Radical cyclization forming five-membered

The strong preference for cyclization in the indicated manner in both sensitized reactions lends support to the view that cycloaddition reactions of triplets involve two steps with the intermediate formation of biradicals. It has recently been shown290 that cyclization of free radicals forms five-membered rings in preference to six-membered rings. 

If fragmentation of the radical cation from 25 afforded radical 26 then five-membered ring products derived from intramolecular cyclization of this radical should be formed. Treatment of 25 with thianthrene radical cation gave 27-29,... 

Six-substituted pyrrolizidinones may also be stereoselectively constructed via the radical cyclization of iV-allyliodolactams75. In all cases the reaction with tributyltin hydride gives only the diastereomer with the ring junction fw/s-orientated with respect to the substituent in the newly formed five-membered ring. 

Radicals of the type 9, generated in other ways, also undergo these cyclizations. Both five- and six-membered rings can be formed in these reactions (see p. 985). 

Intramolecular enone-alkene cycloadditions are also possible. In the case of (3-(5-pentenyl) substituents, there is a general preference for exo-type cyclization to form a five-membered ring.195 This is consistent with the general pattern for radical cyclizations and implies initial bonding at the (3-carbon of the enone. 

The following syntheses of five-membered carbocyclic systems involve radical-induced epoxide fragmentation with radical translocation and cyclization. The resulting bicyclic alcohols are formed as a mixture of two epimeric esters with cw-fused rings.[71]... 

Vinyllithium cyclizations. The vinyl lithiums formed from trisylhydrazones (9, 486) can participate in intramolecular cyclizations. This anionic cyclization is presently limited to formation of five-membered rings. It has the advantage of greater stereoselectivity than a corresponding radical cyclization. 

The radical produced from the oxidative decarboxylation may also be trapped intramolecularly to form five- and six-membered rings (Scheme 17). The Kolbe protocol avoids the use of the toxic organ-otin reagents that are commonly used in the formation of radicals. Moreover, when alkyltin hydride reagents are used, a C—H bond is formed. The Kolbe reaction protocol, on the other hand, allows the radical formed after cyclization to be captured by a different radical in a coelectrolysis experiment, rather than being reduced. This tandem sequence of events has been exploited in the construction of prostaglandin precursor (70) [37-41]. Here, the cyclized... 

The endo-mode of cyclization is found to be the preferred path also in the lower homologues. Reaction (6.2) shows the reactions of two silanes (8) with thermally generated t-BuO radicals to afford the five-membered ring in low yields via a 5-endo-trig cyclization [1], EPR spectra recorded from these two silanes with photogenerated t-BuO radicals are assigned to secondary alkyl radical intermediates formed by an intermolecular addition involving the expected silyl radical and the parent silane [2],... 

Intramolecular cyclization of N-alkenyl-2-bromoindoles has been described. The formation of five as well as six-membered ring in the radical cyclization proceeds in good yield [95TL4857]. A novel intramolecular free radical aromatic ipso substitution reaction has been reported [95CC1353]. Treatment of 138 with tributyltin hydride generates an alkyl radical which attacks the alkene at the carbon bearing the sulfur substituent. This is followed by elimination of the sulfur substituent to provide the cyclized products 139 in moderate yields. The efficiency of the reaction is dependent on the size of the ring formed and on the sulfur substituent. 

The method has been used most often for cyclization reactions. Five- and six-membered rings may be formed efficiently in the common cases and, when fused to an azetidinone, seven-membered rings are formed in synthetically useful yields (equation 168)327. Perhaloalkane-olefin additions have focused on intermolecular cases328 329 in some cases, yields are enhanced by the additional use of trimethylaluminum as a radical initiator328. Several other transition metal complexes are known to initiate the same processes, particularly RuCl2(PPh3)2330. 

The radical intermediates from Cr(II) reduction of alkyl halides can in principle be used synthetically, but have only seen limited attention to this point. co-Haloalkynes (bromides, iodides), in the presence of excess Cr(C104)2, undergo cyclization reactions to form exo-alkylidene cycloalkanes (equation 176)347. These reactions proceed by the radical cyclization of intermediate 42 onto the alkyne unit, which undergoes subsequent reduction by Cr(II) to give a hydrolytically unstable vinylchromium(III). Rings of four, five and six members can be formed. Alternatively, a-iodo esters undergo intramolecular atom transfer radical cyclizations onto alkynes or alkenes with catalytic or stoichiometric amounts of... 

Indium-mediated radical cyclization reactions of aliphatic iodoalkynes proceeds with a catalytic amount of In and I2. Iodoalkyne 94 undergoes an atom-transfer 5-exo cyclization to give five-membered iodoalkene. In contrast, the reaction with In (200mol%) and I2 (100mol%) yields the reductive 5-m -cyclization product via the same 5-exo-cyclization (Scheme 116).387-389 The existence of a vinylindium intermediate formed via the radical 95 has been confirmed by a Pd-catalyzed cross-coupling reaction (Scheme 117).390... 

The preference for formation of a smaller ring is a very powerful one in this reaction, the five-membered ring forms and not the six-membered one, even though cyclization to give a six-mem-bered ring would also give a stabilized radical. 

The formation of ring systems by the anionic cyclization of olefinic alkyl, aryl and vinyl-lithiums is an interesting synthetic transformation that provides a regiospecific and highly stereoselective route to five-membered carbocycles and heterocycles99. Most importantly, it is possible to functionalize the initially formed cyclization product by a tandem reaction with electrophiles, a reaction that is not generally possible in the case of radical cyclizations. 

The cyclization reaction of the hex-l-en-6-yl radical (5) has been studied fairly extensively in solution by conventional analytical techniques. The amounts of cyclohexane and methylcyclopentane that are formed have been found to vary with the experimental conditions and the radical precursor used, but in the main the results show that cyclization to a five-membered ring is highly favoured (Julia, 1966). 

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