Stereodifferentiating process, double

As pointed out in an earlier section, the ees for the asymmetric hydroxylation of acyclic enolates derived from a-branched carbonyl compounds is often low because of the difficulty in generating a specific enolate geometric isomer as well as poor enantiofacial discrimination between the re and si faces of the enolate (Scheme 25). In one example of a double stereodifferentiation process, the asymmetric oxidation of a chiral enolate, was successfully employed to circumvent these difficulties <87JOC5288>. For the matched pair, (—)-(179) and oxaziridine (—)-(114), the de was 88-91% (Equation (43)) whereas with the mismatched pair, (—)-(179) and (+)-(114), the de dropped to 48.4%. The pyrrolidine methanol chiral auxiliary in (180) was removed without racemization by basic hydrolysis affording nonracemic atrolactic acid in 70-89% yield. 

The observation that aldehyde diastereoface selection is interrelated with allylborane geometry has important implications for the related aldol processes. The reactions of (-)-180a and (-)-180b with both enantiomers of aldehyde 181 revealed both consonant and dissonant double stereodifferentiation. For the Cram-selective ( )-crotyl... 

Scheme 47 shows a case 2 example for double stereodifferentiation, the problem being to reduce enone 47-1 preferentially to alcohol 47-2 or 47-3 [110]. The substrate control (DIBAH or L-selectride) is essentially zero, so that the chiral hydride donor must do the job. It can be seen that BINAL-H [ 111 ] is ineffective whereas diborane plus the CBS catalyst [112] shows a very pronounced reagent control so that either one of 47-2 and 47-3 may be generated selectively for the formation of 47-3 the reagent control is much higher than for 47-2, which is surprising in view of the low substrate control of the process. 

Next, the double-stereodifferentiating [27] aldol process with a-chiral aldehydes was examined, seperate experiments using both enantiomeric forms of phenyl propionaldehyde were undertaken. Use of (S)-phenylpropionalde-hyde 28 gave two diastereomers 29 and 30 in a ratio of 2.5 1 and 68% yield. The major one is still the anti-Cram/Felkin compound 29, which is quite unusual because 28 usually provides high selectivity in favor of the Cram/ Felkin adduct 30 [28]. 

In recent years, even chemists have become concerned about terminology to be used for asymmetric syntheses and asymmetric reaction processes . Since catalysis by enzymes represents the ultimate in an asymmetric reaction, it is appropriate to consider briefly a new proposal. Izumi and Tai have proposed that the time has come to abandon the use of stereoselective and stereospecific [62], They point to two components in the transformation of a substrate to a product. The first resides in chemical structures (e.g., a double bond) rather than in a particular steric structure and the reaction is governed by the nature of the reagent or catalyst (whether the process proceeds with retention or inversion whether an addition is syn or anti). In the second component, the reagent or catalyst interacts topologically with the three-dimensional structure of the substrate. This is described as stereodifferentiation and results from the stereo-differentiating ability of the catalyst or reagent. 

It seems likely that biochemists will continue to use a more pragmatic and less comprehensive approach. In biochemical processes, two important features are the structures of substrate and product. The overall steric structure of the substrate (and not just the possession of some structural feature such as a double bond) is important in terms of binding to an enzyme or receptor. Since many enzymatic reactions are readily reversible, overall product structure is important for the same reason. Furthermore, since many enzymes make more than one type of stereodifferentiation, the use of the stereo-differentiating terminology of Izumi and Tai would be somewhat cumbersome. The overall steric structure of molecules (as opposed to isolated structural features) is also important in the area of drug-receptor interactions. 

The usually high stereoselectivity on formation of a new double bond or a stereogenic center is due to the stereodifferentiating ability of envelope-like transition states of this concerted suprafacial process. The envelope conformation of cyclopentane serves as a model for the transition state of the [2,3] sigmatropic rearrangement6,7. 

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