Asymmetric synthesis, definition

Wolfsberg-Helmholtz, 43 zero-overlap, 38, 40 Aromaticity, 150 Aromatic compounds, 150-160 Arsenium ions, 119 Asymmetric synthesis definition, 9 Avoided crossing, 206... 

An interesting aspect of the benzofuran cationic polymerization was uncovered by Natta, Farina, Peraldo and Bressan who reported in 196160,61 that an asymmetric synthesis of an optically active poly(benzofuran) could be achieved by using AlCl2Et coupled with (-)j3-phenylalanine, (+)camphorsulphonic acid or with (-)brucine. The optical activity was definitely due to the asymmetric carbon atoms in the polymer chain, indicating that at least some of the polymer s macromolecules possessed a di-isotactic structure, v/ z.62 ... 

To date, direct asymmetric synthesis of optically active chiral-at-metal complexes, which by definition leads to a mixture of enantiomers in unequal amounts thanks to an external chiral auxiUary, has never been achieved. The most studied strategy is currently indirect asymmetric synthesis, which involves (i) the stereoselective formation of the chiral-at-metal complex thanks to a chiral inductor located either on the ligand or on the counterion and then (ii) removal of this internal chiral auxiliary (Fig. 4). Indeed, when the isomerization of the stereogenic metal center is possible in solution, in-... 

SOME COMMON DEFINITIONS IN ASYMMETRIC SYNTHESIS AND STEREOCHEMISTRY... 

The general subject of asymmetric synthesis has been reviewed extensively (1-5). The term asymmetric synthesis has been defined in more than one way (1,4) however, a useful definition is the one given by Morrison and Mosher (1) a process which converts a prochiral unit [refs. 6 and 7] into a chiral unit so that unequal amounts of stereoisomeric products result. The stereoisomeric products may be enantiomeric or they may be diastereomeric. The substrate molecule must contain either enantiotopic or diastereotopic groups or faces (8,9), since the attack of a reagent at equivalent groups or faces cannot lead to isomeric products. 

This definition refers to an enantiomeric mixture produced in an asymmetric synthesis. In some cases where a diastereomeric mixture is produced, the definition has to be altered accordingly. Percent optical purity is an operational term that depends on optical rotation measurements. It is not necessarily equal to the percent enantiomeric purity (13), which is a more meaningful term and is the extent to which one enantiomer is formed in excess over the other ... 

Asymmetric diarylmethanes, hydrogenolytic behaviors, 29 229-270, 247-252 catalytic hydrogenolysis, 29 243-258 kinetics and scheme, 29 252-258 M0O3-AI2O3 catalyst, 29 259-269 relative reactivity, 29 255-257 schematic model, 29 254 Asymmetric hydrogenations, 42 490-491 Asymmetric synthesis, 25 82, 83 examples of, 25 82 Asymmetry factor, 42 123-124 Atom-by-species matrix, 32 302-303, 318-319 Atomic absorption, 27 317 Atomic catalytic activities of sites, 34 183 Atomic displacements, induced by adsorption, 21 212, 213 Atomic rate or reaction definition, 36 72-73 structure sensitivity and, 36 86-87 Atomic species, see also specific elements adsorbed... 

Basie definitions of terms relating to polymerization reactions [1,2] and stereochemical definitions and notations relating to polymers [3] have been published, but no reference was made explieitly to reaetions involving the asymmetric synthesis of polymers. It is the aim of the present doeument to recommend classification and definitions relating to asymmetrie polymerizations that may produce optically active polymers. 

The third approach is the main topic of this volume. According to the definition given above it involves enantiomerically pure starting materials which at some point must be provided by resolution or ex-chiral-pool synthesis. It is more or less equivalent to the term asymmetric synthesis defined by Marckwald in 19047 as follows Asymmetric syntheses are those reactions which produce optically active substances from symmetrically constituted compounds with the intermediate use of optically active materials but with the exclusion of all analytical processes . In today s language, this would mean that asymmetric syntheses are those reactions, or sequences of reactions, which produce chiral nonracemic substances from achiral compounds with the intermediate use of chiral nonracemic materials, but excluding a separation operation. 

In retrospect, it seems unfortunate that in 1971 Morrison and Mosher8 generalized the definition, while keeping the term, an asymmetric synthesis is a reaction in which an achiral unit in an ensemble of substrate molecules is converted by a reactant into a chiral unit in such a manner that the stereoisomeric products arc produced in unequal amounts ( Footnote The substrate molecule must have either enantiotopic or diastereotopic groups or faces) . Obviously the phrase "an achiral unit in an ensemble of substrate molecules is too inexact and requires a great deal of additional explanation, which was partially given by the footnote (note that molecule, i.e., singular, was used ). Currently, the Morrison-Mosher term appears to be equivalent to stereoselective reaction. Unfortunately, this term was only defined in the modem sense by Izumi in 1971, i.e., in the same year the Morrison-Mosher definition was published. 

One can define diastereoselectivity as the formation of diastereoisomers in a non-statistical ratio in any chemical transformation (formation of transition states included). Such a definition concerns equilibrium as well as nonreversible reactions. An asymmetric synthesis in a restricted sense can be considered as a reaction leading to a product containing at least one new stable dissymmetric center with a definite chirality. Such a reaction may take place in the coordination sphere of a metal ion. First of all the following question has to be answered which are the structural properties in the architecture of the coordination sphere that lead to the following phenomenona ... 

Our objective in this paper is to present precise descriptions for these concepts and thereby attain an objective general definition of asymmetric synthesis . We illustrate use of this definition in a broad variety of stereoselective reactions those reactions generally counted to be asymmetric do in fact turn out to be asymmetric by our criterion, and some of those whose asymmetry is controversial do not constitute asymmetric syntheses by our definition. 

Time reversal, mentioned above in connection with PT-enantiomers, is also at the heart of a distinction between time-dependent and time-independent enantiomorphism. In a series of publications,33-36 Laurence Barron has provided the basis for his argument that The only compelling reason for generalizing Kelvin s definition is to encompass absolute asymmetric synthesis and the concept of chirality in elementary particle physics by including motion-dependent chirality. 37 According to Barron33 ... 

For the purposes of this treatise, the definition of asymmetric synthesis is a modification of that proposed by Morrison and Mosher [1] and as such will be applied to stereospecific reactions in which a prochiral unit in either an achiral or a chiral molecule is converted, by utility of other reagents and/or a catalytic antibody, into a chiral unit in such a manner that the stereoisomeric products are produced in an unequal manner. As such, the considerable body of work devoted to antibody-catalysis of stereoselective reactions including chiral resolutions, isomerizations and rearrangements are considered to be beyond the scope of this discussion. For information regarding these specific topics and more general information regarding the catalytic antibody field the following papers... 

The most quoted definition of an asymmetric synthesis is that of Marckwald [29] ... 

In modem terminology, the core of Marckwald s definition is the conversion of an achiral substance into a chiral, nonracemic one by the action of a chiral reagent. By this criterion, the chiron approach falls outside the realm of asymmetric synthesis. Marckwald s point of reference of course, was biochemical processes, so it follows that modern enzymatic processes [30-32] are included by this definition. Marckwald also asserted that the nature of the reaction was irrelevant, so a self-immolative reaction or sequence such as an intermolecular chirality transfer in a Meerwein-Pondorf-Verley reaction would also be included ... 

Interestingly, the Marckwald definition is taken from a paper that was rebutting a criticism [33] of Marckwald s claim to have achieved an asymmetric synthesis by a group-selective decarboxylation of the bmcine salt of 2-ethyl-2-methylmalonic acid [34,35] ... 

Thus from the very beginning, the definition of what an asymmetric synthesis might encompass, or even if one was possible, has been a matter of debate. On the latter point, the idea that a chemist could synthesize something in optically active form from an achiral precursor was doubted in some circles, even in Marckwald s... 

Asymmetric synthesis, the selective generation of new chirality elements (as one definition goes), has developed from a specialty pursued by outsiders to an art cultured by some learned ones, and now may be considered a standard laboratory methodology for everybody s use. This development has taken place exponentially (explosively ) in the last two decades, triggered by a number of circumstances. Also the practitioners of pharmaceutical, vitamin, and agro synthesis need to produce enantiopure, rather than racemic active compounds (for registration ). 

The asymmetric synthesis of Gliflumide is still underway. We are near the conq)le-tion of the synthesis, and thus far we have definitively shown that the hydroboration protocol can be used with more conqilicated aryl systems than simple monosubsti-tuted styrenes. 

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