Five-membered-ring Carbocyclic Compounds

Ylide reactions have become powerful tools for constructing cyclic compounds, through many types of useful transformations (such as Wittig 

Larhed and others have demonstrated that the yield of Heck reaction product between two small molecules can be dramatically improved using a rapid microwave-assisted intermolecular reaction. For example, the aryl bromide 

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Dipolar cycloaddUions. Interest in 1,3-dipolar cycloadditions increased dramatically during the past 20 years, largely because of the pioneering studies of Huisgen [7, 2] The versatility of this class of pericychc reactions in the synthesis of five-membered-ring heterocyclic compounds is comparable with that of the Diels-Alder reaction in the synthesis of six-membered-ring carbocyclic systems (equation 1)... 

Cyclopentadienyl compounds of the form CpCo(CO)2 are also known to convert l,n-enynes into the tranditional 1,3-diene cycloisomerization products (486, 487). Remarkably, the metathesis reaction is independent of tether length between both unsaturated functional groups, and leads to five-membered ring carbocycles exclusively (Scheme 60). 

In the construction of carbocycles, five-membered ring formation has been used for preparing fused cyclic compounds, such as functionalized diquinanes. ° The reaction of 36 with (TMSlsSiH furnished the expected product 37 in 80% yield and in a or.fi ratio of 82 18, as the result of a kinetic controlled reaction (Reaction 43). 

Heteroaromatic compounds do not undergo the same variety of photocycloadditions with alkenes as do their carbocyclic counterparts. There are very few reports of this type of reaction for six-membered ring compounds such as pyridines, but five-membered ring systems such as furans do give 1,2-cycloadducts with a range of alkenes (e.g. 357). 

Volumes 3 and 4 cover five-membered rings with two heteroatoms, or more than two heteroatoms, respectively, each with their fused carbocyclic compounds. 

The syntheses of l,2,3,5,6,8a-hexahydroindolizine (1) and (-)-swainsonine were successfully carried out via a ROM-RCM strategy, and final CM with ethylene to free the ruthenium. Two different synthetic routes were implemented to achieve a similar compound. In the case of l,2,3,5,6,8a-hexahydroindolizine 1, the six-membered ring was established first using RRM and in the case of (-)-swainsonine, the five-membered ring was established first. In both cases, the ring rearrangement precursors were enantiomerically pure five-membered carbocycles, which can be synthesised efficiently from racemic starting materials. 

We will take a semiempirical approach using numerous molecules, models, assumptions, and estimates rather than doing new calorimetric experiments and/or quantum chemical calculations. Indeed, we will also test what is probably the simplest assumption - that (4n + 2) n electrons found within a conjugated ring species is expected to result in enhanced stability and that this compound is called aromatic. We will consider the dihydroindene (indane) skeleton composed of a benzene ring fused to a nonaromatic five-membered ring that lacks additional double bonds, and will use this carbocyclic hydrocarbon with X = Y = Z = CH2 as a paradigm for many heterocyclic derivatives for which the possible aromaticity is of relevance to the current chapter. Similarly we use indene with -X-Y- = -CH=CH-, Z = CH2 for a variety of unsaturated heterocycles of interest here. 

An interesting carbocyclization process was observed when alkenyl stannanes were treated with electrophilic selenenylating reagents containing a non-nucleo-philic counterion. Thus, Nicolaou showed that compound 213 reacted with AT-PSP 11 to form the intermediate 214 which then afforded the cyclopropane derivative 215 (Scheme 32) [109]. Further examples were reported by Herndon [110]. As indicated in Scheme 32, in the presence of tin tetrachloride, the stannane 216 was converted into the cyclopentane derivative 217. This cyclization reaction proved to be quite general with respect to a variety of substitution patterns but it appears to be restricted to the formation of three- and five-membered ring. 

Another example from the Spanish authors [14, 35] is especially interesting, as the cycloaddition leads to the formation of a compound with a seven-membered ring (Scheme 9). The literature shows that in recent years a tremendous amount of effort has been expended in trying to prepare carbocyclic five-membered rings by a route as simple and elegant as the Diels-Alder reaction for the synthesis of six-membered rings. [4c] Is a counterpart for... 

We have seen both [4+2]- and [2+2]-cycloaddition reactions in previous sections. There is another class of cycloaddition reactions that involve a molecule containing a n bond (an alkene, alkyne, etc.-see 419) with a highly polarized and usually ionic compound that is called a 1,3-dipole. 1,3-Dipoles usually take the form of 418. When these two react, a five-membered ring is generated. Depending on the nature of a-e, carbocyclic or heterocyclic rings can be formed, and a variety of substituents can be incorporated on the ring.337 This section will explore this class of reactions. 

In the majority of dehydration reactions, heterocyclic compounds are formed, rather than carbocyclic compounds. Many possibilities for formation of carbocyclic compounds exist, but these are important only if (a) the heterocyclic or acyclic tautomers cannot undergo further elimination reactions, or (b) the conditions of reaction greatly favor the formation of an acyclic tautomer capable of affording only the carbocyclic compound. Both five- and six-membered carbocyclic compounds have been isolated, with reductic acid being the compound most frequently reported. Ring closure occurs by an inter-molecular, aldol reaction that involves the carbonyl group and an enolic structure. Many examples of these aldol reactions that lead to formation of carbocyclic rings have been studied.47 As both elimination and addition of a proton are involved, the reaction occurs in both acidic and basic solutions. As examples of the facility of this reaction, pyruvic acid condenses spontaneously to a dibasic acid at room temperature in dilute solution, and such 8-diketones as 29 readily cyclize to form cyclohexenones, presumably by way of 30, either in acid or base. 

Dicarbonate 14 was used as the starting material to achieve both cis-and trans- ring rearrangement precursors 15 and 16. ROM-RCM of the five-membered carbocycles 15 and 16 leads to 17 and 18. These compounds contain a terminal double bond at position 9, which can be easily functionalised and are set up to form the tricyclic tetraponerines. 

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