Stereospecific reactions hydrogenation

We have previously seen (Scheme 2.9, enby 6), that the dehydrohalogenation of alkyl halides is a stereospecific reaction involving an anti orientation of the proton and the halide leaving group in the transition state. The elimination reaction is also moderately stereoselective (Scheme 2.10, enby 1) in the sense that the more stable of the two alkene isomers is formed preferentially. Both isomers are formed by anti elimination processes, but these processes involve stereochemically distinct hydrogens. Base-catalyzed elimination of 2-iodobutane affords three times as much -2-butene as Z-2-butene. 

Since the stereochemical course of a catalytic hydrogenation is dependent on several factors, " an understanding of the mechanism of the reaction can help in the selection of optimal reaction conditions more reliably than mere copying of a published recipe . In the first section the factors which can influence the product stereochemistry will be discussed from a mechanistic viewpoint. In subsequent sections the hydrogenation of various functional groups in the steroid ring system will be considered. In these sections both mechanistic and empirical correlations will be utilized with the primary emphasis being placed on selective and stereospecific reactions. 

Enol lactones are assumed to form from iV-methylisoquinolinium salts as a result of a Hofmann-type degradation process. This P elimination is a highly stereospecific reaction in which Z isomers are produced from precursors of erythro configuration and isomers from threo diastereomers(5,97). This fact seems to suggest that syn rather than the more usual anti elimination takes place. Examination of models indicates, however, that there is a preferred conformation in which the C-8 hydrogen is in the syn and coplanar position to the quaternary nitrogen. This hypothesis was proved correct in experiments carried out in vitro (5,14,15,91-94). 

A complicating factor associated with experimental application of the Skell Hypothesis is that triplet carbenes abstract hydrogen atoms from many olefins more rapidly than they add to them. Also, in general, the two cyclopropanes that can be formed are diastereomers, and thus there is no reason to expect that they will be formed from an intermediate with equal efficiency. To allay these problems, stereospecifically deuteriated a-methyl-styrene has been employed as a probe for the multiplicity of the reacting carbene. In this case, one bond formation from the triplet carbene is expected to be rapid since it generates a particularly well-stabilized 1,3-biradical. Also, the two cyclopropane isomers differ only in isotopic substitution and this is anticipated to have only a small effect on the efficiencies of their formation. The expected non-stereospecific reaction of the triplet carbene is shown in (15) and its stereospecific counterpart in (16). 

The concept of alternative reaction pathways leads to the concepts of selectivity and stereospecificity in hydrogenation catalysis. 

The stability of enzyme-NADH was evidenced by its isolation after Sephadex chromatography and led to the direct spectrophotometric demonstration of enzyme-NADH. The formation of enzyme-NADH in this reaction was used to examine the stereospecificity of hydrogen transfer for acceptance from carbon 4 of the sugar nucleotide by enzyme-NAD+ and donation of the same hydrogen back to carbon 6. For both steps / -stereospecificity of hydrogen transfer to the nicotinamide moiety of the pyridine nucleotide was established. 

The interaction of unsaturated molecules, for example olefins and acetylenes, with transition metals is of paramount importance for a variety of chemical processes. Included among such processes are stereospecific polymerization of olefin monomers, the production of alcohols and aldehydes in the hydroformylation reaction, hydrogenation reactions, cyclo-propanation, isomerizations, hydrocyanation, and many other reactions. 

The property that the stereochemical result of an electrocyclic reaction is absolutely predictable is called stereospecificity. A stereospecific reaction will give you one stereochemical result when a cis starting material is used, and the opposite result when a trans starting material is used. Other examples of stereospecific reactions include Sn2 substitutions, catalytic hydrogenation of alkynes or alkenes, and dihydroxylation and bromination of alkenes. 

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