Three-membered carbocycles

Takahashi and coworkers have reported three types of formation of cyclopropane derivatives from five-membered zirconacycles. One is via reaction of carbenes or carbenoids with carbon-carbon double bond in zirconcy-clopentadienes (Eq. 30) [30], the second via jS-elimination from zirconacy-clopentenes (Eq. 31) [31] and the third via intramolecular Michael addition (Eq.32) [32]. 

Both of the carbene species, CX2 and CH2, which were generated in situ by the standard procedures, could smoothly react with one a,jS-C=C bond in zir-conacyclopentadienes without interference with Zr-C bonds to give cyclopropane derivatives after hydrolysis (Eq. 30) [30]. This was the first example of reaction of the a,j3-C=C bond in metallacyclopentadienes. 

The reaction of zirconacyclopentenes with homoallyl bromides afforded al-lylcyclopropane derivatives with diastereoselectivity through intramolecular alkylation (Eq. 31) [31]. A a-substituted homoallylic bromide produced predominantly the cfs-isomer for the disubstituted cyclopropane moiety, while a j0-substituted one gave the trans-isomer as a main product. 

Titanacyclopentenes are formed from the reaction of Cp2TiEt2 and alkynes as described above (Eq.20) [18]. However,interestingly,when a silylated acetylene such as 1-trimethylsilyl-l-propyne was used, l-methyl-l-(trimethylsi-lyl)methyl cyclopropane, other than the expected titanacyclopentene, was formed (Eq. 33) [18]. This reaction chemistry is different from that of analogous zirconocene. Formation of a titanocene-carbene complex is proposed via Michael addition-type reaction in the titanacyclopentene intermediates. 

Cyclobutadiene is one of the most attractive molecules. A conceptually new and simple method using intramolecular coupling of l-metallo-4-halobutadiene was reported to form cyclobutadiene derivatives by Takahashi and coworkers (Eq. 34). l-Zircona-4-halobutadiene derivatives, generated in situ by treatment of zirconacyclopentadienes with one equivalent of iodine, react in the presence 

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About a hundred new structures containing a three-membered carbocyclic ring are added to the CSD in a year. The wealth and diversity of the relevant material render a thorough and systematic treatment of all classes of cyclopropane derivatives impossible. I have selected mainly simple molecules and systems of some structural interest, and have resorted to earlier studies in some cases in order to include some basic molecules. Fused... 

A variety of three-membered carbocycles including cyclopropylcarbonyl and -sulfonyl derivatives, cyclopropylcarbonitriles and -methanols, nitrocyclopropanes, cyclo-propanols and cyclopropylamines have been prepared via the 1,3-elimination of HX. Some representative cyclopropyl derivatives recently prepared by this method are shown in Scheme 116-18 and in equations 8-26. Conversion of chelated homoserine, 5,to chelated 2-amino-4-bromobutyrate and treatment with aqueous base directly affords chelated 1-aminocyclopropane-l-carboxylate (equation 8)19. The 1,3-elimination in 6 interestingly leads to the preferential formation of the cis isomer, from which 7, a key structural element of synthetic pyrethroid insecticides, is obtained (equation 9)20. A sulfur substituent can serve both as an activating group and as a leaving group in this type of reaction and, thus, 1,3-bis(phenylthio)propane affords cyclopropyl phenyl sulfide upon treatment with butyl-... 

The Michael addition of nuleophiles to acceptors carrying a leaving group at the y-posi-tion leads to intermediates capable of undergoing an intramolecular displacement to afford three-membered carbocycles (equation 28). A major side-reaction is direct Sw2... 

Diazo compounds have been extensively used in the preparation of three-membered carbocycles either as carbene sources or as precursors for 1-pyrazolines or 3//-pyrazoles. Nitrogen extrusion from pyrazolines is particularly valuable for the synthesis of alkylcy-clopropanes, since the direct carbene route is impractical, as a matter of fact, owing to rapid intramolecular processes in alkylcarbenes. The cycloaddition of diazo compounds to unsaturated bonds to give 1-pyrazolines and 3/f-pyrazoles usually proceed in a concerted manner, and hence is stereospecific. In the subsequent nitrogen extrusion from the adducts,... 

Cyclopropyl ketones 1 can be made by cyclisation of some derivative of the y-hydroxy-ketone 2. Notice that we proposing to make a three-membered carbocyclic ring from an easily made three-membered Tetracyclic ring. 

But chrysanthemic acid derivatives are by far not the only examples of cyclopropane-containing structures in nature. In fact, the highly strained three-membered carbocycle is virtually ubiquitous. It occurs, for example, in every green plant in the form of 1-aminocyclopropanecarboxylic acid (ACC) 2, a direct precursor to the plant hormone ethylene [3]. In addition, the cyclopropane unit is found in a variety of other natural products, inter alia in terpenes and in various cyclopropanated fatty acids [4]. The biochemical precursors of the latter are unsaturated fatty acids, and in view of the existence of polyunsaturated fatty... 

Reactions of cyclopropane derivatives activated by one type of functional group have been well understood and applied in organic synthesis for quite some time1). The far-reaching analogy between reactivity of olefins and cyclopropanes can be explained by the tc-type orbitals of strained three membered carbocycles and their interaction with the activating substituents 2,3>. 

As mentioned before, this route to heterocycles by ring enlargement of three-membered carbocycles should be extendable to other electrophiles having cumulated double bonds X=Y=Z. Addition of ketenes or allenes, on the other hand, might provide interesting carbocyclic systems. 

Diazo compounds have widely been used in the synthesis of three-membered carbocycles either as car bene sources or as precursors for 1-pyrazolines or 3H-pyrazoles. The latter route is particularly valuable for the alkylmethylenation of activated multiple bonds, since alkylidenes (the former route) generally give very poor results owing to their susceptibilities to rapid intramolecular insertion reactions. 

The cyclopropane chemical reactivity, which closely resembles that of an olefinic double bond, stems from the electronic properties of this three-membered carbocycle Effectively, cyclopropyl and olefinic groups interact with neighbouring 7c-electron systems and p-electron centres they both add acids, halogens and ozone, undergo catalytic hydrogenation and cycloaddition, form metal complexes, etc. 

Draw one canonical form for each of the following aromatic compounds a three-membered carbocyclic cation with 2 electrons (n=0, 3 p sub-orbitals) a five-membered carbocyclic anion with 6 electrons (n= 1, 5 p sub-orbitals) and a six-membered neutral ring containing one nitrogen atom and five carbon atoms (n= 1, 6 p sub-orbitals). 

Treatment of the bis(propynyl)zirconocene 759 with B(C6Fs)3 results in a linear G-G coupling of the alkynyl ligands to form the zwitterionic complex 76 0582,583 (Scheme 186). Complex 760 reacts with nitriles R CN to form initially the 1 1 adduct 761 that concurrently equilibrates with 760 and the metallacyclocumulene 762 (and the nitrile-borane adduct) subsequently, irreversible reaction in the presence of excess nitrile yields the methylene-cyclopropene derivative 763.584,585 Calculations have shown that the conversion 760 —> 763 is probably triggered by nitrile addition to the metal with formation of a planar-tetracoordinate carbon intermediate that features coordination of the three-membered carbocycle through one of its G-G cr-bonds. 

The general tendency of three-membered heterocycles, to react via open chain (1,3-dipolar) isomersis less pronounced for three-membered carbocycles. 

Cyclopropenes may serve as starting materials for the preparation of three-membered carbocycles in two different ways, as indicated by the arrows below ... 

Three-membered carbocycles 3,3-Disubstituted 1,1,2,2-tetracyanocyclopropanes can be obtained by electrolysis of 10 in the presence of ketones and NaBr in ethanol. ... 

Three-membered carbocycles 1,1,2,2-Tetracycanocyclopropane was prepared in a one-pot synthesis from TCNE and diazomethane. First pyrazoline 364 is formed by cycload-... 

A potent and selective inhibitor of biosynthesis of the leukotrienes is the 5,6-methano derivative of leukotriene-A4 ( methano implies a three-membered carbocyclic ring formed by the bivalent substituent CH.j) (Nicolaou, Petasis and Seitz, 1981). Another approach is afforded by the pyrazoline drug 14.22) known as BW 755C which went into clinical trial in 1980. It inhibits an enzyme which synthesizes the leukotrienes (Higgs, Flower and Vane, 1979). 

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