Synclinal preference

A study of the orientation of the reacting double bonds in the transition state of the allylsilane-aldehyde addition to model compounds (34) and (36) has revealed low and high synclinal preference, respectively, which has been attributed to stereoelec-tronic factors as there should be no intrinsic steric bias for double bond alignment (Scheme 23). °... 

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. 

Both anti-synclinal and anft -periplanar TSs are considered to be feasible. These differ in the relative orientation of the C=C and C=0 bonds. The anti-synclinal arrangement is usually preferred.94... 

Intramolecular reactions can also occur between carbonyl groups and allylic silanes. These reactions frequently show good stereoselectivity. For example, 7 cyclizes primarily to 8 with 4% of 9 as a by-product. The two other possible stereoisomers are not observed.98 The stereoselectivity is attributed to a preference for TS 7A over TS 7B. These are both synclinal structures but differ stereoelectronically. In 7A, the electron flow is approximately anti parallel, whereas in 7B it is skewed. It was suggested that this difference may be the origin of the stereoselectivity. 

Synclinal and antiperiplanar conformations of the TS are possible. The two TSs are believed to be close in energy and either may be involved in individual systems. An electronic tt interaction between the stannane HOMO and the carbonyl LUMO, as well as polar effects appear to favor the synclinal TS and can overcome the unfavorable steric effects.161bi 162 Generally the synclinal TS seems to be preferred for intramolecular reactions. The steric effects that favor the antiperiplanar TS are not present in intramolecular reactions, since the aldehyde and the stannane substituents are then part of the intramolecular linkage. 

As can be easily seen by inspection of these illustrations of the SuiCsPa and ShiCsPf phases, while the director tilt in the tilt plane is synclinic for both, the layer interfaces have a different character when observed in projection in the bow plane. The antiferroelectric diastereomer has synclinic character at the layer interfaces, while the ferroelectric diastereomer is anticlinic in the bow plane. This suggests a very simple reason for the tendency toward antiferroelectric bananas, this being basically the same as the tendency toward ferroelectric calamitic smectics preference for synclinic layer interfaces. 

Dioxin prefers the half-chair conformer 44 the corresponding boat and planar conformers proved to be less stable by 10.6 and 12.3 kcalmoP, respectively. If 4//-1,3-dioxin is alkyl-substituted at position 2, the same level of theory indicated the equatorial conformer 45-eq to be more stable than its axial counterpart, 45-ax (Me, 2.95 kcal moP Et, 2.89 kcal mol iso-Vi, 2.97 kcal moP neo-Vc,n, 2.16kcal moP and SiMc3, 4.45 kcal moP ) since the dipole moments of the two conformers are nearly equivalent, the position of the conformational equilibria of 2-alkyl-substituted 4//-1,3-dioxins is influenced by both steric effects (synclinal and H,H-, H,0-nonbonding interactions due to short C-O bonds) and a number of stereoelectronic orbital interactions. 

Finally, the acceptor (activated olefin) may approach the enamine by two different ways, as depicted in Figure 2.11. Stabilizing interactions such as hydrogen bonding, or electrostatic interactions between the catalyst and the olefin, may offset repulsive (steric) interactions preferring transition state I. It is considered, that the acceptor approaches the enamine via an acyclic synclinal transition state, as suggested by Seebach and Golinski [7]. 

The trouble is, in this conformation none of the oxygen lone pairs get the chance to donate into the C-O a orbitals. Although putting the bonds anti-periplanar to one another makes steric sense, electronically, the molecule much prefers to put the lone pairs anti-periplanar to the C-O bonds, so the bonds themselves end up gauche (synclinal) to one another. This is known as the gauche effect, but is really just another way in which the stereoelectronic effects that give rise to the anomeric effect turn up in acyclic systems. 

In all examples examined the syn adduct was strongly favored. It should be noted that the thermal reaction affords the syn adduct which must be formed via a synclinal arrangement because of the cyclic nature of the transition state. Two arguments were advanced to explain the preference for a synclinal transition state in Lewis acid-promoted additions. The first of these entailed Coulombic attractive forces between the developing positive charge at the /3-position of the allylic stannane and the electron-... 

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). 

The results obtained with model systems 5 and 8 demonstrate a clear preference for the synclinal transition structure, but several questions regarding the ability of this model to predict the stereochemical outcome of the intermolecular allyl-silane-aldehyde eondensation are still at issue. Model system 10 was designed to remove any steric bias that may be present in model 5 (Scheme 10-7) [17e]. Cyclization of 10 was induced by various Lewis acids and the results are shown... 

The Lewis acid-promoted cyclization of the deuterium-labeled model 13 is found to give products corresponding to an anti Sp reaction. All of the cycliza-tions with Lewis acids are greater than 95% selective for the anti Sp reaction. The high selectivity observed demonstrates that in a sterically unbiased S/- reaction an anti orientation of the electrophile with respect to silicon is preferred. The products from both the synclinal and antiperiplanar transition structures are found to be anti selective. The arrangement of double bonds in the transition structure does not affect the relative disposition of the silicon electrofuge, which must be disposed away from the approaching electrophile. 

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