Radical-mediated cascade

Malacria, M. (1996) Selective Preparation of Complex Polycyclic Molecules from Acyclic Precursors via Radical Mediated or Transition Metal-Catalyzed Cascade Reactions. Chemical Reviews, 96, 289-306. 

This chapter contains a survey of free-radical-mediated multicomponent reactions (MCRs), which permit the coupling of three or more components. Even though they are not technically classified as MCRs, remarkable intramolecular radical cascade processes have been developed. Some examples, such as those shown in Scheme 6.3, use an isonitrile or acrylonitrile as the intermolecular component for each reaction [6]. These examples demonstrate the tremendous power of the combination of inter- and intramolecular radical cascade processes in organic synthesis. Readers are advised to be aware of remarkable intramolecular aspects of modem radical chemistry through excellent review articles published elsewhere [1, 7]. It should also be noted that there has also been remarkable progress in the area of living radical polymerizations, but this will not be covered here. 

J. Marco-Contelles, Synthesis of polycyclic molecules via cascade radical carbocycliza-tions of dienynes the first SnPh3 radical-mediated (2 + 2 + 2] formal cycloaddition of dodeca-l,6-dien-ll-ynes, Chem. Commun. (Cambridge), (1996)2629-2630. 

INK. Antioxidants can attenuate MAPK activation, suggesting that the MAP kinase cascade, including activation of NF-kB and AP-1, is affected by ROS levels in cells. ° Activation of MAP kinases may to play a role in the pathogenesis of cancer. Application of 12-0-tetradecanoylphorbol-13-acetate (TPA), a tumor promoter, which acts through a fiee-radical-mediated mechanism, to the ears and dorsal skin of mice induced a rapid and sustained activation of ERKl/2 and p38 MAP kinase. NF-kB activation in this model was abolished by the ERKl/2 inhibitor U0126, while SB203580, a p38 inhibitor, had no effect. In human hepatoma cells, ROS-induced in cell proliferation correlated well with ERK activation, but not INK or p38. Pathways recently, p38 MAP kinase has been shown to coprecipitate with p53 and phosphoiylates p 3 93,94 p33 observed to phosphoiylate p53 when exposed to DNA-damaging... 

Pattenden, G. and Schulz, D.J. (1993) Cascade Radical Reactions in Synthesis. A New Radical Mediated Double Ring Expansion-Cyclization Process with Oxime Ethers, Tetrahedron Lett. 34, 6787-6790. 

The chemical syntheses of ( )-estrone and related steroids have attracted the attention of many organic chemists because of their promising biological activities. In this context, a variety of elegant cascade reactions have been developed during the last century. In 2004, the group of Pattenden reported a total synthesis of estrone based on a novel radical-mediated macrocyclization/transannulation cascade reaction (Scheme 13.12) [14]. 

Scheme 13.12 Total syntheses ( )-estrone (87) by using a novel radical-mediated macrocy-clization/transannulation cascade reaction.

Radical-based carbonylation procedures can be advantageously mediated by (TMSlsSiH. Examples of three-component coupling reactions are given in Reactions (74) and (75). The cascade proceeds by the addition of an alkyl or vinyl radical onto carbon monoxide with formation of an acyl radical intermediate, which can further react with electron-deficient olefins to lead to the polyfunctionalized compounds. ... 

Apart from ATRP, the concept of dual initiation was also applied to other (controlled) polymerization techniques. Nitroxide-mediated living free radical polymerization (LFRP) is one example reported by van As et al. and has the advantage that no further metal catalyst is required [43], Employing initiator NMP-1, a PCL macroinitiator was obtained and subsequent polymerization of styrene produced a block copolymer (Scheme 4). With this system, it was for the first time possible to successfully conduct a one-pot chemoenzymatic cascade polymerization from a mixture containing NMP-1, CL, and styrene. Since the activation temperature of NMP is around 100 °C, no radical polymerization will occur at the reaction temperature of the enzymatic ROP. The two reactions could thus be thermally separated by first carrying out the enzymatic polymerization at low temperature and then raising the temperature to around 100 °C to initiate the NMP. Moreover, it was shown that this approach is compatible with the stereoselective polymerization of 4-MeCL for the synthesis of chiral block copolymers. 

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