirred
with 9/1 THF/H2O (50 mL) for 30 min. The mixture was diluted
with Et2O and washed with saturated aqueous NaHCO3 (×1).
The aqueous phase was extracted with Et2O (×2), and the
combined organic phases were dried (MgSO4), filtered, and
concentrated. The residue was chromatographed (30 f 50%
EtOAc/hexanes, 200 g of SiO2), providing anomeric carbamates
26 as an oil (2.7 g, 65%, 70% after accounting for isolated
oxazoline). Data for oxazoline 25: Rf ) 0.38 (5% THF/CH2Cl2);
FTIR (neat) 1730, 1667 cm-1; 1H NMR (400 MHz, C6D6) δ 6.15
(d, J ) 4.8 Hz, 1H), 4.61 (d, J ) 5.1 Hz, 1H), 4.36 (m, 1H),
4.15 (d, J ) 1.6 Hz, 1H), 4.11 (m, 2H), 3.95 (apparent dd, J )
8.1, 5.9 Hz, 1H), 3.73 (dt, J ) 7.8, 4.2 Hz, 1H), 3.45 (t, J ) 8.1
Hz, 1H), 3.26 (s, 3H), 2.26 (m, 1H), 1.98-1.58 (m, 2H), 1.46
(s, 3H), 1.39 (s, 3H), 1.33 (s, 3H), 1.03 (t, J ) 7.3 Hz, 3H), 0.95
1
hexanes); FTIR (neat) 3528, 3324, 1788, 1728 cm-1; H NMR
(500 MHz, CDCl3) δ 5.28 (broad, 1H), 4.82 (d, J ) 8.3 Hz, 1H),
4.41 (pentet, J ) 6.5 Hz, 1H), 4.16 (q, J ) 7.1 Hz, 2H), 4.18-
4.08 (m, 3H), 3.61 (t, J ) 7.8 Hz, 1H), 2.17 (m, 1H), 2.05 (m,
2H), 1.44 (s, 3H), 1.42 (s, 3H), 1.35 (s, 3H), 1.26 (t, J ) 7.0 Hz,
3H), 1.22 (d, J ) 6.5 Hz, 3H); HRMS m/e calcd for C18H28NO8
(M+ + 1) 386.1815, found 386.1822.
(5S)-2,3,4,5,7,9-H exa d eoxy-8-O-[(1,1-d im et h ylet h yl)-
d im et h ylsilyl]-4-[(et h oxyca r b on yl)a m in o]-5-(m et h oxy-
ca r bon yl)-2,5,7-tr im eth yl-10,11-O-(1-m eth yleth ylid en e)-
D-glycer o-D-m a n n o-u n d ec-2-en on ic a cid eth yl ester (27).
Anomeric hemiacetals 26 (2.6 g, 4.9 mmol) and (carbethoxy-
ethylidene)triphenylphosphorane (8.9 g, 24.6 mmol) were
heated in refluxing toluene (225 mL) for 15 h. The reaction
mixture was cooled to ambient temperature, and the solvent
was removed on the rotovap. The residue was chromato-
graphed (30 f 35% EtOAc/hexanes), yielding the R,â-unsatur-
ated ethyl ester 27 as an oil (70%): Rf ) 0.25 (35% EtOAc/
hexanes); [R]2D5 +6.0° (c ) 0.51, CHCl3); FTIR (neat) 3520,
3351, 1714 cm-1; 1H NMR (400 MHz, CDCl3) δ 6.25 (apparent
dd, J ) 10.5, 1.3 Hz, 1H), 5.75 (br d, J ) 9.7 Hz, 1H), 4.72 (t,
J ) 10.2 Hz, 1H), 4.22-3.92 (m, 5H), 4.16 (q, J ) 7.3 Hz, 2H),
3.84 (m, 1H), 3.75 (s, 3H), 3.46 (m, 1H), 3.24 (broad d, J ) 3.0
Hz, 1H), 2.01 (s, 3H), 2.00-1.70 (m, 3H), 1.38 (s, 3H), 1.31 (s,
3H), 1.28 (t, J ) 7.3 Hz, 3H), 1.21 (t, J ) 7.3 Hz, 3H), 1.12 (s,
3H), 0.99 (d, J ) 6.7 Hz, 3H), 0.86 (s, 9H), 0.08 (s, 3H), 0.05
(s, 3H); 13C NMR (101 MHz, CDCl3) δ 176.21, 167.64, 155.81,
135.46, 132.00, 108.82, 75.88, 72.36, 71.96, 69.79, 61.09, 60.84,
53.21, 52.92, 52.41, 38.77, 35.70, 26.93, 25.86, 25.70, 17.85,
15.37, 14.45, 14.17, 13.20, 12.26, -4.37, -4.85; HRMS m/e
calcd for C30H56NO10Si (M+ + 1) 618.3670, found 618.3704.
(s, 9H), 0.91 (d, J ) 6.7 Hz, 3H), 0.13 (s, 3H), 0.00 (s, 3H); 13
C
NMR (101 MHz, C6D6) δ 174.05 (s), 162.97 (s), 108.65 (s),
108.39 (o), 84.19 (o), 74.53 (o), 72.90 (o), 72.71 (o), 70.28 (t),
66.56 (t), 54.59 (s), 51.70 (o), 37.34 (t), 37.14 (o), 27.19 (o), 26.13
(o), 18.16 (s), 16.24 (o), 14.22 (o), 9.46 (o), -4.15 (o), -4.74 (o);
HRMS m/e calcd for C25H46NO8Si (M+ + 1) 516.2994, found
516.2986. Data for carbamates 26: Rf ) 0.13 (5% THF/CH2-
Cl2); FTIR (neat) 3439, 3403, 1730 cm-1 1H NMR data for
;
major anomer (400 MHz, CDCl3) δ 5.54 (broad, 1H), 5.27
(broad, 1H), 4.94 (broad, 1H), 4.25 (m, 1H), 4.18-4.00 (m, 4H),
3.73 (s, 3H), 3.58 (m, 1H), 3.54-3.33 (broad, 1H), 3.50 (t, J )
7.8 Hz, 1H), 2.07-1.55 (m, 3H), 1.38 (s, 3H), 1.34 (s, 3H), 1.26-
1.16 (m, 6H), 0.88 (m, 9H), 0.80 (d, J ) 6.7 Hz, 3H), 0.06 (s,
3H), 0.04 (s, 3H); HRMS m/e calcd for C25H46O8NSi (M+ - OH)
516.2988, found 516.2981.
[3S-[3R,3a R,6â(R*),7R,7a R]]-[6-[(2,2-Dim eth yl-1,3-d iox-
ola n -4-yl)m eth yl]h exa h yd r o-3a ,7-d im eth yl-2-h yd r oxy-4-
oxo-4H-fu r o[3,2-c]p yr a n -3-yl]ca r ba m ic Acid Eth yl Ester
(36). A solution of silyl ether 26 (10 mg, 0.019 mmol) and HF‚
Et3N (17 mg, 0.19 mmol) in CH3CN (1.5 mL) was heated
overnight at 75 °C. The reaction mixture was concentrated,
(5S)-2,3,4,5,7,9-H exa d eoxy-8-O-[(1,1-d im et h ylet h yl)-
d im et h ylsilyl]-4-[(et h oxyca r b on yl)a m in o]-5-(m et h oxy-
ca r bon yl)-6-O-(tr im eth ylsilyl)-2,5,7-tr im eth yl-10,11-O-(1-