Iodohydrins formation

Iodine isocyanate, 22 1,5-Iodohydrin formation, 252 21-Iodo-3 -Hydroxypregn-5-en-20-one acetate, 208 W-iodosuccinimide, 209 Isohexylmagnesium bromide, 68... 

The diastereoselective halohydrin formation, resulting from the reaction of chiral /V -enoyI -2-oxazoI idinones with Br2/l2 and water, promoted in the presence of silver , in aqueous organic solvents, has been found to occur with high regioselectivity and moderate to good diastereoselectivities. The alkenoyl, cinnamoyl, and electron-deficient cinnamoyl substrates readily produced the bromohydrin in aqueous acetone, but no iodohydrin formation was observed under these conditions. On the other hand, ( ) electron-rich cinnamoyl substrates preferred to afford iodohydrins in aqueous acetone with moderate diastereoselectivity enhanced diastereoselectivity was observed for aqueous THF.31... 

Furthermore, it is known that the presence of an oxygenated function on a stereogenic center exerts a strong influence on the 1,2-asymmetric induction, affording high selectivity (95%). For example, in iodohydrin formation from acyclic allylic alcohols 19, a, 2-syn selectivity of 90 - 99% is observed26. 

Further proof of the intermediacy of the iodohydrins 85 in the formation of the hydroxy-tetrahydrofurans 80 came from two sources. Firstly, treatment with potassium carbonate led to formation of the corresponding epoxides. Secondly, by providing a second alkene function, suitably positioned to trap the iodohydrin hydroxyl by a 6-eto-trig iodocyclization, we have been able to intercept these species and hence define a new approach to substituted pyrans. Thus, treatment of the dienyl hydroxy-ester 90 with iodine and NaHCO, resulted in the formation of pyrans 92 in the ratio of 3.2 1. Presumably, initial iodohydrin formation 91 is followed by a relatively non-stereoselective 6-exo cyclization. Further chemistry of such products has yet to be carried out, especially efforts to distinguish the two iodine atoms and to cyclize to give furopyran systems <01M1001>. 

Additional examples of synthetic application of periodic acid as an oxidant include the oxidative iodination of aromatic compounds [1336-1341], iodohydrin formation by treatment of alkenes with periodic acid and sodium bisulfate [1342], oxidative cleavage of protecting groups (e.g., cyclic acetals, oxathioacetals and dithioacetals) [1315, 1343], conversion of ketone and aldehyde oximes into the corresponding carbonyl compounds [1344], oxidative cleavage of tetrahydrofuran-substituted alcohols to -y-lactones in the presence of catalytic PCC [1345] and direct synthesis of nitriles from alcohols or aldehydes using HsIOe/KI in aqueous ammonia [1346],... 

Some 2,3-epoxyamides of aldonic acids have been prepared by reaction of acyclic aldose derivatives with sulfur ylids (Scheme 1). 5y -epoxidation of some racemic 2-benzyloxy-4-alkenamides by way of iodohydrin formation and subsequent base treatment has afforded epoxides such as 2. Epoxidation of hex-2-enopyranosyl phosphonates has been effected with H202/sodium tungstate. ... 

An unusual incorporation of iodine derived from the Na(lO ) used in RuClj/aq. Na(10 )/CCl -CH3CN was noted in the oxidation of the terminal alkene 2-allyl-2,5-dichloro-4-morpholino-cyclopent-4-ene-l,3-dione giving the iodohydrin 5 3,7-dichloro-l-P-hydroxy-3 3-iodomethyl-8-morpholino-2-oxabicyclo[3.3.0]-oct-7-en-6-one and its 3a-epimer. The iodine apparently derives from the formation of or T from the lOj" to which IO is reduced after the RuClj/IO " reaction (Fig. 3.21) [236]. 

Epoxides do not, normally, react with dibromine or diiodine unless a reducing agent is present. This has been demonstrated in formation of bromo- and iodohydrine from oxiranes in presence of sodium thiosulfate1103. 

Epoxides may be prepared from alkenes by the action of a peroxy acid such as m-chloroperbenzoic acid (Scheme 2.20a) or via the formation of a bromohydrin or iodohydrin and the treatment of this with base (Scheme 2.20b). Since the initial electrophile, the bromine or the iodine, is displaced in the second step when the epoxide is formed, the stereochemistry of this epoxidation is likely to differ from that of the reaction with peroxy acid. 

Vo yield [156]. The reaction is explained by the formation of a iodohydrine as intermediate. 

A general approach to P-functional alkanols involves formation of a-substituted samarium reagents and their reaction with carbonyl compounds. Thus, P,P-diiodoalkanols, °. -iodohydrins, " P-phenylselenoalkanols, and P-phenylthio-alkanols are prepared from the corresponding substituted halides. The products with a syn disposition are predominant. 

Reduction of iodohydrins. In Cornforth s stereospecific synthesis of a cis or irons olefin, an intermediate is a chlorohydrin of predictable configuration which cannot be reduced directly to the olefin. The conversion is accomplished by three strictly stereospeciflc steps formation of the epoxide, cleavage with HI (Nal—AcOH—EtCOgH), and reduction of the resulting iodohydrin with stannous chloride, phosphoryl chloride, and pyridine. 

Formation of oxacycles via intramolecular radical addition reactions of oxygen-centered radicals under oxidative and reductive conditions is known [116] (see also Chapter 5.2, Volume 2). However, cyclic ether formation via intramolecular displacement reaction of iodohydrins obtained by hydrogen abstraction of oxy radicals has been more widely used, as exemplified in the reports by Suarez [117]. The usefulness of this reaction was amply demonstrated by Paquette in the synthesis of (-t-)-epoxydiclymene (179) [118] (Scheme 61), in which the strained trans-... 

They also succeeded in discrimination of prochiral iodine atoms. In the reaction of l,l-diiodo-2-phenylethane with a chiral Grignard reagent, one of the iodides preferentially underwent iodine-magnesium exchange subsequent aldol reaction with benzaldehyde in the presence of Me2AlCl resulted in the formation of an iodohydrin with 53% ee [Eq. (38)) (92). 

Asensio and coworkers reported a low temperature oxidation of iodomethane with DMDO to afford a pale yellow precipitate of iodosylmethane (20, Scheme 2.10) [104]. Upon raising the temperature to -40 °C, in the presence of moisture iodosylmethane decomposes to form the unstable hypoiodous acid, HOI, which can be trapped in situ by an alkene to afford iodohydrins. The formation of MelO has also been detected in the photochemical reaction of iodomethane with ozone in an argon matrix at 17 K [105], A similar low-temperature reaction of trilluoroiodomethane affords the unstable CF3IO, which was identified by infrared spectroscopy [106]. 

The argument is closely analogous to that used to explain the regioselectivity of formation of bromoacetoxy compounds (Table 9.2) formed in the addition of bromine to alkenes in acetic acid. Similarly, addition of bromine to alkenes in water produces bromohydrins. Although they are more difficult to synthesize, iodohydrins and fluorohydrins are also known. For a review of the synthesis and reactions of halohydrins, see Rosowsky, A. in Weissberger, A., Ed. Heterocyclic Compounds with Three- and Four-Membered Rings, Part One Wiley-Intersdence New York, 1964 p.l. 

The synthesis of the epoxide 48 is described in Scheme 15.15 in three steps, starting with a diastereoselective allylation of the lithium (Z)-enolate of 50 followed by a diastereoselective conversion of 51 to iodohydrin 52 via NIS-mediated cyclic iodoimidate formation and hydrolysis. Finally a base-mediated conversion of 52 to the epoxide 48 was accomplished, with all three steps giving excellent yields [29]. 

The acceleration of carbocation formation impHes that spiroacetal formation may take place by the cyclization of a carbocation intermediate, but not by cychzation through an iodohydrin intermediate. 

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