Conformations, anomeric effect reaction

Abe H, Shuto S, Matsuda A (2001) Highly a- and P-selective radical C-glycosylation reactions using a controlling anomeric effect based on the conformational restricrion strategy. A study on the conformation - anomeric effect - stereoselectivity relationship in anomeric radical reactions. J Am Chem Soc 123 11870-11882... 

The Ueno-Stork reaction is a radical cyclization of the a-haloacetal of an aUylic alcohol that provides substituted tetrahydrofuran and y-lactone derivatives. The chiral center of the aUylic moiety can control the stereochemical outcome, and the stereoselectivity may also be affected by the conformational anomeric effect. The Ueno-Stork radical cyclization has been applied in the synthesis of (-l-)-eldanolide (Scheme 25.22)," the pheromone of the male African sugarcane stem borer Eldana saccharina, in which bromoacetal 49 evolves to 50. The stereochemical outcome of these reactions is rationalized by a chair-like transition state, in which the adopted conformation maximizes the anomeric effect of the acetal center. 

It is interesting to speculate that asymmetric induction may be the consequence of the exo anomeric effect, a stereoelectronic effect that favors the conformation 5 that places the aglycone O-C bond antiperiplanar to the pyran C(1) —C(2) bond7fi. Related asymmetric induction has also been observed in aldehyde addition reactions of the related, but racemic, pinacol (Z)-y-(tetrahydropyranyloxy)allylboronate49. As indicated in the examples above, however, the level of diastereoselectivity is modest and the only application in asymmetric synthesis is Wuts exo-brevicomin synthesis75. 

The role of steric effects is unclear but the anomeric effect could also contribute to an increase in electron density at nitrogen. X-ray data for the two TV-acyloxy-TV-alkoxyamides, a urea and a carbamate outlined above show clear evidence, both from bond lengths and conformations, of an anomeric interaction RO-N bonds are short when compared to alkoxyamines. This interaction is responsible for SN1, SN2, homolytic and rearrangement reactions of /V-acyloxy-TV-alkoxyamides (vide infra) and has also been supported computationally. Acyloxylation of the hydroxamic esters results in both pyramidalisation as well as anomeric donation from the... 

When reacted with an alcohol in the presence of a catalytic amount of a strong acid, 3,4-dihydro-2/f-pyran yields a base-stable 2-alkoxytetrahydropyran (a cyclic acetal) (Scheme 4.13). The reaction is reversed if the acetal is treated with aqueous acid (see Section 3.3.4, page 54), so that this provides a simple way of protecting alcohols in syntheses where a strong base might otherwise deprotonate them. The conformational preferences of 2-alkoxytetrahydopyrans, mediated by the anomeric effect, were commented upon earlier (Section 1.5.3). 

A similar series of reactions was performed on a 6-azido-6-deoxy-2-ketose.246,252 In most of the foregoing syntheses, the piperidine formed is accompanied by the tautomeric furanose. The tautomers can, however, be separated without occurrence of equilibration (which can be induced by changing the pH of the medium). For the ketose derivative 183, the equilibrium mixture includes246 compound 184 and a dehydration product (182). The conformation and anomeric effect in these piperidines have been studied by n.m.r. spectroscopy,253 and their fragmentation pathways have been determined by mass spectrometry.254... 

The work on pyranoses led Isbell to recognize the importance of conformation on reaction rates. He found that /3-D-glucopyranose was oxidized much more rapidly than the a form, which led him to conclude that the six-membered tetrahy-dropyran ring could not be planar otherwise, the two anomers would have been symmetrical and would have reacted at the same rate (see Fig. 1). Isbell s observation regarding the difference between the reactivity of anomers was the first of a series of phenomena now designated as the anomeric effect. ... 

In the PB reaction of furan derivatives with benzaldehyde (as shown in Scheme 7.13), a site-random - but highly stereoselective - formation of exo-oxetanes was reported (Scheme 7.13) [15q,30]. The highly exo-selective formation of oxetanes was explained by the conformational stability of the intermediary triplet biradicals. The anomeric effect was proposed to play an important role in stabilization of the exo-isomer precursor (Scheme 7.20). Thus, the inside conformer which should... 

The marked stereoselectivity of these radical reactions must be ascribed to the effect of the bulk of the protecting groups. However, the radicals that were manipulated may have also shown an anomeric effect due to the vicinal oxygen. In a furanose sugar it is not easy to evaluate the anomeric effect without ESR, and also, the molecules concerned have two fused five-membered rings. This fixes the conformation into a V-shape. Such molecules are well known to have exo-reactivity and the formation of endo-bonds is difficult. All these effects may be acting together to make this nucleoside chemistry especially stereospecific. 

An alternative access to L-amino acids was found by using chloroform as solvent in the asymmetric Strecker synthesis with galactosyl imines [24], This interesting reverse of asymmetric induction compared to the reactions shown in Scheme 5 can be explained by considering the zinc complex A as the crucial reactive species. Due to the exo anomeric effect, which is a delocalization of the 7r-electrons into the a of the ring C-O-bond, the imines adopt the conformation represented in Scheme 8. 

But we start with a compound that is so simple that it has only one conformation because it has no rotatable bonds dichloromethane. You may have wondered why it is that, while methyl chloride (chloromethane) is a reactive electrophile that takes part readily in substitution reactions, dichloromethane is so unreactive that it can be used as a solvent in which substitution reactions of. other alkyl halides take place. You may think that this is a steric effect indeed, Cl is bigger than H. But CH2CI2 is much less reactive as an electrophile than ethyl chloride or propyl chloride there must be more to its unreactivity. And there is dichloromethane benefits from a sort of permanent anomeric effect . One lone pair of each chlorine is always anti-periplanar to the other C-Cl bond so that there is always stabilization from this effect. 

Although the cost of the correlated models has limited their application to fairly small molecules, -277 implementations of the methodology at simply the Hartree—Pock level have been used to study the basicity of methyl-amines,conformational equilibria in esters and amides,the influence of solvation on the anomeric effect, 5 2 reactions,and even structural properties of biopolymers like In addition, considerable attention... 

As you now know (p. 1134) aU esters and lartones prefer to be in the conformation shown for the first compound so that they can enjoy stabilization by the anomeric effect. The second ester would also prefer o be like this too (first diagram below) but in this conformation it cannot cyclize at all. Even in the less favourable conformation it uses for reaction, it prefers conjugate to dirert substitution as the latter would give a strained truns-cycloheptene. The first compound can enjoy both the anomeric effert and conjugate addition as a frans-alkene in a ten-membered ring is fine. It is better than fine in the heterocyclic product as the lactone also enjoys the anomeric effect... 

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