Cycloalkanes synthesis

PERKIN Carboxylic Acid (Ester) Synthesis Synthesis of cycloalkane cartxixylic acids Irom o,ci>-dihaloalkanes and diethyl sodiummalonate. 

In 1978, a German-Swiss team of organic chemists reported the synthesis of a cycloalkane with 96 carbons in its ring (cyclo-C96Hi92). 

Trost and coworkers137 have reported the polymer-supported palladium catalyzed cyclization of 1, l-bis(phenylsulfonyl)epoxyalkene 235 which gives cycloalkanes 236 and 237 in a 2 1 ratio (equation 143). This method has proven useful for the synthesis of macrocyclic compounds under neutral conditions without using high dilution technique. Temperature and concentrations are critical. The best results are achieved if a reaction mixture of 0.1-0.5 m is added to a preheated (at 65 °C) suspension of the catalyst. 

When cycloaikylidine peroxides (e.g., 59) are heated in an inert solvent (e.g., decane), extrusion of CO2 takes place the products are the cycloalkane containing three carbon atoms less than the starting peroxide and the lactone containing two carbon atoms less" (the Story synthesis). The two products are formed in comparable yields, usually 15-25% each. Although the yields are low, the reaction is... 

Acetylene- and Diacetylene-Expanded Cycloalkanes and Rotanes. 201 1 -42 de Meijere A, Kozhushkov SI, Khlebnikov AF (2000) Bicyclopropylidene - A Unique Tetra-substituted Alkene and a Versatile Cj-Building Block. 207 89-147 de Meijere A, Kozhushkov SI, Hadjiaraoglou LP (2000) Alkyl 2-Chloro-2-cyclopropylidene-acetates - Remarkably Versatile Building Blocks for Organic Synthesis. 207 149-227 Dennig J (2003) Gene Transfer in Eukaryotic Cells Using Activated Dendrimers. 228 227-236 de Raadt A, Fechter MH (2001) Miscellaneous. 215 327-345 Desreux JF, see Jacques V (2002) 221 123-164... 

Synthesis of Alkanes and Cycloalkanes 4.18A Hydrogenation of Alkenes and Alkynes... 

Significant synthetic applications of the nickel-salen catalysts are the formation of cycloalkanes by reduction of <>, -a-dihaloalkanes255,256 and unsaturated halides,257,258 the conversion of benzal chloride (C6H5CHC12) into a variety of dimeric products 259 the synthesis of 1,4-butanediol from 2-bromo- and 2-iodoethanol260 or the reduction of acylhalides to aldehydes261 and carboxylic acids.262... 

The bis(trimethylsiloxy)bicyclo[n.l.O]alkane 231 undergoes the FeCl3-induced ring expansion to the cycloalkane-1,3-dione 232. This method has been applied to the synthesis of macrocyclic tetraketones [128]. (Scheme 92)... 

General Procedure for the Hydroformylation/N,N-acetal Formation. Synthesis of Biaza-cycloalkanes. The unsaturated diamine (leq), [Rh(OAc)2h (0.5 mol % Rh atoms) and BIPHEPHOS (2 mol %) were placed in an autoclave under N2 followed by deoxygenated benzene The vessel was flushed and evacuated three times with CO/H2 (1 1,13 bar) and then pressurized to 28 bar. The reaction was kept at 40-80 °C for 20h. The autoclave was cooled and the gases were released followed by selective extraction of the total product with light petroleum. Concentration of the solvent gave in most cases NMR pure material of the title compounds. 

It has been demonstrated that the reaction of azole A -oxides with cycloalkane thiones offers a simple and efficient route to azole-thiones. The described reaction sequence has subsequently been found to constitute a useful synthesis of imidazole-2(3//)-thiones (see Scheme 16). 

In comparison with the 1,3-oxazines, much less attention has been paid to the synthesis of cycloalkane-fused 1,3-thiazines. Only a few 2-thioxo-, 2-imino-, and 2,4-dioxotetrahydro derivatives are known. The most versatile method for the synthesis of the dihydro derivatives is cycloaddition. 

The enthalpy of fomation of two such species has been measured, namely the cyclopropane and cycloheptane derivatives. The difference between the values for these two species, both as solids, is 238.1 kJmol . Is this difference plausible Consider the difference between the enthalpies of formation of the parent cycloalkanes as solids, 194 kJ mol . The ca 44 kJ mol discrepancy between these two differences seems rather large. However, there are idiosyncracies associated with the enthalpies of formation of compounds with three-membered rings and almost nothing is known at all about the thermochemistry of compounds with seven-membered rings. Rather, we merely note that a seemingly well-defined synthesis of cycloheptyl methyl ketone was shown later to result in a mixture of methyl methylcyclohexyl ketones, and superelectrophilic carbonylation of cycloheptane resulted in the same products as methylcyclohexane, namely esters of 1-methylcyclohexanecarboxylic acid. The difference between the enthalpies of formation of the unsubstituted alicyclic hydrocarbons cycloheptane and methylcyclohexane as solids is 33 kJmol . This alternative structural assignment hereby corrects for most of the above 44 kJ mol discrepancy in the enthalpies of formation of the two oximes. More thermochemical measurements are needed, of oximes and cycloheptanes alike. 

There is some increase in selectivity with functionally substituted carbenes, but the selectivity is still not high enough to prevent formation of mixtures. Phenylchlorocarbene gives a relative reactivity ratio of 2.1 1 0.09 in insertion reactions with isopropylbenzene, ethylbenzene, and toluene.132 For cycloalkanes, tertiary positions are about 15 times more reactive than secondary positions toward phenylchlorocarbene.133 Carbethoxycarbene inserts at tertiary C—H bonds about three times as fast as at primary C—H bonds in simple alkanes.134 Because of low selectivity, intermolecular insertion reactions are seldom useful in synthesis. Intramolecular insertion reaction are of considerably more use. Intramolecular insertion reactions usually occur at the C—H bond that is closest to the carbene, and good yields can frequently be obtained. Intramolecular insertion reactions can provide routes to highly strained structures that would be difficult to obtain in other ways. 

The acyloin condensation was used in an ingenious manner to prepare the first reported catenane (see p. 91).727 The catenane (39) was prepared by a statistical synthesis (p. 91) in the following manner An acyloin condensation was performed on the diethyl ester of the C34 dicarboxylic acid (tetratriacontandioic acid) to give the cyclic acyloin 37. This was reduced by a Clemmensen reduction with DCI in D20 instead of HC1 in H20, thus producing a C34 cycloalkane containing deuterium (38) 728... 

Alkanes and cycloalkanes. Obviously a variety of acyclic and cyclic hydrocarbon structures can be synthesized from the appropriate alkyl- or aryl-thiophenes (Scheme 46). The reaction is especially useful for the construction of macrocycles (Scheme 47). One of the most interesting applications of this reaction is in the synthesis of the chiral hydrocarbon butylethylmethylpropylmethane (210) (80JOC2754). The chiral acid (209) was the precursor, in which the thiophene was the potential n-butyl group. Raney nickel desulfurization, followed by standard manipulations to convert the acetic acid unit into an ethyl group, gave the hydrocarbon (210) (Scheme 48) this had [a]578 = -0.198°. It was established that... 

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. 

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