Asymmetric reactions basic principles

During the development of MRNi, in 1977 (61a, 61b) we proposed an hypothesis about the mechanism of hydrogenation on the surface of metal catalysts (61a, 61b). In 1971-1974 we proposed the name stereo-differentiation, which is the basic principle for the so-called asymmetric reactions (24, 32, 34, 38, 62, 63). These have been the working hypotheses for the development of MRNi. 

This book deals with the basic principles of asymmetric catalysis and places particular emphasis on its synthetic significance. The mechanisms of most of the chemical reactions that I will discuss are obscure and are therefore treated only briefly. My talks at Cornell relied heavily on chemistry developed in our laboratories at Nagoya University, and the materials in Chapters 2, 3, 5, and 6 are highly subjective. Because asymmetric synthesis with molecular catalysts is a very attractive and rich subject, many academic and industrial laboratories all over the world have contributed to its development. In an attempt to balance my coverage of the entire field, I have tried to include most of the major achievements recorded by the fall of 1992 within Chapter 4. 

Asymmetric catalytic addition of dialkylphosphites to a C=0 double bond is a powerful method, and probably the most general and widely applied, for formation of optically active a-hydroxy phosphonates [258], The basic principle of this reaction is shown in Scheme 6.108. Several types of catalyst have been found to be useful. The transition-metal-catalyzed asymmetric hydrophosphonylation using chiral titanium or lanthanoid complexes was developed by several groups [259, 260], The most efficient type of chiral catalyst so far is a heterobimetallic complex consisting... 

The basic principles of asymmetric synthesis have been discussed in a number of recent reviews (2,3). The heart of an asymmetric synthesis is a reaction in which an achiral unit in an ensemble of substrate molecules is converted into a chiral unit in such a manner that the stereoisomeric products are obtained in unequal amounts. For almost all cases this is equivalent to the statement that in an asymmetric reaction a prochiral unit is converted into a chiral unit. 

A recent discovery that has significantly extended the scope of asymmetric catalytic reactions for practical applications is the metal-complex-catalyzed hydrolysis of a racemic mixture of epoxides. The basic principle behind this is kinetic resolution. In practice this means that under a given set of conditions the two enantiomers of the racemic mixture undergo hydrolysis at different rates. The different rates of reactions are presumably caused by the diastereo-meric interaction between the chiral metal catalyst and the two enantiomers of the epoxide. Diastereomeric intermediates and/or transition states that differ in the energies of activation are presumably generated. The result is the formation of the product, a diol, with high enantioselectivity. One of the enantiomers of... 

Not surprisingly, fhe classical Os-catalyzed asymmetric dihydroxylation of olefins (cf. Section 2.2) continues to be of interest. The basic principles, such as type of catalyst, stay relatively fhe same and instead efforts are concentrated on making the reaction more suitable for operation under process-like conditions. A modification fhat could improve fhe operabihty is to replace the conventional t-BuOH/ H2O solvent mixture by ionic liquid containing mixtures, either as a monophasic... 

Sharpless asymmetric epoxidation is the first example of a reaction where an achiral precursor is converted to a chiral substrate with high enantioselectivity. This discovery triggered a flurry of activity, applying the basic principles of asymmetric epoxidation to a variety of other reactions. Sharpless asymmetric epoxidation is very important in the synthesis of natural products since this reaction offers an asymmetric route to many important synthons. One example is the conversion of 224 to 225, in 95% yield (> 15 1 de), in Meyer s synthesis of disorazole Ci, where MS indicates the use of molecular sieves.321 In a second example, taken... 

Non-asymmetrical syntheses result in optically inactive racemic mixtures of the enantiomers. They can be separated by one of the three basic Pasteur methods (or their more recent variants) where, using asymmetrical chemical or biochemical agents, one of the optical isomers is stereoelectively extracted or transformed. The much greater difference between the diastereoisomers obtained containing non-inverse chiral centers (as between the two enantiomers) seems absolutely fundamental in all these methods and techniques based on specific interactions and reactions. The principle that asymmetry is generated or selected by asymmetry has not yet been contradicted. 

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