Electrophilic iodination

Unsaturated carboxylic acid 17 possesses the requisite structural features for an iodolactonization reaction.16 A source of electrophilic iodine could conceivably engage either diastereoface of the A20,21 double bond in 17. The diastereomeric iodonium ion inter-... 

Introduction of iodine by Sandmeyer processes has been discussed [84AHC(35)83], Direct electrophilic iodination is also observed in the 3-position with reagents such as iodine monochloride, iodine-iodic acid-acetic acid, or molecular iodine. With excess reagent, or when C-3 is blocked, 6-iodination follows [84AHC(35)83 84MI15]. 

Electrophilic iodine reagents are extensively employed in iodocyclization (see Section 4.2.1). Several salts of pyridine complexes with 1+ such as bis-(pyridinium)iodonium tetrafluoroborate and b/.s-(collidine)iodonium hexafluorophos-... 

Enhanced stereoselectivity has been found using IBr, which reacts at a lower temperature.81 (Compare Entries 6 and 7 in Scheme 4.4.) Other reagent systems that generate electrophilic iodine, such as KI + KHSOs,82 can be used for iodocyclization. 

As mentioned earlier, metal complexation not only allows isolation of the QM derivatives but can also dramatically modify their reactivity patterns.29o-QMs are important intermediates in numerous synthetic and biological processes, in which the exocyclic carbon exhibits an electrophilic character.30-33 In contrast, a metal-stabilized o-QM can react as a base or nucleophile (Scheme 3.16).29 For instance, protonation of the Ir-T 4-QM complex 24 by one equivalent of HBF4 gave the initial oxo-dienyl complex 25, while in the presence of an excess of acid the dicationic complex 26 was obtained. Reaction of 24 with I2 led to the formation of new oxo-dienyl complex 27, instead of the expected oxidation of the complex and elimination of the free o-QM. Such reactivity of the exocyclic methylene group can be compared with the reactivity of electron-rich enol acetates or enol silyl ethers, which undergo electrophilic iodination.34... 

Furyllithium reacts rapidly with trialkylborons though the furylborons 91 believed to be formed are not actually isolated. Treated with an electrophile (iodine or A-chlorosuccinimide), they transfer one alkyl residue to the furan ring and eject the boron residue in a reaction well known in other series (Scheme 46). The 2-alkylfurans are indeed produced in excellent yields and the method is better than many other syntheses.236... 

Markwell (1982) reported that the reaction mechanism for creating the electrophilic iodine species may be somewhat different for lodobeads than other oxidizing agents. It was demonstrated that the active component remained at or near the surface of the beads during the course of the iodination process. Markwell speculated that an intermediate reactive species, N-iodobenzenesulfonamide, is formed from substitution of the chlorine atoms on the bead (Figure 12.4). It is possibly that this intermediate is involved in the direct iodination of target molecules that approach the bead surface. 

Thioglycosides can be activated by a wealth of strategies,3,4 although our investigations center on the use of electrophilic iodine (7V-iodosuccinimide). 

Quaternary ammonium dichloroiodates [10] are considerably more convenient to use than iodine monochloride for electrophilic iodination reactions and their use in stoichiometric amounts is well documented (see e.g. [II] and references cited therein). Thus, for example, alkenes undergo addition reactions to yield the a-chloro-p-iodoalkanes [11] and enaminones are converted into the corresponding a-iodoenaminones (75-90%) (Scheme 2.4) [12]. 

The synthesis of the heterocyclic diiodides can be tricky (Scheme 8). Direct iodination of quinoline was reported by Kiamuddin et al. [59] to give 5,8-di-iodoquinoline. Their procedure did not furnish any products according to Bunz et al., but classical electrophilic iodination leads to a single product that was identified not to be the 5,8-isomer but 3,6-diiodoquinoline, according to the X-ray crystal structure of a diethynylated derivative [60]. 

Filimonov et al. reported a synthesis of 3,6-diiodocarbazole (387) by iodination of carbazole (1). For the iodination, the required electrophilic iodine was generated by reacting iodine monochloride (ICl) with silver trifluoroacetate (CFsCOOAg) in acetonitrile. Following this procedure, 3,6-diiodocarbazole (387) was obtained in almost quantitative yield (871) (Scheme 5.270). 

Electrophilic iodine reagents have also been employed in iodocyclization. Several salts of pyridine complexes with I+ such as bis(pyiidinium)iodonium tetrafluoroborate and bis(collidine)iodonium hexafluorophosphate have proven especially effective.61 y-Hydroxy- and d-hydroxyalkcncs can be cyclized to tetrahydrofuran and tetrahydropyran derivatives, respectively, by positive halogen reagents.62 (see entries 6 and 8 in Scheme... 

Fluorine has been used for the generation of extremely strong electrophilic halogenating agents in electrophilic iodination and bromination of deactivated aromatic substrates in highly acidic reacton media. Polyhalogenation of more activated aromatic substrates is also possible (Fig. 90) [231-233]. 

Electrophilic iodinations of pyridines are less common iodine in oleum produced only a low yield of 3-iodopyridine (57JCS387). 

Substituted tetrazoles undergo electrophilic iodination to give the 5-iodo-derivatives (146, R = Alk, Ar, CH2 = CH-) in yields of 55-75% on treatment with I2 in acidic permanganate solution (88KGS1699, 92MI417-04). 

JHC993). The analogous reaction of the diacetoxythallium derivative of 3-acetylindole provides the one example of electrophilic iodination of the benzenoid ring of indole (Scheme 21) (79JHC993). 

Radioiodination involves the substitution of radioactive iodine atoms for reactive hydrogen sites in target molecules. The process usually involves the action of a strong oxidizing agent to transform iodide ions into a highly reactive electrophilic iodine II compound (typically I2 or a mixed halogen species such as IC1). Formation of this electrophilic species leads to the potential for rapid iodination of aromatic compounds... 

Markwell (1982) reported that the reaction mechanism for creating the electrophilic iodine species may be somewhat different for IODO-BEADS than other oxidizing agents. She demonstrated that the active component remained at or near the... 

With the weaker electrophile iodine, mixed dihalobutadienes can be synthesized. Similarly, treatment with iodine monochloride converts the stannole into the same product (equation 51). 

Scheme 2. Possible substitution sites for electrophilic iodinations.

It has been demonstrated that when uracils are iodinated with electrophilic iodine (using chloroamine-T and iodide or Iodo-Gen) in aqueous solution, or NIS in ethanol or chloroform-ethanol, addition products (47 or 48) form initially, eliminating water or ethanol when heated (81RTC267) (Scheme 41). 

Reaction of peracetylated sugars with iodine in the presence of hexamethyl-disilazane has been reported to afford the corresponding glycosyl iodide.29 Glycosyl iodides have also been prepared by treatment of glycosyl chlorides or bromides with substoichiometric amounts of iodine and DDQ.30 In this instance, DDQ acts to oxidize iodide remaining after the initial attack on the electrophilic iodine. The benefit of this approach is to limit the amount of free iodide is solution, as recycling of iodine at the expense of DDQ is clearly not cost-effective. 

---