Bicyclic rings, strain

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. 

When the bicyclic thiirene oxide 180164 is dissolved in excess furan, a single crystalline endo-cycloadduct (182) is formed stereospecifically (equation 71)164. This is the first propellane containing the thiirane oxide moiety. Clearly, the driving force for its formation is the release of the ring strain of the starting fused-ring system 180. In contrast, 18a did not react with furan even under forcing conditions. 

The difference in behavior of the cis- and trans-isomers 43 and 45 is ascribed mainly to the greater ring strain in the trans-isomer which results in a more favorable free energy change for its polymerization. This result is similar to that reported for the polymerization of cis- and frans-8-oxabicyclo[4.3. OJnonane 48 and 4936. The molecular weights of the polymers of the bicyclic ether 49 were, however, much higher than those of the polymers of the bicyclic acetal 45. 

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. 

Some information concerning ring strain and amide resonance can be obtained by comparing monocyclic and bicyclic /3-lactams. Monocyclic /3-lac-tams are very resistant to alkaline and acid hydrolysis [70] [71] due to reso-... 

Useful bicyclic ring systems are obtained by (TMS)3Si radical-mediated fragmentation of strained ketoalkene precursors. For example, the ketoalkene 64 reacted with 1.5equiv of silane to give 95% of hydrindanone 65 (Reaction 7.67) [78]. (TMS)3Si radical adds first to the terminal alkene and the carbon-centred radical can relieve the strain by cleaving the adjacent C—C bond. 

Smaller cyclic olefins react with dibromocarbene to give the gem-dibromo-bicyclic systems, but these have not been reported to give allenes on reaction with methyl- or n-butyllithium. One possible reason may be the severe ring strain of cyclic allenes with less than seven carbon atoms. For example, Moore and Ward [14] found that 7,7-dibromobicyclo[4.1.0]heptane reacts with methyllithium to give bicyclic carbene intermediates which can be trapped with olefins (Eq. 4). 

Theorists believe that the symmetry of the n system is imposed by the framework of a bonds. Bond alternation in the n system can be forced by the fusion of strained bicyclic rings [248] such as in [4]phenylene [249], tricyclobutabenzene [250], or trisbicyclo[2.1.1]-hexabenzene [251] ... 

A possible mechanism that features a six-membered transition state is given in Scheme 18 (38, 43). The high catalytic activity stems from the excess strain of the B=N bond in the 5/5-fused bicyclic ring system, which results in strong coordination of the angular nitrogen atom to BH3 to form the active dinuclear species. The rate and stereoselectivities of the reaction of trihalomethyl ketones has been explained on the basis of the X-ray analysis of the substrates. 

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