Substituted carbocycles

In monosubstituted cyclohexanes, two conformers can be discriminated by the equatorial (LXXXa) and axial position (LXXXb) of the substituent. While the energy 

In most cases, steric effects control the axial-equatorial equilibrium and favor the equatorial position of the substituents. Indeed, an axial substituent experiences gauche interactions with C-3 and C-5, while the equatorial substituent is trans to C-3 and C-5 and thus relieves the strain of these gauche, interactions. Furthermore, the two axial hydrogens on C-3 and C-5 experience steric interactions with the hydrogen atom (LXXXa) or the substituent (LXXXb) occupying the C-1 axial position. These diaxial 1 /3 interactions are larger with a substituent than with H. 

A compilation of classical substituents and the free energy difference associated with their axial-equatorial equilibrium in monosubstituted cyclohexanes is given in Table 8 [103]. All these substituents prefer the equatorial position, but a 20-fold variation in —AG° values is apparent. However, a very few substituents are known to prefer the axial position. This is the case for the deuterium atom [104], and for the -HgCl substituent (0.3 kcal/mol [105]). 

Considerable conformational complexity is found in disubstituted cycloalkanes, 

Standard free energy change for the axial-equatorial equilibrium in monosubstituted cyclohexane derivatives (from [103]) 

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There are many more syntheses of heterocyclic propellanes from 1,1,2,2-substituted carbocyclic starting materials. The tetrol discussed above, when treated with KHS04 at 170-190 °C affords the dioxa[3.3.2]propellane shown no isomeric spiran is mentioned. Although the yield is only 50% perhaps some dispiran is hiding in the brauner Ruckstand from which the propellane diether is either crystallized at low... 

Enantioselective hydrogenation of 1,6-enynes using chirally modified cationic rhodium precatalysts enables enantioselective reductive cyclization to afford alky-lidene-substituted carbocycles and heterocycles [27 b, 41, 42]. Good to excellent yields and exceptional levels of asymmetric induction are observed across a structurally diverse set of substrates. For systems that embody 1,2-disubstituted alkenes, competitive /9-hydride elimination en route to products of cycloisomerization is observed. However, related enone-containing substrates cannot engage in /9-hydride elimination, and undergo reductive cyclization in good yield (Table 22.12). 

Scheme 10.2 The allylic alkylation/ring-closing metathesis approach to vicinally substituted carbocycles.

Cyclopentyl isoxazolidine cycloadduct 324 was prepared by intramolecular nitrone cycloaddition by Baldwin et al. (280,281,352,353) as part of studies toward a total synthesis of pretazettine (Scheme 1.69). Related adducts have been prepared elsewhere (354—356) including fluorine-substituted carbocycles (357) and the adducts prepared by lOAC by Shipman and co-workers (333,334) who demonstrated their potential as a route to aminocyclopentitols (Scheme 1.66, Section 1.11.2). Such bicyclic structures have been prepared in rather unique intermolecular fashion by Chandrasekhar and co-workers (357a) from the cycloaddition of C,N-diphenyl nitrone to fulvene (325). 

The extension of direct photooxygenation reactions to polycyclic aromatic hydrocarbons as well as to aryl-substituted carbocyclic and heterocyclic pentadienes is due to the (exclusively preparative) work of Dufraisse and Etienne.5-20-29 Investigations on the mechanisms of these reactions were made by Bowen,2 Livingston,3 and Cherkasov and Vember.30-31... 

These reactions are driven by a combination of factors, including a loss of ring strain or the release of a volatile olefin such as ethylene. They can also be kinetically controlled by the formation of a less reactive carbene complex. An important feature of RRM is the catalytic transfer of stereocentres from the corresponding substituted carbocycles, i.e. the chirality embedded in the carbocyclic starting material is completely transferred to the product side chain. This allows chirality to be introduced by means of side chains at the carbocycle. Synthetically, this... 

Benzeneselenenyl iodide, C6H5SeI (l).6 Presumably, this reagent is formed on treatment of diphenyl diselenide with I2 in CH3CN. As expected, when 1 is generated in the presence of a 1,5- or 1,6-diene, selenium-substituted carbocycles are formed, by way of an intermediate that is trapped by acetonitrile. 

Arylannelation of 1,3-dienes.2 In the presence of catalytic amounts of Pd(OAc)2, BU4NCI (1 equiv.), and a base such as Na2C03 or NaOAc (5 equiv.), an aryl iodide reacts with a 1,3-diene (excess) to afford substituted carbocycles. The overall process is believed to involve an intramolecular carbanion displacement of a 7t-ally[palladium intermediate. 

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