M. Mitani, Y. Tanaka, A. Sawada, A. Misu, Y. Matsumoto
FULL PAPER
0 °C under a nitrogen atmosphere. The resulting mixture was
stirred for 8 h at 0 °C. After the solvent was mostly removed under
reduced pressure, H2O (10 mL) was added to the residue and the
product was extracted with CH2Cl2. The organic layer was dried
with MgSO4, filtered, and concentrated under reduced pressure.
The residue was subjected to column chromatography on silica gel
(eluent: CH2Cl2/hexane, 1:1) to afford 1 (1.219 g, 92%) as a color-
CH2COOCH3), 3.77 (s, 3 H, COOCH3), 4.62 (d, J = 12.0 Hz, 1 H,
CHPh), 4.69 (d, J = 12.0 Hz, 1 H, CHPh), 6.52 (s, 1 H, NH), 7.33
(br. s, 5 H, Ph) ppm. 13C NMR: δ = 26.5, 34.6, 37.3, 51.6, 52.0,
71.5, 76.1, 127.5, 128.1, 128.9, 137.2, 171.1, 172.8 ppm. HRMS
(EI): calcd. for C17H25NO5 [M+] 323.1731; found 323.1746.
Methyl 3-(Benzyloxyamino)-3-(methoxycarbonyl)-5-hexenoate (4e):
Using the procedure described for the formation of 4a, 4e was ob-
tained as a colorless oil (0.189 g, 71%) by the reaction of 1
(1 mmol) with triallylzincate (2 mmol). 1H NMR: δ = 2.48–2.61 (m,
2 H, CH2CH=CH2), 2.83 (d, J = 16.0 Hz, 1 H, CHCOOCH3), 2.88
(d, J = 16.0 Hz, 1 H, CHCOOCH3), 3.66 (s, 3 H, CH2COOCH3),
3.75 (s, 3 H, COOCH3), 4.72 (s, 2 H, CH2Ph), 5.10–5.15 (m, 2 H,
CH2=CH), 5.68–5.78 (m, 1 H, CH2=CHCH2), 6.26 (s, 1 H, NH),
7.33 (br. s, 5 H, Ph) ppm. 13C NMR: δ = 37.3, 38.3, 51.7, 52.3,
67.0, 76.8, 119.5, 127.6, 128.1, 128.2, 131.5, 137.2, 170.8,
172.4 ppm. HRMS (EI): calcd. for C13H16NO5 [M+] 266.1027;
found 266.1001.
1
less oil. H NMR: δ = 3.63 (s, 3 H, CH2COOCH3), 3.66 (s, 2 H,
CH2COOCH3), 3.87 (s, 3 H, COOCH3), 5.33 (s, CH2Ph), 7.34 (br.
s, 5 H, Ph) ppm. 13C NMR: δ = 31.4, 52.3, 53.1, 78.2, 128.1, 128.3,
128.8, 135.9, 145.5, 163.1, 168.1 ppm. HRMS (EI): calcd. for
C13H15NO5 [M+] 265.0949; found 265.0932.
Methyl 3-(Benzyloxyamino)-3-(methoxycarbonyl)-4-methylpentano-
ate (4a): To a CH2Cl2 solution (10 mL) of 1 (0.265 g, 1 mmol),
BF3·OEt2 (0.142 g, 1 mmol) was added at 0 °C under a nitrogen
atmosphere and the solution was stirred for 10 min. To this was
added a triisopropylzincate solution that was generated via stirring
for 1 h after the addition of isopropylmagnesium bromide (1 mmol/
1 mL, 6 mL) to a CH2Cl2 solution (4 mL) of ZnCl2 (0.273 g,
2 mmol) in another flask. After stirring for 24 h at 0 °C, saturated
aqueous ammonium chloride was added to the reaction mixture.
The aqueous phase was separated and extracted with CH2Cl2. The
combined organic layers were dried with MgSO4. After the solvent
was mostly removed under reduced pressure, the residue was sub-
jected to column chromatography on silica gel (eluent: CH2Cl2) to
Methyl 3-(Benzyloxyamino)-3-(methoxycarbonyl)-5-phenylpentano-
ate (4f): Using the procedure described for the formation of 4a, 4f
was obtained as a colorless oil (0.260 g, 70%) by the reaction of 1
(1 mmol) with tris(2-phenylethyl)zincate generated via the addition
of 2-phenylethylmagnesium bromide (1 mmol/1 mL, 12 mL) to a
1
CH2C2 solution (8 mL) of ZnCl2 (0.545 g, 4 mmol). H NMR: δ =
1.96–2.15 (m, 2 H, CH2CH2Ph), 2.54–2.71 (m, 2 H, CH2CH2Ph),
2.93 (s, 2 H, CH2COOCH3), 3.67 (s, 3 H, CH2COOCH3), 3.75 (s,
3 H, COOCH3), 4.76 (s, 2 H, OCH2Ph), 6.31 (s, 1 H, NH), 7.20
(br. s, 5 H, Ph), 7.34 (br. s, 5 H, Ph) ppm. 13C NMR: δ = 30.0,
35.8, 37.4, 51.5, 52.2, 66.8, 77.1, 125.7, 127.5, 128.00, 128.02, 128.1,
128.2, 137.1, 140.8, 170.8, 172.7 ppm. MS (EI): m/z (%) = 312 (18)
[M – COOCH3]+, 91 (100). MS (CI): m/z = 372 [M + 1]+. HRMS
(EI): calcd. for C19H22NO3 [M – COOCH3]+ 312.1598; found
312.1610.
1
afford 4a (0.207 g, 67%) as a colorless oil. H NMR: δ = 0.92 (d,
J = 7.2 Hz, 3 H, CHCH3), 0.97 (d, J = 7.2 Hz, 3 H, CHCH3), 2.17
[septett, J = 7.2 Hz, 1 H, CH(CH3)2], 2.88 (d, J = 16.0 Hz, 1 H,
CHCOOCH3), 2.99 (d, J = 16.0 Hz, 1 H, CHCOOCH3), 3.62 (s, 3
H, CH2COOCH3), 3.76 (s, 3 H, COOCH3), 4.70 (s, 2 H, CH2Ph),
6.47 (s, 1 H, NH), 7.32 (br. s, 5 H, Ph) ppm. 13C NMR: δ = 17.4,
17.8, 32.9, 36.7, 51.7, 52.1, 69.8, 79.0, 127.6, 128.1, 128.2, 137.3,
171.7, 172.4 ppm. HRMS (EI): calcd. for C16H23NO5 [M+]
309.1574; found 309.1556.
Methyl 2-(Benzyloxyimino)propionate (5): Using the procedure de-
scribed for the formation of 1, 5 was obtained as a colorless oil
1
Methyl 3-(Benzyloxyamino)-3-(methoxycarbonyl)pentanoate (4b): (77%) via the reaction of methyl pyruvate. H NMR: δ = 2.05 (s,
Using the procedure described for the formation of 4a, 4b was ob-
tained as a colorless oil (0.242 g, 82%) by the reaction of 1
3 H, CH3C=N), 3.85 (s, 3 H, COOCH3), 5.31 (s, 2 H, CH2Ph),
7.35 (br. s, 5 H, Ph) ppm. 13C NMR: δ = 11.8, 52.8, 77.6, 128.1,
128.2, 128.3, 136.4, 149.1, 164.0 ppm. MS (EI): m/z (%) = 207 (1)
1
(1 mmol) with triethylzincate (2 mmol). H NMR: δ = 0.88 (t, J =
8.0 Hz, 3 H, CH2CH3), 1.72–1.84 (m, 2 H, CH2CH3), 2.85 (d, J = [M+], 176 (10), 91 (100).
16.0 Hz,
1 H, CHCOOCH3), 2.90 (d, J = 16.0 Hz, 1 H,
Methyl 2-(Benzyloxyamino)-2-methylbutanoate (6a): Using the pro-
cedure described for the formation of 4a, 6a was obtained as a
colorless oil (0.201 g, 85%) by the reaction of 5 (0.207 g, 1 mmol)
CHCOOCH3), 3.66 (s, 3 H, CH2COOCH3), 3.75 (s, 3 H, CO-
OCH3), 4.71 (s, 2 H, CH2Ph), 6.72 (s, 1 H, NH), 7.33 (br. s, 5 H,
Ph) ppm. 13C NMR: δ = 14.2, 27.0, 36.9, 51.5, 52.1, 67.4, 78.8,
127.5, 127.9, 128.2, 137.2, 170.9, 172.8 ppm. HRMS (EI): calcd.
for C15H21NO5 [M+] 295.1418; found 295.1412.
1
with triethylzincate (2 mmol). H NMR: δ = 0.86 (t, J = 7.4 Hz, 3
H, CH3CH2), 1.33 (s, 3 H, CH3CCOOCH3), 1.60 (q, J = 7.4 Hz, 2
H, CH2CH3), 3.72 (s, 3 H, COOCH3), 4.68 (d, J = 12.0 Hz, 1 H,
CHPh), 4.75 (d, J = 12.0 Hz, 1 H, CHPh), 6.02 (s, 1 H, NH), 7.33
(br. s, 5 H, Ph) ppm. 13C NMR: δ = 8.2, 19.1, 28.8, 52.1, 66.1,
76.9, 127.5, 128.1, 128.4, 137.6, 175.4 ppm. HRMS (EI): calcd. for
C13H19NO3 [M+] 237.1364; found 237.1387.
Methyl 3-(Benzyloxyamino)-3-(methoxycarbonyl)heptanoate (4c):
Using the procedure described for the formation of 4a, 4c was ob-
tained as a colorless oil (0.233 g, 72%.) by the reaction of 1
1
(1 mmol) with tributylzincate (2 mmol). H NMR: δ = 0.89 (t, J =
7.2 Hz, 3 H, CH2CH3), 1.25–2.00 (m, 6 H, CH2CH2CH2CH3), 2.85
(d, J = 16.0 Hz, 1 H, CHCOOCH3), 2.92 (d, J = 16.0 Hz, 1 H,
CHCOOCH3), 3.66 (s, 3 H, CH2COOCH3), 3.75 (s, 3 H, CO-
OCH3), 4.71 (s, 2 H, CH2Ph), 6.30 (s, 1 H, NH), 7.35 (br. s, 5 H,
Ph) ppm. 13C NMR: δ = 13.8, 19.2, 30.7, 31.0, 31.5, 51.7, 52.3,
66.1, 78.1, 127.8, 128.2, 128.4, 137.2, 168.4, 171.4 ppm. HRMS
(EI): calcd. for C17H25NO5 [M+] 323.1731; found 323.1701.
Methyl 2-(Benzyloxyamino)-2-methylhexanoate (6b): Using the pro-
cedure described for the formation of 6a, 6b was obtained as a
colorless oil (0.188 g, 71%) by the reaction of 5 (1 mmol) with tri-
butylzincate (2 mmol). 1H NMR: δ = 0.88 (t, J = 7.0 Hz, 3 H,
CH3CH2), 1.25–1.30 (m, 4 H, CH3CH2CH2), 1.35 (s, 3 H,
CH3CCOOCH3), 1.51–1.55 (m, 2 H, CH3CH2CH2CH2), 4.67 (d, J
= 11.8 Hz, 1 H, CHPh), 4.73 (d, J = 11.8 Hz, 1 H, CHPh), 6.01 (s,
1 H, NH), 7.33 (br. s, 5 H, Ph) ppm. 13C NMR: δ = 13.9, 19.4,
23.0, 25.7, 35.7, 51.9, 65.6, 76.8, 127.4, 127.9, 128.2, 137.5, 175.3
ppm. HRMS (EI): calcd. for C15H23NO3 [M+] 265.1677; found
265.1692.
Methyl 3-(Benzyloxyamino)-4,4-dimethyl-3-(methoxycarbonyl)pen-
tanoate (4d): Using the procedure described for the formation of
4a, 4d was obtained as a colorless oil (0.220 g, 68%) by the reaction
of 1 (1 mmol) with tri-tert-butylzincate (2 mmol). 1H NMR: δ =
0.98 [s, 9 H, C(CH3)3], 2.85 (d, J = 16.0 Hz, 1 H, CHCOOCH3), Methyl 2-(Benzyloxyamino)-2,3-dimethylbutanoate (6c): To
a
3.00 (d,
J
=
16.0 Hz,
1
H, CHCOOCH3), 3.55 (s,
3
H,
CH2Cl2 solution (10 mL) of 5 (1 mmol), BF3·OEt2 (1 mmol) was
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Eur. J. Org. Chem. 2008, 1383–1391