Conformers chair

Frozen conformational equilibria. Although the rate of the interconversion of the various conformers (chair, boat, twisted) of the oxane derivatives at ambient temperature is fast on the NMR timescale, this ring-inversion process is sufficiently slow at low temperature (T < -60°C) to permit the observation of individual signals for each conformer. Direct integration delivers K and -AG°, respectively [see Eqs. (1) and (2)]. 

A number of cis/trans 4,6-dialkyl-2,2-dimethyl-l,3-dioxanes were studied by C NMR spectroscopy (93JOC5251). The C NMR shifts of C -Me groups (Scheme 8) were found to be very sensitive to the 1,3-dioxane conformation [chair form Me(ax) ca. 19 ppm and Me(eq) ca. 30 ppm— pure 30.89 ppm in the twist-boat form both methyl carbons resonate at ca. 25 ppm (pure 24.70 ppm)]. With these values, AG° of the chair to twist-boat equilibrium was calculated (Table IV). For 13a (nitrile), 13b (alkyne), and 13e (methyl ester) (Scheme 8) in CH2CI2, the temperature dependence of the AG° values was determined. Depending on the substituent, small negative or positive entropy terms were found generally the enthalpy term dominates the -AG° value. In the tram isomers 13, the cyano and alkyne substituents favor the chair conformation, but CHO, ester, alkene, and alkyl substituents, respectively, clearly favor the twist-boat conforma-... 

An especially intriguing problem concerns the stereochemistry of the [7C4 + Tc J-adducts [e.g., 213 and 214]. Dreiding models reveal two stable conformations, chair and boat (Fig. 1). Whereas interconversion appears... 

The situation for 172 was quite similar, but trends between conformers were reversed the solid-state conformer (chair-chair-boat) corresponded to the minor solution isomer of 184, whereas the minor solution isomer of 172 corresponded to the major all-chair conformer of 184. Imakura s desethano artemisinin 171 was found to exist in the all-chair arrangement by X-ray and exhibited a nontempera-ture-dependent proton NMR spectrum. MM2 studies of 171 showed that the all-chair conformer was 4-5 kcal/M more stable than the next lowest energy conformer, a chair-chair-boat, and were thus consistent with experimental observations. Studies to correlate conformer populations and energetics with antimalarial activities have not provided clear answers.141... 

In contrast, when 6-exo cyclizations are effected in the presence of an ot-alkoxy or a-silyloxy substituent, the stereocontrol can be excellent, as has been observed in a Si-tethered cyclization of 54a (Scheme 15) where a single diastereomeric product was obtained [134]. In this case, additional conformational constraints aided the cyclization, as became evident upon finding that the product configuration was inconsistent with the standard Beckwith-Houk chair-equatorial transition state model. For 54a there are two chairlike conformations (chair-equatorial and chair-axial) conceivably leading to cyclization the latter has the C-O and C=N bonds in an anti relationship to minimize dipole repulsion (Scheme 15). The... 

These cyclohexane-like rings are characterized by the presence of various non-planar conformations chair, boat, and twist conformations. The starting point when dealing with the stereochemistry of these six-membered rings is therefore conformational analysis. The method of choice is NMR spectroscopy as a result the preferred conformer(s) and the axial/equatorial position of attached substituents at the preferred conformer(s) are obtained. 

A hypothesis has been advanced to explain the different pharmacological response to opioid agonists and antagonists in terms of conformational differences about the basic center, as discussed in Chapter 13. However, a study by 13C-nmr of two such pairs (morphine-nalorphine, oxymorphone-naloxone) revealed little difference between agonist and antagonist molecules in either piperidine ring conformation (chairs only) or ratio of N- R axial to equatorial forms (83 17 for morphine, virtually 100% eq JV-R for 14-OH derivatives).035 ... 

FIGURE 2.24 Variants of the six-membered ring conformations chair (C), half-chair H), skew (5), boat (B), and envelope ( ). 

Conformation Chair Anomeric effect Hydrox)miethyl Monosaccharides Disaccharides Oligosaccharides Couphng constants Molecular mechanics Molecular dynamics... 

The reason for these conformations is the tendency of R to avoid the neighbourhood of the OH groups . This tendency was also found in calix[4/5]phenols with endo and exo hydroxy groups and one (or two) —CHR—bridges . However, although these conformations (chair, diamond) are strongly preferred, they are not fixed, which follows for the rett and rcct isomers from the fact that cavitands (see Section VII.D) with a (now... 

The hydrogen atoms in the more stable conformation (chair) of cyclohexane fall into two geometrical classes equatorial (e) which encircle the approximate plane of carbon atoms, and axial (a), for which the C—H bonds parallel the threefold axis of symmetry (6, 22). Substituents prefer to take equatorial positions, the energy difference for a methyl group is about 1.8 cal. mole and for i-butyl 5.6 cal. mole (2S). 

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