Catalytic, Enantioselective Piancatelli Rearrangement

Piancatelli重排反应是一种非常有效的转化反应，通过骨架重排和去芳构化反应将呋喃-2-甲醇转化为具有两个新的立体中心的高官能化环戊烯酮。然而，目前对于经典的oxa-Piancatelli重排还不存在高度的对映选择性过程，总共只开发了少数的对映选择性过程。我们打算在这个项目中广泛地研究Bronsted酸催化的第一个高度对映选择性的Piancatelli重排反应。作为底物，我们通常使用3-取代呋喃-2-甲醇，这将产生广泛的高度官能化的环戊酮。BINOL-磷酸将被用作手性催化剂，这在前期工作中导致了高的对映选择性，从而为进一步的工作奠定了坚实的基础。首先，我们将研究甲醇取代度变化较大的仲醇和叔醇的重排反应。除了作为亲核醇与水的骨架重排外，酰胺和氨基甲酸酯还将作为亲核剂在分子间和分子内进行研究。此外，碳亲核试剂将用于开发第一个对映选择性的Carba-Piancatelli重排反应。将特别注意呋喃中的3-给体取代基，它被认为是加速重排的原因。除了芳基以外，还将研究其他+M-取代基，如卤素，以便在产品中建立适合进一步官能化的额外官能团。为了进一步扩大反应的范围，我们将研究将这一方法扩展到容易获得的芳基异苯并呋喃类化合物，这些化合物类似于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-官能化吲哚类化合物。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产品转化为对映体高度浓缩的有价值的精细化学品，如二氢香豆素和二氢喹诺酮类。

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.