Axial radical

Rychnovsky demonstrated that the latter explanation is correct in reductive decyanations, the intermediate radical equilibrates to the most stable (axial) radical, and this equilibration determines the stereochemical outcome. Reductive decyanation of a 52 48 mixture of cyanohydrin acetonides 22 provided the 5yn-product 25 with 99 1 selectivity (Scheme 4). Ab initio calculations revealed a ca. 3.5 kcal/mol enthalpy difference between the axial and equatorial radical... 

Reductive decyanations of 2-cyanotetrahydropyran derivatives with sodium in ammonia yield predominantly axially protonated products. The observations are consistent with the reductive decyanation proceeding via the pyramidal, axial radical which accepts a second electron to give a configurationally stable carbanion, which in turn abstracts a proton from ammonia with retention of configuration (Rych-novsky, S. D. Powers, J. P. LePage, T. J., J. Am. Chem. Soc., 1992, 114, 8375-8384). Provide an explanation for the axial preference of the intermediate free radical on the basis of orbital interactions. Hint The title of the paper by Rychnovsky et al. is Conformation and Reactivity of Anomeric Radicals. ... 

Generally, the reactions are carried out in refluxing benzene solution, since the yield in benzene is better than that in other solvents. Probably, the radicals formed may be somewhat stabilized by the weak orbital-orbital interaction between the radicals and benzene. However, from the environmental point of view, toluene or dioxane is recently used. As substrates, alkyl bromides or alkyl iodides are used, and the reactivity increases in the order prim-alkyl < seoalkyl < te/t-alkyl. Sugar anomeric bromide (3) is generally not so stable, so the reaction is carried out under irradiation conditions with a mercury lamp at room temperature (eqs. 4.2 and 4.3). There are two types of anomeric glycosyl radicals as shown in Figure 4.1. One is the axial radical [I], and the other is the equatorial radical [I ]. The axial radical is more nucleophilic than the equatorial radical due to the stereoelectronic effect, where this effect comes... 

The formed anomeric radical adopts both a form (equatorial radical) [I] and (3 form (axial radical) [II], and these are in equilibrium state. However, the (3 form radical is more reactive and nucleophilic, because of its orbital interaction between the singly occupied radical orbital and the axial lone-pair on the neighboring ring-oxygen atom (like aftfi-periplanar effect) [20-22]. Therefore, the (3 form radical (axial radical) [II] predominantly reacted with a hydrogen donor to generate p-O-glycoside. 

In this synthesis, the reactant was chosen to control stereochemistry and give an equatorial alcohol, due to an intermediate axial radical use of hydride-transfer reagents would tend to afford predominantly the axial alcohol. 

One source of anomeric radicals and evidence for the preference of axial radical orientations has already been introduced in work reported by Vasella et al. [139,140]. The specific reaction, outlined in Scheme 7.77, involves the cleavage of a nitro group under radical forming conditions. 

Rychnovsky has employed highly stereoselective reductive decyanations of cyanohydrin acetonides in the synthesis of vy -l,3-diols [9, 10]. In the reduction of a 52 48 mixture of cyanohydrin acetonides by lithium in ammonia at —78°C, the stereochemistry of the reduction is set during the rapid and non-selective electron transfer to the intermediate axial radical, which generates the configurationally stable axial alkyllithium. Subsequent protonation from the axial direction gives the yy -l,3-diol acetonide with >100 1 stereoselectivity (Scheme 4). The same syn-... 

Treatment with LiDBB generates a single axial alkyllithium reagent via the axial radical, which adds effectively in a 1,2-fashion to the a,)9-unsaturated ketone (Scheme 13). 

An alkylation/reductive decyanation method was developed for the efficient synthesis of xjn-l,3-diols [9, 10]. Cyanohydrin acetonides are rapidly deprotonated by amide bases and alkylated with suitably reactive electrophiles to yield diaste-reomerically pure coupled products. Subsequent exposure to Li/NHa affords exclusively xy -l,3-diol acetonides (see above). Although the alkylation itself is stereoselective, it is noteworthy that the, 2>-syn stereochemistry is ultimately set in the reductive decyanation by virtue of the anomeric axial radical intermediate. This methodology was effectively applied in the total synthesis of the polyene macrolide roflamycoin (Scheme 15) [23]. Noteworthy is the formation of the entire protected polyol segment of roflamycoin by treatment of a late-stage intermediate with Li/ NHa to effect a simultaneous decyanation/debenzylation. 

Ammonia Casale SA Ammonia Natural gas (NG) Process produces anhydrous ammonia from natural gas by applying Casale s high-efficiency secondary reformer design, axial-radial technology for shift conversion, ejector ammonia wash system, axial-radical technology for ammonia converter and advanced waste-heat boiler design in the synthesis loop. 5 2010... 

Fig. 6.19. Four bed Kellogg quench cooled converter after modification to Ammonia Casale s four bed quench cooled axial-radical flow concept (from [591])...

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