Dual Catalysis

Vicinal stereocenters are commonly found in natural products, bioactive molecules, and potential drugs. Constructing vicinal stereocenters through Csp3-Csp3 bond formation is a significant focus in asymmetric catalysis. Over the past five years, our group has concentrated on developing a platform for stereodivergent Csp3-Csp3 coupling reactions using Pd-involved synergistic catalysis. We have integrated the nucleophile-activation modes into the Pd catalysis, allowing us to pursue a series of stereodivergent Csp3-Csp3 coupling reactions of dienes (including 1,3-dienes, alkoxyallenes, and allenamides) with various carbon nucleophiles, such as aldimine esters, aldehydes, oxindoles, and pentafluorophenyl esters. These reactions provide quick access to a variety of chiral scaffolds containing vicinal stereocenters in a stereodivergent manner.

One of the most powerful synthetic tools to emerge over the years to rapidly achieve molecular complexity from readily accessible precursors in an enantioselective manner is asymmetric dual catalysis.[1] In this presentation, we will disclose our recent contributions to this field of asymmetric chemical synthesis with a chiral Brønsted acid at the core of these studies.[2–5] We will highlight a study that realised a method for the chemo- and enantioselective assembly of 1,8-dihydroindeno[2,1-b]pyrroles and pyrrol-2-yl methanols that exploited the gold(I)- and “hidden” chiral Brønsted acid-catalysed reactions of β-amino-1,4-enynols.[2–4] In the presence of a “hidden” chiral N-triflyl phosphoramide, tandem asymmetric dehydrative Nazarov-type electrocyclisation/hydroamination of the substrate was found to selectively occur to afford the synthetically useful indeno-fused pyrrole derivative.[6] On the other hand, changing to a “hidden” chiral phosphoric acid was observed to result in a hydroamination/enantioselective formal 1,3-allylic alcohol isomerisation cascade to give the 1H-pyrrole. An electron-donor acceptor complex, generated from the Hantzsch ester and N-(acyloxy)phthalimide ester, and chiral Brønsted acid catalytic system to enable the Minisci-type C2-alkylation of quinolines, isoquinolines and pyridines under blue light emitting diode light (456 nm) will also be discussed.[5]

Synergistic catalysis has emerged as a powerful synthetic strategy for new reaction development in asymmetric catalysis. Through the synergistic effect between different catalytic systems, the simultaneous activation of different reaction components can be readily realized, which effectively reduces the reaction barriers and improves the reaction activity and efficiency, thus realizing asymmetric chemical transformations that are impossible or inefficient using traditional mono-catalysis, especially stereodivergent synthesis of chiral molecules with multiple stereogenic centers. In this presentation, I will report our recent progress in synergistic catalysis with metallated azomethine ylides as stereochemically controllable nucleophilic reagents.