Which isomer is it, 1,2,5,6- or 1,4,5,8-tetrasubstituted cycloocta-1,3,5,7-tetraene? Synthesis of symmetrically tetrasubstituted cycloocta-1,3,5,7-tetraene derivatives

Ni(0) catalyzed cyclotetramerization [(2 + 2 + 2 + 2) cycloaddition] of propargyl alcohol gave D2 symmetric 1,4,5,8-tetrakis(hydroxymethyl)cycloocta-1,3,5,7-tetraene (1) as the major product contrary to what was reported earlier to be the corresponding C2v symmetric isomer, namely 1,2,5,6-tetrakis(hydroxymethyl)cycloocta-1,3,5,7-tetraene. The structure of 1 has been unambiguously assigned on the basis of single crystal XRD data which showed a very interesting "densely" intermolecularly hydrogen bonded solid state supramolecular structure. Tetrabromide (3) prepared from tetra-alcohol (1) reacted with a variety of nucleophiles, namely carbon, nitrogen, sulfur and phosphorus nucleophiles, to give the corresponding derivatives in good yields. The tetraphosphonate derivative (9) underwent the Wittig-Horner reaction with aromatic aldehydes to give the corresponding tetra-styryl derivatives (10a-i). The reaction of tetrabromide with aniline, benzyl amine and R(+)-α-methylbenzyl amine gave the corresponding C2v symmetric pyrroline fused 1,2,5,6-tetra-substituted cycloocta-1,3,5,7-tetraene derivatives, while all the other derivatives belonged to D2 symmetric 1,4,5,8-tetra-substituted cycloocta-1,3,5,7-tetraene. Quantum mechanical calculations support the above conclusion based on the relative stabilities of the two isomers. The fusion of a 5-membered pyrroline ring with the tub-shaped cyclooctatetraene (COT) ring leads to flattening of the tub (shallow tub) making it easier for the ring inversion of COT through a planar intermediate to take place readily resulting in the formation of C2v symmetric pyrroline fused COT derivatives.