Matched substrate/reagent pair

Additions of enantioenriched allenylzinc reagents to chiral aldehydes provide intermediates that can be employed in the synthesis of polyketide natural products. Matched and mismatched pairing of reagent and substrate can result in enhanced or diminished diastereoselectivity (Eqs. 9.132 and 9.133) [114]. 

When two of the reaction components are chiral (any combination of substrate, reagent, catalyst, or solvent), the chirality elements of each reactant will operate either in concert (matched pair) or in opposition (mismatched pair) and together influence the stereochemical outcome of the reaction. In this case, the reaction is subject to double asymmetric induction. Unless the diastereofadal selectivities of both chiral reactants are in opposition and identical in magnitude, the ratio C D 1. Applications of double asymmetric induction in synthesis will be discussed in Chapter 5. 

These aldols have all had just one chiral centre in the starting material. Should there be more than one, double diastereomeric induction produces matched and mismatched pairs of substrates and reagents, perfectly illustrated by the Evans aldol method applied to the syn and anti aldol products 205 themselves derived from asymmetric aldol reactions. The extra chiral centre, though carrying just a methyl group, has a big effect on the result. The absolute stereochemistry of the OPMB group is the same in both anti-205 and yvn-205 but the stereoselectivity achieved is very different. The matched case favours Felkin selectivity as well as transition state 201 but, with the mismatched pair, the two are at cross purposes. It is interesting than 1,2-control does not dominate in this case.33... 

Asymmetric induction The preferential formation of one enantiomer or diastereo-mer over another, due to the influence of a stereogenic element in the substrate, reagent, catalyst, or environment (such as solvent). Also, the preferential formation of one configuration of a stereogenic element under similar circumstances. When two reactants of a reaction are stereogenic, the stereogenic elements of each reactant may operate either in concert (matched pair) or in opposition (mismatched pair). This phenomenon is known [58,59] as double asymmetric induction, or double diastereoselection. See Section 1.5. 

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... 

If, as in the reaction example in Figure 3.32, during the addition to enantiomerically pure chiral alkenes, substrate and reagent control of diastereoselectivity act in opposite directions, we have a so-called mismatched pair. For obvious reasons it reacts with relatively little diastereoselectivity and also relatively slowly. Side reactions and, as a consequence, reduced yields are not unusual in this type of reaction. However, there are cases in which mismatched paris still give rise to highly diastereoselective reactions, just not as high as the matched pair. 

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. 

Fig. 3.27. Thought experiment III Reagent control of stereoselectivity as a method for enhancing the substrate control of stereoselectivity (matched pair situation).

The most efficient method for the stereoselective formation of amines through rhodium(II)-catalyzed intermolecular C(sp )-H amination, to date, involves a diastereoselective approach based on the synergistic interaction between the stdfonimidamide (S)-7 and the chiral rhodium complex Rh2(S-nta)4 8. Benzylic and allylic amines are isolated from various complex substrates used as the limiting component, in excellent yields of up to 99% and complete stereocontrol (Scheme 34). Of course, the other enantiomer is also efficiendy accessible through the use of the other matched pair of reagents. 

---