Configurational inversion reactions

Not stereospecific racemization ac companies inversion when leaving group IS located at a chirality cen ter (Section 8 10) Stereospecific 100% inversion of configuration at reaction site Nu cleophile attacks carbon from side opposite bond to leaving group (Section 8 4)... 

According to the transition state theory, the pre-exponential factor A is related to the frequency at which the reactants arrange into an adequate configuration for reaction to occur. For an homolytic bond scission, A is the vibrational frequency of the reacting bond along the reaction coordinates, which is of the order of 1013 to 1014 s 1. In reaction theory, this frequency is diffusion dependent, and therefore, should be inversely proportional to the medium viscosity. Also, since the applied stress deforms the valence geometry and changes the force constants, it is expected... 

Evidence for this mechanism is as follows The addition of pyridine to the mixture of alcohol and thionyl chloride results in the formation of alkyl halide with inverted configuration. Inversion results because the pyridine reacts with ROSOCl to give ROSONC5H5 before anything further can take place. The Cl freed in this process now attacks from the rear. The reaction between alcohols and thionyl chloride is second order, which is predicted by this mechanism, but the decomposition by simple heating of ROSOCl is first order. ... 

These reactions are believed to proceed via transmetallation. Configurational inversion occurs at both the transmetallation and addition steps, leading to overall retention of the allylic stereochemistry. 

Differences in chirality of substrate, and nature of solvent, have no effect on the competitive nature of the displacement of 0-alkyl and S-methyl groups in the reactions between (+)-pinacolyl alkoxide and 0-ethyl (and methyl) S-methyl methylphosphonothioates (Scheme 23). For the (R)-( + ) esters, e.g. (210), the displacements are highly stereoselective and occur with configurational inversion,but the enantiomeric esters do not display such stereoselectivity. (-)-Menthol might be considered a mirror image of (S)-pinacol, and similar reactions with the sodium salt of (-)-menthol occur highly stereoselectively... 

Despite what has been said above about displacement reactions leading to inversion of configuration, to racemisation, or to a mixture of both, a number of cases are known of reactions that proceed with actual retention of configuration, i.e. in which the starting material and product have the same configuration. One reaction in which this has been shown to occur is in the replacement of OH by Cl through the use of thionyl chloride, SOCl2 ... 

Because the product is reached by way of two Walden inversion reactions the result is retention of configuration, although not always retention of optical activity. 

The concepts of homo- and heterochirality play an important role in the discussion of the stereochemical aspects of reaction mechanisms. In many textbooks 18> one finds the statement that the Sn2 mechanism is characterized by the fact that it occurs with configurational inversion. 

Figure 6. Effect of carbohydrate configuration on inversion reaction. ...

RCH200 + RCH2Hal -> RCH2-OO-CH2R + HaE. Reactions of KO2 with optically active alkyl halides proceed with the configurational inversion. Moreover, the reactivity changes in the same order as that of the usual Sj. 2 reactions (primary > secondary > tertiary J > Br > Cl) (Sawyer and Gibian 1979). 

The nature of X in the initial CgHi3C H(Me)X defines the relation between the two routes. If X = Br, the configuration inversion does not exceed 8%. If X = OSOjMe, the inversion takes place up to 25%. The bromide ion is more active in elimination than methyl sulfonate ion. Therefore, the electron-transfer contribution to the substitution reaction is higher. 

L. Compounds that can be derived from L-glyceraldehyde without inversion reactions of the chiral center are likewise designated l- (and, their mirror images, d-). X-ray crystallographic studies later showed that D-glyceralde-hyde had the configuration shown below. d- and l-Alanine are also depicted. 

The electrophilic reactivity of lithium carbenoids (reaction b) becomes evident from their reaction with alkyl lithium compounds. A, probably metal-supported, nucleophilic substitution occurs, and the leaving group X is replaced by the alkyl group R with inversion of the configuration . This reaction, typical of metal carbenoids, is not restricted to the vinylidene substitution pattern, but occurs in alkyl and cycloalkyl lithium carbenoids as well ". With respect to the a-heteroatom X, the carbenoid character is... 

If, during ring opening polymerization a tertiary carbon is involved in the reaction, a configurational inversion may occur in which case a change in the stereochemistry of the monomer unit with respect to the monomer will be observed. Thus, the cf5-2,3-epoxybutane gives rise to a polymer with threo monomer units, 39, whereas the trans isomer is transformed into erythro or meso units, 40 (Scheme 8) (81, 82). 

If the product and the starting material have opposite configurations, the reaction occurred with inversion. If the product has the same configuration, the reaction went with retention of configuration. If both process occurred to the same extent, the product would be completely racemized (100% racemization) and if the two processes were not equal, partial racemization would occur. 

The authors proposed a working mechanism to explain the diastereoselectivities (Scheme 8.174). Thus, the prereaction complex 537 reacts with the Chloramine-T to yield an intermediate chlorosulfonium ion 538. Further reaction of 538 with toluenesulfonamide anion effected a configurational inversion to give the observed product. 

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. 

Whereas the phosphetanium (Sect. 2.2) derivatives undergo base-catalyzed hydrolysis with essentially complete retention of configuration, the reaction with the related thietanium salts proceeds with complete inversion of configuration and can be described simply as a direct nucleophilic substitution 35. As far as the author is aware, no exchange evidence of the type er countered in the acid-catalyzed hydrolysis of ethylene phosphate, has been found for the cyclic sulfate esters. Consequently despite the geometrical similarities between the cyclic sulfates and phosphates and the related hybridization of the central atoms, the situation in which a finite pentacovalent intermediate sulfur species exists has not been delineated (restricting the discussion to esters). 

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