References
For reviews on radical cyclizations, see:
1a
Ikeda M.
Sato T.
Ishibashi H.
Rev. Heteroatom Chem.
1998,
18:
169
1b
Jasperse CP.
Curran DP.
Fevig TL.
Chem. Rev.
1991,
91:
1237
1c
Curran DP.
Synthesis
1988,
417 ; and references cited therein
For two recent syntheses of histrionicotoxin, see:
2a
Williams GM.
Roughley SD.
Davies JE.
Holmes AB.
Adams JP.
J. Am. Chem. Soc.
1999,
121:
4900
2b
Davison EC.
Fox ME.
Holmes AB.
Roughley SD.
Smith CJ.
Williams GM.
Davies JE.
Raithby PR.
Adams JP.
Forbes IT.
Press NJ.
Thompson MJ.
J. Chem. Soc., Perkin Trans. 1
2002,
12:
1494 ; and references therein
For recent syntheses of cephalotaxine, see:
3a
Kuehne ME.
Bornmann WG.
Parsons WH.
Spitzer TD.
Blount JF.
Zubieta J.
J. Org. Chem.
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53:
3439
3b
Ikeda M.
Okano M.
Kosaka K.
Kido M.
Ishibashi H.
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276
3c
Isono N.
Mori M.
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115 ; and references cited therein
4a
Ishibashi H.
Kameoka C.
Sato T.
Ikeda M.
Synlett
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4b
Ishibashi H.
Kameoka C.
Kodama K.
Ikeda M.
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489
5 All new compounds were fully characterized by 1H NMR, 13C NMR, MS, HRMS, IR and elemental analyses. The yields are based on isolated, purified (flash chromatography on silica gel) products. A print or word file of the characterization data for all new compounds in this paper can be obtained on request from MC.
6
Middleton DS.
Simpkins NS.
Terrett NK.
Tetrahedron Lett.
1989,
30:
3865
7 Crystallographic data of 6a, 6b, 8, 13 and 15 have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication no. CCDC 241704 (6a), 241705 (6b), 241706 (8), 241707 (13) and 241708 (15), respectively. Copies of these data may be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, by emailing data_request@ccdc.cam.ac.uk, or by contacting The Cambridge Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ, UK; fax: +44 (1223)336033.
8
Representative Procedure for the Preparation of the Cyclization Precursors: (1
S
,4
R
)-4,7,7-Trimethyl-3-oxo-2-oxa-bicyclo[2.2.1]heptane-1-carboxylic acid (3-oxo-cyclopent-1-enyl)-(4-phenylselenyl-butyl)-amide (12).
In a typical experiment, vinylogous amide 9
[6]
(700 mg, 2.27 mmol) was dissolved in anhyd THF (15 mL) and cooled to -78 °C. This solution was treated with a solution of 1.6 M BuLi in hexane (1.56 mL, 2.50 mmol) and stirring was continued for 2 h at this temperature. Finally a solution of (1S)-(-)-camphanic chloride (786 mg, 3.63 mmol) in anhyd THF (5 mL) was added and the mixture was allowed to warm up to r.t. over a period of 15 h. The solvent was evaporated in vacuo and the residue was purified by subsequent flash chromatography on silica gel (Et2O) to yield the pure enaminone 12 (1.02 g, 92%) as a colorless oil; Rf (Et2O) = 0.37; [α]D
20 -193.6 (c 1.00, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 0.96 (s, 3 H), 1.11 (s, 3 H), 1.19 (s, 3 H), 1.69-1.77 (m, 3 H), 1.84 (dd, J = 4.9 Hz, J = 10.2 Hz, 2 H), 1.94-2.04 (m, 2 H), 2.43 (dq, J = 4.2 Hz, J = 10.6 Hz, 2 H), 2.48 (qui, J = 6.3 Hz, 1 H), 2.72-2.76, 3.28-3.32 (m, 2 H), 2.89-2.95 (m, 2 H), 3.65-3.70, 3.77-3.81 (m, 2 H), 5.74 (s, 1 H), 7.24-7.28 (m, 3 H), 7.47-7.49 (m, 2 H). 13C NMR (100 MHz, CDCl3): δ = 9.56 (q), 16.56 (q), 17.65 (q), 26.97 (t), 26.98 (t), 28.36 (t), 29.44 (t), 30.02 (t), 32.56 (t), 34.61 (t), 48.14 (t), 54.01 (s), 56.51 (s), 92.31 (s), 117.66 (d), 126.95 (d), 129.08 (d), 129.64 (s), 132.75 (d), 169.59 (s), 173.46 (s), 177.22 (s), 206.77 (s). MS (EI): m/z (%) = 489 (35)[M+], 487 (17) [M+], 332 (100), 304 (24), 222 (21), 152 (31), 83 (70), 55 (36). HRMS (EI): m/z calcd for C25H31NO4
78Se: 487.1426, found: 487.1426; C25H31NO4
80Se: 489.1418, found: 489.1420. IR (neat): ν = 2969, 2935, 1792, 1682, 1575, 1386, 1375, 1110, 1053 cm-1. Anal. Calcd for C25H31NO4Se: C, 61.47; H, 6.40; N, 2.87. Found: C, 61.31; H, 6.51; N, 2.66.
9
Typical Procedure for the Cyclizations: (1
S
,4
R
,5a
R
,8a
S
)-1-(4,7,7-Trimethyl-3-oxo-2-oxa-bicyclo[2.2.1]heptane-1-carbonyl)-octahydro-cyclopenta[
b
]azepin-6-one (13).
The vinylogous amide 12 (2.54 g, 5.2 mmol) was dissolved in degassed anhyd toluene (210 mL) under an argon atmosphere and brought to a steady reflux. A solution of Bu3SnH (1.96 mL, 7.3 mmol) and ACN (889 mg, 3.6 mmol) in degassed anhyd toluene (50 mL) was added to the refluxing enaminone solution at a rate of 5 mL/h using a syringe pump. After the addition of the tin hydride solution was complete, the reaction mixture was cooled to r.t., and the solvent was removed under reduced pressure. The residue was purified by subsequent flash chromatography on silica gel (pentane-Et2O, 1:1, then Et2O) to give the pure octahydrocyclopenta[b]azepine 13 (763 mg, 44%) as a single stereoisomer as colorless crystals; mp 145.9 °C; Rf (Et2O) = 0.40; [α]D
20 -16.9 (c 1.00, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 1.04 (s, 3 H), 1.12 (s, 3 H), 1.19 (s, 3 H), 1.27-1.31 (m, 2 H), 1.35 (q, J = 10.8 Hz, 1 H), 1.49 (dd, J = 9.2 Hz, J = 11.3 Hz, 1 H), 1.73 (dq, J = 4.1 Hz, J = 9.2 Hz, 1 H), 1.87-1.96 (m, 2 H), 1.99-2.03 (m, 1 H), 2.06-2.09 (m, 1 H), 2.23-2.28 (m, 1 H), 2.29 (d, J = 9.0 Hz, 1 H), 2.41-2.45 (m, 2 H), 2.52 (dd, J = 9.0 Hz, J = 19.5 Hz, 1 H), 2.71 (dq, J = 5.4 Hz, J = 12.4 Hz, 1 H), 3.16 (dd, J = 6.0 Hz, J = 9.9 Hz, 1 H), 4.17 (dq, J = 5.5 Hz, J = 13.7 Hz, 1 H), 4.55 (dd, J = 6.3 Hz, J = 9.5 Hz, 1 H). 13C NMR (100 MHz, CDCl3): δ = 9.62 (q), 16.76 (q), 17.68 (q), 25.37 (t), 27.20 (t), 27.33 (t), 29.31 (t), 31.44 (t), 32.26 (t), 36.24 (t), 44.32 (t), 53.70 (s), 54.13 (d), 55.29 (s), 62.50 (d), 92.56 (s), 167.34 (s), 178.60 (s), 213.09 (s). MS (EI): m/z (%) = 333 (56) [M+], 274 (90), 152 (100), 136 (57), 109 (31), 83 (55), 55 (38). HRMS (EI): m/z calcd for C19H27NO4: 333.1940; found: 333.1942. IR (neat): ν = 3456, 2957, 2935, 2849, 1786, 1747, 1732, 1626, 1427, 1101 cm-1. Anal. Calcd for C19H27NO4: C, 68.44; H, 8.16; N, 4.20. Found: C, 68.40; H, 8.18; N, 4.28.
