Absolute configuration asymmetric reaction

Absolute configurations of the amino acids are referenced to D- and L-glyceraldehyde on the basis of chemical transformations that can convert the molecule of interest to either of these reference isomeric structures. In such reactions, the stereochemical consequences for the asymmetric centers must be understood for each reaction step. Propose a sequence of reactions that would demonstrate that l( —)-serine is stereochemically related to l( —)-glyceraldehyde. 

More recently, the Lewis acid promoted asymmetric 1,4-addition of trimethyl(2-propenyl)silane to chiral a,/ -unsaturated /V-acylamides has been published33. Lewis acid mediated reactions of trimethyl(2-propenyl)silanes with a,/I-unsatu rated AT-acyloxazolidinones or iV-enoylsultams show high chemical yield with good diastereomeric excess. The absolute configuration of the new asymmetric center is controlled by the nature of the Lewis acid used. 

The first asymmetric benzoin reactions were reported by Sheehan and Hannemann nsing chiral thiazolinm salt pre-catalyst 100 of unknown absolute configuration [40], Low yields and enantioselectivities were obtained, and although a wide range of thiazolium salt pre-catalysts have since been studied, of which 101-105 are representative, the enantioselectivities obtained for the condensation of benzaldehyde using thiazolium pre-catalysts are generally poor (Scheme 12.19) [41],... 

In 1960, Montanari and Balenovic and their coworkers described independently the first asymmetric oxidation of sulfides with optically active peracids. However, the sulphoxides were formed in this asymmetric reaction (equation 130) with low optical purities, generally not higher than 10%. The extensive studies of Montanari and his group on peracid oxidation indicated that the chirality of the predominantly formed sulphoxide enantiomer depends on the absolute configuration of the peracid used. According to Montanari the stereoselectivity of the sulphide oxidation is determined by the balance between one transition state (a) and a more hindered transition state (b) in which the groups and at sulphur face the moderately and least hindered regions of the peracid,... 

Zinc-containing compounds have also been used as catalyst. Recently, Trost et al. reported asymmetric aldol reactions of methyl ynones 331 with pyruvaldehyde ketals 330 in the presence of a dinuclear zinc catalyst 329 generated from ZnEt2 and a pentadentate 0,N,0,N,0-ligand (328, Scheme 168).428 This reaction is a unique case of enantioselective autoinduction with product incorporation into the catalyst and a reversal of the absolute configuration. 

On the other hand, optically active telluroxides have not been isolated until recently, although it has been surmised that they are key intermediates in asymmetric synthesis.3,4 In 1997, optically active telluroxides 3, stabilized by bulky substituents toward racemization, were isolated for the first time by liquid chromatography on optically active columns.13,14 The stereochemistry was determined by comparing their chiroptical properties with those of chiral selenoxides with known absolute configurations. The stability of the chiral telluroxides toward racemization was found to be lower than that of the corresponding selenoxides, and the racemization mechanism that involved formation of the achiral hydrate by reaction of water was also clarified. Telluroxides 4 and 5, which were thermodynamically stabilized by nitrogen-tellurium interactions, were also optically resolved and their absolute configurations and stability were studied (Scheme 2).12,14... 

Chapter 1 introduced the nomenclature for chiral systems, the determination of enantiomer composition, and the determination of absolute configuration. This chapter discusses different types of asymmetric reactions with a focus on asymmetric carbon-carbon bond formation. The asymmetric alkylation reaction constitutes an important method for carbon-carbon bond formation. 

In principle, an anisotropic reaction performed on a crystal of polar symmetry may fix the absolute direction of the polar axis. In the case of an asymmetric reaction carried out in a centrosymmetric (enantiopolar) crystal, one may establish the absolute configuration of the chiral product. The degree of reliability of the assignment will depend on knowledge of the various states of the reaction pathway. Here we briefly describe some heterogeneous reactions in polar and enantiopolar crystals that illustrate this approach. 

Reaction of exo-carbinol ( ) — 16 with racemic a-phenylbutyric anhydride afforded the dextrorotatory acid hence the chirality center has the absolute configuration (R). The behavior of the endo isomer 15 was also in accord with this finding the resolved levorotatory acid indicates that the asymmetric C atom has the absolute configuration (S). 

In many studies of asymmetric reductions no attempts were made to rationalize either the extent or the sense of the observed asymmetric induction, that is, the absolute configuration of the predominant enantiomer. It is believed that it is premature in certain cases to attempt to construct a model of the transition state of the key reaction step, given the present state of knowledge about the mechanism of these reduction processes. The complexity of many of the reducing systems developed is shown by the fact that the enantiomeric excess or even the sense of asymmetric induction may depend not only on the nature of the reducing agent and substrate, but also on temperature, solvent, concentration, stoichiometry of the reaction, and in some cases the age of the reagent. 

The first example of asymmetric induction in transfer of chirality from the chiral sulfur atom to the prochiral carbon atom was described by Goldberg and Sahli in 1965 (197). It concerns the pyrolysis of the optically active p-tolyl tra s-4-methylcyclohexyl sulfoxides 258. It was found that on pyrolysis at 200 to 250°C, optically active sulfoxides (R)-258 and (5)-258 yield optically active 4-methylcyclohexenes-l 259, with the absolute R and S configurations, respectively, at the newly formed chiral carbon atoms (Scheme 25). The optical purities of the 4-methylcyclohexenes-l that were formed depended largely on the temperature of pyrolysis. Thus, the values of 42 and 70% optical purity were noted for 259 at 250° and 200°C, respectively. The formation of the cycloolefins 259, whose absolute configurations are the same as those of the starting optically active sulfoxides 258, indicates that the pyrolysis reaction proceeds... 

A highly efficient asymmetric induction was also observed in the addition of the lithium salt of (+)-(5)-34 to acetone (313). The addition product 297 (optical purity ca. 80%) was then oxidized to the corresponding sulfone 298, whose absolute configuration was established as R by means of chemical correlations. The formation of sulfone 298 with the absolute configuration R at carbon proves that, unlike methylation, the addition reaction takes place with retention of configuration. It is worthy of note that the optically active... 

Organosulfur chemistry is presently a particularly dynamic subject area. The stereochemical aspects of this field are surveyed by M. Mikojajczyk and J. Drabowicz. in the fifth chapter, entitled Qural Organosulfur Compounds. The synthesis, resolution, and application of a wide range of chiral sulfur compounds are described as are the determination of absolute configuration and of enantiomeric purity of these substances. A discussion of the dynamic stereochemistry of chiral sulfur compounds including racemization processes follows. Finally, nucleophilic substitution on and reaction of such compounds with electrophiles, their use in asymmetric synthesis, and asymmetric induction in the transfer of chirality from sulfur to other centers is discussed in a chapter that should be of interest to chemists in several disciplines, in particular synthetic and natural product chemistry. 

The Diels-Alder reaction (Figure 7.1) is of great value in synthetic organic chemistry. It is a [4 -I- 2] cycloaddition in which a diene (4-tt component) reacts with a dienophile (2-tt component) to provide a six-membered ring. In the reaction six new stereocenters are formed in a single step. The reaction is stereospecific and the absolute configuration of the newly formed asymmetric centers can be controlled efficiently. 

Now, if we allow one enantiomer of the chiral aldehyde 59 to react with the two enantiomers of the chiral enolate M, in one case the two chiral reagents will both promote the same absolute configuration at the two new chiral centres (65a ). However, no such effect will be observed in the other possible combination (c/. 65) (Scheme 9.21). In the first case, the effective "Cram s rule selectivity" shown by the aldehyde will be greater than in its reactions with achiral enolates. For the selectivities chosen the "Cram anti-Cram ratio" should be in our example of the order of 100 1 (see below 9.3.4., Masamune s "double asymmetric induction"). 

The above-mentioned facts have important consequences on the stereochemical outcome of the kinetic resolution of asymmetrically substituted epoxides. In the majority of kinetic resolutions of esters (e.g. by ester hydrolysis and synthesis using lipases, esterases and proteases) the absolute configuration at the stereogenic centre(s) always remains the same throughout the reaction. In contrast, the enzymatic hydrolysis of epoxides may take place via attack on either carbon of the oxirane ring (Scheme 7) and it is the structure of the substrate and of the enzyme involved which determine the regioselec-tivity of the attack [53, 58-611. As a consequence, the absolute configuration of both the product and substrate from a kinetic resolution of a racemic... 

X-ray crystallographic analysis also revealed that the crystal of thioamide la was chiral, the space group P2i2i2i. The absolute configuration of (-)-rotatory crystals of la, where the optical rotation was assigned on the basis of CD spectra in a KBr pellet, was determined by the X-ray anomalous scattering method as (-)-(M)-la for the helicity. When (-)-rotatory crystals were irradiated at 0 °C until the reaction conversion reached 100% yield, the asymmetric induction in... 

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