Positive charge-induced cleavages

By far, 2-fluoro-2-deoxyfuranoses have been the most studied compounds. Indeed, at a structural level they are the closest analogues of 2-deoxynucleosides. Due to its electronic effect, the fluorine atom in the 2 position inhibits development of a positive charge on the anomeric carbon (which is responsible for the hydrolytic cleavage of nucleosides). In order to enhance the stability of 2-deoxynucleosides in acidic medium, and thus make oral administration of an antiviral compound easier, introduction of a fluorine atom in the 2 position is a commonly used strategy. The resulting protective effect toward proteolysis has been well demonstrated, as exemplified by the fluorinated analogues of ddl and ddA (cf. Chapter 3, Figure 3.13). However, the presence of this fluorine atoms often induces modifications in the antiviral properties of the molecule. ... 

The corrinoid-mediated reduction of polyhaloethenes has been the subject of a recent study, which reports reaction via homolytic C-halogen bond fission. The elimination of a further halogen radical affords haloalkynes, which lead to acetylene itself.56 The electron transfer-induced reductive cleavage of alkyl phenyl ethers with lithium naphthalenide has been re-examined in a study which showed that it is possible to reverse regioselectivity of the cleavage (i.e. ArOR to ArH or ArOH) by introduction of a positive charge adjacent to the alkyl ether bond.57 A radical intermediate has been detected by ESR spectroscopy in the reduction of imines to amines with formic acid58 which infers reacts takes place via Lukasiewicz s mechanism.59... 

In contrast to the reductive cleavage of 1-methylcyclohexene epoxide with LiAlH4 or, better, with LiEtjBH to produce 1-methylcyclohexanol, reduction of the epoxide with sodium cyanoborohydride in the presence of boron trifluoride etherate furnishes cE-2-methylcyclohexanol. In this case, complexation of the epoxide oxygen with the Lewis acid BF3 now directs hydride addition to the more substituted carbon, which can better sustain the induced partial positive charge. 

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