Stereoselective reactions fumaric acid

The biological dehydrogenation of succinic acid described in Section 5 8 is 100% stereoselective Only fumaric acid which has a trans double bond is formed High levels of stereoselectivity are characteristic of enzyme catalyzed reactions... 

Optically inactive starting materials can give optically active products only if they are treated with an optically active reagent or if the reaction is catalyzed by an optically active substance. The best examples are found in biochemical processes. Most biochemical reactions are catalyzed by enzymes. Enzymes are chiral and enantiomerically homogeneous they provide an asymmetric environment in which chemical reaction can take place. Ordinarily, enzyme-catalyzed reactions occur with such a high level of stereoselectivity that one enantiomer of a substance is formed exclusively even when the substrate is achiral. The enzyme ftimarase, for example, catalyzes hydration of the double bond of fumaric acid to malic acid in apples and other fruits. Only the S enantiomer of malic acid is formed in this reaction. 

These terms are best illustrated by examples. Thus, if maleic acid treated with bromine gives the dl pair of 2,3-dibromosuccinic acid while fumaric acid gives the meso isomer (this is the case), the reaction is stereospecific as well as stereoselective because two opposite isomers give two opposite isomers ... 

However, if both maleic and fumaric acid gave the dl pair or a mixture in which the dl pair predominated, the reaction would be stereoselective but not stereospecific. If more or less equal amounts of dl and meso forms were produced in each case, the reaction would be nonstereoselective. A consequence of these definitions is that if a reaction is carried out on a compound that has no stereoisomers, it cannot be stereospecific, but at most stereoselective. For example, addition of bromine to methylacetylene could (and does) result in preferential formation of trans-1,2-dibromopropene, but this can be only a stereoselective, not a stereospecific reaction. 

Any reaction in which only one of a set of stereoisomers is formed exclusively or predominantly is called a stereoselective synthesis.184 The same term is used when a mixture of two or more stereoisomers is exclusively or predominantly formed at the expense of other stereoisomers. In a stereospecific reaction, a given isomer leads to one product while another stereoisomer leads to the opposite product. All stereospecific reactions are necessarily stereoselective, but the converse is not true. These terms are best illustrated by examples. Thus, if maleic acid treated with bromine gives the dl pair of 2,3-dibromosuccinic acid while fumaric acid gives the meso isomer (this is the case), the reaction is stereospecific as well as stereoselective because two opposite isomers give two opposite isomers ... 

Generally speaking, these distinctions have not been observed by biochemists. Stereoselective has been little used, and stereospecific has been used to cover almost all aspects of the impact of stereochemical influences on reactions in living tissues or enzyme systems. Consider, for instance, the enzymatic hydration of fumarate by the enzyme, fumarase. Since there is a relationship between the structure of the substrate and product, the process could be described as stereospecific. Yet the definition of stereospecific requires that it be shown that the isomer of fumaric acid gives rise to a product which is stereochemically different from L-malate. Since the enzyme, however, does not catalyze any reaction with the (Z)-isomer (maleic acid) it is not clear whether stereospecific actually applies. 

Photochemical reaction of bifunctional ketoenamines in CC14 with maleic and fumaric acids and esters can be used for stereoselective synthesis of cis and trans alkyl 7-azabicyclo[2.2.1]heptanecarboxylates in good yield330 (equation 248). 

Typical acyclic olefins of symmetrically substituted types are the esters of maleic and fumaric acids. Though maleimides and maleates are both symmetrical cis-olefins, these two exhibit quite different stereoselectivity in cycloadditions to azomethine ylides. There are relatively limited examples known for the stereoselective cycloadditions of azomethine ylides to symmetrical acyclic olefins. These stereoselective cycloadditions are listed in Table IX, and nonstereoselective reactions in Table X. 

Although the two products come out drawn as mirror images, of course, they are not—they are identical. There is a mirror plane through the molecule, and this is a raeso-compound. You should prove to yourself that exactly the same result is obtained if we initially attack the underneath face of the double bond with the bromine. Since the carbon-carbon double bond of fumaric acid is rather nonnucleophilic, there may be a radical component to this reaction, but as we shall see in a later section, the reaction will probably still be fairly stereoselective. 

The discovery that Lewis acids can promote Diels-Alder reactions has become a powerful tool in synthetic organic chemistry. Yates and Eaton [4] first reported the remarkable acceleration of the reactions of anthracene with maleic anhydride, 1,4-benzoquinone and dimethyl fumarate catalyzed by aluminum chloride. The presence of the Lewis-acid catalyst allows the cycloadditions to be carried out under mild conditions, reactions with low reactive dienes and dienophiles are made possible, and the stereoselectivity, regioselectivity and site selectivity of the cycloaddition reaction can be modified [5]. Consequently, increasing attention has been given to these catalysts in order to develop new regio- and stereoselective synthetic routes based on the Diels-Alder reaction. 

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