Stereochemistry Stereoselective reactions

Stereospecificity of this reaction reaches 15 1 for telomer T3. Telomer T3 is a crystalline product, this allowed the authors to use X-ray diffraction analysis for studying stereochemistry. Stereoselectivity observed in the formation of T3 shows that both addition step and the step of halogen transfer to the growing radical proceed stereoselectively in this case. 

Stereochemical Control Through Reaction Conditions. In the early 1990s it was found that the stereochemistry of reactions of boron enolates of N-acyloxazolidinones can be altered by using a Lewis acid complex of the aldehyde or an excess of the Lewis acid. These reactions are considered to take place through an open TS, with the stereoselectivity dependent on the steric demands of the Lewis acid. With various aldehydes, TiCl4 gave a syn isomer, whereas the reaction was... 

Among chiral auxiliaries, l,3-oxazolidine-2-thiones (OZTs) have attracted important interest thanks to there various applications in different synthetic transformations. These simple structures, directly related to the well-documented Evans oxazolidinones, have been explored in asymmetric Diels-Alder reactions and asymmetric alkylations (7V-enoyl derivatives), but mainly in condensation of their 7V-acyl derivatives on aldehydes. Those have shown interesting characteristics in anti-selective aldol reactions or combined asymmetric addition. Normally, the use of chiral auxiliaries which can accomplish chirality transfer with a predictable stereochemistry on new generated stereogenic centers, are indispensable in asymmetric synthesis. The use of OZTs as chiral copula has proven efficient and especially useful for a large number of stereoselective reactions. In addition, OZT heterocycles are helpful synthons that can be specifically functionalized. 

As we have seen a stereoselective reaction is one in which there is a preponderance of one isomer irrespective of the stereochemistry of the reactant. The enzymatic reduction of pyruvic acid is stereoselective when the chiral molecules of the enzyme complexes with achiral pyruvic acid, they given a preponderance of one form of pyruvic acid-enzyme complex which then gives a single form of lactic acid. 

The dissection of a molecular model into those components that are deemed to be essential for the understanding of the stereochemistry of the whole may be termed factorization (9). The first and most important step toward this goal was taken by van t Hoff and Le Bel when they introduced the concept of the asymmetric carbon atom (10a, 1 la) and discussed the achiral stereoisomerism of the olefins (10b,lib). We need such factorization not only for the enumeration and description of possible stereoisomers, important as these objectives are, but also, as we have seen, for the understanding of stereoselective reactions. More subtle differences also giving rise to differences in reactivity with chiral reagents, but referable to products of a different factorization, will be taken up in Sect. IX. 

Single crystal X-ray analysis has proved to be valuable for the determination of the stereochemistry of chiral 1,3-thiazine derivatives and provided support for the mechanisms in stereoselective reactions <2001EJ03553, 2001EJ03025, 2002TL6067, 2004T1827>. 

It is the purpose of this section to provide the modern vocabulary required for the description of stereoselective reactions. This also implies the description of stereochemical aspects of starting materials and products, i.e., aspects of static stereochemistry. The material has been arranged in logical progression and, whenever possible, rules and directions for use or explicit definitions of important terms are given. 

The previous observation concerning the term stereochemistry leads to the first rule, i.e., that this noun should always mean the entire field rather than a special aspect. Accordingly, when describing a stereoselective reaction the steric course of the reaction or the configuration of a product must be considered, but never "the stereochemistry of the reaction or product . 

The description of a stereoselective reaction primarily requires characterization of enantiomeric and/or diastereomeric products by their configuration (not their stereochemistry , see Introduction). Problems have not arisen with enantiomers but difficulties (see enumerations in refs 1 and 2) are. or perhaps were, apparent for diastereomers, a focal point having been acyclic compounds, in particular aldol addition products. These are pertinent examples to illustrate the problems and their various solutions very well ... 

Introduction of the allene structure into cycloalkanes such as in 1,2-cyclononadiene (727) provides another approach to chiral cycloalkenes of sufficient enantiomeric stability. Although 127 has to be classified as an axial chiral compound like other C2-allenes it is included in this survey because of its obvious relation to ( )-cyclooctene as also can be seen from chemical correlations vide infra). Racemic 127 was resolved either through diastereomeric platinum complexes 143) or by ring enlargement via the dibromocarbene adduct 128 of optically active (J3)-cyclooctene (see 4.2) with methyllithium 143) — a method already used for the preparation of racemic 127. The first method afforded a product of 44 % enantiomeric purity whereas 127 obtained from ( )-cyclooctene had a rotation [a]D of 170-175°. The chirality of 127 was established by correlation with (+)(S)-( )-cyclooctene which in a stereoselective reaction with dibromocarbene afforded (—)-dibromo-trans-bicyclo[6.1 0]nonane 128) 144). Its absolute stereochemistry was determined by the Thyvoet-method as (1R, 87 ) and served as a key intermediate for the correlation with 727 ring expansion induced... 

The following Pd-catalysed stereoselective transformations of 142 and 143 are possible. The Pd-catalysed reaction of the cis product 143 with malonate gives the coproduct 148 with retention of the stereochemistry. However, reaction of 143 without the Pd catalyst affords the trans product 149. The cis product 142 is a mesa form and can be converted to the chiral half ester 150 by enzyme-catalysed partial hydrolysis. 

We have expanded our collection of stereoselective reactions even more in the making of alkenes by the Wittig reaction (chapter 15), from acetylenes (chapter 16), by thermodynamic control in enone synthesis (chapters 18 and 19) and in sigmatropic rearrangements (chapter 35). We have seen that such E- or Z-alkenes can be transformed into three-dimensional stereochemistry by the Diels-Alder reaction (chapter 17), by electrophilic addition (chapters 23 and 30), by carbene insertion (chapter 30) and by cycloadditions to make four-membered rings (chapters 32 and 33). 

The stereochemistry of the product of a reaction will be influenced by the structures of the reagent and substrate and the mechanisms by which they react. For example, the hydroxylation of but-2-ene by osmium tetroxide and water yields a racemate whilst bromination of the same compound with bromine produces a meso compound (Figure 10.5). Flowever, a stereoselective reaction is most likely to occur when steric hindrance at the reaction centre restricts the approach of the reagent to one direction (Figure 10.6). Furthermore, the action of both enzyme and non-enzyme catalysts may also be used to introduce specific stereochemical centres into a molecule. 

Stereochemistry is a concept of paramount importance in chemistry. Stereoselective reactions, be they diastereoselective or enantioselective, are therefore a valuable tool in producing compounds of the desired stereochemistry. Every stereoselective reaction has an energetically preferred transition state that can explain the formation of the major stereoisomer. A reasonable transition state is very important not only in rationalizing the experimental results, but also in further advancing the chemical system that one is studying. 

You have had three chapters in a row about stereochemistry this is the fourth, and it is time for us to bring together some ideas from earlier in the book. We aim firstly to help you grasp some important general concepts, and secondly to introduce some principles in connection with stereoselective reactions in acyclic systems. But, first, some revision. 

The confomiational preferences and stereoselective reactions of a number of macrocyclic systems have been studied. The stereochemical results have been explained on the basis of the model of local conformer control. The epoxidation of a macrocyclic alkene containing the substitution pattern (21) provides a single epoxide having the stereochemistry (22). A macrocycle containing a l,S-diene system adepts the local confoimation (23) that is iree of torsional strain epoxidation of (23) from the less hindered side fiimishes the syn-diepoxide (24). The MCPBA epoxidations of the unsaturated macrocyclic lactones (25) and (2Q are stereoselective (equations 9 and 10). In the epoxidation of (26) six new chiral centres are introduced the reaction product is a 20 1 1 mixture of triepoxides. The tiiepoxide (27) is closely related to the C(9)-C(23) segment of monensin B. 

For a further discussion of these terms and of stereoselective reactions in general, see Eli el, E.L. Wilen, S.H. Mander, L.N. Stereochemistry of Organic Compounds, Wiley-lnterscience, NY, 1994, pp. 835-990. 

The first stereoselective reaction is surprising as it may appear that the initial alkylation decides " stereochemistry. But that is not the case as you will see if you draw the mechanism. The esn enolate is very easily formed as it is stabilized by the pyridine ring and the nitrile as well as by irt ester. Even a weakish base like carbonate is good enough. 

For a stereoselective reaction we can specify two different stereoisomers of the starting materiai and get the same product (first and third exampies). in a stereospecific reaction, different starting materiai stereochemistry means different product stereochemistry. 

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