The rapid synthesis of 1,4-dioxygenated xanthones and related natural products employing the Moore rearrangement as a key transformation has been developed. The approach features an acetylide stitching step to unite a substituted squaric acid with a protected hydroxy benzaldehyde derivative to provide a key intermediate that undergoes facile Moore rearrangement to deliver a hydroxymethyl aryl quinone. Subsequent oxidation, hydroxy group deprotection and cyclization then affords highly functionalized xanthones. The utility of the approach was demonstrated by its application to a concise and efficient synthesis of the naturally-occurring xanthone 1. The structure of a natural product that had been named dulcisxanthone C was also corrected to that of the xanthone 1.

A facile entry to 1,4-dioxygenated xanthones having a variety of substitution patterns and substituents was developed that features a novel application of the Moore cyclization using substrates that were readily assembled in a highly convergent fashion by an acetylide stitching process. The practical utility of the methodology was demonstrated by an efficient synthesis of a naturally-occurring xanthone and correction of the structure of dulcisxanthone C.

Concise Approach to 1,4-Dioxygenated Xanthones via Novel Application of the Moore Rearrangement. -A general route is developed for xanthones (V), which are otherwise difficult to obtain, via Moore rearrangement (II) → (III). Further investigations, i.e. methylation of hydroxyl substituents, reveal that the reported structure (VIIIa) for dulcisxanthone C has to revised to (VIIIb). -(NICHOLS, A. L.; ZHANG, P.; MARTIN*, S. F.; Tetrahedron 68 (2012) 37, 7591-7597, http://dx.

General and Expedient Synthesis of 1,4-Dioxygenated Xanthones. -The desired title compounds are available starting from the corresponding salicylaldehyde substrates. The naturally occurring xanthone (IX) is synthesized in 7 steps and an overall yield of 22%, a significant improvement compared to former procedures. The designed structure (X) for dulcisxanthone C is revised to be consistent with (IX). In the case of precursors (XII), spirocycles (XIII) and xanthones (XIV) are formed as inseparable mixtures. The spirocycles can be easily rearranged to the xanthones under mild conditions. -(NICHOLS, A. L.; ZHANG, P.; MARTIN*, S. F.; Org. Lett. 13 (2011) 17, 4696-4699, http://dx.