Barton fragmentation reaction

Baeyer-Villiger reaction, 9, 3 43, 3 Bamford-Stevens reaction, 23, 3 Barbier Reaction, 58, 2 Bart reaction, 2, 10 Barton fragmentation reaction, 48, 2 Bechamp reaction, 2, 10 Beckmann rearrangement, 11, 1 35, 1 Benzils, reduction of, 4, 5 Benzoin condensation, 4, 5 Benzoquinones ... 

Free-radical cyclization is sometimes followed directly by fragmentation of the new free radical, as in the Barton-McCombie reaction and the free-radical ally-lation reaction. Addition of a radical to a carbonyl group followed by fragmentation can be used to prepare a medium-sized ring from a smaller one. 

Oxidation Reactions. Hypoiodite intermediates may be generated from the reaction of simple alcohols with NIS. When conducted under photochemical irradiation, the products of Barton-type or fragmentation reactions of alkoxyl radical intermediates may be obtained. Aldehydes are oxidized to methyl esters via hemiacetal intermediates by reaction with NIS in methanol at rt. However, such conditions are not effective for the oxidation of simple alcohols. The combination of NIS and Tetrabutylammonium Iodide in dichloromethane has been developed for the oxidation of a variety of alcohols to the corresponding carbonyl corrpounds (eq 8). This reagent system is most widely used for the oxidation of lactols to lactones, in which near-quantitative yields are generally obtained under mild conditions (eq 9). ... 

As discussed in this chapter, various methodologies for C=C bond formation have been developed based on the reaction of W-tosylhydrazones. Traditional base promoted reactions such as the Bamford-Stevens reaction, the Shapiro reaction, the Barton-Kellogg reaction, and Julia-type condensation-fragmentation have already been widely applied for organic synthesis in the past few decades. The palladium catalyzed reaction of A-tosylhydrazones through metal carbene intermediates has attracted increasing attention in recent years. A-Tosylhydrazones are readily available substrates and are stable. They have been proven to be reliable... 

According to the classical definition. Barton esters are mixed anhydrides of carboxylic acids with thio-hydroxamic acid such as I (Scheme Ij. This class of compound was originally developed to allow the transformation of carboxylic acids to a convenient source of radicals for synthetic application. Even now, they are one of the most important entries to C-radicals. Over time, the scope of the reaction was broadened, allowing the generation of heteroatom-centered radicals, particularly oxyl-, aminyl-, and iminyl radicals of synthetic interest. For these transformations, carbonates and carbamates (II), acetates (IV), and ethers (V) were developed (Scheme 1). Finally, oxalates (III) were used for deoxygenation of secondary and tertiary alcohols. The radical fragmentation reaction of these compounds can be carried out either by irradiation or by thermal activation. Both methods are discussed here briefly. 

The thione function of the Barton ester 1 can be replaced by other elements such as Se (13) without significant alteration of the reactivity (Scheme 6). Although the starting esters are more air sensitive than the analogous N-hydroxypyridine 2-thione derivatives (1), the method has some advantages for example, the adducts of the free-radical fragmentation reactions of N-hydroxypyridine-2-selenone derivatives 13 (i.e., alkylpyridylselenides) can usually be more easily modeled and transformed to other chemical functions than thioethers. 

There is quite some evidence for a mechanism as formulated above,especially for the six-membered transition state—the Barton reaction is observed only with starting materials of appropriate structure and geometry, while the photolysis of nitrite esters in general seldom leads to useful products formed by fragmentation, disproportionation or unselective intermolecular hydrogen abstraction. 

The basic transformation that underlies the Barton method is outlined in Scheme 45, steps 1 and 2.152 Thermolysis in refluxing toluene or photolysis with a sunlamp rapidly converts a thiohydroxamate ester (32) to the decarboxylated pyridyl sulfide (33). This pyridyl sulfide is formed by addition of an alkyl radical R to the thiohydroxamate (32) followed by fragmentation of (34) as indicated. In the planning of addition reactions by the Barton method, it is usually assumed that the addition step 1 is rate limiting. However, there is now evidence that step 1 may sometimes be reversible and step 2 may be rate limiting.153... 

Alkoxyl radicals can be generated by a variety of methods including peroxide reduction, nitrite ester photolysis, hypohalite thermolysis, and fragmentation of epoxyalkyl radicals (for additional examples of alkoxyl radical generation, see Section 4.2.S.2). Hypohalites are excellent halogen atom donors to carbon-centered radicals, and a recent example of this type of cyclization from the work of Kraus is illustrated in Scheme 43.182 Oxidation of the hemiketal (57) presumably forms an intermediate hypoiodite, which spontaneously cyclizes to (58) by an atom transfer mechanism. Unfortunately, the direct application of the Barton method for the generation of alkoxyl radicals fails because the intermediate pyridine-thione carbonates are sensitive to hydrolytic reactions. However, in a very important recent development, Beckwith and Hay have shown that alkoxyl radicals are formed from N-alkoxypyridinethiones.183 Al-... 

The driving force for the fragmentation is formation of the C=0 double bond. If R reacts with Bu3SnH, a tributyltin radical is produced which continues the chain. Carried out in this manner this reaction is called the Barton deoxygenation of alcohols, since alcohols are precursors for the thiono esters. 

When the alkoxyl radical and the hydrogen to be abstracted are not properly disposed for the Barton reaction, the reactions of the alkoxyl radical, for example -fragmentation, intramolecular addition to the double bond, disproportionation or a-hydrogen fission, and intermolecular hydrogen abstraction, compete with the Barton reaction or result in an exclusive reaction. Among these reactions, /l-frag-... 

Fig. 1.39. Reduction of an alcohol by means of the radical substitution reaction of Barton and McCombie. In terms of Figure 1.2 a "substitution including a fragmentation" occurs.

Barton oxidation was the key to form the 1,2-diketone 341 in surprisingly high yield, in order to close the five-membered ring (Scheme 38). The conditions chosen for the deprotection of the aldehyde, mercuric oxide and boron trifluoride etherate, at room temperature, immediately led to aldol 342. After protection of the newly formed secondary alcohol as a benzoate, the diketone was fragmented quantitatively with excess sodium hypochlorite. Cyclization of the generated diacid 343 to the desired dilactone 344 proved very difficult. After a variety of methods failed, the use of lead tetraacetate (203), precedented by work performed within the stmcmre determination of picrotoxinin (1), was spectacularly successful (204). In 99% yield, the simultaneous formation of both lactones was achieved. EIcb reaction with an excess of tertiary amine removed the benzoate of 344 and the double bond formed was epoxidized with peracid affording p-oxirane 104 stereoselectively. Treatment of... 

In the Barton reaction, an alkyl nitrite is converted into an alcohol-oxime. The nitrite is photoexcited to a 1,2-diradical. It fragments to NO and an alkoxy radical (RO-), and the latter abstracts H- from the nearest C-H bond. The resulting alkyl radical then combines with NO to give a nitroso compound, which then tautomerizes to the oxime, probably by a polar stepwise mechanism. The Barton reaction has been used for the remote functionalization of hydrocarbons, especially steroids. 

There are a variety of photochemical reactions involving free nitrous oxide (NO) as persistent radical. Often there is an initial fragmentation, as presented in Scheme 6 for TV, 7V-dimethyl-/V-nitro-samine. One example is the Barton reaction of nitrite esters (Scheme 15). It allows the functionalization of methyl groups in steroids and utilizes an intermediate 1,5-hydrogen atom migration, which converts the initially formed oxygen-centered radical to a carbon-centered species.69... 

Use of Tin Hydrides. From the mechanistic point of view, the reductive elimination of methyl xanthate derivatives of (3-hydroxy sulfones entails an interesting variation of the Julia reaction since an initial fragmentation of the C-0 bond through a Barton-McCombie-type radical deoxygenation takes place. Final aryl sulfonyl radical elimination affords the corresponding alkene (Eq. 52).98,99... 

Radical addition-fragmentation processes have been exploited in synthetic organic chemistry since the early 1970 s. Ally transfer reactions with allyl stannancs and the Barton-McCombic deoxygenation process with xanthates arc two examples of reactions known to involve a S[j2 mechanism. However, the first reports of addition-fragmentation transfer agents in polymerization appeared in the... 

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