Enantioselective Organocatalyzed Transformations of β-Ketoesters

Abstract

The β-ketoester structural motif continues to intrigue chemists with its electrophilic and nucleophilic sites. Proven to be a valuable tool within organic synthesis, natural product, and medicinal chemistry, reports on chiral β-ketoester molecular skeletons display a steady increase. With the reignition of organocatalysis in the past decade, asymmetric methods available for the synthesis of this structural unit has significantly expanded, making it one of the most exploited substrates for organocatalytic transformations. This review provides comprehensive information on the plethora of organocatalysts used in stereoselective organocatalyzed construction of β-ketoester-containing compounds.

Bifunctional Ammonium Salt Catalyzed Asymmetric α‐Hydroxylation of β‐Ketoesters by Simultaneous Resolution of Oxaziridines

“…These hybrid catalysts were found to be very promising for a variety of reactions like asymmetric α‐halogenations of β‐ketoesters 2 or cascade reactions, and the modular synthesis approach allows for a rapid fine‐tuning of catalyst structure for a given target reaction . Keeping in mind the high value of chiral α‐hydroxy‐1,3‐dicarbonyl compounds and the resulting current interest in the development of asymmetric synthesis methods, we became interested in testing the potential of our catalyst system for the asymmetric α‐hydroxylation of β‐ketoesters 2 …”

“…[7] Keeping in mind the high value of chiral a-hydroxy-1,3-dicarbonyl compounds and the resulting currenti nteresti nt he development of asymmetric synthesis methods, we becamei nterested in testing the potential of our catalysts ystem for the asymmetric a-hydroxylation of b-ketoesters 2. [8]…”

Selenenate Anions (PhSeO−) as Organocatalyst: Synthesis of trans‐Stilbenes and a PPV Derivative

“…[15] 2-(Chloromethyl)pyridine (1 p) was selected to construct the corresponding heterocyclic stilbene (2 p), which was obtained in 48% yield. First, the deprotonation of benzyl phenyl selenoxide (Scheme 1, A to B) in toluene was confirmed by in situ 1 To further characterize the deprotonated benzyl phenyl selenoxide, we next attempted to isolate it. [16] Based on the proposed mechanism shown in Scheme 1, different selenoxides were synthesized and tested to evaluate their viability as precatalysts in the dehydrohalogen coupling of stilbenes.…”

“…[1] Some of the obvious advantages over more traditional catalysts include its environmentally friendliness, avoidance of heavy and precious transition metals, greater availability of catalysts and ease of handling compared to most transition metal complexes. [1] Some of the obvious advantages over more traditional catalysts include its environmentally friendliness, avoidance of heavy and precious transition metals, greater availability of catalysts and ease of handling compared to most transition metal complexes.…”

Photoredox Catalysis of Aromatic β‐Ketoesters for in Situ Production of Transient and Persistent Radicals for Organic Transformation

“…As the 1,3-dicarbonyl compound, an aromatic bketoester was selected due to the fact that the activation of its unique molecular skeleton is difficult without the aid of external oxidant or reductant. It was expected that both electrophilic and nucleophilic functionalities formed through keto-enol tautomerism [10] of the aromatic b-ketoester would be able to interact with the photoexcited photocatalyst (PC*) to afford ketyl radical A [7,11] and the photocatalyst radical cation (PCC + ). [12] The higher electron affinity and lower LUMO energy of aromatic b-ketoesters compared to alphatic b-ketoester 1y [13] mean that the keto form rather than the enol form acts as an electron acceptor (Table S4 supported by the results of the DFT calculation in the Supporting Information; Scheme 1).…”