Absolute configuration relative assignment

The aldol reaction of 3-pentanone with acetaldehyde provides an example52 of control by an external chiral ligand 9. The relative configuration at the newly created stereogenic centers (syn vs. anti) of the adduct 10 was determined by NMR, while the absolute configuration was assigned by a chemical correlation (see p 452)101 -I02. 

The first diastereoselective and enantioselective allylic alkylation of cyclohexanone (through the magnesium enolate 18a) with diphenylallyl acetate 19a was reported in 2000 by Braun and coworkers [16a]. (7J)-BINAP (23) served as the optimum chiral ligand, and the alkene 20 was obtained as an almost pure diastereomer with an enantiomeric excess of 99% ee. The relative configuration was proven by the crystal structure analysis the absolute configuration was assigned unambiguously by chemical correlation. A first diastereoselective and enantioselective Tsuji-Trost reaction of a lithium enolate derived from... 

The relative configuration of the natural product was confirmed by x-ray diffraction analysis (Figure 14.20) and the absolute configuration was assigned from the starting material (D-glucal). 

One further point needs to be mentioned—the matter of absolute configuration. How do we know that our assignments of R,S configuration are correct in an absolute, rather than a relative, sense Since we can t see the molecules themselves, how do we know that the R configuration belongs to the dextrorotatory enantiomer of lactic acid This difficult question was finally solved in 1951, when J. M. Bijvoet of the University of Utrecht reported an X-ray spectroscopic method for determining the absolute spatial arrangement of atoms in a molecule. Based on his results, we can say with certainty that the R,S conventions are correct. 

Imines 123, generated from a-arylethylamines 122 (Ar = Ph, 4-B1C6H4 or 4-O2NC6H4) and aqueous formaldehyde, react with cyclopentadiene in situ at room temperature to afford mixtures of the bridged dihydropyridines 124 and 125 (equation 67), whose relative configurations were deduced by XH NMR experiments and their absolute configurations assigned by reference to the X-ray structure of the aziridinium derivative 126 (equation 68)60. 

Configurational comparison may also be made by the NMR-CSA method. The relative configurations of two samples of a chiral substance may be determined through observed senses of nonequivalence in the presence of a given CSA. If the nonequivalence behavior of any resonance of a configurationally known compound has been reported, one need determine only the sense of nonequivalence for this resonance (with the same CSA type) to assign the absolute configuration to a sample of the same substance. 

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