The Marriage of Organocatalysis with Metal Catalysis: Access to Multisubstituted Chiral 2,5‐Dihydropyrroles by Cascade Iminium/Enamine–Metal Cooperative Catalysis

Abstract

Organocatalyst and metal cooperate: The integration of iminium catalysis and enamine–metal cooperative catalysis into a single process facilitates the rapid and controlled production of valuable chiral pyrrolines in excellent diastereo‐ and enantioselectivities (see scheme).

Highly Enantioselective Cascade Transformations by Merging Heterogeneous Transition Metal Catalysis with Asymmetric Aminocatalysis

“…Thus, by replacing the enolate-type nucleophile 2 with either propargylic alcohol 5 or propargylic amine 6 1530, it was possible to obtain dihydrofurans 7 and dihydropyrroles 8 generally in good to high yields and high ees , respectively (Table 3). …”

Multi-Bond Forming Processes in Efficient Synthesis

“…[128] Specifically, consecutive use of the Grubbs II catalyst, imidazolidinone 36b, and proline brought about a three component union through olefin metathesis and iminium and enamine catalysis (Scheme 20). [128,129] In the search for a library of potentially bioactive compounds, Waldmann and coworkers recently developed a three-component, one pot sequence that proceeds by a striking 12-step mechanism (Scheme 21). [130] The sequence involves two intermolecular Michael additions and various ring-closing and ring-opening steps.…”

“Organo–Metal” Synergistic Catalysis: The 1+1>2 Effect for the Construction of Spirocyclopentene Oxindoles

“…We also investigated the crude reaction with MS (ESI) and found that the iminium intermediate I was formed by condensation between chiral amine 3 a and enal 2 a 15. Based on these observations and former studies by others,8e,f,l–n we proposed the following mechanistic pathway to account for the chemoselectivty and stereochemistry of this reaction (Scheme ). The reaction first starts by formation of an iminium intermediate, followed by the Michael addition to form the chiral enamine intermediate II .…”

“…Taking this into account, and based on our recent studies on “organo–metal” synergistic catalysis8l and asymmetric construction of spirocyclic oxindoles,4d, 9 we envisioned that spirocyclopentene oxindoles might be synthesized by means of an iminium/enamine–metal synergistic catalysis reaction with the combination of a chiral secondary amine and a transition‐metal complex using rationally designed 3‐substituted oxindoles and readily available α,β‐unsaturated aldehydes as starting materials (Scheme ). If implemented, this tactic might present some advantages: 1) providing an alternative strategy to the synthesis of optically pure spirooxindoles; 2) improving the selectivity of amine‐catalyzed conjugate addition of 3‐substituted oxindoles to α,β‐unsaturated aldehydes; and 3) broadening the utility scope of synergistic catalysis.…”