Chiral methyl groups analysis

If a chiral group is generated in the system to be studied, then chirality analysis of that group typically entails the removal of that moiety in a defined set of reactions such that the stereochemistry is not altered or the reactions have a known stereochemical course. For example, chirality analysis of chiral methyl groups typically involves conversion of the methyl groups into acetic acid. 

A method for the determination of carbon-linked methyl groups (and, by extension, used in the analysis of chiral methyl groups in stereochemical studies of enzyme-catalyzed reactions acting on methyl groups). In this procedure, the methyl groups are converted to acetic acid by oxidation of the metabolite with chromic and sulfuric acids. Milder versions are also available. 

While the configurational analysis of chiral methyl groups is based on the radioactivity of 3H and the kinetic isotope effect kHlk0, neither factor is applicable to a chiral phosphoryl group. Both 170 and l80 are stable isotopes, and... 

Degradation of the product to carve out the chiral methyl group and convert it into a compound suitable for configurational analysis, using only stereospecific reactions of known steric course. 

Since these early studies, numerous additional procedures have been developed for the synthesis of chiral labeled acetic acid and other chiral labeled molecules by chemical (I41-15I) and enzymic methods 152-155). The malate synthase/fumarase system described above continues to be the most widely used method for the stereochemical analysis of chiral labeled acetic acid resulting from the degradation of product molecules containing chiral methyl groups. 

On the basis of this analysis, it may be anticipated that the extent of aldehyde diastereofa-cial selectivity will depend on the difference in size of the R3 aldehyde substituent relative to that of the methyl group. The examples summarized in Table 2 are generally supportive of this thesis, particularly the reactions of (F)-2-butenylboronntc. The data cited for reactions of 3-methoxymethoxy-2-methylbutanal with (Z)-2-butenylboronate and 2-propenylboronate, however, also show that diastereoselectivity depends on the stereochemistry at C-3 of the chiral aldehydes. These data imply that simple diastereoselectivity depends not simply on reduced mass considerations, but rather on the stereochemistry and conformation of the R3 substituent in the family of potentially competing transition states21,60. The dependence of aldehyde diastcrcofacial selectivity on the stereochemistry of remote positions of chiral aldehydes has also been documented for reactions involving the ( )-2-butenylchromium reagent62. 

Very recently (51), nonequivalence has been found in a variety of additional monobasic solutes whose configurational analysis was thought earlier to lie outside the scope of the CSA technique. 2-Butanol, for example, when dissolved in benzene saturated with TFAE, shows nonequivalence in both methyl resonances. A variety of other chiral and prochiral compounds such as 2-propanol, methyl 2-propyl sulfide, 2-aminobutane, and 2-methyl-1-butanol show nonequivalence for their enantiotopic methyl groups under these conditions. The magnitudes of nonequivalence in these instances are small (0.02-0.03 ppm) but, as illustrated in Figure 4 for enriched 2-butanol,... 

Compound 16 is a chiral molecule, as is evident from the diastereotopicity of the geminal Si-methyl groups and the methylene protons. Chirality results from the non-planar ground state about the hydrazine functionality (C2 symmetry) and the substantially high barrier for rotation about this bond (AG > 24 kcal mol 1). A single crystal X-ray analysis for 16 confirmed the nearly 90° dihedral angle about the central N N bond [C(0)NNC(0)] = 83.10°.15>40a... 

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