Catalytic, Enantioselective Piancatelli Rearrangement

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The Piancatelli rearrangement is a very powerful transformation to convert furan-2-carbinols into highly functionalized cyclopentenones with two new stereogenic centers upon skeletal rearrangement and de-aromatization. Currently, however, a highly enantioselective process does not exist for the classic oxa-Piancatelli rearrangement and altogether merely a handful of enantioselective processes have been developed at all. We intend to broadly study the Bronsted acid-catalyzed, first highly enantioselective Piancatelli rearrangement in this project. As substrates we will generally employ 3-donor-substituted furan-2-carbinols which will give rise to a broad range of highly functionalized cyclopentenones. BINOL-phosphoric acids will be utilized as chiral catalysts which have led to high enantioselectivity in the preliminary work and thus constitute a solid foundation for further work. First, we will study the rearrangement of secondary and tertiary carbinols with broad variation of the carbinol substitution. Beyond the skeletal rearrangement with water as nucleophile alcohols, amides and carbamates will be investigated as nucleophiles both in an inter- and intramolecular fashion. In addition, carbon nucleophiles will be employed towards the development of the first enantioselective carba-Piancatelli rearrangement. Special attention will be devoted to the 3-donor substituent within the furan which is considered responsible for the rate acceleration of the rearrangement. Besides aryl groups other +M-substituents such as halogens will be studied with the advantage to establish an additional functional group in the products suitable for further functionalization. To further broaden the scope of the reaction the extension of this methodology to easily accessible arylidene isobenzofuranols will be investigated which are reminiscent of the Piancatelli intermediates. Under the optimized conditions they will be treated with the above-mentioned nucleophiles to furnish chiral 3-functionalized indanones. Finally, a range of follow-up transformations including Baeyer-Villiger-oxidations, Beckmann rearrangements and conjugate additions will be conducted to convert the Piancatelli products into valuable fine chemicals such as dihydrocoumarins and dihydroquinolones in enantiomerically highly enriched form.