Applications stereochemical studies

Application of NMR spectroscopy to heterocyclic chemistry has developed very rapidly during the past 15 years, and the technique is now used almost as routinely as H NMR spectroscopy. There are four main areas of application of interest to the heterocyclic chemist (i) elucidation of structure, where the method can be particularly valuable for complex natural products such as alkaloids and carbohydrate antibiotics (ii) stereochemical studies, especially conformational analysis of saturated heterocyclic systems (iii) the correlation of various theoretical aspects of structure and electronic distribution with chemical shifts, coupling constants and other NMR derived parameters and (iv) the unravelling of biosynthetic pathways to natural products, where, in contrast to related studies with " C-labelled precursors, stepwise degradation of the secondary metabolite is usually unnecessary. 

The ambident behaviour of sulfur in terms of its ability to stabilize adjacent negative and positive charge at carbon has made this element a focal point for new reagents and reactions (JJ. For this reason our concern has focused on the synthesis of new phosphonates containing sulfur and selenium and the exploration of their application in synthetic and stereochemical studies. 

Inasmuch as rate and stereochemical studies were available, and made a consistent picture, the issue of anti or trans mechanisms, e.g. equation (3), seemed settled . There was one notable application of Michael s... 

The assignment of configuration and the measurement of enantiomeric purity is a necessary step in any stereochemical study. Both the physical and chemical techniques used have been described in detail in the case of carbon compounds (92, 93). In this section we give a brief overview of their application to organo-silicon stereochemistry. 

At this time, VCD spectroscopy is a viable technique for elucidating the stereochemistry of chiral organic molecules. Most importantly, it provides a powerful new alternative approach to the determination of absolute configuration. Both the experimental instrumentation and the computational software required for the application of VCD are now commercially available. As a result, the VCD technique is ripe for exploitation by stereochemists. It should be of value, inter alia, in stereochemical studies of candidate pharmaceutical compounds. 

The formation of such Lewis complexes may find increasing application in stereochemical studies. Two cases in point might be cited. First, etherate formation allows the isolation of the optically active tri-2-methylbutyl-aluminum etherate (97). This compound is stable to racemization up to 100°. Second, diphenylpalladium (II) has recently been prepared as its bis-triethylphosphine complex in both a cis- and a irans-planar complex form (20). The latter seems to represent the first example of geometrical isomerism among organometallic compounds (Section II.D). 

The conclusion from these extensive elegant stereochemical studies is that in five-membered ring systems the apicophilicity of endocyclic ligands does not conform to Trippett s relative apicophilicity scale nor to Holmes s preference rules. Clearly, apicophilicity is a redundant term in such species. Relative apicophilicity is an empirically derived parameter formulated for universal application to phosphorus TBP species. The apicophilicity of a particular ligand is independent of the other phosphorus substituents and the nature of the TBP and is a transferable parameter. Since this definition of apicophilicity breaks down in five-membered TBP intermediates. Hall and Inch defined the alternative term apical potentiality . Thus, in the... 

Of the number of chromophoric derivatives of chiral amines for potential use in the establishment of their absolute configuration by BCD measurement only a few have proven to be generally useful. Of these, intensive investigation of the Af-salicylidene (Schiff base) derivatives of chiral primary amines, including unsubstituted and ring-substituted a- and S-arylalkylamines, a-amino acids, unsaturated and satnrated aliphatic and alicyclic amines, and amino sugars, has resulted in the formulation of the salicylidenamino chirality rule ° °. The application of this rule has recently been reviewed and has been successfully used for the establishment of absolute configuration of chiral primary amines in connection with other stereochemical studies. In related studies, the conformations of a series of pyridoxyl-L-a-amino acid Schiff bases were deduced from their CD spectra ... 

Early review R. E. Gawley, Synthesis 1976, 777-794. Improved methodology T. Sato etal, Tetrahedron Letters 31, 1581 (1990). Stereochemical study C. Nussbaumer, Helv. Chim. Acta 73, 1621 (1990). Synthetic applications R. V. Bonnert et al, J. Chem. Soc. Perkin Trans. 11991, 1225 S. Kim, P. L. Fuchs, J. Am. Chem. Soc. 115, 5934 (1993). Cf. Michael Reaction Wichterle Reaction. 

Interest in oxyphosphoranes derived from hexafluoroacetone continues,and their applications in stereochemical studies concerned with phosphorus(v) compounds have been discussed in the review literature. Information concerning the relative apicophilicities of groups (R) has been provided by n.m.r. studies of the pseudorotation (68) (69) in hexafluoroacetone... 

To illustrate the application and configurational analysis of chiral [> 0, 0, 0]thiophosphate, we describe the stereochemical study of 5 -nu-... 

Schafer, L., J. D. Ewbank, K. Siam, N. S. Chiu, and H. L. Sellers. 1988a. Molecular Orbital Constrained Electron Diffraction (MOCED) Studies The Concerted Use of Electron Diffraction and Quantum Chemical Calculations, in Stereochemical Applications of Gas-Phase Electron Diffraction, Hargittai, I., and Hargittai, M., eds., Vol. A, Chap. 9, 301-320. New York, VCH Publisher. 

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