Stereochemical switches

In 1981, a stereoselective palladium-catalyzed 1,4-diacetoxylation of 1,3-dienes with p-benzoquinone (BQ) as the oxidant was reported33. It was found that chloride ions can be used as a stereochemical switch. Thus, in the absence of chloride ions trans diacetoxylation takes place, whereas in the presence of a catalytic amount of chloride ion (as added LiCl) a cis diacetoxylation takes place (Scheme 4). In both cases the reaction is highly 1,4-regioselective. The explanation for... 

Diastereomeric benzylamines are obtained by cinnamylation of imines with alkenylsiladi-oxolane 90. The stereochemical switch requires only a change of the A -substituent. The cognate heterocycle 91 is useful catalyzing addition of ketene silyl ethers to hydrazones. ... 

Scheme 8.36 Stereochemical switch as a result of the employed aryl source.

Synthesis of (i)-Amathaspiramide F Stereochemical Switch of a [2,3]-Stevens Rearrangement... 

Figure 11.3 Typical configuration for the on-line coupling of an achiral and chiral cliro-matograpliic system by means of a switching valve. The non-enantio-resolved solute is isolated on the achiral phase and then stereochemically separated on the chiral phase. Reprinted from G. Subramanian, A Practical Approach to Chiral Separation by Liquid Chromatography, 1994, pp. 357-396, with permission from Wiley-VCH.

In all the reported examples, the enzyme selectivity was affected by the solvent used, but the stereochemical preference remained the same. However, in some specific cases it was found that it was also possible to invert the hydrolases enantioselectivity. The first report was again from iQibanov s group, which described the transesterification of the model compound (13) with n-propanol. As shown in Table 1.6, the enantiopreference of an Aspergillus oryzae protease shifted from the (l)- to the (D)-enantiomer by moving from acetonitrile to CCI4 [30]. Similar observations on the inversion of enantioselectivity by switching from one solvent to another were later reported by other authors [31]. 

An expedient method for the preparation of isochromene carboxylates (203) has been developed, which relies on the regioselective 1,6-addition of various nucleophiles, such as Grignard reagents, alkoxides, and cyanide, to benzopyranylidenetungsten(O) complexes (201), followed by iodine oxidation of the addition intermediates (202)254 DFT calculations have been carried out to rationalize the unusual switch in stereoselectivity, where ynone and ynoate substrates exhibit opposite stereochemical preferences in the stannylcupration.255... 

It must be admitted that 0-0 and a-n switch processes are of limited stereochemical interest. Given the prototypes (92) or (97), the reactions must be syw-stereospecific any other stereochemical result would in fact be used as a criterion of a multi-step mechanism. This is also true of the mixed types, (101)-(104). But these reactions are exceedingly useful as models for orbital-based calculations or estimates of free energies of activation, with the use of extended HMO theory. The four- or six-center process (92)-(104) does not appear to be more complex than the Diels-Alder reaction, which has been investigated theoretically (Herndon and Hall, 1967). 

The stereochemical details are interesting in establishing the mechanism but not important to remember. What is important is that the origin of the two methyl groups in dimethylallyl pyrophosphate is quite distinct and can easily be traced if you always draw the intermediates in the way we have drawn them. We will now switch to labelling to make the point. 

The above result unequivocally demonstrates that the seemingly weak solvation effect can play a decisive role, which controls and even switches the stereochemical outcome of the enantiodifferentiating photoisomerization. Temperature, pressure, and solvation, which function as environmental factors to control the enantiodifferentiation in the excited state, are all entropic in nature. Probably the key is the critical control of the weak interactions involved in the exciplex intermediate, as with the biological and supramolecular interactions in... 

Accordingly, we conducted experiments with CLEAs of MeHnL and PfNLase in tandem in a 90 10 DlPE-bulFer pH 5.5 medium [19]. The reaction proceeded to nearly full conversion (see Figure 16.4a) and the product ee was 94%. Combining both enzymes in a bienzymatic catalyst (combi-CLEA, Figure 16.4b) resulted in further improvement and 98% enantiomerically pure (S)-3a was obtained. It would seem that the nitrile intermediate is immediately hydrolysed in the combiCLEA particles, which supresses dififiision into the water phase and possible racemisa-tion. The amount of (S)-mandeUc amide ((S)-4a, see Figures 16.3 and 16.4, approx. 40%) that accompanied the formation of (S)-3a was more than would be expected from the data in Table 16.1 and made us aware of possible stereochemical effects on the acid/amide mechanistic switch [5] in PfNLase as will be discussed later. 

The examples shown in Scheme 16, which are representative for all other sulfinates studied, demonstrate a high level of stereoselectivity (around 80-90% of the original enantiomeric excess is retained after switching the stereogenic atom from sulfur to carbon). Despite these encouraging results, the somewhat tedious and stereochemically unreliable preparation of the starting sulfinates [47] may be the reason for the reluctance of the chemical community to use this chemistry as an entry to enantiomerically pure 2-alkenyl sulfones. 

To further exemplify the dependence of the stereochemical course of chiral enolate additions catalyzed by phosphoramides, a detailed survey of additions to aldehydes using chiral p-hydroxyenolate 17 and 10 mol % of la was performed. Unlike additions of 15, diastereoselectivities of the resultant aldol products using 17 could be switched depending upon the configuration of the phosphoramide employed (eq 7, Table 6). 

That is, the stereochemical course was switched from anti to syn. Thus, the solvent and salt effects were striking. To summarize these results, in a polar solvent such as DMF, the stereochemistry is always anti the syn stereochemistry results in a less-polar solvent such as THF in the presence of an alkaline-metal fluoride [34],... 

Now, the vinyl cuprate attacks the epoxide at its less substituted end releasing the same oxyanior. which promptly closes the lactone again. Once more there is no change at the chiral centre. Ths switching of an oxygen atom from lactone to epoxide and back again is a popular method d -stereochemical control. 

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