Enantiotopic leaving groups

It should be noted that Trost s DPPBA-derived ligand 21 possesses considerable utility in many other situations of allylic substitution, for example with substrates which are cyclic or which possess enantiotopic leaving groups, or with prochiral nucleophiles.1171... 

The first strategy involves discrimination between enantiotopic leaving groups (Type A). In the second approach, two enantiomers of a racemic substrate converge into a meso-n-al y complex wherein preferential attack of the nucleophile at one of either allylic termini leads to asymmetric induction, a process that may be referred to as a dynamic kinetic enantioselective transformation (Type B). The third requires differentiation between two enantiotopic transition... 

Substrates with Two Geminal Enantiotopic Leaving Groups. 89... 

The exact ee (enantiomeric excess) is very sensitive to reaction variables, such as solvent and additives (such as R4NX salts), which influence the amount of ion pairing in the nucleophile. For substrates with enantiotopic leaving groups, the degree of asymmetric induction depends on the ionization step, and is relatively independent of the nucleophile (equation 64). 

Enantiotopic leaving groups enantioselective ionization of the allylic leaving group during OA of a meso allylic system will lead to one or the other enantiomer of the product (step b, Scheme 12.10a or b). 

Substrates derived from meso-cycloalkenediols such as 41 are a highly versatile starting materials for enantioselective allylic substitutions [15]. Regioselective displacement of one of the enantiotopic leaving groups by the chiral catalyst leads to a chiral allyl intermediate 42 which is attacked regioselectively at the ster-ically less hindered position to afford product 43 (Scheme 17). Products of this type can be converted to variety of useful compounds by a second allylic substitution reaction. 

Enantiodiscrimination during oxidative addition can occur by preferential complexation of one of the enantiomeric conformers of a prostereogenic substrate (equation 1) or by differentiating between two enantiotopic leaving groups of a nte.w-substrate (equation 2). 

Enantioselective allylic substitution can also be achieved by selective cleavage of one of two enantiotopic leaving groups. Hiis selectivity can occur within a cyclic substrate, as shown in Equation D of Scheme 20.10. Enantioselective allylic substitutions can also occur by replacement of one of two enantiotopic leaving groups on the same carbon, as shown for the acetal structure in Equation E of Scheme 20.10. 

Asymmetrically induced Heck reactions can also be performed with substrates containing two enantiotopic leaving groups. Starting from dimedone, novel cyclohexa-l,4-diene-l,5-diol bis(nonafluorobutanesulfonates) such as 309 have been prepared and cycUzed under palladium catalysis to cleanly give bicy-clo[4.2.0]octadienes 370 and bicyclo[4.2.0]octenones, respectively, by an unprecedented 4-exo-trig process (Scheme 8.77, cf. Scheme 8.66). In the presence of a chiral phosphine ligand, the products could be obtained with modest enantiomeric excesses (up to 52% ee) [239]. 

Scheme 8.77 A 4-exo-trig cyclization with intramolecular difTerentiation of enantiotopic leaving groups [239].

These substrates with enantiotopic leaving groups have received considerable attention from Trost s group, and much of the published work has come from this group. " " Thus, ligand 20 has been used in the conversion of the mei o-dibenzoate 122 into the monosubstituted product 123 with excellent enantioselectivity using the diketone 124 as nucleophile in the presence of base (Scheme 27). 

An enantioselective method in which a chiral catalyst is responsible of a desymmetrizing nucleophilic aromatic substitution through discrimination in the displacement of an enantiotopic leaving group has been reported very recently in the heterocyclic series. Under PTC conditions, the chiral counterion 113 (10% mol) directs the substitution of prochiral dichloropyrimidine 112 by PhSKby a tandem desymmetrization/kinetic resolution mechanism, leading to the chiral product 114 (Scheme 8.23) [87]. 

Enantiotopic leaving groups can also differentiated by asymmetric Heck reactions (for a possible substrate, see Scheme 5-30). 

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