Carbon-iodine coupling

Because the by-product of the coupling is a strong acid, bases are usually added to die reaction mixture to scavenge it. For example, 4-iodobromobenzene can be coupled with methyl acrylate to give the 4-bromocinnamate ester in >68% yield. This reaction takes advantage of the faster oxidative addition to the carbon-iodine bond to give a single product. 

The mechanism of this reaction shows that excitation of the substrate gave an n,n triplet state, but this excited state was unable to dissociate the carbon-iodine bond. This was demonstrated by showing that the n,n triplet state, when sensitized by chrysene, did not produce coupling products. Probably, the reaction occurred in an excited a,a triplet state mainly localized on the carbon-iodine bond, and the interaction between this triplet state and aromatic compounds led to homolytic cleavage of the C-I bond with the formation of both a 5-thienyl radical and a complex between the aromatic compound and the halogen atom. The formation of this complex was demonstrated by the presence of a short-lived transient with Amax = 510 nm, showing a second-order decay kinetics and a half-life of ca. 0.4 (is in laser flash photolysis. The thienyl radical thus formed... 

The data shown in Table 6 of I for the polarity of the carbon-halogen bond as a function of the hybridization of the carbon atom and of the nature of the halogen has been completed by the observation of the data for iodoacetylenes18. Although the data for iodoacetylene itself are not available, the data for several substituted iodoacetylenes imply that its coupling constant is approximately 2250 MHz so that the carbon-iodine bond in iodoacetylene has the almost negligible ionic character of 0.02. These results are summarized in Table 3. 

Chloro-4-iodo furans 59 can be valuable building blocks for the synthesis of highly substituted furans as illustrated by the Suzuki coupling of chloro iodo furan 59g with boronic acid 60d (R = p-MeOCeHU) furnishing trisubstituted chloro furan 62 in 59% yield (Scheme 36). Expectedly, the coupling selectively occurs at the carbon-iodine bond. 

The ligand coupling and ligand transfer mechanisms explain a number of transformations of organothallium compounds. The best studied reaction is the carbon-iodine conversion for the synthesis of aryl iodides, but other efficient conversions have been also described. 

Only 2-pyridyl reverse C-nucleosides are known. Coupling saccharide free radicals 831 and 834 with protonated pyridine derivatives gave the 2-pyridyl reverse C-nucleosides 832 and 835, respectively. Free radical 831 was obtained by decarboxylative photolysis of the uronic acid derivative 830 in the presence of hypervalent iodine compounds (92TL7575 (Scheme 232), whereas free radical 834 was obtained by thermal homolysis of the carbon-iodine bond in the 6-iodo-6-deoxy-o-galactopyranose derivative 833 in the presence of benzoyl peroxide (93JOC959) (Scheme 233). 

Monomers Mechanistically, coupling an electron-rich organotin molecule with an electron- deficient halide/triflate molecule promotes the desired C-C formation. Therefore, in order to obtain D-A copolymers of high molecular weight, electron-rich donor moieties are usually di-stannylated, whereas the electron-deficient acceptor moieties are typically halogenated. lodinated acceptors are generally more reactive due to the labile carbon-iodine bond, which also lowers the stability of the iodinated acceptors. On the other hand, chlorinated acceptors are relatively rare because of their low reactivity. Therefore, with a good balance of reactivity and stability, brominated acceptors are the most common ones for polymerization. 

Displacements by thiophenoxide ion have an interesting possibility - the nucleophile can attack one electron at a time, transferring an electron to produce a thiophenoxy radical while reductively cleaving the electrophile to form an alkyl radical. Then the two radicals, in a solvent cage, can couple (Fig. 1.23). In an exploration of this process, called the SET mechanism, we used thiophenoxide with the sodium salt of p-carboxybenzyl iodide, and with the corresponding mesylate. We saw that there was a large acceleration by added ethanol in the iodide case, but not with the mesylate. We proposed that in the iodide displacement this reflected the conversion of thiophenoxide ion, with its delocalized charge, into the much more hydrophobic thiophenoxy radical at the transition state. Other evidence as well supported the SET mechanism. The carbon-iodine bond is more easily reductively cleaved than is the carbon-mesylate bond. 

Ruthenium catalyst 6 enables the cycloaddition of iododiynes while preserving the reactive carbon-iodine bonds hence, the resulting iodoarenes can be applied to further cross-coupling reactions [49], Yamamoto et al. exploited ruthenium-catalyzed [2 + 2 + 2] cycloaddition for the construction of an interesting spirocyclic C-arylglycoside motif, which is found in bioactive natural products (i.e., papula-candins) (Scheme 3.29). In this study, idododiyne precursor 145 was prepared and... 

The living cationic polymerizations discussed above are invariably based on the nucleophilic iodide counteranion (activation of the carbon-iodine terminal bond Eq. 3). It is expected, however, that similar living processes are equally possible with other counteranions that can exert, as the iodide anion does, a suitably strong nucleophilic interaction with the growing carbocation. We have in fact found the phosphate anions to meet this requirement (10). Similarly to hydrogen iodide, monoacidic phosphate esters [H0P(0)R 2 R alkyl, alkoxyl, etc.] like diphenyl phosphate ( ) form a stable adduct 5) with a vinyl ether (Eq. 5). Zinc chloride or iodide then activates the phosphate bond in 5 by increasing its polarization (as in 6), and living cationic polymerization proceeds via an intermediate (7) where the carbocationic site is stabilized by a phosphate anion coupled with the zinc halide activator. 

With Phenylpropanolamine at hand (or ephedrine and pseudo-ephedrine) one would next need to reduce that alpha carbon OH group to get the final amine. Strike understands that the current favorite methods for doing this involve lithium and amine. HI and red P or other iodine related protocols. So when you meth heads ruin every aspect of those methods as well, what will you do then The following are a couple of OH reduction methods (Strike thinks) that have applicable use [99-100]. 

Sulfonic acids are prone to reduction with iodine [7553-56-2] in the presence of triphenylphosphine [603-35-0] to produce the corresponding iodides. This type of reduction is also facile with alkyl sulfonates (16). Aromatic sulfonic acids may also be reduced electrochemicaHy to give the parent arene. However, sulfonic acids, when reduced with iodine and phosphoms [7723-14-0] produce thiols (qv). Amination of sulfonates has also been reported, in which the carbon—sulfur bond is cleaved (17). Ortho-Hthiation of sulfonic acid lithium salts has proven to be a useful technique for organic syntheses, but has Httie commercial importance. Optically active sulfonates have been used in asymmetric syntheses to selectively O-alkylate alcohols and phenols, typically on a laboratory scale. Aromatic sulfonates are cleaved, ie, desulfonated, by uv radiation to give the parent aromatic compound and a coupling product of the aromatic compound, as shown, where Ar represents an aryl group (18). 

As inert as the C-25 lactone carbonyl has been during the course of this synthesis, it can serve the role of electrophile in a reaction with a nucleophile. For example, addition of benzyloxymethyl-lithium29 to a cold (-78 °C) solution of 41 in THF, followed by treatment of the intermediate hemiketal with methyl orthoformate under acidic conditions, provides intermediate 42 in 80% overall yield. Reduction of the carbon-bromine bond in 42 with concomitant -elimination of the C-9 ether oxygen is achieved with Zn-Cu couple and sodium iodide at 60 °C in DMF. Under these reaction conditions, it is conceivable that the bromine substituent in 42 is replaced by iodine, after which event reductive elimination occurs. Silylation of the newly formed tertiary hydroxyl group at C-12 with triethylsilyl perchlorate, followed by oxidative cleavage of the olefin with ozone, results in the formation of key intermediate 3 in 85 % yield from 42. 

A Fischer reagent had been made with pyridine, iodine, sulphur trioxide and formamide, instead of methanol. The bottle detonated after being stored for a couple of months. The authors put it down to the decomposition of formamide into ammonia and carbon oxide, which created the overpressure that caused the bottle to detonate. 

Buchberger et al. [104] carried out a selective determination of iodide in brine. The performance of a potentiometric method using an ion-selective electrode and of liquid chromatography coupled with ultraviolet detection at 230 nm were compared as methods for the determination of iodide in the presence of other iodide species. Satisfactory results were obtained from the potentiometric method provided the solution was first diluted tenfold with 5 M sodium nitrate, and external standards were used. Better reproducibility was, however, achieved with HPLC, provided precautions were taken to prevent reduction of iodine to iodide in the mobile phase, for which extraction of iodine with carbon tetrachloride prior to analysis was recommended. This was the pre-... 

Similar coupling and iodination reactions are observed with thienyl iodide, as shown in Eq. 2.38 [35]. Thus, carbon—carbon bond formation occurs with the first molecule of thienyl iodide, and subsequent Cu/I exchange occurs with the second molecule. 

The Merck process group in Rahway has developed two syntheses of rizatriptan (4) utilizing palladium catalyzed indolization reactions (Schemes 19 and 20). Both routes start from the iodoaniline 51, which was prepared by reaction of 47 with iodine monochloride in the presence of CaCOa. " Palladium catalyzed coupling of iodoaniline 51 with bis-triethylsilyl protected butynol in the presence of NaaCOa provided a mixture of indoles 52a and 52b. This mixture was desilylated with aqueous HCl in MeOH to furnish the tryptophol 53 in 75% yield from 51. Protection of the alkyne prevented coupling at the terminal carbon of the alkyne and tnethylsilyl (TES) was found to be optimal because it offered the correct balance between reactivity (rate of coupling) and... 

Chlorine, though capable of sotting iodine free from its combinations in aqueous solutions, is now rarely employed to detect iodine, since an excess of the agent converts the iodine into a colorless combination of chloride of this element. Bromine comports itself differently, for although it is capable cf liberating it, still none of the iodine is redissolved. Be LuCCA has made this behavior the basis of a method for the analysis of iodides by means of a standard solution of bromide, coupled with the uso of sulphide of carbon, which takes up the iodine as it is liberated by the bromine liquor. From the volume of the latter which is expended in setting free the whole of the iodine—ascertained by the sulphide of carbon being colorless when drawn off with the pipette—its quantity is found. 

---