Loss of optical activity

Partial but not complete loss of optical activity m S l reactions probably results from the carbocation not being completely free when it is attacked by the nucleophile Ionization of the alkyl halide gives a carbocation-hahde ion pair as depicted m Figure 8 8 The halide ion shields one side of the carbocation and the nucleophile captures the carbocation faster from the opposite side More product of inverted configuration is formed than product of retained configuration In spite of the observation that the products of S l reactions are only partially racemic the fact that these reactions are not stereospecific is more consistent with a carbocation intermediate than a concerted bimolecular mechanism... 

Each act of proton abstraction from the a carbon converts a chiral molecule to an achi ral enol or enolate ion The sp hybridized carbon that is the chirality center m the start mg ketone becomes sp hybridized m the enol or enolate Careful kinetic studies have established that the rate of loss of optical activity of sec butyl phenyl ketone is equal to Its rate of hydrogen-deuterium exchange its rate of brommation and its rate of lodma tion In each case the rate determining step is conversion of the starting ketone to the enol or enolate anion... 

Just as selective oxidation can be carried out on these systems, reduction also occurs with considerable selectively. Hydrogenation of binaphthol (Pd catalyst) in glacial acetic acid at room temperature for seven days affords the octahydro (bis-tetrahydro) derivative in 92% yield with no apparent loss of optical activity when the reaction is conducted on optically pure material. The binaphthol may then be converted into the bis-binaphthyl crown in the usual fashion. 

The d5Tiamic stereochemistries of M(dtc)3 and [M(dtc)3] (M = Fe, Co, or Rh) complexes have been studied (315). The cobalt complex is non-rigid, but the mechanism of optical inversion could not be determined. The Rh complex is stereochemically rigid up to 200°. The optical inversion of (-l-)546 [Colpyr-dtcla] in chloroform has been studied, by loss of optical activity, by polarimetry (316). 

There are two possible structures for simple alkyl radicals. They might have sp bonding, in which case the structure would be planar, with the odd electron in ap orbital, or the bonding might be sp, which would make the structure pyramidal and place the odd electron in an sp orbital. The ESR spectra of CHs and other simple alkyl radicals as well as other evidence indicate that these radicals have planar structures.This is in accord with the known loss of optical activity when a free radical is generated at a chiral carbon. In addition, electronic spectra of the CH3 and CD3 radicals (generated by flash photolysis) in the gas phase have definitely established that under these conditions the radicals are planar or near planar. The IR spectra of CH3 trapped in solid argon led to a similar conclusion. " °... 

Despite the usual loss of optical activity noted above, asymmetric radicals can be prepared in some cases. For example, asymmetric nitroxide radicals are known. An anomeric effect was observed in alkoxy radical (31), where the ratio of 31a/31b was 1 1.78. ... 

Evidence for this mechanism is that optically active PhCHDCHs labeled in the ring with C and treated with GaBr3 in the presence of benzene gave ethylbenzene containing no deuterium and two deuteriums and that the rate of loss of radioactivity was about equal to the rate of loss of optical activity." The mechanism of intramolecular rearrangement is not very clear. The 1,2 shifts of this kind have been proposed " ... 

To test this hypothesis, a-naphthaldehyde, which is apparently inert toward photoreduction, was irradiated in the presence of optically active 2-octanol. If a reversible hydrogen abstraction were to occur, a loss of optical activity in the 2-octanol should result. The results showed no loss in optical activity thus the question of a reversible reaction has been answered/33 ... 

Here it is found that the rate of loss of optical activity and the rate of isomerisation are identical, and if the reaction is carried out in the presence of D20 (five moles per mole of substrate) no deuterium is incorporated into the product. The reaction is thus wholly intramolecular under these conditions—no carbanion is involved—and is believed to proceed via a bridged T.S. such as (30). With a number of substrates features of both inter- and intra-molecular pathways are observed, the relative proportions being dependent not only on the substrate, but to a considerable extent on the base and solvent employed also. 

This all suggests slow, rate-limiting breaking of the C—H bond to form the stabilised carbanion intermediate (54), followed by fast uptake of D from the solvent D20. Loss of optical activity occurs at each C—H bond breakage, as the bonds to the carbanion carbon atom will need to assume a planar configuration if stabilisation by delocalisation over the adjacent C=0 is to occur. Subsequent addition of D is then statistically equally likely to occur from either side. This slow, rate-limiting formation of a carbanion intermediate, followed by rapid electrophilic attack to complete the overall substitution, is formally similar to rate-limiting carbocation formation in the SNi pathway it is therefore referred to as the SE1 pathway. 

The main lines of this approach were later embodied in an enantioselective synthesis of (—)-a-allokainic acid (Scheme 34) (179). The sole stereo center of die ene reaction starting material was derived from a glutamic acid derivative (132) to avoid loss of optical activity via double bond migration (see Scheme 33), the a acid function of kainic acid had to be reduced before the pyrolysis step... 

Optically active iV-unprotected-2-pyrrolidinones 194 were obtained from selenocarboxylate or allylamine via radical cyclization and subsequent one-step cleavage of the C-O and C-N bond of the inseparable mixture of the two bicyclic oxyoxazolidinones 192 and 193 with -Bu4NF. The initial radical reaction is highly stereoselective. Products were obtained with ee up to 90%. The mandelic acid 195, which served as the chiral auxiliary in this method, was recovered with no loss of optical activity (Equation 33) <2003T6291>. 

Superimposability and Loss of Optical Activity In a situation where molecules exist as C (WjXY), that is when two of the four groups become identical, as may be observed in bromochloromethane and isopropylchloride as shown below ... 

Superimposability and loss of optical activity, and (Hi) Specific optical rotation. 

Seebach and Daum (75) investigated the properties of a chiral acyclic diol, 1,4-bis(dimethylamino)-(2S,35)- and (2K,3/ )-butane-2,3-diol (52) as a chiral auxiliary reagent for complexing with LAH. The diol is readily available from diethyl tartrate by conversion to the dimethylamide and reduction with LAH. The diol 52 could be converted to a 1 1 complex (53) with LAH (eq. [18]), which was used for the reduction of aldehydes and ketones in optical yields up to 75%. Since both enantiomers of 53 are available, dextro- or levorotatory products may be prepared. The chiral diol is readily recoverable without loss of optical activity. The (- )-52-LAH complex reduced dialkyl and aryl alkyl ketones to products enriched in the (S)-carbinol, whereas (+ )-52-LAH gives the opposite result. The highest optical yield of 75% was obtained in the reduction of 2,4,6-... 

Fig. 10.4 More examples of 3-20-KIE s. (Top, solvolysis of a t-butyl substituted adamantine. Bottom, racemization (loss of optical activity) of a dihydrophenanthrene derivative (Mislow, K., and coworkers, J. Am. Chem. Soc. 86, 1733 (1964))...

Racemization, which results in the loss of optical activity of a chiral compound, is considered to be one of the fundamental processes in dynamic stereochemistry. Quite generally, racemization can be caused by supplying adequate energy by heating or irradiation, or it may be effected by chemical reactions. 

The behavior of chiral phenyl /-butyl sulfoxide 219 and a-phenyl-ethyl phenyl sulfoxide 220 is completely different in strongly acidic media and in the presence of halide ions. Two reactions were found (266) to occur in parallel. One results in the loss of optical activity, and the second leads to the decomposition of the sulfoxide. It was observed that the racemization process is not accompanied by [ 0] oxygen exchange. In the case of sulfoxide 220 the complete loss of optical activity at chiral sulfur is accompanied by partial racemization at the chiral carbon center. These results are consistent with a sulfenic acid-ion-pair mechanism formulated by Modena and co-workers (266) as follows (it is obvious that the formation of achiral sulfenic acid is responsible for racemization). 

Whereas racemization is the complete loss of optical activity with time, epimerization is the reversible interconversion of diastereoisomers to an equilibrium mixture which is not necessarily optically inactive. Diastereoisomers arise from the combination of the two chiral centers in 9, namely the metal centered, R and S, and the resolved (S) optically active ligand center. The diastereoisomers (RS) and (SS) differ in their properties. 

The convenience of this method is related to the ease of formation of the lithium derivative. At present, only optically active germyllithiums are available. However, this reaction is suitable method of introduction of a chiral ligand without loss of optical activity, and the ligand is strongly bonded to the transition metal as revealed by the reactivity of these complexes. 

The loss of optical activity accompanying deprotonation of (/f)-2,2,6-trimethyl-cyclohexanone by lithium diisopropylamide (LDA, which exists as a dimer) in THF is governed by the rate equation v = /c [ketone] [LDA]°-, which is consistent with a rate-determining proton transfer involving amine monomer. ... 

No other semicyclic or exocylic diolefins were produced, although loss of optical activity was somewhat faster than dehydrogenation. 

Whilst this may appear a problem in stereochemistry, it is actually mechanism based and depends upon the nature of the reaction intermediates. The loss of optical activity is because we form a racemic product, i.e. a mixture of enantiomers, or produce a compound that is no longer chiral. 

When this strategy was applied to the chiral azide 343, a severe loss of optical activity occurred, but the synthetic sequence was continued to afford the target molecule 347 in almost racemic form (66) (Scheme 9.66). 

Notice the similarity of steric courses in the substitution reactions of the free ion and the ion pair, and the complete loss of optical activity for every act of substitution. 

Solvolysis of optically active 5-tosyloxypenta-l, 2-dienes leads to methylenecyclobutanols with inversion of configuration at the carbon bearing the leaving group, without loss of optical activity.13 Once again there is competition between the homoallyl and 1234-1243 rearrangement. 

It seemed likely that mechanism B would produce a symmetrical trigonal bipyramid and thus lead to racemization if an optically active substrate was used in the reaction. Mechanism A would certainly lead to total racemization, but mechanism C would not cause loss of optical activity. On the other hand it is possible to draw an asymmetric trigonal pyramid or an asymmetric tetragonal pyramid as a five-coordinate intermediate in mechanism B. The latter seem unlikely in organic solvents with weak donor properties. Furthermore, recent evidence suggests a symmetric trigonal pyramid as an intermediate in the racemization of trisacetylacetonate (50). 

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