Absolute configuration reagents

In the following sections, the plant species that are sources of monoterpenes are not recorded unless of some special significance, and similarly for points of stereochemistry, absolute configuration, reagents, and reaction conditions. 

If the amount of the sample is sufficient, then the carbon skeleton is best traced out from the two-dimensional INADEQUATE experiment. If the absolute configuration of particular C atoms is needed, the empirical applications of diastereotopism and chiral shift reagents are useful (Section 2.4). Anisotropic and ring current effects supply information about conformation and aromaticity (Section 2.5), and pH effects can indicate the site of protonation (problem 24). Temperature-dependent NMR spectra and C spin-lattice relaxation times (Section 2.6) provide insight into molecular dynamics (problems 13 and 14). 

In order to prove the utility of this method and to ascertain the absolute configuration of the products, (S)-alanine has been enantioselectively prepared. The key step is the addition of methyllithium to the AjA -dimethyl hydrazone acetal 4c, derived from diol 3c. In accordance with 13C-NMR investigations it can therefore be assumed that all major diastereomers resulting from the addition of organolithium reagents to hydrazone acetals 4a-c derived from diols 3a, 3b or 3c (Table 3, entries 1 -6) have an S configuration at the newly formed stereogenic center. 

The enantiomeric excess was determined by HNMR with ( + )-(/ )-binaphthol as a chiral shift reagent. The absolute configuration of the adducts was not determined. 

NMR can be a powerful tool for determination of enantiomeric excess or absolute configuration of the optically active compounds, however, these processes require the use of some auxiliaries, for example, chiral lanthanide shift reagents or chiral derivatising agent. In many cases, the starting point for determination of enantiopurity of amines, amino acids or diols is the formation of chiral imines. 

Oxazolidinones have also been used as intermediates in simple transformations utilising their peculiar reactivity. The absolute configuration of WBoc-P-aminoalcohol 213 can be easily inverted via Sn2 cyclisation to oxazolidinone 214 <00TL10071>. Treatment with Olah s reagent (HF-Pyridine) of 4-alkyl-5,5-diphenyl-oxazolidinones 216 afforded the corresponding a-(fluorodiphenylmethyl)alkylamines 217 <00TA2033>. 

Similarly, 2-anthrylmethoxyacetic acid (2ATMA 64) can also be used as a chiral anisotropic reagent (Fig. 1 23).80 The advantage of using this compound is that the absolute configuration assignment can be accomplished from only one isomer of the ester without calculating the AS value (Ss — SR) ... 

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 36d-LAH complex was applied to the reduction of ketone oximes and their O-tetrahydropyranyl and O-methyl derivatives to optically active amines (69). Results for a variety of phenyl alkyl and dialkyl ketones are shown in Table 4. The predominant amines formed all were of the S absolute configuration with optical purities up to 56%. The oxime hydroxy group presumably reacts with the less hindered H2 in the 36d-LAH complex (cf. Scheme 6) to form an oxime complex (45), which probably undergoes infermolecular hydride transfert of H2 from a second molecule of the 36d-LAH complex (Scheme 8). Asymmetric reduction with the ethanol-modified 36d-LAH reagent gave amines of R con-... 

The reduction of phenyl mesityl ketone was studied with LAH modified with amino alcohols 65 to 72 in ether (the ratio LAH alcohol ketone = 1.1 1.1 1) (83). Optical yields were modest, with the highest 39%, obtained with 65 as the chiral auxiliary reagent. It was observed that there is a relationship between the preferred enantiomeric product and the structure and absolute configuration of the carbons carrying the hydroxy and amino groups. Thus the threo... 

Relationship between Amino Alcohol Auxiliary Reagent and Absolute Configuration of... 

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"). 

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