Non-isohypsic transformations

Non-isohypsic transformations are feasible only for certain types of derivatives, namely those especially apt to undergo oxidation or reduction. 

Non-isohypsic Transformations as Pathways Connecting Different Oxidation Levels... 

Non-isohypsic transformations are especially important in the syntheses of various nitrogen-containing derivatives. A common route for obtaining amines is the reduction of nitrogen-containing derivatives of carboxylic acids (nitriles or amides), aldehydes and ketones (imines) ... 

Another non-isohypsic transformation, addition of halogens to a double bond, is probably the oldest known reaction of unsaturated compounds. It is widely used for both industrial and laboratory purposes. The products formed, 1,2-dihaloalkanes, are valuable for conversion into vinyl halides (such as vinyl chloride monomers for the production of PVC) or alkynes ... 

As we have already shown, the creation of novel carbon-carbon bonds usually results in the formation of functionalized derivatives (the Wurtz coupling and Friedel-Crafts alkylation are probably the only exceptions). That is why a set of special reductive methods was devised to remove residual functionality that is unwanted in the final structure. The well-known hydrogenation of alkenes and alkynes belongs to this group of non-isohypsic transformations. Several other pathways available for the reductive removal of various functions will briefly be considered below. 

As illustrated, the major steps in the conversion of 140 to 139 correspond to non-isohypsic transformations of functional groups the reduction of an aldehyde to a primary alcohol, the oxidation of a secondary alcohol to a ketone, and the oxidation of a primary alcohol to a carboxylic acid. The introduction and removal of the isopropylidene protecting groups and the use of the bacterium Aeetobacter suboxydans (a non-typical oxidizing agent) ensures selectivity in the reactions of the polyfunctional intermediate compounds. 

The basic route to the synthesis of epoxides and, in general, vicinal bifunctional derivatives is a non-isohypsic (oxidative) transformation of alkenes (to be discussed below), Epoxides can also be formed directly as a result of certain C-C bond-forming reactions such as the Darzens reaction (modification of a classical aldol-like reaction with a-chloro esters 130 as a methylene component)... 

A thoughtful reader would have noticed that, while plenty of methods are available for the reductive transformation of functionalized moieties into the parent saturated fragments, we have not referred to the reverse synthetic transformations, namely oxidative transformations of the C-H bond in hydrocarbons. This is not a fortuitous omission. The point is that the introduction of functional substituents in an alkane fragment (in a real sequence, not in the course of retrosynthetic analysis) is a problem of formidable complexity. The nature of the difficulty is not the lack of appropriate reactions - they do exist, like the classical homolytic processes, chlorination, nitration, or oxidation. However, as is typical for organic molecules, there are many C-H bonds capable of participating in these reactions in an indiscriminate fashion and the result is a problem of selective functionalization at a chosen site of the saturated hydrocarbon. At the same time, it is comparatively easy to introduce, selectively, an additional functionality at the saturated center, provided some function is already present in the molecule. Examples of this type of non-isohypsic (oxidative) transformation are given by the allylic oxidation of alkenes by Se02 into respective a,/3-unsaturated aldehydes, or a-bromination of ketones or carboxylic acids, as well as allylic bromination of alkenes with NBS (Scheme 2.64). 

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