Symmetrically tetrasubstituted [2.2]paracyclophanes: their systematization and regioselective synthesis of several types of bis-bifunctional derivatives by double electrophilic substitution.

The possible number of chiral and achiral tetrasubstituted [2.2]paracyclophanes possessing different types of symmetry (C(2), C(i), C(s), C(2v), C(2h)) is evaluated and a unified independent trivial naming descriptor system is introduced. The reactivity and regioselectivity of the electrophilic substitution of the chiral pseudo-meta- and achiral pseudo-para-disubstituted [2.2]paracyclophanes are investigated in an approach suggested to be general for the synthesis of bis-bifunctional [2.2]paracyclophanes. The mono- and diacylation of chiral pseudo-meta-dihydroxy[2.2]paracyclophane 14 with acetylchloride occur ortho-regioselectively to produce tri- 22, 23 and symmetrically 21 tetrasubstituted acyl derivatives. The same reaction with benzoylchloride is neither regio-, nor chemoselective, and gives rise to a mixture of ortho-/para-, mono-/diacylated compounds 27-31. The double acylation of pseudo-meta-dimethoxy[2.2]paracyclophane 18 is completely para-regioselective. Electrophilic substitution of pseudo-meta-bis(methoxycarbonyl)[2.2]paracyclophane 20 regioselectively generates the pseudo-gem-substitution pattern. Formylation of this substrate produces the monocarbonyl derivatives 35 only, whereas the Fe-catalyzed bromination may be directed towards mono- 36 or disubstitution 37 products chemoselectively by varying the reactions conditions. The diacylation and dibromination reactions of the respective achiral diphenol 12 and bis(methoxycarbonyl) 40 derivatives of the pseudo-para-structure retain regioselectivities which are characteristic for their pseudo-meta-regioisomers. Imino ligands 26, 25, and 39, which were obtained from monoacyl- 22 and diacyldihydroxy[2.2]paracyclophanes 21, 38, are tested as chiral ligands in stereoselective Et(2)Zn addition to benzaldehyde producing 1-phenylpropanol with ee values up to 76 %.