Mutual kinetic resolution

Thought Experiment I on the Hydroboration of Chiral Alkenes with Chiral Boranes Mutual Kinetic Resolution... 

We thus summarize the yield ratios of the conceivable hydroboration products E, F, G, and H should be much little little none. One enantiomer of E comes from the reaction of the S-alkene with the, S, S -borane the other enantiomer of E comes from the reaction of the //-alkene with the //.//-borane. Thus, each enantiomer of the reagent has preferentially reacted with one enantiomer of the substrate. The diastereoselectivity of this reaction thus corresponds to a mutual kinetic resolution. 

The condition for the occurrence of a mutual kinetic resolution is therefore that considerable substrate control of stereoselectivity and considerable reagent control of stereoselectivity occur simultaneously. 

Fig. 10.40. Catalytic asymmetric addition of Et2Zn to Ph— C(=0)H. Chiral amplification through a mutual kinetic resolution of the (auxiliary/ZnEt)2 complex which is produced from two molecules of chiral aminoalcohol and diethylzinc each.

The occurrence of chiral amplification in this case is explained by the mechanism of Figure 8.31. When chiral amplification is observed one always finds—as is the case here—that two molecules of the chiral auxiliary become linked to each other, albeit indirectly (i.e., via another component of the reaction mixture). In other words, a derivative of the dimer of the chiral auxiliary is formed. When chiral amplification occurs, this derivative of the dimer exists in the form of only two of its three conceivable stereoisomers. The reason for this is a mutual kinetic resolution (cf. Section 3.4.3). 

Information about the degree of configurational stability of allenyltitanium compounds has been provided by Hoffmann and Hoppe (Scheme 35). Racemic allenyltitanium reagent (3) is prepared by sequential treatment of 3-methoxy-1,2-butadiene (2) with n-butyllithium and titanium tetraisopropoxide. In the reaction of the racemate with one equivalent of (S)-(4) or its racemate, products (5)-(8) are formed in 70-90% total yield in the ratios shown in Scheme 35. Since the product ratios from the two experiments are different, the equilibrium between the enantiomers of (3) must be slow compared to the rate of reaction of (3) with (4). Thus, (S)-(3) leads to (5) + (6) and (R)-(3) leads to (7) + (8) (i.e. 51 49). From experiment B, the combinations (S)-(3) + (S)-(4) and (/ )-(3) -t- (/ )-(4) are shown to react considerably more rapidly than that of the (R)/(.S) pairs (mutual kinetic resolution). ... 

However, the use of this approach points up the origin of the observed mutual kinetic resolution. In part, at least, it is a consequence of the inherent diastereoface selectivity exhibited by the two reactants. Thus, if we ignore the threo isomers, the approximation used in Figure 2 leads to a prediction that the rate of the reaction will be approximately seven times the rate of the R S reaction. 

I believe that the phenomenon of double stereodifferentiation with mutual kinetic resolution may have general ramifications beyond the specific aldol condensations being discussed here. We can generalize as shown below ... 

That is, in order for the phenomenon to be observed, both reactants must show inherent diastereoface selectivity in their reactions with achiral partners. If one of the reactants shows no inherent diastereoface selectivity in its reactions with achiral reactants, then mutual kinetic resolution will not be observed regardless of the stereoselectivity of the other reactant. For an example, consider the case of an enzyme which mediates some reaction, say reduction of the carbonyl group. We can let the enzyme be A and assume that, because of its uniquely-evolved molecular structure, it shows very high inherent diastereoface selectivity (thus, it will reduce prochiral carbonyl compounds to chiral alcohols with very high enantiomeric excess). For B, let us take a chiral aldehyde that shows no inherent diastereoface selectivity in its... 

In concluding this discussion, it must be noted that a few examples of mutual kinetic resolution , i.e., the diastereoselective reaction between two racemic reactants leading to a mixture of diastereoisomers, have been reported [28,34]. The racemic nature of the products excludes these reactions from the interest of the present chapter. 

Scheme 2.3 An example of mutual kinetic resolution between two racemic reactants (Ref [32b]).

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