Conformationally mobile systems

When two or more groups which impart the same conformational bias are present, shift additivity will provide reasonable predictions. For example, the methyl groups in exo-3-exo-8-dimethyl-cis-decalin (next page) are either both equatorial or both axial, with the former arrangement obviously favored. Since this conformation preserves the spatial orientation of the methyl group in the monosubstituted model, then shift additivity will hold so long as the effect of the methyl group is assessed relative to the shifts of the conformationally fixed parent obtained at low temperature. 

The same problem occurs with the bicyclo[3.3.1]nonane system when there is an endo substituent at both C-3 and at C-7 resulting in a double twist boat conformation. Since each of the model, monosubstituted compounds will be predominately in a boat - chair arrangement, they will not serve as good sources for A6 effects for the disubstituted system and their use results in sizable orors for C-3 and C-7. 

While it is not possible to use models in the above case, the simple system developed in Chapter 1 is still applicable, so long as the stereochemical factors discussed in Chapter 3 are incorporated as well. Thus, in the above example, C-3 is in a six-membered ring (27.3) with one additional a oxygen substituent (+8.0 + 38.0) but is 3° with two P substituents (2 -1.5) and has a gauche interaction with a y group (C-9, -3.0) for a predicted shift of 67.3 (68.0 obs). Similar treatment of C-7 leads to a predicted shift of 29.3 (28.1 obs). 

The configuration of this chirality center will be R in all of the drawings. To see why this works, build a molecular model and rotate it around to convince yourself. 

When a Fischer projection has multiple chirality centers, this process is simply repeated for each chirality center. 

PRACTICE the skill 5.29 Identify the configuration of the chirality centers shown below  

30 Determine the configuration for every chirality center in each of the following compounds. 

31 Draw the enantiomer of each compound in the previous problem. - need more PRACTICE Try Problems 5.39h, 5.41a,b, 5.43c, 5.53c,e, 5.54-5.56 

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By chance rather than by design, the third chapter in this volume also emanates from Israel. Bernard S. Green, Rina Arad-Yellin, and Mendel D. Cohen have surveyed organic reactions in the solid state from the standpoint of the stereochemist. In the first part of the chapter, the authors discuss the stereochemical consequences of the crystallization of conformationally mobile systems. Conformational, crystal-field, and hydrogen-bonding effects, among others, are responsible for the selective crystallization of stereoisomers that may not be dominant in solution. The second part of the chapter is concerned with the stereochemical consequences of chemical, and especially photochemical, reactions in the solid state. 

In conformationally mobile systems in which the required antl-periplanar arrangement is readily achieved (even though this may not be the favored conformation), the reaction is usually complete within hours at 0-25°, or after a few minutes at the reflux temperature. Thus, l,2-0-isopropylidene-6-0-p-tolylsulfonyl-a-D-glucofuranose (I) affords 5,6-anhydro-l,2-0-isopropylidene-a-D-glucofuranose (2) within... 

The kinetic method may be conveniently illustrated by reference to the methylation of the trans (2-H,9a-//)-2-methylquinolizidine (116) (Fig. 8) because this gives rise to an 50 50 mixture of the two methiodides.134 The basic expression required for the analysis of this system is that worked out for conformationally mobile systems in general by Eliel and by Winstein and Holness.3,1690 If c(l — x) and cx denote the concentrations of the transfused and cis-fused conformers of the methylquinolizidine at equilibrium,... 

Cotton effect for deuterium a and /i positions of chair cyclohexanone. And application of those data to conformationally mobile systems led to the interesting stereochemical conclusion that deuterium prefers the more sterically crowded axial configuration in 3-deuteriocyclohexanone55,69. 

In conformationally mobile systems, both syn and anti eliminations are theoretically possible. The anti elimination should be favored electronically over the syn elimination because the electron pair of the C-H bond is anti-periplanar to the leaving group. It has also been suggested (84, 85) that the syn elimination might require a configurational inversion at the C-H bond, so the electron pair of that bond becomes antiperi planar to the C-X bond (297-298). 

Seeman, J. I. Secor, H. V. Hartung, H. Gal-zerano, R. Steric effects in conformationally mobile systems. The methylation of 1-methyl-2-arylpyrrolidines related to nicotine. /. Am. Chem. Soc. 1980, 102, 7741-7747. 

An interesting study of conformationally mobile systems involves iodo-methylation of nicotine derivatives 47, where steric effects of substituents at position-2 and -6 modify the alkylation rate at the pyridine nitrogen and at the two nitrogens (N trans and N cis) of the pyrrolidine conformers (80JA7741 81JOC3040) (Scheme 26b). 

Biological Discrimination of Enantiomers 189 5-6 Racemic Mixtures 191 5-7 Enantiomeric Excess and Optical Purity 192 5-8 Chirality of Conformationally Mobile Systems 193 5-9 Chiral Compounds without Asymmetric Atoms 195 5-10 Fischer Projections 197... 

This finding leads to a general principle we can use with conformationally mobile systems ... 

Treatment of the silyl enol ethers of IV-acyloxazolidinones with selected electrophiles that do not require Lewis acid activation similarly results in high induction of the same enolate face (eq 13). The facial bias of this conformationally mobile system improves with the steric bulk of the sUyl group. 

The outcome of this reaction depends on the relative magnitude of the various rate constants (activation barriers). If the conformational equilibration is rapid compared with product formation, essentially all of the reaction will be channelled through the more reactive conformer (Fig. 6a). For that reason the relative population of the conformers is irrelevant in the reactions of conformationally mobile systems... 

In E2, the two groups to be eliminated must be coplanar. In conformationally mobile systems like acyclic molecules, or in cyclohexanes, anti-coplanar is the preferred orientation where the H and leaving group are 180° apart. In rigid systems like norbomanes, however, SYN-coplanar (angle 0°) is the only possible orientation and E2 will occur, although at a slower rate than anti-coplanar. 

In the early days of physical organic chemistry, there was discussion about whether the effects of substituents in saturated systems was through bonds (inductive effects) or through space (field effects),but the consensus view was that it was not useful to try to distinguish them. These recent data are a decided upset to the consensus and must throw into question any Hammett-type reactivity parameter derived from a conformationally mobile system in any area of physical organic chemistry. 

In all four cases (239 - 242), there is little conformational mobility and steric interactions are more important than in a conformationally mobile system. Similarly, cis-decalin (243) and trans-decalin (244) show the same bent and extended forms with both six-membered rings in a chair conformation, There is a... 

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