Barton method

The activation energy E can be estimated from two dynamic DSC experiments at different heating rates. If the values of da/df and temperature are known at a fixed conversion a, E can be obtained according to the Barton equation [26]  

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An alternative method is the deoxygenation of the anomeric carboxylic acid 52, producing 55 [27], The functionalized precursor, in particular the O-acyl-thiohydroxamate ester 54, which is formed in situ after exposure of the carboxylic acid 52 to the salt 53, is decarboxylated by the Barton method. 

Deoxygenation of Anomeric Carboxylic Acids Using the Barton Method [27]. 

Scheme 44 summarizes an addition reaction by the Barton method. Thiohydroxamate esters (32) are readily prepared and isolated, but, more typically, they are generated in situ. Experimental procedures have been described in detail148151 and often entail the slow addition of an acid chloride to a refluxing chlorobenzene solution of the readily available sodium salt (31), dimethylaminopyridine (DMAP, to catalyze the esterification), and excess alkene. The products are usually isolated by standard aqueous work-up and chromatographic purification. 

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... 

Recent work by Newcomb has resulted in the emergence of a second method for the cyclizations of amminium radical cations that shows good synthetic potential.175-176 As illustrated in Scheme 42, AMiy-droxypyridine-2-thione carbamates can be generated and cyclized by analogy to the Barton method (which uses thione esters). In Scheme 42, the preparation of the precursors and two variants on the cyclization, reductive trapping and thiopyridyl trapping are illustrated. 

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-... 

A template is described as temporary or external if it is eliminated like a homogeneous catalyst at the end of a synthesis and is therefore not incorporated into the end product [27]. Sulfur or nitrogen, which can be eliminated by pyrolysis from the product after a successful reaction, can be regarded as the best-known exo templates. For example, McMurry et al. [28] used extrusion of Na and S (Barton method) from the thiadiazolines 25 in the preparation of the 16-membered hydrocarbon macrocycle 26 (Scheme 7). 

The Liu synthesis of Aa-methyl-A18-isokoumidine (137) (214) starts from L-tryptophan (138), which was transformed to intermediate 139 in six steps. The Dieckmann condensation of 139 afforded the /3-ketoester 140. Oxidative free radical cyclization of /3-ketoester 140, initiated with Mn(0Ac)3, H20/Cu/(0Ac)2 H2O, followed by the removal of the Na-protecting group, led almost quantitatively to 141. Hydrolysis and decarboxylation using the Barton method afforded, via compound 142, intermediate 143. Treatment of 143 with (CH3)2S = CH2/dimethyl sulfoxide (DMSO) THF yielded the epoxy derivative 144, which was reduced with A1H2C1 in THF to the, not yet naturally found, jVa-methyl-A18-isokoumidine (137) (Scheme 12). 

Stereoselective C—C bond formation also occurs in the addition of chiral dimethylpyrrolidine amide substituted radicals to ethyl acrylate2, The radicals are generated via irradiation of alkyl thiohydroxamates ( Barton method )3. Reactions at different temperatures yield isomeric mixtures of monoadducts (35-50%) and diadducts (15-25%). High levels of asymmetric induction are observed in the production of the monoadduct. The diadduct is a 1 1 mixture of C-4 diastereomers, presumably possessing the S configuration at C-2. 

Method A Mercury method NaBH4. CH2C12. B Barton method CH2C12, hv. 

The Barton method yields a 70—80% oxidized leady oxide. At high reactor temperatures, the oxide is entirely orthorhombic. At low temperatures, tet-PbO is formed along with ortho-rhomb-PbO. Small amounts of PbO and Pb304 can also be obtained by this method. 

The first C-unsusbstituted silole to be isolated, 1,1-dimethylsUole (4), was reported simultaneously by Dubac and coworkers , and Bums and Barton in 1981. This silole was prepared by dehydration of 1,1-dimethyl-l-sUacyclopentA-en-3-ol in the gas phase on alumina or thoria - (Scheme 2). In the presence of acidic reagents, the reaction results in C—Si rather than fi C—H bond cleavage, giving the dienic sUoxane (Me2SiC4H5)20. The Barton method consists of the flash vacuum p3Tolysis of 3-(benzoyloxy)-l,l-dimethyl-l-silacyclopent-4-ene at 540 °C (equation 2). 

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