Dimeric orsellinic acid derivatives:: Valuable intermediates for natural product synthesis

Herein we report on the synthesis of dimeric orsellinates by the Ullmann reaction as well as by biomimetic oxidative phenolic coupling. The Ullmann reaction gives the 5,5'- and 3,3'-coupled dimeric orsellinates 9 and 10 regioselectively. Oxidative phenolic coupling reaction of methyl 2-hydroxy-4-methoxy-6-methylbenzoate (2) affords the regioisomeric dimeric orsellinates 11 (3,3'), 12 (5,5') and 13 (3,5') simultaneously, which can be separated easily by column chromatography. The atropisomers of the 5,5'- and 3,3'-coupled dimers 9 and 10 were partially resolved using chiral column chromatography. Additionally, the enantiomers of 3,3'-dimeric biaryl 11 could be obtained in pure form by derivatizing racemic 11 with chiral auxiliaries, separating the diastereomers by column chromatography and cleaving the auxiliary groups. Thereby the absolute configuration of the biaryl axis in camphanate ester (M)-18 could be determined by X-ray structure analysis. The dimeric orsellinates rac-10 and (P)-10 were used for the synthesis of the dimeric dihydroanthracenones 21a-b by a tandem Michael-Dieckmann reaction. ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007).