Radical reactions heterocyclic synthesis

Synthesis of heterocycles by forming C—X bonds by radical reactions is not a generally applicable method, and seems not to be useful for making small rings. However, the attack of thiol radicals on double bonds can be a practical synthetic route, such as in the conversion of 1-hexene-7-thiol to thiepane (Section 5.17.3.3.1). 

The majority of sequential radical reactions deal with cyclizations as the key steps. The constructions of carbocycles, oxygen, and nitrogen heterocycles using (TMSlsSiH as a mediator are many and represents the expansion and importance of these synthetic approaches. For example, Nicolaou and coworkers found that (TMSlsSiH serves as a superior reagent in the radical-based approach toward the synthesis of azadirachtin, an antifeedant agent currently used as an insecticide, and in other related systems. ° ° Here below we collected a number of reactions mostly from the recent work in the area of intramolecular reactions. 

A general synthesis of spiro-piperidinyl heterocycles 116 was obtained from intermediate 115 via an efficient radical reaction <96TL(37)5233>. 

Two types of addition to pyrimidine bases appear to exist. The first, the formation of pyrimidine photohydrates, has been the subject of a detailed review.251 Results suggest that two reactive species may be involved in the photohydration of 1,3-dimethyluracil.252 A recent example of this type of addition is to be found in 6-azacytosine (308) which forms a photohydration product (309) analogous to that found in cytosine.253 The second type of addition proceeds via radical intermediates and is illustrated by the addition of propan-2-ol to the trimethylcytosine 310 to give the alcohol 311 and the dihydro derivative 312.254 The same adduct is formed by a di-tert-butyl peroxide-initiated free radical reaction. Numerous other photoreactions involving the formation by hydrogen abstraction of hydroxyalkyl radicals and their subsequent addition to heterocycles have been reported. Systems studied include 3-aminopyrido[4,3-c]us-triazine,255 02,2 -anhydrouri-dine,256 and sym-triazolo[4,3-fe]pyridazine.257 The photoaddition of alcohols to purines is also a well-documented transformation. The stereospecific addition of methanol to the purine 313, for example, is an important step in the synthesis of coformycin.258 These reactions are frequently more... 

Radical, Cyclic Transition State and Ring-Opening Reactions Reactions in the Side Chain of 1,3-Heterocycles Synthesis of 1,3-Heterocycles... 

Intramolecular addition of vinyl radicals to olefins as a method for heterocycle synthesis has been examined. The vinyl radicals can be conveniently generated from vinyl bromides and samarium(II) diiodide [95JOC7424], The intermediate radical after cyclization undergoes a further electron transfer from samarium to furnish a carbanion which is quenched at the end of the reaction. A samarium(II) diiodide mediated aryl radical cyclization onto a dihydrofuran has been reported [95T8555],... 

Other radical methods for heterocycle synthesis involve SrnI reactions. The synthesis of indoles [95BCSF306], imidazoles [95JOC8015], imidazopyrimdines [95T9643], and substituted 1,3-dioxanes [95JCS(P1)609] have been reported. 

Synthesis of heterocycles by intramolecular radical reactions of carbohydrate derivatives 92MI18. 

Cyclic enamines, ynamines and ureas, preparative methods 86MI12. Design of free radical reactions for the synthesis of heterocycles 88S417, 88S489. 

Stereoselective radical reactions of carbonyl derivatives of heterocycles 00MI12. Suzuki-Miyaura cross-coupling reaction in organic synthesis (review contains many examples of reactions with participation of heterocycles) 02T9633. Tautomerism in diazoles, pyridines, and nucleic bases 02UK1120. 

Intramolecular radical addition with heterocycle formation 75KGS579. Intramolecular Wittig reaction in heterocyclic synthesis 80T1717. Isoureas, use in heterocyclic synthesis 8OOPP311. 

Radical reactions represent a well-established method for the formation of cyclic molecules. The sequencing of a radical addition followed by a radical cyclization provides the opportunity of increasing molecular complexity in a single reaction. In recent years, attention has focused on novel ways to initiate the radical chain reaction for the synthesis of heterocyclic ring systems. 

This chapter describes in general terms the types of reactivity found in the typical six- and five-membered aromatic heterocycles. We discuss electrophilic addition (to nitrogen) and electrophilic, nucleophilic and radical substitution chemistry. This chapter also has discussion of orf/to-quinodimethanes, in the heterocyclic context. Organometallic derivatives of heterocycles, and transition metal (especially palladium)-catalysed chemistry of heterocycles, are so important that we deal with these aspects separately, in Chapter 4. Emphasis on the typical chemistry of individual heterocyclic systems is to be found in the summary chapters (7, 10, 13, 15, 19 and 23), and a more detailed examination of typical heterocyclic reactivity and many more examples for particular heterocyclic systems are to be found in the chapters - Pyridines Reactions and Synthesis , etc. 

Radical translocation reactions in synthesis of heterocycles 01CSR94. 

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