1,5-enantioselective induction

Before 1968, attempts to perform enantioselective hydrogenations had either used a chiral auxiliary attached to the substrate [1] or a heterogeneous catalyst that was on a chiral support, usually derived from Nature [2]. Since the disclosure of chiral phosphine ligands to bring about enantioselective induction in a hydrogenation, many systems have been developed, as evidenced in this book. The evolution of these transition-metal catalysts has been discussed in a number of reviews [3-12]. 

During the late 1960s, Homer et al. [13] and Knowles and Sabacky [14] independently found that a chiral monodentate tertiary phosphine, in the presence of a rhodium complex, could provide enantioselective induction for a hydrogenation, although the amount of induction was small [15-20]. The chiral phosphine ligand replaced the triphenylphosphine in a Wilkinson-type catalyst [10, 21, 22]. At about this time, it was also found that [Rh(COD)2]+ or [Rh(NBD)2]+ could be used as catalyst precursors, without the need to perform ligand exchange reactions [23]. 

Lewis acid catalysis is not limited to cases in which increased yields or enhanced selectivities are desired. Lewis acids offer also the possibility to induce chiral information leading to enantioselective product formation. The enantioselective induction by chiral Lewis acids found widespread application in organic synthesis, especially in the synthesis of natural products with many chiral centres. An enantioselective Diels-Alder reaction is the key step in the synthesis of an iodolactone prostaglandine precursor (Scheme 6).88... 

Diastereomer analysis on the unpurified aldol adduct 52b revealed that the total syn anti diastereoselection was 400 1 whereas enantioselective induction in the syn products was 660 1. On the other hand, Evans in some complementary studies also found that in the condensation of the chiral aldehyde 53 with an achiral enolate 56a only a slight preference was noted for the anti-Cram aldol diastereomer 58a (58a 57a = 64 36). In the analogous condensation of the chiral enolate 56b. however, the yn-stereoselection was approximately the same (57b 58b > 400 1) as that noted for enolate 49 but with the opposite sense of asymmetric induction (Scheme 9.17). Therefore, it can be concluded that enolate chirality transfer in these systems strongly dominates the condensation process with chiral aldehydes. 

This reversed reactivity mode allows the use of chiral nucleophilic catalysts for enantioselective induction. 

Enantioselective reduction of prochiral ketones by transfer hydrogenation is catalysed by amino acid derivatives. A mechanistic suggestion for the origin of enantioselective induction has been proposed.306 ,/M Jnsaluralcd nitriles are efficiently reduced by a Cu(I)-H species in the presence of bisphosphine ligands. The active Cu(I)-H species was generated by the reaction of copper(II) acetate and polymethylhydrosilane.307... 

Furthermore, 1-Cu has been applied as a catalyst in the asymmetric substitution reaction of Grignard reagents with allylic substrates (eq 7). Under optimized experimental conditions, the y-product is obtained selectively in quantitative yield. However, the enantioselective induction is low to moderate (up to 40%). 

Bao and Wulff compared catalysts prepared from vaulted biaryls and from bromo-borane dimethylsulfide with those generated from linear biaryls with regard to their capacity to provide enantioselective induction in the Diels-Alder reaction of cyclo-pentadiene and methacrolein (Eqs 6 and 7) [7]. Because the (5) enantiomers of vaulted biaryls result in induction opposite to that resulting from use of the (5) enantiomer of binaphthol, and because effective catalysts cannot be generated from binaphthol and phenylboron dichloride, suggest that the catalysts obtained from vaulted biaryls do not have the same structure as the Cs-symmetrical catalyst produced from binaphthol. 

Williams ML, Wainer IW, Embree L, Barnett M, Granvil CL, Ducharme MP. Enantioselective induction of cyclophosphamide metabohsm by phenytoin. Chirality 1999 ll(7) 569-74. 

While effective bimetallic catalyst design has the potential to lead to an enhancement of the reaction rate, the use of chiral bimetallic catalysts has also been explored to enhance the enantioselectivity of a reaction. Such bimetallic chiral induction is excellently demonstrated by the use of digold catalysts for the hydroamination of prochiral substrates such as allenes and alkenes [59]. The bimetallic Au catalyst 66, for example, was shown to be an effective catalyst for the hydroamination of amino-allenes in the presence of a silver salt activator (Scheme 24) [106]. The highest enantioselective induction for this reaction was achieved with a 1 1 ratio of AgBp4 to 66 (51 % ee) suggesting that the monocationic... 

The intended use of a chiral NHC complex, however, led only to very low enantioselective induction in this reaction [40]. 

The creation of an asymmetric environment around a metallic center in order to suit the partners of an organic transformation allows enantioselectivity induction in catalytic processes. Palladium complexes bearing NHC groups are emerging as effective catalysts for enantioselective and nonstereospecific organic transformations. 

Chiral rhodium complexes have provided high yields but moderate ee values in the asymmetric hydrosilylation of acetophenone [56,125]. Chiral iridium complexes, in which the NHC bears a hydroxyamide, provided moderate to good yields (up to 85%) in the hydrosilylation of a wide range of aryl methyl ketones. More importantly, high enantioselective induction was observed (up to 92%) at room temperature [126]. 

Also, the cationic polycyclization of polyenes is possible with designed thioureas bearing an additional aromatic moiety in order to stabilize some interesting cation-jt interactions for enantioselectivity induction next to the traditional anion binding (Scheme 7.37) [55]. 

Various substituents (X) can be introduced at the 3,3 -positions of the chiral backbone, effectively providing the requisite chiral envirorunent for highly enantioselective induction. 

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