Preparation of Cycloalkanes

Figure 5.5. Preparation of cycloalkanes on cross-linked polystyrene [45-48],...

Cycloalkanes,6 Treatment of <, o>-diiodides with r-BuLi in pentane-ether at - 23° provides an attractive route to three-, four-, and five-membered cycloalkanes. The corresponding dibromides do not undergo the same clean cyclization. The reaction is not useful for preparation of cycloalkanes containing more than five carbon atoms. 

Preparation of 2-Cycloalkenones and Cycloalkane-1,3-diones BY Iron(III) Chloride-Induced Ring Opening of 1-Trimethyi,-siLYLOxY- AND 1,2-Bis(trimethylsilyloxy)bicyclo[w.1.0]alkanes... 

In the linear versus cyclic case, n-hexane oxidizes 18.9 times as fast as cyclohexane (see Fig. 6-6) however, under slightly different conditions (same temperature and pressure, acetone solvent) and a slightly different preparation of TS-1, n-hexane oxidizes only 4.8 times as fast as cyclohexane.45 These differences in TOFs between the linear and cyclic isomers are also attributed to the size restrictions of the zeolite. When the channel diameter is increased, as in the Ti-(1 catalyst (-6.5 A), larger cycloalkanes, such as cyclododecane, can be oxidized.45... 

The tellurolate-promoted anfi -debromination by method G is extended to the preparation of conjugated dienes, starting from 1,2,3,4-tetrabromoalkanes and cycloalkanes, 1, 4-dibromo-2-aIkenes and aUylic dibromides. ... 

The most versatile method for the preparation of m-hexahydro-1,3-benzoxazines and the related cycloalkane e -fused dihydrooxazines is amidoalkylation via 1,4-polar cycloaddition of the amidomethyl ion 172 to a cycloalkene. The addition is stereospecifically cis, and in accordance with the Markownikov rule is generally regiospecific. 

Introduction of the allene structure into cycloalkanes such as in 1,2-cyclononadiene (727) provides another approach to chiral cycloalkenes of sufficient enantiomeric stability. Although 127 has to be classified as an axial chiral compound like other C2-allenes it is included in this survey because of its obvious relation to ( )-cyclooctene as also can be seen from chemical correlations vide infra). Racemic 127 was resolved either through diastereomeric platinum complexes 143) or by ring enlargement via the dibromocarbene adduct 128 of optically active (J3)-cyclooctene (see 4.2) with methyllithium 143) — a method already used for the preparation of racemic 127. The first method afforded a product of 44 % enantiomeric purity whereas 127 obtained from ( )-cyclooctene had a rotation [a]D of 170-175°. The chirality of 127 was established by correlation with (+)(S)-( )-cyclooctene which in a stereoselective reaction with dibromocarbene afforded (—)-dibromo-trans-bicyclo[6.1 0]nonane 128) 144). Its absolute stereochemistry was determined by the Thyvoet-method as (1R, 87 ) and served as a key intermediate for the correlation with 727 ring expansion induced... 

ALKANES, CYCLOALKANES AND THEIR DERIVATIVES Preparation of add anhydrides... 

Catalytic reforming has become the most important process for the preparation of aromatics. The two major transformations that lead to aromatics are dehydrogenation of cyclohexanes and dehydrocyclization of alkanes. Additionally, isomerization of other cycloalkanes followed by dehydrogenation (dehydroisomerization) also contributes to aromatic formation. The catalysts that are able to perform these reactions are metal oxides (molybdena, chromia, alumina), noble metals, and zeolites. 

In addition to the alkylations discussed above, some special reactions have been reported that enable the solid-phase synthesis of cycloalkanes. These include the intramolecular ene reaction and the cyclopropanation of alkenes (Figure 5.5 see also [44]). Cyclobutanes have been prepared by the reaction of polystyrene-bound carbanions with epichlorohydrin, and by [2 + 2] cycloadditions of ketenes to resin-bound alkenes. 

In general, thermodynamically stable trans olefins are formed, while cis olefins are obtained in the case of 1,2-dixanthates derived from cycloalkan-l,2-diols. Here, instead of the Bu3SnH/AIBN system, environmentally benign Ph4Si2H2/AIBN, Ph2SiH2/AIBN, and Af-ethylpiperidine hypophosphite/AIBN systems can also be used. As a typically useful method, preparation of D4T (2/,3/-didehydro-3/-deoxythymidine) analogue, which has the same potent anti-HIV activity as AZT, is shown in eq. 7.16. In practice, D2C (2/,3/-dideoxycytidine) and D4C (2/,3/-didehydro-2/,3/-dideoxycytidine) were also prepared by this method [39, 40]. 

The reaction tolerated various functional groups, thus allowing the in situ preparation of allylboron compounds possessing a carbonyl group (Equation (32)).236 The tandem diboration-intramolecular allylboration provided a diastereoselective access to the cycloalkanes bearing 1,3-diols. 

Reductive dehalogenation is an efficient method of synthesis of cyclopropanes spiroannulated to five- and higher-membered carbocycles (i.e. compounds in which spiroannulation does not result in accumulation of extra strain) . The required gem-(dihalomethyl)cycloalkanes are usually prepared by halogenation of the precursor diols (equation 1). The cyclization is most efficiently accomplished in the Zn-alcohol-water system . For example, spiro[2.5]octane 7 was prepared in 91% yield using this procedure. This method is useful even for a one-step preparation of bis-spirocyclopropyl compounds as exemplified in equation 2. However, the application of the reductive dehalogenation method to the synthesis of more strained SPC (i.e. spirohexane or spiropentane) often leads to rearranged products. For example, methylenecyclopentane was the only product obtained from bis(bromomethyl)cyclobutane (equation 3) ... 

The preparation of thiamacrocycles of the cyclophane type by substitution of thiolates on suitable substrates usually leads to the desired products in good yields [55], favoured by the rigid group principle [56] and by application of the dilution principle [1]. On the other hand yields of conformative flexible thia-cycloalkanes under similar conditions as a rule are not satisfactory and often low... 

Asinger, F., Vogel, H. H. The preparation of alkanes and cycloalkanes, in Houben-Weyl, Methoden der Organischen Chemie (ed. Muller,... 

For some time the main emphasis of Friedel-Crafts reactions was chiefly on aromatic compounds. The development of aliphatic Friedel-Crafts chemistry was of minor importance until World War 2, when isomerization of alkanes and cycloalkanes, preparation of high-octane aviation gasoline and synthetic rubber, and polymerization of alkenes achieved considerable importance these contributed to the growth of aliphatic Friedel-Crafts chemistry. 

The preparation of allyltitanium compounds including those having functional groups is described by reaction of allylic halides or allylic alcohol derivatives with the system Ti(OPr1)4/MgXPr1 (X = C1, Br) (Scheme 7).24 Analogous allyltitanium complexes have also been reported by treatment of Ti(n) species with allylic alcohol derivatives, which proceeds via an oxidative addition pathway. Their reactions have been studied.25-27 These compounds are used to promote efficient syntheses of alkylidenecyclopropane and cycloalkane derivatives by regioselective reactions with carbonyl compounds,28,29 the stereoselective syntheses of optically active substituted piperidines and pyrrolidines... 

The silyl-Hilbert-Johnson method of nucleoside synthesis, using trimethylsilyltriflate as catalyst, is useful for the preparation of N-3 nucleosides (e.g., from 4-carbamoylimidazolium-5-olate) <84JHC529>, and a similar silyl displacement method has been used to make 1-alkylthio- and 1-phenylthio-l-trimethylsilyloxyalkanes and -cycloalkanes. This latter process uses 1-trimethyl-silylimidazole (177) and trimethylsilyltriflate as catalyst <84CHE662, 90S104>. The use of two equivalents of the thiol prevents the formation of imidazole adducts (Scheme 116) <90S104>. 

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