A-hydroxy carbon radical

Oxidation of benzyl alcohol catalysed by chloroperoxidase exhibits a very high prochiral selectivity involving only the cleavage of the pro-S C-H bond. The reaction mechanism involved the transfer of a hydrogen atom to the ferryl oxygen of the iron-oxo complex. An a-hydroxy-carbon radical and the iron-hydroxy complex P-Fe -OH form. They may lead to the hydrated benzaldehyde or stepwise with the formation of the intermediate a-hydroxy cation. 

Synthesis of a-Hydroxy-y-lactones by Addition of a-Hydroxy Carbon Radicals to Unsaturated Esters... 

This new method for the construction of a-hydroxy-y-lactones is quite general for a variety of alcohols and a,P-unsaturated esters (Figure 6.9). The preparation of a-hydroxy-y-spirolactones from cyclic alcohols is especially notable, because these spirolactones have been very difficult to synthesize until now. The reaction can be explained by Scheme 6.18 (i) in situ generation of an a-hydroxy carbon radical from an alcohol assisted by NHPI/Co(II)/02, (ii) the addition of the radical to methyl acrylate, (iii) trapping of the adduct radical by O2, and (iv) intramolecular cydization to give a-hydroxy-y-butyrolactone. Considering the low-cost material, reaction efficiency, and reaction simplicity, this method provides an innovative approach to a-hydroxy-y-lactones which has considerable industrial potential. 

T. Iwahama, S. Sakaguchi, Y. Ishii, Catalytic a-hydroxy carbon radical generation and addition. Synthesis of a-hydroxy-y-lactones from alcohols, a,p-unsaturated esters and dioxygen, Chem. Commun. (2000) 613-614. 

Benzophenone (Amax = 340 nm, log e = 2.5, n-ir electronic transition) can be used as a photochemical reagent and eq. 4.25 shows a radical Michael-addition reaction with benzophenone. The formed benzophenone biradical (triplet state, Tx) abstracts an electron-rich a-hydrogen atom from methyl 3-hydroxypropanoate (62) to generate an electron-rich a-hydroxy carbon-centered radical [III], then its radical adds to the electron-deficient (3-carbon of a, (3-unsaturated cyclic ketone (63) through the radical Michael addition. The electrophilic oxygen-centered radical in the benzophenone biradical abstracts an electron-rich hydrogen atom from methyl 3-hydroxypropanoate (62) [70]. So, an a-hydroxy carbon-centered radical [III] is formed, and an electron-deficient a-methoxycarbonyl carbon-centered radical [III7] is not formed. 

Irradiation of a methanolic solution of l-methyltricyclo[4.1.0.0 ]heptane (22) in the presence of naphthalene-l-carbonitrile gave 6-methoxy-7-methylbicyclo[3.1.1]heptane (23a, 93Vo, isolated yield 56%). In an aqueous system, the corresponding hydroxy derivative 23b was isolated in 70% yield. The orientation of addition was anti-Markovnikov and the substituents were located in the less hindered positions. The same bond was cleaved when the 2-/er/-butyl derivative 24 was submitted to this reaction. With two methyl substituents, i.e. 26, a mixture of two stereoisomers 27A,B and a dehydrogenated product 28 was obtained whose formation could be explained by the occurence of a tertiary carbon radical. ... 

The radical carbon atom forms a covalent bond with the oxygen atom attached to the carbon chain, which leads to the formation of a cyclic ether with the elimination of a hydroxy free radical. 

Deprotonation provides the necessary electron push to kick out the electron pair joining C(6) with the nitrobenzene oxygen. If, however, N(l) is alkylated (as with the nucleosides and nucleotides), OH catalysis is much less efficient since it now proceeds by deprotonation from N(3) (with the uracils) or from the amino group at C(4) (with the cytosines). In these cases the area of deprotonation is separated from the reaction site by a (hydroxy)methylene group which means that the increase in electron density that results from deprotonation at N(3) is transferable to the reaction site only through the carbon skeleton (inductive effect), which is of course inefficient as compared to the electron-pair donation from N(l) (mesomeric effect) [26]. Reaction 15 is a 1 1 model for the catalytic effect of OH on the heterolysis of peroxyl radicals from pyrimidine-6-yl radicals (see Sect. 2.4). 

The carbon-centered hydroxy-containing radical CH2OH formed in reactions (37) and (39) is encountered frequently as an intermediate in tropospheric organic oxidations. It is commonly referred to as an a-hydroxy radical. These types of radicals react in a... 

Desaturation of alkyl groups. This novel reaction, which converts a saturated alkyl compound into a substituted alkene and is catalyzed by cytochromes P-450, has been described for the antiepileptic drug, valproic acid (VPA) (2-n-propyl-4-pentanoic acid) (Fig. 4.29). The mechanism proposed involves formation of a carbon-centered free radical, which may form either a hydroxy la ted product (alcohol) or dehydrogenate to the unsaturated compound. The cytochrome P-450-mediated metabolism yields 4-ene-VPA (2-n-propyl-4pentenoic acid), which is oxidized by the mitochondrial p-oxidation enzymes to 2,4-diene-VPA (2-n-propyl-2, 4-pentadienoic acid). This metabolite or its Co A ester irreversibly inhibits enzymes of the p-oxidation system, destroys cytochrome P-450, and may be involved in the hepatotoxicity of the drug. Further metabolism may occur to give 3-keto-4-ene-VPA (2-n-propyl-3-oxo-4-pentenoic acid), which inhibits the enzyme 3-ketoacyl-CoA thiolase, the terminal enzyme of the fatty acid oxidation system. 

Thioethers have also been prepared on cross-linked polystyrene by radical addition of thiols to support-bound alkenes and by reaction of support-bound carbon radicals (generated by addition of carbon radicals to resin-bound acrylates) with esters of l-hydroxy-l,2-dihydro-2-pyridinethione ( Barton esters Entry 6, Table 8.5). Additional methods include the reaction of metallated supports with symmetric disulfides (Entries 7-9, Table 8.5) and the alkylation of polystyrene-bound, a-lithiated thioani-sole [65],... 

An a-hydroxy tertiary amine is oxidized with difficulty. At 60°, however, 2-(7V, Ar-diethylamino)ethanol took up lead tetraacetate, but scission occurred between the carbon-nitrogen bond (instead of between the carbon-carbon bond), possibly by a free-radical mechanism.196... 

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