Hypoiodite-type reaction

Hypoiodite-type reaction. Treatment of the allylic alcohol 1 with QHsI (OAc)2 and iodine generates an alkyloxy radical, which undergoes -scission to a followed by cyclization to a cis-hydroazulenone ring system (2). The CH2I group of 2 can be reduced to a methyl group by a catalytic amount of BusSnH (60% yield). Treatment of 2... 

TBS-Protected 7-lactol is obtained through the formation of hypoiodite, followed by the formation of an alkoxyl radical, 1,5-H shift, and then formation of 8-iodoalcohol, and finally polar cyclization. The Fenton system with ROOH and Fe2+ also generates alkoxyl radical, RO. These reactions indicate that the Barton (-type) reactions are remote functionalization of non-activated C-H bonds at the 8- or e-position. 

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-... 

Instead of alkyl nitrite, other alkoxyl radical precursors such as ROOH, ROOR, ROI, ROC1, etc. can also be used for the same type of reaction. The high reactivity of these compounds comes from the weak bond dissociation energies in O-O, 0-1, and O-Cl bonds. Another simple method is as follows. Photolytical treatment of alcohol (5) with NIS (AModosuccinimide) provides the tetrahydrofuran skeleton (6), through the formation of alkyl hypoiodite (ROI), homolytic cleavage of the 0-1 bond to form an alkoxyl radical, 1,5-H shift to form a carbon-centered radical, reaction with ROI to form 8-iodoalcohol, and finally ionic cyclization to form a tetrahydrofuran skeleton, together... 

Structures (316) with an oxetan ring, recently proposed250 for two iodo-compounds obtained during the hypoiodite reaction of cholesterol, have now been revised.251 Spectroscopic and X-ray data show the compounds to be iodo-acetals (317), converted by de-iodination and reaction with BF3-acetic anhydride into the dihydropyran (318). Photolysis of the oxime of a l,5-dien-3-one gave mainly rearranged ketonic products, isomers of type (319), which are also obtained by photo-rearrangement of the l,5-dien-3-one.252... 

Reactions with lead tetraacetate and iodine are frequently complicated by bifunctional attack, leading to lactols (9) after hydrolysis of intermediate a -iodo-ethers (8). This does not arise in reactions with lead tetraacetate alone (section 5). In general terms, the hypoiodite reaction sequences appear to be of the type depicted in Fig. 48 [34]. 

Normally the rate of oxidation of D-glucose by hypoiodite is independent of the type of buffer. However, with borate buffers the rate is decreased to 5% of the normal value. This effect is attributed to complex formation in the 1,2-position, since the rates of oxidation of 2,3,4,6-tetramethyl- and 2,3,6-trimethyl-D-glucose are approximately the same in borate buffers as in buffers of other types. These rates are about two-thirds of those for D-glucose in normal buffers. The effect of borate as a buffer has been confirmed by other workers. The original Romijn method used a borate buffer and the reaction was found to be too slow for a convenient analytical method. Pacsu found the same effect in the... 

For effecting oxidative cyclizations of the types noted, superior results have been obtained with use of the combination lead tetraacetate-iodine, a method introduced by the Ciba-Basel group Ch. Meystre, Heusler, Kalvoda, P. Wieland, Anner, and Wettstein. Known as the hypoiodite reaction because the combination generates HOI, the method appears to be simpler and more efficient than lead tetraacetate alone, and than any of three other methods not employing lead tetraacetate. An improved procedure is as follows. Pregnenolone acetate (5) is first reduced with lithium tri-f-butoxyaluminum hydride in tetrahydrofurane to 3 8-acetoxy-20 -hydroxy-A -pregnene (6) the 20a-isomer is formed in minor amount. At the end... 

This sensitive test permits use of the readily available sodium hypochlorite in place of sodium hypoiodite for recognition of methyl carbonyl or methylcarbinol structures. It is useful also when detection of a haloform by infrared spectroscopy or gas-liquid chromatography is unsatisfactory, as may happen in certain reactions in which haloform-type cleavage occurs to a slight extent. ... 

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). ... 

It has been suggested that nodosin (66) is biosynthesized from isodocarpin (64) via the isodoacetal-like intermediate (157). To prepare such an intermediate dihydroisodocarpin (158), dihydroenmein-3-acetate (159), and isodotricin-3-acetate (160), were subjected to the hypoiodite reaction (Scheme 32) but instead products of type (161) were obtained 118). 

The aldehyde (or hemiacetal) group is the most easily oxidized common group found in carbohydrates. Bromine and hypoiodite convert it readily to the carboxyl (or lactone) group. Most other agents simultaneously attack other points of the molecule, although nitric acid (or nitrous acid) may have some value for this type of reaction. 

The hemlacetal nature of the anomeric hydroxyl group makes it the most reactive of that type. Direct oxidation can be carried out with several reagents, most classically, hypoiodite. This results in rapid oxidation to the aldono-lactone and is only exhibited by aldoses. Alternatively, reaction with alcohols results in the formation of full acetals (glycosides). A very large variety of such structures have been made. 

The application of hypoiodite photolysis for remote functionalization has been mostly in the steroid field. There has been, however, a resurgence of appHcations in the field of spiroacetal-type compounds. The reaction was originally found in 1966 by Mihailovic and collaborators, who described remote functionalization by a thermal reaction of alcohols with lead tetraacetate. ... 

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