Cascade radical cyclization

Cascade Radical Cyclizations of Biradicals Generated from Enyne-Allenes 1119... 

Scheme 20.46 Cascade radical cyclization leading to an indan derivative.

Scheme 40 Preparation of tricyclic p-lactams 116 and 119 using cascade radical cyclization...

Cascade radical cyclization of A-chloro-A -allyl ( )-4,7-octadienamine 6 in the presence of titanium(lll) chloride gave in high yield (GC) a mixture of the bicyclic compounds 7 (two unseparable diastereomers with undetermined configuration) and the tricyclic compounds 8 (two diastereomers) in which the cis-syn-cis azatriquinane structure predominated14,0. The product 8 was obtained pure after column chromatography and its structure was assigned by high field ]H NMR. 

Wang, K. K. Cascade Radical Cyclizations via Biradicals Generated from Enediynes, Enyne-Allenes, and Enyne-Ketenes. Chem. Rev. 

Haney, B.P., and Curran, D.P., Round trip radical reactions from acyclic precursors to tricy-clo[5.3.1.0 - ]undecanes. A new cascade radical cyclization approach to ( )-isogymnomitrene and ( )-gymnomitrene, J. Org. Chem., 65, 2007, 2000. 

Zhang, J., and Xu, X., Total synthesis of 6-ep/-sarsolilide A, Tetrahedron Lett., 41, 941, 2000. Boehm, H.M.. I landa, S., Pattenden, G., Roberts. L.. Blake, A.J., and Li, W.-S., Cascade radical cyclizations leading lo steroid ring constructions. Regio- and stereo-chemical studies using ester- and fluoroalkene substituted polyene acyl radical intermediates.,/. Chem. Soc., Perkin Trans. 1, 3522, 2000. Hampton, A.. Sasaki, T, and Paul, B., Synthesis of 6 -cyano-6 -deoxyhomoadenosine-6 -phosphonic acid and its phosphoryl and pyrophosphoryl anhydrides and studies of their interactions with adenine nucleotide utilizing enzymes, J. Am. Chem. Soc.. 95. 4404, 1973. 

Hollingworth, G. J., Pattenden, G. and Schulz, D. J. (1995) Cascade Radical Cyclization-Fragmentation-Transannular-Ring Expansion Reactions Involving Oximes. A New Approach to Synthesis of Angular Triquinanes, Aust. J. Chem. 48, 381-399. 

Synthesis and Cascade Radical Cyclizations of Enyne-Alienes... 

Scheme 5. Cascade Radical Cyclization of Biradicals from Enyne-Allenes.

In Stephenson s work, the double cyclization product 90 was also obtained in good yields as a single diastereoisomer (Eq. (13.8)). This cascade radical cyclization strategy was also used by other groups for the efficient syntheses of oxindoles (Eq. (13.9)) [28] and 6-trifuoromethyl phenanthridines (Eq. (13.10)) [29]. 

To explain the transformation of anilide 14 into tetracyele 15 we should follow the different steps of the mechanism previously discussed. SET from the anilide to the IBX-THF oxidant reagent leads to radical cation 16 that after loss of a proton will be transformed into radical 17. Cyclization into the C=C double bond will lead to cyclic radical 18. At this point, the reaction could end by capture of a hydrogen atom. However, in this ease, vinylcyclopropane radieal 18 is transformed into benzylie radieal 19 by rupture of flie adjacent cyclopropyl ring. Oxidation of this radical in the reaction medium (IBX-THF) leads to cation 20 which cyclizes to 22 (the cyclization is better understood via canonical form 21). Finally, rearomatiza-tion and loss of a proton in 22 yields the observed product 15. The overall reaction is a cascade radical cyclization (Scheme 39.8). 

A new synthetic pathway to generate the chlorosubstituted benzoenyne-allenes in situ for the subsequent cascade radical cyclizations was established. This pathway was adopted for the preparation of the C44H26 hydrocarbon having a carbon framework represented on the surface of Cgo. Using different combinations of benzoenediynes and diaryl ketones for condensation, it is possible that a variety of other polycyclic aromatic hydrocarbons could also be likewise synthesized [280]. 

Wang, K.K. (1996) Cascade radical cyclizations via biradicals generated from enediynes, enyne-allenes, and enyne-ketenes. Chemical Reviews, 96(1), 207-222. 

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