Conformations synclinal

The synclinal conformation (sc) is appropriate for overlap of an oxygen nonbonded pair with the a C—Cl orbital. The preferred ap relationship, requires an antiperiplanar alignment of a lone-pair orbital with the bond to the electronegative substituent. Because of the donor-acceptor nature of the interaction it is enhanced in the order F < O < N for the donor (D) atom and N < O < F for the acceptor (A) atom. 

Peptides built from y-amino acids with L-amino acid-derived chirahty centers form a right-handed (P)-2.6i4 hehx of ca. 5 A pitch with both ethane bonds in a -y)-synclinal conformation (mean values for dihedral angles 9 and 82 of central residues 2-5 in compounds 141 are 72.5 and 64.3°, respectively Fig. 2.36 A and B Tab. 2.8). 

In addition to this extended conformation there are two gauche (skewed or synclinal) conformations which are only slightly less stable than the staggered conformation and in which A and B interfere only if they are very bulky. In one of the two gauche conformations B lies to the right of A and in the other to the left of A when viewed down the axis. 

Deduce the symmetry point group of (S,S)-tartaric acid in the +synclinal conformation. 

In order to ascertain which symmetry elements are present in raeso-tartaric acid, it is necessary to look at the various conformations of the molecule. The symmetrical highest energy conformer, i.e. the synperiplanar conformer (sp), has a plane of symmetry in which both enantiomorphic halves of the molecule are reflections of each other. No other symmetry elements are present in this conformation (point group Cs). In the ap conformation of raeso-tartaric acid the only symmetry element present is a centre of symmetry (disregarding the fact that the centre of symmetry is equivalent to any of the infinite number of S2 axes). The symmetry point group is therefore Cj. All other conformations, e.g. the +synclinal conformation (+sc) of raeso-tartaric acid shown below, are chiral and do not possess any symmetry elements and therefore belong to the point group C. ... 

If we managed to slow down the rapid interconversions in butane (by cooling to very low temperature, for example), we would be able to isolate the three stable conformations—the anti-periplanar and the two synclinal conformations. These different stable conformations of butane are some sort of isomers. They are called con/b rmational isomers or conformers for short. 

As demonstrated by the spectra of 1,2-dichloroethane shown in Fig. 4.1-11C, two halogen atoms in 1,2-position also show in-phase as well as out-of-phase vibrations. The antiperiplanar conformation is subject to the exclusion rule op. Raman 750 cm Oa . IR 708 cm. In the case of the synclinal conformation, on the other hand, the in-phase vibration at 645 cm is stronger both in the IR and in the Raman spectrum than the out-of-phase vibration at 677 cm. Freely rotating 1,2-dihalogen compounds therefore show four different C-Cl stretching vibrations (Fig. 4.1-11C). 

Conformational isomerism is believed to be of great significance for drug-receptor and drug-enzyme interactions. For example, experimental data suggest that catecholamines such as norepinephrine and dopamine interact with their receptors in the antiperiplanar conformation. Furthermore, the preferred (pharmaco-phoric) conformation of acetylcholine at its muscarinic receptor sites is the synclinal conformer (Fig. 19). 

Dautzenberg and Knozinger also pointed out that adsorbed alcohol can exist in two conformations, with respect to the a-Me group and the variable )3-R group, namely antiperiplanar and synclinical. The former is thermodynamically more stable and would lead to rra s -2-olefin by anti-elimination. Reaction is nevertheless more probable for the synclinical conformation because the approach of jS-H to a basic site is less hindered for the latter. 

Similarly, vinylcyclopropane (1) gives only [2 -I- 2] cycladdition products with TONE, leaving the three-membered ring intact (see Section 2.2.1.2.2.). Preorientation of the vinylcyclopropane in the synperiplanar or synclinal conformation (rule 1), as realized in the bicyclohexene system 2, should enhance the reactivity towards dienophiles however, this is clearly insufficient. Additional strain (rule 2) or jc-donor substitution (3, rule 3) are further options to enhance the reactivity per se they seem to be insufficient. The combination of two activating principles, however, realized in homofuran (4, rule 1 -t- 3) or benzvalene (6, rule 1 -f 2) sufficiently peps up the reactivity of the embedded vinylcyclopropane system such that homo-diene-type cycloadditions occur (see Section 2.2.1.2.1.). 

The gauche (or synclinal) conformation is higher in energy (by 4 Id mol 1) as the two methyl groups are near one another (60° separation), resulting in steric strain. Steric strain is the repulsive interaction between two groups, which are closer to one another than their atomic radii allow. 

N-C1-C2-C3 bond ( ) of the allylic amine is antiperiplanar due to A1-3 strain in the synclinal conformation (Figure 6.2a). Coordination of the catalyst to the nitrogen (step 1 in Scheme 6.1c) will only increase the energetic bias in favor of the antiperiplanar conformation." The second step of the reaction sequence is the migratory insertion of the metal into the Ci-H bond to give a Jt-bonded a,P-unsaturated iminium ion. Figure 6.2b shows that only the 5-trans conformer of this species is accessible, because of severe A1-3 interactions between the diethylamino substituents and the C3 substituent in the s-cis conformation. 

Low temperature H and NMR studies indicated that only the nitrogen of allylic amines is bound to the metal. No evidence could be found for an A - r-chelate that might stabilize the synclinal conformation [11]. 

Fig. 13.10. Superposition of retinol, retinal, and retinoic acid in the conformations adopted at the active site of RBP, and in various small molecule crystal structures. For clarity, the H atoms have been omitted. TVvo distinct conformations are observed for the single bond between the )8-ionone ring and the isoprene chromophore. The synclinal conformation, adopted at the receptor site, corresponds to the global energy minimum of the isolated molecule...

Thus the synclinal conformer of fluoromethanol (121) appears to be preferred due to overlap repulsion as well. This conclusion is of significance, since it provides additional proof for the role of destabilizing interactions in the origin of the anomeric effect. Though the importance of destabilizing interactions involving lone electron pairs seems to be well established even in the... 

Mechanistically, when R =H, the usual syn selectivity is observed due to the preference of the reactants to adopt an antiperiplanar transition state, which places the aldehyde carbonyl and olefin opposite each other. When the j -methyl substituent is added, the transition state prefers the synclinal conformation (495) therefore leading to the formation of 494. 

It must be emphasized that the experimentally determined synclinal conformation of acetylcholine Is only that measured In aqueous solution (NMR) or the crystalline state (x-ray). This may not be the conformation preferred by the receptors. Indeed, the conformation of receptor-bound acetylcholine could be much different and might not be a thermodynamically preferred conformation. 

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