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 %.

Novel multichiral diols and diamines by highly stereoselective pinacol coupling of planar chiral [2.2]paracyclophane derivatives.

The TiCl4/Zn-mediated intermolecular pinacol coupling of the planar chiral carbonyl compounds [2.2]paracyclophane-4-carbaldehyde, 4-acetyl[2.2]paracyclophane (ketone) and the four regioisomeric 5-, 7-, 12- and 13-methoxy[2.2]paracyclophane-4-carbaldehydes as well as the pTosOH-Zn/Cu-promoted coupling of their N-substituted imines is described. Coupling of the enantiomerically pure substrates (most of carbonyl compounds and all imines) occurs stereoselectively giving rise to diastereomerically pure 1,2-diols and 1,2-diamines. Racemic aldehydes and ketone react with different degrees of stereoselectivity (depending on the substituents in certain positions) and produce one to three diastereomers. 7-methoxy[2.2]paracyclophane-4-carbaldehyde undergoes a tandem pinacol coupling-pinacol rearrangement to yield bis-(7-methoxy[2.2]paracyclophane-4-yl)acetaldehyde. Coupling of the racemic imines produces a mixture of single racemic D,L-diamine and single meso-diamine in each case. The stereoselective formation of the asymmetric centres is governed by the planar chiral [2.2]paracyclophanyl moiety. The techniques elaborated are extended to the intramolecular coupling of [2.2]paracyclophane-4,13-dicarbaldehyde and its bis-N-phenylimine, resulting in stereoselective formation of the chiral triply-bridged diol and exclusive formation of the meso-diamine. X-Ray investigations of several diols and diamines have been carried out and the structural features of these derivatives are discussed.