Iodination reagents iodine azide, addition

Iodine azide is a highly selective reagent addition to the 16-double bond of androsta-4,16-diene-3-ones is possible and some selectivity in addition to the 16-double bond of A -dienes has been observed.Hydroxy groups in the steroid should be protected, e.g., by acetylation, since in some instances oxidized side products are formed. 

In the case of electrophilic addition, the reactions of tricyclic dienes 1 with several electrophilic reagents have been investigated.1 7 Interestingly, some of these compounds undergo addition reactions with remarkable syn stereoselectivity. For example, the reaction of dimethyl tricy-clo[4.2.2.02,5]deca-3,9-diene-7,8-dicarboxylate with iodine azide solution, prepared in situ from an excess of sodium azide and iodine monochloride, in acetonitrile at — 5 C provided the. yyn-4-azido-3-iodo derivative 2 (Table 1) in 90% yield.1,2,4,6 The formation of the 5,>,n-4-azido-3-iodo derivative 2 is thought to be the first example of a syn addition of iodine azide to an alkene.1,2 The formation of the syn-product is best explained by the twist strain theory,8 according to which the syn transition structure A is favored over the an/7-coplanar transition structure B.1... 

Under a nitrogen atmosphere, even iodine azide undergoes addition to alkenes with a reversal of the regiochemistry, consistent with a radical pathway24,38 41. Furthermore, the solvent and the source of iodine azide affect the nature of the reagent and consequently the regio- and stereoselectivity of the addition14 16 42,43. 

The addition of iodine azide to double bonds gives p-iodo azides. The reagent can be prepared in situ from KI—NaNa in the presence of Oxone -wet alumina. The addition is stereospecific and anti, suggesting that the mechanism involves a cyclic iodonium ion intermediate. The reaction has been performed on many double-bond compounds, including allenes and a,p-unsaturated ketones. Similar reactions can be performed with BrNa and CfNa. 1,4-Addition has been found with acyclic conjugated dienes. In the case of BrNa, both electrophilic and free-radical mechanisms are important, whUe with CIN3 the addi-... 

Generally, iodine azide adds to an alkene by an ionic pathway, yielding a tram addition product however, in a few cases nitrile reagents compete successfully with azide ion in attacking the iodonium intermediate. Thus, ci-pinene was converted into tetrazole (125) in a one-pot reaction in near quantitative yield (Scheme 59).This type of process is far from general. 

Aziridines2 )3-Iodoazides, available by the addition of iodine azide to olefins, undergo reduction of the azide function followed by base-catalyzed ring closure to aziridines. The most satisfactory reagent for this purpose is lithium aluminum hydride, which can accomplish both reaction steps since it is a Lewis acid as well as a reducing agent. Competing side reactions are elimination of the elements... 

Two groups have investigated the details of the stereochemistry and mechanism for electrophilic additions to the cyclobutene double bond in the tricyclo[4,2,2,0 ]deca-3,7-diene (875) and its derivatives. With iodine azide, for example, a reagent which normally leads to trans-adducts by an anti-coplanar addition mechanism, addition to (875) occurs only by syn-attack at the sterically unhindered side of the cyclobutene double bond> " a result explained in terms of twist-strain... 

In addition, this type of aromatic ring activation by the SET oxidation strategy using hypervalent iodine reagents was utilized for the total synthesis of a sulfur-containing pyrroloiminoquinone alkaloid, ( )-makaluvamine F [119-121]. The reaction for the construction of the a-amino dihydrobenzothiophene part involved the efficient cyclization of the benzyl thioether. Hypervalent iodine reagent was iteratively utihzed for the successive oxidative transformation, that is, the azidation at the a-position of the sulfur group of the dihydrobenzothiophene via a Pummerer-like mechanism (Scheme 24). 

Following these early contributions, in 2001, Bols et al. reported that iodonium azide (IN3) could be employed to azidate ethereal C-H bonds (Scheme 6.13a, method A) [59]. Mechanistic studies revealed that the reaction proceeds via a free-radical chain mechanism (Scheme 6.13b). Initiation occurs by weak I-N3 bond homolysis to give the iodine radical and the azide radical, which abstracts the H atom of the substrate to give the benzylic radical A. The benzylic radical A reacts with IN3 to provide the product. In addition, the same group found that the reagent combination PIDA/TMSN3 that acts as a substitute of hazardous IN3 could also perform direct azidation of ethereal C-H bonds (Scheme 6.13a, method B) [60]. The mechanism is similar to the one suggested in Scheme 6.12b. 

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