Asymmetric using chiral catalysts

In summary, asymmetric cycloadditions are powerful methods for the synthesis of complex chiral molecules because multiple asymmetric centers can be constructed in one-step transformations. Among them, reactions using chiral catalysts are the most effective and promising, and fruitful results have been reported in asymmetric Diels-Alder reactions. 

Using chiral catalysts, not only various enantioselective Mukaiyama and vinylogous Mukaiyama aldol reactions have been developed but also asymmetric reactions of a,a-difluoro silyl enol ethers (1) with carbonyl compounds have been reported ... 

As an alternative to the stoichiometric enantioselective hydroboration, catalytic hydroboration using chiral catalysts has been also developed for enantioselective hydroboration The catalytic hydroboration-amination methodology has been successfully applied as a one-pot reaction for the asymmetric synthesis of primary... 

In order to place later chapters in proper context, the first chapter offers a comprehensive overview of industrially important catalysts for oxidation and reduction reactions. Chapters 2 and 3 describe the preparation of chiral materials by way of the asymmetric reduction of alkenes and ketones respectively. These two areas have enjoyed a significant amount of attention in recent years. Optically active amines can be prepared by imine reduction using chiral catalysts, as featured in Chapter 4, which also discloses a novel reductive amination protocol. 

Makosza and co-workers have reported the preparation of epoxides from a-halo carbanions and ketones, according to the Darzens reaction, under PT conditions, using TEBA72,73 or dibenzo-18-crown-6.74 The ratio of isomers depends on the reaction conditions.75,76 Asymmetric induction has been reported in the Darzens reaction using chiral catalysts.77,78 The use of several chloro carbanions as well as K2C03 and Na2C03 in the solid state has also been studied. 

There are several possibilities for asymmetric synthesis in catalysed cyclopropanation and very substantial progress has already been made especially with catalyst development. The option of covalently attaching chiral auxiliaries to diazo compounds or to substrates, e.g. alkenes for cyclopropanation, has been discussed above in the subsection on diastere-oselectivity. The fact that many of the processes require metal catalysis makes the alternative option of using chiral catalysts particularly attractive and potentially more rewarding for commercial exploitation. The double option of combining the use of a chiral catalyst with a diazo compound carrying a chiral auxiliary is also available. For convenience, the double option is also included in this subsection. 

Mikami reported a highly enantioselective carbonyl-ene reaction where a chiral titanium complex 11 prepared from enantiomerically pure binaphthol (BINOL) and Ti(0-i-Pr)2Br2 catalyzed a glyoxylate-ene reaction with a-methylstyrene to give chiral homoallyl alcohol 12 with 94.6% ee [22]. In this reaction, a remarkable asymmetric amplification was observed and almost the same enantioselectivity (94.4% ee) was achieved by using chiral catalyst prepared... 

There is an interesting theoretical report concluding that the polymerization giving an atactic polymer can be asymmetric synthesis polymerization without using chiral catalysts [95]. According to the report, when DP of an atactic polymer exceeds 70, the polymer sample cannot be a racemic mixture because the number of possible diastereomers is far larger than that of polymer chains and only one antipode of enantiomer can exist for some of the diastereomeric chains. However, the polymer sample does not show optical activity due to compensation of optical rotations contributed from different diastereomers (cryptochirality). 

Enantioselective conjugate addition of dialkylzincs to enones using chiral catalysts asymmetric synthesis of -substituted ketones... 

The most successful asymmetric variants of the Abramov reaction employ chiral substrates, either chiral carbonyl compounds or aldimines, or chiral phosphorus(III) reagents.5,51,86,88 However, the Pudovik reaction using chiral catalysts is a superior route for the asymmetric synthesis of a-hydroxy- and a-aminophosphonates (Section 6). 

HOMOGENEOUS ASYMMETRIC HYDROGENATION OF C=C BONDS USING CHIRAL CATALYSTS... 

Table 19 Asymmetric Diels-Alder Reactions using Chiral Catalysts Comparison of Eu(hfc)j with Menthol...

This chapter begins with a detailed examination of the evolution of the theory of nucleophilic attack on a chiral aldehyde or ketone, from Cram s original rule of steric control of asymmetric induction to the Felkin-Anh-Heathcock formulation. Then follows a discussion of Cram s simpler rigid model (chelate rule), then carbonyl additions using chiral catalysts and chiral (nonenolate) nucleophiles. The chapter concludes with asymmetric 1,4-additions to conjugated carbonyls and azomethines. 

In this section, the asymmetric synthesis of the vicinal thio- and selenoalcohols 42 — 45 is described based on the highly enantio- and diastereoselective addition of diethylzinc reagent to racemic a-thio- and selenoaldehydes 41, catalyzed by 20o (( —)-DFPE) and S,R)-2Qo ((+)-DFPE) (Scheme 3-20). Although the enantio-selective addition of dialkylzinc reagents to achiral aldehydes using chiral catalysts has been well investigated [10], there are no known catalytic enantio- and di-asteroselective dialkylzinc additions to aldehydes with chiral centers, except for the alkylation of a-methyl- [58, 59], a-chloro- [59], and j5-alkoxyaldehydes [60]. The reaction of diethylzinc with racemic a-thio- and selenoaldehydes 41 was carried out in the presence of 20o or (S,il)-20o (5 — 50 mol%) in hexane at room temperature for 12 —16h. The results are summarized in Table 3-11. 

The treatment of the dienediol bisnonaflate 309 containing an ( >— 1)-alkenyl substituent with the typical Heck precatalyst cocktail in the presence of an external alkene, such as an acrylate, gives rise to the formation of the bicyclic tetraene 310 by an intramolecular Heck coupling followed by an intermolecular Heck coupHng (Scheme 8.66) [239]. This reaction can be performed using chiral catalysts to achieve asymmetric induction with up to 30% ee (cf. Scheme 8.77). 

They should therefore not be used under such conditions. Nonetheless, many ionic liquids are good solvents for a wide range of organometallic compounds, thus enabling them to be used in homogeneous catalysis. Asymmetric syntheses may be carried out using chiral catalysts in achiral ionic liquids. EnantiomericaUy pure ionic liquids containing chiral cations such as 9.26 (mp 327 K) and 9.27 (mp <255 K) are also available. 

The aldol reaction is one of the most useful carbon-carbon bond forming reactions in which one or two stereogenic centers are constructed simultaneously. Diastereo-and enantioselective aldol reactions have been performed with excellent chemical yield and stereoselectivity using chiral catalysts [142]. Most cases, however, required the preconversion of donor substrates into more reactive species, such as enol silyl ethers or ketene silyl acetals (Scheme 13.45, Mukaiyama-type aldol addition reaction), using no less than stoichiometric amounts of silicon atoms and bases (Scheme 13.45a). From an atom-economic point of view [143], such stoichiometric amounts of reagents, which afford wastes such as salts, should be excluded from the process. Thus, direct catalytic asymmetric aldol reaction is desirable, which utilizes unmodified ketone or ester as a nucleophile (Scheme 13.45b). Many researchers have directed considerable attention to this field, which is reflected in the increasing... 

Examples of this kind of enantiomorphic or chiral selectivity are now being found in organic synthesis. Asymmetric synthesis, for example, has been demonstrated with stereo-controlled Michael addition in the synthesis of beta-lactams using chiral catalysts, where an acyl ligand such as acetyl is bound to cyclo-pentadiene carbonyl triphenylphosphine. Essentially complete enantiomorphic selectivity has been achieved in this Michael addition synthesis. Another case is enantio-morhic ketone reduction in ethylbenzene reduction in the ethylation of benzaldehyde. Using chiral catalysts, 97% selectivity has been achieved. Closely related research involves the making of catalytic antibodies and hybrid enzymes. ... 

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