Bicyclo ring systems formation

As indicated by the conversion of 70 to 71, the electroreductive cyclization reaction provides as excellent method for the assembly of the bicyclo[3.2.1]oc-tane ring system. Several additional examples are portrayed in the following equations. In general, the use of an unsaturated nitrile rather than the corresponding ester is preferred, as this precludes lactone formation, and therefore... 

Due to the plethora of bicyclo[5.3.0]ring systems in natural products and the limited number of efficient methods that facilitate the construction of seven-membered rings the synthesis of bicyclo[5.3.0]compounds based on a PK reaction has recently been a subject of intense interest. Generally, the preparation of larger ring systems [n.3.0] (n>4) has proven challenging with traditional PK reaction catalysts. One of the few examples reported is the Co2(CO)g catalyzed formation of the azabicyclo[5.3.0j-decenonone derivative 15 (X = OTBS) from the conformationally restricted substrate 14... 

Gorman and Gassman905 have shown that undecatetraenes undergo cyclization (intramolecular Diels-Alder reaction) in the presence of triflic acid to provide bicyclo[4.3.0]nonyl [Eq. (5.332)], bicyclo[4.4.0]decyl, and bicyclo[5.4.0]undecyl [Eq. (5.333)] ring systems, depending on the methyl-substitution pattern. On the basis of a comparative study with varied tetraenes, they concluded that product formation, at least in some cases, could be best interpreted by a stepwise... 

For the period 1995-2006, the formation of fused-ring thietanes from three-membered rings is exclusively confined to the transformation of oxiranes fused to complex ring systems. It was reported <1997PS389> that the 5- y-acetyl-2,3-epoxide derived from D-xylose 116 was easily converted to 2-oxa-6-thia-bicyclo[3.2.0]heptane 117 by the action of sodium acetate (Equation 34). 

The formation of the bicyclo[3.1.0]hexane ring system, found in the thujane terpenes for example, can also involve intramolecular anionic displacement from a cyclohexanone substituted in the 4-position by a leaving group. 

The formation of six-membered rings by contraction from larger, cyclopropane containing, ring systems is rare, but a few examples have been described. The rhodium(I)-catalyzed conversion of bicyclo[6.1.0]nona-2,4,6-trienes 21 to c/s-3a,7a-dihydroindene 22 was more efficient than the straight thermal process. ... 

The minimum energy reaction path after transit through the Cl has also been investigated. Two major reaction channels were identified that lead to the two products. These channels are sufficiently comparable in terms of their topological features that product formation can occur along both routes in approximately equal amounts. It would be expected that substituents that favored one or the other pathway would alter the relative yields of the two types of products. There is also a minor channel that can lead to formation of the bicyclo[3.1.0]hex-2-ene ring system. This situation is represented schematically in Figure 12.31. 

A synthetically useful example of this process is the conversion of 117 to 120, which involves a 1,2-alkyl shift, and was part of Hwu s synthesis of (-)-solavetivone. 38 jhe alkyl fragment is actually part of the bicyclic ling system, one arm of the bicyclo[4.4.0]decane ring system. Reaction of the OH unit with the Lewis acid resulted in formation of the tertiary cation 118, which was followed by a 1,2-alkyls shift to give 119, where the new cation is stabilized by the adjacent silicon of the trimethylsilyl group. 39 Loss of the trimethylsilyl group from 119 gives spiran (120). 

Some perspective is necessary here. As indicated in Chapter 7, Section 4.1 on the Cope rearrangement, the free energy for formation of a cyclohexane-1,4-diyl is 50-53 kcal/mol and that for formation of two allyl radicals is roughly 57 kcal/mol. However, in the current system, the diyl is destabilized by roughly 20 kcal/mol due to the bicyclo[2.2.1]ring system that must be generated. Such a species is kinetically inaccessible due, in part, to a substantial negative entropy despite the fact that the activation enthalpy for its formation would appear to be 50-55 kcal/mol. 

The Weiss-Cook reaction entails the formation of c/5-bicyclo[3.3.0]octane ring systems from the condensation of 1,2-dicarbonyl compounds with 3-oxoglutarate diester derivatives. Decarboxylation of the immediate reaction product affords access to the parent carbon scaffold. 

The most intriguing feature of the final assembly of brevianamides A and B is the mechanism of formation of the novel bicyclo [2.2.2] ring system common to this family of metabolites. Porter and Sammes [14] were the first to suggest the involvement of an intramolecular Diels-Alder reaction for the formation of this ring system and drew the structure shown in Fig. 2 to illustrate this provocative idea. 

Shortly after the publication of the Diels-Alder hypothesis by Porter and Sammes, Birch [15] speculated on the possible modes of formation of the bicyclo [2.2.2] ring system and stated An alternative suggestion (Porter and Sammes 1970) is the occurrence of a Diels-Alder type reaction on a pyrazine, which is perhaps unlikely in view of the unactivated nature of the double bond. Birch offered two other mechanisms, one involving the intermediacy of an epidithiapiperazinedione as shown in Fig. 3, (although he also admits that no sulfur compounds could be detected in the mold products) and also alludes to a radical process no details are given on the latter concept. 

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