Cyclization, radicals metal catalyzed

The use of hydrogen as terminal reductant has been accomplished by its activation with transition metal complexes. The resulting weak M-H bonds can be used in both radical generation and reduction through HAT. In this manner, conceptually novel radical chain reactions, such as hydrogen mediated cyclizations, or metal catalyzed processes with coupled catalytic cycles for radical generation and reduction, have been realized. The latter transformations are especially attractive for enantioselective synthesis. 

A review for radical cyclizations inclviding metal catalyzed systems B. Giese, B. Kop-ping, T. Gobel, f. Dickhaut, G. Thoma,... 

Organic halides play a fundamental role in organic chemistry. These compounds are important precursors for carbocations, carbanions, radicals, and carbenes and thus serve as an important platform for organic functional group transformations. Many classical reactions involve the reactions of organic halides. Examples of these reactions include the nucleophilic substitution reactions, elimination reactions, Grignard-type reactions, various transition-metal catalyzed coupling reactions, carbene-related cyclopropanations reactions, and radical cyclization reactions. All these reactions can be carried out in aqueous media. 

To achieve low radical concentrations, most radical reactions are traditionally performed as chain reactions. Atom or group transfer reactions are one of the two basic chain modes. In this process the atom or group X is the chain carrier. A metal complex can promote such chain reactions in two ways. On one hand, the catalyst acts only to initiate the chain process by generating the initial radical 29A from substrate 29 (Fig. 10). This intermediate undergoes the typical radical reactions, such as additions or cyclizations leading to radical 29B, which stabilizes to product 30 by abstracting the group X from 29. A typical example is the use of catalytic amounts of cobalt(II) salts in oxidative radical reactions catalyzed by /V-hydroxyphthalimide (NHPI), which is the chain carrier [102]. 

Transition-metal catalyzed tandem hydrosilylation/cyclization of dienes is a well known process, hi order to render this reaction environmentally benign, Studer developed metal-free conditions using a silylated cyclohexadi-ene reagent 114 (Scheme 33) [108-110]. Thereby, the silyl radical released upon rearomatization of radical intermediate 115 reacts with a diene to form a /1-silyl radical 116, which undergoes cyclization into 117. Reduction of 117 with cyclohexadiene 114 affords again 115, as well as 118, thus allowing for... 

This catalytic sequence is known as Kharasch addition or atom transfer radical addition (ATRA) [4]. Various polyhalogenated compounds such as CCI4 and CCI3CO2R are used as the organic halides, and transition metal salts or complexes are used as the catalyst [3]. Intramolecular version of the Kharasch addition reaction (atom transfer radical cyclization, ATRC) has opened novel synthetic protocols to the synthesis of carbocyde or heterocyles catalyzed by transition metals [5-7], and this has become a very important field in free radical cydization in organic synthesis. Transition metal-catalyzed Kharasch reactions sometimes afford telomers or poly-... 

Reduction of alkylidene malonates (60) in MeOH in an undivided cell using alkali metal halides as supporting electrolytes results in the unusual formation of 3,4-disubsti-tuted 1,1,2,2-cyclobutanetetracarboxylates, 61 [141]. Cyclobutane formation requires 4-7 F and is not a radical anion-catalyzed cycloaddition. The process was explained by the mechanism in Scheme 11, where the cyclization takes place by chemical oxidation of the... 

Nagashima, H., Wakamatsu, H., Ozaki, N., Ishii, T., Watanabe, M., Tajima, T., Itoh, K. Transition metal catalyzed radical cyclization new preparative route to y-lactams from allylic alcohols via the [3.3]-sigmatropic rearrangement of allylic trichloroacetimidates and the subsequent ruthenium-catalyzed cyclization of N-allyltrichloroacetamides. J. Org. Chem. 1992, 57, 1682-1689. 

Radical- and metal-catalyzed cyclizations play an important role in the synthesis of benzazepines. Although the product radical has no stabilizing features, treatment of the pentenylamides (164 ... 

Negishi, E.-i., Ma, S., Sugihara, T. and Noda, Y. (1997) Synthesis of hydrazulenes via Zr-promoted bicyclization of enynes and transition metal-catalyzed or radical cyclization of alkenyl iodides. Efficient synthesis of ( )-7-e/n -)3-bulnesene. J. Org. Chem., 62,1922-3. 

Free-radical cyclization in the synthesis of N-heterocycles 97T17543. N-Heterocycles based on aromatic unsaturated ketones 98MI13. N-Heterocycles, formation in transition metal-catalyzed eiyne metathesis 98YGK433. 

Nagasbima H, Ozaki N, Ishii M, Seki K, Washiyama M, Itoh K. Transition metal-catalyzed radical cyclizations a low-temperature process for the cyclization of N-protected N-allyltrichloroacetamides to trichlorinated y-lactams and applications to the stereoselective preparation of P,7-disubstituted y-lactams. J. Org. Chem. 1993 58(2) 464— 470. 

Another synthetic application starting with functionalized alkynes is the tandem addition-cyclization process. Such processes in the presence of radical initiators have been reported. The first metal-catalyzed version is exemplified by the following experiments [22] thus, when 1,6-heptadiyne is treated with HP(0)(0Me)2 in the presence of Pd(OAc)2 and dppben [l,2-bis(diphenylphosphino)benzene] at 130 C, cyclized product 8 is formed in 76% yield (Scheme 17). N, A -dipropargyl-p-tosylamide reacts similarly, but the major product is pyrrole derivative 9 due to extensive double bond isomerization. Extensimi to //-phosphinate and sec-phosphine oxide is also... 

The converse situation in which ring closure is initiated by the attack of a carbon-based radical on the heteroatom has been employed only infrequently (Scheme 18c) (66JA4096). The example in Scheme 18d begins with an intramolecular carbene attack on sulfur followed by rearrangement (75BCJ1490). The formation of pyrrolidines by intramolecular attack of an amino radical on a carbon-carbon double bond is exemplified in Scheme 19. In the third example, where cyclization is catalyzed by a metal ion (Ti, Cu, Fe, Co " ), the stereospecificity of the reaction depends upon the choice of metal ion. 

By contrast, for iodide 18 having the triple bond activated by a phenyl group, conversion to the cyclic organozinc species 25 occurred effectively and the latter could be efficiently functionalized, provided that traces of moisture were excluded by pre-treatment of zinc powder with Mel. The substituted benzylidene cyclopentanes 26 and 27 were respectively obtained after iodinolysis and palladium-catalyzed cross-coupling reaction with benzoyl chloride (equation 10). However, it could not be assessed whether the formation of organozinc 25 was attributable to an anionic or a radical cyclization pathway (or both) as, had iodide 26 been produced by a radical iodine atom-transfer, it would have been converted to 25 by reaction with metallic zinc due to the presence of the activating phenyl group21. 

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