Inversion or retention

Stereochemical analysis can add detail to the mechanistic picture of the Sj l substitution reaction. The ionization mechanism results in foimation of a caibocation intermediate which is planar because of its hybridization. If the caibocation is sufficiently long-lived under the reaction conditions to diffirse away from the leaving group, it becomes symmetrically solvated and gives racemic product. If this condition is not met, the solvation is dissymmetric, and product with net retention or inversion of configuration may be obtained, even though an achiral caibocation is formed. The extent of inversion or retention depends upon the details of the system. Examples of this effect will be discussed in later sections of the chapter. 

An enantioconvergent transformation leads to a single enantiomeric product from a racemate [51]. Each enantiomer is transformed via independent pathways by the same catalyst or by two different catalysts (Figure 6.6). For example, the hydrolysis of epoxides may proceed with high regio- and stereoselectivity vdth inversion or retention of configuration. Several enantioconvergent transformations of epoxides are reported in the last section of this chapter. 

The mechanisms of most alcohol reductions are obscure. Hydrogenolysis of benzyl alcohols can give inversion or retention of configuration, depending on the catalyst. - ... 

En route to a compound of known configuration, a reaction is performed directly affecting the chiral unit. The success of this classical and extensively used procedure is, of course, dependent on an unambiguous knowledge of the stereochemical course of the reaction used. A list of reactions at stereogenic centers and their steric course (inversion or retention), as well as known anomalies, has been compiled198. Some examples from the recent literature may serve to illustrate the procedure. 

The stereochemical outcome of Friedel-Crafts alkylation may be either inversion (nucleophilic displacement) or racemization (involvement of a trivalent flat carbocation). Most transformations were shown to occur with complete racemization. In a few instances, inversion or retention was observed. For example, the formation of (—)-l,2-diphenylpropane [(—)-28] from (—)-26 was interpreted to take place through the 27 nonsymmetrically Jt-bridged carbocation, ensuring 50-100% retention of configuration 136... 

The second step (glycosylation step) should consist of a sterically uniform, high-yielding glycosyl transfer to the acceptor however, by a truly catalytic process, where diastereocontrol may be derived from the glycosyl donor anomeric configuration (by inversion or retention), by anchimeric assistance, by influence of the solvent, by thermodynamics, or by any other effects. 

Inversion or retention Equation 12-5 pictures the reaction of a glycoside (such as a glucose unit at... 

Thus, it is quite difficult to derive a relationship between substitution stereochemistry and any physical property of the leaving group (basicity, electronegativity, or polarizability). This failure prompted us to consider an empirical relationship between the observed stereochemistry (inversion or retention) and the ability of the leaving group to be displaced (23. 33). 

On submitting D-isomannide 2,5-dinitrate (15) to flash vacuum thermolysis, 1,4 3,6-dianhydro-D-mannopyranose (145) was obtained as the main product (75 - 80% yield), accompanied by 5 -10% of the monoketone 8a. In contrast, when D-isosorbide 2,5-dinitrate (14) was treated under the same conditions, a 6 3 1 mixture consisting217 of 8a, 145, and its D-gluco epimer 146 resulted (see Scheme 40). These results could be explained by a restricted number of rearrangements of intermediate radicals, with inversion or retention of configuration, respectively. By reduction with sodium borohydride, 8a was stereoselectively converted into D-isomannide (4). 

Whatever the method of control may be it seems evident that it is by no means completely efficient for the solid polymer is always a rather small fraction of the total. Price believes, presumably because any optical activity tends to be concentrated in the crystalline phase, that the amorphous and crystalline polymers are products of two different reactions, one in solution and the other heterogeneous (27). While this view is not impossible, it could be argued that solution reaction might be expected to lead to either inversion or retention of configuration and, hence, optically active polymer. Furthermore, some reports suggest rather strongly that the distinction between the two types of polymer is a rather arbitrary one based in part on polymer symmetry and in part on molecular weight. 

This apparent indetermination is not a failure of FO theory, but rather an illustration of its ability to provide more balanced conclusions, as opposed to the rules of aromaticity which can sometimes be a little too categorical. The absence of any overwhelming drive for either inversion or retention implies that by a judicious choice of the reaction conditions it is possible to obtain SN2 reactions with retention of configuration.148 To promote them, the overlap of the nucleophile with the carbon atom must be increased, whereas its overlap with the leaving group must diminish. This may be achieved by reducing the mixing coefficient in the o CY orbital ... 

At least three genereil pathways need to be considered for the ringopening reactions of cyclopropanes with electrophiles, each of which could proceed with either inversion or retention. The most straightforward mechanism would involve a direct, single-step reaction leading to a carbonium ion, a reaction which could truly be considered an Se2 process. 

If we postulate that all of these pathways are allowed, that each can lead either to inversion or retention, and further that edge and corner substituted cyclopropanes are in equilibrium with one another, then obviously nearly any experimental result can be accommodated. Unfortunately the situation is nearly this bad at the present time. In the following we will examine the present status of the experimental evidence. 

Cyclopropanes can undergo attack by electrophiles with either inversion or retention of configuration at the carbon to which the electrophile becomes attached. The stereochemistry at this center, plus the fact that the nucleophile enters with inversion in nearly all cases, can best be accounted for by an intermediate, corner-substituted cyclopropane for many ring-opening reactions. In some cases a direct, single step process may compete with this mechanism. The possibility of an edge-substituted cyclopropane as a reaction intermediate under special circumstances cannot be ruled out at present. 

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