Reactions stereospecific

The anti addition of a halogen to an alkene provides us with an example of what is called a stereospecific reaction. 

Consider the reactions of cis- and trani-2-butene with bromine shown below. When trans-l-h x sa.Q adds bromine, the product is the meso compound, (2/ ,3S)-2,3-dibromobutane. When cw-2-butene adds bromine, the product is a racemic mixture of (2R,3R)-2,3-dibromobutane and (2S,3S)-2,3-dibromobutane  

The reactants ci5 -2-butene and trans-2-ha ene are stereoisomers they are diastereomers. The product of reaction 1, (2) ,35)-2,3-dibromobutane, is a meso compound, and it is a stereoisomer of both of the products of reaction 2 (the enantiomeric 2,3-dibromobutanes). Thus, by definition, both reactions are stereospedlic. One stereoisomeric form of the reactant (e.g., trans-2-h itene) gives one product (the meso compound), whereas the other stereoisomeric form of the reactant (cM-T-butene) gives a stereoisomericaUy different product (the enantiomers). 

We can better understand the results of these two reactions if we examine their mechanisms. The first mechanism in the following box shows how cM-2-butene adds bromine to yield intermediate bromonium ions that are achiral. (The bromonium ion has a plane of symmetry.) These bromonium ions can then react with bromide ions by either path (a) or path (b). Reaction by path (a) yields one 2,3-dibromobutane enantiomer reaction by path (b) yields the other enantiomer. The reaction occurs at the same rate by either path therefore, the two enantiomers are produced in equal amounts (as a racemic form). 

The second mechanism in the box shows how trans-2-hutsae reacts at the bottom face to yield an intermediate bromonium ion that is chiral. (Reaction at the other face would produce the enantiomeric bromonium ion.) Reaction of this chiral bromonium ion (or its enantiomer) with a bromide ion either by path (a) or by path (b) yields the same achiral product, mcso-2,3-dibromobutane. 

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Figure 10.3-40. The rating for the disconnection strategy carbon-heteroatom bonds is illustrated, Please focus on the nitrogen atom of the tertiary amino group. It is surrounded by three strategic bonds with different values. The low value of 9 for one ofthese bonds arises because this bond leads to a chiral center. Since its formation requires a stereospecific reaction the strategic weight of this bond has been devalued. In contrast to that, the value of the bond connecting the exocyclic rest has been increased to 85, which may be compared with its basic value as an amine bond.

The same regioselective and stereospecific reactions are observed in decalin systems. The 3/3-formate 605 is converted into the a-oriented (j-allylpalladium complex 606, and the hydride transfer generates the fra .s-decalin 607, while the cis junction in 610 is generated from the 3tt-formate 608 by attack of the hydride from the /3-side (609). An active catalyst for the reaction is prepared by mixing Pd(OAc)2 and BU3P in a 1 I ratio with this catalyst the reaction proceeds at room temperature. The reaction proceeded in boiling dioxane when a catalyst prepared from Pd(OAc)2 and BujP in a 1 4 ratio was used[390]. 

Bromine addition to alkenes is an example of a stereospecific reaction A stereospecific reaction is one m which stereoisomeric starting materials yield products... 

A common misconception is that a stereospecific reaction is simply one that is 100% stereoselective The two terms are not synonymous however A stereospecific reac tion IS one which when carried out with stereoisomeric starting materials gives a prod uct from one reactant that is a stereoisomer of the product from the other A stereo selective reaction is one m which a single starting material gives a predominance of a... 

Recall from Section 7 13 that a stereospecific reaction is one in which each stereoiso mer of a particular starting material yields a different stereoisomeric form of the reaction product In the ex amples shown the product from Diels-Alder cycloaddi tion of 1 3 butadiene to as cinnamic acid is a stereo isomer of the product from trans cinnamic acid Each product although chiral is formed as a racemic mixture... 

In describing the stereochemical features of chemical reactions, we can distinguish between two types stereospecific reactions and stereoselective reactions. A stereospecific reaction is one in which stereoisomeric starting materials aflFord stereoisomerically different products under the same reaction conditions. A stereoselective reaction is one in which a single reactant has the capacity of forming two or more stereoisomeric products in a particular reaction but one is formed preferentially. 

Some stereospecific reactions are listed in Scheme 2.9. Examples of stereoselective reactions are presented in Scheme 2.10. As can be seen in Scheme 2.9, the starting materials in these stereospecific processes are stereoisomeric pairs, and the products are stereoisomeric with respect to each other. Each reaction proceeds to give a single stereoisomer without contamination by the alternative stereoisomer. The stereochemical relationships between reactants and products are determined by the reaction mechanism. Detailed discussion of the mechanisms of these reactions will be deferred until later chapters, but some comments can be made here to illustrate the concept of stereospecificity. 

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. 

The di-TT-methane rearrangement is a stereospecific reaction. There are several elements of stereochemistry to be considered. It is known that the double bond that remains uncyclized retains the E or Z configuration present in the starting material. This result excludes any intermediate with a freely rotating terminal radical. The concerted... 

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. 

Stereospecific reaction (Section 7.13) Reaction in which stereoisomeric starting materials give stereoisomeric products. Terms such as syn addition, anti elimination, and inversion of eonfiguration describe stereospecific reactions. 

Fumarate is hydrated in a stereospecific reaction by fumarase to give L-malate (Figure 20.17). The reaction involves fraw5-addition of the elements of water across the double bond. Recall that aconitase carries out a similar reaction. 

The hydroboration is a y -stereospecific reaction. For example reaction with 1-methylcyclopentene 11 yields the l,2-tra 5-disubstituted product 12 only ... 

Scheme 8 presents the sequence of reactions that led to the synthesis of the B-ring of vitamin B12 by the Eschenmoser group. An important virtue of the Diels-Alder reaction is that it is a stereospecific process wherein relative stereochemical relationships present in the diene and/or the dienophile are preserved throughout the course of the reaction.8 Thus, when the doubly activated dienophile 12 (Scheme 8) is exposed to butadiene 11 in the presence of stannic chloride, a stereospecific reaction takes place to give compound 27 in racemic form. As expected, the trans relationship between... 

This stereospecific reaction is, therefore, a rare example of stereochemical control by nucleophilic solvent assistance of an ionization process. 

Any reaction in which only one of a set of stereoisomers is formed exclusively or predominantly is called a stereoselective synthesis. 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. 

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. 

Cycloadditions with the Si(lOO) surface were theoretically [133] concluded to be reactions in the pseudoexcitation band. The conclusion is applicable to thermal [2+2] cycloaddition reactions of unsaturated bonds between heavy atoms. In fact, Sekiguchi, Nagase et al. confirmed that a Si triple bond underwent the stereospecific reactions with alkenes [137] along the path typical of [2+2] cycloaddition in the pseudoexcitation band. The stereospecific [2+2] cycloadditions of were designed by Inagaki et al. (Scheme 28) [138]. 

The thermal solid-to-solid cyclization reaction of diallene derivatives also proceeds stereospecifically. Reaction of 1,6-diphenyl-1,6-di(p-tolyl)hexa-2,4-diyne-l,6-diol (113) with HBr gave meso- (114) and rac-3,4-dibromo-l,6-di-... 

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). 

The involvement of organocopper intermediates in various cross-coupling reactions carried out in the presence of Cu1 is often suggested, although in the majority of cases no experimental proof is provided, and the actual role of Cu1 may be different (Section 9.6.3.2.1). The potential of copper-mediated cross-coupling can be shown by the stereospecific reaction of 3-trimethylsilylallylic alcohols, which takes place via a prior transmetalation of Si to Cu (37).157... 

Ajtai, K. (1992) Stereospecific reaction of muscle fiber proteins with the 5 or 6 iodoacetamido derivative of tetramethylrhodamine Only the 6 isomer is mobile on the surface of SI. Biophys. J. 61, A278, Abstract 1647. 

Vinyl halides (example 17, Table VII) were first observed by Kroper to form acrylic esters by reaction with carbon monoxide under pressure and tetracarbonylnickel in methanol at 100°C. These reactions were later shown to occur under much milder conditions. Highly stereospecific reactions were observed c/s-vinyl halides gave cis-carbonylation products and trans-vinyl halides trans-carbonylation products (example 18, Table VII). Retention of configuration of alkyl substrates in carbonylation seems to be a general feature in carbon monoxide chemistry (193a). 

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