Chirality 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. 

When one of the reactants is chiral, asymmetric induction can provide enantioselective products ... 

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

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]. 

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]. 

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. 

A more eflicient and general synthetic procedure is the Masamune reaction of aldehydes with boron enolates of chiral a-silyloxy ketones. A double asymmetric induction generates two new chiral centres with enantioselectivities > 99%. It is again explained by a chair-like six-centre transition state. The repulsive interactions of the bulky cyclohexyl group with the vinylic hydrogen and the boron ligands dictate the approach of the enolate to the aldehyde (S. Masamune, 1981 A). The fi-hydroxy-x-methyl ketones obtained are pure threo products (threo = threose- or threonine-like Fischer formula also termed syn" = planar zig-zag chain with substituents on one side), and the reaction has successfully been applied to macrolide syntheses (S. Masamune, 1981 B). Optically pure threo (= syn") 8-hydroxy-a-methyl carboxylic acids are obtained by desilylation and periodate oxidation (S. Masamune, 1981 A). Chiral 0-((S)-trans-2,5-dimethyl-l-borolanyl) ketene thioketals giving pure erythro (= anti ) diastereomers have also been developed by S. Masamune (1986). 

Chiral boron(III) Lewis acid catalysts have also been used for enantioselective cycloaddition reactions of carbonyl compounds [17]. The chiral acyloxylborane catalysts 9a-9d, which are also efficient catalysts for asymmetric Diels-Alder reactions [17, 18], can also catalyze highly enantioselective cycloaddition reactions of aldehydes with activated dienes. The arylboron catalysts 9b-9c which are air- and moisture-stable have been shown by Yamamoto et al. to induce excellent chiral induction in the cycloaddition reaction between, e.g., benzaldehyde and Danishefsky s dienes such as 2b with up to 95% yield and 97% ee of the cycloaddition product CIS-3b (Scheme 4.9) [17]. 

With an appropriate chiral reactant, high enantioselectivity can be achieved, as a result of asymmetric induction If both reactants are chiral, this procedure is called the double asymmetric reaction and the observed enantioselectivity can be even higher. 

Early work on the use of chiral phase-transfer catalysis in asymmetric Darzens reactions was conducted independently by the groups of Wynberg [38] and Co-lonna [39], but the observed asymmetric induction was low. More recently Toke s group has used catalytic chiral aza crown ethers in Darzens reactions [40-42], but again only low to moderate enantioselectivities resulted. 

Chiral, nonracemic allylboron reagents 1-7 with stereocenters at Cl of the allyl or 2-butenyl unit have been described. Although these optically active a-substituted allylboron reagents are generally less convenient to synthesize than those with conventional auxiliaries (Section 1.3.3.3.3.1.4.), this disadvantage is compensated for by the fact that their reactions with aldehydes often occur with almost 100% asymmetric induction. Thus, the enantiomeric purity as well as the ease of preparation of these chiral a-substituted allylboron reagents are important variables that determine their utility in enantioselective allylboration reactions with achiral aldehydes, and in double asymmetric reactions with chiral aldehydes (Section 1.3.3.3.3.2.4.). 

The premier example of this process in an ylide transformation designed for [2,3]-sigmatropic rearrangement is reported in Eq. 15 [107]. The threo product 47 is dominant with the use of the chiral Rh2(MEOX)4 catalysts but is the minor product with Rh2(OAc)4. That this process occurs through the metal-stabilized ylide rather than a chiral free ylide was shown from asymmetric induction using allyl iodide and ethyl diazoacetate [107]. Somewhat lower enantioselectivities have been observed in other systems [108]. 

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