Catalytic, Enantioselective Piancatelli Rearrangement

Piancatelli重排反应是一种非常有效的转化反应，通过骨架重排和脱芳构化将呋喃-2-甲醇转化为具有两个新的立体中心的高度官能化的环戊烯酮。然而，目前，对于经典的oxa-Piancatelli重排不存在高度对映选择性的方法，并且总共仅开发了少数对映选择性方法。本项目旨在广泛研究布朗斯台德酸催化的首次高对映选择性的Piancatelli重排反应。作为底物，我们通常使用3-供体取代的呋喃-2-甲醇，其将产生宽范围的高度官能化的环戊烯酮。BINOL-磷酸将被用作手性催化剂，这导致了高的对映体选择性的初步工作，从而构成了坚实的基础，为进一步的工作。首先，我们将研究具有广泛变化的甲醇取代的仲甲醇和叔甲醇的重排。除了骨架重排与水作为亲核醇，酰胺和氨基甲酸酯将被调查作为亲核试剂在分子间和分子内的方式。此外，碳亲核试剂将用于发展第一个对映选择性carba-Piancatelli重排反应。特别注意将致力于3-供体取代基内的呋喃被认为是负责的速率加速重排。除了芳基之外，将研究其他+M-取代基如卤素，其优点在于在产物中建立适合于进一步官能化的额外官能团。为了进一步拓宽反应的范围，将这种方法扩展到容易获得的亚芳基异苯并呋喃醇将被研究，这让人想起Piancatelli中间体。在优化的条件下，它们将与上述亲核试剂反应，得到手性3-官能化茚满酮。最后，将进行一系列后续转化，包括Baeyer-Villiger氧化、Beckmann重排和共轭加成，以将Piancatelli产物转化为对映体高度富集形式的有价值的精细化学品，如二氢香豆素和二氢喹诺酮。

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.