Asymmetric Michael Addition of Oxindoles to Allenoate Catalyzed by N‐Acyl Aminophosphine: Construction of Functionalized Oxindoles with Quaternary Stereogenic Center

Abstract

A novel reaction between ethyl allenoate and oxindoles that enables the asymmetric synthesis of 3,3‐bisubstituted oxindoles with our previously established bifunctional N‐acyl aminophosphine catalysts is reported. These products bearing a chiral quaternary carbon center at the C‐3 position of the oxindoles may have potential significance in the synthesis of related structures. The best performance of these processes provides adducts with 92% yield and 94% ee.

Highly enantioselective construction of tertiary thioethers and alcohols via phosphine-catalyzed asymmetric γ-addition reactions of 5H-thiazol-4-ones and 5H-oxazol-4-ones: scope and mechanistic understandings

“…The mechanism of the γ-addition of 5 H -thiazol-4-one to allenoate is shown in Scheme 5 , which follows the general mechanism described in the literature for γ-addition reactions. 19 , 20 The reaction is initiated by the nucleophilic attack of the phosphorus atom on allenoate to form intermediate B , which is weakly basic. Deprotonation of the donor 5 H -thiazol-4-one by B then affords the corresponding enolate, which subsequently attacks the γ-carbon of the allenoate to give intermediate E .…”

“… 18 Very recently, we disclosed the utilization of 2,3-butadienoates in phosphine-catalyzed enantioselective γ-addition reactions. 19 , 20 To further expand the range of phosphine-mediated asymmetric reactions, we envisaged that 5 H -thiazol-4-ones and 5 H -oxazol-4-ones could serve as valuable donors in phosphine-catalyzed γ-addition reactions to allenoates ( Scheme 1 ). The chiral heteroatom-containing adducts formed have masked functionalities, and can be manipulated easily to give tertiary thiols/thioethers and alcohols.…”

Applications of Chiral Phosphine‐Based Organocatalysts in Catalytic Asymmetric Reactions

“…The obtained γ addition products ( 85 ) were utilized in the formal total synthesis of two natural products and in the preparation of biologically relevant molecules and structural scaffolds. By employing the same substrates, Zhao′s group also achieved a highly enantioselective phosphine‐catalyzed enantioselective γ addition of oxindoles with ethyl allenoate by using different amino‐acid‐based bifunctional chiral phosphine ( 86 ) as a catalyst 55b. A variety of 3‐substituted oxindoles smoothly underwent this reaction, thereby affording the corresponding γ‐addition products in high yields with excellent enantioselectivities (Scheme ).…”

Phosphine-Catalyzed Doubly Stereoconvergent γ-Additions of Racemic Heterocycles to Racemic Allenoates: The Catalytic Enantioselective Synthesis of Protected α,α-Disubstituted α-Amino Acid Derivatives

“…In recent years, nucleophilic catalysis by chiral tertiary phosphines has emerged as a powerful strategy for the enantioselective synthesis of a wide array of useful compounds. 1 Exemplary of this approach is the phosphine-catalyzed addition of nucleophiles to the γ-position of electron-deficient alkynes and allenes, 2 which furnishes α,β-unsaturated carbonyl compounds that are well-suited for further stereoselective functionalizations ( eqs 1 3 and 2 4 ). 5 …”