Radical intramolecular

R = H) undergoes a variety of enzyme-catalyzed free-radical intramolecular cyclization reactions, followed by late-stage oxidations, eliminations, rearrangements, and O- and N-alkylations. Working from this generalization as an organizing principle, the majority of known AmaryUidaceae alkaloids can be divided into eight stmctural classes (47). 

Analogously silylated cyclohexadiene 25 having propargyl alcohol as a pendant was used in the radical intramolecular hydrosilylation followed by ionic ring opening to provide alcohol 26 in 55 % yield (Scheme 6.6) [6]. The cyclization of silyl radical 27 to radical 28 represents an example of a 5-endo-dig process. 

The synthesis of oxygen heterocycles in which cyclization onto a pendant alkyne is a key step has also been achieved. Reaction (7.36) shows an example of iodoacetal 29 cyclization at low temperature that afforded the expected furanic derivative in moderate Z selectivity [47]. A nice example of Lewis acid complexation which assists the radical cyclization is given by aluminium tris(2,6-diphenyl phenoxide) (ATPH) [48]. The (3-iodoether 30 can be com-plexed by 2 equiv of ATPH, which has a very important template effect, facilitating the subsequent radical intramolecular addition and orienting the (TMS)3SiH approach from one face. The result is the formation of cyclization products with Z selectivity and in quantitative yield (Reaction 7.37). 

Sonochemically induced cation-radical intramolecular cyclization on action of an iodo-nium salt was also demonstrated (Arizawa et al. 2001). Being oxidized with phenyliodonium bis(trifluoroacetate), l-(3-anisyl)-2-(l,3-cyclohexadien-2-yl) ethane formed the cation-radical and then 5 -methoxyspiro[cycloxehane-l,T-indan]-2,6-dione. The yield of this final product was high enough. 

Radical intramolecular cyclization of ethylene mercaptans leads to thiophene as well as thietane derivatives. ... 

As Scheme 44 exemplifies, the radical intramolecular aminocarbonylation of alkynes 326 and 327 and an azaenyne 328 afforded the corresponding Q-methylene lactams (329, 330 and 331, respectively) in moderate to good yields.i i "... 

S. Velazquez, S. Huss, and M.-J. Camarasa, Stereoselective synthesis of [3.3.0] fused lactones (y-butyrolactones) of sugars and nucleosides by free radical intramolecular cyclization, J. Chem. Soc. Chem. Commun. p. 1263 (1991). 

This chapter begins with an introduction to the basic principles that are required to apply radical reactions in synthesis, with references to more detailed treatments. After a discussion of the effect of substituents on the rates of radical addition reactions, a new method to notate radical reactions in retrosynthetic analysis will be introduced. A summary of synthetically useful radical addition reactions will then follow. Emphasis will be placed on how the selection of an available method, either chain or non-chain, may affect the outcome of an addition reaction. The addition reactions of carbon radicals to multiple bonds and aromatic rings will be the major focus of the presentation, with a shorter section on the addition reactions of heteroatom-centered radicals. Intramolecular addition reactions, that is radical cyclizations, will be covered in the following chapter with a similar organizational pattern. This second chapter will also cover the use of sequential radical reactions. Reactions of diradicals (and related reactive intermediates) will not be discussed in either chapter. Photochemical [2 + 2] cycloadditions are covered in Volume 5, Chapter 3.1 and diyl cycloadditions are covered in Volume 5, Chapter 3.1. Related functional group transformations of radicals (that do not involve ir-bond additions) are treated in Volume 8, Chapter 4.2. 

The extension of the above radical intramolecular cyclization of /V-haloaryl-p-lactams to 2-azetidinones bearing the proradical center at C3 was also explored. The treatment of haloarenes 109a-c under similar conditions for the preparation of benzocarbapenems and benzocarbacephems 104—108 gave the fused tricyclic (1-lactams llOa-c (Scheme 37, Table 2). Compounds 110a and 110b were obtained as mixtures of diastereomers, which are epimers at the newly formed C5 stereocenter, while the amino derivative 110c could be prepared as a single isomer. 

The C(2)-C(3) olefin of a l,4-benzodiazepin-5-one regiospecifically captured an alkyl radical intramolecularly in a 5-f vo-/r/g-proccss that is the critical step in an approach to the constmction of the fused tricyclic system found in the pyrrolo[2,l-f][l,4]benzodiazepine class of antitumor antibiotic. Treatment of the alkyl bromide 46 with Bu3SnH afforded the tricyclic product 47 in 90% yield, a reaction that proceeded with equal efficiency with the alkoxy aryl ring substituents found in the naturally occurring ( )DC-81 (Scheme 18) <19990L1835>. 

Rauk A, Armstrong DA, Berges J (2001) Glutathione radical intramolecular H abstraction by thiyl radical. Can J Chem 79 405-417... 

The radical intramolecular cyclization of a-anilino-oi-(chloromethylcarbonyl)phenylacetonitriles 150 is induced by tri- -butyltinhydride/azoisobutyronitrile to afford l-aryl-2-cyano-2-phenylazetidin-3-ones 151 (Equation 34) <1997JCM254>. 

Cyclization of the enediynes 221 (X = 0 and CH2) in DMF were brought about by potassium carbonate and potassium iodide. The thermal stability of the cyclized products 222 (X = 0 and CH2) was evident and the occurrence of a radical intramolecular cyclization process at higher temperatures was shown <1996CG749>. 

An intramolecular radical cyclization on carbohydrate derivatives was the method developed by Lundt and Homeman in a highly stereocontrolled synthesis of functionalized cyclopentanes [9]. Due to the neutral conditions required for the cyclization step, which prevented competing side reactions such as P-elimination and base-promoted epimerization, the potential of the employed radical intramolecular reaction versus the classical carbanionic carbon-carbon bond forming reactions was demonstrated. 

Free-radical intramolecular cyclization in synthesis of heterocycles 93 KGS1011. 

So far, two different mechanisms of single strand break formation based on adiabatically stable anions have been proposed. The first mechanism, suggested by the Leszczynski group, assumes the formation of stable anions of 3 - and 5 -phosphates of thymidine and cytidine in which the cleavage of the C-O bond take place via the SN2-type process. The second reaction sequence, proposed by us, starts from the electron induced BFPT process followed by the second electron attachment to the pyrimidine nucleobase radical, intramolecular proton transfer, and the C-O bond dissociation. In both mechanisms the bottleneck step is associated with very low kinetic barrier which enables the SSB formation to be completed in a time period much shorter than that required for the assay of damage. 

A The initial reaction produces the diazonium salt from the amino group of the substituted benzophenone. In the presence of Ciu warming results in the loss of nitrogen and the generation of an aryl radical. Intramolecular attack at the ortfw position of the adjacent phenyl ring yields the tricyclic molecule fluorenone (Scheme 8,21),... 

Norrish type II It is a non-radical intramolecular process. The abstraction of a H-atom from the y-carbon results in its subsequent decomposition into an olefin... 

Chow, Y. L., Mojelsky, T. W., Magdzinski, L. J., Tichy, M. Chemistry of amidyl radicals. Intramolecular hydrogen abstraction as related to amidyl radical configurations. Can. J. Chem. 1985, 63, 2197-2202. 

Trapping the carbon-centred radical intramolecularly, particularly with an alkene, has been used extensively in organic synthesis. This valuable strategy has found many important apphcahons for the preparahon of carbocyclic and heterocyclic natural products. Intramolecular reachons are inherently more favourable than the corresponding intermolecular reachons due to entropic factors and are typically fast processes that provide a a-bond at the expense of a ir-bond. 

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