Trans-Decalin, conformation

Examine the structure of cyclodecane, a molecule which contains the same number of carbons as decalin, but only has one ring (a model of the most stable conformation is provided). Compare it to cis and trans decalin. Make a plastic model of cyclodecane. Is it flexible or locked What conformational properties of cyclodecane can be anticipated from the properties of decalins What properties cannot be anticipated How do you account for this ... 

The trans-decation has a center of symmetry, midway between C9 and C10 and is therefore an optically inactive molecule. The cis-decation is dissymmetric and has two interconvertible conformations, but the trans-decalin is a rigid molecule. 

In the trans-decalin systems 329T, the substituents occupy well-defined axial or equatorial positions, whereas in the mobile ds-decalin system 329C, the substituents occupy either the equatorial or the axial orientation and, if the framework equilibrium is unbiased (as in decalin itself), the preferred conformation will be that with the equatorial substituent. Although this is mainly true for the 1,3-hetero analogs as well, there are also other factors (discussed later) to be taken into account. 

At this point, it probably will be helpful to construct models of cis- and trans-decalins to appreciate the following (a) The two compounds cannot interconvert unless C-C or C-H bonds first are broken, (b) traw -Decalin is a relatively rigid system and, unlike cyclohexane, the two rings cannot flip from one chair form to another. Accordingly, the orientation of the substituent is fixed in the chair-chair conformation of trans-decalm, (c) The chair-chair forms of cw-decalin are relatively flexible, and inversion of both rings at once occurs fairly easily (the barrier to inversion is about 14 kcal mole-1). A substituent therefore can interconvert between axial and equatorial conformations (Figure 12-24). 

The protonation leads specifically to the trans-decalin system, though reduction could apparently give rise to two stereoisomeric products. The guiding principle appears to be that protonation of the intermediate allylic anion 12 takes place axially, orthogonal to the plane of the double bond, and to the most stable conformation of the carbanion which allows the best sp3-orbital overlap on the /Tcarbon with the -orbital system of the double bond. 

A mild procedure for regioselective ring-opening./. Org. Chem. 1985, 50, 1557-1560. Smissman, E. E. Parker, G. R. Conformational aspects of systems related to acetylcholine. 5. Synthesis of the dl-2(e)-methyl-, dl- 3(e)-mefhyl, and dl-2(e),3(e)-dimethyl-3(a)-trimeth-ylammonium-2(a)-acetoxy-trans-decalin halides./. Med. Chem. 1973, 36, 23—27. Carbonelle, A.-C. Gott, V. Roussi, G. 

Build models of cis- and trans- decalin and examine the conformational mobility of each. 

Figure 9.4 shows stereogenic epoxide formations with S ylides and a ketone. The substrate is a conformationally fixed—because it represents a trans-decalin—cyclohexanone. Both the dimethylsulfoxonium methylide and the dimethylsulfonium methylide convert this cyclohexanone into an epoxide diastereoselectively. As Figure 9.4 shows, the observed diastereoselectivities are complementary. The sulfoxonium methylide attacks the carbonyl carbon equatorially, whereas the attack by the sulfonium ylide takes place axially. 

This sequence serves to exemplify the formation and aspects of reactivity of toluene-p-sulphonate esters in monosaccharide systems, and further to illustrate the selective protection afforded to hydroxyl groups by the formation of cyclic acetals by reaction with carbonyl compounds. Thus reaction of methyl a-D-glucopyranoside (26) with benzaldehyde in the presence of zinc chloride gives the 4,6-acetal (27) (Expt 5.118), wherein two fused six-membered rings of the trans-decalin type are present. As a cognate preparation the reaction of benzaldehyde with methyl a-D-galactopyranoside results in a similar conversion to a 4,6-acetal, but in this case the product is the conformationally flexible system of the cis-decalin type, the most likely conformation being that shown below. 

The frans-fused 6/6 systems—trans-decalins—have been very widely studied because they appear in steroids (Chapter 51). Their conformation is discussed in Chapter 18 and conformational control simply extends what we saw with simple six-membered rings. 

Zonfirming the conformations experimentally means measuring coupling constants in the f NMR so we need to look at the vital protons (marked H on the diagrams below) and der whether they can be seen in the spectrum. Fortunately, the interesting protons are all next nctional groups so they can be seen. We probably can t see the axial proton at the ring junction. e first example but trans-decalins must have axial protons there, so that is not so important. 

The two isomers have ds and trans ring junctions so we should first make conformational drawings. The trans compound is easy as it has a fixed conformation like a trans-decalin (p. 463). The ds mpound can have two conformations as both rings can flip. 

The formation of the intermediate iminium ion (23) in the reaction thus involves loss of the 60-H which is trans diaxial, i.e. antiperiplanar, to the N—O bond of (22). Although the IV-oxide (22) could conceivably undergo the Polonovski reaction via its alternative c -decalin conformer, this is highly improbable because in this conformation the three ring substituents would be axially oriented. Accordingly, the structure of an A(-oxide cannot always be correlated with that of the firee base because of the possibility of nitrogen inversion (compare 21 with 22). 

The most potent members of all of these series of decalin-derived molecules have anti-planar Tg stereochemistry. In the series of cyclohexane-derived compounds (231), the XRy2Ii)-trans compound was an extremely weak muscarinic and the ( )-cis-isomer was completely inert (275). Casy (256) suggested that an energetically unfavored trans-diaxial conformer (antiplanar Tg) for structure (231) may be the pharmacologically active form of the molecule. However, introduction of at-bu-tyl group into the cyclohexane system to sta-... 

Since both isomers 2 and 5 are trans-decalins, an additional criterion of identity is the order of elution. The effect of a methyl group to increase retention times of the monomethyldecalins (see Table XXIV) is in the order eqiiatorial-2 (20.4), eqtuitorial-1 (22.5), axial-2 (23.6), and axial-1 (27.3). In isomer 2, the methyls are equatorial-l, axial-2 (22.6 + 23.6 = 46.1) in isomer 6, they are axial-l, equatorial-2 (27.3 + 20.4 = 47.7). Thus isomer 2 would be expected to be eluted faster than isomer 5. Where there is a difference in conformational energy, the dimethyl conformational energies. In the 10 sets, comprising all 34 dimethyl-irana-decalins, there is only one exception to this rule. 

No reaction—the bromines are trans, but they are diequatorial because of the locked conformation of the trans-decalin system. E2 can occur only when the bromines are trans diaxial. 

Among the most important of the bicyclic hydrocarbons are the two stereoisomeric bicyclo[4.4.0]decanes, called cis- and franx-decalin. The hydrogen substituents at the ring junction positions are on the same side in c/x-decalin and on opposite sides in trans-decalin. Both rings adopt the chair conformation in each stereoisomer. 

Miscellaneous Photochemical Reactions.—14a-Steroids are converted into an equilibrium mixture of 14oc- and 14j8-isomers ca. 1 19) on irradiation at 254 nm, in cyclohexane containing mercuric chloride or bromide/ The reaction comprises abstraction of 14-H and recombination, probably involving bromine atoms. Other isomerisations at tertiary hydrogen permit equilibrations, e.g. of cis- and trans-decalins, but the 5)3 — 5a-steroid conversion is very slow compared with reaction at C-14. Distortion from ideal bond-angles at C-14 probably loosens the hydrogen atom here. Axial secondary methyl substituents can also be epimerised into the more stable equatorial conformation. 

In both cis- and trans-decalin, the cyclohexane rings can be in chair conformations. The relative energies will depend on the number of axial substituents. 

There is an important difference between the cis- and /rani-decalin systems with respect to their conformational flexibility. Owing to the nature of its ring fusion, trans-decalin is incapable of chair-chair inversion c/x-decalin is conformationally mobile and undergoes ring inversion at a rate only slightly slower than cyclohexane (AG = 12.3-12.4 kcal/mol). The/ranx-decalin system is a conformationally locked system and can be used to compare properties and reactivity of groups in axial or equatorial environments. 

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