The Journal of Organic Chemistry
Article
Prepared by method A from 18d (165 mg, 1.49 mmol), NaHMDS
(1.71 mL, 1.71 mmol, 1 M in THF) in THF (10 mL), and i-AmONO
(240 μL, 1.79 mmol) at −78 °C for 20 min. The crude product (295
mg, E/Z = 2.8:1) was repeatedly purified by flash chromatography
(hexane/EtOAc 5:1 and CH Cl /Et O 10:1) yielding 95 mg (28%) of
2
2
2
19d as a 1.2:1 E/Z mixture as a colorless oil and 103 mg (49%) of 21
as a separable 6:1 mixture of unassigned diastereomers as colorless
−
1
solids. 19d: R 0.48, 0.37 (hexane/EtOAc 2:1); IR (film) ν[
̃
cm ]:
f
3
1
450−3220 (br), 2958 (m), 2928 (w), 2871 (w), 1720 (s), 1451 (w),
404 (m), 1371 (m), 1278 (w), 1166 (vs), 1051 (w), 911 (s), 831
1
(w), 730 (s), 648 (w); H NMR (400 MHz, CDCl
3
): δ 8.80 (br. s,
Z
E
E
1H, NOH ), 8.35 (br. s, 1H, NOH ), 7.40 (t, J = 6.1 Hz, 1H, H-6 ),
49
1
Z
EZ
H NMR
6.73 (br. t, J = 5.5 Hz, 1H, H-6 ), 4.10 (t, J = 6.9 Hz, 4H, H-1′ ),
Z
E
(
400 MHz, C D , major isomer): δ 3.08 (dquint, J = 13.7, 2.1 Hz, 1H,
2.46−2.33 (m, 2H, H-5 ), 2.31−2.18 (m, 2H, H-5 ), 1.83−1.63 (m,
EZ EZ EZ EZ
6
6
1
3
1
H-9equat.), 2.16-0.90 (m, 14H), 0.17 (s, 9H, SiMe); C{ H} NMR
8H, H-2 , H-4 , H-3′ ), 1.51 (q, J = 6.9 Hz, 4H, H-2′ ), 1.30−
EZ EZ
(
3
101 MHz, C D ): δ 142.0 (s, C-1), 118.6 (s, C-10), 37.5 (d, C-5),
6.1 (t), 31.7 (t), 31.4 (t), 27.5 (t), 26.9 (t), 26.7 (t), 22.3 (t), 0.8 (q,
1.20 (m, 2H, H-3 ), 1.05−1.02 (m, 2H, H-7a ), 0.98-0.92 (m, 2H,
EZ EZ 13 1
6
6
H-7b ), 0.91 (d, J = 6.6 Hz, 12H, H-4′ ); C{ H} NMR (101
EZ Z E
SiMe).
Cleavage by method B from silyl enol ether (1.00 g, 4.46 mmol),
MeLi (3.6 mL, 5.8 mmol, 1.6 M in diethyl ether), and i-AmONO
900 μL, 6.7 mmol), giving a crude solid 7:1 20c/19c mixture (1.11
MHz, CDCl ): δ 173.2 (s, C-1 ), 152.1 (d, C-6 ), 151.6 (d, C-6 ),
3
EZ
EZ
E
EZ
63.3 (t, C-1′ ), 37.5 (t, C-2′ ), 29.6 (t, C-5 ), 25.2 (d, C-3′ ), 25.1
Z
E
Z
Z
(t, C-5 ), 24.3 (t, C-4 ), 23.8 (t, C-4 ), 22.60 (q, C-4′ ), 22.57 (q, C-
E
Z
E
E
Z
(
4′ ), 21.4 (d, C-3 ), 21.1 (d, C-3 ), 18.35 (d, C-2 ), 18.34 (d, C-2 ),
Z E
g). Purification yielded 725 mg of a 10:1 mixture of (E)-20c and 19c
as a colorless solid and 91 mg of a 4:1 mixture of (Z)-20c and 19c;
13.58 (t, C-7 ), 13.56 (t, C-7 ); MS (ESI+) m/z, (%): 493 (4, [2M +
+
+
+
K] ), 477 (7, [2M + Na] ), 250 (100, [M + Na] ), 228 (8, [M +
H] ); HRMS (ESI+) m/z: [M + Na] calcd for C12H21NNaO
+
+
overall yield: 725 mg (58%) over 2 steps from 18c. R 0.42, 0.35
3
f
−
1
(
3
(
1
(
(
hexane/EtOAc 5:1); (E)-20c: mp 55−56 °C; IR (film) ν
500−3050 (br.), 2954 (m), 2925 (s), 2857 (m), 1730 (vs), 1670
w), 1462 (w), 1449 (w), 1418 (w), 1397 (w), 1386 (w), 1368 (w),
316 (w), 1253 (m), 1162 (vs), 1145 (m), 1078 (w), 1051 (w), 981
̃
250.1414; found: 250.1412.
A
21 : mp 131−133 °C (dec.). R
0.18 (hexane/EtOAc 2:1); IR
f
−1
(film) ν[cm ]: 3600−2700 (br.), 3024 (w), 2929 (w), 2874 (w),
̃
1689 (vs), 1611 (m), 1430 (m), 1354 (w), 1335 (w), 1286 (m), 1233
(w), 1189 (w), 1090 (w), 1054 (w), 1020 (m), 1004 (w), 921 (vs),
1
w), 910 (s), 880 (w), 862 (w), 736 (s), 704 (w), 666 (w); H NMR
1
400 MHz, CDCl ): δ 8.75−8.25 (br. s, 1H, NOH), 4.08 (t, J = 6.9
903 (s), 854 (m), 831 (m), 799 (w), 747 (m), 728 (m); H NMR
3
Hz, 2H, H-1′), 2.66−2.59 (m, 1H, H-7a), 2.36−2.27 (m, 3H, H-7b,
H-2), 2.28−2.19 (m, 1H, H-5), 1.87−1.80 (m, 1H, H-4a), 1.76−1.54
(400 MHz, CDCl
6.0, 1.4 Hz, 1H, H-5a), 2.24 (ddd, J = 19.3, 13.6, 6.6 Hz, 1H, H-5b),
.13 (dddd, J = 13.9, 6.7, 2.5, 1.6 Hz, 1H, H-4a), 2.09−1.99 (m, 2H,
H-4b, H-2), 1.99−1.89 (m, 1H, H-3), 1.41 (td, J = 6.0, 4.2 Hz, 1H, H-
3
): δ 10.58 (br. s, 1H, NOH), 3.04 (ddt, J = 19.1,
2
(
m, 8H, H-3, H-8, H-9, H-10a, H-3′), 1.50 (q, J = 6.9 Hz, 2H, H-2′),
1
.45−1.33 (m, 2H, H-4b, H-10b), 0.91 (d, J = 6.7 Hz, 6H, H-4′);
1
3
1
13
1
7
a), 1.27 (ddd, J = 9.3, 8.0, 5.9 Hz, 1H, H-7b); C{ H} NMR (101
C{ H} NMR (101 MHz, CDCl ): δ = 173.9 (s, C-1), 162.7 (s, C-
3
MHz, CDCl ): δ 195.0 (s, C-1), 151.7 (s, C-6), 26.8 (d, C-2), 20.11
6
), 63.1 (t, C-1′), 41.7 (d, C-5), 37.5 (t, C-2′), 34.4 (t, C-2), 32.8 (t,
3
(
(
d, C-3), 20.10 (t, C-5), 18.5 (t, C-4), 11.4 (t, C-7); MS (EI) m/z,
C-4), 30.4 (t C-10), 26.2 (t, C-8/9), 25.2 (d, C-3′), 23.6 (t, C-8/9),
•+
+
%): 139 (97, [M] ), 122 (100, [M − OH] ), 94 (30, [M − CO −
2
3.1 (t, C-7), 22.8 (t, C-3), 22.6 (q, C-4′). MS (ESI+) m/z, (%): 561
+
+
•+
+ + +
OH] ), 81 (25), 67 (25, [pentadienyl] ); HRMS (EI) m/z: [M]
calcd for C H NO 139.0633; found: 139.0636.
(
[
5, [2M + Na] ), 308 (6, [M + K] ), 292 (100, [M + Na] ), 270 (7,
M + H] ); HRMS (ESI+) m/z: [M + Na] calcd for C H NNaO
+
+
7
9
2
1
5
27
3
B
1
21 : colorless paste. R = 0.33 (hexane/EtOAc 2:1); IR (film)
f
2
8
3
92.1883; found: 292.1883. (Z)-20c: H NMR (400 MHz, CDCl ): δ
3
−
1
ν
1
̃
.75−7.75 (br. s, 1H, NOH), 4.08 (t, J = 6.9 Hz, 2H, H-1′), 3.52−
.45 (m, 1H, H-5), 2.33 (t, J = 6.6 Hz, 2H, H-2), 2.25−2.20 (m, 1H,
(
(
1
s), 986 (m), 945 (vs), 922 (m), 868 (m), 832 (w), 796 (m), 760
m), 673 (m), 635 (m); H NMR (400 MHz, CDCl ): δ = 15.27 (s,
H, NOH), 2.64 (dddd, J = 16.7, 5.2, 2.2, 1.0 Hz, 1H, H-5a), 2.37
H-7a), 2.15 (ddd, J = 14.1, 13.6, 4.9 Hz, 1H, H-7b), 1.90−1.83 (m,
1
1
H, H-8a), 1.73−1.40 (m, 10H, H-3, H-4, H-9, H-8b, H-10, H-3′),
3
1
.50 (q, J = 6.9 Hz, 2H, H-2′), 0.91 (d, J = 6.6 Hz, 6H, H-4′);
13
1
(ddd, J = 16.6, 14.0, 5.4 Hz, 1H, H-5b), 2.21 (ddt, J = 13.8, 5.1, 2.3
Hz, 1H, H-4a), 2.12−2.03 (m, 1H, H-4b), 2.03−1.94 (m, 2H, H-2,
H-3), 1.61−1.55 (m, 1H, H-7a), 1.34 (ddd, J = 9.4, 8.0, 5.7 Hz, 1H,
C{ H} NMR (101 MHz, CDCl ): δ 173.9 (s, C-1), 163.2 (s, C-6),
3
6
4
2
3.1 (t, C-1′), 37.5 (t, C-2′), 34.4 (t, C-2), 32.0 (d, C-5), 30.2 (t, C-
/10), 30.1 (t, C-4/10), 28.7 (t, C-7), 27.1 (t, C-8), 25.2 (d, C-3′),
2.8 (t, C-3), 22.6 (q, C-4′), 20.7 (t, C-9); MS (ESI+) m/z, (%): 561
1
3
1
H-7b); C{ H} NMR (101 MHz, CDCl ): δ = 198.0 (s, C-1), 145.5
3
+
+
+
(s, C-6), 26.3 (d, C-2), 24.7 (t, C-5), 20.3 (t, C-4), 19.7 (d, C-3), 11.7
(
(
10, [2M + Na] ), 292 (100, [M + Na] ), 270 (5, [M + H] ); HRMS
ESI+) m/z: [M + Na] calcd for C H NNaO 292.1883; found:
•
+
+
(t, C-7); MS (EI) m/z, (%): 139 (93, [M] ), 122 (100, [M −
1
5
27
3
+
+
+
OH] ), 94 (28, [M − CO − OH] ), 81 (31), 67 (24, [pentadienyl] ).
Isopentyl (1S*,2R*)-2-(3-(Hydroxyimino)propyl)cyclopropane-1-
carboxylate (19d) and (1S*,6R*)-3-(hydroxyimino)bicyclo[4.1.0]-
3
1
(
(
412 mg) was distilled using a Kugelrohr apparatus to yield 169 mg
1
21%) of clear light oil, bp 80-85 °C (15 mbar). H NMR (400 MHz,
CDCl ): δ 2.29 (ddd, J = 18.3, 5.3, 3.7 Hz, 1H), 2.05 (dddd, J = 18.2,
3
1
1.5, 6.8, 0.8 Hz, 1H), 2.00−1.86 (m, 2H), 1.78−1.55 (m, 4H), 1.21
1
3
1
(
q, J = 5.3 Hz, 1H), 1.05 (ddd, J = 9.8, 8.2, 5.3 Hz, 1H); C{ H}
NMR (101 MHz, CDCl ): δ 209.5 (s), 36.8 (t), 26.0 (d), 21.4 (t),
3
1
7.9 (t), 17.6 (d), 10.3 (t).
R
J. Org. Chem. XXXX, XXX, XXX−XXX