Stereochemical problems, application

Williams, D.H. Budzikiewicz, H. Pelah, Z. Djerassi, C. Mass Spectroscopy and Its Application to Structural and Stereochemical Problems. XLIV. Fragmentation Behavior of Monocychc Ketones. Monatsh. Chem. 1964,95,166-177. 

Due to the difficulties in interpretation and the sensitivity of vibrations in the fingerprint and skeletal regions to structural alterations, the application of ROA to stereochemical problems remains limited. However, the recent advances in experimental techniques and theoretical descriptions are promoting increased research activity in ROA. Especially in aqueous solution, where VCD signals are obscured by the solvent and in low frequency regions, in which VCD spectra are not yet available, Raman optical activity remains a promising tool for stereochemical investigations. 

As noted eailier, the dynamic sensitivity of VCD carries it beyond the Bom-Oppenheimer approximation (17, 18). Even though non-Bom-Oppenheimer calculations have recently been initiated (116-119), the use of molecular orbital methods to describe these vibrationally induced currents is lagging behind the measurement and interpretation of VCD based on such currents. Nevertheless, the empirical basis that is now emerging for understanding VCD intensities based on chirally oriented oscillators and induced currents makes possible the immediate application of this methodology to stereochemical problems of widespread interest. 

The large number and variety of applications of the chiral derivatization approach attest to the success, viability, and importance of the technique. It is expected that despite the predictable advances to be realized in the near future in the development of direct chromatographic— mainly chiral-stationary-phase-based—separations of enantiomers, the indirect approach will continue to be widely used to solve stereochemical problems in the pharmaceutical, pharmacological, and toxicological arenas. 

The stereochemical problem was solved by application of the reductive cleavage reaction. Treatment of 0,0-dimethylliensinine (LXIV) with sodium in liquid ammonia afforded (— )-0-methylarmepavine (I) and the (— )-A,0-dimethylcoclaurine IV. Accordingly (Section I), lien-sinine was assigned the RR-configuration as shown in the formula (39). 

The excellence of n.m.r. spectroscopy for elucidating structural and stereochemical problems is unsurpassed, and is nowhere better illustrated than in the field of cyclic acetals. There are many authoritative reviews on this topic,72a72e and, in this article, the discussion will be confined to two main aspects the application of n.m.r. spectroscopy to the study of (a) diastereoisomerism, and (b) conformation. 

The subject of substituent chemical shifts is dealt with in greater detail in Section 11,1 (see p. 65), together with applications to stereochemical problems. 

Although the determination of both the configuration and the conformation of carbohydrates involves the same general considerations, the quantitative nature of the latter requires a rather more fundamental approach. Accordingly, the following discussion is divided into two main sections the first refers to the development and applications of nuclear magnetic resonance to stereochemical problems, and deals mainly with substituent resonances the second discusses in some detail the Karplus relationship and the determination of carbohydrate conformations. 

Some of the applications of proton magnetic resonance spectroscopy to stereochemical problems in carbohydrate chemistry have been described in Section V. This technique also has some value in direct structural investigations on cyclic acetals, particularly in diagnosing pyranose-furanose equilibria. The method is especially useful for those acetals which could... 

The applications of n.m.r. to stereochemical problems in phosphine oxides have included the structure of phosphetan 1-oxides, and the barriers to rotation in the oxide (7a) and the sulphide (7b). Extensive use of n.m.r. 

Summarizing this chapter, it can be stated that the linking of NMR spectrometers (from 400 to 750 MHz) to various separation techniques has been developed into rather a powerful tool. Stereochemical problems in metabolism studies can be easily solved if the concentration of the present compounds is above the detection threshold. The coupling of capillary separation techniques together with NMR detection will stimulate high-throughput screening applications in modem dmg development. 

Coulomb polarization is the underlying cause of many interesting stereochemical trends and what we have already discussed is a mere isolated application of the concept. A related stereochemical problem is the question of whether a reaction complex, e.g., the four-electron-three-orbital (4/3) system XAX, is symmetrical or unsymmetrical assuming that the three centers lie on the same line. If we view the system as a composite of X2 and A and we assume zero nonbonded AO overlap, the approximate wavefunction of the symmetrical species is as shown below, with being defined as in Figure 2. 

Copper and cobalt complexes of amino acids have found applications in the solution of stereochemical problems, as mentioned in section IV.C.2. 

Budzikiewicz, H. Brauman, J.I. Djer-assi, C. Mass Spectrometry and Its Application to Stractural and Stereochemical Problems. LXVII. Retro-Diels-Alder Fragmentation of Organic Molecules Under Electron Impact. Tetrahedron 196S,21,1855-1879. 

Mandelbaum A (1977) Application of mass spectrometry to stereochemical problems. In Kagan H (ed) Stereochemistry, vol. 1, pp 137-180. Stuttgart Georg Thieme Publishing. 

Splitter J and Turecek F (1994) Application of Mass Spectrometry to Stereochemical Problems. New York VCH. 

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