Isoinversion

Thus, inversion (and hence racemization, which is produced by repeated acts of inversion) occurs without exchange. A single act of inversion without exchange is called isoinversion. 

The isoinversion process can take place by a pathway in which a positive species migrates in a stepwise fashion around a molecule from one nucleophilic position to another. For example, in the exchange reaction of 3-carboxamido-9-methylfluorene (3) with Pt3N in t-BuOH, it has been proposed that the amine removes a proton from... 

Optimization of Enantiomeric Ratio E by Choice of Temperature 5.7.3.1 Derivation of the Isoinversion Temperature... 

The results of the temperature dependence of the reaction rates of the enantiomers of secondary alcohols with a secondary alcohol dehydrogenase (SADE1) from the thermophilic bacterium Thermoanaerobacter ethanolicus demonstrated a temperature-dependent reversal of stereospecificity (Pham, 1990) (Figure 5.16). At T < 26°C, (S)-2-butanol was a better substrate than (i )-2-butanol on the basis of kCSLt/KM values however, at T> 26°C, (R)-2-butanol was a better substrate than (S)-2-butanol. (S)-2-Pentanol was the preferred substrate at T < 60°C however, the data predict that (i )-2-pentanol would be preferred at T > 70°C. (S)-2-Elexanol was predicted to be the preferred enantiomer only at T > 240°C. Therefore, the concept of isoinversion temperature is as valid for enzyme reactions as for others only the range of catalytically accessible temperatures is smaller. 

The isoinversion principle. A general selection model in chemistry, Angew. Chem. 1991, 103, 480-518 Angew. Chem,... 

Samarium iodobinaphtholate (222) has been reported to act as an efficient enantioselective catalyst for the Michael addition of aromatic amines to fumaryl oxazolidinone (220), affording the aspartic acid derivatives (221) in good yields. Elucidation of the influence of temperature on the addition of p-anisidine revealed an isoinversion effect with a maximum ee of 88% at —40 °C.257 A non-enantioselective version of this reaction has also been reported.258... 

N Plath, M.W., and Runsink, J. (1989) Chiral Induction in photochemical reactions 10. The principle of isoinversion A model of stereoselection developed from the diastereoselectivity of the Patemo-Biichi reaction. Journal of the American Chemical Society, 111, 5367-5373. 

An interesting result has been obtained with respect to the stereoselectivity of the addition of benzoyl nitrene to compounds 104a-104d The ratio of the two diastereomers depends on the temperature, such that an inversion of the diastereoselectivity can be observed at a distinct temperature (isoinversion principle [47]). Such an effect may indicate a reversible first bond formation between the benzoyl nitrene and the alkene [45]. 

Isoracemisation The situation in which racemisation occurs faster than isotope exchange at the chiral centre. The first step must be isoinversion. 

Frequently, the differences in entropy between two diastereomeric transition states are small, and the enthalpy term predominates. However, the entropy term cannot always be neglected, and sometimes it may even dominate according to the reaction conditions [2], In some cases, the observed selectivity can be inverted by changing the temperature of the reaction, and the temperature at which AAH = TAAS is called the isokinetic temperature (isoinversion). The occurrence of an isokinetic temperature in the normal operating range is not veiy frequent, but it is observed sometimes in multistep processes (see below). The ratio of the diastereo-isomeric products formed in kinetically controlled reactions is given by the relationship... 

Based on the pioneering study of the influence of the reaction temperature on diastereoselectivity137, 138, it is now known that enthalpy and entropy effects oppose each other in the transformation of 1 to 2136. Comparison of different systems at a single temperature may therefore be meaningless, since the results obtained below an isoselective temperature140 will be reversed above that temperature136. This principle of isoinversion may have to be taken into account in a comprehensive discussion of the above reactions141. 

Once again it is emphasized that the temperature dependence of these reactions can be treated according to the principle of isoinversion (see also Section 2.1.5.)136 U1. 

Both chiral proton sources (/J)-12 and (S)-13 produce enantiomerically enriched (-R)-ll at — 78 °C191. But already at — 40°C, only racemic 11 is obtained192. If, however, mandelic acid is employed as an ester of a Merrifield resin [(S)-14], the situation changes dramatically now at — 40r,C, 94% ee in (-R)-ll is observed with much smaller selectivities at lower and higher temperatures192. This is obviously another example of the already mentioned isoinversion principle (Section 2.1.5.)l40,141. 

From a liner plot of the difference between 5AAH and 5AAH, where 5AAH and 5AAH are the differences in the activation parameters for the high- and low-temperature regions, an isoinversion temperature 7] = 218K can be defined [47]. 

According to the principle of isoinversion and generalization of the model of diastereoselection developed for the Patemo-Buchi reaction [47], the enantioselective protonation of photoenols can be rationalized, if we assume a preequilibrium between the photoenol [48] and a supramolecule formed by hydrogen bonding between the aminogroup from one or other enantio-face and the enol intermediate (Scheme 5). 

Glyoxylates of chiral alcohols have been intensively studied as carbonyl components. According to the mechanistic studies of Scharf and coworkers, the outcome of the cycloaddition is in particular depending upon the reaction temperature (isoinversions... 

Imidazolide ionic liquids [Bmimjlm (2 mol%) have been reported to catalyse aza-Michael addition of, for example, imidazole to acrylates and acrylonitriles. Samarium diiodide has been identified as an efficient catalyst for the aza-Michael addition of 0-benzylhydroxylamine to a,/8-unsaturated Af-acyloxazolidinones. The 1,1-bi-2-naphthol (BINOL)-Sml complex afforded the Michael adducts with <88% ee. An isoinversion effect with temperature was observed for the highest enantiomeric excess at -40°C.205... 

The process of inversion (racemization) without exchange is called isoinversion. This involves an ion-pair mechanism. Indeed, in the presence of a crown ether, to separate the ions, the percentage of racemate increases (307). In fact, the stereochemical course of many metal-alkoxide catalyzed reactions in nonpolar solvents can be drastically modified by addition of catalytic amounts of crown ethers to the medium. For this reason, ion pairs, in low dielectric media, play a remarkable role as intermediates in reactions in which the negative ion is a carbanion. For example. Cram studied the rate of exchange (ke) and racemization kj as a function of the substituents present with deuterium-labeled 9-methylfluorene (309). The most interesting case was kjk < 0.5, racemization without exchange. This happens for X = di-... 

It should be noted that isoinversion can also occur without a conducted tour mechanism. This has been observed again with 9-methylfluorene and t rt-butanol solvent, but with n-propylamine replaced by the base penta-methylguanidine. That an alternative mechanism is operative is indicated by the fact that a substituent such as dimethylamide no longer needs to be present. The base can provide a charge delocalization pathway for travel of the deuteron from one side of the planar ring system to the other without solvent exchange. The deuteron can thus add to either side of the plane, as is illustrated below ... 

J. N. Roitenan and D. J. Cram (1971), Electrophilic substitution at saturated carbon. XLV. Dissection of mechanisms of base-catalyzed hydrogen-deuterium exchange of carbon acids into inverson, isoinversion, and racemization pathways. J. Amer. Chem. Soc. 90, 2225-2230. 

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