Conformation problems, solution

Describing the ensemble of conformations would imply knowing the structure and the relative population of each conformer in solution. In many cases this problem is underdetermined, since the number of NMR-derived experimental restraints is smaller than the degrees of freedom of the system. In consequence,... 

The fundamental work of Lemieux and coworkers21 introduced the successful application of H-n.m.r. spectroscopy to structural problems in the carbohydrate field. Since then, numerous studies have been devoted to the (partial) determination of primary structures of carbohydrates and derivatives thereof, as well as to the elucidation of their conformation in solution, by means of H-n.m.r. spectroscopy. An exhaustive discussion of all these contributions is beyond the scope of this article. For comprehensive reviews, see Refs. 22-28. 

E° must be computed by means of a different method. For large solutes, molecular mechanics methods could be appropriate, when dealing with molecular conformation problems. The description of chemical reactions requires a separate discussion. 

It is appropriate at this point to indicate our personal motivation for carrying out structural studies, the types of compounds we study, and the experimental conditions we employ. In a very general sense we are interested in the bonding of small molecules and ions, e.g., 02, N2, NO, N2 R+, olefins, and acetylenes, to transition-metal complexes. Because of our interest in bonding, we seek the best solutions we can attain. Rapid, qualitative answers to conformational problems are not our interest. Since those transition-metal systems that bind small molecules generally have the metal in a low oxidation state, and since a low oxidation state is usually stabilized by ligands of the type PR3 (R = alkyl or aryl), solution to our problems involves typically the determination of a large number of structural parameters. With only a few exceptions the intensity data are obtained at room temperature on a Picker FACS-1 computer-controlled diffractometer. Usually the ratio of observations to variables is at least 10, and it is often 20 to 30. 

H- and 13C-NMR spectroscopy have helped to solve several configurational and conformational problems in hydantoinsj71,79,184-186 and the energy barrier for free rotation about the N—C bond in 3-aryl-2-thiohydantoins has been calculated by H-NMR experiments.187 Diaste-reomeric solute-solvent interactions of 1- and 3-arylhydantoins in chiral solvents have been studied.188... 

A-Benzyl PRT groups. An obvious solution to the conformation problem discussed above is the use of or/Z/u-halobenzyl PRT groups instead of the benzoyl derivatives [117]. Ito [121] and Undheim [122] have demonstrated the synthetic potential of this approach. Under classical tin hydride conditions, excellent yields for the alkylation of amines have been obtained as shown in Scheme 33 (Eq. 33.1) [122]. Starting from a chiral 1,3-oxazolidine, a novel approach for the functionalization of aminoalcohols has been reported [123]. When samarium iodide was used for such reactions, the formation of an organosamarium intermediate at the a-N position was achieved. This corresponds to the metallation of an amine under non-basic conditions. Subsequent reaction of the organosamarium species with electrophiles such as ketones [121, 124, 125[ (Eq. 33.2) and isocyanides [121, 124[ has been reported. 

In principle, in order to solve a conformational problem, one must find a solution of the Schrodinger equation for a given system of nuclei and electrons to obtain the dependence of energy on geometry of this system. This solution... 

Bastiansen O (1949) The moteodar structure of biphenyl and some of its derivatives. Act. Chem. Scand. 3 408 See also Bastiansen O, Traetteberg M Tetrahedron 17 147 (1962) d Atmibale A, Lunazzi L, Boicelli AC, Macciantelli D (1973) The conformational problem of biphenyl in solution as investigated by the liquid crystal magnetic resonance spectrum of 3,3, 5,5 -tetrachlorobiphenyl. J. Chem. Soc. Perkins II 1396 see also Schmid ED, Brosa BJ (1972) Chem. Phys., 56 6267... 

Nuclear magnetic resonance is an extremely versatile method for the examination of both the static and dynamic aspects of conformational problems. The technique has primarily been adopted for solution studies. 

---