Asymmetric iodination

Another approach for the chemoselective and asymmetric iodination of unactivated C H bonds was reported with a palladium catalyst using a chiral auxiliary (Scheme 5.19). Excellent diastereoselectivities were induced by chelating the auxiliary to the palladium catalyst center followed by an electrophilic C—H activation and iodination. Studies showed that I2 acts as both the reactant and the activator to form the reactive catalyst precursor, Pd3(OAc)3. After the reaction was completed, the formed Pdl2 was precipitated from the solution and could be reused several times without losing reactivity and selectivity. 

The combination of a hindered oxazoline auxiliary, Pd(OAc)2, h, and PhI(OAc)2 was shown to be a powerful protocol for the selective catalytic and asymmetric iodination of unactivated C-H bonds of methyl, cyclopropyl, and aryl groups for instance, compounds 152, 154, and 156 were easily converted under mild conditions into iodo derivatives 153,155, and 157 in good yields and excellent diastereoselectivity <05AG(E)2112>. 

Asymmetric iodination of 4-pentenamides derived from (2R,5R)-b s-(methoxymethyl)-pyrrolidine 1.65 (R = CT OMe) by I2 and s-collidine has been carried out at room temperature by Taguchi and coworkers [1074] with a high selectivity. 

Dimeric and polymeric (dimethylaminomethyl)phenylindium iodides associated by asymmetric iodine bridges (In-12.838 A, In- - -I 3.405 and In-I 2.837 and In- - -I 4.262 A) have been reported [143a]. 

Giri R, Chen X, Yu J-Q (2005) Palladium-catalyzed asymmetric iodination of imactivated C-H bonds under mild conditions. Angew Chem IntEd 44(14) 2112-2115... 

Such bifunctional catalysis by a chiral secondary amino alcohol catalyst is also effective for the direct asymmetric iodination of aldehydes with N-iodosuccinimide, in which a slightly modified catalyst [17b with a bis(pentafluorophenyl) hydroxymethyl group] displayed remarkable catalytic and chiral efficiencies (Scheme 7.30) [53]. 

Kano T, Ueda M, Maruoka K. Direct asymmetric iodination of aldehydes using an axiaUy chiral bifunctional amino alcohol catalyst. J. Am. Chem. Soc. 2008 130(12) 3728-3729. 

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). 

A valuable feature of the Nin/Crn-mediated Nozaki-Takai-Hiyama-Kishi coupling of vinyl iodides and aldehydes is that the stereochemistry of the vinyl iodide partner is reflected in the allylic alcohol coupling product, at least when disubstituted or trans tri-substituted vinyl iodides are employed.68 It is, therefore, imperative that the trans vinyl iodide stereochemistry in 159 be rigorously defined. Of the various ways in which this objective could be achieved, a regioselective syn addition of the Zr-H bond of Schwartz s reagent (Cp2ZrHCl) to the alkyne function in 165, followed by exposure of the resulting vinylzirconium species to iodine, seemed to constitute a distinctly direct solution to this important problem. Alkyne 165 could conceivably be derived in short order from compound 166, the projected product of an asymmetric crotylboration of achiral aldehyde 168. 

Recently, two new axially chiral compounds 44 and 45 have been prepared [44, A-acryl-A-allyl-o-t-butylanilide 45, A-(o-t-butylphenyl)-2-methyl-maleimide]. This represents the first instance of using nonbiaryl axially chiral ligands in asymmetric Dield-Alder reactions. In the presence of iodine, high endo-facial and diastereofacial selectivities have been obtained in 44/45-medi-ated reactions.10... 

Asymmetric Diels-Alder reactions have been carried out to investigate the efficacy of anilide 44 and imide 45 as dienophiles. In the presence of iodine, the asymmetric Diels-Alder reaction of anilide (+)-44 shows a remarkable improvement in both reactivity and stereoselectivity (Table 5-1). Therefore, it is believed that, in the presence of I2, Diels-Alder reactions of A -al I yl ic enamides take place through an activating process involving the formation of a cationic iodocyclization intermediate. 

TABLE 5-1. Iodine-Mediated Asymmetric Diels-Alder Reaction of ( + )-44... 

Asymmetric oxidation of sulfides to sulfoxides occurs in the presence of chiral catalysts. It was found (53) that oxidation of benzyl methyl sulfide with iodine suspended in (i )-2-methyl-2-phenylsuccinate 33 buffer gives optically active benzyl methyl sulfoxide 34 having 6.35% optical purity. Much higher asymmetric... 

A single paper from Charette and coworkers details the catalytic asymmetric hydrogenation of W-iminopyridinium ylides to substituted piperdines using PHOX ligand 82 in combination with iodine (Table 17) [81]. 

A very successful example for the use of dendritic polymeric supports in asymmetric synthesis was recently described by Breinbauer and Jacobsen [76]. PA-MAM-dendrimers with [Co(salen)]complexes were used for the hydrolytic kinetic resolution (HKR) of terminal epoxides. For such asymmetric ring opening reactions catalyzed by [Co(salen)]complexes, the proposed mechanism involves cooperative, bimetallic catalysis. For the study of this hypothesis, PAMAM dendrimers of different generation [G1-G3] were derivatized with a covalent salen Hgand through an amide bond (Fig. 7.22). The separation was achieved by precipitation and SEC. The catalytically active [Co "(salen)]dendrimer was subsequently obtained by quantitative oxidation with elemental iodine (Fig. 7.22). 

Iodinated contrast agents with polyhydroxylated carbon side-chains contain a number of asymmetric carbon atoms yielding numerous optical isomers which relate to each other as enantiomers or diastereoisomers. Sterically hindered non-asymmetric carbon or nitrogen atoms might result in additional asymmetry centres while the partial double bond character of the acyl-carbon-nitrogen bond of amide functions can lead to cisitrans isomerism. Such isomers are labelled rotamers when heating in solution is able to modify their ratio. Isomerism of iodixanol has been described by Priebe et al. [122], Fossheim et al. [123] and by Molander et al. [115]. 

While the research filed of selenium catalyzed reactions appears to be promising, the application of iodine as a catalyst is of course limited, since the development of an asymmetric version is not possible. Furthermore, much care has to be taken, that the iodine is the active catalyst and not traces of HI. 

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