Bicyclic compounds, conformations

The bicyclic compound decahydronaphthalene, or bicyclo[4.4.0]decane, has two fused six-mem-bered rings. It exists in cis and trans forms (see Fig. 1.10), as determined by the configurations at the bridgehead carbon atoms. Both cis- and rran -decahydronaphthaiene can be constructed with two chair conformations. 

In some molecules, the twist conformation is actually preferred. In all cis-2,5-di-fert-butyl-l,4-cyclohexanediol, hydrogen bonding stabilizes the otherwise high-energy form and 1,3-dioxane 89 exists largely as the twist conformation shown. Of course, in certain bicyclic compounds, the six-membered ring is forced to maintain a boat or twist conformation, as in norbornane or twistane. 

Intramolecular cyclopropanation is a useful method for construction of [n.l.0]-bicyclic compounds.17-21 225 275 As a matter of course, alkenyl and diazo groups of the substrate are connected by a linker and the transition-state conformation of intramolecular cyclization is influenced by the length and the shape of the linker. Thus, the enantioselectivity of the reaction often depends upon the substrates used. Use of a catalyst suitably designed for each reaction is essential for achieving high enantioselectivity. 

Cyclohexane sometimes adopts a twist-boat conformation, but never a true boat structure, which represents an energy maximum, But boat structures are important in some bicyclic compounds where the compound simply doesn t have any choice in the conformation it adopts. The simplest compound locked into a boat structure is norbornane. The CH2 bridge has to be diaxial (otherwise it can t reach), which means that the cyclohexane ring part of the structure has no choice but to be a boat,... 

In contrast to the results for monocyclic compounds, in bicyclic compounds the rigidity of bridged structure frequently permits more substantial effects than in acyclic or monocyclic compounds. The bridging locks the cyclohexane ring into the boat and/or twist-bond conformation. For example, bicyclo [2.2.1] heptane and bicyclo [2.2.2] octane have one and two boat cyclohexane rings respectively. The enthalpies of the boat and twist-boat conformers of cyclohexane are 27 and 23 kJ/mol higher than that of the chair conformer. Therefore, bicyclo [2.2.1] heptane and bicyclo [2.2.2] octane have ring strains of 64 and 54 kJ/mol, respectively, as shown in Table 4. 

Several comprehensive summaries of the conformation of monocyclic compounds8, t7 99 100"101) and bicyclic compounds77,1035 are available. However, only a few conformational analyses of bicyclic compounds having oxygen atoms have been done. 

First of all, the stereochemistry about the cyclobutane in the photoadducts is cis in almost all cases (equations 64-68). There are rare exceptions, but these usually result from systems where the cy-cloalkenone is larger than six members or when the tethering chain can easily accommodate the trans cyclobutane (equations 6 72). " The most noteworthy exception is the recent example reported by Winkler in which dioxolenone (35) produced exclusively the trans cycloadduct (36) which was readily converted to the smallest known inside-outside bicycloalkanone (37). This photoproduct presumably arises from initial cyclization in the chair-like conformation (38) (equation 73). Similarly, (39) has been converted to the carbon skeleton of the naturally occurring inside-outside bicyclic compound ingenol (equation 74). ... 

In a study related to the conformational properties of the cyclohexane-fused six-membered heterocycles, new bicyclic dithiolanes, 285-/ra r (Scheme 52) and 285-crr (not shown), were prepared along the reaction pathway, as precursors used further for the syntheses of 2-methyl substituted and unsubstituted /ra r-fused 4a,5,6,7,8,8a-hexahydro-2//,4//-1,3-benzodithiines, exemplified by structure 288-/ra ir (R=R = H) <2002JOC1910>. Thus, ditosylation of cis-Z-hydroxymethyl cyclohexanol 284, and subsequent reaction with sodium sulfide and sulfur, provided a mixture of new bicyclic products 285 and 286, albeit in very low yields, with configurational inversion at C-1. These were reduced by LiAlH4 to provide /ra r-2-mercaptomethyl cyclohexanethiol 2 l-trans. Upon acetalization or transacetalization, the desired 2SS-trans derivative was obtained. The same methodology with the precursor 2E4-trans was extended to the preparation of the r-fused bicyclic compounds 285-288. 

Regioselectivity is markedly enhanced in conformationally more biased systems such as carbohydrates and fused bicyclic compounds. Some examples are shown in Scheme 17. - ... 

Heathcock s diastereoselective aldol method (chapter 4) gave the required anti-aldol 144 but only in low yield. Removal of the /V-ben/yl group allowed the amine to cyclise onto the aryl ester and the bicyclic compound 145 of fixed conformation is formed. Notice that all the substituents are on the outside (exo face) of the folded molecule (chapter 21). The further development of 145 into lactacystin can be found in the paper.22... 

A conjugated diene that is locked in an s-cis conformation, such as 1,3-cyclopentadi-ene, is highly reactive in a Diels-Alder reaction. When the diene is a cyclic compound, the product of a Diels-Alder reaction is a bridged bicyclic compound—a compound that contains two rings that share two nonadjacent carbons. 

You have already seen, in our discussions of the n + 1 Rule, that in a hydrocarbon chain the protons attached to the same carbon may be treated as a group and do not split one another. How, then, can it be said that coupling exists in such cases if no spin-spin splitting is observed The answer comes from two sources. First is the fact that geminal coupling is often observed in cyclic compounds that are conformationally rigid—for instance, bicyclic compounds such as bicyclo[2.1. Ijhexane. 

Syn eliminations may occur in compounds that cannot adopt a conformation in which the H and X groups are antiperiplanar. This is apparent in some bridged bicyclic compounds, where anti elimination is disfavoured by steric or conformational factors (2.7), and in compounds where a strongly electron-attracting substituent on the p-carbon atom favours elimination in that direction, outweighing other effects. Elimination by a syn pathway preserves the requirement for coplanarity of the breaking ct-bonds however, in most cases anti ehmination is preferred. 

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