Ground state, strain

Similarly, partially fluorinated and perfluorinated methylenecyclopropanes [57, 52], cyclopropenes [55, 84, 55], cyclobutenes [75, 56], and bicychc alkenes [57, 55, 59, 90] apparently denve dienophilic reactivity from relief of their ground-state strain during reaction Thus 2,2-difluoromethylenecyclopropane and perfluoromethylenecyclopropane undergo exclusive [244] cycloadditions [57, 52] (equations 72 and 73), whereas (difluoromethylene)cyclopropane undergoes only [24-2] cycloadditions [57]... 

However, steric factors are also important.74 Ruchardt and coworkers showed, for a series of acyclic alkyl derivatives, that a good correlation exists between kd and ground state strain.75,76 Additional factors are important for bicyclic and other conformationally constrained azo-compounds.49 51 77 Wolf78 has described a scheme for calculating kd based on radical stability (HOMO Jt-deloealization energies) and ground state strain (stcric parameters). 

Fig. 1. Correlation between Thermal Stability and Ground State Strain Eg for hydrocarbons 26 (results from Table 5)...

The interaction between two adjacent bulky groups can depend on steric factors which are not necessarily related to the stability of the radicals produced on homolysis. It is estimated from linear free energy relationships that only 65-70% of the ground-state strain energy is relieved in the transition state for homolysis of a bond between two quaternary centres (Ruchardt and Beckhaus, 1980, 1986). Thus steric constraints to delocalization in the radicals produced may persist. A pertinent example is 2,3-di(l-adamantyl)-2,3-dimethylbutane [123] which has four such centres, linked by the long C-C bonds characteristic of this sort of structure. The strongest... 

The Thorpe-Ingold effect 208 Effects on the formation of larger rings 216 The relief of ground-state strain 217 Orbital steering 222... 

An important question is how far these very large EM s are relevant to the problem of the high efficiency of enzyme catalysis. Ground state strain is built into a molecule when it is synthesized, and organic chemists are very adept at making highly strained compounds. The equivalent process in an enzyme reaction is the formation of the enzyme-substrate complex, and the possibility... 

The data in the tables can generally be interpreted satisfactorily without invoking such orientation effects. This is not to say that they do not exist at all, but simply that they must be relatively small. The major difficulty in identifying any small effect is the elimination of all other possibilities. Storm and Koshland (1972ab) have made the best attempt to do this in their discussion of the relative rates of lactonization of the series of hydroxy and thioacids B.2.1-9 and C.2.1-5, but these rates were found to parallel the equilibrium constants for the lactonization, and it seems probable that the dominant effect controlling reactivity in these systems—and not corrected for—is the relief of ground-state strain discussed above. 

R—C —OMe in the transition state, whereas the larger substituents are assumed to lower the barrier further by increasing the ground state strain. However, as discussed for compounds 9, Sect. II-B-2, the effect on both die C=C and theC—N barriers of going from R = HtoR = Me clearly indicates that already Me makes a sizable contribution to the ground state strain, since R = Me can hardly stabilize the transition state for the C—N rotation. This interpretation is... 

In symmetric overcrowded or otherwise strained ethylenes, the strain may be partially released by rotation around the C=C bond or by other deformations, and the barrier to E-Z isomerization may be lowered compared to that of ethylene by ground state strain and by delocalization of the double-bond ir electrons into unsaturated substituents, forming a diradical transition state. The importance of the delocalization effect is illustrated by the low barrier (AC o = 23.2 kcal/ mol) in the diphenoquinone 125 (145), in which the ground state strain must be rather low. 

The hypothesis that 128 is twisted in solution and that the transition state to E-Z isomerization has perpendicular fluorene groups was supported by a study of 2,3,2, 3 -dibenzo-annelated 128 (159). In this, the steric situation around the double bond is similar to that in 128a, but an improved stabilization of the diradical perpendicular transition state should lead to a lower barrier to E-Z isomerization, as is found (AG 53 = 23.5 kcal/mol). A close approach of the 1 and 1 (8 and 8 ) positions in 128 is indicated by a through-space H- F coupling of 7 Hz in ( )-l, 1 -difluoro-128 (160). In this compound the barrier to E-Z exchange is >25.6 kcal, because of the small contribution of the fluorine atoms to the ground state strain. 

A recent example of a chemical study showing how strain effects could be important in an enzymatic reaction, dealt with the hydrolysis of benzaldehyde di-t-butyl acetal [18] (Anderson and Fife, 1971b). As shown by a Stuart-Briegleb model, substantial ground-state strain is present which would be partially relieved in the... 

General acid catalysis by H2PO4 and imidazolium cation has recently been detected in hydrolysis of 2-methoxy-3,3-dimethyl-oxetane [69] (Atkinson and Bruice 1974). Such catalysis must be due to relief of ground state strain as the ring breaks to give an open-... 

It was all the more satisfying to find a linear correlation (Fig. 1) between the thermal stability of most aliphatic compounds of Table 5 as expressed by ti/2 = Ih or by AG (300 °C), and their ground state strain. The strain energies were obtained by force field calculations and confirmed for a selected number of examples by the determination of heats of combustion This proves that C-C-bond... 

This suggests that at the transition state of this homolytic cleavage reaction 40% of the ground state strain is still present. Under the reasonable assumption that the radicals, which are the cleavage products, are more or less strain-free this means,... 

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