Intermediate, Iodonium

The anomalous iodoacetamide-fluoride reaction violates this rule, in that a less stable -halonium complex (18) must be involved, which then opens to (19) in the Markownikoff sense. This has been rationalized in the following way estimates of nonbonded destabilizing interactions in the possible products suggest that the actual product (16) is more stable than the alternative 6)5-fluoro-5a-iodo compound, so the reaction may be subject to a measure of thermodynamic control in the final attack of fluoride ion on the iodonium intermediate. To permit this, the a- and -iodonium complexes would have to exist in equilibrium with the original olefin, product formation being determined by a relatively high rate of attack upon the minor proportion of the less stable )9-iodonium ion. 

Disubstituted alkenes undergo iodohydroxylation regioselectively when the allylic position bears a hydroxyl group [110]. The attack on the distal carbon of the iodonium intermediates is favored on the polarity alternation basis. 

Owing to the Curtin-Hammett principle, the ratio of the iodonium intermediates 39 and 40 does not reflect the distribution of the conformers in 38 (5H4 4H5 = 95 5). Thus, both the 2-deoxy-2-iodo-ot-mannoside 50 and the 2-deoxy-2-iodo-P-glucoside 51 are formed in almost equimolar amounts. Similar results are observed in glycals with nitrile or carboxamide functions [11]. 

The mechanism of glycal addition was further examined by Horton and coworkers,86 who have used this method to form (7S,9S)-4-demethoxy-7-0-(2,6-dideoxy-2-iodo-a-L-mannopyranosyl)-adriamycinone87 and -daunomycinone,88 which are iodinated analogs of natural antitumor compounds. The nature of the solvent was found to be critical. In particular, they were able to generalize that in non-coordinating polar solvents, where no possibility for interaction with iodine exists—that is, no lone-pair interactions—the formation of the iodonium intermediate was irreversible, and the resultant stereochemistry reflects the electronic... 

Anodic iodination 24°) involves an iodonium intermediate, probably N-iodo-acetonitrilium perchlorate (29) undergoing electrophilic aromatic substitition (Eq. (100) ). A radical cation (28) as intermediate is improbable in this case. Electrolysis of iodine and aromatics in CH3CN/LiC104 yields the corresponding... 

The side chain R in these enals contained functionalities such as a double bond, or an acetoxy group, which were unaffected. The reaction proceeds again through a vinyl iodonium intermediate which serves as a reactive allyl cation. In this way the umpolung of allylsilanes is achieved and, indirectly, the reactivity of allyl halides is considerably increased. 

H < Cl < Br < I [80], so that proton addition is most likely to lead to an "open carbonium ion (i), while at the other extreme "electrophilic iodine seems invariably to give an "iodonium intermediate (3). The differential bonding expressed by diagram (2) is considered to represent the structures of intermediates derived from those unsymmetrical olefins which react in the Markownikoff sense [3S]> a-nd at the same time exhibit stereoselectivity in forming only trans addition products. 

R and R" are cis in the starting compound, they will be trans in the product (2) there is retention of configuration within the migrating group R. " " Since vinylic boranes can be prepared from alkynes (15-16), this is a method for the addition of R and H to a triple bond. If R = H, the product is a (Z)-alkene. The mechanism is believed to involve an iodonium intermediate, such as 92, and attack by iodide on boron. When R is vinylic, the product is a conjugated diene." " ... 

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. 

Three-membered rings other than epoxide follow the same ring opening pathways. An example of such an opening is the iodolactonization reaction discussed in Section 2.10.C. Reaction of 189 with base in the presence of iodine likely gives a carboxylate anion-iodonium intermediate (190). Displacement of iodide by carboxylate, (path a) is a 5-exo process and is favored over the analogous 6-endo process (path b). The final product is iodolactone 191. 2 jt is noted that this reaction may not proceed by discreet iodination to give 190. 

The observed yn-stereoselectivity of this difluorination is explained by a two-step mechanism involving the flnfi-addition of the reagent to the double bond through cyclic iodonium intermediate 34 in the first step and then nucleophilic substitution of iodotoluene with fluoride anion in 35 in the second step (Scheme 3.13) [35]. 

In a series of communications, McNelis and coworkers have reported the scope of reactions of the reagent combination PhI(OH)OTs-halogen or PhI(OH)OTs-M-halosuccinimide with alkynols, resulting in the formation of various haloenones [125-133], All these oxidative rearrangements involve iodonium intermediates and are highly regio- and stereoselective. For example, bromoethynyl alcohols 109 are cleanly converted into (3,(3-dihaloenones 110 by reaction with the PhI(OH)OTs-l2 system (Scheme 3.44) [127,128]. 

A similar hydroxylation of aromatic, heteroaromatic and aliphatic ketones can also be performed using [bis(trifluoroacetoxy)iodo]benzene imder acidic conditions (Scheme 3.57) [183]. A plausible mechanism for this hydroxylation involves initial electrophilic addition of PhI(OCOCF3)2 to the enolized ketone and subsequent nucleophilic substitution in the iodonium intermediate. 

Hennecke developed enantioselective haloetherification reactions via desymmetrisation of in situ generated meso-iodonium intermediates (Scheme 2.37). Chiral sodium phosphate 58 was used for the cyclisation of symmetrical ene-diol substrates 59 with l-iodopyrrolidin-2-one (60), and the corresponding iodoetherification products 61 were obtained with up to 71% ee. 

Finally it seems worthwhile to mention other pathways, probably ionic, for the cyclization of unsaturated mercaptans. Thus iodine addition in the presence of potassium carbonate to form a sulfenyl iodide which cyclizes via iodonium intermediates has been proposed. This cyclization reaction has been used recently by Nicolaou to prepare 6,9-thiaprostacyclin, a stable and biologically potent analog of prostacyclin PGIj in a reaction involving cyclization of a 4-pentene-l-thiol leading to the iodomethylated five-membered ring. The high selectivity toward formation of the (Cy5) compound in the Cy5/Cy6... 

Verma et al. [62] observed a chemoselective behavior of iodine in diSeient solvents in the electrophilic iodocyclization of o-alkynyl aldehydes. o-Alkynyl aldehydes on reaction with in CH C with appropriate nucleophiles provided pyrano[4,3-6]quinolines 40 via the formation of cyclic iodonium intermediate 39. In case of using alcohols as a solvent as well as nucleophile, o-alkynyl esters 42 were obtained selectively in good to excellent yields via the formation of hypoio-dide intermediate 41. Subsequently, o-alkynyl esters 42 were converted into py-ranoquinolinones and isocoumarins by electrophilic iodocyclization. The developed oxidative esterification provides a novel access for the chemoselective synthesis of esters 43 from aldehydes without oxidizing primary alcohol present in the substrate (Scheme 10.28). 

As an alternative to our synthetic routes described so far, we also evaluated a more direct approach to the isochromanone fragment. As shown in Scheme 12, the concept to access 63 relied on a three-step, tandem process. The sequence was based on an iodocyclization of a suitable benzoic acid-derived alkene 64. After formation of putative iodonium intermediate 66... 

Iodotoluene difluoride reacts with steroidal silyl enol ethers to give a-fluoro-ketones. Whilst the reaction is slower than with xenon difluoride, the rea nt may find use since the stereochemical outcomes of the reactions differ, suggesting an electrophilic mechanism for the latter reagent, but a nucleophilic mechanism (via an iodonium intermediate) for the iodo-arene derivative. 

A variety of substituted indoles (45) can be synthesized from the reaction of N-aryl enamines (44) with PIDA (Scheme 8.16). The formation of the iodonium intermediate 46 followed by an intramolecular SN2"-type cycliza-tion gives the intermediate 47, which tautomerizes to 45 after the formation of deprotonated 48. 

Bartlett conducted a study of iodolactonization reactions with a range of acyclic substrates and reported notable selectivity trends [38]. In the absence of base, the initial formation of the iodonium intermediate is reversible, and the stereochemical outcome of the cyclizations are under thermodynamic control. Consequently, lactonization of 202, 205, and 208 afford products with vicinal anti relative configurations 20i/204 (dr=10 l. Equation 32), 206/207 (cir=20 l. Equation 33), and 209 (dr>20 l. Scheme 9.27). 

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