Double stereodifferentiation mismatched pairs

Double stereodifferentiation This refers to the addition of a chiral enolate or allyl metal reagent to a chiral aldehyde. Enhanced stereoselectivity can be obtained when the aldehyde and reagent exhibit complementary facile preference (matched case). Conversely, diminished results might be observed when their facial preference is opposed (mismatched pair). 

The observed high degree of selectivity is a result of the fact that substrate induction and reagent induction reinforce each other and are thus intensified. This is therefore a case of double stereodifferentiation.70 The two compounds constitute what is known as a matched pair. In a mismatched pair the two inductive tendencies would be in competition, and selectivity would be reduced... 

Thought Experiments II and III on the Hydroboration of Chiral Alkenes with Chiral Boranes Reagent Control of Diastereoselec-tivity, Matched/Mismatched Pairs, Double Stereodifferentiation... 

Conversely, the addition of enantiomerically pure chiral dialkylboranes to enantiomerically pure chiral alkenes can also take place in such a way that substrate control and reagent control of diastereoselectivity act in the same direction. Then we have a matched pair. It reacts faster than the corresponding mismatched pair and with especially high diastereoselectivity. This approach to stereoselective synthesis is also referred to as double stereodifferentiation. 

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. 

Interestingly, the reactions of (i )-2,3-0-isopropyUdene-D-glyceraldehyde (35) with l-methoxy-2,4-dimethyl-3-(trimethylsiloxy)butadiene, catalyzed by (-f)-34 and (-)-34, respectively, involved a high degree of double stereodifferentiation. The matched combination of (-)-34 with R)-35 gave one of the four possible diastereomeric pyrone products in 93.1% selectivity. On the other hand, the mismatched pair showed almost no selectivity (Scheme 21) [38]. 

Bisituselectivity is operative in double differentiation, double stereodifferentiation, and double asymmetric induction, and, has led to the terms matched/mismatched pairs. 

Diastereoselective aldol reactions have been extensively utilized in the synthesis of complex natural products, including macrolides [4] and ionophores [5]. In this context, iterative approaches are often exploited to append propionate units one at a time. This approach leads to double stereodifferentiation [6] in tvhich the reactant pairs can be either matched or mismatched . The chirality of the t vo reactants reinforce each other if they are matched. As a result, the diastereoselectivity is often higher than vould... 

For discussion of synthesis design based on the manipulation of competing regiodirecting effects, see [4] this same concept has been discussed in terms of matched and mismatched pairs of substituents (see [5]), by an extension of the nomenclature used for double stereodifferentiation, but since double stereodifferentiation effects can arise... 

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