Strain in Ring Systems

Molecules which contain rings comprise an important subset of organic compounds. In many respects their behavior and properties are identical to those of functionally analogous open-chain systems. In other respects, however, the greater structural order imposed by a ring causes the properties of cyclic compounds to be quite different than analogous open-chain systems. These differences 

It is possible to measure the heats of combustion for a series of saturated hydrocarbons and thereby determine how much energy is released (—A//comb) when a -CH2-group in a saturated hydrocarbon reacts with oxygen. Thus the heat of combustion of an open-chain methylene group is —157.4 kcal/mol. (The heat of combustion is negative because heat is evolved.) 

Hydrocarbon - A//comb/-C H2-unit (kcal/mol) A(A//comb) vs. Open Chain (kcal/mol) Total Strain (kcal/mol) 

The smaller bond angles prevent normal overlap along the intemuclear axis (dotted line). Overlap occurs outside the intemuclear axis and a bent bond is formed (also referred to as a r bond). The r bond is weaker than a a bond due to nonoptimal overlap and thus is of higher energy. This type of strain is termed angle strain (sometimes called Baeyer strain). It comes about because normal bond angles are not possible and thus nonoptimal overlap results. Angle strain 

To achieve a bond angle of 90°, cyclobutane must be planar. This would force the adjacent C-H bonds to be eclipsed and would also raise the energy of the system. As a compromise, cyclobutane folds diagonally by 35°. While this raises the angle strain somewhat, it decreases the eclipsing interactions so that the lowest possible energy is attained. While each methylene group is less strained than one in cyclopropane, the total molecular strain is similar to that of cyclopropane. 

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In 1980, a Merck group disclosed the results of a model study which amply demonstrated the efficiency with which the strained bicyclic ring system of thienamycin can be constructed by the carbene insertion cyclization strategy.12 Armed with this important precedent, Merck s process division developed and reported, in the same year, an alternative route to carbene precursor 4.13 Although this alternative approach suffers from the fact that it provides key intermediate 4, and ultimately thienamycin, in racemic form, it is very practical and is amenable to commercial scale production. The details of this interesting route are presented in Schemes 4-6. 

These examples illustrate the issues that must be considered in analyzing the stereoselectivity of enolate alkylation. The major factors are the conformation of the enolate, the stereoelectronic requirement for an approximately perpendicular trajectory, the steric preference for the least hindered path of approach, and minimization of torsional strain. In cyclic systems the ring geometry and positioning of substituents are often the dominant factors. For acyclic enolates, the conformation and the degree of steric discrimination govern the stereoselectivity. 

The reaction of azetidines with dinitrogen pentoxide is found to reflect the reduced ring strain in this system compared to aziridines.Accordingly, while the carbamate and V-alkyl... 

Levoglucosan 14, which is derived from Z)-glucose, has a strained ether ring system. Oxidation in methanol causes carbon-carbon bond cleavage to yield D-arabinose. High yields are obtained in methanol with addition of sodium methoxide... 

In later works, the name seems to include highly congested and strained multi-ring systems. 

This was followed by a long series of studies in which the rearrangement of other strained organic ring systems was catalyzed by transition metal salts or complexes. A typical example is the conversion of quadricyclene to norbomadiene, catalyzed by Rh(I) or Pd(II) (equation 4), for which Halpem provided the accepted mechanism. An extensive review of this early work is available. 

The stepwise, oxidative cycloaddition mechanism [particularly with d metal systems 1 )] could intervene in the valence isomerizations of strained, cyclobutane ring systems where energy factors and difficulties in attaining bidentate coordination work in its favor. For the other processes, however, where bidentate coordination is either very favorable or guaranteed, its contribution to catalytic chemistry would seem to be significantly less. 

The question of how the value of Jch is affected by location of the cyclopropane ring in more strained fused ring systems has been addressed by consideration of bicyclo[ 1.1.0]butane, 40. Wiberg s group showed that for this compound,... 

The hrst example, reported by Craig and Munasinghem [135] and shown in Scheme 7.88, illustrates the types of strained fused-ring systems available from the delivery of nucleophilic species to adjacent centers. 

In addition to torsional strain (eclipsing interaction) and steric strain (nonbonded interaction), the compression of internal bond angles in ring systems leads to an additional type of strain angle strain. 

A route " in which the 3,4-bond is made by an intramolecular pinacol reaction is nicely illustrated by the formation of a tricyclic thiophene with two cyclobutane fused rings. In this example, it was necessary to force the double dehydration required for aromatisation, because of the strain in the system. Starting materials for this route are easily obtained from sodium sulfide and two mole equivalents of a 2-bromo-ketone. 

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