Subscribe to RSS
DOI: 10.1055/s-2005-865236
Concise Synthesis of the Tricyclic Skeleton of Cylindricines Using a Radical Cascade Involving 6-Endo Selective Cyclization
Publication History
Publication Date:
14 April 2005 (online)
![](https://www.thieme-connect.de/media/synlett/200507/lookinside/thumbnails/10.1055-s-2005-865236-1.jpg)
Abstract
On treatment with Bu3SnH and azobis(cyclohexanecarbonitrile) (ACN), enamide 19 underwent a 6-endo-trig/5-endo-trig radical cascade to afford perhydropyrrolo[2,1-j]quinoline derivative 21, a cylindricine skeleton.
Key words
cyclizations - cylindricine - regioselectivity - radical cascade - acyl radical
-
1a
Blackman AJ.Li C.Hockless DCR.Skelton BW.White AH. Tetrahedron 1993, 49: 8645 -
1b
Li C.Blackman AJ. Aust. J. Chem. 1994, 47: 1355 -
1c
Li C.Blackman AJ. Aust. J. Chem. 1995, 48: 955 - 2
Biard JF.Guyot S.Roussakis C.Verbist JF.Vercauteren J.Weber JF.Boukef K. Tetrahedron Lett. 1994, 35: 2691 - Total synthesis of cylindricines:
-
3a
Snider BB.Liu T. J. Org. Chem. 1997, 62: 5630 -
3b
Liu JF.Heathcock CH. J. Org. Chem. 1999, 64: 8263 -
3c
Molander GA.Ronn M. J. Org. Chem. 1999, 64: 5183 -
3d
Trost BM.Rudd MT. Org. Lett. 2003, 5: 4599 -
3e
Canesi S.Bouchu D.Ciufolini MA. Angew. Chem. Int. Ed. 2004, 43: 4336 -
3f
Arai T.Abe H.Aoyagi S.Kibayashi C. Tetrahedron Lett. 2004, 45: 5921 -
3g
Liu J.Hsung RP.Peters SC. Org. Lett. 2004, 6: 3989 - Total synthesis of lepadiformine:
-
4a
Greshock TJ.Funk RL. Org. Lett. 2001, 3: 3511 -
4b
Abe H.Aoyagi S.Kibayashi C. J. Am. Chem. Soc. 2000, 122: 4583 -
4c
Abe H.Aoyagi S.Kibayashi C. Angew. Chem. Int. Ed. 2002, 41: 3017 -
4d
Sun P.Sun C.Weinreb SM. J. Org. Chem. 2002, 67: 4337 ; see also ref. 3g - We previously reported that radical-induced 7-endo-trig/5-endo-trig radical cascade gave a cephalotaxine skeleton. See:
-
5a
Taniguchi T.Ishita A.Uchiyama M.Tamura O.Muraoka O.Tanabe G.Ishibashi H. J. Org. Chem. 2005, in press - See also:
-
5b
Ishibashi H.Sato T.Ikeda M. Synthesis 2002, 695 -
5c
Ishibashi H.Ishita A.Tamura O. Tetrahedron Lett. 2002, 43: 473 - Reviews on radical cascade:
-
6a
McCarroll AJ.Walton JC. Angew. Chem. Int. Ed. 2001, 40: 2224 -
6b
McCarroll AJ.Walton JC. J. Chem. Soc., Perkin Trans. 1 2001, 3215 - 7
Grillot A.-L.Hart DJ. Tetrahedron 1995, 51: 11377 - 8
Booth H.Griffiths V. J. Chem. Soc., Perkin Trans. 2 1975, 111 - Reviews on the synthesis of five- and six-membered heterocyclic compounds using radical cyclization:
-
10a
Majumdar KC.Mukhopadhyay PP.Basu PK. Heterocycles 2004, 63: 1903 -
10b
Li JJ. Alkaloids: Chemical Perspectives Vol. 5:Pelletire SW. Wiley; New York: 2001. Chap. 4. - 13 Radical reactions of some sterically fixed 3-bromo-N-(cyclohex-1-enyl)propionamides, which are closely related to compound 8, leading to the formation of 6-endo cyclization product or a mixture of 6-endo and 5-exo cyclization products have been reported. See:
Schultz AG.Guzzo PR.Nowak DM. J. Org. Chem. 1995, 60: 8044 - 14 An analogous example on the aryl radical cyclization:
Ishibashi H.Kato I.Takeda Y.Kogure M.Tamura O. J. Chem. Soc., Chem Commun. 2000, 1527 -
15a
Aubé J.Milligan GL. J. Am. Chem. Soc. 1991, 113: 8965 -
15b
Hunter R.Richards P. Synlett 2003, 271 - A review on acyl radical:
-
17a
Chatgilialoglu C.Crich D.Komatsu M.Ryu I. Chem. Rev. 1999, 99: 1991 - Leading references on acyl radical cyclizations:
-
17b
Wong LS.-M.Sherburn MS. Org. Lett. 2003, 5: 3603 -
17c
Yoshikai K.Hayama T.Nishimura K.Yamada K.Tomioka K. J. Org. Chem. 2005, 70: 681 - 18
Masamune S.Hayase Y.Schilling W.Chan WK.Bates GS. J. Am. Chem. Soc. 1977, 99: 6756
References
The structure of compound 9 was determined by its 13C NMR spectrum, which showed the presence of a quaternary carbon atom (δ = 66.3 ppm).
11Enamide 10 was synthesized by treatment of the imine, prepared from ethylamine and cyclohexanone, with 3-bromopropionyl chloride in the presence of NaHCO3.
1213C NMR spectrum of compound 11 showed the presence of a quaternary carbon atom (δ = 64.0 ppm) and the IR spectrum of 11 exhibited absorption at 1665 cm-1 due to the five-membered lactam.
16Crystallographic data of 13 and 21 have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication no. CCDC 262989 (13) and 262990 (21), 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.
19The structure of compound 20 was confirmed by transforming it to compound 8 by removal of the carbonyl group of the ketone.
20(7a S *,11a S *)-Octahydro-3 H -pyrrolo[2,1- j ]quinoline-3,7 (7a H )-dione ( 21). To a boiling solution of 19 (530 mg, 1.46 mmol) in toluene (70 mL) was added dropwise a solution of Bu3SnH (649 mg, 2.20 mmol) and ACN (71.5 mg, 0.292 mmol) in toluene (70 mL) over 3 h using a syringe pump. The reaction mixture was cooled to r.t. and the solvent was removed under reduced pressure. The residue was purified by flash chromatography on silica gel (hexane-EtOAc, 1:1) to give 21 (113 mg, 37%) as colorless crystals; mp 106-107 °C (hexane). IR (CHCl3): ν = 1715, 1680 cm-1. 1H NMR (270 MHz, CDCl3): δ = 1.19-1.79 (m, 9 H), 2.00 (td, J = 8.3, 13.5 Hz, 1 H), 2.16 (ddd, J = 6.6, 8.3, 13.5 Hz, 1 H), 2.25-2.31 (m, 1 H), 2.33-2.53 (m, 3 H), 3.04 (ddd, J = 6.3, 10.2, 13.5 Hz, 1 H), 4.38 (ddd, J = 2.3, 6.3, 13.5 Hz, 1 H). 13C NMR (67.8 MHz, CDCl3): δ = 20.5, 21.7, 22.3, 29.0, 29.4, 32.4, 35.0, 39.7, 55.2, 64.6, 173.1, 207.3. Anal. Calcd for C12H17NO2: C, 69.54; H, 8.27; N, 6.76. Found: C, 69.31; H, 8.42; N, 6.61.