Hypoiodite reaction

Although such alkoxides have never been isolated it is assumed that with bulky alcohols such as steroidal alcohols, the main contributing structure in such an equilibrium (especially when excess lead tetraacetate is present) is the one in which n = 1. An advantage of this procedure held in common with the hypoiodite reaction is the fact that the alcohol derivative is formed in situ. Intermolecular hydrogen abstraction e.g., reaction with solvent)... 

The homolysis of tertiary hypochlorites for the production of oxy radicals is well known." The ease with which secondary hypohalites decompose to ketones has hampered the application of hypohalites for transannular reactions. However the tendency for the base-catalyzed heterolytic decomposition decreases as one passes from hypochlorites to hypobromites tohypoidites. Therefore the suitability of hypohalites for functionalization at the angular positions in steroids should increase in the same order. Since hypoidites (or iodine) do not react readily with ketones or carbon-carbon double bonds under neutral conditions hypoiodite reactions are more generally applicable than hypochlorite or hypobromite decompositions. 

A considerable extension of the synthetic utility of the hypoiodite reaction is achieved if the steroid hypoiodite (2) is generated from the alcohol and acetyl hypoiodite and then decomposed in a nonpolar solvent. In this case ionic hydrogen iodide elimination in the 1,5-iodohydrin intermediate (3) is slow, thereby allowing (3) to be converted into an iodo hypoiodite (5). 

No systematic study of the minimal required amount of lead tetraacetate has been made. In cases where the product of the hypoiodite reaction is an iodo ether (20-hydroxy steroids) the reaction can be interrupted at the iodohydrin stage by reducing the amount of iodine to about 0.5 mole. For the oxidation of iodo ethers to lactones, chromium trioxide-sulfuric acid in acetone has been used. Silver chromate is often added to the reaction mixture but comparable yields are obtained without the addition of silver salt. 

The intramolecular formation of 18-cyano-20-ketones in 30-50% yield from 20-cyanohydrins in the hypoiodite reaction is particularly interesting. The reaction is considered to occur through the following steps ... 

Hydroxy-2,2,4-trimethyl-3-pentenoic acid 0-lactone, see Dimethylke-tene 8-lactone dimer Hypoiodite reaction, 46, 62... 

This hypoiodite reaction can also be used for ring expansion of cyclic ketones.2 Thus Barbier cyclization of a-(w-iodopropyl)cyclododecanone (3) furnishes the bicyclic alcohol 4, which undergoes regioselective cleavage to a 15-membered iodo... 

For the substitution of the angular methyl groups in steroids five methods are known (a) homolysis of N-chloramines [Loffier-Freytag reaction (only C-18)] (b) oxidation of alcohols with lead tetraacetate (c) photolysis of nitrite esters (d) homolysis of hypochlorites (e) the hypoiodite reaction. ... 

The preparation of the title lactone has been described by a multistep synthesis from holarrhimine. The method described in detail above is essentially an application of the hypoiodite reaction published by Ch. Meystre and co-workers. These authors also describe the isolgition of the intermediate hemiacetal in pure form. Saturated lactones epimeric at C-20 have also been obtained by chromic acid oxidation of 18,20-dihydroxy compounds which were in turn prepared by treatment of 20-hydroxypregnanes with lead tetraacetate, acetolysis of the resulting 18,20 3-oxides, and hydrolysis. Saturated lactones of the... 

Chemistry of the Tetracyclic Diterpenoids.—The transannular hypoiodite reactions of 6-hydroxy-17-norkauranes have been studied with the object of functionalizing the methyl groups of ring A. Whereas the 6a-alcohols afford the 6—20 ethers, the 6/3-alcohols produce substitution at C-19. 

Wittig-Horner reaction (see p. 241). Photolysis of the nitrite of the 21-chloro-20-hydroxy-compound (194) gave the 18-oximino-compound (195) which on Jones oxidation was converted into the chlorolactone (196). Hypoiodite reaction of the 21-chloro-20-hydroxy-compound (194) also gives the chloro-lactone (196) which with modification gives 18-hydroxy-11-deoxycorticosterone (see also ref. 198). 

Ring expansion via the hypoiodite reaction.1 Irradiation of 1, formed by... 

Medium-sized lactones A new method for synthesis of lactones that is particularly useful in the case of medium sized ones involves the hypoiodite reaction with a catacondensed lactol such as 1, which results in cleavage to the ten-membered isomeric iodo lactone 2. Phoracantholide I (3) is obtained on reductive removal of iodine. 

The photolysis of alkyl hypohalites, especially alkyl hypoiodites [29], can be used in a manner similar to the organic nitrites for functionalization of an unactivated carbon atom. Scheme 25 outlines a general scheme for remote functionalization by the hypoiodite reaction. Readers requiring more information on this subject are advised to refer to review articles [2c, 16, 20],... 

Ring expansion of cycloalkanones.1 The hypoiodite reaction can also be used for a four-atom ring expansion of cyclic ketones via the corresponding lactols (cf., 13, 150). 

The cyclic vinyl ether (182),170 postulated last year as an intermediate in the 21-acetoxylation of the hemiacetal (183), can be prepared in good yield by heating the hemiacetal with aluminium isopropoxide in toluene under argon, followed by direct chromatography on basic alumina.171 The vinyl ether was converted into the 20,21-diol (184) either by reaction with osmium tetroxide or by acetoxylation with lead tetra-acetate, followed by hydrolysis. The hypoiodite reaction, followed by oxidation, allows direct conversion of a 21-acetoxypregnan-20/3-ol (185) into the 18-iodo-20-ketone (186), which is solvolysed in the presence of silver acetate to provide a new route to the 21-acetate of 18-hydroxydeoxycorticosterone hemiacetal (187).171... 

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]. 

GoebeP made a study of the effect of the rate of addition of alkali upon the formation of iodate from hypoiodite (reaction 15). He found... 

Burke, S. D., Silks, L. A., Ill, Strickland, S. M. S. Remote functionalization and molecular modeling. Observations relevant to the Barton and hypoiodite reactions. Tetrahedron Lett. 1988, 29, 2761-2764. 

---