Conformational analysis of six-member

The principles involved in the conformational analysis of six-membered rings containing one or two trigonal atoms, for example, cyclohexanone and cyclohexene are similar. The barrier to interconversion in cyclohexane has been calculated to be 8.4-12.1 kcal mol . Cyclohexanone derivatives also assume a chair conformation. Substituents at C2 can assume an axial or equatorial position depending on steric and electronic influences. The proportion of the conformation with an axial X group is shown in Table 4.4 for a variety of substituents (X) in 2-substituted cyclohexanones. 

Carbocyclic molecules occupy a special position in stereochemistry. While Barton s proposal (80) triggered explosive developments in the conformational analysis of six-membered ring compounds (80a), the inability of the qualitative theory to interpret the behavior of rings other than six membered prompted Hendrickson to utilize the MM method (9b). Further developments in this area have been well summarized (10, 81). Some of the more recent topics are mentioned below. 

Conformational Analysis of Six-membered Rings (KeUie and Riddell). Conformational Analysis and Steric Effects in Metal Chelates 8 225... 

B-1995MI201 E. Kleinpeter in Methods in Stereochemical Analysis Conformational Analysis of Six-Membered Sulfur-Containing... 

The principles involved in the conformational analysis of six-membered rings containing one or two trigonal atoms, e.g., cyclohexanone and cyclohexene, are similar.242... 

In the conformational analysis of six-membered rings, we deal with ring reversal equilibria and kinetics. To this is added in derivatives of piperidine the need to understand the equilibrium and kinetics of N inversion. Obviously, the sign of AG° is important for it determines the conformer favored at equilibrium. Less obviously, but of equal importance is the fact that the energy barrier between two conformations of N substituents consists of two half barriers AG x ts and AG q ls where AG° is the difference between the half barriers. It is important that in any precise discussion of the kinetics of N inversion that the half barrier under discussion should be clearly defined.2 Neglect of this in the past has led to much confusion and controversy the concept of half barriers is explained in detail in Ref. 2. 

B-1995MI201 E. Kleinpeter Conformational analysis of six-membered sulfur-containing, heterocycles, in Conformational Behaviour... 

The application of /hc couplings in conformational analysis of six-membered heterocycles has been shortly overviewed by Juaristi et al. and by Alabugin et a/. The couplings have been also shortly addressed by Ribeiro and Rittner in their work on the role of hyperconjugation in the conformational analysis of methylcyclohexane and methylheterocyclohexanes. 

E. Kleinpeter, Conformational Behaviour of Six-Membered Rings (E. Juaristi, ed.), VCH, New York (1995) Conformational Analysis of 6-Membered Sulfur-Containing Heterocycles, p. 201. 

E. Juaristi, Conformational Behavior of Six-Membered Rings Analysis, Dynamics, and Stereoelec-tronic Effects Methods in Stereochemical Analysis, Wiley-VCH, Weinheim, 1995. 

Conformational analysis of N-heterocycles, general aspects 83IZV2432. Conformational equilibria of six-membered saturated N-heterocycles ... 

Conformation analysis of saturated six-member 0-heterocycles 98AHC (69)217. 

Polycyclic compounds are common in nature, and many valuable substances have fused-ring structures. For example, steroids, such as the male hormone testosterone, have 3 six-membered rings and 1 five-membered ring fused together. Although steroids look complicated compared with cyclohexane or decalin, the same principles that apply to the conformational analysis of simple cyclohexane lings apply equally well (and often better) to steroids. 

The C,C-coupling reactions of six-membered cyclic nitronates were studied in most detail (274, 478). Here silyl ketene acetal was also used as the test nucleophile. The configurations of most of the starting nitronates and the resulting nitroso acetals were determined by NMR spectroscopy and X-ray diffraction, and also a conformational analysis was performed (see Tables 3.24 and 3.25). 

Conformational Analysis of Saturated Six-Membered Oxygen-Containing Heterocyclic Rings... 

The best method used in the conformational analysis of saturated six-membered heterocyclic rings in the solid state is single-crystal X-ray structural analysis. The conformation in solution is not always identical. For solutions, H NMR spectroscopic analysis has been employed widely in the field of conformational analysis. The following methods deserve special mention. 

Conformational Analysis of Sulphur-Containing Six-Membered Heterocycles N. S. Zefirov and I. V. Kazimirchik, Russ. Chem. Rev. (Engl. Transl.), 1974, 43, 107-114. 

Conformational Analysis of Five- and Six-Membered Rings and Related Non-Bridged Systems (Saturated Heterocyclic) , F. G. Riddell, in Aliphatic, Alicyclic and Saturated Heterocyclic Compounds , ed. W. Parker, Royal Society of Chemistry, London, 1974, vol. 1, pt. 3, pp. 69-91. 

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