Rings and Strain

Scheme 3.8 Alternating ROMP monomers exhibiting different steric demand and ring strain...

The use of theoretical methods in the study of bicyclic systems with P-, As-, Sb-, or Bi- bridgehead atoms has contributed to an increased understanding of the geometry, stability, and ring-strain effects of these systems. In addition, important data relating to basicity and the interpretation of nuclear magnetic resonance (NMR) and X-ray data have been generated. A vast majority of the work done has focused on P. 

Table 4.6 Heats of Combustion and ring Strain of Cycloalkanes...

The solid-state structures of orthorhombic S864 and monoclinic Se866 are shown in Figure 15. As may be seen from the average E-E-E bond and EE EE torsion angles, this structure is almost completely relaxed and consequently lone pair repulsion and ring strain are lowest in this arrangement. Other S8 structures were assessed by quantum chemical calculations.69... 

Several compounds containing Tt-bonds show reactions with 1 which most likely proceed via [2+1] or [4+1] cycloaddition processes, but no detailed mechanistic studies have been performed so far. Not unexpectedly, the electron-rich species 1 preferentially reacts with electron-poor substrates, and ring-strained or dipolar intermediates rearrange or react further to more stable products in a sometimes rather complicated and surprising fashion. In a few cases even the pentamethylcyclopentadienyl substituents at silicon are involved in the reaction pathways. 

Figure 5.30 Alternative water pentamer isomers having partial anticooperativity, (a)-(c), or higher coordination and ring strain, (d). Labels in (a)-(c) correspond to clockwise monomer numbering from the top (see the text). (Species (a)-(c) have been optimized under the constraint of planar equilateral skeletal geometry to prevent rearrangement to Wsc [Fig. 5.29(a)] and are therefore only near-stationary points on the potential-energy surface.)...

As discussed above, many cyclopropylamines are good inhibitors of MAOs. In addition, as discussed in Section 3.2, fluorine substitution had substantial effects on the inhibition of MAOs by such analogues as allylamines. We undertook a broadly based study of the effects of fluorine substituted on the cyclopropyl ring of cyclopropyl amines on potency and selectivity of amine oxidase inhibition. In addition to effects on amine pKg and lipophilicity, we expected additional consequences resulting from altered geometry and ring strain due to the presence of fluorine. 

Another example is the indirect acetonylation of a 1,2,3,4-tetrahydropyridine derivative at the (3-position of the enamide system [99]. The reaction involves a double alkylation to furnish an acetylcyclopropane which undergoes fragmentation on acid treatment. It is noted that polarity alternation and ring strain relief allow the facile and regiospecific C-C bond cleavage to proceed, the intervention of a cyclopropane intermediate also leads to disjoint system. This is a fundamental strategy [100] which has been frequently employed to gain access to compounds with disjoint functionalities. 

Where more than one possible shape exists, the shape depends upon the number and position of lone pairs. Lone pairs, n electrons, and ring strain can distort the predicted bond angles. Lone pairs and x electrons require more room than bonding pairs. For example, the lone pairs on water make the bond angle 104.5°. 

The thermochemistry of some cephams and cephems has been investigated by high-level ab initio methods. Particular attention has been paid to estimate the magnitudes of amide resonance and ring strain <2006JPCA10521>. Determination of the kinetic parameters for interactions of three cephalosporins with PBPs has been reported <2006JBC10035>. 

The regiochemistry of the reaction between an n. T-unsaturated ketone and a ketene is the opposite, even in an intramolecular reaction 8.53 —> 8.54, which involves substantial twisting and ring strain. This time it is in the sense easily explicable by the frontier orbitals. The LUMO of the unsaturated ketone and the LUMO of the ketene show that the initial bonding will be between the [3 carbon of the enone and the carbonyl carbon of the ketene, and there is an orthogonal orbital on the other carbon atom of the ketene able to complete the cycloaddition, just as we saw earlier (see pages 212 and 253) for thermal reactions. 

The factors most commonly mentioned as important in studies of copolymerization of these cyclic compounds are relative basicity and ring strain. It seems fairly well established that relative basicity plays an important role in controlling the relative reactivity of cyclic ethers. This lends further support to the belief that propagation proceeds by nucleophilic attack of monomer oxygen in the cationic copolymerizations. Basicity seems to be less important than other factors such as ring strain in determining relative reactivity of cyclic sulphides. 

We performed calculations for model hydrogen-substituted analogs of the discussed monomers, because calculations for methyl siloxanes would require much more computational time. However, the results of basicity and ring strain calculations for hydrogen siloxanes reproduce reasonably well the trends observed for methyl analogs [7]. Another simplification is that the presented results are... 

This mechanism is consistent with the observed features of polymerization of D2. The kinetic differences between the polymerizations of D3, D4 and D2 can be explained by differences in basicity and ring strain of these monomers, as discussed above. 

Numerous more recent experiments (reviewed in ref. 12) have confirmed the general accuracy of the mechanism shown in Scheme 4, and the actual intermediate involved depends upon the relative stabilities of the zwitterions/oxyallyl cations and the corresponding cyclopropanones. These will be affected by the choice of solvent and structural features of the starting ketone, such as the degree of substitution and ring strain (in cyclic halo ketones). A recent example in which an oxyallyl intermediate and a cyclopropanone intermediate were both intercepted is shown in Scheme 8. ... 

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