Meta- and paracyclophane

Gibson, S.E., Jones, J.O., KaUndjian, S.B. er al. (2004) Synthesis of meta- and paracyclophanes containing unsaturated amino acid residues. Tetrahedron, 60, 6945-58. 

The resonance structures 65 suggest that the pseudo-meta and pseudo-geminal positions are the preferred sites for substitution however, it has been observed (e.g. in the bromination and acetylation of 4-bromo[2.2]paracyclophane (67)) that there is predominant formation of pseudo-ortho and pseudo-para products 8 3b>8 5> (see Table 3) ... 

While for several phanes such as [njparacyclophanes, dioxa[n]para or [2.2]meta-paracyclophanes, the assignments by this rule were in agreement with the experimental results, they had to be revised for [2.2]meta- and [m][n]paracyclophanes after the application of more reliable methods. These discrepancies were discussed in previous sections (2.6.1, 2.9.1). A quadrant rule proposed for cyclic ketones includes also the configurational assignment to oxo[2.2]metacyclophanes (61-63) and stereoisomeric alcohols derived therefrom 113). 

Different types of cyclophanes, such as ortho-, meta-, or paracyclophanes, were obtained via the intermolecular Pd-catalyzed [4 - - 2] cross-benzannulation of cyclic enynes with diynes [2Id]. For example, cyclophane-type compound 78, containing both meta- and orthocyclophane motifs, was synthesized upon reaction of enyne 79 and diyne 80 (Scheme 14.30). 

If one now considers disubstituted Pc derivatives, particular descriptors are employed to designate the relation between the two positions. For substituents on the same phenyl ring, ortho, meta, and para prefixes are still valid, while inter-ring disubstitution gives rise to pseudo-gem, pseudo-ortho, pseudo-para, and pseudo-meta prefixes (Figure 8.3). Finally, a last remark about the configurational stability of Pc derivatives chiral [2.2]paracyclophanes can indeed racemize above 200°C by a process that was proven to involve benzylic-bond homolytic scission, rotation, and recombination of the diradical. 

Fig. 1. Plane of Chirality Enantio-morphous figures and corresponding torsional angles A—X—Y—Z 7). Molecular examples ([n]paracyclophane, [2.2]meta-cyclophane, bridged[10]anulene and ( )-cyclooctene) with descriptors (/ , S)...

The nomenclature of phanes is simple 32) It mainly defines the length(s) of the bridge(s) and their positions in the ring as illustrated by the following examples [6]para-cyclophane (2) 1,10-dioxa [10]paracyclophane (6), [2.2]paracyclophane (7), [2.2]meta-(8) and [2.2]metaparacyclophane (9) and [8](2,5)pyridinophane (70). The formulae show also the kind of projection used in this survey to illustrate stereochemical relations. 

Pyramidalization is not limited to superphanes. Suitably short para and meta bridges induce significant departures from planarity also in cyclophanes. Typical examples, where the deformation is spread over more than one formal double bond, are given by the highly strained [2.2]paracyclophane (73) and the [m]paracyclophanes (m = 6-12) (74) (87). Evidence for a still smaller member of this family of compounds, [4]paracyclophane 75, has recently been reported (88). Essentially no structural or computational results have been reported for betweenanenes. These are bicyclic compounds of type 76, in which formally two trans-cycloalkcnes share the double bond. This structural relationship suggests a /llu-type deformation for the highly shielded double bond, similar to that found in overcrowded olefins (89). 

In 2010, Collins and coworkers [62] developed additives to aid Ru-catalyzed olefin metathesis macrocyclizations (Scheme 12.36). The macrocyclization to form strained paracyclophanes is challenging, and control of the substrate conformation is often crucial toward ensuring product cyclization. As such, the authors developed a quinolinium-based additive that interacts with the substrate, enforcing conformations conducive to ring closure, even under elevated temperatures in the presence of a competing ir-rich solvent like toluene. The macrocyclization to form the [12] and [13]paracyclophanes 121, 122, 124, and 125 or the [12]meta-cyclophane 123 were all possible through the addition of the quinolinium salt 126 to the olefin metathesis reaction mixture. No macrocyclization products... 

There are several stereoisomers in disubstituted [2.2]paracyclophane, such as ortho-, meta-, para-, pstudo-ortho-, pseudo-m fa-, pseudo-para-, and pseudo-g mma/-disubstituted [2.2]paracyclophanes. Iron-catalyzed dibromination of commercially available [2.2]paracyclophane yields the mixtures of the dibromo[2.2]paracyclo-phane isomers, and pseudo-para-dibromo[2.2]paracyclophane 9 can be obtained by recrystallization as it has the poorest solubility in common organic solvents [76]. Thermal isomerization of 9 in triglyme afforded the psowdo-ortho isomer 38, as shown in Scheme 10. This transformation is an equilibrium reaction when the reaction was allowed to cool to room temperature, pseudo-para isomer 9 was precipitated as a result of its low solubility and was readily separated by simple filtration to obtain pseudo-arf/za isomer 38 in moderate isolated yield [76]. V ondo-ortho-dibromo[2.2]paracyclophane 38 was converted into pseudo-arf/ a-diethynyl[2.2] paracyclophane 40 via pseudo-arf/ a-diformyl[2.2]paracyclophane 39 (Scheme 10) [77]. Sonogashira-Hagihara coupling polymerization of 40 with 12 afforded the corresponding jc-stacked polymer 41 in 23 % isolated yield with the of 3,800 [78]. 

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