Enantioselective (8+3) Cycloadditions by Activation of Donor-Acceptor Cyclopropanes Employing Chiral Brønsted Base Catalysis.
David A McLeodMathias Kirk ThøgersenCasper Larsen BarløseMette Louise SkipperErlaitz Basabe ObregónKarl Anker JørgensenPublished in: Angewandte Chemie (International ed. in English) (2022)
A novel enantioselective (8+3) cycloaddition between donor-acceptor cyclopropanes and heptafulvenoids catalysed by a chiral bifunctional Brønsted base is described. Importantly, the reaction, which leverages an anionic activation strategy, is divergent from prototypical Lewis-acid activation protocols. A series of cyclopropylketones react with tropones affording the desired (8+3) cycloadducts in high yield and enantiomeric excess. For barbiturate substituted heptafulvenes, the (8+3) cycloaddition with cyclopropylketones proceeds in good yield, excellent diastereoselectivity and high enantiomeric excess. The experimental work is supported by DFT calculations, which indicate that the bifunctional organocatalyst activates both the donor-acceptor cyclopropane and tropone; the reaction proceeds in a step-wise manner with the ring-closure being the stereodetermining step.