Glycals addition mechanisms

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... 

The determination of the lifetime of the ionic intermediates using the azide-clock method has been however useful in showing that electrophilic addition of Br2 can occur, even through a fully concerted mechanism, definable as SN2-like. Bromination of cyclic enol ethers (glycals) 8-10 in methanol in the presence of... 

The addition of chloro azide CIN3 on the double bond of glycals proceeds by either an ionic or a radical mechanism depending on experimental conditions. Under UV irradiation, in solvents of low polarity and in the absence of oxygen, radical addition is predominantly regio- and stereoselective [51, 52]. The double bond reactivity is affected by the substituent at C-3 position and its inductive effect. Therefore, the presence of acetates lowers the reactivity, but azidosides are formed following Scheme 25. 

The cis addition of nitrosyl chloride to substituted cyclic enol ethers and O-protected glycals, rationalized as either molecular addition through a four-centered polar transition state or by radical mechanism, generally takes place with complete simple and induced diastereose-lectivity45-47. 

The addition of chlorine azide to acetylated or benzylated glycals afforded different mixtures of stereo- and rcgioisomcrs, depending on the experimental conditions (in the dark, or under irradiation with a mercury lamp), since an ionic or a concerted mechanism of addition as well as... 

Taking into account the lack of chemoselectivity and stereoselectivity of these silver ion-mediated reactions, it is reasonable to postulate an SNl-type mechanism for this process, leading to the formation of oxonium ion 14, despite the electron-withdrawing effect of the CF3 group (see Scheme 6.8). The stereochemical outcome should be ascribed to the steric or electronic preference of methanol addition to two possible diastereo-faces of the trifluoromethyl oxonium ion 14, in which the interactions are probably different from those in nonfluorinated DHA derivatives. In order to disfavor the formation of oxonium 14, the reaction was performed without silver salt in MeOH. While the reaction rate did not decrease significantly, only 23% of glycal 18 was obtained. Furthermore, the... 

Sodium Azide/Ammonium Cerium(IV) Nitrate. Silyl enol ethers give a-azido ketones on treament with sodium azide and anhydrous ammonium cerium(IV) nitrate in anhydrous acetonitrile (see Eq. 97).297 325 33i With a glycal, the 2-azido-1-hydroxy nitrate derivative is formed.332 Low yields due to hydrolysis of the silyl enol ether may be improved by use of the triisopropylsilyl (TIPS) derivatives,331 although with a sterically encumbered taxane-derived enol ether the TMS derivative gives higher yields than the TIPS derivative.325 The mechanism is believed to involve addition of an azide radical to the double bond. 

In accordance with expectations, methoxymercuration of glycals and their acetates has been found, by two independent groups working concurrently, to give rise to methyl glycosides having C-2-mercury bonds, and it is considered that the mechanism of the addition involves the formation of 1,2-mercm-inium ions which are attacked at C-1 hy the solvent. 

Figure 6. Possible mechanism of addition of fluorine to glycals with Xep2. (a) Electrophilic addition of F from XeF2-BF3 complex, (b) addition of F on carboxonium ion,...

They observed mainly a-glycoside products in their examples using glycals with all equatorial substituents. Danishefsky [84] has obtained, in allal series, a P-glycoside with the BMLF protocol. Earlier physical organical studies had shown that the hydration of enol ethers occurs via an AdE2 (addition-electrophilic-bimo-lecular) mechanism, i.e., a first step of protonation to form an oxocarbenium ion followed by a second step of nucleophilic addition [85, 86] (Fig. 5.45). 

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