Ring systems cyclohexane derivatives

In cyclic systems, the usual simple requirements of Saytzev or Hofmann rules may be overridden by other special requirements of the system, e.g. the preference for elimination from the truns-diaxial conformation in cyclohexane derivatives (cf. p. 255). Another such limitation is that it is not normally possible to effect an elimination so as to introduce a double bond on a bridgehead carbon atom in a fused ring system (Bredt s rule), e.g. (47) (48) ... 

Recently a new ring system, 2-oxa-4,10-diazaadamantane, was prepared as its derivatives from 2,4-dinitrophenol (217).241 2,4-Diacetylaminophenol (218) is reduced to the cyclohexane derivative (219), which is cyclized either... 

Bridging allenes such as 32 in the 4- and 5-positions by a butano fragment results in either the ds-cyclohexane derivative 347 or its trans-isomer. When the former is thermally isomerized the 10-membered ring system 348 is generated in practically quantitative yield, whereas trans-347 yields the diastereomer 349 [146],... 

Finally, also in connection with functional groups, there is a set of heuristic principles" which refer to the stability of aromatic and conjugated systems, as well as to the relationship between more or less unsaturated cyclohexane rings and benzene rings ("HPs-6"). For instance, through a series of well known reactions, it is possible to establish a relationship between p-methylanisole and cyclohexane derivatives with different levels of unsaturation (Scheme 4.13) ... 

In principle, a number of different types of acetal or ketal might be produced. In this section, we want to exemplify a small number of useful reactions in which two of the hydroxyl groups on the sugar are bound up by forming a cyclic acetal or ketal with a snitable aldehyde or ketone reagent. Aldehydes or ketones react with 1,2- or 1,3-diols under acidic conditions to form cyclic acetals or ketals. If the diol is itself cyclic, then the two hydroxyl groups need to be cA-oriented to allow the thermodynamically favourable fused-ring system to form (see Section 3.5.2). Thus, dx-cyclohexan-1,2-diol reacts with acetone to form a cyclic ketal, a 1,2-O-isopropylidene derivative usually termed, for convenience, an acetonide. 

Hydrogenative ring opening of cycloalkanes is also a well-studied area.16 252 253 289-292 Mainly cyclopropanes and cyclopentanes were studied, since three- and five-membered adsorbed carbocyclic species are believed to be intermediates in metal-catalyzed isomerization of alkanes (see Section 4.3.1). Ring-opening reactivity of different ring systems decreases in the order cyclopropane > cyclobutane > cyclopentane > cyclohexane.251 Cyclopropane and its substituted derivatives usually react below 100°C. 

Many newer methods for generating cyclohexane derivatives from carbohydrates still depend on the intramolecular attack of nucleophilic carbon species at electrophilic centers, and the range of options is now extensive. Thus, the nucleophiles may be carb-anions stabilized by carbonyl, phosphonate, nitro, or dithio groups, and they may bond to carbonyl carbon atoms, or to those that carry appropriate leaving groups or are contained in epoxide rings, or as jj-centers of a,p-unsaturated carbonyl systems. Otherwise, the nucleophilic activity at the 7-centers of allylsilanes or a-positions of vinyl silanes may be used to react with electrophilic carbon atoms. 

Free radical reactions are used less frequently, to effect six- rather than five-membered ring closures, because carbohydrate-derived hept-6-enyl radicals are less available than are hex-5-enyl analogues, these being the species required for normal exo ring closure processes. Such reactions can, however, be used with good efficiency to produce cyclohexane ring systems bearing a carbon substituent (see Chap. 25). 

Ring systems phenyl, pyridine, pyrane, thiophene, pyrimidine, dioxolan, naphthalene, cyclohexane,. .. and derivatives... 

Further investigations on the synthesis of ring system 8 started from the 1,3,5-trisila-cyclohexane derivatives. A reaction sequence is proposed in Eq. (25). 

Configurational isomerism is encountered in bi- and polysubstituted cyclic molecules, as well as in fused ring systems. In the simple case of bisubstituted monocyclic systems, cis-trans-isomehsm exists provided that the two substituents are not gemi-nal. Thus, 1,2-, 1,3- and 1,4-disubstituted cyclohexane derivatives (LII) show this... 

Control of the stereochemistry of the Diels-Alder reaction by means of a chiral center in the substrate is a versatile means of synthesizing cychc systems stereoselec-tively [347]. For preparation of ring systems with multi-stereogenic centers, in particular, the diastereoselective Diels-Alder reaction is, apparently, one of the most dependable methods. The cyclization of optically active substrates has enabled asymmetric synthesis. Equation (147) shows a simple and very efficient asymmetric Diels-Alder reaction, starting from commercially available pantolactone [364,365], in which one chlorine atom sticking out in front efficiently blocks one side of the enone plane. A fumarate with two chiral auxiliaries afforded virtually complete stereocontrol in a titanium-promoted Diels-Alder reaction to give an optically active cyclohexane derivative (Eq. 148) [366,367]. A variety of diastereoselective Diels-Alder reactions mediated by a titanium salt are summarized in Table 13. 

Having discussed the electron-transfer reactions of cyclopropane derivatives in some detail, we only touch briefly on the related reactions of the larger ring systems. Cyclobutane, cyclohexane, and cyclooctane have degenerate HOMOs (Section 2.3.1) thus, their radical cations are Jahn-Teller active. It is reasonable to expect that suitable substitution will lift the degeneracy and favor one radical cation structure over the other. Qualitative predictions of the preferred structure are readily derived. 

As for derivatives of unstrained ring systems, we mention—in passing—the electron-transfer oxidation of various mono-, di-, or trialkylcyclohexanes, which were studied in significant detail. Interestingly, the radical cations of 1-alkyl and 1,1-dialkyl derivatives have been assigned a SOMO resembling the ag SOMO of the cyclohexane radical cation [169-171]. A more detailed discussion would exceed the scope of this review. 

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