Stereoselectivity Stereospecific, definition

Let us now define three terms that refer to reactions stereoselective, stereospecific and stereoelectronic. There has been a difference of opinion about the use of the first two we shall use the definitions suggested by Zimmerman2 and now adopted by most authors. 

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. 

Of course, the trans isomer will give the opposite results the threo pair if the addition is syn and the erythro pair if it is anti. The threo and erythro isomers have different physical properties. In the special case where Y=W (as in the addition of Br2), the erythro pair is a meso compound. In addition to triple-bond compounds of the type ACsCA, syn addition results in a cis alkene and anti addition in a trans alkene. By the definition given on page 166 addition to triple bonds cannot be stereospecific, though it can be, and often is, stereoselective. 

A stereospecific chemical reaction is one in which starting substrates or reactants, differing only in their configuration, are converted into stereoisomeric products. Note, with this definition a stereospecific reaction has to be stereoselective whereas the inverse statement (that is, with respect to a stereoselective reaction or process) is not necessarily true. 2. Referring to reactions that act on only one stereoisomer (or, have a preference for one stereoisomer). Thus, many enzyme-catalyzed reactions are stereospecific, and characterization of that stereospecificity is always an issue to be addressed for a particular enzyme. 

The term stereoselective is often confused with the term stereospecific, and the literature abounds with views as to the most satisfactory definition. To offer some clarification, it is perhaps timely to recall a frequently used term, introduced a decade or so ago, namely the stereoelectronic requirements of a reaction. All concerted reactions (i.e. those taking place in a synchronised process of bond breaking and bond forming) are considered to have precise spatial requirements with regard to the orientation of the reactant and reagent. Common examples are SN2 displacement reactions (e.g. Section 5.10.4, p. 659), E2 anti) elimination reactions of alkyl halides (e.g. Section 5.2.1, p.488), syn (pyrolytic) elimination reactions (Section 5.2.1, p.489), trans and cis additions to alkenes (e.g. Section 5.4.5, p. 547), and many rearrangement reactions. In the case of chiral or geometric reactants, the stereoisomeric nature of the product is entirely dependent on the unique stereoelectronic requirement of the reaction such reactions are stereospecific. 

Our overall plan in this paper is this. Initially, we shall set down a few definitions, and a point of view. We shall then describe a number of principles or causes of stereoselection associated with bonding, steric, thermodynamic, electrical, mechanical, etc., factors, inherent in the stereoprocess. The relation between the properties of intermediates, e.g. carbanion or syn-anti isomers, etc., rate and equilibrium conditions and stereoselectivity will be dealt with. Throughout, we shall examine representative systems and reactions to see how relevant the principles of stereoselection are. No attempt will be made to venture into several important areas, e.g. enzyme stereospecificity, stereoregular polymers, etc. 

It will be appreciated that, with these definitions, any stereospecific process is also stereoselective however, not all stereoselective reactions are stereospecific. In some papers, the terms are modified with the prefixes, enantio- or diastereo-. 

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. 

The postulation that the "biradical-like" transition state [135] (and not a freely rotating acyl alkyl biradical intermediate) is the precursor of the oxacarbene intermediate [136] is made primarily to accomodate the fact that the ring-expansion reaction is stereoselective. Transition state [135] could also decay by S-cleavage and/or decarbonylation [both stereospecific (23), although definitive evidence concerning this point is not available in the solution phase. Finally [135] could decompose back to the starting cyclobutanone, which would explain the observed lack of efficiency in the previously described photolyses. (See Section II.E for a further discussion of this point.)... 

Recently, the stereochemical definitions of the addition of carbenes to C-C double bonds have been summarized. The term stereoselectivity refers to the degree of selectivity for the formation of cyclopropane products having endo vs. exo or, alternatively, syn vs. anti orientation of the substituents in the carbene species relative to substituents in the alkene substrate. The term stereospecificity refers to the stereochemistry of vicinal cyclopropane substituents originating as double-bond substituents in the starting alkene, i.e. a cyclopropane-forming reaction is stereospecific if the cisjtrans relationship of the double-bond substituents is retained in the cyclopropane product. Diastereofacial selectivity refers to the face of the alkene to which addition occurs relative to other substituents in the alkene substrate. Finally, enantioselectivity refers to the formation of a specific enantiomer of the cyclopropane product. 

Introduction and definitions Stereoselective and stereospecific Aldol Stereochemistry... 

For the purposes of this treatise, the definition of asymmetric synthesis is a modification of that proposed by Morrison and Mosher [1] and as such will be applied to stereospecific reactions in which a prochiral unit in either an achiral or a chiral molecule is converted, by utility of other reagents and/or a catalytic antibody, into a chiral unit in such a manner that the stereoisomeric products are produced in an unequal manner. As such, the considerable body of work devoted to antibody-catalysis of stereoselective reactions including chiral resolutions, isomerizations and rearrangements are considered to be beyond the scope of this discussion. For information regarding these specific topics and more general information regarding the catalytic antibody field the following papers... 

Following our definition of stereospecificity given above, it follows that both stereoselective reactions (transformations (155-163a/b) and nonstereoselective ones (transformations 157a/b-163a/b) can be stereospecific. Therefore, the first part of the statement "all stereospecific processes are stereoselective, but all stereoselective processes are stereospecific " is not true. By our definition, all stereospecific processes are not stereoselective for example, stereospecific transformations 157a/b-163a/b can be nonstereoselective. 

Another source of uncertainty in the use of stereochemical terminology concerns the terms stereospecific and stereoselective, which were proposed by Zimmerman and co-workers. Adams reviewed the varied definitions of these terms and recommended that they be used as follows ... 

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