Allylation of Nitro Group-Stabilized Carbanions
J . Org. Chem., Vol. 61, No. 26, 1996 9095
(R)-6-(3′-H yd r oxyp r op yl)-6-n it r o-1,4-d ioxa sp ir o[4.5]-
d eca n e (6). A solution of (R)-5 (1.01 g, 4.44 mmol) in 5 mL
of THF was added to a solution of 9-BBN (2.17 g, 8.89 mmol)
in 10 mL of THF at 0 °C. The mixture was stirred for 3.5 h at
0 °C and for 1 h at rt and then treated with 0.1 mL of water.
After the mixture was cooled to 0 °C, 3 N NaOH (2.6 mL) and
30% H2O2 (3.65 mL) was carefully added in this order. Water
was added and extracted with AcOEt three times. The
combined organic phases were washed with brine, dried over
Na2SO4, and concentrated under reduced pressure. The
residue was purified by chromatography on silica gel (hexane/
211.1207, found 211.1196. Anal. Calcd for C11H19NO2: C,
66.97; H,9.71; N, 7.10. Found: C, 66.71; H, 10.00; N, 6.97.
(R)-1,3-Dioxola n e-2-sp ir ocycloh exa n e-2′-sp ir o-2′′-1′′-
(eth oxyca r bon yl)a za cyclop en ta n e (10). A solution of ethyl
chloroformate (603 mg, 5.56 mmol) in 3 mL of CH2Cl2 was
slowly added to a solution of (R)-9 (182.2 mg, 0.92 mmol) in
1.3 mL of Et3N. After 1 h of stirring at rt, the mixture was
combined with water and extracted with AcOEt three times.
The combined organic phases were dried over MgSO4 and
concentrated under reduced pressure. The residue was puri-
fied by bulb-to-bulb distillation (180 °C/0.2 mmHg) to afford
224.9 mg (90%) of (R)-10: [R]25D +7.0 (c 1.46, CHCl3); 1H NMR
(200 MHz, CDCl3, TMS) δ 1.19-2.84 (m, 9H), 1.25 (t, 3H),
1.91-2.15 (m, 1H), 2.21-2.37(m, 1H), 3.12-3.34 (m, 1H),
3.35-3.66 (m, 2H), 3.76-3.96 (m, 4H), 4.02-4.23 (m, 2H); 13C-
{1H} NMR (50 MHz, CDCl3, TMS) δ 14.8, 21.6, 23.3, 23.5, 34.4,
35.1, 36.6, 49.6, 65.0, 65.1, 66.2, 70.0, 113.0, 155.4; HRMS (EI)
calcd for C14H23NO4 (M+) 269.1626, found 269.1625. Anal.
Calcd for C14H23NO4: C, 62.43; H, 8.61; N, 5.20. Found: C,
61.65; H, 8.45; N, 5.27.
AcOEt) to afford 1.04 g (95%) of (R)-6: [R]25 -3.9 (c 1.71,
D
CHCl3); 1H NMR (200 MHz, CDCl3, TMS) δ 1.10-1.14 (m, 4H),
1.14-1.85 (m, 5H), 1.92-2.15 (m, 2H), 2.44 (dddd, J ) 9.9,
9.9, 3.8, 1.2 Hz, 1H), 3.52-3.80 (m, 2H), 3.86-4.02 (m, 4H)
(OH not detected); 13C{1H} NMR (50 MHz, CDCl3, TMS) δ 21.6,
22.4, 26.2, 27.7, 29.3, 33.6, 62.2, 65.1, 65.2, 95.0, 109.9. Anal.
Calcd for C11H19NO5: C, 53.86; H, 7.80; N, 5.74. Found: C,
54.08; H, 8.00; N, 5.55.
(R)-6-[2′-(Met h oxyca r b on yl)et h yl]-6-n it r o-1,4-d ioxa -
sp ir o[4.5]d eca n e (7). PDC (5.57 g, 14.79 mmol) was added
to a solution of (R)-6 (1.04 g, 4.23 mmol) in 11 mL and stirred
at rt for 36 h. The mixture was diluted with ether, passed
through a pad of Celite, and concentrated by heating at 45 °C
under a reduced pressure. This procedure was repeated once
more to give crude carboxylic acid (961 mg). For esterification,
the carboxylic acid was dissolved in 5 mL of THF and 10 mL
of ether and treated with a solution of CH2N2 in ether. The
excess CH2N2 was decomposed with AcOH. The mixture was
washed with saturated aqueous NaHCO3, extracted with ether
three times, dried over MgSO4, and concentrated under
reduced pressure. Purification of the residue by MPLC (silica
(R)-6-Oxo-1-(et h oxyca r b on yl)-1-a za sp ir o[4.5]d eca n e
(11). A solution of (R)-10 (224.9 mg, 0.84 mmol) in 0.5 mL of
CH2Cl2 was treated with 22 mL of 10% hydrochloric acid and
stirred for 19 h at rt. The mixture was extracted with AcOEt
three times, and the combined organic phases were washed
with brine, dried over MgSO4, and concentrated under reduced
pressure. The residue was purified by MPLC (silica gel,
hexane:AcOEt ) 1:1) followed by bulb-to-bulb distillation to
afford 132 mg (70%) of (R)-11: [R]25 -10.2 (c 1.14, CHCl3);
D
1H NMR (200 MHz, CDCl3, TMS) δ 1.23 (dt, J ) 14.2, 7.2 Hz,
3H), 1.47-2.17 (m, 9H), 2.23-2.45 (m, 1H), 2.46-2.80 (m, 2H),
3.46-3.67 (m, 2H), 4.03-4.22 (m, 2H); 13C{1H} NMR (50 MHz,
CDCl3, TMS) δ 14.0 and 14.7 (2 s), 22.3 and 22.9 (2 s), 23.3
and 23.5 (2 s), 24.6 and 24.7 (2 s), 35.6 and 36.7 (2 s), 37.1
and 38.2 (2 s), 39.8 (s), 47.8 and 48.4 (2 s), 60.77 and 60.85 (2
s), 71.1 and 71.5 (2 s), 154.5 and 154.9 (2 s), 208.0 and 208.3
(2 s). Anal. Calcd for C12H19NO3: C, 63.98; H, 8.50; N, 6.22.
Found: C, 63.82; H, 8.65; N, 6.03.
gel, hexane:AcOEt ) 2:1) afforded 597 mg (52%) of (R)-7: [R]25
D
-5.8 (c 0.92, CHCl3); 1H NMR (200 MHz, CDCl3, TMS) δ 1.17-
1.47 (m, 1H), 1.47-1.82 (m, 5H), 1.97 (dtd, J ) 13.8, 4.0, 1.7
Hz, 1H), 2.10-2.34 (m, 3H), 2.46 (dddd, J ) 15.9, 12.3, 3.8,
1.1 Hz, 1H), 2.91 (dddd, J ) 17.5, 11.6, 3.1, 1.4 Hz, 1H), 3.68
(s, 3H), 3.86-4.02 (m, 4H); 13C{1H} NMR (50 MHz, CDCl3,
TMS) δ 21.6, 22.3, 26.5, 28.2, 29.5, 33.5, 51.8, 65.2, 94.3, 109.7,
172.6. Anal. Calcd for C12H19NO6: C, 52.74; H, 7.01; N, 5.13.
Found: C, 52.75; H, 7.15; N, 5.06.
(R)-1-(Eth oxyca r bon yl)-6-(m eth oxyim in o)-1-a za sp ir o-
[4.5]d eca n e (12). A solution of (R)-11 (122 mg, 0.54 mmol)
in 1.3 mL of pyridine was treated with H2NOMe‚HCl (301 mg,
3.60 mmol) and stirred for 23 h at rt. The reaction mixture
was diluted with 3 mL of water, made alkaline with 3 N
NaOH, and extracted with CH2Cl2 three times. The combined
organic phases were washed with brine, dried over MgSO4,
and concentrated under reduced pressure. The residue was
purified by PTLC (silica gel, hexane:AcOEt ) 1:1) to afford
120 mg (87%) of (R)-12: [R]25D +16.7 (c 1.44, CHCl3); 1H NMR
(200 MHz, CDCl3, TMS) δ 1.24 (dt, J ) 6.7, 6.7 Hz, 3H), 1.30-
1.97 (m, 9H), 2.02-2.16 (m, 1H), 2.48-2.68 and 2.84-3.03 (m,
1H + 1H′), 3.18-3.25 and 3.25-3.32 (m, 1H + 1H′), 3.36-
(R)-1,3-Dioxola n e-2-sp ir ocycloh exa n e-2′-sp ir o-5′′-2′′-
p yr r olid in on e (8). Raney Ni (W7) (ca. 200 mg) was added
to a solution of (R)-7 (113 mg, 0.413 mmol) in MeOH (2 mL),
and the mixture was stirred in an autoclave at 30 °C at a
hydrogen pressure of 100 atm. After the mixture was stirred
for 2 d, progress of the reaction was checked by TLC, which
indicated the remains of the starting material. Raney Ni (ca.
200 mg) was added, and the mixture was again subjected to
the hydrogenation for 4 d. After the completion of reaction
was confirmed by TLC, the mixture was passed through a pad
of Celite and evaporated. The residue was then purified by
chromatography on silica gel (hexane:AcOEt, Et2NH) followed
by bulb-to-bulb distillation (200 °C/0.2 mmHg) to afford 52 mg
(60%) of (R)-8: [R]25D -9.6 (c 1.07, CHCl3); 1H NMR (200 MHz,
CDCl3, TMS) δ 1.18-1.93 (m, 9H), 2.22-2.40 (m, 2H), 2.44-
2.65 (m, 1H), 3.83-4.10 (m, 4H), 5.64 (br s, 1H); 13C{1H} NMR
(50 MHz, CDCl3, TMS) δ 21.7, 22.9, 28.5, 30.5, 32.0, 37.5, 64.5,
65.3, 65.7, 111.0, 177.9; HRMS (EI) calcd for C11H17NO3 (M+)
211.1207, found 211.1196. Anal. Calcd for C11H17NO3: C,
62.53; H, 8.16; N, 6.66. Found: C, 61.97; H, 8.24; N, 6.59.
(R)-1,3-Dioxola n e-2-sp ir ocycloh exa n e-2′-sp ir o-2′′-p yr -
r olid in e (9). LiAlH4 (168 mg, 4.42 mmol) was added at 0 °C
to a solution of (R)-8 (232.6 mg, 1.10 mmol) in 5 mL of THF.
The mixture was then refluxed for 40 h and quenched at 0 °C
by sequential additions of water (168 µL), 15% NaOH (168 µL),
and water (504 µL). After the mixture was stirred at rt for 30
min, the aluminum salts were filtered off with a pad of Celite
and washed with THF. The filtrate and washings were
combined and concentrated under reduced pressure. The
residue was then purified by bulb-to-bulb distillation (120 °C/
0.2 mmHg) to afford 182 mg (84%) of (R)-9: [R]25D -0.9 (c 0.86,
CHCl3); 1H NMR (200 MHz, CDCl3, TMS) δ 1.22-1.98 (m,
13H), 2.83-3.04 (m, 2H), 3.92-4.11 (m, 4H); 13C{1H} NMR
(50 MHz, CDCl3, TMS) δ 22.7, 23.1, 26.1, 32.2, 32.3, 37.3, 46.7,
64.8, 65.0, 67.0, 112.3; HRMS (EI) calcd for C11H19NO3 (M+)
3.50 (m, 1H), 3.77 (s, 3H), 3.96-4.27 (m, 2H);
13C{1H} NMR
(50 MHz, CDCl3, TMS) δ 14.7 and 14.9 (2 s), 21.2 and 21.4 (2
s), 23.1 and 23.2 (2 s), 23.36 and 23.43 (2 s), 23.9 (s), 36.2 and
37.1 (2 s), 38.5 and 39.6 (2 s), 47.9 and 48.5 (2 s), 60.2 and
60.4 (2 s), 61.6 (s), 65.7 and 66.4 (2 s), 154.4 and 155.7 (2 s),
157.3 and 157.9 (2 s). Anal. Calcd for C13H22N2O3: C, 61.39;
H, 8.72; N, 11.01. Found: C, 61.11; H, 8.95; N, 10.89.
(R)-1-Meth yl-1-a za sp ir o[4.5]d eca n -6-a m in e (13).13 Li-
AlH4 (170 mg, 4.47 mmol) was added to a solution of (R)-12
(105 mg, 0.414 mmol) in 4.5 mL of THF at 0 °C. After 7 h of
stirring at rt, the mixture was diluted with 5 mL of ether and
cooled to 0 °C before being quenched by sequential additions
of water (170 µL), 15% NaOH (170 µL), and water (510 µL).
The mixture was stirred for 1 h at rt, and aluminum salts were
filtered off with a pad of Celite and washed with THF. The
combined filtrate and washings were concentrated under
reduced pressure. The residue was purified by bulb-to-bulb
distillation (180 °C/16 mmHg) to afford 65 mg (93%) of (R)-
1
13: [R]25 -1.20 (c 1.25, CHCl3); H NMR (200 MHz, CDCl3,
D
TMS) δ 1.10-1.95 (m, 14H), 2.23 (s, 3H), 2.46-2.67 (m, 2H),
2.87-2.98 (m, 1H).
(2R,5′R)-N-(1′-Meth yl-1′-a za sp ir o[4.5]d ec-6′-yl)-2-m eth -
oxy-2-p h en yla ceta m id e (14). A solution of (R)-13 (6.5 mg,
38.5 µmol) in 150 µL of CH2Cl2 was added to a mixture of (R)-
R-methoxy-R-phenylacetic acid (13 mg, 78.2 µmol), DCC (15.7