Attempts to find a solution to the problem of atropisomer interconversion in 1,8-diarylnaphthalenes and 5,6-diarylacenaphthenes

摘要

A series of sterically restricted 5,6-diarylacenaphthenes 5, 11, 12, 13 and 14 have been prepared via Suzuki cross-ncouplings of the appropriate boronic acids with 5,6-dibromoacenaphthene 3 in an attempt to prevent atropisomerninterconversion in these systems. Attempts to further functionalise bis(p-methoxyphenyl) system 5 in the positionnortho to the methyl ethers by Friedel–Crafts acylation or metallation were unsuccessful; however, two unexpectednproducts were obtained. p,pu0001-Dimethoxybiphenyl 6 results from an unexpected rearrangement of 5 under stronglynbasic conditions and is dependent on the base used, whilst acylated derivative 7 results from a Friedel–Craftsnacylation of the acenaphthene scaffold in the 3-position, rather than the desired functionalisation of the peri-arylnrings, presumably due to the difficulty in forming a tetrahedral intermediate. The oxygen functionality in 5 has beennused, following methyl ether cleavage via diphenol 8 and allylation via 9, to demonstrate the viability of a doublenClaisen rearrangement yielding 11 after acetylation. However, the broad n1nH NMR exhibited by 11 clearly showednthat this system is not configurationally stable, hence steps were required to access more sterically demanding systemsnwhich would be configurationally stable. Molecular mechanics and semi-empirical simulations were carried out onnrelated biaryl systems to determine if a single bulky substituent in the 3-position of the peri-aryl rings would bensufficient to prevent atropisomer interconversion. The modelling showed that the energies of the syn- and anti-natropisomeric forms, e.g. for 12–14, were surprisingly similar. With the objective of preparing conformationallynstable molecules in this class in mind, 12–14 were prepared in remarkable yield for such a hindered system. In spitenof extensive attempts to determine whether 13 was configurationally stable, enantiomeric separation could not benachieved. Unsuccessful attempts were thus made to detect the presence of stable atropisomeric forms of 13 throughnthe synthesis of bis(benzyl ether) 19, in which the benzylic protons could act as enantiotopic reporters. In additionnmandelate ester 20 was prepared and it was shown by n1nH NMR that a mixture of anti- and syn-diastereoisomersnhad been obtained. It was therefore concluded that steric groups in the 3-position of the peri-aryl rings cannot benused to prevent atropisomer interconversion in 1,8-diarylnaphthalenes and 5,6-diarylacenaphthenes. During attemptsnto access diphenols 18 and 24, other by-products were isolated, i.e. 21 and 25 respectively, resulting from a stericnstrain-induced 1,2-aryl shift.