Chiral Bases as Catalysts

In addition to nitrogen bases, the potential of chiral phosphanes as catalysts has also been assessed. Early work on the use of P-chiral phosphines in intramolecular... 

In addition to Lewis acid catalysts, chiral bases catalyze the Diels-Alder reaction.100101 Although the use of bases as catalysts does show promise, especially for acid-sensitive functionality, the current level of asymmetric induction may not be acceptable for scale up. In addition, only a limited number of dienes and dienophiles have been shown to undergo the chiral-base catalyzed Diels-Alder reaction. 

Ester Enolate Aldol Additions to Aldehydes. Among the first examples of aldol additions employing chiral Lewis bases as catalysts were the additions of trichlorosilyl ketene acetals to aldehydes. Silyl ketene acetal 7 could be generated by metathesis of methyl tributylstannylacetate with SiCL. Treatment of 7 with benzaldehyde and 10 mol % of a phosphoramide in CH2CI2 at —78°C afforded aldol products in good to high yields with moderate enantioselectivities for all phosphoramides employed. Reaction of 7 with pivalaldehyde provided aldol products in similar yields and with slightly improved enantioselectivities. The increase in stereoselection is presumably attributed to a less com-... 

Intramolecular asymmetric induction has also been used in electrochemistry as in the reduction of optically active alcohol esters or amides of a-keto [469,470] and unsaturated [471] acids and oximes [472] and in the oxidation of olefins [473]. A maximum asymmetric yield of 81% was obtained in the reduction of (5 )-4-isopropyl-2-oxazolidinone phenyl-glyoxylate [470]. Nonaka and coworkers [474,475] found that amino acid A-carboxy anhydrides were polymerized with various electrogenerated bases as catalyst to give the poly(amino acids) with high chirality in high yields. Conductive chiral poly(thiophenes) prepared by electropolymerization can be used for chiral anion recognition [476]. 

Since its discovery by Roelen in 1938 [l],the hydroformylation process was exclusively based on cobalt as catalyst metal, until the development of rhodium-phosphine complexes in the late 1960s [2]. Industrial efforts have been focused on the preparation of norraaZ-aldehydes (linear aldehydes) from 1-alkenes. In contrast, asymmetric hydroformylation, which requires iso-aldehydes (branched aldehydes) to be formed from 1 -alkenes, was first examined in the early 1970s by four groups independently, using Rh(I) complexes of chiral phosphines as catalysts [3,4,5,6]. Since then, a number of chiral ligands have been developed for... 

A more recent alternative approach, developed by Jacobsen and co-workers, concerns the catalytic asymmetric epoxidation of unfunctionalized olefins using cheap NaOCl as oxidant in the presence of Mn complexes of chiral Schiff bases as catalysts, the so-called salene (Fig. 3-4). Values of 97% e.e. have been achieved using cis-disubstituted or trisubstituted alkenes. Equation 3-15 describes the Jacobsen epoxidation of olefins schematically. 

Higher levels of enantioselectivities in the a-oxytosylation of ketones were achieved in several recent works. Chi Zhang and coworkers have evaluated spirobiindane-based chiral iodoarenes as catalyst and were able to obtain a-tosyloxylated ketones in up to 58% enantiomeric excess using catalyst 12 (Figure 4.1) [28]. Moran and Rodriguez have prepared several chiral aryl iodides (e.g., structures 13 and 14, Figure 4.1) and... 

The main drawback in Sharpless epoxidation is that the substrate must bear a functional group to achieve the precoordination required for high enantioselec-tivity (as in the case of allyl alcohol). This restriction is not applicable to the epoxidation of alkyl- and aryl-substituted olefins with manganese complexes of chiral Schiffs bases as catalysts. Very high enantioselectivities can be obtained in these reactions (Jacobsen, 1993). The most widely used catalysts that give high enantioselectivity are those derived from the Schiff bases of chiral diamines such as [SiS] and [RR] 1,2-diphenylethylenediamine and [SS] and [RR] cyclohexyl-1,2-diamine. An example is the synthesis of cromakalim. 

Two examples of hetero-Michael reactions have been reported using these kinds of bis-cinchona alkaloid-based chiral Bronsted bases as catalysts. One of them refers to a sulfa-Michael reaction and the other is a case of an aza-Michael reaction. 

Different from the hydroxyalkylation reactions using carbonyl compounds as substrates, Nicolaou s and Macmillan s groups developed independently the intramolecular asymmetric Friedel-Crafts-type a-arylation of aldehydes with electron-enriched arenes based on the SOMO activation strategy. Using chiral imidazolidione as catalyst, a series of cyclic aldehydes were obtained in good yields and enantioselectivities with cerium ammonium nitrate (CAN) as single electron transfer oxidant [46]. 

Besides the use of chiral bases or catalysts in solution, a rather interesting and unique approach that belongs to the present category involves the utilization of inclusion complexes of the stabilized ylides [104]. In the solid state, an achiral stabilized ylide such as 190 is reacted with a symmetrically substituted prochiral cyclohexanone such as 189 in the presence of a chiral host molecule. The best result was obtained using the chiral host molecule 191, which gave the dissymmetric alkene 192 with up to 57% ee. 

R] For Chiral Lewis Bases as Catalysts, see Kocovsky, P. Maikov, A. I. in Enantioselective Catalysis - Reactions and Experimental Procedures, Dalko, P. I. Ed., Wiley, 2007. 

Chiral Brpnsted Bases as Catalysts in Asymmetric Mannich Reactions... 

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