The use of anthrone in cycloaddition reactions was first investigated in the early 1980s, when it was used as a template in the first stereospecific synthesis of conduritol A. The major benefit of this approach is the oxide-anion accelerated retro-Diels-Alder reaction, which can relieve the substrate from the template at room temperature, avoiding the use of harsh conditions such as flash vacuum pyrolysis. Organocatalysed asymmetric cycloadditions of anthrone have been widely studied, with Rios reporting ee’s of up to 99% using a bifunctional thiourea catalyst. Since cycloadditions of anthrone allow for opportunities to make a variety of pharmaceuticals and natural products, such as the caspase inhibitor, Berkeleyamide A, and Salinosporamide A, which has shown to be cytotoxic to cancer cells, it is a strategy worthy of exploration. In this work, unusual and unexpected results were found following reinvestigations into organocatalysed anthrone cycloadditions by both Rios and Kagan. Mechanistic studies have been carried out in order to establish the role of the catalyst within the reaction. There have been interesting solvent and substrate effects in maleimide cycloadditions, which have led to ee’s in excess of 79% and conversions over 90%. The potential for elaboration of this work to various targets, including Berkeleyamide A, thereby negating the use of protecting groups, has been investigated.

Re-examination of the enantioselectivity in asymmetric organocatalysed cycloadditions of anthrone

256th National Meeting (2018)

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