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DOI: 10.1055/s-0028-1087561
Stereoselective Synthesis of 8-Substituted 6-Azabicyclo[3.2.1]octan-3-ones
Publication History
Publication Date:
16 February 2009 (online)
Abstract
The vinylogous imide photocycloaddition-retro-Mannich-Mannich cascade leads to the stereoselective synthesis of 8-substituted azabicyclooctanones.
Key words
photochemistry - Mannich bases - annulations - asymmetric synthesis - bicyclic compounds
- 1
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2b The first total synthesis
of sarain A has recently been described:
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An improved synthesis of 22 will be reported separately.
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References and Notes
All new compounds were purified chromatographically (>95%) and were fully characterized by ¹H NMR, ¹³C NMR, IR, and HRMS.
5Compound 14 (major): ¹H
NMR (500 MHz, CDCl3, * de-notes rotamer peak): δ = 4.01
(s, 0.5 H), 3.89* (s, 0.5 H), 3.69 (s, 1.5 H), 3.68* (s,
1.5 H), 3.63 (ddd, J = 11.0, 5.3, 1.5 Hz,
0.5 H), 3.56* (ddd, 10.7, 5.0, 1.7 Hz, 0.5 H), 3.28 (d, J = 11.1
Hz, 0.5 H), 3.23* (d, J = 10.9
Hz, 0.5 H), 2.85 (ddd, J = 17.4,
2.4, 2.4 Hz, 0.5 H), 2.73* (ddd, J = 17.3,
2.2, 2.2 Hz, 0.5 H), 2.75-2.38 (m, 3), 2.34 (br s, 1 H),
2.28 (m, 1 H), 1.08 (d, J = 2.6
Hz, 1.5 H), 1.07* (d, J = 2.7 Hz, 1.5 H). ¹³C NMR
(125 MHz, CDCl3, * denotes rotamer peak): δ = 209.0, 208.8*,
155.342, 59.3, 59.2*, 52.5, 52.4*, 49.9, 49.5*,
48.9, 48.8*, 47.6, 47.1*, 43.1, 42.3*,
41.8, 41.6*, 39.6, 38.7*, 29.7, 16.6, 16.5*.
IR (neat): 2957, 1701, 1452, 1387, 1191, 1114 cm-¹.
HRMS (CI): m/z calcd for C10H15NO3 [M+]: 197.1052;
found: 197.1056.
Compound 15 (minor): ¹H
NMR (500 MHz, CDCl3, * de-notes rotamer peak): δ = 4.13
(s, 0.5 H), 4.03* (s, 0.5 H), 3.67 (s, 1.5 H), 3.65* (s,
1.5 H), 3.50 (m, 0.5 H), 3.46* (m, 0.5 H), 3.33 (d, J = 10.6 Hz,
0.5 H), 3.28* (d, J = 10.4,
0.5 H), 2.72 (d, J = 17.8
Hz, 0.5 H), 2.61 (m, 1.5 H), 2.32-2.44 (m, 3 H), 1.22 (d, J = 3.0 Hz,
1.5 H), 1.21 (d, J = 3.0 Hz, 1.5 H). ¹³C
NMR (125 MHz, CDCl3): δ = 208.9, 208.8*,
155.0, 154.9*, 56.4, 56.3*, 52.9, 52.6*,
52.4, 52.3*, 43.1, 43.0*, 42.3, 41.8*,
37.7, 37.4*, 36.9, 36.8*, 11.4, 11.3*.
IR (neat): 2960, 2921, 2853, 1705, 1451, 1393, 1350, 1311, 1258, 1190,
1118 cm-¹. ESI-HRMS: m/z calcd
for C10H14NO3 [MH+]:
198.1130; found: 198.1123.
Compound 28: ¹H
NMR (500 MHz, CDCl3, * denotes rotamer peak): δ = 4.00
(d, J = 4.2
Hz, 0.5 H), 3.89 (m, 2.5 H), 3.76 (m, 2 H), 3.73 (s, 3 H), 3.69
(s, 3 H), 3.67 (d, J = 10.9 Hz, 0.5 H),
3.61 (d, J = 10.9
Hz, 0.5 H), 3.41 (m,
1 H), 2.83 (br, 1 H), 1.80-2.14
(m, 4 H), 1.31 (s, 3 H). ¹³C NMR (125
MHz, CDCl3, * denotes rotamer peak): δ = 174, 155.7,
107.0, 64.2, 63.2, 58.9, 58.8*, 53.1, 52.4*, 52.2,
51.9, 48.1, 47.9*, 39.5, 38.7*, 38.3, 38.0*,
36.4, 35.2*, 22.4, 22.3*. IR (neat): 2955, 2885,
1700, 1451, 1389, 1195, 1116, 1062, 1023 cm-¹.
HRMS (CI): m/z calcd for C14H21NO6 [MH+]:
300.1447; found: 300.1445.