Asymmetric catalyst directed

Table 5. Direct catalytic asymmetric aldol reactions promoted by heteropolyme-tallic asymmetric catalyst and following Baeyer-Villiger oxidations.

The asymmetric synthesis of allenes by stereoselective manipulations of enantio-merically pure or enriched substrates relies on the availability of such optically active substrates. In contrast, a direct synthesis of allenes by the reaction of prochiral substrates in the presence of an external asymmetric catalyst is an almost ideal process [102]. Most of the catalytic asymmetric syntheses in organic chemistry involve the creation of chiral tetrahedral carbon centers [103], whereas the asymmetric synthesis of allenes requires the construction of an axis of chirality. 

The chapter by Reetz includes many examples and explanations of methods illustrating how directed evolution has been applied to prepare new enzyme catalysts. Directed evolution of enantioselective enzymes has emerged as a fundamentally new approach to asymmetric catalysis. It involves the combination... 

Bidentate ferrocene ligands containing a chiral oxazoline substituent possess both planar chiral and center chiral elements and have attracted much interest as asymmetric catalysts.However, until recently, preparation of such compounds had been limited to resolution. In 1995, four groups simultaneously communicated their results on the asymmetric synthesis of these structures using an oxazoline-directed diastereoselective lithiation (Scheme 8.141). " When a chiral oxazolinylferrocene 439 was metalated with butyllithium and the resulting aryllithium species trapped with an electrophile, diastereomer 442 was favored over 443. The structure of the major diastereomer 442 was confirmed, either by conversion to a compound of known stereochemistry or by X-ray crystallography of the product itself or of the corresponding palladium complex. ... 

In the special case in which the substrate is already enantiomerically pure (as in entry 5), it should be clear from Figure 6A.2 that asymmetric epoxidation will be successful (with regard to diastereomeric purity) only when the choice of catalyst directs delivery of oxygen to the face of the olefin opposite that of the C-1 substituent. Such choice of catalyst is further illustrated in Scheme 6A.2, wherein the two sequential epoxidations each proceed with better than 97% diastereoselectivity. The bisepoxide is obtained in an overall yield of 80% [130c],... 

Since asymmetric induction decreases rapidly when the distance between the inducing asymmetric center and the new asymmetric center to be formed in the product increases (25), we assumed that the metal atom approached by the substrate (that is the atom of the catalyst directly interacting with the unsaturated atom of the substrate that becomes chiral during the reaction) is chiral (5). Complexes containing chiral metal atoms are known in the literature (31) furthermore, the... 

A new catalyst salt (20) that consists of an achiral ammonium ion and a chiral phosphate anion and which catalyses highly enantioselective transfer hydrogenations of ,/J-unsaturated aldehydes to the corresponding saturated derivatives has been developed. The underlying principle, namely asymmetric counteranion-directed catalysis, is claimed to be a new strategy for highly enantioselective synthesis.357... 

Interestingly, the same concept involving a catalyst-directing group allowed also to make efficient use of 1,3 asymmetric induction. This, of course, is a much more difficult situation, since additional degrees of freedom have to be controlled in the course of the stereo-... 

The design for a direct catalytic asymmetric aldol reaction of aldehydes and unmodified ketones with bifunctional catalysts is shown in Figure 36. A Brpnsted basic functionality (OM) in the heterobimetallic asymmetric catalyst (I) could deprotonate the a-proton of a ketone to generate the metal enolate (II), while at the same time a Lewis acidic functionality (LA) could activate an aldehyde to give (III), which would then react with the metal enolate (in a chelation-controlled fashion) in an asymmetric environment to afford a P-keto metal alkoxide (IV). 

Scheme 24. Asymmetric counteranion-directed catalysis catalyst synthesis and screening...

Scheme 28. Asymmetric counteranion-directed catalysis transfer hydrogenation of different enones with catalyst 35...

S.C. PanandB. List s paper spans the whole field of current organocat-alysts discussing Lewis and Brpnsted basic and acidic catalysts. Starting from the development of proline-mediated enamine catalysis— the Hajos-Parrish-Eder-Sauer-Wiechert reaction is an intramolecular transformation involving enamine catalysis—into an intermolecular process with various electrophilic reaction partners as a means to access cY-functionalized aldehydes, they discuss a straightforward classification of organocatalysts and expands on Brpnsted acid-mediated transformations, and describe the development of asymmetric counteranion-directed catalysis (ACDC). 

An intramolecular diastereoselective Refor-matsky-type aldol approach was demonstrated by Taylor et al. [47] with an Sm(II)-mediated cy-clization of the chiral bromoacetate 60, resulting in lactone 61, also an intermediate in the synthesis of Schinzer s building block 7. The alcohol oxidation state at C5 in 61 avoided retro-reaction and at the same time was used for induction, with the absolute stereochemistry originating from enzymatic resolution (Scheme II). Direct re.solution of racemic C3 alcohol was also tried with an esterase adapted by directed evolution [48]. In other, somewhat more lengthy routes to CI-C6 building blocks, Shibasaki et al. used a catalytic asymmetric aldol reaction with heterobimetallic asymmetric catalysts [49], and Kalesse et al. used a Sharpless asymmetric epoxidation [50]. 

We speculated that it might be possible to develop a direct catalytic asymmetric aldol reaction of aldehydes and unmodified ketones by employing heterobimetallic catalysts. Our initial concerns were dominated by the possibility that our heterobimetallic asymmetric catalysts would be ineffective at promoting aldol reactions because... 

In this contribution we first give a short description of the historical development of enantioselective C=N hydrogenations. Then, an overview on effective enantioselective catalysts for different types of C=N groups is presented, that is directed to the synthetic chemist involved in synthesis planning. The detailed discussion of the chemistry of selected asymmetric catalysts is meant for the catalyst specialist. Finally, the most useful methods are briefly assessed from a preparative as well as a technical point of view. 

Alternatively, the epoxidation of enones has also been covered using primary amine catalyst 28c or by applying the asymmetric counterion-directed... 

Barbas and researchers identified that the diamine la TFA salt can catalyse the asymmetric intermolecular direct aldol reactions of a,a-dialkylaldehydes with aromatic aldehydes (Scheme 9.2). The bifunctional catalytic system exhibited excellent reactivity to give products with moderate diastereo- and enantioselectivities. Notably, L-proline is an ineffective catalyst for this class of aldol reactions. The re-face attack of an enamine intermediate on an aryl aldehyde was proposed, causing the observed stereochemistry. 

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