Chair conformations stability

We have explored other factors in a preliminary way to ascertain their influence on pV geometry and ring conformation and have isolated the monocyclic phosphorane (O) for study. X-ray analysis (40) shows the usual (a-e) ring orientation but the presence of a chair conformation. This represents the first example of the appearance of the chair conformation stabilized in the absence of hydrogen bonding interactions. Comparison with the related dithiaphosphorinane P analog (P) shows the same (a-e) ring orientation but in the normally observed boat conformation (40). 

The dibenzylphosphono-tetrahydrophosphinine oxide (52) was transformed into the free phosphonic acid (53) by debenzylation that was found to exist in a half-chair conformation stabilized by an intramolecular H-bonding (Scheme 24, Fig. 11) [34],... 

The six-membered rings 8.12a and 8.12b adopt chair conformations with all three halogen atoms in axial positions. This arrangement is stabilized by the delocalization of the nitrogen lone pair into an S-X a bond (the anomeric effect) All the S-N distances are equal within experimental error [ld(S-N)l = 1.60 (8.12a)/ 1.59 A (8.12b) ]. 

The vibrational spectrum of 1,4-dioxin was studied at the MP2 and B3-LYP levels in combination with the 6-3IG basis set [98JST265]. The DPT results tend to be more accurate than those obtained by the perturbational approach. The half-chair conformation of 4//-1,3-dioxin 164 was found to be more stable than the corresponding conformations of 3,4-dihydro-1,2-dioxin 165,3,6-dihydro-1,2-dioxin 166, and of 2,3-dihydro-1,4-dioxin 167 (Scheme 114) [98JCC1064, 00JST145]. The calculations indicate that hyperconjugative orbital interactions contribute to its stability. 

Trioxane 210 has been used as a model system by Gu and coworkers to study the antimalarial drug artemisinin 211 (Scheme 137) [97CPL234, 99JST103]. It is the boat/twist form rather than the chair conformer of 210 that describes the subunit in 211. Moreover, geometric parameters and vibrational frequencies can only reliably be computed at the DFT level and by post-Hartree-Fock methods. B3-LYP/6-31G calculations on the conformers of 3,3,6,6-tetramethyl-1,2,4,5-tetroxane show that the chair conformer is stabilized with respect to the twisted conformer by about -2.8 kcal/mol [00JST85]. No corresponding boat conformer was found. 

The substitution of a heteroatom for an a-sulfoxy methylene group substantially increases the preference for an axial orientation of the sulfoxide oxygen320, despite the smaller space requirement of the sulfur with its lone pairs, compared to that of a methylene group321, at least in the case of 1,3-dithiolane oxides. The substituting heteroatom, therefore, should decrease the conformation stability (i.e. lower the barrier to chair-chair interconversion). 

Optimization of the valence and dihedral angles yields planar cyclic structures for the 3- to 5-ring intermediates in contrast to a chair conformation for that of the 6-ring. In the cases of n = 4, 5, 6 the oxygen atom is placed almost in the plane of the three C-atoms directly bonded to it. Therefore, an intramolecular solvation of the cationic chain end by methoxy groups which are bonded to the polymer backbone is preferred in the gas phase. The calculations show that for a non-polar solvent such as CH2C12 a decrease in stability of the cyclic intermediates exists. But this decrease does not result in a total break of the intramolecular solvation (Table 13). An equilibrium between open chain and cyclic intermediates must only be taken into account in more polar solvents, due to the competition of intra- and intermolecular solvation. 

Because of the greater stability of the chair, more than 99% of the molecules are estimated to be in a chair conformation at any given moment. 

A comparison of the structures of products and initial 1,3,5-diazapho-sphorinane reactants reveals a correlation between the number of added borane molecules and the predominant conformation of the initial compounds. l,3-Dibenzyl-5-phenyl-l,3,5-diazaphosphorinane (45) adopts a chair conformation. The substituents at the phosphorus atom and at one of the nitrogen atoms are equatorial, and another nitrogen possesses an axial substituent. In other 1,3,5-diazaphosphorinanes, all the substituents are equatorial. The number of borane molecules added is likely to be determined by the same factors as their conformational stability. There is steric hindrance when the three BH3 groups are axial. 

Fig. 35. Dominant stabilizing orbital interactions in the boat and chair conformers of...

The antibodies can also act like entropy traps by stabilizing a particular conformation of a substrate that is favorable to the formation of the TS. It is the case of the antibody 1F7 catalyzing the transformation of chorismate into prephenate," which stabilizes, thanks to several hydrogen bonds and an ionic bond between an arginine (Arg H95) and a carboxylate substituent of the substrate, the conformation of the chorismate which will give rise to the TS in a chair conformation for this reaction (Figure 11). 

In the conformational equilibria of 2,2-di-Me-5-R-5-R -l,3-dioxanes (R = Me, CH2OH, CH2OAC R = NHBz, NO2), both the NHBz and the nitro group prefer the axial position in the chair conformations in the case of R = CH2OH, intramolecular hydrogen bonding proved to further stabilize this conformational behavior (Scheme 10) (85KGS468). 

The inverting GH 95 1,2-oc-L-fucosidase (EC 3.2.1.63) from Bifidobacterium bifi-dum in complex (PDB 2EAC) with 1-deoxy-L-fuconojirimycin (20) showed the inhibitor in C4 chair conformation, resembling L-fucose and the entrance to the active site was narrowed by the gate keeper loops.315 A calcium ion associated with the protein was not involved in the catalytic process but was considered to stabilize the enzyme. 

At the MP2 level of theory, the half-chair conformer of 4//-l,3-dithiin 55 is 2.0kcalmoP more stable than the boat conformer (Equation 4) <1998JCC1064> and has a calculated twist angle of 33.2° the relative stability of the halfchair conformer was attributed to absent lone-pair-lone-pair repulsions and a decrease of torsional strain owing to an... 

The chair conformation of the six-membered ring in such compounds can be stabilized by hydrogen bonding by incorporation of an additional hydroxyl group, for example, compound 6 <2005JOC7107>. 

The configurational assignment can be made indirectly by the analysis of Cotton effects due to enone helicity. Thus, while in the parent molecule 1 the enone chromophore is slightly twisted in the sense opposite to that shown in Figure 7 (ra > 0), nonbonded interactions further stabilize the half-chair conformer with > Oof the a-methyl derivative 2a, while an inverted half-chair conformer (w < 0) is preferred for the /i-methyl derivative 2b55. 

The transition state for the substitution step requires that, for maximum stability, the incoming nucleophile be coplanar with the three-membered oxide ring, and, for an epoxide on a pyranose ring (for which a half-chair conformation is expected, by analogy with... 

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